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/index.php/Vernon_Coleman

# Vernon Coleman Template:Animal rights Vernon Coleman (born in Walsall, West Midlands, England) is a British writer. A former general practitioner, he is the author of 90 books, including non-fiction works about human health, politics, cricket, and animal issues, and a range of novels. According to his website, his books have sold over two million copies in the UK, and have been translated into 23 languages. One of his novels, 'Mrs Caldicot's Cabbage War', has been turned into a movie starring Pauline Collins. Coleman is also a syndicated newspaper columnist, focusing on the politics of medicine. He is an outspoken critic of medical malpractice, the power of pharmaceutical companies, vaccination, conventional cancer treatment, and animal testing. He is the author of How to Stop Your Doctor Killing You (2003). A general practitioner for about ten years, mostly during the 1970s, his first books included The Medicine Men (1975), and Paper Doctors (1976). Body Power came in 1983, and has been reprinted a number of times. Alice's Diary (1989) and Alice's Adventures (1992) concern Alice (1983-1992) and her half sister Thomasina (1983-2000), real cats who shared their lives with Vernon Coleman. One of his latest books, Health Secrets Doctors Share With Their Families (2005) was written jointly with his wife, Donna Antoinette Coleman. Ho worked as a tabloid newspaper columnist, producing a spoof "agony uncle" column in the Sunday People which became memorable for the vehemence of his opinions - such as when he told a pro-hunt supporter that he should be "buried from the neck down in the fast lane of the M4." A collection of similarly-worded "replies" to readers' letters was published in the book I Hope Your Penis Shrivels Up in 1993. Coleman's wife Donna (born 1972) is also an experienced researcher and writer on health topics. She is co-author with him of How To Conquer Health Problems Between Ages 50 and 120 (2003), and Health Secrets Doctors Share With Their Families (2005). She shares her husband's long held view that the potential benefits of vaccinations are generally overstated, and the risks played down. She has a severely disabled sister.

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/index.php/Vero_cell

# Vero cell The Vero lineage was isolated from kidney epithelial cells extracted from African green monkey (Cercopithecus aethiops). The lineage was developed on 27 Mar 1962, by Yasumura and Kawakita at the Chiba University in Chiba, Japan. The original cell line was named after an acronym of "Verda Reno" and was matched to the word "Vero", which means "green kidney" and "truth" in esperanto, respectively. The Vero cell lineage is continuous and aneuploid. A continuous cell lineage can be replicated through many cycles of division and not become senescent. Aneuploidy is the characteristic of having an abnormal number of chromosomes.

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/index.php/Vertebra

# Vertebra There are normally thirty-three (33) vertebrae in humans, including the five that are fused to form the sacrum (the others are separated by intervertebral discs) and the four coccygeal bones which form the tailbone. The upper three regions comprise the remaining 24, and are grouped under the names cervical (7 vertebrae), thoracic (12 vertebrae) and lumbar (5 vertebrae), according to the regions they occupy. This number is sometimes increased by an additional vertebra in one region, or it may be diminished in one region, the deficiency often being supplied by an additional vertebra in another. With the exception of the first and second cervical, the true or movable vertebrae (the upper three regions) present certain common characteristics which are best studied by examining one from the middle of the thoracic region. A typical vertebra consists of two essential parts: an anterior (front) segment, which is the vertebral body; and a posterior part – the vertebral (neural) arch – which encloses the vertebral foramen. The vertebral arch is formed by a pair of pedicles and a pair of laminae, and supports seven processes, four articular, two transverse, and one spinous, the latter also being known as the neural spine. When the vertebrae are articulated with each other, the bodies form a strong pillar for the support of the head and trunk, and the vertebral foramina constitute a canal for the protection of the medulla spinalis (spinal cord), while between every pair of vertebrae are two apertures, the intervertebral foramina, one on either side, for the transmission of the spinal nerves and vessels. Two transverse processes and one spinous process are posterior to (behind) the vertebral body. The spinous process comes out the back, one transverse process comes out the left, and one on the right. The spinous processes of the cervical and lumbar regions can be felt through the skin. Superior and inferior articular facets on each vertebra act to restrict the range of movement possible. These facets are joined by a thin portion of the neural arch called the pars interarticularis. These are generally small and delicate. Their spinous processes are short (with the exception of C2 and C7, which have palpable spinous processes), and often split. Numbered top-to-bottom from C1-C7, atlas (C1) and axis (C2), are the vertebrae that allow the neck and head so much movement. For the most part, the atlanto-occipital joint allows the skull to move up and down, while the atlanto-axial joint allows the upper neck to twist left and right. The axis also sits upon the first intervertebral disk of the spinal column. All mammals except manatees and sloths have seven cervical vertebrae, whatever the length of the neck. Their spinous processes have surfaces that articulate with the ribs. Some rotation can occur between the thoracic vertebrae, but their connection with the rib cage prevents much flexion or other excursion. They may also be known as 'dorsal vertebrae', in the human context. These vertebrae are very robust in construction, as they must support more weight than other vertebrae. They allow significant flexion and extension, moderate lateral flexion (sidebending), and a small degree of rotation. The discs between these vertebrae create a lumbar lordosis (curvature that is concave posteriorly) in the human spine. There are 3-5 vertebrae (Co1-Co5), again fused, with no intervertebral discs. Many animals have a greater number of 'tail vertebrae' and, in animals, they are more commonly known as caudal vertebrae. Pain at the coccyx (tailbone) is known as coccydynia. During the fourth week of embryonic development, the sclerotomes shift their position to surround the spinal cord and the notochord. The sclerotome is made of mesoderm and originates from the ventromedial part of the somites. This column of tissue has a segmented appearance, with alternating areas of dense and less dense areas. As the sclerotome develops, it condenses further eventually developing into the vertebral body. Development of the appropriate shapes of the vertebral bodies is regulated by HOX genes. The notochord disappears in the sclerotome (vertebral body) segments, but persists in the region of the intervertebral discs as the nucleus pulposus. The nucleus pulposus and the fibers of the annulus fibrosus make up the intervertebral disc. The primary curves (thoracic and sacral curvatures) form during fetal development. The secondary curves develop after birth. The cervical curvature forms as a result of lifting the head and the lumbar curvature forms as a result of walking. There are various defects associated with vertebral development. Scoliosis can result from improper fusion of the vertebrae. In Klippel-Feil anomaly patients have two or more cervical vertebrae that are fused together, along with other associated birth defects. One of the most serious defects is failure of the vertebral arches to fuse. This results in a condition called spina bifida. There are several variations of spina bifida that reflect the severity of the defect.

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/index.php/Vertebral_arteries

# Vertebral artery They arise, one on each side of the body, then enter deep to the transverse process of the level of the 6th cervical vertebrae (C6). The basilar artery is the main blood supply to the brainstem and connects to the Circle of Willis to potentially supply the rest of the brain if there is compromise to one of the carotids. In front of it are the internal jugular and vertebral veins, and it is crossed by the inferior thyroid artery; the left vertebral is crossed by the thoracic duct also. The second part runs upward through the foramina in the transverse processes of the upper six cervical vertebræ, and is surrounded by branches from the inferior cervical sympathetic ganglion and by a plexus of veins which unite to form the vertebral vein at the lower part of the neck. It is situated in front of the trunks of the cervical nerves, and pursues an almost vertical course as far as the transverse process of the atlas, above which it runs upward and lateralward to the foramen in the transverse process of the atlas. The third part issues from the latter foramen on the medial side of the Rectus capitis lateralis, and curves backward behind the superior articular process of the atlas, the anterior ramus of the first cervical nerve being on its medial side; it then lies in the groove on the upper surface of the posterior arch of the atlas, and enters the vertebral canal by passing beneath the posterior atlantoöccipital membrane. This part of the artery is covered by the Semispinalis capitis and is contained in the suboccipital triangle—a triangular space bounded by the Rectus capitis posterior major, the Obliquus superior, and the Obliquus inferior. The fourth part pierces the dura mater and inclines medialward to the front of the medulla oblongata; it is placed between the hypoglossal nerve and the anterior root of the first cervical nerve and beneath the first digitation of the ligamentum denticulatum.

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/index.php/Vertebral_column

# Vertebral column In human anatomy, the vertebral column (backbone or spine) is a column of 33 vertebrae, the sacrum, intervertebral discs, and the coccyx situated in the dorsal aspect of the torso, separated by spinal discs. It houses the spinal cord in its spinal canal. Viewed laterally the vertebral column presents several curves, which correspond to the different regions of the column, and are called cervical, thoracic, lumbar, and pelvic. The cervical curve, convex forward, begins at the apex of the odontoid (tooth-like) process, and ends at the middle of the second thoracic vertebra; it is the least marked of all the curves. The thoracic curve, concave forward, begins at the middle of the second and ends at the middle of the twelfth thoracic vertebra. Its most prominent point behind corresponds to the spinous process of the seventh thoracic vertebra. This curve is known as a tt curve. The lumbar curve is more marked in the female than in the male; it begins at the middle of the last thoracic vertebra, and ends at the sacrovertebral angle. It is convex anteriorly, the convexity of the lower three vertebrae being much greater than that of the upper two. This curve is described as a lordotic curve. The thoracic and pelvic curves are termed primary curves, because they alone are present during fetal life. In the early embryo, the vertebral column is C-shaped, and the cervical and lumbar curvatures are not yet present in a newborn infant. The cervical and lumbar curves are compensatory or secondary, and are developed after birth, the former when the child is able to hold up its head (at three or four months) and to sit upright (at nine months), the latter at twelve or eighteen months, when the child begins to walk. The thoracic portion of the vertebral column also has a slight lateral curvature, the convexity of which is directed toward the right side. This may be produced by muscular action, most persons using the right arm in preference to the left, especially in making long-continued efforts, when the body is curved to the right side. In support of this explanation it has been found that in one or two individuals who were left-handed, the convexity was to the left side. This curvature is regarded by others as being produced by the aortic arch and upper part of the descending thoracic aorta – a view which is supported by the fact that in cases of situs inversus where the viscera are transposed and the aorta is on the right side, the convexity of the curve is directed to the left side. When viewed from in front, the width of the bodies of the vertebrae is seen to increase from the second cervical to the first thoracic; there is then a slight diminution in the next three vertebrae; below this there is again a gradual and progressive increase in width as low as the sacrovertebral angle. From this point there is a rapid diminution, to the apex of the coccyx. The posterior surface of the vertebral column presents in the median line the spinous processes. In the cervical region (with the exception of the second and seventh vertebrae) these are short and horizontal, with bifid extremities. In the upper part of the thoracic region they are directed obliquely downward; in the middle they are almost vertical, and in the lower part they are nearly horizontal. In the lumbar region they are nearly horizontal. The spinous processes are separated by considerable intervals in the lumbar region, by narrower intervals in the neck, and are closely approximated in the middle of the thoracic region. Occasionally one of these processes deviates a little from the median line — a fact to be remembered in practice, as irregularities of this sort are attendant also on fractures or displacements of the vertebral column. On either side of the spinous processes is the vertebral groove formed by the laminae in the cervical and lumbar regions, where it is shallow, and by the laminae and transverse processes in the thoracic region, where it is deep and broad; these grooves lodge the deep muscles of the back. Lateral to the vertebral grooves are the articular processes, and still more laterally the transverse processes. In the thoracic region, the transverse processes stand backward, on a plane considerably behind that of the same processes in the cervical and lumbar regions. In the cervical region, the transverse processes are placed in front of the articular processes, lateral to the pedicles and between the intervertebral foramina. In the thoracic region they are posterior to the pedicles, intervertebral foramina, and articular processes. In the lumbar region they are in front of the articular processes, but behind the intervertebral foramina. The lateral surfaces are separated from the posterior surface by the articular processes in the cervical and lumbar regions, and by the transverse processes in the thoracic region. They present, in front, the sides of the bodies of the vertebrae, marked in the thoracic region by the facets for articulation with the heads of the ribs. More posteriorly are the intervertebral foramina, formed by the juxtaposition of the vertebral notches, oval in shape, smallest in the cervical and upper part of the thoracic regions, and gradually increasing in size to the last lumbar. They transmit the spinal nerves and are situated between the transverse processes in the cervical region, and in front of them in the thoracic and lumbar regions. T3 is at level of medial part of spine of scapula. T7 is at inferior angle of the scapula. L4 is at highest point of iliac crest. S2 is at the level of posterior superior iliac spine. T12 can be found by identifying the lowest pair of ribs and tracing them to their thoracic attachment. Furthermore, C7 is easily localized as a prominence at the lower part of the neck. The vertebral canal follows the different curves of the column; it is large and triangular in those parts of the column which enjoy the greatest freedom of movement, such as the cervical and lumbar regions; and is small and rounded in the thoracic region, where motion is more limited. Occasionally the coalescence of the laminae is not completed, and consequently a cleft is left in the arches of the vertebrae, through which a protrusion of the spinal membranes (dura mater and arachnoid), and generally of the spinal cord (medulla spinalis) itself, takes place, constituting the malformation known as spina bifida. This condition is most common in the lumbosacral region, but it may occur in the thoracic or cervical region, or the arches throughout the whole length of the canal may remain incomplete.

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/index.php/Vertebral_subluxation

# Vertebral subluxation Vertebral subluxation is a chiropractic term that is used by some chiropractors to describe a myriad of signs and symptoms thought to occur as a result of a misaligned or dysfunctional spinal segment. Since its conception by DD Palmer, the definition has undergone many refinements in an effort to describe the conditions that chiropractors treat. In 1996, the Association of Chiropractic Colleges, representing all chiropractic colleges, unified the definition as, "a complex of functional and/or structural and/or pathological articular changes that compromise neural integrity and may influence organ system function and general health." The concept of chiropractic vertebral subluxation remains a uniquely chiropractic construct that does not enjoy mainstream medical support. It should not be confused with the orthopedic subluxation. While the orthopedic and medical definition of a subluxation includes objectively verifiable misalignment and sometimes nerve damage, it is considered an uncommon occurrence. Chiropractors who believe in the vertebral subluxation complex propose that it can negatively affect general health by altering the proper circulation of information via the nervous system. Although not always painful, some chiropractors claim that a subluxation interferes with the proper function and healing of your body due to the role of the nervous system as a controller of many bodily functions. A vertebral subluxation is theorized to affect one spinal disc (i.e. degenerative disc disease), a section of the spine, or the entire spine. For example, a functional scoliosis or abnormal curvature of the spine, viewed in chiropractic terms, may be due to a subluxation of one vertebra that causes a distortion of the entire spine. Chiropractic treatment of vertebral subluxation focuses on delivering a chiropractic adjustment to the affected part of the spine in an effort to reduce the subluxation. Spinal manipulation is the primary procedure used by chiropractors in the adjustment. It has been shown to help some symptoms of subluxations such as low back pain, neck pain and tension type headaches, but there are only limited clinically controlled studies to evaluate the effects on organ function. The chiropractic vertebral subluxation is not defined the same way as the medical subluxation. In the following statements, the World Health Organisation explains the difference by starting with a standard chiropractic definition: In the chiropractic system developed by Daniel D. Palmer in the late 1800's, Palmer originally believed that he had discovered the cause of all diseases suffered by mankind — the vertebral subluxation. Chiropractors use and have used various terms to express this concept: subluxation, vertebral subluxation (VS), vertebral subluxation complex (VSC), "killer subluxations," the "silent killer," or a "bone out of place" (BOOP). As a continuation of the brain, the spinal cord contains nerve tracts which are the neurological pathways through which the brain communicates with most of the body. While the brain is protected by the skull, the spinal cord is protected by the vertebral column. As nerves branch off the spinal cord, they form the spinal nerve roots which exit the vertebral column through an opening made by two adjacent vertebrae, called the intervertebral foramen. V. Strang, D.C., describes several hypotheses on how a misaligned vertebra may cause interference to the nervous system in his book, Essential Principles of Chiropractic. The vertebral subluxation has been described as a syndrome with signs and symptoms which include: altered alignment; aberrant motion; palpable soft tissue changes; localized/referred pain; muscle contraction or imbalance; altered physiological function; reversible with adjustment/manipulation; focal tenderness. Others believe that a subluxation itself is a sign, not a syndrome. When chiropractors believe a vertebral subluxation is present they may apply a specific adjustment to the spinal bone considered to be subluxated. While there are a number of different chiropractic techniques, each can be characterized by the description of having a short-lever, high velocity, low amplitude (HVLA) thrust and specific line of correction. While chiropractors do attempt to direct treatment at specific movement segments of the spinal column, no other profession claims to intend to treat vertebral subluxations. Once these bones or vertebrae are theoretically restored to their proper position and/or motion, the spinal cord and/or its nerve roots are no longer considered to be hindered or compressed. Thus, without interference from a subluxation, the brain is considered to be enabled to transmit and receive all the messages through the spinal cord and nerve roots to all the parts of the body supplied by those nerves. The spine is considered "in line" and thus it is assumed the body functions in a coordinated manner resulting in increased health. The investigation of vertebral subluxation has been ongoing since it was first postulated in 1895. The early practitioners used palpation and the anatomy of the nervous system as a guide (meric system). In their efforts to be more specific, they seized the newly discovered X-ray technology and introduced the neurocalometer (a heat sensing device). It was during those early years that the medical establishment first criticized the chiropractic profession, saying that the conditions that those early chiropractors were treating were only psychophysiologic disorders. To prove that chiropractic patients had real conditions, BJ Palmer opened a research clinic as a part of the Palmer College of Chiropractic. When a patient entered the clinic, they were first examined by medical doctors and a diagnosis was formulated. They were then sent to the chiropractic part of the clinic, treated, and sent back to the medical doctors for evaluation. Since then, chiropractors have sought a greater understanding of the mechanisms and effects of the vertebral subluxation. Today we see motion x-rays, surface EMG, and digital thermography. As research projects are able to employ new techniques and technologies to evaluate nervous system function and effects, further support for chiropractic principles has surfaced. Chiropractors have long suggested that spinal joint fixation that results from subluxation will result in degenerative effects that break down the spinal joints. A 2004 research team at the National University of Health Sciences evaluated changes of the lumbar vertebral column following fixation (immobility) by surgically fusing spinal joints in experimental rats. The fixated joints showed significant degeneration compared to the mobile joints, confirming that surgical fixation results in time-dependent degenerative changes of the zygapophysial joints. Chiropractic also asserts that spinal health and function are directly related to general health and well being. Research concerning the intricate functioning of the nervous system suggests that this speculation may have some support. Seaman reviewed the work of several researchers concerning autonomic nervous system relationship to the somatic tissues of the spine. He noted that Feinstein et al. were the first to clearly describe some symptoms associated with noxious irritation of spinal tissues. They injected hypertonic saline into interspinous tissues and paraspinal muscles of normal volunteers for the purpose of characterizing local and referred pain patterns that might develop. His observations included: Feinstein referred to these symptoms as autonomic concomitants . It is likely that these autonomic concomitants were caused by nociceptive stimulation of autonomic centers in the brainstem, particularly the medulla. Feinstein indicated that "this is an example of the ability of deep noxious stimulation to activate generalized autonomic responses independently of the relay of pain to conscious levels." In other words, pain may not be the symptomatic outcome of nociceptive stimulation of spinal structures. Such a conclusion has profound implications for the chiropractic profession. Clearly, patients do not need to be in pain to be candidates for spinal adjustments. Considering this phenomenon, Seaman suggests that the chiropractic concept of joint complex (somatic) dysfunction should be incorporated into the differential diagnosis of pain and visceral symptoms because these dysfunctions often generate symptoms similar to those produced by true visceral disease and notes that this mimicry leads to unnecessary surgical procedures and medications. Researchers at the RMIT University-Japan, Tokyo studied reflex effects of subluxation with regards to the autonomic nervous system. They found that "recent neuroscience research supports a neurophysiologic rationale for the concept that aberrant stimulation of spinal or paraspinal structures may lead to segmentally organized reflex responses of the autonomic nervous system, which in turn may alter visceral function." Professor Philip S. Bolton of the School of Biomedical Sciences at University of Newcastle, Australia writes in JMPT, "The traditional chiropractic vertebral subluxation hypothesis proposes that vertebral misalignment cause illness, disease, or both. This hypothesis remains controversial." His objective was, "To briefly review and update experimental evidence concerning reflex effects of vertebral subluxations, particularly concerning peripheral nervous system responses to vertebral subluxations. Data source: Information was obtained from chiropractic or, scientific peer-reviewed literature concerning human or animal studies of neural responses to vertebral subluxation, vertebral displacement or movement, or both." He concluded, "Animal models suggest that vertebral displacements and putative vertebral subluxations may modulate activity in group I to IV afferent nerves. However, it is not clear whether these afferent nerves are modulated during normal day-to-day activities of living and, if so, what segmental or whole-body reflex effects they may have." Conclusions: Monitoring mixed-nerve root discharges in response to spinal manipulative thrusts in vivo in human subjects undergoing lumbar surgery is feasible. Neurophysiologic responses appeared sensitive to the contact point and applied force vector of the spinal manipulative thrust. Further study of the neurophysiologic mechanisms of spinal manipulation in humans and animals is needed to more precisely identify the mechanisms and neural pathways involved. Researchers at the Department of Physiology, University College London studied the effects of compression upon conduction in myelinated axons. Using pneumatic pressure of varying degrees on the sciatic nerves of frog specimens, the studied supported the idea of nerve conduction failure as a result of compression. An area of debate among chiropractors is whether "vertebral subluxation" is a metaphysical concept (as posited in B. J. Palmer's philosophy of chiropractic) or a real phenomenon. Since its inception, the concept of vertebral subluxation has been a source of definitional debate. Tedd Koren, DC offers this explanation as a possible cause of the confusion:

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/index.php/Vertebral_vein

# Vertebral vein The vertebral vein is formed in the suboccipital triangle, from numerous small tributaries which spring from the internal vertebral venous plexuses and issue from the vertebral canal above the posterior arch of the atlas. They unite with small veins from the deep muscles at the upper part of the back of the neck, and form a vessel which enters the foramen in the transverse process of the atlas, and descends, forming a dense plexus around the vertebral artery, in the canal formed by the foramina transversaria of the cervical vertebrae. This plexus ends in a single trunk, which emerges from the foramen transversarium of the sixth cervical vertebra, and opens at the root of the neck into the back part of the innominate vein near its origin, its mouth being guarded by a pair of valves.

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/index.php/Vertebrate_and_Genome_Annotation_Project

# Vertebrate and Genome Annotation Project The Vertebrate and Genome Annotation (Vega) project provides manual curation of vertebrate genomes for the scientific community . The Vega data repository is publicly available, regularly updated and includes annotations of several finished vertebrate genome sequences: human, mouse, zebrafish, pig and dog .

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/index.php/Verteporfin

# Verteporfin Verteporfin is a photosensitizing agent that is FDA approved for the treatment of patients with predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis. Common adverse reactions include injection site reaction, blurred vision, photopsia, reduced visual acuity, visual field defect.

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/index.php/Vertigo

# Vertigo Diagnostic study of choice | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | Echocardiography or Ultrasound | CT | MRI | Other Imaging Findings | Other Diagnostic Studies

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/index.php/Vertigo_resident_survival_guide

# Vertigo resident survival guide Vertigo is a specific type of dizziness, and a major symptom of a balance disorder. Vertigo is characterized by a sudden spinning sensation that occurs internally or externally, and usually occurs when you move your head quickly. This sensation occurs while the body is actually stationary with respect to the surroundings. The effects of vertigo may be slight; it can cause nausea and vomiting and, in severe cases, it may give rise to difficulties with standing and walking.

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/index.php/Vertigo_resident_survival_guide_(pediatrics)

# Vertigo resident survival guide (pediatrics) Vertigo can be described as a subjective sensation of movement such as spinning, turning or whirling of patients or respective surroundings. Vertigo is a symptom, not a diagnosis. It results from a dysfunction either in the vestibular or central nervous system; thus can be classified as a peripheral or central vertigo respectively. Some conditions can present with a subjective feeling of dizziness without vertigo hence named as pseudo-vertigo. Most children or adolescents have secondary vertigo as a result of various conditions such as otitis media, benign paroxysmal positional vertigo, head trauma, or any CNS infection. Successful management of vertigo usually consists of identifying the root cause and specifically targeting the underlying condition.

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/index.php/Very_low_calorie_diet

# Very low calorie diet Very low calorie diet (VLCD) is a diet with very or extremely low calorie consumption per day. It is defined medically as a diet of 800 kilocalories per day or less. VLCDs are formulated, nutritionally complete, liquid meals containing 3350 kJ (800 kcal) or less per day. VLCDs also contain the recommended daily requirements for vitamins, minerals, trace elements, fatty acids and protein. The VLCD products are usually a powder which is mixed with water, juice or other low calorie liquid. A VLCD diet is aimed primarily for severely or morbidly obese adults who must lose significant amounts of weight quickly, in order to live. It is also for those individuals who wish to lose some of their weight as rapidly as possible in a safe manner. Because of the extremely low calories per day, a VLCD diet cannot be used by children no matter how obese. The average weight loss on the VLCD program is in the range of 3 to 5 pounds per week, but it is to be remembered that at first you only lose excess liquid from your body. A 1997 study concludes that the short-term use of a VLCD is very effective in rapidly improving glycaemic control and promoting substantial weight loss in obese patients with Type 2 diabetes. Moreover, a VLCD increases insulin sensitivity and reduces the substrate for gluconeogenesis. Thus VLCD treatment may improve glycaemic control more than calorie restriction alone. A slowing of one's metabolism can occur as your body adapts so the brain and central nervous system, as well as other bodily systems, will cease to work efficiently. An imbalance in minerals and electrolytes can occur. Osteoporosis can be another danger, especially for women as can anaemia (a lack of iron in the blood). If taken to extremes, women can find that menstruation (periods) becomes irregular or stops altogether. A lack of serotonin in the brain can lead to clinical depression. The lack of essential nutrients on a very low calorie diet leads to a deterioration in the condition of hair and nails.

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/index.php/Very_low_density_lipoprotein_physiology

# Very low density lipoprotein physiology Very Low-Density Lipoprotein (VLDL) is a lipoprotein subclass. It is assembled in the liver from cholesterol and apolipoproteins. It is converted in the bloodstream to low-density lipoprotein (LDL). VLDL particles have a diameter of 30-80 nm. VLDL transports endogenous products where chylomicrons transport exogenous (dietary) products. Nascent VLDL circulates in blood and picks up apolipoprotein C-II and apolipoprotein E donated from High-Density Lipoprotein (HDL). At this point, the nascent VLDL becomes a mature VLDL. Once in circulation, the VLDL will come in contact with Lipoprotein lipase (LPL) in the capillary beds in the body (adipose, cardiac, and skeletal muscle). The LPL will remove triglycerides from the VLDL for storage or energy production. The VLDL now meets back up with HDL where apoC-II is transferred back to the HDL (but keeps apoE). In addition to this, the HDL transfers cholesteryl esters to the VLDL in exchange for phospholipids and triglycerides (via cholesteryl ester transfer protein). As more and more triglycerides are removed from the VLDL because of the action of the LPL enzyme, the composition of the molecule changes, and it becomes intermediate density lipoprotein (IDL). The other 50% of IDL lose their apoE. When their cholesterol content becomes greater than the triglyceride content, they become low-density lipoprotein (LDL), with the primary apolipoprotein being apoB-100. The LDL is taken into a cell via the LDL receptor (endocytosis) where the contents are either stored, used for cell membrane structure, or converted into other products (steroid hormones or bile acids).

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/index.php/Vesicle_(biology)

# Vesicle (biology) In cell biology, a vesicle is a relatively small and enclosed compartment, separated from the cytosol by at least one lipid bilayer. If there is only one lipid bilayer, they are called unilamellar vesicles; otherwise they are called multilamellar. Vesicles store, transport, or digest cellular products and waste. This biomembrane enclosing the vesicle is similar to that of the plasma membrane. Because it is separated from the cytosol, the intravesicular environment can be made to be different from the cytosolic environment. Vesicles are a basic tool of the cell for organizing metabolism, transport, enzyme storage, as well as being chemical reaction chambers. Many vesicles are made in the Golgi apparatus, but also in the endoplasmic reticulum, or are made from parts of the plasma membrane. Some vesicles are made when part of the membrane pinches off the endoplasmic reticulum or the Golgi complex. Others are made when an object outside of the cell is surrounded by the cell membrane. The assembly of a vesicle requires numerous coats to surround and bind to the proteins being transported. One family of coats are called adaptins. These bind to the coat vesicle (see below). They also trap various transmembrane receptor proteins, called cargo receptors, which in turn trap the cargo molecules. The vesicle coat serves to sculpt the curvature of a donor membrane, and to select specific proteins as cargo. It selects cargo proteins by binding to sorting signals. In this way the vesicle coat clusters selected membrane cargo proteins into nascent vesicle buds. There are three types of vesicle coats: clathrin, COPI and COPII. Clathrin coats are found on vesicles trafficking between the Golgi and plasma membrane, the Golgi and endosomes, and the plasma membrane and endosomes. COPI coated vesicles are responsible for retrograde transport from the Golgi to the ER, while COPII coated vesicles are responsible for anterograde transport from the ER to the Golgi. Surface markers called SNAREs identify the vesicle's cargo, and complementary SNAREs on the target membrane act to cause fusion of the vesicle and target membrane. Such v-SNARES are hypothesised to exist on the vesicle membrane, while the complementary ones on the target membrane are known as t-SNAREs. Regulatory Rab proteins are thought to inspect the joining of the SNAREs. Rab protein is a regulatory GTP-binding protein, and controls the binding of these complementary SNAREs for a long enough time for the Rab protein to hydrolyse its bound GTP and lock the vesicle onto the membrane. Fusion requires the two membranes to be brought within 1.5 nm of each other. For this to occur water must be displaced from the surface of the vesicle membrane. This is energetically unfavourable, and evidence suggests that the process requires ATP, GTP and acetyl-coA, fusion is also linked to budding, which is why the term budding and fusing arises. Membrane proteins serving as receptors are sometimes tagged for degregation by the attachment of ubiquitin. After arriving an endosome via the pathway described above, vesicles begin to form inside the endosome, taking with them the membrane proteins meant for degregation; When the endosome either matures to become a lysosome or is united with one, the vesicles are completely degregaded. Without this mechanism, only the extracellular part of the membrane proteins would reach the lumen of the lysosome, and only this part would be degraded . It is because of these vesicles that the endosome is sometimes known as a multivesicular body. However the pathway to their formation is not completely understood. Unlike the other vesicles described above, the outer surface of the vesicles is not in contact with the cytosol.

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# Vesicular glutamate transporter 1 The protein encoded by this gene is a vesicle-bound, sodium-dependent phosphate transporter that is specifically expressed in the neuron-rich regions of the brain. It is preferentially associated with the membranes of synaptic vesicles and functions in glutamate transport. The protein shares 82% identity with the differentiation-associated Na-dependent inorganic phosphate cotransporter and they appear to form a distinct class within the Na+/Pi cotransporter family.

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# Vesicular monoamine transporter VMAT is the main target of methamphetamine. By acting as a competitive antagonist, methamphetamine blocks the presynaptic cell's ability to use VMAT to package the above mentioned neurotransmitters into vesicles. The result is increased neurotransimtter release that is not dependent on the phasic activity of the presynaptic cell.

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# Vesicular monoamine transporter 1 Vesicular monoamine transporter 1 (VMAT1) also known as chromaffin granule amine transporter (CGAT) or solute carrier family 18 member 1 (SLC18A1) is a protein that in humans is encoded by the SLC18A1 gene. VMAT1 is an integral membrane protein, which is embedded in synaptic vesicles and serves to transfer monoamines, such as norepinephrine, epinephrine, dopamine, and serotonin, between the cytosol and synaptic vesicles. SLC18A1 is an isoform of the vesicular monoamine transporter. The idea that there must be specific transport proteins associated with the uptake of monoamines and acetylcholine into vesicles developed due to the discovery of specific inhibitors which interfered with monoamine neurotransmission and also depleted monoamines in neuroendocrine tissues. VMAT1 and VMAT2 were first identified in rats upon cloning CDNAs for proteins which gave non-amine accumulating recipient cells the ability to sequester monoamines. Subsequently, human VMATs were cloned using human cDNA libraries with the rat homologs as probes, and heterologous-cell amine uptake assays were performed to verify transport properties. Across mammalian species, VMATs have been found to be structurally well conserved; VMAT1s have an overall sequence identity exceeding 80%. However, there exists only a 60% sequence identity between the human VMAT1 and VMAT2. VMAT1 is an acidic glycoprotein with an apparent weight of 40 kDa. Although the crystallographic structure has not yet been fully resolved, VMAT1 is known to have either twelve transmembrane domains (TMDs), based on Kyte-Doolittle hydrophobicity scale analysis or ten TMDs, based on MAXHOM alignment. MAXHOM alignment was determined using the "profile-fed neural network systems from Heidelberg" (PHD) program. The main difference between these two models arises from the placement of TMDs II and IV in the vesicle lumen or the cytoplasm. VMATs are found in a variety of cell types throughout the body, however, VMAT1 is found exclusively in neuroendocrine cells, in contrast to VMAT2, which is also found in the PNS and CNS. Specifically, VMAT1 is found in chromaffin cells, enterochromaffin cells, and small intensely fluorescent cells (SIFs). Chromaffin cells are responsible for releasing the catecholamines (norepinephrine and epinephrine) into systemic circulation. Enterochromaffin cells are responsible for storing serotonin in the gastrointestinal tract. SIFs are interneurons associated with the sympathetic nervous system which are managed by dopamine. VMAT1 is found in both large dense-core vesicles (LDCVs) as well as in small synaptic vesicles (SSVs). This was discovered via studying rat adrenal medulla cells (PC12 cells). LDCVs are 70-200 nm in size and exist throughout the neuron (soma, dendrites, etc.). SSVs are much smaller (usually about 40 nm) and typically exist as clusters in the presynaptic cleft. The active transport of monoamines from the cytosol into storage vesicles operates against a large (>105) concentration gradient. Secondary active transport is the type of active transport used, meaning that VMAT1 is an antiporter. This transport is facilitated via proton gradient generated by the protein proton ATPase. The inward transport of the monoamine is coupled with the efflux of two protons per monoamine. The first proton is thought to cause a change in VMAT1's conformation, which pushes a high affinity amine binding site, to which the monoamine attaches. The second proton then causes a second change in the conformation which pulls the monoamine into the vesicle and greatly reduces the affinity of the binding site for amines. A series of tests suggest that His419, located between TMDs X and XI, plays the key role in the first of these conformational changes, and that Asp431, located on TMD XI, does likewise during the second change. Several reuptake inhibitors of VMATs are known to exist, including reserpine (RES), tetrabenazine (TBZ), dihydrotetrabenazine (DTBZOH), and ketanserin (KET). It is thought that RES exhibits competitive inhibition, binding to the same site as the monoamine substrate, as studies have shown that it can be displaced via introduction of norepinephrine. TBZ, DTBZOH, and KET are thought to exhibit non-competitive inhibition, instead binding to allosteric sites and decreasing the activity of the VMAT rather than simply blocking its substrate binding site. It has been found that these inhibitors are less effective at inhibiting VMAT1 than VMAT2, and the inhibitory effects of the tetrabenazines on VMAT1 is negligible. The expression of VMAT1 in healthy endocrine cells was compared to VMAT1 expression in infants with hyperinsulinemic hypoglycemia and adults with pancreatic endocrine tumors. Through immunohistochemistry (IHC) and in situ hybridization (ISH), they found VMAT1 and VMAT2 were located in mutually exclusive cell types, and that in insulinomas VMAT2 activity disappeared, suggesting that if only VMAT1 activity is present in the endocrine system, this type of cancer is likely. VMAT1 also has effects on the modulation of gastrin processing in G cells. These intestinal endocrine cells process amine precursors, and VMAT1 pulls them into vesicles for storage. The activity of VMAT1 in these cells has a seemingly inhibitory effect on the processing of gastrin. Essentially, this means that certain compounds in the gut can be taken into these G cells and either amplify or inhibit the function of VMAT1, which will impact gastrin processing (conversion from G34 to G17). Additionally, VMAT1 is known to play a role in the uptake and secretion of serotonin in the gut. Enterochromaffin cells in the intestines will secrete serotonin in response to the activation of certain mechanosensors. The regulation of serotonin in the gut is critically important, as it modulates appetite and controls intestinal contraction. Presence of VMAT1 in cells has been shown to protect them from the damaging effects of cooling and rewarming associated with hypothermia. Experiments were carried out on aortic and kidney cells and tissues. Evidence was found that an accumulation of serotonin using VMAT1 and TPH1 allowed for the subsequent release of serotonin when exposed to cold temperatures. This allows cystathionine beta synthase (CBS) mediated generation of H2S. The protection against the damage caused by hypothermia is due to a reduction in the generation of reactive oxygen species (ROS), which can induce apoptosis, due to the presence of H2S. VMAT1 (SLC18A1) maps to a shared bipolar disorder(BPD)/schizophrenia locus, which is located on chromosome 8p21. It is thought that disruption in transport of monoamine neurotransmitters due to variation in the VMAT1 gene may be relevant to the etiology of these mental disorders. One study looked at a population of European descent, examining the genotypes of a bipolar group and a control group. The study confirmed expression of VMAT1 in the brain at a protein and mRNA level, and found a significant difference between the two groups, suggesting that, at least for people of European descent, variation in the VMAT1 gene may confer susceptibility. A second study examined a population of Japanese individuals, one group healthy and the other schizophrenic. This study resulted in mostly inconclusive findings, but some indications that variation in the VMAT1 gene would confer susceptibility to schizophrenia in Japanese women. While these studies provide some promising insight into the cause of some of the most prevalent mental disorders, it is clear that additional research will be necessary in order to gain a full understanding.

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# Vesicular monoamine transporter 2 The vesicular monoamine transporter 2 (VMAT2) also known as solute carrier family 18 member 2 (SLC18A2) is a protein that in humans is encoded by the SLC18A2 gene. VMAT2 is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from cellular cytosol into synaptic vesicles. In nigrostriatal pathway and mesolimbic pathway dopamine-releasing neurons, VMAT2 function is also necessary for the vesicular release of the neurotransmitter GABA. VMAT2 is believed to possess at least two distinct binding sites, which are characterized by tetrabenazine (TBZ) and reserpine binding to the transporter. Amphetamine (TBZ site) and methamphetamine (reserpine site) bind at distinct sites on VMAT2 to inhibit its function. VMAT2 inhibitors like tetrabenazine and reserpine reduce the concentration of monoamine neurotransmitters in the synaptic cleft by inhibiting uptake through VMAT2; the inhibition of VMAT2 uptake by these drugs prevents the storage of neurotransmitters in synaptic vesicles and reduces the quantity of neurotransmitters that are released through exocytosis. Although many substituted amphetamines induce the release of neurotransmitters from vesicles through VMAT2 while inhibiting uptake through VMAT2, they facilitate the release of monoamine neurotransmitters into the synaptic cleft by simultaneously reversing the direction of transport through the primary plasma membrane transport proteins for monoamines (i.e., the dopamine transporter, norepinephrine transporter, and serotonin transporter) in monoamine neurons. VMAT2 is essential for enabling the release of neurotransmitters from the axon terminals of monoamine neurons into the synaptic cleft. If VMAT2 function is inhibited or compromised, monoamine neurotransmitters such as dopamine cannot be released into the synapse via typical release mechanisms (i.e., exocytosis resulting from action potentials). Cocaine users display a marked reduction in VMAT2 immunoreactivity. Sufferers of cocaine-induced mood disorders displayed a significant loss of VMAT2 immunoreactivity; this might reflect damage to dopamine axon terminals in the striatum. These neuronal changes could play a role in causing disordered mood and motivational processes in more severely addicted users. Geneticist Dean Hamer has suggested that a particular allele of the VMAT2 gene correlates with spirituality using data from a smoking survey, which included questions intended to measure "self-transcendence". Hamer performed the spirituality study on the side, independently of the National Cancer Institute smoking study. His findings were published in the mass-market book The God Gene: How Faith Is Hard-Wired Into Our Genes. Hamer himself notes that VMAT2 plays at most a minor role in influencing spirituality. Furthermore, Hamer's claim that the VMAT2 gene contributes to spirituality is controversial. Hamer's study has not been published in a peer reviewed journal and a reanalysis of the correlation demonstrates that it is not statistically significant.

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# Vesicular stomatitis virus Template:Taxobox begin |- |align=center|File:Vesicular stomatitis virus (VSV) EM 18 lores.jpg |- |colspan=2 align=center|Vesicular stomatitis virus |- Template:Taxobox begin placement virus Template:Taxobox group v entry Template:Taxobox ordo entry Template:Taxobox familia entry Template:Taxobox genus entry Template:Taxobox species entry Template:Taxobox species entry Template:Taxobox species entry Template:Taxobox end placement Template:Taxobox end Vesicular stomatitis virus (VSV) is a virus in the family Rhabdoviridae, order Mononegavirales. The well-known Rabies virus belongs to the same family. VSV can infect insects and mammals. It has particular importance to farmers in certain regions of the world where it can infect cattle. It is also a common laboratory virus used to study the properties of viruses in the Rhabdoviridae family, as well as to study viral evolution. VSV is an arbovirus: Natural VSV infections encompass two steps, cytolytic infections of mammalian hosts and transmission by insects. In insects, infections are non-cytolytic persistent. Vesicular stomatitis virus (VSV) is the prototypic member of the Vesiculovirus genera of the Rhabdovirus family. The genome of the virus is a single molecule of negative-sense RNA that encodes five major proteins: glycoprotein (G), matrix protein (M), nucleoprotein, large protein (L) and phosphoprotein. The G protein enables viral entry to the cell by mediating both virus attachment to the host cell and fusion of the viral envelope with the endosomal membrane following endocytosis. The mRNA encoding the vesicular stomatitis virus M protein is 831 nucleotides long, and encodes a protein of 229 amino acids. The predicted M protein sequence does not contain any long hydrophobic or nonpolar domains that might promote membrane association. The protein is rich in basic amino acids and contains a highly basic amino terminal domain. The VSVG does not follow the same path as most vesicles because transport of the G protein from the endoplasmic reticulum to the plasma membrane is interrupted by incubation at 15°C. Under this condition, the molecules accumulate in both the endoplasmic reticulum (ER) and a subcellular vesicle fraction of low density called the lipid-rich vesicle fraction. The material in the lipid-rich vesicle fraction appears to be a post-ER intermediate in the transport process to the plasma membrane (PM). When synthesized in polarized epithelial cells, the envelope glycoproteins hemagglutinin of VSVG are targeted to the apical and basolateral plasma membranes. VSVG is also a common coat protein for lentiviral vector expression systems used to introduce genetic material into in vitro systems or animal models. It has the advantage or allowing the virus to infect non-dividing cells like B cells in vitro.

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# Vestibular nerve The vestibular nerve is one of the two branches of the Vestibulocochlear nerve (the cochlear nerve being the other). It goes to the semicircular canals via the vestibular ganglion. It receives positional information. Axons of the vestibular nerve synapse in the vestibular nucleus on the lateral floor and wall of the fourth ventricle in the pons and medulla. It arises from bipolar cells in the vestibular ganglion, ganglion of Scarpa, which is situated in the upper part of the outer end of the internal auditory meatus.

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# Vestibular nuclei The fibers of the vestibular nerve enter the medulla oblongata on the medial side of those of the cochlear, and pass between the inferior peduncle and the spinal tract of the trigeminal. They then divide into ascending and descending fibers. The latter end by arborizing around the cells of the medial nucleus, which is situated in the area acustica of the rhomboid fossa. The ascending fibers either end in the same manner or in the lateral nucleus, which is situated lateral to the area acustica and farther from the ventricular floor. Some of the axons of the cells of the lateral nucleus, and possibly also of the medial nucleus, are continued upward through the inferior peduncle to the roof nuclei of the opposite side of the cerebellum, to which also other fibers of the vestibular root are prolonged without interruption in the nuclei of the medulla oblongata. A second set of fibres from the medial and lateral nuclei end partly in the tegmentum, while the remainder ascend in the medial longitudinal fasciculus to arborize around the cells of the nuclei of the oculomotor nerve. Fibres from the lateral vestibular nucleus also pass via the vestibulospinal tract, to anterior horn cells at many levels in the spinal cord, in order to co-ordinate head and trunk movements.

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# Vestibular system The vestibular system, or balance system, is the sensory system that provides the dominant input about our movement and orientation in space. Together with the cochlea, the auditory organ, it is situated in the vestibulum in the inner ear (Figure 1). As our movements consist of rotations and translations, the vestibular system comprises two components: the semicircular canals, which indicate rotational movements; and the Otoliths, which indicate linear translations. The vestibular system sends signals primarily to the neural structures that control our eye movements, and to the muscles that keep us upright. The projections to the former provide the anatomical basis of the vestibulo-ocular reflex, which is required for clear vision; and the projections to the muscles that control our posture are necessary to keep us upright. Our world has three spatial dimensions. Accordingly, our vestibular system contains three semicircular canals in each labyrinth. They are approximately orthogonal to each other, and are called The canals are cleverly arranged in such a way that each canal on the left side has an almost parallel counterpart on the right side. Each of these three pairs works in a push-pull fashion: when one canal is stimulated, its corresponding partner on the other side is inhibited, and vice versa. This push-pull system allows us to sense all directions of rotation: while the right horizontal canal gets stimulated during head rotations to the right (Fig 2), the left horizontal canal gets stimulated (and thus predominantly signals) by head rotations to the left. The vestibular system needs to be fast: if we want clear vision, head movements need to be compensated almost immediately. Otherwise our vision corresponds to a photograph taken with a shaky hand. To achieve clear vision, signals from the semicircular canals are sent as directly as possible to the eye muscles. This direct connection involves only three neurons, and is correspondingly called Three-neuron-arc (Fig 3). Using these direct connections, eye movements lag the head movements by less than 10 ms, one of the fastest reflexes in the human body. The automatic generation of eye movements from movements of the head is called vestibulo-ocular reflex, or short VOR. This reflex, combined with the push-pull principle described above, forms the physiological basis of the Rapid head impulse test or Halmagyi-Curthoys-test: when the function of your right balance system is reduced by a disease or by an accident, quick head movements to the right cannot be sensed properly any more. As a consequence, no compensatory eye movements are generated, and the patient cannot fixate a point in space during this rapid head movement. Another way of testing the VOR response is to attempt to induce nystagmus (compensatory eye movements in the absence of head motion) by pouring cold or warm water into the ear. The mechanics of the semicircular canals can be described by a damped oscillator. If we designate the deflection of the cupula with <math> heta</math>, and the head velocity with <math>\dot q</math>, the cupula deflection is approximately α is a proportionality factor, and s corresponds to the frequency. For humans, the time constants T1 and T2 are approximately 3 ms and 5 s, respectively. As a result, for typical head movements, which cover the frequency range of 0.1 Hz and 10 Hz, the deflection of the cupula is approximately proportional to the head-velocity (!). This is very useful, since the velocity of the eyes must be opposite to the velocity of the head in order to have clear vision. Signals from the vestibular system also project to the Cerebellum (where they are used to keep the VOR working, a task usually referred to as Learning or Adaptation) and to different areas in the cortex. The projections to the cortex are spread out over different areas, and their implications are currently not clearly understood. While the semicircular canals respond to rotations, the otoliths sense linear accelerations. We have two on each side, one called Utricle, the other Saccule. Figure 4C shows a cross section through an otolith: the otoconia crystals in the Otoconia Layer (Fig. 4, top layer) rest on a viscous gel layer, and are heavier than their surroundings. Therefore they get displaced during linear acceleration, which in turn deflects the Hair cells (Fig. 4, bottom layer) and thus produces a sensory signal. Most of the utricular signals elicit eye movements, while the majority of the saccular signals projects to muscles that control our posture. While the interpretation of the rotation signals from the semicircular canals is straightforward, the interpretation of otolith signals is more difficult: since gravity is equivalent to a constant linear acceleration, we somehow have to distinguish otolith signals that are caused by linear movements from such that are caused by gravity. We can do that quite well, but the neural mechanisms underlying this separation are not yet fully understood. Diseases of the vestibular system can take different forms, and usually induce vertigo and instability, often accompanied by nausea. The most common ones are Vestibular neuritis, a related condition called Labyrinthitis, and BPPV. In addition, the function of the vestibular system can be affected by tumors on the cochleo-vestibular nerve, an infarct in the brain stem or in cortical regions related to the processing of vestibular signals, and cerebellar atrophy. Less severe, but often also with large consequences, is vertigo caused by the intake of large amounts of alcohol. BPPV, which is short for Benign Paroxysmal Positional Vertigo, is probably caused by pieces that have broken off from the Otoliths, and have slipped into one of the semicircular canals. In most cases it is the posterior canal that is affected. In certain head positions, these particles push on the cupula of the canal affected, which leads to dizziness, vertigo and nystagmus.

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# Vestibulo-ocular reflex The vestibulo-ocular reflex (VOR) or oculovestibular reflex is a reflex eye movement that stabilizes images on the retina during head movement by producing an eye movement in the direction opposite to head movement, thus preserving the image on the center of the visual field. For example, when the head moves to the right, the eyes move to the left, and vice versa. Since slight head movements are present all the time, the VOR is very important for stabilizing vision: patients whose VOR is impaired find it difficult to read using print, because they cannot stabilize the eyes during small head tremors. The VOR reflex does not depend on visual input and works even in total darkness or when the eyes are closed. The "gain" of the VOR is defined as the change in the eye angle divided by the change in the head angle during the head turn. If the gain of the VOR is wrong (different than 1)—for example, if eye muscles are weak, or if a person puts on a new pair of eyeglasses—then head movements result in image motion on the retina, resulting in blurred vision. Under such conditions, motor learning adjusts the gain of the VOR to produce more accurate eye motion. This is what is referred to as VOR adaptation. The main neural circuit for the horizontal VOR is fairly simple. Vestibular nuclei in the brainstem receive signals related to head movement from the Scarpa's ganglion located on CN VIII, or the vestibular nerve. From this Vestibular nuclei excitatory fibers cross to the contralateral CN VI nerve nucleus. There they synapse with 2 additional pathways. One projects directly to the lateral rectus of eye. Another nerve tract projects from the CN VI nucleus by the abducens internuclear interneurons or abducens interneurons to the oculomotor nuclei, which contain motorneurons that drive eye muscle activity, specifically activating the medial rectus muscles of the eye. Another pathway directly projects from the vestibular nucleus through the ascending tract of Dieters to the ipsilateral medial rectus motoneurons. In addition there are inhibitory vestibular pathways to the ipsilateral CN VI nucleus. However no direct vestibular neuron medial rectus motoneuron pathway exists. The cerebellum is essential for motor learning to correct the VOR in order to ensure accurate eye movements. Motor learning in the VOR is in many ways analogous to classical eyeblink conditioning, since the circuits are homologous and the molecular mechanisms are similar.

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# Vestibulocochlear dysfunction progressive familial Vestibulocochlear dysfunction progressive familial, known also as familial progressive vestibulocochlear dysfunction is an autosomal dominant disease that results in sensorineural hearing loss and vestibular areflexia. Patients report feelings of vague dissiness, blurred vision, dysequilibrium in the dark, and progressive hearing impairment. The disease is an inherited autosomal dominant disease, but the physiological cause of the dysfunction is still unclear. An acidophyllic mucopolysaccharide-containing substance was discovered, especially in cochleas, Otolithic organs|maculas, and crista ampullaris of patients with DFNA9 (a chromosome locus), as well as severe degeneration of vestibular and cochlear sensory axons and dendrites. It is suggested that the mucopolysaccharide deposit could cause strangulation of nerve endings. The Otolithic organs|maculas and crista ampullaris are what allow for non-visual sensation of head movements. The crista ampullaris resides in the semicircular canals of the inner ear and detects angular acceleration, while the maculas are housed within the vestibule of the inner ear and detect linear acceleration. When affected, these organs can lead to vertigo and nausea because the body would always feel off-balance.

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# Vestibulocochlear nerve The vestibulocochlear nerve (also known as the auditory or acoustic nerve) is the eighth of twelve cranial nerves, and is responsible for transmitting sound and equilibrium (balance) information from the inner ear to the brain. This nerve, along which the sensory cells (the hair cells) of the inner ear transmit information to the brain. It consists of the cochlear nerve, carrying information about hearing, and the vestibular nerve, carrying information about balance. It emerges from the medulla oblongata and enters the inner skull via the internal acoustic meatus (or internal auditory meatus) in the temporal bone, along with the facial nerve. The eighth cranial nerve has two prime roles. It is needed to convey information of vestibular sensation - that is, the position and movement of the head. Secondly, it is used for hearing. The nerve splits into two large divisions - the cochlear nerve and the vestibular nerve. Broadly speaking, the cochlear nerve innervates the cochlea, while the vestibular nerve goes to the vestibular apparatus. How hearing information is coded on the nerve has long been a matter of scientific debate between two competing theories, a place theory and a rate theory. Some older texts call the nerve the acoustic or auditory nerve , but these terms have fallen out of widespread use because they fail to recognize the nerve's role in the vestibular system. Vestibulocochlear nerve is therefore preferred by most.

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# Vestibulospinal tract The vestibulospinal tract is one of the descending spinal tracts of the ventromedial pathway. It originates from the vestibular nuclei of the medulla, which conducts information from the vestibular labyrinth in the inner ear. The medial part of the vestibulospinal tract project bilaterally down the spinal cord and triggers the cervical spinal circuits, controlling a right position of the head and neck. The lateral part of the vestibulospinal tract projects ipsilateral down to the lumbar region. There it helps to maintain an upright and balanced posture by stimulating extensor motor neurons in the legs.

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# Vestigiality Vestigiality describes homologous characters of organisms which have lost all or most of their original function in a species through evolution. These may take various forms such as anatomical structures, behaviors and biochemical pathways. Some of these disappear early in embryonic development, but others are retained in adulthood. All such characters can in turn can be traced to the genes which code for such characters. Some genes no longer code for anything, and can thus be said vestigial themselves, or junk DNA. Vestigial structures are often called vestigial organs, although many of them are not actually organs. These are typically in a degenerate, atrophied, or rudimentary condition, and tend to be much more variable than similar parts. Although structures usually called "vestigial" are largely or entirely functionless, a vestigial structure may retain lesser functions or develop minor new ones. However, care must be taken not to apply the label of vestigiality to exaptations, in which a structure originally used for one purpose is modified for a new one. For example, the wings of penguin would not be vestigial, as they have been modified for a substantial new purpose (underwater locomotion), while those of an emu would be, as they have no major purpose anymore (not even for display as in ostriches). Vestigial characters range on a continuum from detrimental through neutral to marginally useful. Some may be of some limited utility to an organism but still degenerate over time; the important point is not that they are without utility, but that they do not confer a significant enough advantage in terms of fitness to avoid the random force of disorder that is mutation. It is difficult however to say that a vestigial character is detrimental to the organism in the long term - the future is unpredictable, and that which is of no use in the present may develop into something useful in the future. Vestigiality is one of several lines of evidence for biological evolution. Vestigial structures have been noticed since ancient times, and the reason for their existence was long speculated upon before Darwinian evolution provided a widely-accepted explanation. In the 4th century BC, Aristotle was one of the earliest writers to comment, in his History of Animals, on the vestigial eyes of moles, calling them "stunted in development". However, only in recent centuries have anatomical vestiges become a subject of serious study. In 1798, Étienne Geoffroy Saint-Hilaire noted on vestigial structures: His colleague, Jean-Baptiste Lamarck, named a number of vestigial structures in his 1809 book Philosophie Zoologique. Lamarck noted "Olivier's Spalax, which lives underground like the mole, and is apparently exposed to daylight even less than the mole, has altogether lost the use of sight: so that it shows nothing more than vestiges of this organ." Charles Darwin was very familiar with the concept of vestigial structures, though the term for them did not yet exist. He listed a number of them in The Descent of Man, including the muscles of the ear, wisdom teeth, the appendix, the tail bone, body hair, and the semilunar fold in the corner of the eye. Darwin also noted, in The Origin of Species, that a vestigial structure could be useless for its primary function, but still retain secondary anatomical roles: "An organ serving for two purposes, may become rudimentary or utterly aborted for one, even the more important purpose, and remain perfectly efficient for the other.... [A]n organ may become rudimentary for its proper purpose, and be used for a distinct object." Darwin however still often refers to the 'use and disuse' of structures having some role in heredity, with inheritance of acquired characters being treated as an important aspect besides the central force of natural selection. In the final chapter of The Origin of Species he describes the process: "This has been effected chiefly through the natural selection of numerous successive, slight, favourable variations; aided in an important manner by the inherited effects of the use and disuse of parts". In 1893, Robert Wiedersheim published a list of 86 human organs that had, in his words, "lost their original physiological significance". Theorizing that they were vestiges of evolution, he called them "vestigial". Since his time, the function of some of these structures has been discovered, while other anatomical vestiges have been unearthed, making the list primarily of interest as a record of the knowledge of human anatomy at the time. Later versions of Wiedersheim's list were expanded to as many as 180 human "vestigial organs". This is why the zoologist Newman stated in the Scopes Monkey Trial that "There are, according to Wiedersheim, no less than 180 vestigial structures in the human body, sufficient to make of a man a veritable walking museum of antiquities." Vestigial structures are often homologous to structures that are functioning normally in other species. Therefore, vestigial structures can be considered evidence for evolution, the process by which beneficial heritable traits arise in populations over an extended period of time. The existence of vestigial traits can be attributed to changes in the environment and behavior patterns of the organism in question. As the function of the trait is no longer beneficial for survival, the likelihood that future offspring will inherit the "normal" form of it decreases. In some cases the structure becomes detrimental to the organism (for example the eyes of a mole can become infected ). In many cases the structure is of no direct harm, yet all structures require extra energy in terms of development, maintenance, and weight, and are also a risk in terms of disease (e.g. infection, cancer), providing some selective pressure for the removal of parts that do not contribute to an organism's fitness. A structure that is not harmful will obviously take longer to be 'phased out' than one that is. However, some vestigial structures may persist due to limitations in development, such that complete loss of the structure could not occur without major alterations of the organism's developmental pattern, and such alterations would likely produce numerous negative side-effects. The toes of many animals such as horses, who stand on a single toe, are still evident in a vestigial form and may become evident, although rarely, from time to time in individuals. The vestigial versions of the structure can be compared to the original version of the structure in other species in order to determine the homology of a vestigial structure. Homologous structures indicate common ancestry with those organisms that have a functional version of the structure. Vestigial traits are still considered adaptations. This is because an adaptation is defined as a trait that has been favored by natural selection. Adaptations therefore need not be adaptive, as long as they were at some point. In whales and other cetaceans, one can find small vestigial leg bones deeply buried within the back of the body. These are remnants of their land-living ancestors' legs. Many whales also have undeveloped, unused, pelvis bones in the anterior part of their torsos. The eyes of certain cavefish and salamanders are vestigial, as they no longer allow the organism to see, and are remnants of their ancestors' functional eyes. Boas and replace.pys have vestigial pelvis remanents which are externally visible as two small anal spurs on each side of the cloaca. These spurs are sometimes used in copulation, but are not essential, as no colubroid snake (the vast majority of species) possesses these remnants. Furthermore, in most snakes the left lung is greatly reduced or absent. Amphisbaenians, which independently evolved limblessness, also retain vestiges of the pelvis as well as the pectoral girdle, and have lost their right lung. Crabs have small tails tucked between their rear legs that are probably vestigial, as they are no longer in use. The working version of these tails can be found in their close crustacean relative, the lobster.[citation needed] Certain species of moths (for example the Gypsy moth) have females that, although flightless, still carry small wings. These wings have no use, and are vestigial to the versions in species whose females can fly.[citation needed] Human vestigiality is related to human evolution, and includes a variety of characters occurring in the human species. Many of these are also vestigial in other primates and related animals. The relative usefulness of these characters is a subject of debate. Structures that have been or still are considered vestigial no longer include the vermiform appendix, which produces good bacteria. Darwin, Charles (1871). The Descent of Man, and Selection in Relation to Sex. John Murray: London. the coccyx, or tailbone (a remnant of a lost tail); the plica semilunaris on the inside corner of the eye (a remnant of the nictitating membrane); and, as pictured, muscles in the ear and other parts of the body. Humans also bear some vestigial behaviors and reflexes. The formation of goose bumps in humans under stress is a vestigial reflex; its function in human ancestors was to raise the body's hair, making the ancestor appear larger and scaring off predators. Raising the hair is also used to trap an extra layer of air, keeping an animal warm. This reflex formation of goosebumps when cold is not vestigial in humans, but the reflex to form them under stress is. Infants are also able to support their own weight while hanging from a rod, responding to certain tacticle stimuli. An ancestral primate would have had sufficient body hair for an infant to cling to, allowing its mother to escape from danger, such as climbing up a tree in the presence of a predator. There are also vestigial molecular structures in humans, which are no longer in use but may indicate common ancestry with other species. One example of this is L-gulonolactone oxidase, a gene, that is functional in most other mammals, which produces a enzyme that can make vitamin C. A mutation inactivated the gene in an ancestor of the current group of primates, and it now remains in the human genome as a vestigial sequence called a pseudogene. Vestigial structures are not only found in animals; plants also are known to have vestigial parts. Dandelions and other asexually reproducing plants produce unneeded flower petals. These petals were once used to attract pollinating insects, but are now no longer needed.[citation needed]

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/index.php/Veterans_health_information_systems_and_technology_architecture

# Veterans health information systems and technology architecture The Veterans Health Information Systems and Technology Architecture (VistA) is an enterprise-wide information system built around an electronic health record, used throughout the United States Department of Veterans Affairs (VA) medical system, known as the Veterans Health Administration (VHA). By 2001, the VHA was the largest single medical system in the United States, providing care to 4 million veterans, employing 180,000 medical personnel and operating 163 hospitals, over 800 clinics and 135 nursing homes. By 2008, VA was providing electronic health records capability for over 8.9 Million active patients. VistA is thereby one of the most widely used EHRs in the world. The Department of Veterans Affairs (VA) has had automated data processing systems within its medical facilities since before 1985, beginning with the Decentralized Hospital Computer Program (DHCP) information system, including extensive clinical and administrative capabilities. In 1995, DHCP was enshrined as a recipient of the Computerworld Smithsonian Award for best use of Information Technology in Medicine. VistA supports both ambulatory and inpatient care, and includes several significant enhancements to the original DHCP system. The most significant is a graphical user interface known as the Computerized Patient Record System (CPRS) for clinicians released in 1997. In addition, VistA now includes computerized order entry, bar code medication administration, electronic prescribing and clinical guidelines. CPRS provides a client-server interface for health care providers to review and update a patient's electronic medical record. This includes the ability to place orders, including medications, special procedures, x-rays, patient care nursing orders, diets, and laboratory tests. CPRS is flexible enough to be implemented in a wide variety of settings for a broad spectrum of health care workers and provides a consistent, event-driven, Windows-style interface. For its development of VistA, the Department of Veterans Affairs (VA) / Veterans Health Administration (VHA) was named the recipient of the prestigious Innovations in American Government Award presented by the Ash Institute of the John F. Kennedy School of Government at Harvard University in July, 2006. The adoption of VistA has allowed the VA to achieve a pharmacy prescription accuracy rate of 99.997%, and the VA outperforms most public sector hospitals on a variety of criteria, enabled by the implementation of VistA. The VistA system is public domain software, available through the Freedom Of Information Act directly from the VA website, or through a growing network of distributors. The VistA Software Alliance is a non-profit trade organization that both promotes the widespread adoption of versions of VistA for provider environments. VistA was developed using the M or MUMPS language/database. The VA currently runs a majority of VistA systems on InterSystems Caché. VistA can also run on GT.M, an open source database engine for Linux and Unix computers. Although initially separate releases, publicly available VistA distributions are now often bundled with the database in an integrated package. This has considerably eased installation. The Veterans Administration has also developed VistA Imaging, a coordinated system for communicating with PACS (radiology imaging) systems and for integrating others types of image-based information, such as EKGs, pathology slides, and scanned documents, into the VistA electronic medical records system. This type of integration of information into a medical record is critical to efficient utilization. VistA Imaging has been made freely available in the public domain for private/public hospital use through the Freedom of Information Act. It is available through the Department of Veteran's Affairs software request office. The VistA electronic healthcare record has been widely credited for reforming the VA healthcare system, improving safety and efficiency substantially. The remarkable results have spurred a national impetus to adopt electronic medical records similar to VistA nationwide. VistA Web collectively describes a set of protocols that in 2007 was being developed and used by the VHA to transfer data (from VistA) between hospitals and clinics within the pilot project. This is the first effort to view a single patient record so that VistA becomes truly interoperable among the 128 sites running VistA today. BHIE enables real-time sharing of electronic health information between DoD and VA for shared patients of allergy, outpatient pharmacy, demographic, laboratory, and radiology data. This became a priority during the Second Iraq War, when a concern for the transition of healthcare for soldiers as they transferred from active military status to veteran status became a national focus of attention. Clinical Data Repository/ Health Data Repository or CHDR supports interoperability between DoD's Clinical Data Repository (CDR) & VA's Health Data Repository (HDR). Represents the development of interoperability between the DoD Clinical Data Repository (CDR) and Health VA Data Repository (HDR). It leverages DoD AHLTA experiences and lessons learned and provides the cornerstone for interoperability between electronic health records for DoD and VA The first phase will include bidirectional real time exchange of computable pharmacy, allergy, demographic and laboratory data. In Phase 2 additional Drug – Drug interaction checking and Drug – Drug Allergy interaction checking will be added. As of March 2007, Completed deployment at El Paso, Augusta, Pensacola, Puget Sound, Chicago, San Diego, and Las Vegas. The combination of VistA and the interoperable projects listed above in the VA/DoD systems will continue to expand to meet the objectives of President Bush's statements that all citizens will have an electronic record by 2014. The VHA has also started a pilot project, known as HealtheVet (HeV) that is the next generation of VistA. Preliminary plans have begun for the vision of HeV that evolve around moving away from the MUMPS and Delphi coding and towards more state of the art programming languages and enhanced functionality. MyHealtheVet is another initiative that allows veterans to access, and create a copy of, their health records online. A national release of the project is underway. This will allow veterans to port their health records to institutions outside the VA health system or keep a personal copy of their health records, a Personal Health Record (PHR). Because of the success of these programs, a national move to standardize healthcare data transmission across the country was started. Text based information exchange is standardized using a protocol called HL7 (Health Level 7), which is approved by the American National Standards Institute. DICOM is an international image communications protocol standard. VistA is compliant with both. VistA has been interfaced with commercial off-the-shelf products. Standards and protocols used by VA are consistent with current industry standards and includine: HL7, DICOM, and other protocols. Under the Freedom of Information Act (FOIA), the VistA system, the CPRS interface (a CPOE), and unlimited ongoing updates (500-600 patches per year) are provided as public domain (but not free and open source) software. This was done by the US government in an effort to make VistA available as a low cost electronic medical record system (EMR / EHR) for non-governmental hospitals and other healthcare entities. It has been adopted by companies such as OHUM,Blue Cliff, DSS, Inc., and Medsphere, to a variety of environments, from individual practices to clinics to hospitals, to regional healthcare co-ordination between far-flung islands. In addition, VistA has been adopted within similar provider environments worldwide. Universities, such as UC Davis and Texas Tech implemented these systems. VistA as other EMR/EHR systems can be interfaced with other healthcare databases not initially used by the VA system, including billing software, lab databases, and images databases (radiology, for example). There have been many champions of VistA as the electronic healthcare record system for a universal healthcare plan. VistA can act as a standalone system, allowing self-contained management and retention of healthcare data within an institution. Combined with BHIE (or other data exchange protocol) is can be part of a peer-to-peer model of universal healthcare. It is also scalable to be used as a centralized system (allowing regional or even national centralization of healthcare records). It is, therefore, the electronic records system most adapatable to a variety of healthcare models. In addition to the unwavering support of congressional representatives such as Congressman Sonny Montgomery of Mississippi, numerous IT specialists, physicians, and other healthcare professionals have donated significant amounts of time in adapting the VistA system for use in non-governmental healthcare settings. The ranking member of the House Veterans Affairs Committee's Oversight and Investigation Subcommittee, Rep. Ginny Brown-Waite of Florida, recommended that the Department of Defense (DOD) adopt VA's VistA system following accusations of inefficiencies in the DOD healthcare system. The DOD hospitals use Armed Forces Health Longitudinal Technology Application (AHLTA) which has not been as successful as VistA and has not been widely adapted to non-military environments, as VistA has. In November 2005, the U.S. Senate passed the Wired for Health Care Quality Act, introduced by Sen. Enzi of Wyoming with 38 co-sponsors, that would require the government to use the VA's technology standards as a basis for national standards allowing all health care providers to communicate with each other as part of a nationwide health information exchange. The legislation would also authorize $280 million in grants, which would help persuade reluctant providers to invest in the new technology. There has been no action on the bill since December 2005. Two similar House bills were introduced in late 2005 and early 2006; no action has been taken on either of them, either.

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/index.php/Veyron-s

# Veyron-s Veyron-S is a brandname for herbal nutritional supplement manufactured by Veyron Enterprise of Hong Kong. It is marketed as a herbal remedy to help men with erectile dysfunction problems. As a supplement, it is not approved by the FDA to diagnose, treat, or prevent any condition of disease. In January 2007, Veyron-S has been tested by Hong Kong Standards and Testing Centre.

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/index.php/Viaspan

# Viaspan ## Contents Viaspan®, also known as University of Wisconsin solution (UW solution), was the first solution thoughtfully designed for use in organ transplantation, and became the first intracellular-like preservation medium. Developed by Folkert Belzer and James Southard for pancreas preservation in the late 1980s, the solution soon displaced EuroCollins solution as the preferred medium for cold storage of livers and kidneys, as well as pancreas. The solution has also been used for hearts and other organs. Viaspan remains what is often called the gold standard for organ preservation , despite the development of other solutions that are in some respects superior .

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/index.php/Vibration

# Vibration Vibration refers to mechanical oscillations about an equilibrium point . The oscillations may be periodic such as the motion of a pendulum or random such as the movement of a tire on a gravel road. Vibration is occasionally "desirable". For example the motion of a tuning fork, the reed in a woodwind instrument or harmonica, or the cone of a loudspeaker is desirable vibration, necessary for the correct functioning of the various devices. More often, vibration is undesirable, wasting energy and creating unwanted sound -- noise. For example, the vibrational motions of engines, electric motors, or any mechanical device in operation are typically unwanted. Such vibrations can be caused by imbalances in the rotating parts, uneven friction, the meshing of gear teeth, etc. Careful designs usually minimize unwanted vibrations. The study of sound and vibration are closely related. Sound, or "pressure waves", are generated by vibrating structures (e.g. vocal cords); these pressure waves can also induce the vibration of structures (e.g. ear drum). Hence, when trying to reduce noise it is often a problem in trying to reduce vibration. Free vibration occurs when a mechanical system is set off with an initial input and then allowed to vibrate freely. Examples of this type of vibration are pulling a child back on a swing and then letting go or hitting a tuning fork and letting it ring. The mechanical system will then vibrate at one or more of its "natural frequencies" and damp down to zero. Forced vibration is when an alternating force or motion is applied to a mechanical system. Examples of this type of vibration include a shaking washing machining due to an imbalance, transportation vibration (caused by truck engine, springs, road, etc), or the vibration of a building during an earthquake. In forced vibration the frequency of the vibration is the frequency of the force or motion applied, with order of magnitude being dependent on the actual mechanical system. Vibration testing is accomplished by introducing a forcing function into a structure, usually with some type of shaker. Generally, one or more points on the structure are kept at a specified vibration level. Two typical types of vibration tests performed are random- and sine test. Sine tests are performed to survey the structural response of the device under test (DUT). A random test is generally conducted to replicate a real world environment. The fundamentals of vibration analysis can be understood by studying the simple mass-spring-damper model. Indeed, even a complex structure such as an automobile body can be modeled as a "summation" of simple mass-spring-damper models. The mass-spring-damper model is an example of a simple harmonic oscillator. The mathematics used to describe its behavior is identical to other simple harmonic oscillators such as the RLC circuit. Note: In this article the step by step mathematical derivations will not be included, but will focus on the major equations and concepts in vibration analysis. Please refer to the references at the end of the article for detailed derivations. To start the investigation of the mass-spring-damper we will assume the damping is negligible and that there is no external force applied to the mass (i.e. free vibration). The force applied to the mass by the spring is proportional to the amount the spring is stretched "x" (we will assume the spring is already compressed due to the weight of the mass). The proportionality constant, k, is the stiffness of the spring and has units of force/distance (e.g. lbf/in or N/m) If we assume that we start the system to vibrate by stretching the spring by the distance of A and letting go, the solution to the above equation that describes the motion of mass is: This solution says that it will oscillate with simple harmonic motion that has an amplitude of A and a frequency of <math>f_n.</math> The number <math>f_n</math> is one of the most important quantities in vibration analysis and is called the undamped natural frequency. For the simple mass-spring system, <math>f_n</math> is defined as: Note: Angular frequency <math>\omega</math> (<math>\omega=2 \pi f</math>) with the units of radians per second is often used in equations because it simplifies the equations, but is normally converted to "standard" frequency (units of Hz or equivalently cycles per second) when stating the frequency of a system. If you know the mass and stiffness of the system you can determine the frequency at which the system will vibrate once it is set in motion by an initial disturbance using the above stated formula. Every vibrating system has one or more natural frequencies that it will vibrate at once it is disturbed. This simple relation can be used to understand in general what will happen to a more complex system once we add mass or stiffness. For example, the above formula explains why when a car or truck is fully loaded the suspension will feel "softer" than unloaded because the mass has increased and therefore reduced the natural frequency of the system. These formulas describe the resulting motion, but they do not explain why the system oscillates. The reason for the oscillation is due to the conservation of energy. In the above example we have extended the spring by a value of A and therefore have stored potential energy (<math> frac {1}{2} k x^2</math>) in the spring. Once we let go of the spring, the spring tries to return to its un-stretched state and in the process accelerates the mass. At the point where the spring has reached its un-stretched state it no longer has energy stored, but the mass has reached its maximum speed and hence all the energy has been transformed into kinetic energy (<math> frac {1}{2} m v^2</math>). The mass then begins to decelerate because it is now compressing the spring and in the process transferring the kinetic energy back to its potential. This transferring back and forth of the kinetic energy in the mass and the potential energy in the spring causes the mass to oscillate. In our simple model the mass will continue to oscillate forever at the same magnitude, but in a real system there is always something called damping that dissipates the energy and therefore the system eventually bringing it to rest. We now add a "viscous" damper to the model that outputs a force that is proportional to the velocity of the mass. The damping is called viscous because it models the effects of an object within a fluid. The proportionality constant c is called the damping coefficient and has units of Force over velocity (lbf s/ in or N s/m). The solution to this equation depends on the amount of damping. If the damping is small enough the system will still vibrate, but eventually, over time, will stop vibrating. This case is called underdamping--this case is of most interest in vibration analysis. If we increase the damping just to the point where the system no longer oscillates we reach the point of critical damping (if the damping is increased past critical damping the system is called overdamped). The value that the damping coefficient needs to reach for critical damping in the mass spring damper model is: To characterize the amount of damping in a system a ratio called the damping ratio (also known as damping factor and % critical damping) is used. This damping ratio is just a ratio of the actual damping over the amount of damping required to reach critical damping. The formula for the damping ratio (<math>\zeta </math>) of the mass spring damper model is: The value of X, the initial magnitude, and <math> \phi </math>, the phase shift, are determined by the amount the spring is stretched. The formulas for these values can be found in the references. The major points to note from the solution are the exponential term and the cosine function. The exponential term defines how quickly the system "damps" down – the larger the damping ratio, the quicker it damps to zero. The cosine function is the oscillating portion of the solution, but the frequency of the oscillations is different from the undamped case. The frequency in this case is called the "damped natural frequency", <math> f_d </math>, and is related to the undamped natural frequency by the following formula: The damped natural frequency is less than the undamped natural frequency, but for many practical cases the damping ratio is relatively small and hence the difference is negligible. Therefore the damped and undamped description are often dropped when stating the natural frequency (e.g. with 0.1 damping ratio, the damped natural frequency is only 1% less than the undamped). The plots to the side present how 0.1 and 0.3 damping ratios effect how the system will "ring" down over time. What is often done in practice is to experimentally measure the free vibration after an impact (for example by a hammer) and then determine the natural frequency of the system by measuring the rate of oscillation as well as the damping ratio by measuring the rate of decay. The natural frequency and damping ratio are not only important in free vibration, but also characterize how a system will behave under forced vibration. In this section we will look at the behavior of the spring mass damper model when we add a harmonic force in the form below. A force of this type could, for example, be generated by a rotating imbalance. The result states that the mass will oscillate at the same frequency, f, of the applied force, but with a phase shift <math> \phi </math>. The plot of these functions, called "the frequency response of the system", presents one of the most important features in forced vibration. In a lightly damped system when the forcing frequency nears the natural frequency (<math>r pprox 1 </math>) the amplitude of the vibration can get extremely high. This phenomenon is called resonance (subsequently the natural frequency of a system is often referred to as the resonant frequency). In rotor bearing systems any rotational speed that excites a resonant frequency is referred to as a critical speed. If resonance occurs in a mechanical system it can be very harmful-- leading to eventual failure of the system. Consequently, one of the major reasons for vibration analysis is to predict when this type of resonance may occur and then to determine what steps to take to prevent it from occurring. As the amplitude plot shows, adding damping can significantly reduce the magnitude of the vibration. Also, the magnitude can be reduced if the natural frequency can be shifted away from the forcing frequency by changing the stiffness or mass of the system. If the system cannot be changed, perhaps the forcing frequency can be shifted (for example, changing the speed of the machine generating the force). Resonance is simple to understand if you view the spring and mass as energy storage elements--with the mass storing kinetic energy and the spring storing potential energy. As discussed earlier, when the mass and spring have no force acting on them they transfer energy back forth at a rate equal to the natural frequency. In other words, if energy is to be efficiently pumped into both the mass and spring the energy source needs to feed the energy in at a rate equal to the natural frequency. Applying a force to the mass and spring is similar to pushing a child on swing, you need to push at the correct moment if you want the swing to get higher and higher. As in the case of the swing, the force applied does not necessarily have to be high to get large motions; the pushes just need to keep adding energy into the system. The damper, instead of storing energy, dissipates energy. Since the damping force is proportional to the velocity, the more the motion the more the damper dissipates the energy. Therefore a point will come when the energy dissipated by the damper will equal the energy being fed in by the force. At this point, the system has reached its maximum amplitude and will continue to vibrate at this level as long as the force applied stays the same. If no damping exists, there is nothing to dissipate the energy and therefore theoretically the motion will continue to grow on into infinity. In a previous section only a simple harmonic force was applied to the model, but this can be extended considerably using two powerful mathematical tools. The first is the Fourier transform that takes a signal as a function of time (time domain) and breaks it down into its harmonic components as a function of frequency (frequency domain). For example, let us apply a force to the mass-spring-damper model that repeats the following cycle--a force equal to 1 newton for 0.5 second and then no force for 0.5 second. This type of force has the shape of a 1 Hz square wave. The Fourier transform of the square wave generates a frequency spectrum that presents the magnitude of the harmonics that make up the square wave (the phase is also generated, but is typically of less concern and therefore is often not plotted). The Fourier transform can also be used to analyze non-periodic functions such as transients (e.g. impulses) and random functions. With the advent of the modern computer the Fourier transform is almost always computed using the Fast Fourier Transform (FFT) computer algorithm in combination with a window function. In the case of our square wave force, the first component is actually a constant force of 0.5 newton and is represented by a value at "0" Hz in the frequency spectrum. The next component is a 1 Hz sine wave with an amplitude of 0.64. This is shown by the line at 1 Hz. The remaining components are at odd frequencies and it takes an infinite amount of sine waves to generate the perfect square wave. Hence, the Fourier transform allows you to interpret the force as a sum of sinusoidal forces being applied instead of a more "complex" force (e.g. a square wave). In the previous section, the vibration solution was given for a single harmonic force, but the Fourier transform will in general give multiple harmonic forces. The second mathematical tool, "the principle of superposition", allows you to sum the solutions from multiple forces if the system is linear. In the case of the spring-mass-damper model, the system is linear if the spring force is proportional to the displacement and the damping is proportional to the velocity over the range of motion of interest. Hence, the solution to the problem with a square wave is summing the predicted vibration from each one of the harmonic forces found in the frequency spectrum of the square wave. We can view the solution of a vibration problem as an input/output relation--where the force is the input and the output is the vibration. If we represent the force and vibration in the frequency domain (magnitude and phase) we can write the following relation: <math>H(\omega)</math> is called the frequency response function (also referred to the transfer function, but not technically as accurate) and has both a magnitude and phase component (if represented as a complex number, a real and imaginary component). The magnitude of the frequency response function (FRF) was presented earlier for the mass-spring-damper system. For example, let us calculate the FRF for a mass-spring-damper system with a mass of 1 kg, spring stiffness of 1.93 N/mm and a damping ratio of 0.1. The values of the spring and mass give a natural frequency of 7 Hz for this specific system. If we apply the 1 Hz square wave from earlier we can calculate the predicted vibration of the mass. The figure illustrates the resulting vibration. It happens in this example that the fourth harmonic of the square wave falls at 7 Hz. The frequency response of the mass-spring-damper therefore outputs a high 7 Hz vibration even though the input force had a relatively low 7 Hz harmonic. This example highlights that the resulting vibration is dependent on both the forcing function and the system that the force is applied. The figure also shows the time domain representation of the resulting vibration. This is done by performing an inverse Fourier Transform that converts frequency domain data to time domain. In practice, this is rarely done because the frequency spectrum provides all the necessary information. The frequency response function (FRF) does not necessarily have to be calculated from the knowledge of the mass, damping, and stiffness of the system, but can be measured experimentally. For example, if you apply a known force and sweep the frequency and then measure the resulting vibration you can calculate the frequency response function and then characterize the system. This technique is used in the field of experimental modal analysis to determine the vibration characteristics of a structure. The simple mass-spring damper model is the foundation of vibration analysis, but what about more complex systems? The mass-spring-damper model described above is called a single degree of freedom (DOF) model since we have assumed the mass only moves up and down. In the case of more complex systems we need to discretize the system into more masses and allow them to move in more than one direction--adding degrees of freedom. The major concepts of multiple degrees of freedom (MDOF) can be understood by looking at just a 2 degree of freedom model as shown in the figure. m_2 \ddot{x_2} - { c_2 } \dot{x_1}+ { (c_2+c_3) } \dot{x_2} - { c_3 } \dot{x_3} - { k_2 } x_1+ { (k_2+k_3) } x_2 -{ k_3 } x_3= f_2 \! </math> where <math>egin{bmatrix}M\end{bmatrix}</math>, <math>egin{bmatrix}C\end{bmatrix}</math>, and <math>egin{bmatrix}K\end{bmatrix}</math> are symmetric matrices referred respectively as the mass, damping, and stiffness matrices. The matrices are NxN square matrices where N is the number of degrees of freedom of the system. In the following analysis we will consider the case where there is no damping and no applied forces (i.e. free vibration). The solution of a viscously damped system is somewhat more complicated and is shown in Maia, Silva. . Note: Using the exponential solution of <math> egin{Bmatrix} X\end{Bmatrix}e^{i\omega t}</math> is a mathematical trick used to solve linear differential equations. If we use Euler's formula and take only the real part of the solution it is the same cosine solution for the 1 DOF system. The exponential solution is only used because it easier to manipulate mathematically. The solution to the problem results in N eigenvalues (ie. <math>\omega_1^2,\omega_2^2,..\omega_N^2</math>), where N corresponds to the number of degrees of freedom. The eigenvalues provide the natural frequencies of the system. When these eigenvalues are substituted back into the original set of equations, the values of <math>egin{Bmatrix}X\end{Bmatrix}</math> that correspond to each eigenvalue are called the eigenvectors. These eigenvectors represent the mode shapes of the system. The solution of an eigenvalue problem can be quite cumbersome (especially for problems with many degrees of freedom), but fortunately most math analysis programs have eigenvalue routines. A simple example using our 2 DOF model can help illustrate the concepts. Let both masses have a mass of 1 kg and the stiffness of all three springs equal 1000 N/m. The mass and stiffness matrix for this problem are then: Since the system is a 2 DOF system, there are two modes with their respective natural frequencies and shapes. The mode shape vectors are not the absolute motion, but just describe relative motion of the degrees of freedom. In our case the first mode shape vector is saying that the masses are moving together in phase since they have the same value and sign. In the case of the second mode shape vector, each mass is moving in opposite direction at the same rate. When there are many degrees of freedom, the best method of visualizing the mode shapes is by animating them. An example of animated mode shapes is shown in the figure below for a cantilevered I-beam. In this case, a finite element model was used to generate the mass and stiffness matrices and solve the eigenvalue problem. Even this relatively simple model has over a 100 degrees of freedom and hence as many natural frequencies and mode shapes. In general only the first few modes are important. The eigenvectors have very important properties called orthoganility properties. These properties can be used to greatly simplify the solution of multi-degree of freedom models. It can be shown that the eigenvectors have the following properties: <math>egin{bmatrix} ^\diagdown m_{r\diagdown} \end{bmatrix}</math> and <math>egin{bmatrix} ^\diagdown k_{r\diagdown} \end{bmatrix}</math> are diagonal matrices that contain the modal mass and stiffness values for each one of the modes. (Note: Since the eigenvectors (mode shapes) can be arbitrarily scaled, the orthogonality properties are often used to scale the eigenvectors so the modal mass value for each mode is equal to 1. The modal mass matrix is therefore an identity matrix) This equation is the foundation of vibration analysis for multiple degree of freedom systems. A similar type of result can be derived for damped systems. . The key is that the modal and stiffness matrices are diagonal matrices and therefore we have "decoupled" the equations. In other words, we have transformed our problem from a large unwieldy multiple degree of freedom problem into many single degree of freedom problems that can be solved using the same methods outlined above. Written in this form we can see that the vibration at each of the degrees of freedom is just a linear sum of the mode shapes. Furthermore, how much each mode "participates" in the final vibration is defined by q, its modal participation factor.

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# Vibrio cholerae Vibrio cholerae is a gram negative bacterium with a curved-rod shape that causes cholera in humans. V. cholerae and other species of the genus Vibrio belong to the gamma subdivision of the Proteobacteria.  There are two major strains of V. cholerae, classic and El Tor, and numerous other serogroups. V. cholerae was first isolated as the cause of cholera by Italian anatomist Filippo Pacini in 1854, but his discovery was not widely known until Robert Koch, working independently thirty years later, publicized the knowledge and the means of fighting the disease. V. cholerae occurs naturally in the plankton of fresh, brackish, and salt water, attached primarily to copepods in the zooplankton. Coastal cholera outbreaks typically follow zooplankton blooms. This makes cholera a typical zoonosis. V. cholerae colonizes the gastrointestinal tract, where it adheres to villous absorptive cells via pili, and secretes a binary toxin, called cholera toxin (CT). The two CT subunits are named A and B, and are synthesised in a 1:5 ratio. B subunits bind and internalize A subunits, which are processed to A1. The A1 form catalyses ADP ribosylation from NAD to the regulatory component of adenylate cyclase, thereby activating it. Increased adenylate cyclase activity increases cyclic AMP (cAMP) synthesis causing massive fluid and electrolyte efflux, resulting in diarrhea. CT is encoded by the ctxAB genes on a specific filamentous bacteriophage. Transduction of this phage is dependent upon bacterial expression of the Toxin Coregulated Pilus (TCP), which is encoded by the V. cholerae pathogenicity island (VPI). VPI is generally only present in virulent strains and is laterally transferred. VPI was originally thought to encode a filamentous phage responsible for transfer. This theory was discredited by a study of 46 diverse V. cholerae isolates which found no evidence of VPI phage production. The generalized transduction phage CP-T1 has been shown to transduce the entire VPI which is then integrated at the same chromosomal location. Also, VPI has been shown to excise and circularize to produce pVPI via a specialised mechanism involving VPI-encoded recombinases. It is not known whether pVPI is involved in CP-T1 transduction or if it is perhaps a component of an alternative VPI mobilization mechanism. Additionally, it produces two different proteases called chitinase and mucinase. Chitinase is responsible for the ability of Vibrio cholerae to enter copapods. Mucinase is a non-specific protease that assists entry into the human gastro-intestinal tract. Finally, Vibrio cholerae produces what is called a ZOT toxin, termed as "Zona Occludans Toxin". This toxin specifically attacks the zona occludans or "tight" junctions joining epithelial cells.

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# Vibrio harveyi Vibrio harveyi is a species of bioluminescent marine bacteria. Ecologically similar to Vibrio fischeri, V. harveryi has both a free-living form, as well a symbiotic relationship with other marine organisms. V. harveyi may be a more common cause of luminous vibriosis in commercially farmed marine invertebrates. Based on samples taken by vessels, Vibrio harveyi is thought to be the cause of the milky seas effect, in which, during the night, a uniform white glow is emitted from the seawater. Some glows can cover nearly 6,000 square miles.

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# Vibrio vulnificus ## Historical Perspective Vibrio vulnificus is a species of Gram-negative, motile, curved, rod-shaped bacteria in the genus Vibrio. Present in marine environments such as estuaries, brackish ponds, or coastal areas, V. vulnificus is closely related to V. cholerae, the causative agent of cholera. , ## Treatment Vibrio vulnificus causes an infection often incurred after eating seafood, especially oysters; the bacteria can also enter the body through open wounds when swimming or wading in infected waters, or via puncture wounds from the spines of fish such as tilapia. Symptoms include vomiting, diarrhea, abdominal pain, and a blistering dermatitis that is sometimes mistaken for pemphigus or pemphigoid. Severe symptoms and even death can occur if the bacterium enters the bloodstream—something more common in people with compromised immune systems or liver disease. ## Prognosis Vibrio vulnificus infection has a mortality rate of 50% with the majority of patients dying within the first 48 hours of infection. The optimal treatment is not known, but in one retrospective study of 93 patients in Taiwan, use of a third-generation cephalosporin and a tetracycline (e.g., ceftriaxone and doxycycline) were associated with an improved outcome. Prospective clinical trials are needed to confirm this finding, but in vitro data supports the supposition that this combination is synergistic against Vibrio vulnificus. Vibrio vulnificus often causes large, disfiguring ulcers which require extensive debridement or even amputation.

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/index.php/Vicarious_nucleophilic_substitution

# Vicarious nucleophilic substitution Vicarious nucleophilic substitution in organic chemistry is a special type of nucleophilic aromatic substitution in which a nucleophile replaces hydrogen and not an aromatic substituent like a halogen that is ordinarily encountered in this reaction type. This reaction type was introduce in 1987 by Mieczyslaw Makosza and Jerzy Winiarski . It is typically encountered with nitroarenes and especially with carbon nucleophiles resulting in new alkylated arenes. Carbon nucleophiles carry a electron-withdrawing group and a nucleofuge:

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# Vicks Sinex Vicks Sinex is a brand of topical nasal decongestant spray produced by Vicks a division of Procter & Gamble. The active ingredient contained in the Sinex nasal spray is Oxymetazoline which acts to relieve blocked nasal passages. The recommended dosage is 1-2 sprays in each nostril every 6-8 hours. Excessive use of this product could lead to a dependency on it whereby the nasal passages block without use of Oxymetazoline again. Thus it is not recommended that Sinex be used for more than 7 days. Extra ingredients include camphor, eucalyptol, and menthol, which give Sinex Nasal Spray products the characteristic aroma of Vicks products. Sinex products also contain the antibacterial Benzalkonium Chloride. Sinex Nasal Spray may contain Phenylephrine as an active ingredient in other non-UK countries.

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# Vicky Belo Template:Primarysources Victoria G. Belo, popularly known as Dr. Vicky Belo, is a renowned cosmetic surgeon in the Philippines. She is famous for having performed dermatological services on high-profile members of the Philippine showbiz. Belo earned a Bachelor of Science in Psychology from the University of the Philippines, Diliman in 1978. She attended the University of Santo Tomas Faculty of Medicine and Surgery and graduated with a Doctor of Medicine degree in 1985. She obtained a Diploma in Dermatology from the Institute of Dermatology in Bangkok, Thailand, in 1990. Belo trained in Dermatologic Surgery at the Scripps Clinics in San Diego, California. She also trained in Cutaneous Laser Surgery at Harvard Medical School in Boston, Massachusetts, in 1993. She studied Skin Rejuvenation and Laser Surgery at St. Francis Memorial Hospital in the University of California at San Francisco in 1995.She studied Advance Techniques in Phlebology at the Pauline Raymond-Martimbeau Vein Institute in Texas. She took an intensive course in Liposuction under Dr. Jeffrey Klein in San Juan Capistrano, California; and in Laser Assisted Liposuction under Dr. Rodrigo Neira. Belo has pioneered the following procedures in cosmetic surgery in the Philippines: First Skin Laser Carbon Dioxide in 1990; Tumescent Liposuction in 1991; Ultrapulse Laser for Resurfacing and Blepharoplasty in 1994; Versapulse Laser for Tattoos and Veins in 1996; Botox in 1997; Restylane/Perlane, Microdermabrasion, and Power Peel in 1998; Endermology in 1999; Laser Assisted Liposuction in 2000; Intense Pulse Light (IPL) and Light Sheer Hair Removal in 2001; Aptos Thread Facelifts and Lift 6 in 2002; Cool Glide, Clearlight for Acne, and Stem Cell Auto Grafting (SCAG) in 2003; Electro-Optical Synergy (ELOS) Technology: Polaris, Aurora and Velasmooth (Lipolite), and Mesotherapy in 2004; and Thermage, Multiclear, Jet Peel, and Carboxytherapy in 2005. She is a frequent resource speaker and guest lecturer in several organizations in the Philippines and abroad, such as the International Society of Cosmetic Laser Surgeons in Washington, D.C.; the American Society of Dermatologic Surgery in Portland, Oregon; the World Congress on Liposuction Surgery in Pasadena, California; the American Academy of Cosmetic Surgery; and the International Darmstadt Convention on Intense Pulsed Light Therapy (Quantum SR): Asian Experience in Frankfurt, Germany and USA. Belo is the Medical Director of the Belo Medical Group. The Group owns and operates six (6) medical clinics in highly urbanized locations in Metro Manila--Medical Plaza in Makati City, Tektite Towers in Ortigas Center, Westgate in Alabang, Tomas Morato in Quezon City, Connecticut Street in Greenhills, and Rustan's Shopping Mall in Makati City. Belo is not a member of the Philippine Dermatological Society because she did not train in dermatology locally and passed the local dermatological exam. Nevertheless, she is a member of the American Academy of Dermatology, the American Society of Dermatologic Surgery, the American Academy of Cosmetic Surgery, the American Society of Lipoplastic Surgery, the American Society of Hair Restoration Surgery, the International Society of Cosmetic Laser Surgeons (ISCLS), the International Society of Dermatologic Surgery, the Foundation for Facial Plastic Surgery, and is a Founding Officer of the Philippine Liposuction Surgery. However the American Academy of Dermatology is not the certifying body for dermatology and one can only be called a dermatologist after being Board Certified by the American Board of Dermatology.It is interesting to note that the Phillipines does not recognize Miss Bello as a dermatologist and neither does the United States.She is however a highly skilled aesthetic physician with a special interest in dermatology. Belo is a former aerobics and group fitness trainer. She hoards chocolate bars and candies imported from trips in the United States and Europe, keeping all of them inside her refrigerator. She is famous for being associated both professionally and personally with prominent members of the Philippine showbiz, such as multi-awarded actress and singer Sharon Cuneta, and talkshow host Boy Abunda.

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# Vicodin Vicodin is a trademarked brand narcotic analgesic product containing hydrocodone and paracetamol (acetaminophen or more completely para-acetylaminophenol). It is usually found in tablet form with either the names Vicodin, Vicodin ES, or Vicodin HP imprinted on one side. Analgesics with the same chemical composition and a similar physical appearance are found under many other trade names, including Anexsia, Anolor DH5, Bancap HC, Dolacet, Lorcet, Lortab, and Norco. The hydrocodone/paracetamol drug formula is also available under generic brands. The paracetamol in the formula increases the effects of the hydrocodone. Hydrocodone also comes in a combination with ibuprofen, available under the trade name Vicoprofen. Vicodin is made as a mixture of hydrocodone and paracetamol. Paracetamol, which is also called acetaminophen, acts as an analgesic/antipyretic. Hydrocodone is a synthetic mixture of the opiate codeine modified by an added hydrogen and the opiate alkaloid thebaine. Codeine acts as an antitussive, antidiarrheal and analgesic, while thebaine is added for its stimulatory effects. Non-active ingredients included in each pill as well: colloidal silicon dioxide, starch, croscarmellose sodium, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, povidone, and stearic acid. In the United States, Vicodin production is regulated in part by the Controlled Substances Act of 1970. This guarantees that all manufacturing, importing, possession, and distribution of drugs is to be overseen and regulated by the federal government. In the U.S. Hydrocodone is a Schedule III drug. Other drugs on this list include anabolic steroids, dihydrocodeine, dronabinol, phendimetrazine, ketamine, paregoric, and Xyrem; codeine and hydrocodone are also Schedule III but only when compounded with paracetamol or with an NSAID. Schedule III drugs are classified by the U.S. government as potentially causing moderate or low physical dependence or a high psychological dependence if abused. There is a high inclination for abuse of this drug. The principal constituent of Vicodin, hydrocodone, has the same basic structure as morphine but is metabolized by different enzymes. There are three variations of Vicodin, with different amounts of hydrocodone / paracetamol (acetaminophen) in each. Hydrocodone is a strong drug which has similar effects as morphine, because of this, the pills are made with much less hydrocodone than paracetamol. The theory of using the mix comes from the idea that these drugs alleviate pain using different mechanisms and also that the adverse side effects of each separate drug are reduced by using reduced dosages of both drugs in order to get the same analgesic effect. Both hydrocodone and acetaminophen are white crystalline powders, which are then manufactured into pill form. There is also a theory that the acetaminophen is added in order to reduce abuse potential, as multiple doses will result in nausea symptoms and stomach complications. Manufacturers of hydrocodone (generic or otherwise) include Abbott Laboratories (makers of trademark Vicodin), Amerisource Health Services Corp, Cardinal Health, Drx Pharmaceutical Consultants Inc, Eckerd Corp, Hospira Inc, Knoll Laboratories Div Knoll Pharmaceutical Co, Mallinckrodt Pharm. Quality Care, Pdrx Pharmaceuticals Inc, Physicians Total Care Inc, Rx Pak Div of Mckesson Corp, Sandhills Packaging Inc, and Watson Pharmaceuticals. Besides the activity of hydrocodone and acetaminophen on their own, there is observed a factor of analgesia related to the two substances in tandem which is not altogether understood, but this independent synergy has been observed to be related to the inhibition of prostaglandins. The pharmacokinetics of a mixed drug such as Vicodin depends on the kinetics of the drugs that comprise it. We will look at the two main constituents separately, hydrocodone and paracetamol. Hydrocodone: acts at mu opioid receptors. Hydrocodone must be metabolized to its active state, hydromorphone. This metabolism occurs by the activity of cytochrome P450 2D6. Cytochrome 3A4 forms the active substrate norhydrocodone. Cytochromes are haemoprotiens found in the cells of all living organisms and are involved primarily with the electron transport chain producing ATP. Hydrocodone passes through the Blood Brain Barrier because of its modifications, the brain is typically where the analgesic effects are being carried out. Many of the side effects of this drug are caused by the fact that it so readily crosses the BBB. The half-life of hydrocodone is approximately 3.8 hrs. Paracetamol: the major active metabolites are sulphates and glucuronide conjugates. Its main mode of action is to inhibit the activity of the enzyme cyclooxygenase (COX). COX enzymes are necessary for the production of prostaglandins. Prostaglandins are a form of hormone (although rarely classified as such), which are indicated to be mediators of pain, fever and inflammation. The half-life of paracetamol may be measured either by salivary or plasma counts. Both measurements give a varying half-life between 1 and 4 hours. Peak levels are reached between 40–60 minutes after ingestion. It has been proposed that paracetamol aids in the reduction of pain by increasing seratonergic neurotransmissions. Paracetamol is a peripherally acting drug, and hence does not cross the BBB as readily as hydrocodone. Vicodin, like other opioid analgesics, is used to manage pain. It is most commonly prescribed for relief of moderate to moderately severe pain of acute, chronic, or post-operative types. It can also be used to treat severe cough. This drug is classified under pregnancy category C. Although not enough research has been done to deem this drug safe for pregnant women, if the positive effects outweigh the possible negatives, then it can be taken. If taken in the time before delivery, it may give rise to respiratory depression in the baby. Mothers who use any opioids regularly during pregnancy run the risk of their babies being substance dependent and therefore going through withdrawal symptoms after birth. Withdrawal symptoms include: excessive crying, vomiting, irritability, tremors and fever. Nursing mothers should not use this drug as paracetamol is transferred through breast milk and it is unknown if hydrocodone is. Side effects for Vicodin are most commonly upset stomach, nausea, and altered mental status (eg. dizziness, light headedness). Other more rare side effects include allergic reaction, seizures, clammy skin, hallucinations, severe weakness, dizziness, hyperventilation, unconsciousness, jaundice (yellowing of eyes or skin), unusual fatigue, bleeding, bruising, stomach pain , constipation, dry mouth, decreased appetite, muscle twitches, sweating, hot flashes, itching, tinnitus, hearing loss, decreased urination, and altered sex drive. Vicodin also has depressant effects on the central nervous system. However, some of the less mundane effects can be desirable effects that are sought after by some. Those effects include euphoria and drowsiness, as well as slowing of the pulse. Unlike NSAIDs, Paracetamol does not cause ulcers. Liver damage can manifest ranging from abdominal pain to outright liver failure, and can necessitate a liver transplant to avoid death. Paracetamol dosages should never exceed 4g a day; this is especially important and may be a smaller number when dealing with mixed drugs like Vicodin. It is imperative that users of this drug follow physician prescribed dosages. Tolerance to this drug may develop rapidly, especially if it is misused. This tolerance will usually manifest itself by analgesic effects wearing off faster, and people needing higher dosages to reach the analgesic effects. It is commonly misused or used excessively because people take too much in order to relieve their pain faster. Taking more of the drug does increase its efficacy but it also increases its addictive properties. When tolerance does develop, people are often forced to seek out more and more Vicodin, but as it is a controlled substance, there are regulations on how much can be legally prescribed. This often leads to societal/legal consequences as people will visit many doctors and/or try to buy the drug illegally. The withdrawal effects of Vicodin include things such as insomnia, night sweats, tremors, and agitation. People looking for the secondary effects of the drug often abuse many forms of prescription drugs. Vicodin is a potentially addictive drug, specifically due to the hydrocodone in it. People who are using Vicodin for non-medicinal purposes are typically using it to get the euphoric effects sometimes associated with it. Ten percent of American high school seniors have abused Vicodin; 4.7 percent report abusing Oxycontin in the past year. There have been reports of severe hearing loss and deafness associated with the abuse of Vicodin. If taken at the normal prescribed dosages, the risk of hearing loss is very minimal. It is interesting to note that in people who use these drugs for recreational purposes there are sex differences. Women tend to feel less "in control on their thoughts" and more report, "feeling bad" more often than men. People given logic examinations while under the influence of this drug showed an increase in incorrect answers, but spent more time on the exams. This suggests that this drug may be aiding in attention. It is again important to note that clinically prescribed dosages do not produce these effects; these effects are related to taking more of the drug than typically prescribed. On Jun 30 2009 an FDA advisory panel recommended that Vicodin and another painkiller, Percocet, be removed from the market because they have allegedly caused over 400 deaths a year. The problem is with Paracetamol overdose and liver damage.

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# Vicriviroc Vicriviroc, previously named SCH 417690 and SCH-D, is a pyrimidine CCR5 entry inhibitor of HIV-1. It was developed by the pharmaceutical company Schering-Plough. Merck decided to not pursue regulatory approval for use in treatment-experienced patients because the drug did not meet primary efficacy endpoints in late stage trials. Clinical trials continue in patients previously untreated for HIV. The mechanisms of a number of available anti-HIV drugs prevent either viral reverse transcriptase enzyme or protease enzyme, allowing the virus to enter the cell before these drugs take effect. However, CCR5 inhibitors such as vicriviroc, as well as other entry inhibitors of HIV-1, inhibit the initial stages of the virus life cycle. HIV binds to and fuses with the target T-cells or macrophages with the help of gp120 and gp41, the only two proteins that are currently known to be exhibited on the surface of the viral envelope. One molecule of each protein associates noncovalently with the other on the viral membrane, and three of these units aggregate to form the gp120/gp41 heterotrimer, which traps the gp41 in a conformationally metastable state. Membrane fusion begins with the binding of gp120 to CD4, a glycoprotein which is expressed on the surface of the target cell. Upon binding, gp120 undergoes a conformational change, which causes the formation of the coreceptor binding site on gp120. All strains of HIV-1 use one of two coreceptors: CCR5 or CXCR4; coreceptor specificity will be described below. Once gp120 binds to the coreceptor, gp41 undergoes a conformational change that releases it from its once-metastable position. This change causes the hydrophobic N-terminus of the gp41 protein, also known as the fusion domain, to insert into the host cell membrane and anchor the virus into place. The insertion of gp41 into the target cell causes a subtle rearrangement in the gp41 protein that brings together two trimeric coiled coils, HR1 and HR2, to form a six-helix bundle. The bundle allows the viral and cellular membranes to approximate and eventually fuse together, leading to the release of the viral genome into the cytoplasm of the target cell. The two coreceptors involved in the entry of HIV-1, CCR5 and CXCR4, belong to the larger family of 7-transmembrane segment (7TM) G-protein coupled receptors. HIV-1 can thus be classified according specificity for one coreceptor or the other. R5 virus, also known as M-tropic HIV-1, targets macrophages and uses CCR5 as the coreceptor. X4 virus, or T-tropic HIV-1, targets T-cells and uses CXCR4 as the coreceptor. Dual-tropic strains of HIV-1, which utilize both receptors, also exist. Selectivity for one coreceptor or the other is especially dependent upon the V3 loop, a highly variable and structurally flexible region of gp120 that is composed of approximately 35 amino acids. Tropism can be predicted through the 11/25 method, which looks for basic amino acids at positions 11 and 25 in the V3 loop and suggests the presence of an X4 virus. Coreceptor usage, however, can change throughout the course of infection. 90% of patients in early phases of HIV-1 infection have R5 virus. However, after five years of infection, about 50% of all patients have detectable amounts of X4 virus. Causes for this switch are currently unclear. However, viral changes from CCR5 to CXCR4 coreceptor usage have been associated with a faster rate of CD4+ T-cell loss, rapid viral progression, and an increased rate of development of AIDS and death. A focus on the CCR5 co-receptor as a potential target for anti-HIV medications began in 1996 with the discovery of CCR5-Δ32, or CCR5 delta-32, a mutational variant of the CCR5 coding gene. The deletion of 32 base pairs in this gene results in nonfunctional CCR5 receptors. While the frequency of this mutation within Caucasian populations is 0.0808, people of African or Asian descent do not appear to possess this allele. Δ32 homozygotes, or individuals who possess two copies of the Δ32 variant, have no functional CCR5 receptors and are consequently highly resistant to HIV infection. Individuals who inherit one copy of Δ32 variant and one copy of the normal CCR5 gene are CCR5 heterozygotes. Δ32 heterozygotes are still susceptible to HIV-1 infection, but the progression of the disease is significantly delayed compared to those with two normal copies of the CCR5 gene. CCR5 antagonists have been developed which cause deformation in the CCR5 co-receptor, leading to the cell's failure to bind with the HIV gp120 protein. In 2001, Schering-Plough developed one of the first small molecule CCR5 antagonists, SCH-C or SCH 351125, which inhibited replication of a number of HIV-1 isolates that used CCR5 as a coreceptor for binding. However, SCH-C caused a modest but dose-dependent prolongation of the corrected cardiac QT interval (QTc), leading to examination of alternative compounds whose antiviral and pharmacokinetic properties exceeded those of first-generation compounds like SCH-C. Vicriviroc was discovered in high-throughput screening and structure-activity relationships (SAR) analysis. When compared with SCH-C, vicriviroc consistently and more actively inhibits viral replication, binds with higher affinity to CCR5 than SCH-C, and possesses a lower affinity for the human ether a-go-go related gene transcript ion channel, which may suggest a lower risk of cardiac effects. Vicriviroc is a noncompetitive allosteric antagonist of CCR5. It is orally administered and, because it is effective at nanomolar concentrations, it can be administered once daily. Vicriviroc binds to a small hydrophobic pocket between the transmembrane helices near the extracellular surface of the CCR5 receptor. Binding to this pocket induces a conformational change of the extracellular segment of CCR5 and prevents binding of gp120 to the target cell, consequently preventing the virus from entering the target cell at all. Specific binding interactions between CCR5 and vicriviroc were first described in 2008. Specifically, the trifluoromethyl phenyl group of vicriviroc may interact strongly with I198 residue on the fifth transmembrane helix (TM5) of CCR5 through hydrophobic interactions. Additionally, electrostatic interactions may form between the positively charged tertiary nitrogen group of vicriviroc and the hydrophilic region provided by E238 residue on TM7 of CCR5. Other strong interactions predicted by the group include the Y108 residue on TM3 and Y251 on TM6. Currently, vicriviroc is undergoing critical trials. Vicriviroc demonstrated a significant decrease of HIV RNA in R5-infected subjects. The mean decline from baseline of HIV RNA achieved 1.5 log10 or greater in all treatment groups (10, 25, 50 mg, b.i.d.) in a 14-day monotherapy trial in HIV-infected adults. A phase II trial in treatment-naïve HIV-1 infected subjects was discontinued after the rate of virologic relapse in those subjects who were administered vicriviroc increased compared to control subjects; however, further investigations suggest that the administered dosage of vicriviroc may have been too low. A new Phase II trial of treatment-naive HIV-1 patients is currently underway. A 48-week phase II trial (ACTG5211) examining the safety and efficacy of 5, 10, and 15 mg doses of vicriviroc found that patients in the 10 mg and 15 mg vicriviroc treatment groups achieved a median decrease in viral load of 1.92 and 1.44 (log10 copies/mL) and a median increase in CD4 cell count of 130 and 96 (cell/uL) from baseline, respectively. More patients in the vicriviroc groups had undetectable virus at 48 weeks (HIV-1 RNA <400/<50 copies/ml) compared to those in the placebo group (57/37 percent and 43/27 percent vs. 14/11 percent, respectively). The results from a 48-week phase II trial (VICTOR-E1) examining administration of 20 or 30 mg dosages of vicriviroc in addition to > 3-drug optimized background therapy (OBT) regimen that included a ritonavir-boosted protease inhibitor were reported in February 2008. Investigators concluded that, "'Vicriviroc 30 or 20 mg once daily plus ritonavir-containing OBT provided sustained viral suppression in treatment-experienced subjects and increased CD4 cell counts regardless of the number of active drugs in OBT.'" As of May 2008, two phase III trials (VICTOR-E3 and VICTOR E4) in treatment-experienced patients were initiated. The late stage clinical trials by did not meet their primary efficacy endpoints and Merck has decided as of January 2010 to not pursue regulatory approval for the drug. Available clinical trial data suggest that a new method of combating HIV-1 may be found in CCR5 antagonists. Studies into vicriviroc are ongoing, and another CCR5 antagonist, maraviroc, is currently on the market. However, concerns have arisen regarding the use of CCR5 antagonists as anti-HIV treatments because such drugs may facilitate the emergence of resistant strains of HIV-1. Two possibilities for such resistance have been hypothesized: HIV-1 may evolve to use only CXCR4 as the coreceptor; or HIV-1 may mutate in such a way that it is still able to interact with CCR5, despite the presence of a receptor antagonist. In fact, maraviroc-resistant variants of HIV-1 have already been generated in vitro by mutating residues in the V3 loop of gp120.

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# Victor A. Marcial-Vega Victor A. Marcial-Vega is a radiation oncologist from San Juan, Puerto Rico. He is best known for his work in the field of alternative medicine. He graduated with an M.D. from the University of Puerto Rico Medical School in 1984, and completed his internship and residency in radiation oncology in 1988 at the Johns Hopkins Hospital and School of Medicine in Baltimore, Maryland. He has taught at Washington University and at the University of Miami. He practices medicine in Puerto Rico and in the Miami, Florida area. He is the Medical Director for the Atlantis Energy Network, based in Coral Gables, Florida, and has also been the Medical Director of Health Horizons, a natural healing products company based in Miami. He is a proponent of nutripathy, the theory that a blood acidity that is too high has a negative impact on human health, and also promotes the use of wolfberry, which he believes purifies one's blood, reduces blood acidity and uric acid levels, and allows for proper white and red blood cell activity. He has also promoted EDTA chelation therapy, ozone therapy , and the use of colloidal silver , as therapies to assist with the treatment of cancer and other diseases.

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# Victor Babeş Victor Babeş (July 4, 1854—October 19, 1926) was a Romanian physician, biologist, and one of the earliest bacteriologists. He made early and significant contributions to the study of rabies, leprosy, diphtheria, tuberculosis, and other infectious diseases. Born in Vienna (at the time, the capital of the Austrian Empire) to an ethnic Romanian family from the Banat, he studied in Budapest, then in Vienna, where he received his doctorate in Science. Attracted by the discoveries of Louis Pasteur, he left for Paris, and worked first in Pasteur's laboratory, and then with Victor André Cornil. In 1885 he discovered a parasitic sporozoan of the ticks, named Babesia (of the genus Babesiidae), and which causes a rare and severe disease called babesiosis. In the same year, he published the first treaty of bacteriology in the world, Bacteria and their role in the histopathology of infectious diseases, which he co-authored with Cornil. Babeş' scientific endeavours were wide-ranging. He was the first to demonstrate the presence of tuberculous bacilli in the urine of infected patients. He also discovered cellular inclusions in rabies-infected nerve cells. Of diagnostic value, they were to be named after him (Babeş-Negri bodies). Babeş was one of the founders of serum therapy, and was the first to introduce rabies vaccination to Romania. His work also had a strong influence upon veterinary medicine, especially concerning prophylaxis and serum medication. He became a professor of Pathology and Bacteriology at the Carol Davila University of Medicine and Pharmacy in Bucharest. He was also a member of the Romanian Academy (in 1893), of the Paris Académie Nationale de Médecine, and an officer of the French Légion d'honneur.

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# Victor Ling Dr. Victor Ling is an award-winning Canadian researcher in the field of medicine. Ling's research focuses on drug resistance in cancer. He is best known for his discovery of P-glycoprotein, one of the proteins responsible for multidrug resistance. Ling was born in China, and emigrated to Canada as a child. He received his bachelor's degree in 1966 from the University of Toronto and his PhD in 1969 from the University of British Columbia. In 2006, he was awarded an honorary doctorate from Trinity Western University. He undertook post-doctoral training with nobel-laureate Dr. Fred Sanger at Cambridge University. Ling is currently Assistant Dean of the Faculty of Medicine at the University of British Columbia and Vice-President, Discovery at the BC Cancer Agency in Vancouver, British Columbia.

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/index.php/Victorian_College_of_Pharmacy

# Victorian College of Pharmacy The Victorian College of Pharmacy is the Parkville campus of Monash University, located in Victoria, Australia. It is a centre of research and teaching in the fields of pharmaceuticals and medicinal chemistry. It is particularly well known for its research in drug development and formulation science, including the discovery and development of the world's first successful anti-influenza drug, Relenza. The college/campus is made up of 4 buildings, the latest one being first occupied in 2007. The newest, fourth building is primarily a research building, to complement the college's strong research background. The campus is situated on Royal Parade in the suburb of Parkville, around 2km north of the Melbourne CBD. Royal Parade is home to a number of other research institutions, including the University of Melbourne, the CSIRO's Division of Health Sciences and the Royal Melbourne Hospital. Pharmaceutical company CSL Limited is also based in Parkville. The campus offers courses in Pharmacy and Pharmaceutical Science. It requires high ENTER scores from Year 12 applicants, as the degrees are high demand courses. College of Pharmacy students can also take simultaneous degrees in commerce or engineering at Monash University's Clayton Campus. The College also offers postgraduate degrees by coursework or research, from graduate diploma through to PhD level. The College currently has around 1100 students and around 140 staff. It is planning to expand its teaching to offer a Bachelor of Pharmacy at the University's Malaysia campus, which will commence in 2008. The College is also exploring the possibilities of developing postgraduate pharmacy education at the University's South Africa campus. The Victorian College of Pharmacy is one of the oldest educational institutions in Australia. It was founded in 1881 as the School of the Pharmaceutical Society of Victoria. After being housed in various places in Melbourne, it moved to its present location in 1960. In its early years, the College was essentially run as a private institution, with the majority of its funding coming from tuition fees and the donations of benefactors. In 1967, the College reached an agreement with the Federal and State governments for it to receive government financial assistance. In 1974, fees for tertiary education in Australia were abolished, meaning that funding for the College began to be sourced primarily from the Federal Government. After the introduction of the unified national system of higher education in 1988, known as the Dawkins reforms, it was clear that the College had to combine with a university. Negotiations were started with University of Melbourne, which was seen as the obvious partner, given their close proximity. However, these negotiations collapsed in 1990. The College then began discussions with Monash University, which were successful. The transfer was finalised on 1 July 1992 and the College is now the Faculty of Pharmacy of Monash University. It celebrated its 125th anniversary in 2006. The College has produced a number of graduates who have become leaders in pharmaceutical and health sciences. Additionally, the College's alumni includes graduates who have become well-known in fields outside of science, including many politicians and senior public servants, and national leaders such as Weary Dunlop.

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# Victory V Victory V is a British brand of liquorice-flavoured lozenges. Originally manufactured in Nelson, Lancashire, they were devised by Thomas Fryer and Edward Smith MD in the mid-1800s and were initially made by hand to ensure that each sweet contained the correct amount of therapeutic ingredients; ether, liquorice and chloroform. Victory V lozenges are available in specialist shops and online, but no longer contain chloroform or ether. Today they are manufactured by Ernest Jackson & Co. Ltd. in Devon.

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/index.php/Vidarabine

# Vidarabine In the 1950s two nucleosides were isolated from the Caribbean sponge Tethya crypta: spongothymidine and spongouridine; which contained D-arabinose rather than D-ribose. These compounds led to the synthesis of a new generation, sugar modified nucleoside analog vidarabine, and the related compound cytarabine. In 2004 these were the only marine related compounds in clinical use. The drug was originally intended as an anti-cancer drug. The anti-viral activity of vidarabine was first described by M. Privat de Garilhe and J. De Rudder in 1964. It was the first nucleoside analog antiviral to be given systemically and was the first agent to be licensed for the treatment of systematic herpes virus infection in man. It was University of Alabama at Birmingham researcher and physician Dr. Richard Whitley in 1976 where the clinical effectiveness of vidarabine was first realized, and vidarabine was used in the treatment of many viral diseases. Vidarabine is an analog of adenosine with the D-ribose, replaced with D-arabinose. As you can see from figure 1.1 that it is a stereoisomer of adenosine. It has a half-life of 60 minutes, and its solubility is 0.05%, and is able to cross the blood–brain barrier (BBB) when converted to its active metabolite. Vidarabine works by interfering with the synthesis of viral DNA. It is a nucleoside analog and therefore has to be phosphorylated to be active. This is a three step process in which vidarabine is sequentially phosphorylated by kinases to the triphosphate ara-ATP. This is the active form of vidarabine and is both an inhibitor and a substrate of viral DNA polymerase. When used as a substrate for viral DNA polymerase, ara-ATP competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where ara-ATP is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Uniquely to vidarabine, the diphosphorylated vidarabine (ara-ADP) also has an inhibitory effect. Other nucleoside analogs need to be triphosphorlated to give any antiviral effect, but ara-ADP inhibits the enzyme ribonucleotide reductase. This prevents the reduction of nucleotide diphosphates, causing a reduction of viral replication. Vidarabine is more toxic and less metabolically stable than many of the other current antivirals such as acyclovir and ganciclovir. Viral strains resistant to vidarabine show changes in DNA polymerase. It is prone to deamination by adenosine deaminase to inosine. This metabolite still possesses antiviral activity, but is 10-fold less potent than vidarabine. 60% of vidarabine eliminated by the kidney is excreted as 9-β-D-arabinofuranosylhypoxanthine in the urine. Some breakdown of the purine ring may also occur, forming uric acid. Structural modifications of vidarabine have proven partially effective at blocking deamination, such as replacement of the amine with a methoxy group (ara-M). This results in about a 10-fold greater selectivity against Varicella Zoster Virus than ara-A, however analog of vidarabine is inactive against other viruses due to it not being able to be phosphorylated. The use of an inhibitor of adenosine deaminase to increase the half-life of vidarabine has also been tried, and drugs such as dCF and EHNA have been used with a small amount of success. Chemical synthesis of Vidarabine was first attained in 1960, as a part of studies on developing potential anticancer agents by B. R. Baker et al. based on unique biological properties of 1-β-D-arabinofuranosyluracil (ara-U). More specifically some of its important reactions include treatments with 2'-deoxyribonucleoside phosphorylase, methyltransferase, or nucleoside phosphorylase, affording the corresponding 5'-phosphate, giving rise to no methylation at its 5-position, or no cleavage of the glycosyl bond in contrast to 5-fluoro-2'-deoxyuridine, respectively. This earlier work gave impetus to further synthetic studies on the nucleosides with the β-D-arabinofuranosyl moiety including Vidarabine, and the isolation of Vidarabine from the fermentation culture broth of Streptomyces antibioticus. In addition to the potential anticancer properties antiviral activity of Vidarabine was also demonstrated in 1965. Particularly worthy of mention is the collaboration of efficient chemical and enzymatic reactions, i.e., transesterification from ethylene carbonate to uridine accompanied by spontaneous intramolecular elimination of carbon dioxide giving 2,2'-O-anhydro-1-β-D-arabinofuranosyluracil (anhydro-ara-U); and acid-hydrolysis of anhydro-ara-U giving ara-U; and subsequent enzymatic transglycosylation of the sugar moiety of ara-U to the 9-position of adenine with perfect retention of the β-configuration. Ultimately, in 1984, these pioneering syntheses led to the first commercial synthesis of Vidarabine in Japan under the trade name of "Arasena-A." An enzymatic approach duplicating the same concept was also later reported. Vidarabine is less susceptible to the development of drug resistant strains than other antivirals such as IDU, and has been used successfully in the treatment of IDU resistant viral strains. The half-life of the active triphosphate metabolite (ara-ATP) is three times longer in HSV-infected cells compared with uninfected cells, however the mechanism of selectivity is not known. Vidarabine is an antiviral, active against herpes viruses, poxviruses, rhabdoviruses, hepadnaviruses and some RNA tumour viruses. A 3% ophthalmic ointment Vira-A is used in the treatment of acute keratoconjuctivitis and recurrent superficial keratitis caused by HSV-1 and HSV-2. Vidarabine is also used to treat herpes zoster in AIDS patients, reducing lesions formation and the duration of viral shedding. Many of the previous uses of vidarabine have been superseded by acyclovir, due to the hospitalisation required for intra venous dosing, and acyclovir has a higher selectivity, lower inhibitory concentration and higher potency. Toxic side effects are rare, but have been reported with high concentrations of vidarabine, such as nausea, vomiting, leukopenia and thrombocytopenia in patients receiving high intravenous doses daily.

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# Vildagliptin {{drugbox | IUPAC_name = (2S)-1-{2-[(3-hydroxy-1-adamantyl)amino]acetyl}pyrrolidine-2-carbonitrile | image = Vildagliptin.svg | width = 140px | CAS_number = 274901-16-5 | ATC_prefix = A10 | ATC_suffix = BH02 | PubChem = 6918537 | DrugBank = | C = 17 |H = 25 |N = 3 |O = 2 | molecular_weight = 303.399 g/mol | bioavailability = 85% | protein_bound = 9.3% | metabolism = Mainly hydrolysis to inactive metabolite; CYP450 not appreciably involved | elimination_half-life = 2 to 3 hours | excretion = Renal | pregnancy_category = Not recommended | legal_status = | routes_of_administration = Oral }} Vildagliptin, previously identified as LAF237, is a new oral anti-hyperglycemic agent (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucaon release by the alpha cells of the islets of Langerhans in the pancreas. Vildagliptin has been submitted to the U.S. Food and Drug Administration for approval, and will be marketed as Galvus by Novartis. The Food and Drug Administration demanded additional clinical data before it can approve vildagliptin including extra evidence that skin lesions and kidney impairment seen during an early study on animals have not occurred in human trials. Vildagliptin is currently approved for use in the European Union, although it is not yet marketed. The recent finding of liver toxicity problems among clinical trial patients could delay the European debut of this drug.

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# Viloxazine Viloxazine (Emovit®, Vivalan®, Vivarint®, Vicilan®) is a bicyclic antidepressant morpholine derivative that inhibits the reuptake of norepinephrine. It is a racemic compound with two isomers, the S(-)-isomer being five times as pharmacologically active as the R(+)-isomer. Viloxazine hydrochloride was approved in Italy, Belgium, the United States, England, Ireland, Germany, Portugal, Spain, the former Yugoslavia, France, Slovakia, for the treatment of clinical depression. Viloxazine has undergone two randomized controlled trials for nocturnal enuresis (bed-wetting) in children, both of those times versus imipramine. , By 1990, it was seen as a less cardiotoxic alternative to imipramine, and to be especially effective in heavy sleepers. While viloxazine may be effective in clinical depression, it did relatively poorly in a double-blind randomized controlled trial versus amisulpride in the treatment of dysthymia, according to Leon and colleagues at the University of Valle in Colombia. In 1976, Lippman and Pugsley reported that viloxazine, like imipramine, inhibited norepinephrine reuptake in the hearts of rats and mice; unlike imipramine, (or desipramine or amitriptyline, for that matter) it did not block reuptake of norepinephrine in neither the medullae nor the hypothalami of rats. As for serotonin, while its reuptake inhibition was comparable to that of desipramine (i.e., very weak), viloxazine did potentiate serotonin-mediated brain functions in a manner similar to amitriptyline and imipramine, which are relatively potent inhibitors of serotonin reuptake. Unlike any of the other drugs tested, it did not exhibit any anticholinergic effects. Side effects include nausea, vomiting, insomnia, loss of appetite, increased erythrocyte sedimentation, EKG and EEG anomalies, epigastric pain, diarrhea, constipation, vertigo, orthostatic hypotension, edema of the lower extremities, dysarthria, tremor, psychomotor agitation, mental confusion, inappropriate secretion of antidiuretic hormone, increased transaminases, seizure, (there were three cases worldwide, and most animal studies (and clinical trials that included epilepsy patients) indicated the presence of anticonvulsant properties, so is not completely contraindicated in epilepsy ), and increased libido. Viloxazine is known to increase plasma levels of phenytoin by an average of 37%. It is also known to significantly increase plasma levels of theophylline and decrease its clearance from the body, sometimes resulting in accidental overdose of theophylline.

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# Vimentin Vimentin is a type III intermediate filament (IF) protein that is expressed in mesenchymal cells. IF proteins are found in all animal cells as well as bacteria. IF, along with tubulin-based microtubules and actin-based microfilaments, comprises the cytoskeleton. All IF proteins are expressed in a highly developmentally-regulated fashion; vimentin is the major cytoskeletal component of mesenchymal cells. Because of this, vimentin is often used as a marker of mesenchymally-derived cells or cells undergoing an epithelial-to-mesenchymal transition (EMT) during both normal development and metastatic progression. A vimentin monomer, like all other intermediate filaments, has a central α-helical domain, capped on each end by non-helical amino (head) and carboxyl (tail) domains. Two monomers are likely co-translationally expressed in a way that facilitates their formation of a coiled-coil dimer, which is the basic subunit of vimentin assembly. The α-helical sequences contain a pattern of hydrophobic amino acids that contribute to forming a "hydrophobic seal" on the surface of the helix. In addition, there is a periodic distribution of acidic and basic amino acids that seems to play an important role in stabilizing coiled-coil dimers. The spacing of the charged residues is optimal for ionic salt bridges, which allows for the stabilization of the α-helix structure. While this type of stabilization is intuitive for intrachain interactions, rather than interchain interactions, scientists have proposed that perhaps the switch from intrachain salt bridges formed by acidic and basic residues to the interchain ionic associations contributes to the assembly of the filament. Vimentin plays a significant role in supporting and anchoring the position of the organelles in the cytosol. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either laterally or terminally. The dynamic nature of vimentin is important when offering flexibility to the cell. Scientists found that vimentin provided cells with a resilience absent from the microtubule or actin filament networks, when under mechanical stress in vivo. Therefore, in general, it is accepted that vimentin is the cytoskeletal component responsible for maintaining cell integrity. (It was found that cells without vimentin are extremely delicate when disturbed with a micropuncture). Transgenic mice that lack vimentin appeared normal and did not show functional differences. It is possible that the microtubule network may have compensated for the absence of the intermediate network. This result supports an intimate interactions between microtubules and vimentin. Moreover, when microtubule depolymerizers were present, vimentin reorganization occurred, once again implying a relationship between the two systems. On the other hand, wounded mice that lack the vimentin gene heal slower than their wild type counterparts. In essence, vimentin is responsible for maintaining cell shape, integrity of the cytoplasm, and stabilizing cytoskeletal interactions. Vimentin has been shown to eliminate toxic proteins in JUNQ and IPOD inclusion bodies in asymmetric division of mammalian cell lines. Also, vimentin is found to control the transport of low-density lipoprotein, LDL, -derived cholesterol from a lysosome to the site of esterification. With the blocking of transport of LDL-derived cholesterol inside the cell, cells were found to store a much lower percentage of the lipoprotein than normal cells with vimentin. This dependence seems to be the first process of a biochemical function in any cell that depends on a cellular intermediate filament network. This type of dependence has ramifications on the adrenal cells, which rely on cholesteryl esters derived from LDL. Methylation of the vimentin gene has been established as a biomarker of colon cancer and this is being utilized in the development of fecal tests for colon cancer. Statistically significant levels of vimentin gene methylation have also been observed in certain upper gastrointestinal pathologies such as Barrett's esophagus, esophageal adenocarcinoma, and intestinal type gastric cancer. High levels of DNA methylation in the promotor region have also been associated with markedly decreased survival in hormone positive breast cancers. Downregulation of vimentin was identified in cystic variant of papillary thyroid carcinoma using a proteomic approach. See also Anti-citrullinated protein antibody for its use in diagnosis of rheumatoid arthritis.

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# Viminol Viminol (marketed under the brandname Dividol) is a drug which is an opioid analgesic. It has an unusual chemical structure that is not similar to other opioids. Viminol has both antitussive (cough suppressing) and analgesic (pain reducing) effects. It has six different stereoisomers which have varying properties, with the R2 isomer being a μ-opioid full agonist slightly more potent than morphine, while the S2 isomer is an antagonist. Since vimonol is supplied as a racemic mixture of isomers, the overall effect produces a mixed agonist-antagonist profile similar to that of opioids such as pentazocine, although with somewhat less side effects. However, since viminol is supplied as a racemic mixture of agonist and antagonist isomers, the abuse potential and respiratory depression tends to be less than that of μ-opioid full agonist drugs.

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# Vin Mariani Vin Mariani (French: Mariani's wine) was a tonic created circa 1863 by Angelo Mariani, a chemist who became intrigued with coca and its economic potential after reading Paolo Mantegazza's paper on coca's effects. In 1863 Mariani started marketing a wine called Vin Mariani which was made from Bordeaux wine treated with coca leaves. The ethanol in the wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drink's effect. It originally contained 6 mg of cocaine per fluid ounce of wine, but Vin Mariani which was to be exported contained 7.2 mg per ounce in order to compete with the higher cocaine content of similar drinks in the United States. This tonic was copied by John S. Pemberton in 1884, originally as a cocawine called Pemberton's French Wine Coca. In 1885, when Atlanta and Fulton County passed Prohibition legislation, Pemberton responded by developing Coca-Cola, essentially a carbonated, non-alcoholic version of Mariani's wine with the addition of cola. The beverage was named Coca-Cola because originally, the stimulant mixed in the beverage was coca leaves from South America. In addition, the drink was flavored using kola nuts, the beverage's source of caffeine. Therefore, Angelo Mariani is sometimes thought of as the "grandfather of Coca-Cola." When cocaine is administered on its own it yields two key active compounds, benzoylecgonine and ecgonine methyl ester. When combined with alcohol, as in Vin Mariani, the mixture forms a powerful psychoactive: cocaethylene (which is both more euphorigenic and has higher cardiovascular toxicity than cocaine by itself). Vin Mariani was very popular in its day, even among royalty such as Queen Victoria of Great Britain and Ireland. Pope Leo XIII and later Pope Saint Pius X were both Vin Mariani drinkers. Pope Leo awarded a Vatican gold medal to the wine, and also appeared on a poster endorsing it.

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# Vinblastine Vinblastine is an antineoplastic agent that is FDA approved for the treatment of palliative treatment of Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system),Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated),Histiocytic lymphoma,Mycosis fungoides (advanced stages),Advanced carcinoma of the testis,Kaposi's sarcoma, Letterer-Siwe disease (histiocytosis X). There is a Black Box Warning for this drug as shown here. Common adverse reactions include leukopenia,alopecia,constipation, anorexia, nausea, vomiting, abdominal pain, ileus, vesiculation of the mouth, pharyngitis, diarrhea,Hypertension, Malaise, bone pain, weakness, pain in tumor-containing tissue, dizziness, jaw pain, skin vesiculation,. Current principles of chemotherapy for many types of cancer include the concurrent administration of several antineoplastic agents. For enhanced therapeutic effect without additive toxicity, agents with different dose-limiting clinical toxicities and different mechanisms of action are generally selected. Therefore, although vinblastine sulfate is effective as a single agent in the aforementioned indications, it is usually administered in combination with other antineoplastic drugs. Such combination therapy produces a greater percentage of response than does a single-agent regimen. These principles have been applied, for example, in the chemotherapy of Hodgkin's disease. Sternberg CN, de Mulder PH, Schornagel JH, Théodore C, Fossa SD, van Oosterom AT, et al. (2001). "Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924". J. Clin. Oncol. 19 (10): 2638–46. PMID 11352955.

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/index.php/Vinca

# Vinca Vinca (from Latin vincire "to bind, fetter") is a genus of five species in the family Apocynaceae, native to Europe, northwest Africa and southwest Asia. The common name, shared with the related genus Catharanthus, is Periwinkle. They are subshrubs or herbaceous, and have slender trailing stems 1-2 m (3-6 feet) long but not growing more than 20-70 cm (8-30 inches) above ground; the stems frequently take root where they touch the ground, enabling the plant to spread widely. The leaves are opposite, simple broad lanceolate to ovate, 1-9 cm (0.25-3.5 inches) long and 0.5-6 cm (0.25-2.25 inches) broad; they are evergreen in four species, but deciduous in the herbaceous V. herbacea, which dies back to the root system in winter. The flowers, produced through most of the year, are salverform (like those of Phlox), simple, 2.5-7 cm (1-3 inches) broad, with five usually violet (occasionally white) petals joined together at the base to form a tube. The fruit consists of a group of divergent follicles; a dry fruit which is dehiscent along one rupture site in order to release seeds. Two species, the Small Periwinkle V. minor and the Large Periwinkle V. major, are very popular ornamental plants in gardens, grown for dense evergreen ground cover and their delicate violet flowers. V. major has broader leaves with a hairy margin and larger flowers, is less cold hardy, and has twice as many chromosomes as V. minor. A variegated selection of V. major is commonly cultivated. Both species are considered invasive weeds in parts of the United States and Australia. They do not respond to common herbicides and require hormone based sprays to control. This plant was formerly used in homeopathy for catarrh, dyspepsia but due to the nature and effects of the alkaloids vincamine, isovincamine and vincamidine, it is rarely used. This plant also contains tannin. All parts of the periwinkles may cause stomach distress if ingested.

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# Vincamine Vincamine is a peripheral vasodilator that increases blood flow to the brain (sold under the trademark Oxybral SR) . Generic drugs containing vincamine exist in specific regions. Most common drug preparations are in the sustained release forms. Vincamine is a monoterpenoid indole alkaloid found in the leaves of Vinca minor, comprising about 25-65% of the indole alkaloids found in Vinca minor by weight. It can be synthesized from related alkaloids. Vincamine is often used as a nootropic agent to combat the effects of aging, or in conjunction with other nootropics (such as piracetam) for a variety of purposes.

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# Vincent T. DeVita DeVita earned his Bachelor of Science degree from the College of William and Mary in 1957. He was awarded his MD degree with distinction from the George Washington University School of Medicine in 1961. DeVita spent the early part of his career at the National Cancer Institute (NCI). In 1980, the president of the United States appointed him as director of the NCI and the National Cancer Program, a position he held until 1988. While at the NCI, he was instrumental in developing combination chemotherapy programs that ultimately led to an effective regimen of curative chemotherapy for Hodgkin's disease and diffuse large cell lymphomas. Along with colleagues at the NCI, he developed the four-drug combination, known by the acronym MOPP, which increased the cure rate for patients with advanced Hodgkin's disease from nearly zero to over 70%. DeVita was the Director of Yale Cancer Center 1993–2003. He is currently the chair of the Yale Cancer Center advisory board and is professor of internal medicine and of epidemiology and public health at Yale's medical school. DeVita currently serves on the editorial boards of numerous scientific journals and is the author or co-author of more than 450 scientific articles. He is one of the three editors of Cancer: Principles and Practice of Oncology and serves as the editor-in-chief of The Cancer Journal. Vincent DeVita diagnosed his son Ted as a child with aplastic anemia. Ted thereafter was placed in a sterile environment for his safety. Ted's situation, and that of David Vetter, inspired the 1976 TV movie The Boy in the Plastic Bubble starring John Travolta. Template:WH Template:WikiDoc Sources

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/index.php/Vincristine

# Vincristine sulfate Vincristine sulfate is a mitotic inhibitor that is FDA approved for the treatment of acute leukemia, Hodgkin's disease, non-Hodgkin's malignant lymphomas, rhabdomyosarcoma, neuroblastoma, Wilms' tumor. There is a Black Box Warning for this drug as shown here. Common adverse reactions include alopecia, constipation, nausea and vomiting. Vincristine sulfate is indicated in acute leukemia. Has also been shown to be useful in combination with other oncolytic agents in Hodgkin's disease, non-Hodgkin's malignant lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms' tumor. The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vincristine sulfate has been reported to reduce blood levels of the anticonvulsant and to increase seizure activity. Dosage adjustment should be based on serial blood level monitoring. The contribution of vincristine sulfate to this interaction is not certain. The interaction may result from reduced absorption of phenytoin and an increase in the rate of its metabolism and elimination. Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily, or in patients with hepatic dysfunction. Concurrent administration of vincristine sulfate with itraconazole (a known inhibitor of the metabolic pathway) has been reported to cause an earlier onset and/or an increased severity of neuromuscular side effects. This interaction is presumed to be related to inhibition of the metabolism of vincristine. Pregnancy Category (FDA): D Vincristine sulfate can cause fetal harm when administered to a pregnant woman. When pregnant mice and hamsters were given doses of vincristine sulfate that caused resorption of 23% to 85% of fetuses, fetal malformations were produced in those that survived. Five monkeys were given single doses of vincristine sulfate between days 27 and 34 of their pregnancies; 3 of the fetuses were normal at term, and 2 viable fetuses had grossly evident malformations at term. In several animal species, vincristine sulfate can induce teratogenesis as well as embryo death at doses that are nontoxic to the pregnant animal. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while receiving this drug, she should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Pregnancy Category (AUS): D There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Vincristine sulfate in women who are pregnant. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in bhuman milk and because of the potential for serious adverse reactions due to vincristine sulfate in nursing infants, a decision should be made either to discontinue nursing or the drug, taking into account the importance of the drug to the mother. Neither in vivo nor in vitro laboratory tests have conclusively demonstrated the mutagenicity of this product. Fertility following treatment with vincristine sulfate alone for malignant disease has not been studied in humans. Clinical reports of both male and female patients who received multiple-agent chemotherapy that included vincristine sulfate indicate that azoospermia and amenorrhea can occur in postpubertal patients. Recovery occurred many months after completion of chemotherapy in some but not all patients. When the same treatment is administered to prepubertal patients, permanent azoospermia and amenorrhea are much less likely. Patients who received chemotherapy with vincristine sulfate in combination with anti-cancer drugs known to be carcinogenic have developed second malignancies. The contributing role of vincristine sulfate in this development has not been determined. No evidence of carcinogenicity was found following intraperitoneal administration of vincristine sulfate in rats and mice, although this study was limited. Folinic acid has been observed to have a protective effect in normal mice that were administered lethal doses of vincristine sulfate. Isolated case reports suggest that folinic acid may be helpful in treating humans who have received an overdose of vincristine sulfate. It is suggested that 100 mg of folinic acid be administered intravenously every 3 hours for 24 hours and then every 6 hours for at least 48 hours. Theoretically (based on pharmacokinetic data), tissue levels of vincristine sulfate can be expected to remain significantly elevated for at least 72 hours. Treatment with folinic acid does not eliminate the need for the above-mentioned supportive measures. Most of an intravenous dose of vincristine is excreted into the bile after rapid tissue binding. Because only very small amounts of the drug appear in dialysate, hemodialysis is not likely to be helpful in cases of overdosage. An increase in the severity of side effects may be experienced by patients with liver disease that is severe enough to decrease biliary excretion. Enhanced fecal excretion of parenterally administered vincristine has been demonstrated in dogs pretreated with cholestyramine. There are no published clinical data on the use of cholestyramine as an antidote in humans. There are no published clinical data on the consequences of oral ingestion of vincristine. Should oral ingestion occur, the stomach should be evacuated. Evacuation should be followed by oral administration of activated charcoal and a cathartic. Treatment of patients following intrathecal administration of vincristine sulfate injection has included immediate removal of spinal fluid and flushing with Lactated Ringer's, as well as other solutions and has not prevented ascending paralysis and death. In one case, progressive paralysis in an adult was arrested by the following treatment initiated immediately after the intrathecal injection: The mechanisms of action of vincristine sulfate remain under investigation. The mechanism of action of vincristine sulfate has been related to the inhibition of microtubule formation in mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. Vincristine Sulfate, USP is a white to slightly yellow powder. It is soluble in methanol, freely soluble in water, but only slightly soluble in 95% ethanol. In 98% ethanol, vincristine sulfate, USP has an ultraviolet spectrum with maxima at 221 nm (∈ +47,100). Pharmacokinetic studies in patients with cancer have shown a triphasic serum decay pattern following rapid intravenous injection. The initial, middle, and terminal half-lives are 5 minutes, 2.3 hours, and 85 hours respectively; however, the range of the terminal half-life in humans is from 19 to 155 hours. The liver is the major excretory organ in humans and animals. The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily. This metabolic pathway may be impaired in patients with hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes . About 80% of an injected dose of vincristine sulfate appears in the feces and 10% to 20% can be found in the urine. Within 15 to 30 minutes after injection, over 90% of the drug is distributed from the blood into tissue, where it remains tightly, but not irreversibly, bound.

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/index.php/Vincristine_liposome

# Vincristine liposome Vincristine liposome is an mitotic inhibitor that is FDA approved for the treatment of adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies. There is a Black Box Warning for this drug as shown here. Common adverse reactions include constipation , nausea , pyrexia , fatigue , peripheral neuropathy , febrile neutropenia , diarrhea , anemia , decreased appetite, and insomnia.

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/index.php/Vinculin

# Vinculin In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton. Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane. Binding alternately to talin or α-actinin, vinculin's shape and, as a consequence, its binding properties are changed. The vinculin gene occurs as a single copy and what appears to be no close relative to take over functions in its absence. Its splice variant metavinculin (see below) also needs vinculin to heterodimerize and work in a dependent fashion. Vinculin is a 117-kDa cytoskeletal protein with 1066 amino acids. The protein contains an acidic N-terminal domain and a basic C-terminal domain separated by a proline-rich middle segment. Vinculin consists of a globular head domain that contains binding sites for talin and α-actinin as well as a tyrosine phosphorylation site, while the tail region contains binding sites for F-actin, paxillin, and lipids. Essentially, there is an 835 amino acid N-terminal head, which is split into four domains. This is linked to the C-terminal tail with a linker region. The recent discovery of the 3D structure sheds light on how this protein tailors its shape to perform a variety of functions. For example, vinculin is able to control the cell's motility by simply altering its shape from active to inactive. When in its 'inactive' state, vinculin's conformation is characterized by the interaction between its head and tail domains. And, when transforming to the 'active' form, such as when talin triggers binding, the intramolecular interaction between the tail and head is severed. In other words, when talin's binding sites (VBS) of α-helices bind to a helical bundle structure in vinculin's head domain, the 'helical bundle conversion' is initiated, which leads to the reorganization of the α-helices (α1- α-4), resulting in an entirely new five-helical bundle structure. This function also extends to cancer cells, and regulating their movement and proliferation of cancer to other parts of the body. Cell spreading and movement occur through the process of binding of cell surface integrin receptors to extracellular matrix adhesion molecules. Vinculin is associated with focal adhesion and adherens junctions, which are complexes that nucleate actin filaments and crosslinkers between the external medium, plasma membrane, and actin cytoskeleton. The complex at the focal adhesions consists of several proteins such as vinculin, α-actin, paxillin, and talin, at the intracellular face of the plasma membrane. In more specific terms, the amino-terminus of vinculin binds to talin, which, in turn, binds to β-integrins, and the carboxy-terminus binds to actin, phospholipids, and paxillin-forming homodimers. The binding of vinculin to talin and actin is regulated by polyphosphoinositides and inhibited by acidic phospholipids. The complex then serves to anchor actin filaments to the membrane and thus, helps to reinforce force on talin within the focal adhesions. The loss of vinculin impacts a variety of cell functions; it disrupts the formation of the complex, and prevents cell adhesion and spreading. The absence of the protein demonstrates a decrease in spreading of cells, accompanied by reduced stress fiber formation, formation of fewer focal adhesions, and inhibition of lamellipodia extension. It was discovered that cells that are deficient in vinculin have growth cones that advance more slowly, as well as filopodia and lamellipoida that were less stable than the wild-type. Based on research, it has been postulated that the lack of vinculin may decrease cell adhesion by inhibiting focal adhesion assembly and preventing actin polymerization. On the other hand, overexpression of vinculin may restore adhesion and spreading by promoting recruitment of cytoskeletal proteins to the focal adhesion complex at the site of integrin binding. Vinculin's ability to interact with integrins to the cytoskeleton at the focal adhesion appears to be critical for control of cytoskeletal mechanics, cell spreading, and lamellipodia formation. Thus, vinculin appears to play a key role in shape control based on its ability to modulate focal adhesion structure and function. Vinculin is present in equilibrium between an active and inactive state. The active state is triggered upon binding to its designated partner. These changes occur when vinculin interacts with focal adhesion points to which it is binding to. When vinculin resides in its inactive form, the protein is kept designated to the cytoplasm unlike the focal adhesion points bound from the active state. The molecule talin is thought to be the major initiator of vinculin activation due to its presence in focal complexes. The combinatorial model of vinculin states that either α-actinin or talin can activate vinculin either alone or with the assistance of PIP2 or actin. This activation takes place by separation of the head-tail connection within inactive vinculin. Vinculin binding sites are predominantly found in talin and talin-like molecules, enabling binding of vinculin to talin, stabilising integrin-mediated cell-matrix junctions. Talin, in turn, links integrins to the actin cytoskeleton. The consensus sequence for Vinculin binding sites is LxxAAxxVAxxVxxLIxxA, with a secondary structure prediction of four amphipathic helices. The hydrophobic residues that define the VBS are themselves 'masked' and are buried in the core of a series of helical bundles that make up the talin rod. Smooth muscles and skeletal muscles (and probably to a lower extent in cardiac muscle) in their well-differentiated (contractile) state co-express (along with vinculin) a splice variant carrying an extra exon in the 3' coding region, thus encoding a longer isoform meta-vinculin (meta VCL) of ~150KD molecular weight — a protein whose existence has been known since the 1980s. Translation of the extra exon causes a 68- to 79-amino acid acid-rich insert between helices I and II within the C-terminal tail domain. Mutations within the insert region correlate with hereditary idiopathic dilated cardiomyopathy. The length of the insert in metavinculin is 68 AA in mammals and 79 in frog. Compared metavinculin sequences from pig, man, chicken, and frog, and found the insert to be bipartite: the first part variable and the second highly conserved. Both vinculin isoforms co-localize in muscular adhesive structures, such as dense plaques in smooth muscles, intercalated discs in cardiomyocytes, and costameres in skeletal muscles. Metavinculin tail domain has a lower affinity for the head as compared with the vinculin tail. In case of metavinculin, unfurling of the C-terminal hydrophobic hairpin loop of tail domain is impaired by the negative charges of the 68-amino acid insert, thus requiring phospholipid-activated regular isoform of vinculin to fully activate the metavinculin molecule. In cases of Small Intestinal Bacterial Overgrowth presented as IBS symptoms, anti-cdtb antibodies have been identified to affect vinculin function, which is required in gut motility.

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/index.php/Vindesine

# Vindesine Vindesine is an anti-mitotic vinca alkaloid used in chemotherapy. It is used to treat many different types of cancer, including leukaemia, lymphoma, melanoma, breast cancer, and lung cancer.

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/index.php/Vinflunine

# Vinflunine Vinflunine (INN, trade name Javlor) is a novel fluorinated Vinca alkaloid undergoing research for the treatment of bladder cancer. It was originally discovered by the team of the Professor Jean-Claude Jacquesy (UMR CNRS 6514 - Poitiers University), developed by Laboratoires Pierre Fabre and was licensed to Bristol-Myers Squibb for development in certain countries, including the United States.

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/index.php/Vinorelbine

# Vinorelbine Vinorelbine is an antineoplastic that is FDA approved for the treatment of single agent or in combination with cisplatin for the first-line treatment of ambulatory patients with unresectable, advanced nonsmall cell lung cancer (NSCLC). There is a Black Box Warning for this drug as shown here. Common adverse reactions include alopecia, injection site reaction, diarrhea, nausea, vomiting, asthenia, neuromyopathy.

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/index.php/Vinpocetine

# Vinpocetine Vinpocetine (brand names: Cavinton, Intelectol; chemical name: ethyl apovincaminate) is a semisynthetic derivative of the vinca alkaloid vincamine (sometimes described as "a synthetic ethyl ester of apovincamine"), an extract from the lesser periwinkle plant. Vinpocetine was first isolated from the plant in 1975 by the Hungarian chemist Csaba Szántay. The mass production of the synthetic drug was started in 1978 by the Hungarian pharmaceutical company Richter Gedeon. Vinpocetine is reported to have cerebral blood-flow enhancing and neuroprotective effects, and is used as a drug in Eastern Europe for the treatment of cerebrovascular disorders and age-related memory impairment. Vinpocetine is not approved in the United States for pharmaceutical use, but it can be sold as a dietary supplement. Vinpocetine is widely marketed as a supplement for vasodilation and as a nootropic for the improvement of memory and cerebral metabolism. Vinpocetine has been identified as a potent anti-inflammatory agent that might have a potential role in the treatment of Parkinson's disease and Alzheimer's disease. As of 2003 only three controlled clinical trials had tested "older adults with memory problems". However, a 2003 Cochrane review determined that the results were inconclusive. Prior to 2003, a different study from 1985 had tested young, healthy adults, but this study had 12 subjects and used a short treatment period. Vinpocetine is widely used in the body building community as a vasodilator. Although no studies have been conducted on the effectiveness of vinpocetine on performance enhancement during exercise, both beneficial and adverse effects have been reported on body building forums.[citation needed] Kindling models in rats has shown Vinpocetine to exhibit anticonvulsant properties, the most pronounced anticonvulsant effects were observed in Pentylenetetrazole (PTZ)-kindled rats although there was also an effect on amygdala-kindled and neocortically-kindled rats. Vinpocetine has also been shown to abolished [3H]Glu release after in vivo exposure to 4-aminopyridine (4-AP) which suggests an important mechanism for vinpocetine anticonvulsant potential. Vinpocetine has been identified as a novel anti-inflammatory agent. Vinpocetine inhibits the up-regulation of NF-κB by TNFα in various cell tests. Reverse transcription polymerase chain reaction also shows that it reduced the TNFα-induced expression of the mRNA of proinflammatory molecules such as interleukin-1 beta, monocyte chemoattractant protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1). In mice, vinpocetine reduced lipopolysaccharide inoculation induced polymorphonuclear neutrophil infiltration into the lung. Neuroinflammatory processes can result in neuronal death in Parkinson's disease (PD) and Alzheimer's disease (AD). It has been suggested that "it would be interesting to test whether vinpocetine's antiinflammatory properties would have a protective effect in models of neurodegenerative conditions such as AD and PD." Vinpocetine has been shown to selectively inhibit voltage-sensitive Na+ channels, resulting in a dose-dependent decrease in evoked extracellular Ca+ ions in striatal nerve endings. The Na+ channel inhibiting properties of vinpocetine are thought to contribute to a general neuroprotective effect through blockade of excitotoxicity and attenuation of neuronal damage induced by cerebral ischemia/reperfusion. Vinpocetine is also a phosphodiesterase (PDE) type-1 inhibitor, (with an IC50 of approximately 10−5 M.) leading to increases in intracellular levels of cyclic guanosine 3'5'-monophosphate (cGMP), an action that causes the vasorelaxant effects of vinpocetine on cerebral smooth muscle tissue. Increases in neuronal levels of DOPAC, a metabolic breakdown product of dopamine, have been shown to occur in striatal isolated nerve endings as a result of exposure to vinpocetine. Such an effect is consistent with the biogenic pharmacology of reserpine, a structural relative of vinpocetine, which depletes catecholamine levels and causes depression as a side effect of the cardiovascular and anti-psychotic effects. However, this effect tends to be reversible upon cessation of Vinpocetine administration, with full remission typically occurring within 3–4 weeks. Vinpocetine is generally well-tolerated in humans. No serious side effects have thus far been noted in clinical trials, although none of these trials were long-term. Some users have reported headaches, especially at doses above 15 milligrams per day, as well as occasional upset stomach. Adverse drug-herb interactions have not been prevalent, and vinpocetine appears safe to take with other medications, including diabetes drugs, as well as blood thinners like Coumadin. However, it should be carefully noted that the safety of vinpocetine in pregnant women has not been evaluated. Vinpocetine has been implicated in one case to induce agranulocytosis, a condition in which granulocytes are markedly decreased. Some people have anecdotally noted that their continued use of vinpocetine reduces immune function. Commission E warned that vinpocetine reduced immune function and could cause apoptosis (cellular death) in the long term.

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/index.php/Vintafolide

# Vintafolide {{Drugbox | IUPAC_name =N-(4-{[(2-Amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-L-γ-glutamyl-L-α-aspartyl-L-arginyl-L-α-aspartyl-L-α-aspartyl-L-cysteine disulfide with methyl (5S,7R,9S)-5-ethyl-9-[(3aR,4R,5S,5aR,10bR,13aR)-3a-ethyl-4,5-dihydroxy-8-methoxy-6-methyl-5-({2-[(2-sulfanylethoxy)carbonyl]hydrazinyl}carbonyl)-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazol-9-yl]-5-hydroxy-1,4,5,6,7,8,9,10-octahydro-2H-3,7-methanoazacycloundecino[5,4-b]indol-9-carboxylate | synonyms = EC-145 | image = Vintafolide.png | width = 250px | alt = Vintafolide structure | image2 = | width2 = | CAS_number_Ref =  Y | CAS_number = 742092-03-1 | ATC_prefix = L01 | ATC_suffix = CA06 | PubChem = | IUPHAR_ligand = | DrugBank_Ref = | DrugBank = | ChemSpiderID_Ref =  Y | ChemSpiderID = 27444385 | UNII_Ref =  Y | UNII = | KEGG_Ref =  Y | KEGG = | ChEBI_Ref =  Y | ChEBI = | ChEMBL_Ref =  Y | ChEMBL = | C=86 | H=109 | N=21 | O=26 | S=2 | | molecular_weight = 1917 g/mol | smiles = [H]/N=C()/NCCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CSSCCOC(=O)NNC(=O)[C@@]1([C@H]2[C@]3(CCN4[C@H]3[C@]([C@H]1O)(C=CC4)CC)c5cc(c(cc5N2C)OC)[C@]6(C[C@@H]7C[C@](CN(C7)CCc8c6[nH]c9c8cccc9)(CC)O)C(=O)OC)O)C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CC[C@@H](C(=O)O)NC(=O)c1ccc(cc1)NCc1cnc2c(n1)c(=O)[nH]c(n2)N | StdInChI = 1S/C86H109N21O26S2/c1-6-82(129)35-42-36-85(78(127)132-5,64-47(21-26-106(39-42)41-82)46-12-8-9-13-50(46)95-64)49-30-48-57(34-58(49)131-4)105(3)75-84(48)23-27-107-25-11-22-83(7-2,74(84)107)76(125)86(75,130)77(126)103-104-81(128)133-28-29-134-135-40-56(73(123)124)100-70(119)55(33-62(113)114)99-69(118)54(32-61(111)112)98-67(116)51(14-10-24-90-79(87)88)96-68(117)53(31-60(109)110)94-59(108)20-19-52(72(121)122)97-66(115)43-15-17-44(18-16-43)91-37-45-38-92-65-63(93-45)71(120)102-80(89)101-65/h8-9,11-13,15-18,22,30,34,38,42,51-56,74-76,91,95,125,129-130H,6-7,10,14,19-21,23-29,31-33,35-37,39-41H2,1-5H3,(H,94,108)(H,96,117)(H,97,115)(H,98,116)(H,99,118)(H,100,119)(H,103,126)(H,104,128)(H,109,110)(H,111,112)(H,113,114)(H,121,122)(H,123,124)(H4,87,88,90)(H3,89,92,101,102,120)/t42-,51-,52-,53-,54-,55-,56-,74-,75+,76+,82-,83+,84+,85-,86-/m0/s1 | StdInChI_Ref = | StdInChIKey_Ref =  Y | StdInChIKey = KUZYSQSABONDME-QRLOMCMNSA-N }} Vintafolide is an investigational targeted cancer therapeutic currently under development by Endocyte and Merck & Co. It is a small molecule drug conjugate consisting of a small molecule targeting the folate receptor, which is overexpressed on certain cancers, such as ovarian cancer, and a potent chemotherapy drug, vinblastine. It is being developed with a companion imaging agent, etarfolatide, that identifies patients that express the folate receptor and thus would likely respond to the treatment with vintafolide. A Phase 3 study evaluating vintafolide for the treatment of platinum-resistant ovarian cancer (PROCEED trial) and a Phase 2b study(TARGET trial) in non-small-cell lung carcinoma (NSCLC) are ongoing. Vintafolide is designed to deliver the toxic vinblastine drug selectively to cells expressing the folate receptor using folate targeting. A Marketing Authorization Application (MAA) filing for vintafolide and etarfolatide for the treatment of patients with folate receptor-positive platinum-resistant ovarian cancer in combination with doxorubicin, pegylated liposomal doxorubicin (PLD), has been accepted by the European Medicines Agency. The drug received an orphan drug status in Europe in March 2012. Merck & Co. acquired the development and marketing rights to this experimental cancer drug from Endocyte in April 2012. The drug received orphan drug status in Europe in March 2012. Endocyte remains responsible for the development and commercialization of etarfolatide, a non-invasive companion imaging agent used to identify patients expressing the folate receptor that will likely respond to treatment with vintafolide. Vintafolide is designed to deliver the toxic vinblastine drug selectively to cells expressing the folate receptor using folate targeting. Merck ($MRK) and partner Endocyte ($ECYT) have stopped a late-stage study of the ovarian cancer-treating vintafolide on the advice of a data safety monitoring board, saying the much-hyped drug failed to move the needle on progression-free survival. Folate is required for cell division, and rapidly dividing cancer cells often express folate receptors in order to capture enough folate to support rapid cell growth. Elevated expression of the folate receptor occurs in many diseases, including other aggressively growing cancers and inflammatory disorders. Vintafolide binds to the folate receptor and is subsequently taken up by the cell through a natural internalization process called endocytosis. Once inside the cell, vintafolide's linker releases the chemotherapy drug which kills the cell.

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/index.php/Vinyl_chloride

# Vinyl chloride Vinyl chloride monomer (VCM), also known as chloroethene in IUPAC nomenclature, is an important industrial chemical chiefly used to produce its polymer, polyvinyl chloride (PVC). At room temperature, VCM is a toxic, colorless gas with a sickly sweet odor. Vinyl chloride was first produced in 1835 by Justus von Liebig and his student Henri Victor Regnault. They obtained it by treating ethylene dichloride with a solution of potassium hydroxide in ethanol. In 1912, Frans, a German chemist working for Griesheim-Elektron, patented a means to produce vinyl chloride from acetylene and hydrogen chloride using mercuric chloride as a catalyst. While this method was widely used during the 1930s and 1940s, it has since been superseded by more economical processes A vinyl chloride monomer manufacturing plant generally consists of seven (7) different plant areas, 1) the Ethylene Dichloride (EDC) production area; 2) the Reactors that convert EDC to VCM; 3) the Distillation towers that separate and purify the VCM product; 4) the Oxychlorination process area; 5) the By-product Recovery area; 6) the Environmental Protection area (Waste Treatment and Hazardous Waste storage); 7) the VCM and By-product storage . VCM is a chemical intermediate. It is not a final product. Due to the hazardous nature of VCM to human health there are no end products that use vinyl chloride in its monomer form. Once VCM has been polymerized it is very stable and non-hazardous and can be used for a great number of end products. VCM liquid is fed to polymerization reactors where it is converted from a monomer to a polymer PVC . The final product of the polymerization process is PVC in either a flake or pellet form. Literally, tens of billions of pounds of PVC is sold on the global market each year. From its flake or pellet form PVC is sold to companies that heat and mold the PVC into end products such as PVC pipe and bottles. Until 1974, VCM was used in aerosol spray propellant. Prior to the removal of VCM from hair spray the accumulation of vinyl chloride vapor in hair salons may have exceeded the NOAEL (NO Adverse Effect Level) exposure guidelines. Vinyl chloride depresses the central nervous system, and inhaling its vapors produces symptoms similar to alcohol intoxication. These include headache, dizziness, and loss of coordination, and in severe cases may progress to hallucination, unconsciousness, and death by respiratory failure. In the late 1960s, Dr. John Creech and Dr. Maurice Johnson were the first to clearly link and recognize the carcinogenicity of VCM to humans when workers in the PVC section of a B.F. Goodrich plant near Louisville, Kentucky, were diagnosed with liver angiosarcoma, a rare disease. Since that time, studies of PVC workers in Australia, Italy, Germany, and the UK have all associated certain types of occupational cancers with exposure to vinyl chloride. The link between angiosarcoma of the liver and long-term exposure to vinyl chloride is the only one which has been confirmed by the International Agency for Research on Cancer. All the cases of angiosarcoma developed from exposure to vinyl chloride monomer, were in workers who were exposed to very high VCM levels, routinely, for many years.

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/index.php/Vinyl_ether

# Vinyl ether Vinyl ether, also known as divinyl ether, divinyl oxide, Vinethene (pharmaceutical trade name) and ethenoxyethene (IUPAC), is a clear, nearly colorless, volatile liquid which was briefly used as an inhalation anesthetic. It can be cyclopolymerized by itself and serves as a cross-linker in copolymerizations. Much to the dismay of some pharmacologists, the synthesis and isolation of pure vinyl ether proved to be a difficult challenge for chemists; vinyl ether was suspected to be a nearly ideal anesthetic as its structure was the combination of an alkene and an ether. In practice, vinyl ether proved to have favorable properties that allowed its brief usage as an anesthetic; on the other hand, it left many unimpressed. Aggravated by the issue of potentially toxic degradation over long-term storage and possible hepatic toxicity, vinyl ether began to leave the operating theater. Today, vinyl ether is a relic in the field of anesthesiology; however, the analytical techniques used to study its pharmacology laid the groundwork for the testing of new anesthetic agents. The first preparation of vinyl ether was reported in 1887 by Semmler. (Major, 1935) This chemist reported the production of vinyl ether from its sulfur substituted analogue, divinyl sulfide (obtained from the essential oil of Allium Ursinum L.), by reaction with silver oxide. Semmler's product which boiled at 39 °C was found to be sulfur free and molecular weight determinations were theoretically in accordance with vinyl ether. In 1899, Knorr and Matthes attempted a synthesis of vinyl ether by exhaustive methylation of morpholine. (Major, 1935) They attained such a small quantity of product that no characterization was possible. Cretcher et al. reported, in 1925, what would become the foundation for one industrial method used to produce vinyl ether. It was stated that the action of heated sodium hydroxide upon β,β`-dichlorodiethyl ether produced a liquid boiling at 39 °C (among other identified products). (Major, 1935) However, in a subtly modified process Hibbert et al. reported the isolation of a product boiling at 34-35 °C, "divinyl ether". Finally, in 1929, a patent issued to Merck & Co reported isolation of vinyl ether boiling ca. 28 °C. The currently accepted boiling point of vinyl ether is 28.3 °C; the Merck patent, therefore, was the first to report the isolation of a pure product. Even before its isolation and characterization, the application of an unsaturated ether as an anesthetic interested some pharmacologists. One such pharmacologist, Chauncey Leake, was particularly captivated by the then theoretical vinyl ether. Leake predicted that vinyl ether would combine the properties of two anesthetic agents, ethyl ether, and ethylene. (Mazurek, 2007) As an anesthetic ethylene has many favorable properties, although its very low potency often requires hypoxic conditions to achieve full anesthesia. Ethyl Ether on the other hand is a fairly potent anesthetic but falls short of ethylene in some respects. In comparison to ether, ethylene has a much lower occurrence of post operative nausea; additionally, ethylene has faster induction and recovery times than ether. (McIntosch, 1925) Solely guided by predictions based upon structure, Leake perused the usage of vinyl ether as an inhalation anesthetic. (The Science News Letter, 1934) As vinyl ether was unknown in its pure form, Leake approached organic chemists at Berkeley asking them to synthesize this novel anesthetic. (Mazurek, 2007) Leake's colleagues however, were unable to prepare vinyl ether; later though, Leake received help from two Princeton chemists, Randolph Major and W. T. Ruigh. Using samples received from Princeton, in 1930, Leake and fellow researcher Mei-Yu Chen published a brief study characterizing the anesthetic effects of vinyl ether upon mice. In the conclusion of this study, they cordially invited further research of this drug. (Mazurek, 2007) This invitation was accepted; in 1933 Samuel Gelfan and Irving Bell of the University of Alberta published the first human trials of vinyl ether. They reported the experience of Gelfan himself as he was anesthetized with vinyl ether via the open drop technique. (The Science News Letter, 1934) Although, according to Leake, anesthesiologist Mary Botsford at the University of California was the first to clinically administer vinyl ether for a hysterectomy in early 1932. (Mazurek, 2007) Thenceforth, vinyl ether was studied extensively at other institutions, though political climate at Berkeley hindered further study by Leake. Vinyl ether had some success but its usage was limited by aforementioned concerns of liver toxicity and degradation upon long term storage. (Mazurek, 2007) Vinyl Ether is a volatile, flammable liquid with a sweet, ethereal non-irritating odor (described to be similar to ethyl chloride). It is practically insoluble in water (.53g/100g water at 37 °C) but miscible with ethanol, ethyl ether, oils and other organic solvents. Vinyl Ether is a rather unstable compound which with exposure to light or acid fumes decomposes to acetaldehyde and polymerizes into a glassy solid. Like many other ethers vinyl ether is also liable to form peroxides upon exposure to air and light. For these reasons vinyl ether is sold with inhibitors such as poly-phenols and amines to quell polymerization and peroxide formation. (Major, 1937) The anesthetic product was inhibited with .01% phenyl-α-napthylamine which gave it a faint violet fluorescence. (Finer, 1965) Vinyl Ether rapidly decolorizes a solution of bromine in carbon tetrachloride; it is also rapidly oxidized by aqueous potassium permanganate; sulfuric acid reacts with vinyl ether producing a black tarry resin and some acetaldehyde. (Major, 1935) In the United States, vinyl ether was sold under the trade name Vinethene. In addition to the normal inhibitors, vinyl ether intended for anesthetic use contained some ethanol (1.5-5%) to prevent frosting of the anesthetic mask. (Major, 1937) Despite inhibitors manufacturers warned that once opened vinyl ether should be used quickly. (Stumpf, 1935) Vinyl ether has a rapid onset with little excitement upon induction. Induction causes little coughing however produces increased salivation. (Finer, 1965) During anesthesia vinyl ether can cause some patients to twitch. In rare cases this twitching can lead to convulsions; these convulsions are treatable. (Martin, 1941) Additionally, morphine-atropine pre-medication usually prevents this problem. (Finer, 1965) The recovery from vinyl ether is rapid with only rare cases of post operative nausea and vomiting, although headache after anesthesia sometimes occurs. (Finer, 1965) Short operations pose little danger to the patient. Longer operations which use greater than 200ml of anesthetic can be dangerous due to hepatic and renal toxicity. In an attempt to circumvent the toxicity of vinyl ether while maintaining its favorable properties it was mixed 1:4 with ethyl ether producing 'Vinethene Anesthetic Mixture' (V.A.M.). V.A.M. shows smoother induction and recovery than ethyl ether alone yet is relatively non-toxic for longer procedures. (Finer, 1965) Though compared to ethyl ether V.A.M is less suitable for cases requiring deep anesthesia. (Martin, 1941) Vinyl ether is a potent anesthetic giving it a large safety margin; the ratio of the anesthetic to lethal does for vinyl ether is 1 to 2.4 (ethyl ether: 1:1.5). (Anderson, 1937) However, this potency is hard to control with simplistic equipment. While anesthetic machines were numerous during the years of vinyl ether's popularity, the simplistic 'open drop technique' also maintained its prevalence. Anesthetic machines of the time could suitably contain vinyl ether's potency, however, via the open drop technique smooth anesthesia for long procedures was hard to sustain. (Martin, 1941) Further aggravating this problem, warm temperatures increase the volatility of vinyl ether making it even harder to regulate via the open drop technique. (Stumpf, 1935) Overall, vinyl ether's only strengths compared to ethyl ether are favorable induction and recovery. During anesthesia vinyl ether has no particularly wonderful properties and is harder to control than other agents. Therefore, vinyl ether was commonly used as a preliminary anesthetic before administration of diethyl ether. Additionally, vinyl ether was only used for short operations or analgesia, e.g. dentistry and obstetrics. Vinyl ether was used infrequently for long operations because of toxicity, cost, and superior alternatives. Also, experiments were conducted with ethyl vinyl ether, a compound with one vinyl and one ethyl group. This substance produced results placing it between diethyl ether and divinyl ether both in terms of toxicity and speed of induction and recovery, producing promising results similar to V.A.M. (Grosskreutz, Davis 1956) Despite much simpler synthesis (vinylization of ethanol with acetylene) ethyl vinyl ether didn't enter widespread use in anasthetics, as superior halogenated ethers replaced it shortly after its first trials.

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/index.php/Viologen

# Viologen The Viologens are diquaternary derivatives of 4,4'-bipyridyl. The name comes from the fact that this class of compounds is easily reduced to the radical mono cation, which is intensely blue coloured. In an experimental electrolysis setup, viologen in solution with sodium sulfate is reduced at the cathode with simultaneous formation of hydrogen gas. oxygen generated at the anode is capable of oxidizing the radical ion back to the viologen. Viologens are investigated for use in electrochromic systems because of their ability to change color reversibly many times upon reduction and oxidation. Paraquat is a viologen used as a herbicide. In extended viologens conjugated oligomers such as based on aryl, ethylene and thiophene units are inserted between the pyridine units. The bipolaron di-oktyl bis(4-pyridyl)biphenyl viologen 2 in scheme 2 can be reduced by sodium amalgam in DMF to the neutral viologen 3. The resonance structures of the quinoid 3a and the diradical 3b contribute equally to the hybrid structure. The driving force for the contributing 3b is the restoration of aromaticity with the biphenyl unit. From X-ray crystallography it is established that the molecule is coplanar and with slight nitrogen pyramidalization and that the central carbon bonds a longer (144 pm) than what would be expected for a double bond (136 pm). Further research shows that the diradical exists as a mixture of triplets and singlets although remarkably an ESR signal is absent. In this sense the molecule resembles Chichibabin's hydrocarbon discovered in 1907. The blue color in solution and metallic green color as crystals are also in common. Compound 3 is a very strong reducing agent with a redox potential of - 1.48 V again because aromaticity is restored. The compound is also a liquid crystal with multiple liquid crystal phases in the melt as a result of the molecule's structure with a flat and rigid core and flexible linear alkyl arms.

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/index.php/Viomycin

# Viomycin Viomycin sulfate (Viocin®) is an polypeptide antibiotic used in the treatment of tuberculosis. It is produced by the actinomycete Streptomyces puniceus, that binds to RNA and inhibits prokaryotic protein synthesis and certain forms of RNA splicing.

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/index.php/Viperidae

# Viperidae The Viperidae are a family of venomous snakes commonly referred to as vipers, although the term viperids is more specific and distinguishes them from the viperines (subfamily Viperinae). These snakes are found all over the world, except in Australia and Madagascar. All have relatively long hinged fangs that permit deep penetration and injection of venom. Four subfamilies are currently recognized. All viperids have a pair of relatively long solenoglyphous (hollow) fangs, that are used to inject venom from glands located towards the rear of the upper jaws. Each of the two fangs is at the front of the mouth on a short maxillary bone that can rotate back and forth. When not in use, the fangs fold back against the roof of the mouth and are enclosed in a membranous sheath. The left and right fangs can be rotated together or independently. During a strike, the mouth can open nearly 180° and the maxilla rotates forward, erecting the fang. The jaws close on impact and powerful muscles that surround the venom glands contract to inject the venom as the fangs penetrate. This action is very fast; in defensive strikes it can be more a stab than a bite. Viperids use this mechanism both to immobilize their prey and in self-defense. Almost all vipers have keeled scales, a stocky build with a short tail, and, due to the location of the venom glands, a triangular-shaped head distinct from the neck. Their eyes have vertically elliptical, or slit-shaped, pupils that can open wide to cover most of the eye or close almost completely, which helps them to see in a wide range of light levels. Typically, vipers are nocturnal and ambush their prey. Compared to many other snakes, vipers often appear rather sluggish. Most are ovoviviparous, giving birth to live young, but a few lay eggs; the word "viper" is derived from Latin vivo = "I live" and pario = "I give birth". Experiments have shown that these snakes are capable of making decisions on how much venom to inject depending on the circumstances. In all cases, the most important determinant of venom expenditure is generally the size of the snake, with larger specimens being capable of delivering much more venom. Also, the species is important, since some are likely to inject more than others, how much venom is available, the accuracy of the strike, and the number of bites already delivered in a short space of time. In predatory bites, factors that influence the amount of venom injected include the size of the prey, the species of prey, and whether the prey item is held or released. The need to label prey for chemosensory relocation after a bite and release may also play a role. In defensive bites, the amount of venom injected may be determined by the size or species of the predator (or antagonist), as well as the assessed level of threat, although larger assailants and higher threat levels may not necessarily lead to larger amounts of venom being injected. Viperid venoms typically contain an abundance of protein-degrading enzymes, called proteases, that produce symptoms such as pain, strong local swelling and necrosis, blood loss from cardiovascular damage complicated by coagulopathy, and disruption of the blood clotting system. Death is usually caused by collapse in blood pressure. This is in contrast to elapid venoms that generally contain neurotoxins that disable muscle contraction and cause paralysis. Death from elapid bites usually results from asphyxiation because the diaphragm can no longer contract. However, this rule does not always apply: some elapid bites include proteolytic symptoms typical of viperid bites, while some viperid bites produce neurotoxic symptoms. Proteolytic venom is also dual-purpose: it is used for defense and to immobilize prey, as with neurotoxic venoms, and also many of the enzymes have a digestive function, breaking down molecules in prey items, such as lipids, nucleic acids, and proteins. This is important, as many vipers have weak digestive systems. Due to the nature of proteolytic venom, a viperid bite is often a very painful experience and should always be taken seriously, even though it is not necessarily fatal. Even with prompt and proper treatment, a bite can still result in a permanent scar, and in the worst cases the affected limb may even have to be amputated. A victim's fate is impossible to predict as this depends on many factors, including (but not limited to) the species and size of the snake involved, how much venom was injected (if any), and the size and condition of the patient before being bitten. The patient may also be allergic to the venom and/or the antivenin. That Viperidae is attributed to Oppel (1811), as opposed to Laurenti (1768) or Gray (1825), is subject to some interpretation. However, the consensus among leading experts is that Laurenti used viperae as the plural of vipera (Latin for "viper", "adder", or "snake") and did not intend for it to indicate a a family group taxon. Rather, it is attributed to Oppel, based on his Viperini as a distinct family group name, despite the fact that Gray was the first to use the form Viperinae.

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/index.php/Viral

# Virus A virus (from the Latin virus meaning "toxin" or "poison"), is a sub-microscopic infectious agent that is unable to grow or reproduce outside a host cell. Each viral particle, or virion, consists of genetic material, DNA or RNA, within a protective protein coat called a capsid. The capsid shape varies from simple helical and icosahedral (polyhedral or near-spherical) forms, to more complex structures with tails or an envelope. Viruses infect cellular life forms and are grouped into animal, plant and bacterial types, according to the type of host infected. Biologists debate whether or not viruses are living organisms. Some consider them non-living as they do not meet the criteria of the definition of life. For example, unlike most organisms, viruses do not have cells. However, viruses have genes and evolve by natural selection. Others have described them as organisms at the edge of life. Viral infections in human and animal hosts usually result in an immune response and disease. Often, a virus is completely eliminated by the immune system. Antibiotics have no effect on viruses, but antiviral drugs have been developed to treat life-threatening infections. Vaccines that produce lifelong immunity can prevent viral infections. The word is from the Latin virus referring to poison and other noxious substances, first used in English in 1392. Virulent, from Latin virulentus, "poisonous", dates to 1400. A meaning of "agent that causes infectious disease" is first recorded in 1728, before the discovery of viruses by the Russian-Ukrainian biologist Dmitry Ivanovsky in 1892. The adjective viral dates to 1948. Today, virus is used to describe the biological viruses discussed above and as a metaphor for other parasitically-reproducing things, such as memes or computer viruses (since 1972). The term virion is also used to refer to a single infective viral particle. The English plural form of virus is viruses. Viral diseases such as rabies, yellow fever and smallpox have affected humans for centuries. There is hieroglyphical evidence of polio in ancient Egyptian medicine, though the cause of this disease was unknown at the time. In the 10th century, Muhammad ibn Zakarīya Rāzi (Rhazes) wrote the Treatise on Smallpox and Measles, in which he gave the first clear descriptions of smallpox and measles. In the 1020s, Avicenna wrote The Canon of Medicine, in which he discovered the contagious nature of infectious diseases, such as tuberculosis and sexually transmitted diseases, and their distribution through bodily contact or through water and soil; stated that bodily secretion is contaminated by "foul foreign earthly bodies" before being infected; and introduced the method of quarantine as a means of limiting the spread of contagious disease. When the Black Death bubonic plague reached al-Andalus in the 14th century, Ibn Khatima discovered that infectious diseases are caused by microorganisms which enter the human body. The etiologic cause of the bubonic plague would later be identified as a bacterium. Another 14th century Andalusian physician, Ibn al-Khatib (1313-1374), wrote a treatise called On the Plague, in which he stated how infectious diseases can be transmitted through bodily contact and "through garments, vessels and earrings." In 1717, Mary Montagu, the wife of an English ambassador to the Ottoman Empire, observed local women inoculating their children against smallpox. In the late 18th century, Edward Jenner observed and studied Miss Sarah Nelmes, a milkmaid who had previously caught cowpox and was found to be immune to smallpox, a similar, but devastating virus. Jenner developed the smallpox vaccine based on these findings. After lengthy vaccination campaigns, the World Health Organization (WHO) certified the eradication of smallpox in 1979. In the late 19th century, Charles Chamberland developed a porcelain filter with pores small enough to remove cultured bacteria from their culture medium. Dimitri Ivanovski used this filter to study an infection of tobacco plants, now known as tobacco mosaic virus. He passed crushed leaf extracts of infected tobacco plants through the filter, then used the filtered extracts to infect other plants, thereby proving that the infectious agent was not a bacterium. Similar experiments were performed by several other researchers, with similar results. These experiments showed that viruses are orders of magnitude smaller than bacteria. The term virus was coined by the Dutch microbiologist Martinus Beijerinck, who showed, using methods based on the work of Ivanovski, that tobacco mosaic disease is caused by something smaller than a bacterium. He coined the Latin phrase "contagium vivum fluidum" (which means "soluble living germ") as the first idea of the virus. The first human virus identified was Yellow Fever virus. In the early 20th century, Frederick Twort discovered that bacteria could be infected by viruses. Felix d'Herelle, working independently, showed that a preparation of viruses caused areas of cellular death on thin cell cultures spread on agar. Counting the dead areas allowed him to estimate the original number of viruses in the suspension. The invention of electron microscopy provided the first look at viruses. In 1935, Wendell Stanley crystallized the tobacco mosaic virus and found it to be mostly protein. A short time later, the virus was separated into protein and nucleic acid parts. In 1939, Max Delbrück and E.L. Ellis demonstrated that, in contrast to cellular organisms, bacteriophage reproduce in "one step", rather than exponentially. A major problem for early virologists was the inability to propagate viruses on sterile culture media, as is done with cellular microorganisms. This limitation required medical virologists to infect living animals with infectious material, which is dangerous. The first breakthrough came in 1931, when Ernest William Goodpasture demonstrated the growth of influenza and several other viruses in fertile chicken eggs. However, some viruses would not grow in chicken eggs, and a more flexible technique was needed for propagation of viruses. The solution came in 1949 when John Franklin Enders, Thomas H. Weller and Frederick Chapman Robbins together developed a technique to grow the polio virus in cultures of living animal cells. Their methods have since been extended and applied to the growth of viruses and other infectious agents that do not grow on sterile culture media. The origin of modern viruses is not entirely clear. It may be that no single mechanism can account for their origin. They do not fossilize well, so molecular techniques have been the most useful means of hypothesising how they arose. Research in microfossil identification and molecular biology may yet discern fossil evidence dating to the Archean or Proterozoic eons. Two main hypotheses currently exist. Small viruses with only a few genes may be runaway stretches of nucleic acid originating from the genome of a living organism. Their genetic material could have been derived from transferable genetic elements such as plasmids or transposons, that are prone to moving within, leaving, and entering genomes. New viruses are emerging de novo and therefore, it is not always the case that viruses have "ancestors". Viruses with larger genomes, such as poxviruses, may have once been small cells that parasitized larger host cells. Over time, genes not required by their parasitic lifestyle would have been lost in a streamlining process known as "retrograde-evolution" or "reverse-evolution". The bacteria Rickettsia and Chlamydia are living cells that, like viruses, can only reproduce inside host cells. They lend credence to the streamlining hypothesis, as their parasitic lifestyle is likely to have caused the loss of genes that enabled them to survive outside a host cell. It is possible that viruses represent a primitive form of self replicating DNA and are a precursor to life as it is currently defined. Other infectious particles which are even simpler in structure than viruses include viroids, satellites, and prions. In taxonomy, the classification of viruses is difficult owing to the lack of a fossil record and the dispute over whether they are living or non-living. They do not fit easily into any of the domains of biological classification, and classification begins at the family rank. However, the domain name of Acytota (without cells) has been suggested. This would place viruses on a par with the other domains of Eubacteria, Archaea, and Eukarya. Not all families are currently classified into orders, nor all genera classified into families. In 1962, André Lwoff, Robert Horne, and Paul Tournier were the first to develop a means of virus classification, based on the Linnaean hierarchical system. This system based classification on phylum, class, order, family, genus, and species. Viruses were grouped according to their shared properties (not of their hosts) and the type of nucleic acid forming their genomes. Following this initial system, a few modifications were made and the International Committee on Taxonomy of Viruses was developed (ICTV). The International Committee on Taxonomy of Viruses (ICTV) developed the current classification system and put in place guidelines that put a greater weighting on certain virus properties to maintain family uniformity. A universal system for classifying viruses, and a unified taxonomy, has been established since 1966. In determining order, taxonomists should consider the type of nucleic acid present, whether the nucleic acid is single- or double-stranded, and the presence or absence of an envelope. After these three main properties, other characteristics can be considered: the type of host, the capsid shape, immunological properties and the type of disease it causes. The system makes use of a series of ranked taxons. The general structure is as follows: The recognition of orders is very recent; to date, only three have been named, and most families remain unplaced. The committee does not formally distinguish between subspecies, strains, and isolates. In total there are three orders, 56 families, nine subfamilies, and 233 genera. ICTV recognizes about 1,550 virus species, but about 30,000 virus strains and isolates are being tracked by virologists. The Nobel Prize-winning biologist David Baltimore devised the Baltimore classification system. The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification. The Baltimore classification of viruses is based on the mechanism of mRNA production. Viruses must generate positive strand mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. This classification places viruses into seven groups: As an example of viral classification, the chicken pox virus, Varicella zoster (VZV), belongs to family Herpesviridae, subfamily Alphaherpesvirinae and genus Varicellovirus. It remains unranked in terms of order. VZV is in Group I of the Baltimore Classification because it is a dsDNA virus that does not use reverse transcriptase. A complete virus particle, known as a virion, consists of nucleic acid surrounded by a protective coat of protein called a capsid. Viruses can have a lipid "envelope" derived from the host cell membrane. A capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological and antigenic distinction. Virally coded protein subunits will self-assemble to form a capsid, generally requiring the presence of the virus genome. However, complex viruses code for proteins which assist in the construction of their capsid. Proteins associated with nucleic acid are known as nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. Electron microscopy is the most common method used to study the morphology of viruses. To increase the contrast between viruses and the background, electron-dense "stains" are used. These are solutions of salts of heavy metals such as tungsten, that scatter the electrons from regions covered with the stain. When virus particles are coated with stain (positive staining), fine detail is obscured. Negative staining overcomes this problem by staining the background only. A medium-sized virion next to a flea is roughly equivalent to a human next to a mountain twice the size of Mount Everest. Some filoviruses have a total length of up to 1400 nm, however their capsid diameters are only about 80 nm. Most viruses which have been studied have a capsid diameter between 10 and 300 nanometres. Most viruses are unable to be seen with a light microscope but some are as large or larger than the smallest bacteria and can be seen under high optical magnification. More commonly, both scanning and transmission electron microscopes are used to visualize virus particles. An enormous variety of genomic structures can be seen among viral species; as a group they contain more structural genomic diversity than the entire kingdoms of either plants, animals, or bacteria. A virus may employ either DNA or RNA as the nucleic acid. Rarely do they contain both, however cytomegalovirus is an exception to this, possessing a DNA core with several mRNA segments. By far most viruses have RNA. Plant viruses tend to have single-stranded RNA and bacteriophages tend to have double-stranded DNA. Some virus species possess abnormal nucleotides, such as hydroxymethylcytosine instead of cytosine, as a normal part of their genome. Viral genomes may be circular, such as polyomaviruses, or linear, such as adenoviruses. The type of nucleic acid is irrelevant to the shape of the genome. Among RNA viruses, the genome is often divided up into separate parts within the virion and are called segmented. Double-stranded RNA genomes and some single-stranded RNA genomes are segmented. Each segment often codes for one protein and they are usually found together in one capsid. Every segment is not required to be in the same virion for the overall virus to be infectious, as demonstrated by the brome mosaic virus. A viral genome, irrespective of nucleic acid type, may be either single-stranded or double-stranded. Single-stranded genomes consist of an unpaired nucleic acid, analogous to one-half of a ladder split down the middle. Double-stranded genomes consist of 2 complementary paired nucleic acids, analogous to a ladder. Viruses, such as those belonging to the Hepadnaviridae, contain a genome which is partially double-stranded and partially single-stranded. Viruses that infect humans include double-stranded RNA (e.g. Rotavirus), single-stranded RNA (e.g. Influenza virus), single-stranded DNA (e.g. Parvovirus B19) and double-stranded DNA (Herpes virus). For viruses with RNA as their nucleic acid, the strands are said to be either positive-sense (called the plus-strand) or negative-sense (called the minus-strand), depending on whether it is complementary to viral mRNA. Positive-sense viral RNA is identical to viral mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation. DNA nomenclature is similar to RNA nomenclature, in that the coding strand for the viral mRNA is complementary to it (-), and the non-coding strand is a copy of it (+). Genome size in terms of the weight of nucleotides varies between species. The smallest genomes code for only four proteins and weigh about 106 Daltons, the largest weigh about 108 Daltons and code for over one hundred proteins. RNA viruses generally have smaller genome sizes than DNA viruses due to a higher error-rate when replicating, resulting in a maximum upper size limit. Beyond this limit, errors in the genome when replicating render the virus useless or uncompetitive. To compensate for this, RNA viruses often have segmented genomes where the genome is split into smaller molecules, thus reducing the chance of error. In contrast, DNA viruses generally have larger genomes due to the high fidelity of their replication enzymes. There is an evolutionary advantage in having a segmented genome. Different strains of a virus with a segmented genome, from a pig or a bird or a human for example, such as Influenza virus, can shuffle and combine with other genes producing progeny viruses or (offspring) that have unique characteristics. This is called reassortment or viral sex. This is one reason why Influenza virus constantly changes. Genetic recombination is the process by which a strand of DNA is broken and then joined to the end of a different DNA molecule. This can occur when viruses infect cells simultaneously and studies of viral evolution have shown that recombination has been rampant in the species studied. Recombination is common to both RNA and DNA viruses. Viruses undergo genetic change by several mechanisms. These include a process called genetic drift where individual bases in the DNA or RNA mutate to other bases. Most of these point mutations are silent in that they do not change the protein that the gene encodes, but others can confer evolutionary advantages such as resistance to antiviral drugs. Antigenic shift is where there is a major change in the genome of the virus. This occurs as a result of recombination or reassortment (see above). When this happens with influenza viruses, pandemics may result. By genome rearrangement the structure of the gene changes although no mutations have necessarily occurred. RNA viruses are much more likely to mutate than DNA viruses for the reasons outlined above. Viruses often exist as quasispecies or swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such quasispecies are a prime target for natural selection. Viral populations do not grow through cell division, because they are acellular; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves. A virus can still cause degenerative effects within a cell without causing its death; collectively these are termed cytopathic effects. Animal DNA viruses, such as herpesviruses, enter the host via endocytosis, the process by which cells take in material from the external environment. Frequently after a chance collision with an appropriate surface receptor on a cell, the virus penetrates the cell, the viral genome is released from the capsid, and host polymerases begin transcribing viral mRNA. New virions are assembled and released either by cell lysis or by budding off the cell membrane. Animal RNA viruses can be placed into about four different groups depending on their modes of replication. The polarity of the RNA largely determines the replicative mechanism, as well as whether the genetic material is single-stranded or double-stranded. Some RNA viruses are actually DNA-based but use an RNA-intermediate to replicate. RNA viruses are dependent on virally encoded RNA replicase to create copies of their genomes. Reverse transcribing viruses replicate using reverse transcription, which is the formation of DNA from an RNA template. Reverse transcribing viruses containing RNA genomes use a DNA intermediate to replicate, whereas those containing DNA genomes use an RNA intermediate during genome replication. Both types use the reverse transcriptase enzyme to carry out the nucleic acid conversion. Both types are susceptible to antiviral drugs that inhibit the reverse transcriptase enzyme, e.g. zidovudine and lamivudine. An example of the first type is HIV which is a retrovirus. Retroviruses often integrate the DNA produced by reverse transcription into the host genome. This is why HIV infection can at present, only be treated and not cured. Bacteriophages infect specific bacteria by binding to surface receptor molecules and then enter the cell. Within a short amount of time, in some cases, just minutes, bacterial polymerase starts translating viral mRNA into protein. These proteins go on to become either new virions within the cell, helper proteins which help assembly of new virions, or proteins involved in cell lysis. Viral enzymes aid in the breakdown of the cell membrane, and in the case of the T4 phage, in just over twenty minutes after injection over three hundred phages could be released. Viruses have been described as "organisms at the edge of life", but argument continues over whether viruses are truly alive. According to the United States Code they are considered microorganisms in the sense of biological weaponry and malicious use. Scientists, however, are divided. Things become more complicated as they look at viroids and prions. Viruses resemble other organisms in that they possess genes and can evolve in infected cells by natural selection. They can reproduce by creating multiple copies of themselves through self-assembly. Viruses do not have a cell structure (regarded as the basic unit of life), although they do have genes. Additionally, although they reproduce, they do not self-metabolize and require a host cell to replicate and synthesize new products. However, bacterial species such as Rickettsia and Chlamydia are considered living organisms but are unable to reproduce outside a host cell. An argument can be made that accepted forms of life use cell division to reproduce, whereas viruses spontaneously assemble within cells. The comparison is drawn between viral self-assembly and the autonomous growth of non-living crystals. Virus self-assembly within host cells has implications for the study of the origin of life, as it lends credence to the hypothesis that life could have started as self-assembling organic molecules. If viruses are considered alive, then the criteria specifying life will have to exclude the cell. If viruses are said to be alive, the question could follow of whether even smaller infectious particles, such as viroids and prions, are alive. Examples of common human diseases caused by viruses include the common cold, the flu, chickenpox and cold sores. Serious diseases such as Ebola, AIDS, avian influenza and SARS are caused by viruses. The relative ability of viruses to cause disease is described in terms of virulence. Other diseases are under investigation as to whether they too have a virus as the causative agent, such as the possible connection between Human Herpesvirus Six (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome. There is current controversy over whether the borna virus, previously thought of as causing neurological diseases in horses, could be responsible for psychiatric illnesses in humans. Viruses have different mechanisms by which they produce disease in an organism, which largely depends on the species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In multicellular organisms, if enough cells die the whole organism will start to suffer the effects. Although viruses cause disruption of healthy homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the herpes simplex virus, which cause cold sores, to remain in a dormant state within the human body. This is called latency and is a characteristic of the herpes viruses including the Epstein-Barr virus, which causes glandular fever, and the Varicella zoster virus, which causes chicken pox. Latent chickenpox infections return in later life as the disease called shingles. Some viruses can cause life-long or chronic infections, where the viruses continue to replicate in the body despite the hosts' defense mechanisms. This is common in Hepatitis B virus and Hepatitis C Virus infections. People chronically infected with the Hepatitis B virus are known as carriers who serve as reservoirs of infectious virus. In some populations, with a high proportion of carriers, the disease is said to be endemic. When diagnosing Hepatitis B virus infections, it is important to distinguish between acute and chronic infections. Viral epidemiology is the branch of medical science dealing with the transmission and control of virus infections in humans. Transmission of viruses can be vertical, that is from mother to child, or horizontal, which means from person to person. Examples of vertical transmission include Hepatitis B virus and HIV where the baby is born already infected with the virus. Another, more rare, example is the Varicella zoster virus, which although causing relatively mild infections in humans, can be fatal to the foetus and newly born baby. Horizontal transmission is the most common mechanism of spread of viruses in populations. Transmission can be exchange of blood by sexual activity, e.g. HIV, Hepatitis B and Hepatitis C; by mouth by exchange of saliva, e.g. Epstein-Barr virus, or from contaminated food or water, e.g. Norovirus; by breathing in viruses in the form of aerosols, e.g. Influenza virus; and by insect vectors such as mosquitoes, e.g. dengue. The rate or speed of transmission of viral infections depends on factors that include population density, the number of susceptible individuals, (i.e. those who are not immune), the quality of health care and the weather. Native American populations were devastated by contagious diseases, particularly smallpox, brought to the Americas by European colonists. It is unclear how many Native Americans were killed by foreign diseases after the arrival of Columbus in the Americas, but the numbers have been estimated to be close to 70% of the indigenous population. The damage done by this disease significantly aided European attempts to displace and conquer the native population. A pandemic is a world-wide epidemic. The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus. The victims were often healthy young adults, in contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients. The Spanish flu pandemic lasted from 1918 to 1919. Older estimates say it killed 40–50 million people, while more recent research suggests that it may have killed as many as 100 million people, or 5% of the world's population in 1918. Most researchers believe that HIV originated in sub-Saharan Africa during the twentieth century; it is now a pandemic, with an estimated 38.6 million people now living with the disease worldwide. As of January 2006, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on June 5, 1981, making it one of the most destructive epidemics in recorded history. Several highly lethal viral pathogens are members of the Filoviridae. Filoviruses are filament-like viruses that cause viral hemorrhagic fever, and include the Ebola and Marburg viruses. The Marburg virus attracted widespread press attention in April 2005 for an outbreak in Angola. Beginning in October 2004 and continuing into 2005, the outbreak was the world's worst epidemic of any kind of viral hemorrhagic fever. Viruses are an established cause of malignancy in humans and other species. The main viruses associated with human cancers are human papillomavirus, hepatitis B and hepatitis C virus, Epstein-Barr virus, and human T-lymphotropic virus. Hepatitis viruses, including hepatitis B and hepatitis C, can induce a chronic viral infection that leads to liver cancer. Infection by human T-lymphotropic virus can lead to tropical spastic paraparesis and adult T-cell leukemia. Human papillomaviruses are an established cause of cancers of cervix, skin, anus, and penis. Within the Herpesviridae, Kaposi's sarcoma-associated herpesvirus causes Kaposi's sarcoma and body cavity lymphoma, and Epstein–Barr virus causes Burkitt's lymphoma, Hodgkin's lymphoma, B lymphoproliferative disorder and nasopharyngeal carcinoma. Because viruses use the machinery of a host cell to reproduce and reside within them, they are difficult to eliminate without killing the host cell. The most effective medical approaches to viral diseases so far are vaccinations to provide resistance to infection, and antiviral drugs which treat the symptoms of viral infections. The body's first line of defense against viruses is the innate immune system. This comprises cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognize, and respond to, pathogens in a generic way, but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host. RNA interference is an important innate defense against viruses. Many viruses have a replication strategy that involves double-stranded RNA dsRNA. When such a virus infects a cell, it releases its RNA molecule or molecules, which immediately bind to a protein complex called Dicer that cuts the RNA into smaller pieces. A biochemical pathway called the RISC complex is activated which degrades the viral mRNA and the cell survives the infection. Rotaviruses avoid this mechanism by not uncoating fully inside the cell and by releasing newly produced mRNA through pores in the particle's inner capsid. The genomic dsRNA remains protected inside the core of the virion. When the adaptive immune system of a vertebrate encounters a virus, it produces specific antibodies which bind to the virus and render it non-infectious. This is called humoral immunity. Two types of antibodies are important. The first called IgM is highly effective at neutralizing viruses but is only produced by the cells of the immune system for a few weeks. The second, called, IgG is produced indefinitely. The presence of IgM in the blood of the host is used to test for acute infection, whereas IgG indicates an infection sometime in the past. Both types of antibodies are measured when tests for immunity are carried out. A second defense of vertebrates against viruses is called cell-mediated immunity and involves immune cells known as T cells. The body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed by T killer cells and the virus-specific T-cells proliferate. Cells such as the macrophage are specialists at this antigen presentation. Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing the amino acid sequence of the proteins on the surface of the virion. These persistent viruses evade immune control by sequestration, blockade of antigen presentation, cytokine resistance, evasion of natural killer cell activities, escape from apoptosis, and antigenic shift. Other viruses, called "neurotropic viruses", are disseminated by neural spread where the immune system may be unable to reach them. Vaccination is a cheap and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity (illness) and mortality (death) associated with viral infections such as polio, measles, mumps and rubella. Smallpox infections have been eradicated. Currently vaccines are available to prevent over thirteen viral infections of humans, and more are used to prevent viral infections of animals. Vaccines can consist of live-attenuated or killed viruses, or viral proteins (antigens). Live vaccines contain weakened forms of the virus that causes the disease. Such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity, (who are described as immunocompromised), because in these people, the weakened virus can cause the original disease. Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine. Subunit vaccines are safe for immunocompromised patients because they cannot cause the disease. The Yellow Fever virus vaccine, a live-attenuated strain called 17D, is arguably the safest and most effective vaccine ever generated. Over the past twenty years, the development of antiviral drugs has increased rapidly. This has been driven by the AIDS epidemic. Antiviral drugs are often nucleoside analogues, (fake DNA building blocks), which viruses incorporate into their genomes during replication. The life-cycle of the virus is then halted because the newly synthesized DNA is inactive. This is because these analogues lack the hydroxyl groups which along with phosphorus atoms, link together to form the strong "backbone" of the DNA molecule. This is called DNA chain termination. Examples of nucleoside analogues are aciclovir for Herpes virus infections and lamivudine for HIV and Hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs. Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the HIV-1 protease for it to become fully infectious. There is a class of drugs called protease inhibitors which have been designed to inactivate the enzyme. Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease is chronic, and without treatment, they are infected and infectious for the remainder of their lives. However, there is now an effective treatment using the nucleoside analogue drug ribavirin combined with interferon. The treatment of chronic carriers of the Hepatitis B virus by using a similar strategy using lamivudine is being developed. Viruses are important to the study of molecular and cellular biology as they provide simple systems that can be used to manipulate and investigate the functions of cells. The study and use of viruses have provided valuable information about aspects of cell biology. For example, viruses have been useful in the study of genetics and helped our understanding of the basic mechanisms of molecular genetics, such as DNA replication, transcription, RNA processing, translation, protein transport, and immunology. Geneticists often use viruses as vectors to introduce genes into cells that they are studying. This is useful for making the cell produce a foreign substance, or to study the effect of introducing a new gene into the genome. In similar fashion, virotherapy uses viruses as vectors to treat various diseases, as they can specifically target cells and DNA. It shows promising use in the treatment of cancer and in gene therapy. Eastern European scientists have used phage therapy as an alternative to antibiotics for some time, and interest in this approach is increasing, due to the high level of antibiotic resistance now found in some pathogenic bacteria. Current trends in nanotechnology promise to make much more versatile use of viruses. From the viewpoint of a materials scientist, viruses can be regarded as organic nanoparticles. Their surface carries specific tools designed to cross the barriers of their host cells. The size and shape of viruses, and the number and nature of the functional groups on their surface, is precisely defined. As such, viruses are commonly used in materials science as scaffolds for covalently linked surface modifications. A particular quality of viruses is that they can be tailored by directed evolution. The powerful techniques developed by life sciences are becoming the basis of engineering approaches towards nanomaterials, opening a wide range of applications far beyond biology and medicine. Because of their size, shape, and well-defined chemical structures, viruses have been used as templates for organizing materials on the nanoscale. Recent examples include work at the Naval Research Laboratory in Washington, DC, using Cowpea Mosaic Virus (CPMV) particles to amplify signals in microarray based sensors. In this application, the virus particles separate the fluorescent dyes used for signaling in order to prevent the formation of non-fluorescent dimers that act as quenchers. Another example is the use of CPMV as a nanoscale breadboard for molecular electronics. In April 2006, scientists at the Massachusetts Institute of Technology (MIT) created nanoscale metallic wires using a genetically-modified virus. The MIT team was able to use the virus to create a working battery with an energy density up to three times more than current materials. The potential exists for this technology to be used in liquid crystals, solar cells, fuel cells, and other electronics in the future. The ability of viruses to cause devastating epidemics in human societies has led to the concern that viruses could be weaponized for biological warfare. Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory. The smallpox virus devastated numerous societies throughout history before its eradication. It currently exists in several secure laboratories in the world, and fears that it may be used as a weapon are not totally unfounded. The vaccine for smallpox is not safe, and during the years before the eradication of smallpox disease more people became seriously ill as a result of vaccination than did people from smallpox and smallpox vaccination is no longer universally practiced. Thus, the modern global human population has almost no established resistance to smallpox; if it were to be released, a massive loss of life could be sustained before the virus is brought under control. Norovirus. This RNA virus causes winter vomiting disease. It is often in the news as a cause of gastro-enteritis on cruise ships and in hospitals.

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# Viral envelope Many viruses (e.g. influenza and many animal viruses) have viral envelopes covering their protein capsids. The envelopes are typically derived from portions of the host cell membranes (phospholipids and proteins), but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells. Glycoproteins on the surface of the envelope serve to identify and bind to receptor sites on the host's membrane. The viral envelope then fuses with the host's membrane, allowing the capsid and viral genome to enter and infect the host. Usually, the cell from which the virus itself buds from goes on to survive, and shed more viral particles for an extended period. Interestingly, the lipid bilayer envelope of these viruses is relatively sensitive to desiccation, heat and detergents, and so these viruses are easier to sterilize than non-enveloped viruses - in other words they cannot survive outside host environment and must transfer directly from host to host.

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/index.php/Viral_gastroenteritis_(patient_information)

# Viral gastroenteritis (patient information) Viral gastroenteritis is inflammation of the stomach and intestines from a virus. The infection can lead to diarrhea and vomiting. It is sometimes called the "stomach flu." Viral gastroenteritis is a leading cause of severe diarrhea in both adults and children. Many types of viruses can cause gastroenteritis. The most common ones are: Tests that examine stool samples may be used to identify the specific virus. This is usually not needed for viral gastroenteritis. A stool culture may be done to identify a bacterial cause for diarrhea. The goal of treatment is to prevent dehydration by making sure the body has as much water and fluids as it should. Fluids and electrolytes (salt and minerals) lost through diarrhea or vomiting must be replaced by drinking extra fluids. Even if you are able to eat, you should still drink extra fluids between meals. People with diarrhea who are unable to drink fluids because of nausea may need intravenous (directly into a vein) fluids. This is especially true in small children. Antibiotics do not work for viruses. Drugs to slow down the amount of diarrhea (anti-diarrheal medications) should not be given without first talking with your health care provider. They may cause the infection to last longer. DO NOT give these anti-diarrheal medications to children unless directed to do so by a health care provider. People taking water pills (diuretics) who develop diarrhea may be told by their health care provider to stop taking the diuretic during the acute episode. However, DO NOT stop taking any prescription medicine without first talking to your doctor. The risk of dehydration is greatest in infants and young children, so parents should closely monitor the number of wet diapers changed per day when their child is sick. Most infectious organisms are transmitted by unwashed hands. The best way to prevent viral gastroenteritis is to handle food properly and wash hands thoroughly after using the toilet. Vaccination to prevent severe rotavirus infection is recommended for infants starting at an age of 2 months.

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# Viral gastroenteritis epidemiology and demographics Viral gastroenteritis affects people in all parts of the world. Each virus has its own seasonal activity. For example, in the United States, rotavirus and astrovirus infections occur during the cooler months of the year (October to April), whereas adenovirus infections occur throughout the year. Norovirus outbreaks can occur in institutional settings, such as schools, child care facilities, and nursing homes, and can occur in other group settings, such as banquet halls, cruise ships, dormitories, and campgrounds. Viral gastroenteritis occurs in people of all ages and backgrounds. However, some viruses tend to cause diarrheal disease primarily among people in specific age groups. Rotavirus and norovirus infections are the most common cause of diarrhea in infants and young children under 5 years old. Adenoviruses and astroviruses cause diarrhea mostly in young children, but older children and adults can also be affected. Norwalk and Noroviruses are more likely to cause diarrhea in older children and adults.

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# Viral gastroenteritis history and symptoms The main symptoms of viral gastroenteritis are watery diarrhea and vomiting. The affected person may also have headache, fever, and abdominal cramps ("stomach ache"). In general, the symptoms begin 1 to 2 days following infection with a virus that causes gastroenteritis and may last for 1 to 10 days, depending on which virus causes the illness. Symptoms can be listed as follows:

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# Viral gastroenteritis laboratory findings Rotavirus infection can be diagnosed by laboratory testing of a stool specimen. Tests to detect other viruses that cause gastroenteritis are not in routine use, but the viral gastroenteritis unit at the CDC can assist with special analysis upon request.

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# Viral gastroenteritis medical therapy The most important aspect of treating viral gastroenteritis in children and adults is to prevent dehydration. This treatment should begin at home. A physician may give specific instructions about what kinds of fluid to give. CDC recommends that families with infants and young children keep a supply of oral rehydration solution (ORS) at home at all times and use the solution when diarrhea first occurs in the child. Medications, including antibiotics (which have no effect on viruses) and other treatments, should be avoided unless specifically recommended by a physician. The goal of treatment is to prevent dehydration by making sure the body has as much water and fluids as it should. Fluids and electrolytes (salt and minerals) lost through diarrhea or vomiting must be replaced by drinking extra fluids. Even if the patient is ablee to eat, he should still drink extra fluids between meals. People with diarrhea who are unable to drink fluids because of nausea may need intravenous (directly into a vein) fluids. This is especially true in small children. Antibiotics do not work for viruses. Drugs to slow down the amount of diarrhea (anti-diarrheal medications) should not be given without first talking with your health care provider. They may cause the infection to last longer. Do not give these anti-diarrheal medications to children unless directed to do so by a health care provider. People taking water pills (diuretics) who develop diarrhea may be told by their health care provider to stop taking the diuretic during the acute episode. However, do not stop taking any prescription medicine without first talking to your doctor. The risk of dehydration is greatest in infants and young children, so parents should closely monitor the number of wet diapers changed per day when their child is sick.

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# Viral gastroenteritis overview Gastroenteritis is the inflammation of the stomach and the small and large intestines. Viral gastroenteritis is an infection caused by a variety of viruses that results in vomiting or diarrhea. It is often called the "stomach flu," although it is not caused by the influenza viruses. Many different viruses can cause gastroenteritis, including rotaviruses, noroviruses, adenovirus type 40 or 41, sapoviruses, and astroviruses. Viral gastroenteritis is not caused by bacteria (such as Salmonella or Escherichia coli) or parasites (such as Giardia), or by medications or other medical conditions, although the symptoms may be similar. Currently, there is a licensed rotavirus vaccine available that protects against severe diarrhea from rotavirus infection in infants and young children. Studies into a norovirus vaccine are underway. Persons can reduce their chance of getting infected by frequent handwashing, prompt disinfection of contaminated surfaces with household chlorine bleach-based cleaners, and prompt washing of soiled articles of clothing. If food or water is thought to be contaminated, it should be avoided.

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# Viral hemorrhagic fever (patient information) Viral hemorrhagic fevers (VHFs) refer to a group of illnesses that are caused by several distinct families of viruses. The term "viral hemorrhagic fever" commonly describes a severe multi-organ syndrome. In this condition the vascular system is usually affected, diminishing the body's ability to regulate itself. The symptoms may include bleeding, however, this is seldom life-threatening. The severity of the disease will depend on the underlying virus causing it, and can range from mild to life-threatening. Geographically, these viruses are distributed over the globe. However, since each virus has its own host, some diseases are more commonly seen in certain areas than others. Because the incubation period may be as long as 21 days, patients may not develop illness until returning from travel; therefore, a thorough travel and exposure history are critical. Some VHFs are spread on person to person basis, through direct contact with symptomatic patients, body fluids, cadavers or through inadequate infection control measures (filoviruses, arenaviruses, CCHF virus). Zoonotic spread includes the following: US-based clinicians should notify CDC's Viral Special Pathogens Branch immediately of any suspected cases of VHF occurring in patients residing in or requiring evacuation to the United States: 404-639-1115 or the CDC Emergency Operations Center at 770-488-7100 after hours. CDC also provides consultation for international clinicians and health ministries. Whole blood or serum may be tested for virologic (RT-PCR, antigen detection, virus isolation) and immunologic (IgM, IgG) evidence of infection. Tissue may be tested with the following tests: Postmortem skin biopsies fixed in formalin and blood collected within a few hours after death by cardiac puncture can be used for diagnosis. Samples should be sent for testing to a reference laboratory with biosafety level 3 and 4 capability. In most cases there is no specific treatment, with supportive care being the only remaining alternative. Ribavirin, an anti-viral drug, has been effective for treating Lassa fever, New World arenaviruses, and likely CCHF. However, it is not approved by the Food and Drug Administration (FDA) for these indications. Convalescent-phase plasma is effective in treating Argentine hemorrhagic fever. Investigational vaccines exist for Argentine hemorrhagic fever and RVF however, neither is approved by FDA or commonly available in the United States. The CDC in conjunction with the WHO, has developed practical, hospital-based guidelines, titled Infection Control for Viral Haemorrhagic Fevers In the African Health Care Setting.

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# Viral hemorrhagic fever epidemiology and demographics Taken together, the viruses that cause VHFs are distributed over much of the globe. However, because each virus is associated with one or more particular host species, the virus and the disease it causes are usually seen only where the host species live(s). Some hosts, such as the rodent species carrying several of the New World arena viruses, live in geographically restricted areas. Therefore, the risk of getting VHFs caused by these viruses is restricted to those areas. Other hosts range over continents, such as the rodents that carry viruses which cause various forms of hantavirus pulmonary syndrome (HPS) in North and South America, or the different set of rodents that carry viruses which cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. A few hosts are distributed nearly worldwide, such as the common rat. It can carry Seoul virus, a cause of HFRS; therefore, humans can get HFRS anywhere where the common rat is found. While people usually become infected only in areas where the host lives, occasionally people become infected by a host that has been exported from its native habitat. For example, the first outbreaks of Marburg hemorrhagic fever, in Marburg and Frankfurt, Germany, and in Yugoslavia, occurred when laboratory workers handled imported monkeys infected with Marburg virus. Occasionally, a person becomes infected in an area where the virus occurs naturally and then travels elsewhere. If the virus is a type that can be transmitted further by person-to-person contact, the traveler could infect other people. For instance, in 1996, a medical professional treating patients with Ebola hemorrhagic fever (Ebola HF) in Gabon unknowingly became infected. When he later traveled to South Africa and was treated for Ebola HF in a hospital, the virus was transmitted to a nurse. She became ill and died. Because more and more people travel each year, outbreaks of these diseases are becoming an increasing threat in places where they rarely, if ever, have been seen before.

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# Viral hemorrhagic fever future or investigational therapies Scientists and researchers are challenged with developing containment, treatment, and vaccine strategies for these diseases. Another goal is to develop immunologic and molecular tools for more rapid disease diagnosis, and to study how the viruses are transmitted and exactly how the disease affects the body (pathogenesis). A third goal is to understand the ecology of these viruses and their hosts in order to offer preventive public health advice for avoiding infection.

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# Viral hemorrhagic fever history and symptoms Signs and symptoms of VHFs include (by definition) fever and bleeding diathesis. Specific signs and symptoms vary by the type of VHF, but initial signs and symptoms often include marked fever, fatigue, dizziness, muscle aches, loss of strength, and exhaustion. Patients with severe cases of VHF often show signs of bleeding under the skin, in internal organs, or from body orifices like the mouth, eyes, or ears. However, although they may bleed from many sites around the body, patients rarely die because of blood loss. Severely ill patient cases may also show shock, nervous system malfunction, coma, delirium, and seizures. Some types of VHF are associated with renal (kidney) failure.

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# Viral hemorrhagic fever medical therapy Medical management of VHF patients may require intensive supportive care. Antiviral therapy with intravenous ribavirin may be useful in Bunyaviridae and Arenaviridae infections (specifically Lassa fever, RVF, CCHF, and HFRS due to Old World Hantavirus infection) and can be used only under an experimental protocol as a US FDA approved investigational new drug (IND). Convalescent plasma may be effective in Argentine or Bolivian hemorrhagic fevers (also available only as IND).

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# Viral hemorrhagic fever overview The viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses that are caused by five distinct families of RNA viruses: the Arenaviridae, Filoviridae, Bunyaviridae, Togaviridae, and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in extreme cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, whilst others, such as the African Ebola virus, can cause severe, life-threatening disease. In conjunction with the World Health Organization, CDC has developed practical, hospital-based guidelines, titled Infection Control for Viral Haemorrhagic Fevers In the African Health Care Setting. The manual can help health-care facilities recognize cases and prevent further hospital-based disease transmission using locally available materials and few financial resources.

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# Viral hemorrhagic fever pathophysiology The diversity of clinical features seen among the VHF infections probably originates from varying mechanisms of pathogenesis. An immunopathogenic mechanism, for example, has been identified for dengue hemorrhagic fever, which usually occurs among patients previously infected with a heterologous dengue serotype. An influential theory explaining this phenomenon is called "antibody-dependent enhancement." In contrast, disseminated intravascular coagulation (DIC) is thought to underlie the hemorrhagic features of Rift Valley, Marburg and Ebola fevers. In most VHFs, however, the etiology of the coagulopathy is most likely multifactorial (e.g., hepatic damage, consumptive coagulopathy, primary marrow dysfunction, etc). The reasons for variation among patients infected with the same virus are unknown but stem from a complex system of virus-host interactions. Moreover, why some infected persons develop full-blown VHF while others do not also remains an unresolved issue. Virulence of the infecting agent clearly plays an important role. The "VHF syndrome" (capillary leak, bleeding diathesis and hemodynamic compromise leading to shock) occurs in a majority of patients manifesting disease from filoviruses, CCHF and the South American hemorrhagic fever viruses, while it occurs in a small minority of patients with dengue, RVF and Lassa fever. Viruses associated with most VHFs are zoonotic. This means that these viruses naturally reside in an animal reservoir host or arthropod vector. They are totally dependent on their hosts for replication and overall survival. For the most part, rodents and arthropods are the main reservoirs for viruses causing VHFs. The multimammate rat, cotton rat, deer mouse, house mouse, and other field rodents are examples of reservoir hosts. Arthropod ticks and mosquitoes serve as vectors for some of the illnesses. However, the hosts of some viruses remain unknown -- Ebola and Marburg viruses are well-known examples. Viruses causing hemorrhagic fever are initially transmitted to humans when the activities of infected reservoir hosts or vectors and humans overlap. The viruses carried in rodent reservoirs are transmitted when humans have contact with urine, fecal matter, saliva, or other body excretions from infected rodents. The viruses associated with arthropod vectors are spread most often when the vector mosquito or tick bites a human, or when a human crushes a tick. However, some of these vectors may spread virus to animals, livestock, for example. Humans then become infected when they care for or slaughter the animals. Some viruses that cause hemorrhagic fever can spread from one person to another, once an initial person has become infected. Ebola, Marburg, Lassa and Crimean-Congo hemorrhagic fever viruses are examples. This type of secondary transmission of the virus can occur directly, through close contact with infected people or their body fluids. It can also occur indirectly, through contact with objects contaminated with infected body fluids. For example, contaminated syringes and needles have played an important role in spreading infection in outbreaks of Ebola hemorrhagic fever and Lassa fever.

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# Viral hemorrhagic fever primary prevention With the exception of yellow fever and Argentine hemorrhagic fever, for which vaccines have been developed, no vaccines exist that can protect against these diseases. Therefore, prevention efforts must concentrate on avoiding contact with host species. If prevention methods fail and a case of VHF does occur, efforts should focus on preventing further transmission from person to person, if the virus can be transmitted in this way.Because many of the hosts that carry hemorrhagic fever viruses are rodents, disease prevention efforts include For those hemorrhagic fever viruses that can be transmitted from one person to another, avoiding close physical contact with infected people and their body fluids is the most important way of controlling the spread of disease. Barrier nursing or infection control techniques include isolating infected individuals and wearing protective clothing. Other infection control recommendations include proper use, disinfection, and disposal of instruments and equipment used in treating or caring for patients with VHF, such as needles and thermometers.

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# Viral hemorrhagic fever risk factors The likelihood of acquiring VHF is considered low in persons who do not meet any of these criteria. Even following travel to areas where VHF has occurred, persons with fever are more likely to have infectious diseases other than VHF (e.g., common respiratory viruses, endemic infections such as malaria or typhoid fever). Clinicians should promptly evaluate and treat patients for these more common infections while awaiting confirmation of a VHF diagnosis. In Africa, transmission of VHF in healthcare settings has been associated with reuse of contaminated needles and syringes and with provision of patient care without appropriate barrier precautions to prevent exposure to virus-containing blood and other body fluids (including vomitus, urine, and stool). The transmission risks associated with various body fluids have not been well defined because most caregivers who have acquired infection had contacts with multiple fluids. The risk for person-to-person transmission of hemorrhagic fever viruses is greatest during the latter stages of illness when virus loads are highest; latter stages of illness are characterized by vomiting, diarrhea, shock, and, in less than half of infected patients, hemorrhage. No VHF infection has been reported in persons whose contact with an infected person occurred only during the incubation period (i.e., before onset of fever). The incubation period for VHF ranges from 2 days to 3 weeks, depending on the viral agent. There are reports of Ebola virus transmission occurring within a few days after onset of fever; however, the presence of other symptoms in the source patients and the level of exposure to body fluids among secondary cases are unknown in these instances (CDC, unpublished data, 1995). In studies involving three monkeys experimentally infected with Ebola virus (Reston strain), fever and other systemic signs of illness preceded detection of infectious virus in the animals' pharynx by 2-4 days, in the conjunctiva and on anal swabs by 5-6 days, and in the nares by 5-10 days.

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# Viral load Viral load is a measure of the severity of a viral infection, and can be calculated by estimating the amount of virus in an involved body fluid, for example, it can be given in RNA copies per milliliter of blood plasma. Determination of viral load is part of the therapy monitoring during chronic viral infections and in immunocompromised patients, e.g. after bone marrow or solid organ transplantation. Currently, routine testing is available for HIV-1, cytomegalovirus, hepatitis B virus, and hepatitis C virus. These tests have been approved by the Food and Drug Administration in the United States for use in monitoring the health of people with HIV, in conjunction with other markers. Higher numbers in the viral load tests indicate an increased risk of getting sick from opportunistic diseases. These tests are also approved for monitoring the effects of anti-HIV therapy, to track viral suppression and detect treatment failure. Successful combination antiretroviral therapy should give a fall in viral load of 1.5 to 2 logs (30-100 fold) within six weeks, with the viral load falling below the limit of detection within four to six months. An inexpensive, largely manual HIV viral load assay has also been developed which depends on measuring virus-associated reverse transcriptase (RT) activity (ExaVir Load Version 2)([Cavidi AB] , Uppsala, Sweden). This test has a lower limit of detection of 400 RNA copies/ml. The test was developed primarily for use in resource-limited environments, such as southern Africa. Viral load tests can also be used to diagnose HIV infection, especially in children under 18 months born to mothers with HIV, where the presence of maternal antibodies prevents the use of antibody-based (ELISA) diagnostic tests. Persons with HIV are most contagious during the earliest stages of infection, when an antibody test would yield a negative result. Therefore, the importance of viral load testing is deemed important for yielding an earlier HIV diagnosis. Since persons are most contagious during early infection, widespread testing could provide significant public health benefits. The results of these tests are usually given as number of HIV RNA copies per milliliter (ml) of blood. The PCR test may give the number of HIV RNA copies per 0.05/ml, so one would multiply the result by 20 to get the standard result.

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# Viral shedding Template:Viral life cycle Viral shedding refers to the successful production of virus progeny and that the progeny is leaving the cell to infect other host cells. Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods . The term is used to refer to shedding from a single cell, shedding from one part of the body into another part of the body, and shedding from bodies into the environment where the viruses may infect other bodies. "Budding" through the cell envelope, in effect using the cell's membrane for the virus itself is most effective for viruses that need an envelope in the first place. These include enveloped viruses such as HSV, SARS or smallpox. Prior to budding, the virus may put its own receptor onto the surface of the cell in preparation for the virus to bud through, forming an envelope with the viral receptors already on it. This process will slowly use up the cell membrane and eventually lead to the demise of the cell. This is also how antiviral responses are able to detect virus infected cells . By forcing the cell to undergo apoptosis or cell suicide, release of progeny into the extracellular space is possible. However, apoptosis does not necessarily result in the cell simply popping open, spilling its contents into the extracellular space. Rather, apoptosis is usually controlled and results in the cell's genome being chopped up, before apoptotitic bodies of dead cell material clump off the cell to be absorbed by macrophages. This is a good way for a virus to get into macrophages either to infect them or simply travel to other tissues in the body. Although this process is primarily used by non-enveloped viruses, enveloped viruses may also use this. HIV is an example of an enveloped virus that exhibits this process for the infection of macrophages . It may not be in a virus's best interest to kill the cell in order to escape it for further infection of other host cells. It is then reverse endocytotic release of viral progeny is used to release viral particles. Viral progeny are synthesized within the cell and the host cell's transport system is used to enclose vacuoles of virus progeny for release into the extracellular space. This is used primarily by non-enveloped viruses, although enveloped viruses display this too. An example is the use of recycling viral particle receptors in the enveloped varicella-zoster virus .

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/index.php/Viral_vector

# Viral vector Viral vectors are a tool commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (in vivo) or in cell culture (in vitro). Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect. Delivery of genes by a virus is termed transduction and the infected cells are described as transduced. Molecular biologists first harnessed this machinery in the 1970s. Paul Berg used a modified SV40 virus containing DNA from the bacteriophage lambda to infect monkey kidney cells maintained in culture. Viral vectors were originally developed as an alternative to transfection of naked DNA for molecular genetic experiments. Compared to traditional methods such as calcium phosphate precipitation, transduction can ensure that nearly 100% of cells are infected without severely affecting cell viability. Furthermore, some viruses integrate into the cell genome facilitating stable expression. However, transfection is still the method of choice for many applications as construction of a viral vector is a much more laborious process. Protein coding genes can be expressed using viral vectors, commonly to study the function of the particular protein. Viral vectors, especially retroviruses, stably expressing marker genes such as GFP are widely used to permanently label cells to track them and their progeny, for example in xenotransplantation experiments, when cells infected in vitro are implanted into a host animal. Genes inserted into the vector can encode shRNAs and siRNAs used to efficiently block or silence production of a specific protein. Such knock-down experiments are much quicker and cheaper to carry out than gene knockout. But as the silencing is sometimes non-specific and has off-target effects on other genes, it provides less reliable results. In the future gene therapy may provide a way to cure genetic disorders, such as severe combined immunodeficiency or cystic fibrosis. Several gene therapy trials have used viruses to deliver 'good' genes to the cells of the patient's body. There have been a huge number of laboratory successes with gene therapy. However, several problems of viral gene therapy must be overcome before it gains widespread use. Immune response to viruses not only impedes the delivery of genes to target cells but can cause severe complications for the patient. In one of the early gene therapy trials in 1999 this led to the death of Jesse Gelsinger, who was treated using an adenoviral vector. Some viral vectors, for instance lentiviruses, insert their genomes at a seemingly random location on one of the host chromosomes, which can disturb the function of cellular genes and lead to cancer. In a severe combined immunodeficiency retroviral gene therapy trial conducted in 2002, two of the patients developed leukemia as a consequence of the treatment. Adeno-associated virus-based vectors are much safer in this respect as they always integrate at the same site in the human genome. Viruses expressing pathogen proteins are currently being developed as vaccines against these pathogens, based on the same rationale as DNA vaccines. T-lymphocytes recognize cells infected with intracellular parasites based on the foreign proteins produced within the cell. T cell immunity is crucial for protection against viral infections and such diseases as malaria. A viral vaccine induces expression of pathogen proteins within host cells similarly to the Sabin Polio vaccine and other attenuated vaccines. However, since viral vaccines contain only a small fraction of pathogen genes, they are much safer and sporadic infection by the pathogen is impossible. Adenoviruses are being actively developed as vaccines. Retroviruses are the one of mainstays of current gene therapy approaches. The recombinant retroviruses such as the Moloney murine leukemia virus have the ability to integrate into the host genome in a stable fashion. They contain a reverse transcriptase which allows integration into the host genome. They have been used in a number of FDA-approved clinical trials such as the SCID-X1 trial. The primary drawback to use of retroviruses such as the Moloney retrovirus involves the requirement for cells to be actively dividing for transduction. As a result, cells such as neurons are very resistant to infection and transduction by retroviruses. There is a concern for insertional mutagensis due to the integration into the host genome which can lead to cancer or leukemia. Lentiviruses are a subclass of Retroviruses. They are widely adapted as vectors thanks to their ability integrate into the genome of non-dividing as well as dividing cells. The viral genome in the form of RNA is reverse-transcribed when the virus enters the cell to produce DNA, which is then inserted into the genome at a random position by the viral integrase enzyme. The vector, now called a provirus, remains in the genome and is passed on to the progeny of the cell when it divides. The site of integration is unpredictable, which can pose a problem. The provirus can disturb the function of cellular genes and lead to activation of oncogenes promoting the development of cancer, which raises concerns for possible applications of lentiviruses in gene therapy. For safety reasons lentiviral vectors never carry the genes required for their replication. To produce a lentivirus, several plasmids are transfected into a so-called packaging cell line, commonly HEK 293. One or more plasmids, generally referred to as packaging plasmids, encode the virion proteins, such as the capsid and the reverse transcriptase. Another plasmid contains the genetic material to be delivered by the vector. It is transcribed to produce the single-stranded RNA viral genome and is marked by the presence of the ψ (psi) sequence. This sequence is used to package the genome into the virion. As opposed to lentiviruses, adenoviral DNA does not integrate into the genome and is not replicated during cell division. This limits their use in basic research, although adenoviral vectors are occasionally used in in vitro experiments. Their primary applications are in gene therapy and vaccination. Since humans commonly come in contact with adenoviruses, which cause respiratory, gastrointestinal and eye infections, they trigger a rapid immune response with potentially dangerous consequences. To overcome this problem scientists are currently investigating adenoviruses to which humans do not have immunity.

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/index.php/Viramidine

# Viramidine Viramidine (ICN 3142, also known as taribavirin) is an anti-viral drug in Phase III human trials, but not yet approved for pharmaceutical use. It is a prodrug of ribavirin, active against a number of DNA and RNA viruses. Viramidine has better liver-targeting than ribavirin, and has a shorter life in the body due to less penetration and storage in red blood cells. It is expected eventually to be the drug of choice for viral hepatitis syndromes in which ribavirin is active. These include hepatitis C and perhaps also hepatitis B and yellow fever. Viramidine is as active against influenza as ribavirin in animal models, with slightly less toxicity, so it may also eventually replace ribavirin as an anti-influenza agent. Viramidine is being developed by Valeant Pharmaceuticals International, the parent company of Ribapharm, the company which first reported synthesis and testing of the drug in 1973. Valeant is testing the drug as a treatment for chronic hepatitis C.

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/index.php/Virchow%27s_triad

# Virchow's triad It is named after the eminent German physician Rudolf Virchow (1821-1902). However, the elements comprising Virchow's triad were neither proposed by Virchow, nor did he ever suggest a triad to describe the pathogenesis of venous thrombosis. In fact, it was decades following Virchow's death before a consensus was reached proposing that thrombosis is the result of alterations in blood flow, vascular endothelial injury, or alterations in the constitution of the blood. Still, the modern understanding of the factors leading to embolism are similar to the description provided by Virchow. Its nebulous origins notwithstanding, Virchow's triad remains a useful concept for clinicians and pathologists alike in understanding the contributors to thrombosis. The origin of the term "Virchow's Triad" is of historical interest, and has been subject to reinterpretation in recent years. While both Virchow's and the modern triads describe thrombosis, the previous triad has been characterized as "the consequences of thrombosis", and the modern triad as "the causes of thrombosis". Rudolf Virchow elucidated the etiology of pulmonary embolism, whereby thrombi occurring within the veins, particularly those of the extremities, become dislodged and migrate to the pulmonary vasculature. He published his description in 1856 In detailing the pathophysiology surrounding pulmonary embolism, he alluded to many of the factors known to contribute to venous thrombosis. While these factors had already been previously established in the medical literature by others, for unclear reasons they ultimately became known as Virchow's triad. This eponym did not emerge in the literature until long after Virchow's death. One estimate of the first use of the phrase dates it to the early 1950s. Although the concept of the triad is usually attributed to Virchow, he did not include endothelial injury in his description. This has been attributed to a dispute Virchow had with Jean Cruveilhier, who considered local trauma of primary importance in the development of pulmonary artery thrombosis.

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/index.php/Viremia

# Viremia Viremia is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body. It is similar to bacteremia, a condition where bacteria enter the bloodstream. The name comes from combining the word virus with the Greek word for blood (haima). Secondary viremia occurs when primary viremia has resulted in infection of additional tissues via bloodstream, in which the virus has replicated and once more entered the circulation. Usually secondary viremia results in higher viral shedding and viral loads within the bloodstream due to the possibility that the virus is able to reach its natural host cell from the bloodstream and replicate more efficiently than the initial site. An excellent example to profile this distinction is the rabies virus. Usually the virus will replicate briefly within the first site of infection, within the muscle tissues. Viral replication then leads to viremia and the virus spreads to its secondary site of infection, the Central nervous system (CNS). Upon infection of the CNS, secondary viremia results and symptoms usually begin. Vaccination at this point is useless, as the spread to the brain is unstoppable. Vaccination must be done before secondary viremia takes place for the individual to avoid brain damage or death. Active viremia is caused by the replication of viruses which results in viruses being introduced into the bloodstream. Examples include the measles, in which primary viremia occurs in the epithelial lining of the respiratory tract before replicating and budding out of the cell basal layer (viral shedding), resulting in viruses budding into capillaries and blood vessels. Passive viremia is the introduction of viruses in the bloodstream without the need of active viral replication. Examples include direct inoculation from mosquitoes, through physical breaches or via blood transfusions.

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/index.php/Virginia_Mason_Medical_Center

# Virginia Mason Medical Center Virginia Mason Medical Center (VMMC), founded in 1920, is a private, non-profit organization located on Seattle, Washington's First Hill offering a system of integrated health services. Gary S. Kaplan, MD, serves as chairman and CEO, and J. Michael Rona is president, although Rona announced his resignation on April 20, 2007 . The medical center includes: The organization was named after the daughters of its two founders: Dr. Tate Mason's daughter, Virginia Mason, and Dr. John Blackford's daughter, Virginia Mason Blackford.

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/index.php/Virginiamycin

# Virginiamycin Virginiamycin is a streptogramin antibiotic similar to pristinamycin and quinupristin/dalfopristin. It is a combination of pristinamycin IIA (virginiamycin M1) and virginiamycin S1. Virginiamycin is used in the fuel ethanol industry to prevent microbial contamination. It is also used in agriculture, specifically in livestock, to accelerate the growth of the animals and to prevent and treat infections. Antibiotics also save as much as 30% in feed costs among young swine, although the savings fade as pigs get older, according to a USDA study.

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/index.php/Virilization

# Virilization In biology and medicine, virilization refers to the biological development of sex differences, changes which make a male body different from a female body. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology of gender contexts: prenatal sexual differentiation, the postnatal changes of normal male puberty, and excessive androgen effects in girls or women. In the prenatal period, virilization refers to closure of the perineum, thinning and rugation of the scrotum, growth of the phallus, and closure of the urethral groove to the tip of the penis. In this context masculinization is synonymous with virilization. Prenatal virilization of genetic females and undervirilization of genetic males are common causes of ambiguous genitalia and intersex conditions. Undervirilization can occur if a genetic male cannot produce enough androgen or the body tissues cannot respond to it. Extreme undervirilization occurs when no significant androgen can be produced or the body is completely insensitive to it, and results in a female body. Partial undervirilization produces ambiguous genitalia part way between male and female. The mildest degree of undervirilization may be a slightly small penis with hypospadias. Examples of undervirilization are androgen insensitivity syndrome, 5 alpha reductase deficiency, and some forms of congenital adrenal hyperplasia. Prenatal virilization (or masculinization) of a genetically female fetus can occur when an excessive amount of androgen is produced by the fetal adrenal glands or is present in maternal blood. In the severest form of congenital adrenal hyperplasia complete masculinization of a genetically female fetus results in an apparently normal baby boy with no palpable testes. More often, the virilization is partial and the genitalia are ambiguous. In common as well as medical usage, virilization often refers to the process of normal male puberty, in which testosterone changes a boy's body into a man's. These effects include growth of the penis and testes, accelerated growth, development of pubic hair and other androgenic hair of face, torso, and limbs, deepening of the voice, increased musculature, thickening of the jaw, prominence of the neck cartilage, and broadening of the shoulders. Virilization can occur in childhood in either boys or girls due to excessive amounts of androgens. Typical effects of virilization in children are pubic hair, accelerated growth and bone maturation, increased muscle strength, acne, adult body odor, and sometimes growth of the penis. In a boy, virilization may signal precocious puberty, while congenital adrenal hyperplasia and androgen producing tumors (usually) of the gonads or adrenals are occasional causes in both sexes. Virilization in a woman can manifest as clitoral enlargement, increased muscle strength, acne, hirsutism, frontal hair thinning, deepening of the voice, and menstrual disruption due to anovulation. Some of the possible causes of virilization in women are:

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/index.php/Virkon

# Virkon Virkon is a brand name for a powerful, multi-purpose disinfectant. The solution is used in many areas, including hospitals, laboratories, nursing homes, funeral homes, medical, dental and veterinary facilities, and anywhere else where control of pathogens is required. It is typically used for cleaning up hazardous spills, disinfecting surfaces and soaking equipment. Virkon has a remarkable spectrum of activity against viruses, fungi, spores and bacteria, including mycobacteria such as tuberculosis. It is also effective against SARS and Avian influenza. However, for full effectiveness it must be sprayed liberally on a surface and allowed to sit for at least two (and up to ten) minutes before being wiped off. It is most often sold as pink tablets or powder which dissolve readily in water. It is intended to be mixed with water to form a 1% to 3% solution (by weight, i.e. 10g to 30g per litre). The pink colour is useful in that in helps gauge the concentration when preparing the Virkon, and importantly, as the Virkon ages it discolours, making it obvious when it needs to be replaced. The solution is generally stable for five to seven days. Virkon has a faint lemon odor, but the scent is still considered unpleasant by some. It is relatively safe in terms of skin contact, but can cause eye damage and should not be used as a hand-washing liquid. When ordered in bulk, Virkon costs about 35 US cents per litre to produce, which is comparable to most bleaches. Nevertheless, some facilities prefer to produce their own alternative disinfectants to save costs. Virkon is a registered trademark of Antec International, a subsidiary of DuPont. As of 2006, DuPont has been slowly rebranding Virkon as a part of its "RelyOn" disinfectant range.

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/index.php/ViroPharma

# ViroPharma ViroPharma Incorporated, a pharmaceutical company, develops and sells drugs that address serious diseases treated by physician specialists and in hospital settings. The company focuses on product development activities on viral diseases, including those caused by cytomegalovirus (CMV) and hepatitis C virus (HCV) infections. ViroPharma Incorporated was founded in 1994 by Claude H. Nash (Chief Executive Officer), Mark A. McKinlay (Vice President, Research & Development), Marc S. Collett (Vice President, Discovery Research), Johanna A. Griffin (Vice President, Business Development), and Guy D. Diana (Vice President, Chemistry Research.) Maribavir is an oral antiviral drug candidate licensed from GlaxoSmithKline in 2003 for the prevention and treatment of human cytomegalovirus disease in hematopoietic stem cell/bone marrow transplant patients. In March 2006, the company announced that a Phase II study with maribavir demonstrated that prophylaxis with maribavir displays strong antiviral activity, as measured by statistically significant reduction in the rate of reactivation of CMV in recipients of hematopoietic stem cell/bone marrow transplants. In an intent-to-treat analysis of the first 100 days after the transplant, the number of subjects who required pre-emptive anti-CMV therapy was statistically significantly reduced (p-value = 0.051 to 0.001) in each of the maribavir groups compared to the placebo group (57% for placebo vs. 15%, 30%, and 15% for maribavir 100 mg twice daily, 400 mg daily, and 400 mg twice daily, respectively). In February 2006, ViroPharma announced that the United States Food and Drug Administration (FDA) had granted the company Fast Track status for Maribavir. The Fast Track program is designed to facilitate the development, and expedite the review, of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. In September 2006, ViroPharma announced the start of a Phase III clinical study to evaluate the prophylactic use for the prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplant patients. In November 2005, ViroPharma announced preliminary results from a proof of concept study. In this study, HCV-796 demonstrated antiviral effects in adult patients with chronic hepatitis C infection. The patient cohort with the highest exposure to HCV-796 achieved a peak mean HCV viral load reduction of 1.4 log10, or 96 percent, on day four of a 14 day dosing period. HCV-796 was generally well tolerated, with a favorable pharmacokinetic profile and no dose-limiting toxicities. In August 2006, the company released results of a Phase I study of HCV-796 in combination with pegylated interferon that demonstrated a 3.3 to 3.5 log10 decrease in viral load. Oral pleconaril was ViroPharma's first compound, licensed from Sanofi in 1997. Pleconaril is active against viruses in the picornavirus family. ViroPharma's first indication was for enteroviral meningitis, but that indication was abandoned when the clinical trials did not demonstrate efficacy. In 2001, ViroPharma submitted an New Drug Application of pleconaril to the FDA for the common cold. On 2002-03-19, the FDA Antiviral Advisory Committee recommended that the company had failed to show adequate safety, and the FDA subsequently issued a not-approvable letter. After the Advisory Committee meeting the stock price fell from 22 USD at the beginning of 2002 to an all time low of 0.87 USD on 2002-10-28. (The stock price recovered in 2005.) In November 2003, ViroPharma licensed pleconaril to Schering-Plough, who are developing an intranasal formulation for the common cold and asthma exacerbations. (Schering-Plough Development Pipeline). In August 2006, Schering-Plough started a Phase II clinical trial.

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/index.php/Virodhamine

# Virodhamine Virodhamine (O-arachidonoyl ethanolamine) is an endocannibinoid and a nonclassic eicosanoid, derived from arachidonic acid. O-Arachidonoyl ethanolamine is arachidonic acid and ethanolamine joined by an ester linkage, the opposite of the amide linkage found in anandamide. Based on this opposite orientation, the molecule was named virodhamine from the Sanskrit word virodha, which means opposition. It is an antagonist of the CB1 receptor and an agonist of CB2. Concentrations of virodhamine in the human hippocampus are similar to anandamide, but they were 2- to 9-fold higher in peripheral tissues that express CB2. Virodhamine lowers body temperature in mice, demonstrating cannabinoid activity in vivo.

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/index.php/Virokine

# Virokine The word "virokine" was originally coined by Dr. Bernard Moss. It is used to designate viral proteins that interfere with immune response by reducing cytokine levels or effectiveness. They may do so by suppressing cytokine secretion, competing for cytokine receptors, interfering with cytokine signalling pathways, or otherwise antagonizing cytokines of the host organism. Many virokines are similar to host cytokines and may have been acquired by gene transfer from the host and subsequently modified.

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/index.php/Virola

# Virola Virola, also known as Epená, is a genus of medium-sized trees native to the South American rainforest and closely related to other Myristicaceae, such as nutmeg. It has glossy, dark leaves with clusters of tiny yellow flowers and emits a pungent odor. The dark-red resin of the tree bark contains several hallucinogenic alkaloids, most notably 5-MeO-DMT(Virola calophylla), 5-OH-DMT (Bufotenine), and also N,N-DMT, perhaps the most "powerful" member of the Dimethyltryptamine family; it also contains beta-carboline harmala alkaloids, MAOIs that greatly potentiate the effects of DMT. The bark resin is prepared and dried by a variety of methods, often including the addition of ash or lime, presumably as basifying agents, and a powder made from the leaves of the small Justicia bush. Ingestion is similar to that of Yopo, consisting of assisted insufflation, with the snuff being blown through a long tube into the nostrils by an assistant. According to Schultes, the use of Virola in magico-religious rituals is restricted to tribes in the Western Amazon Basin and parts of the Orinoco Basin. The tops of Virola oleifera have been shown to produce lignan-7-ols and verrucosin that have antifungal action regarding Cladosporium sphaerospermum in doses as low as 25 micrograms. Lignan-7-ols oleiferin-B and oleiferin-G worked for C. cladosporoides starting as low as 10 micrograms.

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/index.php/Virology

# Virology Virology, often considered a part of microbiology or of pathology, is the study of biological viruses and virus-like agents: their structure and classification, their ways to infect and exploit cells for virus reproduction, the diseases they cause, the techniques to isolate and culture them, and their potential uses in research and therapy. A major branch of virology is virus classification. Viruses can be classified according to the host cell they infect: animal viruses, plant viruses, fungal viruses, and bacteriophages (viruses infecting bacteria, which include the most complex viruses). Another classification uses the geometrical shape of their capsid (often a helix or an icosahedron) or the virus's structure (e.g. presence or nhnm a lipid envelope). Viruses range in size from about 30 nm to about 450 nm, which means that most of them cannot be seen with light microscopes. The shape and structure of viruses can be studied with electron microscopy, with NMR spectroscopy, and most importantly with X-ray crystallography. The most useful and most widely used classification system distinguishes viruses according to the type of nucleic acid they use as genetic material and the viral replication method they employ to coax host cells into producing more viruses: In addition virologists also study subviral particles, infectious entities even smaller than viruses: viroids (naked circular RNA molecules infecting plants), satellites (nucleic acid molecules with or without a capsid that require a helper virus for infection and reproduction), and prions (proteins that can exist in a conformation which induces other protein molecules to assume that same conformation). The latest report by the International Committee on Taxonomy of Viruses (2005) lists 5450 viruses, organized in over 2,000 species, 287 genera, 73 families and 3 orders. The taxa in virology are not necessarily monophyletic. In fact, the evolutionary relationships of the various virus groups remain unclear, and three hypotheses regarding their origin exist: Of particular interest here is mimivirus, a giant virus that infects amoebae and carries much of the molecular machinery traditionally associated with bacteria. Is it a simplified version of a parasitic prokaryote, or did it originate as a simpler virus that acquired genes from its host? While viruses reproduce and evolve, they don't engage in metabolism and depend on a host cell for reproduction. The often-debated question of whether they are alive or not is a matter of definition that does not affect the biological reality of viruses. One main motivation for the study of viruses is the fact that they cause many important infectious diseases, among them the common cold, influenza, rabies, measles, many forms of diarrhea, hepatitis, yellow fever, polio, smallpox and AIDS. Some viruses, known as oncoviruses, contribute to certain forms of cancer; the best studied example is the association between Human papillomavirus and cervical cancer. Some subviral particles also cause disease: Kuru and Creutzfeldt-Jakob disease are caused by prions, and hepatitis D is due to a satellite virus. When the immune system of a vertebrate encounters a virus, it produces specific antibodies which bind to the virus and mark it for destruction. The presence of these antibodies is often used to determine whether a person has been exposed to a given virus in the past, with tests such as ELISA. Vaccinations protect against viral diseases, in part, by eliciting the production of antibodies. Specifically constructed monoclonal antibodies can also be used to detect the presence of viruses, with a technique called fluorescence microscopy. A second defense of vertebrates against viruses, cell-mediated immunity, involves immune cells known as T cells: the body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed and the virus-specific T-cells proliferate. This mechanism is jump-started by certain vaccinations. RNA interference, an important cellular mechanism found in plants, animals and many other eukaryotes, most likely evolved as a defense against viruses. An elaborate machinery of interacting enzymes detects double-stranded RNA molecules (which occur as part of the life cycle of many viruses) and then proceeds to destroy all single-stranded versions of those detected RNA molecules. Every lethal viral disease presents a paradox: killing its host is obviously of no benefit to the virus, so how and why did it evolve? Today it is believed that most viruses are relatively benign in their natural host; the lethal viral diseases are explained as resulting from an "accidental" jump of the virus from a species in which it is benign to a new one that is not accustomed to it (see zoonosis). For example, serious influenza viruses probably have pigs or birds as their natural host, and HIV is thought to derive from the benign monkey virus SIV. While it has been possible to prevent (certain) viral diseases by vaccination for a long time, the development of antiviral drugs to treat viral diseases is a comparatively recent development. The first such drug was interferon, a substance that is naturally produced by certain immune cells when an infection is detected, thus stimulating other parts of the immune system. Bacteriophages, the viruses which infect bacteria, can be relatively easily grown as viral plaques on bacterial cultures. Bacteriophages occasionally move genetic material from one bacterial cell to another in a process known as transduction, and this horizontal gene transfer is one reason why they served as a major research tool in the early development of molecular biology. The genetic code, the function of ribozymes, the first recombinant DNA and early genetic libraries were all arrived at using bacteriophages. Certain genetic elements derived from viruses, such as highly effective promoters, are commonly used in molecular biology research today. Growing animal viruses outside of the living host animal is more difficult. Classically, fertilized chicken eggs have often been used, but cell cultures are increasingly employed for this purpose today. Since viruses that infect eukaryotes need to transport their genetic material into the host cell's nucleus, they are attractive tools for introducing new genes into the host (known as transformation or transfection), and this approach of using viruses as gene vectors is being pursued in the gene therapy of genetic diseases. An obvious problem to be overcome in viral gene therapy is the rejection of the transforming virus by the immune system. Oncolytic viruses are viruses that preferably infect cancer cells. While early efforts to employ these viruses in the therapy of cancer failed, there have been reports in 2005 and 2006 of encouraging preliminary results. A very early form of vaccination known as variolation was developed several thousand years ago in China. It involved the application of materials from smallpox sufferers in order to immunize others. In 1796 Edward Jenner used cowpox to successfully immunize a young boy against smallpox, and this practice was widely adopted. Vaccinations against other viral diseases followed, including the successful rabies vaccination by Louis Pasteur in 1886. The nature of viruses however was not clear to these researchers. In 1892 Eugene A. Rolfjohns showed that a disease of tobacco plants, tobacco mosaic disease, could be transmitted by extracts that were passed through filters fine enough to exclude even the smallest known bacteria. In 1898 Martinus Beijerinck, also working on tobacco plants, found that this "filterable agent" grew in the host and was thus not a mere toxin. The question of whether the agent was a "living fluid" or a particle was however still open. In 1903 it was suggested for the first time that transduction by viruses might cause cancer. Such an oncovirus in chickens was described by Francis Peyton Rous in 1911; it was later called Rous sarcoma virus 1 and understood to be a retrovirus. Several other cancer-causing retroviruses have since been described. The existence of viruses that infect bacteria was first recognized by Frederick Twort in 1911, and, independently, by Felix d'Herelle in 1917. Since bacteria could be grown easily in culture, this led to an explosion of virology research. An important investigator in this area, Max Delbrück, described the basic life cycle of a virus in 1937: rather than "growing", a virus particle is assembled from its constituent pieces in one step; eventually it leaves the host cell to infect other cells. The Hershey-Chase experiment in 1952 showed that only DNA and not protein enters a bacterial cell upon infection with bacteriophage T2. Transduction of bacteria by bacteriophages was first described in the same year. While plant viruses and bacteriophages can be grown comparatively easily, animal viruses normally require a living host animal, which complicates their study immensely. In 1931 it was shown that influenza virus could be grown in fertilized chicken eggs, a method that is still used today to produce vaccines. In 1937, Max Theiler managed to grow the yellow fever virus in chicken eggs and produced a vaccine from an attenuated virus strain; this vaccine saved millions of lives and is still being used today. In 1949 John F. Enders, Thomas Weller and Frederick Robbins reported that they had been able to grow poliovirus in cultured human embryonal cells, the first significant example of an animal virus grown outside of animals and chicken eggs. This work aided Jonas Salk in deriving a polio vaccine from killed polio viruses; this vaccine was shown to be effective in 1955. The first virus which could be crystalized and whose structure could therefore be elucidated in detail was tobacco mosaic virus (TMV), the virus that had been studied earlier by Ivanovski and Beijerink. In 1935, Wendell Stanley achieved its crystallization for electron microscopy and showed that it remains active even after crystallization. Clear X-ray diffraction pictures of the crystallized virus were obtained by Bernal and Fankuchen in 1941. Based on such pictures, Rosalind Franklin proposed the full structure of the tobacco mosaic virus in 1955. Also in 1955, Heinz Fraenkel-Conrat and Robley Williams showed that purified TMV RNA and its capsid (coat) protein can assemble by themselves to form functional viruses, suggesting that this simple mechanism is likely the natural assembly mechanism within the host cell. In 1965, Howard Temin described the first retrovirus: a RNA-virus that was able to insert its genome in the form of DNA into the host's genome. Reverse transcriptase, the key enzyme that retroviruses use to translate their RNA into DNA, was first described in 1970, independently by Howard Temin and David Baltimore. The first retrovirus infecting humans was identified by Robert Gallo in 1974. Later it was found that reverse transcriptase is not specific to retroviruses; retrotransposons which code for reverse transcriptase are abundant in the genomes of all eukaryotes. About 10-40% of the human genome derives from such retrotransposons. In 1975 the functioning of oncoviruses was clarified considerably. Until that time, it was thought that these viruses carried certain genes called oncogenes which, when inserted into the host's genome, would cause cancer. Michael Bishop and Harold Varmus showed that the oncogene of Rous sarcoma virus is in fact not specific to the virus but is contained in healthy animals of many species. The oncovirus can switch this pre-existing benign proto-oncogene on, turning it into a true oncogene. In 1977, Frederick Sanger achieved the first complete sequencing of the genome of any organism, a bacteriophage. In the same year, Richard Roberts and Phillip Sharp independently showed that the genes of adenovirus contain introns and therefore require gene splicing. It was later realized that almost all genes of eukaryotes have introns as well. The first cases of AIDS were reported in 1981, and HIV, the retrovirus causing it, was identified in 1983 by Robert Gallo and Luc Montagnier. Tests detecting HIV infection by detecting the presence of HIV antibody were developed. Subsequent tremendous research efforts turned HIV into the best studied virus. Human Herpes Virus 8, the cause of Kaposi's sarcoma which is often seen in AIDS patients, was identified in 1994. Several anti-retroviral drugs were developed in the late 1990s, decreasing AIDS mortality dramatically in developed countries. The first attempts at gene therapy involving viral vectors began in the early 1980s, when retroviruses were developed that could insert a foreign gene into the host's genome. They contained the foreign gene but did not contain the viral genome and therefore could not reproduce. Tests in mice were followed by tests in humans, beginning in 1989. The first human studies tried to correct the genetic disease severe combined immunodeficiency (SCID), but clinical success was limited. In the period from 1990 to 1995, gene therapy was tried on several other diseases and with different viral vectors, but it became clear that the initially high expectations were overstated. In 1999 a further setback occurred when 18-year-old Jesse Gelsinger died in a gene therapy trial. He suffered a severe immune response after having received an adenovirus vector. Success in the gene therapy of two cases of X-linked SCID was reported in 2000.

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