Persius/hicric huggingface dataset:
Doxycycline hyclate clinical pharmacology

# Clinical Pharmacology
Doxycycline is primarily bacteriostatic and thought to exert its antimicrobial effect by the inhibition of protein synthesis.  Doxycycline is active against a wide range of gram-positive and gram-negative organisms.
The drugs in the tetracycline class have closely similar antimicrobial spectra and cross resistance among them is common.  Microorganisms may be considered susceptible to doxycycline (likely to respond to doxycycline therapy) if the minimum inhibitory concentration (MIC) is not more than 4 mcg/mL.  Microorganisms may be considered intermediate (harboring partial resistance) if the MIC is 4 to 12.5 mcg/mL and resistant (not likely to respond to therapy) if the MIC is greater than 12.5 mcg/mL.

## Susceptibility Plate Testing
If the Kirby-Bauer method of disc susceptibility testing is used, a 30 mcg doxycycline disc should give a zone of at least 16 mm when tested against a doxycycline-susceptible bacterial strain.  A tetracycline disc may be used to determine microbial susceptibility.  If the Kirby-Bauer method of disc susceptibility testing is used, a 30 mcg tetracycline disc should give a zone of at least 19 mm when tested against a tetracycline-susceptible bacterial strain.
Tetracyclines are readily absorbed and are bound to plasma proteins in varying degree.  They are concentrated by the liver in the bile, and excreted in the urine and feces at high concentrations and in a biologically active form.
Following a single 100 mg dose administered in a concentration of 0.4 mg/mL in a one-hour infusion, normal adult volunteers averaged a peak of 2.5 mcg/mL, while 200 mg of a concentration of 0.4 mg/mL administered over two hours averaged a peak of 3.6 mcg/mL.
Excretion of doxycycline by the kidney is about 40 percent/72 hours in individuals with normal function (creatinine clearance about 75 mL/min).  This percentage of excretion may fall as low as 1 to 5 percent/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min).  Studies have shown no significant difference in serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function.
Hemodialysis does not alter this serum half-life of doxycycline.
Doxycycline monohydrate adverse reactions

# Adverse Reactions
Due to oral doxycyclines virtually complete absorption, side effects to the lower bowel, particularly diarrhea, have been infrequent. The following adverse reactions have been observed in patients receiving tetracyclines.
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region. Hepatotoxicity has been reported. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Rare instances of esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of drugs in the tetracycline class. Most of these patients took medications immediately before going to bed. (See DOSAGE AND ADMINISTRATION.)
Skin: Maculopapular and erythematous rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above. (See WARNINGS.)
Renal Toxicity: Rise in BUN has been reported and is apparently dose related. (See WARNINGS.)
Hypersensitivity Reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus.
Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported with tetracyclines.
Other: Bulging fontanels in infants and intracranial hypertension in adults. (See PRECAUTIONS-General.)
When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid gland. No abnormalities of thyroid function are known to occur.
Left atrial enlargement electrocardiogram

# Overview
Left atrial enlargement may be observed among patients with pressure or volume overload of the left atrium.

# Differential Diagnosis of Left Atrial Enlargement
- Atrial aneurysm
- Infective endocarditis
- Left heart failure
- Mitral regurgitation
- Mitral stenosis
- Mitral valve prolapse
- Myxedema
- Patent Ductus Arteriosus
- Ventricular septal defect

# EKG in Left Atrial Enlargement
Left atrial enlargement produces a broad, bifid P wave in lead II (P mitrale) and enhances the terminal negative portion (negative deflection) of the P wave in V1.
In lead I and/or II the following may be seen:
- Bifid P wave with > 40 ms between the two peaks
- Total P wave duration > 110 ms
In lead V1, the following may be seen:
- Biphasic P wave with terminal negative portion > 40 ms duration (>0.04 sec or 1 small square)
- Biphasic P wave with terminal negative portion > 1mm deep

# Examples of Left Atrial Enlargement on EKG
- Left atrial enlargement
- 12 lead EKG: Left atrial enlargement
- Left atrial enlargement as seen in lead V1.
- Left atrial enlargement, a 12 lead ECG

# See Also
- Left atrial enlargement chest x-ray
- Left atrial enlargement causes
Eletriptan patient counseling information

# Patient Counseling Information
See FDA Approved Patient Labeling (Patient Information)
Myocardial Ischemia and/or Infarction, Prinzmetal's Angina, Other Vasospastic Reactions, and Cerebrovascular Events
Inform patients that RELPAX may cause serious cardiovascular adverse reactions such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular reactions can occur without warning symptoms, instruct patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and instruct them to ask for medical advice when observing any indicative sign or symptoms. Instruct patients to seek medical advice if they have symptoms of other vasospastic reactions .

### Anaphylactic/Anaphylactoid Reactions
Inform patients that anaphylactic/anaphylactoid reactions have occurred in patients receiving RELPAX. Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens .

### Medication Overuse Headache
Inform patients that use of drugs to treat acute migraines for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) .

### Serotonin Syndrome
Inform patients about the risk of serotonin syndrome with the use of RELPAX or other triptans, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) .

### Pregnancy
Inform patients that RELPAX should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus .

### Nursing Mothers
Inform patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed .
Experimental autoimmune encephalomyelitis
Experimental autoimmune encephalomyelitis (EAE) is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including  the disease multiple sclerosis. EAE was motivated by observations during the convalescence from viral diseases by Thomas M. Rivers, D. H. Sprunt and G. P. Berry in 1933. Their findings upon a transfer of inflamed patient tissue to primates was published in the Journal of Experimental Medicine article (Vol. 58, No. 1, pp. 39-56). It was previously referred to as Experimental allergic encephalomyelitis. EAE can be induced by inoculation with whole CNS tissue, purified myelin basic protein (MBP) or myelin proteolipid protein (PLP), together with adjuvants. It may also be induced by the passive transfer of T cells specifically reactive to these myelin antigens. EAE may have either an acute or a chronic relapsing course. Acute EAE closely resembles the human disease acute disseminated encephalomyelitis, while chronic relapsing EAE resembles multiple sclerosis. EAE is also the prototype for T-cell-mediated autoimmune disease in general.

# EAE in mice
Demyelination is produced by injection of brain extracts (like myelin basic protein). The Blood-brain barrier is opened by injection of Freund adjuvant (adjuvant serves as BBB breaker).
Immune system of the animal goes wild and multiple small disseminated lesions of demyelination (as well as micro-necroses) appear simultaneously in the brain.
Sharing some features, mostly demyelination, this model, first introduced in 1930s, cannot be considered equivalent to human MS. EAE either kills animals or leaves them with permanent disabilities, animals with EAE also suffer severe nerve inflammation, and the time course of EAE is entirely different to MS, being the main antigen (MBP) in charge.
Fluticasone Topical (patient information)

# Why this medication is prescribed
Fluticasone, a corticosteroid, is used to reduce inflammation and relieve itching, redness, dryness, and scaling associated with various skin disorders.
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

# How this medication should be used
Fluticasone comes as an ointment and cream to apply to the skin. It usually is applied two to four times a day at evenly spaced intervals. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use fluticasone exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.
Do not stop using fluticasone without talking to your doctor.
Thoroughly clean the affected area, allow it to dry, and then gently rub the medication in until most of it disappears. Use just enough medication to cover the affected area. You should wash your hands after applying the medication. The scalp lotion should be applied directly from the squeeze bottle to the affected area.

# Special precautions
Before using fluticasone:
- tell your doctor and pharmacist if you are allergic to fluticasone or any other drugs.
- tell your doctor and pharmacist what prescription and nonprescription medications you are using, especially skin products containing hydrocortisone and vitamins.
- tell your doctor if you have any other illnesses, infections, or allergies.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking fluticasone, call your doctor.

# What to do if you forget a dose
Apply the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not apply a double dose to make up for a missed one.

# Side effects
Fluticasone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- itching
- burning
- swelling
- redness
- skin rash
- numbness of the fingers

# Storage conditions needed for this medication
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

# Other information
Keep all appointments with your doctor. Fluticasone is for external use only. Do not let it get into your eyes, nose, or mouth, and do not swallow it. Do not apply dressings, bandages, cosmetics, lotions, or other skin medications to the area being treated unless your doctor tells you.
Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.

# Brand names
- Cutivate
GA responsive complex gene transcriptions
"Functional analyses of a number of hydrolase gene promoters, induced by gibberellin (GA) in aleurone cells following germination, have identified a GA-responsive complex as a tripartite element containing a pyrimidine box motif 5-CCTTTT-3."
"Although this GARC  may not always be tripartite, most often it includes three sequence motifs, the TAACAAA box or GA responsive element (GARE), the pyrimidine box CCTTTT, and the TATCCAC box (Skriver et al., 1991;Gubler and Jacobsen, 1992; Rogers et al., 1994)."
Various "GA-responsive complexes (GARCs)  mediate the regulation of GA-regulated gene expression by GAMYB. Several GA-responsive cis-acting elements (GARE) and GARE-like elements (TAACAA/GA, or TAACGTA) have been identified in the promoters of hydrolase genes expressed in the aleurone (Ueguchi-Tanaka et al. 2000; Sutoh and Yamauchi 2003; Washio 2003), expansin genes expressed in internodes (Lee et al. 2001), and many GAMYB-regulated genes expressed in anthers (Tsuji et al. 2006)."

# Acknowledgements
The content on this page was first contributed by: Henry A. Hoff.
Initial content for this page in some instances came from Wikiversity.
GDP-fucose protein O-fucosyltransferase 1
GDP-fucose protein O-fucosyltransferase 1 (POFUT-1) is an enzyme belonging to the O-Fuc family of proteins all are involved in the transferring of o-fucose from GDP--L-fucose to substrates. POFUT-1 responsible for adding fucose sugars in O linkage to serine or threonine residues between the second and third conserved cysteines in EGF-like repeats on the Notch protein.  The protein is an inverting glycosyltransferase, which means that the enzyme uses GDP--L-fucose as a donor substrate and transfers the fucose in O linkage to the protein producing fucose--O-serine/threonine.
When the gene for POFUT1 is knocked out, or the expression is decreased to very low levels, all Notch signaling is destroyed, which means that fucose on Notch is essential for Notch function.  Why this is the case is not yet well understood.
Almost all glycosyltransferases reside in the Golgi apparatus.  However, POFUT1 as well as the related enzyme POFUT2 have recently been shown to reside in the endoplasmic reticulum.

# Names For GDP-fucose protein O-fucosyltransferase 1
- Protein O-fucosyltransferase
- O-FucT-1
- FUT12
- OFUCT1
- O-FUT

# Pathway
POFUT-1 is involved in the attachment of Fucose sugars to a lot of proteins, However a key pathway is the Post-transitional Modification of NOTCH signal proteins.

## Pathway in detail
Pre-NOTCH proteins are translated and deposited in to the endoplasmic reticulum and are then first modified by POFUT-1 then by PGLUT-1 then exported the Golgi apparatus.  in the endoplasmic reticulum POFUT-1 utilizes its sub-strait GDP--L-fucose as a donor for the five carbon sugar Fucose. fucose is then attached to a serine amino acid residue.  Once Pre-notch is done being modified by POFUT-1 and POFUT-2, it is then exported to the Golgi apparatus where it is further modified and exported and incorporated into the cell membrane.

# Prevalence
As NOTCH signaling is conserved in most multi-cellular life, so to are the processes that are involved in the pathway. Because of NOTCH presence in most life forms, not just limited to the kingdom Animlia, it is also present in the kingdom plantae and kingdom fungi. There are several different Homologs in POFUT-1 present in many kingdoms of life.

# Drugs and research that targets POFUT-1
Because POFUT-1 is a key protein in the production of NOTCH signaling protein it has been the target of much research to disrupt it for the purpose of cancer treatment and prevention.
GDP-fucose protein O-fucosyltransferase 2
GDP-fucose protein O-fucosyltransferase 2 (POFUT2) is an enzyme responsible for adding fucose sugars in O linkage to serine or threonine residues in Thrombospondin repeats.  The protein is an inverting glycosyltransferase, which means that the enzyme uses GDP--L-fucose as a donor substrate and transfers the fucose in O linkage to the protein producing fucose--O-serine/threonine.
Almost all glycosyltransferases reside in the Golgi apparatus.  However, POFUT2 as well as the related enzyme POFUT1 have recently been shown to reside in the endoplasmic reticulum.
The malaria parasite Plasmodium falciparum requires POFUT2 for efficient transmission to mosquitoes and infection of human liver cells.
Gonadotropin-releasing hormone antagonist

# Overview
A gonadotropin-releasing hormone antagonist (GnRH antagonist) is a synthetic peptide that competes with the neurohormone GnRH for its receptor, thus decreasing or blocking GnRH action. As a result endogenous pituitary output of FSH and LH is shut down.
GnRH antagonists are also derivatives of the natural GnRH decapeptide with multiple amino acid substitutions. These substitutions modify the agent so that it blocks the receptor and decreases FSH and LH secretions within hours. In contrast to GnRH agonists, antagonists have no flare effect, thus their therapeutic effect is immediately apparent.  However, there action is short-lived and daily injections are necessary to maintain their effect. Typically endogenous FSH and LH activity returns about 40 hours after  cessation of GnRH antagonist administration, although with a higher dose the return to normal pituitary function will be postponed for longer. Unlike the GnRH agonists, long acting or depot forms of  the agent are not currently available, thus GnRH antagonists are not used in the long term therapy of patients with cancer where hormone levels need to be kept low for a long time. As of 2006, Histrelin (as Supprelin-LA) is awaiting approval for use as a 12-month depot injection.
The main application of GnRH antagonists is currently short term use in  the prevention of endogenous ovulation in patients who undergo exogenous stimulation with FSH in the preparation for IVF. Typically they are administered in the mid- to late follicular phase in stimulated cycles prior to the administration of hCG.  Because they decrease luteal competence, patients are usually given some form of luteal support after egg retrieval.
GnRH antagonists for long term use are under investigation (i.e. abarelix), their advantage over GnRH agonist would be that they lack the initial flare stimulation and induce quickly a hypogonadal situation.
Food and Drug Administration (FDA)-approved medications are used by as injectables:
- Abarelix (Plenaxis)
- Cetrorelix (Cetrotide), by Serono
- Ganirelix (Antagon), by Organon International.
GnRH antagonists are pregnancy category X  agents.
Growth hormone treatment for bodybuilding
Growth hormone (GH) has attracted increasing interest and use by amateur and professional bodybuilders, as well as professional athletes to increase performance and muscle growth. GH is used by many bodybuilders or athletes whose performance has plateaued - even with the use of anabolic steroids. It is also reputed to promote fat loss.
GH is also a favoured drug of many professional athletes and Olympic athletes, due to the fact that, as of 2005, there is no conclusive test to determine the presence of exogenous GH. Dosages for sport-related performance enhancement can be as low as 2IU/day, all the way up to 10IU/day taken by some professional bodybuilders.
Relatively few side effects are seen at doses of <4IU/day, but doses of 8+IU/day have been known to have permanent side-effects (see acromegaly). Bodybuilders have also used insulin in combination with HGH to achieve further muscle size, density, vascularity, and the appearance of paper-thin skin sucked tightly to the muscle. The recreational use of insulin for aesthetic reasons is very dangerous and can lead to very serious health risks, including diabetes and permanent insulin resistance.
Unlike anabolic steroids which must be cycled on and off to avoid permanently suppressing the body's hypothalamic-pituitary-gonadal axis (HPGA), GH does not suppress the HPGA and - in that respect, can be used without a break, for as long as desired. In fact, substantial results are usually only seen after continuous use of at least two months. Usually the illegal use of GH depends how long said individual can afford to stay on for, as GH is very expensive, costing typically at least $500USD/month, but can cost (dependent on dosage and black-market cost) up to $4000USD/month. GH is also stacked with anabolic steroids, especially potent androgens, like testosterone to work in synergy.
The use of the acronyms "HGH" or "hGH" (human growth hormone) in products sold over the internet is associated with misleading intentions (See HGH quackery).
HIV coinfection with hepatitis c overview

# Overview
HIV has been an important and familiar health and social crisis for two decades. Less familiar, but also important, is HCV infection. In HIVHCV co-infected patients, the Hepatitis C (HCV) viral load is higher than in HCV-mono-infected patients in both the plasma and liver tissue.
Similarity between Hepatitis C with HIV: These two viruses are similar in a number of ways, and infection with both is a serious problem. Both HCV and HIV are transmitted by exposure to infected blood. About one-quarter of the people infected with HIV also have HCV.

# Treatment

## Medical Therapy
The primary objective of HCV therapy is permanent eradication of the virus. The secondary potential benefit of eradication is a reduction in the risk of liver failure and liver cancer.
The introduction in the mid-1990s of highly active antiretroviral therapy (HAART) for HIV has caused a sharp drop in the number of deaths from AIDS. This means that people with HIV are living longer. Therefore, if they are co-infected, the complications from
HCV have more time to develop. These complications (cirrhosis, liver cancer, end-stage liver disease) generally develop over 20-30 years.
Liver disease from HCV is now the leading non-AIDS cause of death in the U.S. in co-infected individuals with HIV. Treatment for each disease is complicated, expensive, and has side effects. This poses difficult issues for patients who are living with both HIV and HCV. Finally, co-infection is important because it has a disproportionate impact on certain communities, including those in prison and jail and communities of color.