bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Streptozotocin‐Induced Diabetes on the Rat Seminal Vesicle
Authors: MORRISON J.F.B. , DHANASEKARAN S. , SHEEN RAJAN , FRAMPTON C.M. , MENSAH‐BROWN ERIC
Published: December 2006

Abstract:  In the streptozotocin (STZ)‐diabetic rat major increases in noradrenaline concentration and content of the seminal vesicles were evident as early as 7 weeks following induction of hyperglycemia and returned toward normal after 34 weeks of hyperglycemia. There were significant reductions in the concentration and content of dopamine at 19–42 weeks of diabetes, and small occasionally significant reductions in the content of serotonin and adrenaline, particularly around 19–26 weeks after STZ treatment. The uptake of tritiated noradrenaline in the diabetics was increased at 12 weeks compared to the controls, and decreased to control levels with increasing age. Release of tritiated noradrenline was increased in response to electrical field stimulation and high potassium solutions, and raising calcium concentration caused increased release at rest and during electrical stimulation. Immunohistochemical demonstration of tyrosine hydroxylase was increased during the period when the noradrenaline concentration and content were elevated. It is concluded that there are significant changes in the sympathetic innervation of the seminal vesicle during the course of STZ diabetes, and that alterations in the reuptake, release, and synthesis of the neurotransmitter noradrenaline may contribute to changes in the concentration of the amine in the tissue. It is possible that the changes observed are related to the remodeling and regrowth of sympathetic nerve endings damaged in the early stages of hyperglycemia. These changes may also contribute to disorders of ejaculation in diabetes.
Functional Capacity of Macrophages Determines the Induction of Type 1 Diabetes
Authors: MENSAH‐BROWN EPK , SHAHIN A. , PAREKH KHATIJA , HAKIM A. AL , SHAMISI M. AL , HSU D.K. , LUKIC M.L.
Published: December 2006

Abstract:  Macrophages are potent immune regulators and are critical in the development and pathogenesis of autoimmune diabetes. They are said to be the first cell type to infiltrate the pancreatic islet, serve as antigen‐presenting cells, and are important as effector cells during diabetogenesis. The article examines the role of macrophages in autoimmune diabetes with particular emphasis on the role of galectin‐3, a β‐galactoside‐binding lectin, and T1/ST2, an IL‐1 receptor‐like protein, both of which play significant roles in the immunomodulatory functions of macrophages. Multiple low‐dose streptozotocin (MLD‐STZ) induces infiltration of mononuclear cells in the islets of susceptible strains leading to insulitis. Deletion of the galectin‐3 gene from C57BL/6 mice significantly attenuates this effect as evaluated by quantitative histology of mononuclear cells and loss of insulin‐producing β cells. In contrast, deletion of the ST2 gene enhanced insulitis after MLD‐STZ treatment when compared with relatively resistant wild‐type BALB/c mice. Thus, it appears that functional capacity of macrophages influences their participation in T helper (Th) 1‐mediated autoimmunity and the development of autoimmune diabetogenesis.
Diabetic Patients
Authors: ADILI FATEMEH , LARIJANI BAGHER , HAGHIGHATPANAH MOHAMMADREZA
Published: December 2006

Abstract:  This study was undertaken to consider the psychological aspect of diabetes with regard to improving clinical outcomes. The review was limited to literature reports on the causes, solutions, and treatments of some common psychological problems known to complicate diabetes management. A literature search was undertaken using Pub‐Med, CINAHL, Proquest, Elsevier, Blackwell Synergy, Ovid, Ebsco, Rose net, and Google websites, including studies published in English journals between 1995 and 2006. Therefore about 88 articles were selected based on the inclusion criteria. In earlier studies, relatively little empirical research was found to substantiate the effect of psychological counseling in complicated diabetes. The greatest deficits were seen in areas of mental health, self‐esteem parent impact, and family cohesion. There were some different factors, which influence the psychological aspect of diabetic patients, such as age, gender, place of living, familial and social support, motivation, energy, life satisfaction, and lifestyle. There are various types of solutions for coping with the psychological problems in diabetic clients. The most essential solution lies in educating the patients and healthcare providers on the subject. Before initiating each educational intervention, a thorough assessment would be crucial. Treatment plans may benefit from cognitive behavior therapy (CBT), behavior family therapy, improving family communication, problem‐solving skills, and providing motivation for diabetic patients. Moreover, it seems that the close collaboration between diabetologists and psychologists would be fruitful.
Effects of Streptozotocin‐Induced Diabetes on Contraction and Calcium Transport in Rat Ventricular Cardiomyocytes
Authors: BRACKEN NICHOLAS , HOWARTH FRANK C. , SINGH JAIPAUL
Published: December 2006

Abstract:  Cardiovascular diseases are the major cause of morbidity and mortality in diabetic patients. Contractile function of the heart is frequently compromised in the clinical setting and in experimental models of diabetes mellitus (DM). This article investigated the effect of streptozotocin (STZ)‐induced type 1 DM on contraction, L‐type calcium (Ca2+) current (ICa2+L), and on cytosolic calcium concentrations [Ca2+]i in ventricular myocytes of the rat heart. After 4–10 weeks of STZ treatment, blood glucose levels in diabetic animals were significantly (P < 0.05) higher compared to age‐matched controls. Diabetic rats have significantly (P < 0.05) reduced body, reduced heart weight, and reduced viability of ventricular myocytes compared to controls. The amplitude of ICa2+L and amplitude of contraction were significantly reduced (P < 0.05) at test potentials in the range –10 mV to +20 mV and –30 mV to +40 mV, respectively, in myocytes from diabetic animals compared to age‐matched controls. Moreover, there was a significant (P < 0.05) delay in electrically stimulated and caffeine‐evoked time to half relaxation of the Ca2+ transient in myocytes from diabetic animals compared to controls. A similar effect was obtained in myocytes treated with a combination of caffeine and nickel chloride (NiCl2). It is concluded that the diabetes‐induced voltage‐dependent decrease in contraction is associated with reduced Ca2+ channel activities and prolonged diastolic cytosolic Ca2+ compared to age‐matched control. Taken together, the results suggest that Ca2+ homeostasis is deranged during DM and this may be expressed at the level of the Na+/Ca2+ exchanger.
A Controlled Study of Psychosocial Factors in Young People with Diabetes in the United Arab Emirates
Authors: EAPEN VALSAMMA , MABROUK ABDEL AZIM , SABRI SUFIAN , BIN‐OTHMAN SALEM
Published: December 2006

Abstract:  Psychosocial factors were studied in 30 young people with diabetes and 30 control subjects in the UAE. Patients perceived themselves more negatively than their parents on several domains. Also, they had lower scores in the areas of physical appearance and athletic competence when compared to control subjects. There were significant gender differences, with girls perceiving themselves more negatively. Better maternal education and availability of social support were associated with a positive self‐image in the child. Parents of children exhibiting behavioral/emotional problems had a higher score on the parental General Health Questionnaire. Awareness and understanding of these psychosocial variables can help healthcare providers to target these issues as part of comprehensive diabetes management.
Changes of the Different Neuropeptide‐Containing Nerve Fibers and Immunocells in the Diabetic Rat's Alimentary Tract
Authors: FEHÉR ERZSÉBET , BATBAYAR BAYARCHIMEG , VÉR ÁGOTA , ZELLES TIVADAR
Published: December 2006

Abstract:  Peripheral neuropathy is a common complication of diabetes mellitus, where neuropeptides and immunocells might play important roles in the pathogenesis of the disease. In this article we have quantified the different neuropeptide‐containing nerve fibers and immunocells in the streptozotocin‐induced diabetic rat's alimentary tract (tongue, duodenum, colon) using immunohistochemical and immunocytochemical methods. The immunoreactive (IR) nerve fibers were found in all layers of the alimentary tract and their distribution pattern was similar in both control and diabetic groups. Mast cell–nerve fiber contacts were rarely found in the controls. However, after 4 weeks duration of diabetes the number of IR nerve fibers and the immunocompetent cells increased significantly (P < 0.05), and the number of mast cell–nerve fiber contacts was even more significantly increased (P < 0.001). The distance between nerve fibers and immunocells was about 1 μm or even less. Some of the mast cells were degranulated in the vicinity of nerve fibers. No immunocompetent cells were IR for any antisera in the control. However, after the streptozotocin treatment, a large number of the immunocompetent cells showed immunoreactivity for SP and NPY. Counting all immunocompetent cells in whole sections showed that 12.3% of them were IR for SP and 25.4% were IR for NPY. Increased number of SP‐containing nerve fibers and immunocells in diabetes mellitus might be the reason for painful neuropathy and might amplify the inflammatory reaction in an axon reflex manner; the released histamine and leukotrienes, cytokines, and chemokines might cause inflammations and lesions of the mucosa.
Alterations in Atrial Natriuretic Peptide and Its Receptor Levels in Long‐Term, Streptozotocin‐Induced, Diabetes in Rats
Authors: OBINECHE ENYIOMA , CHANDRANATH IRWIN , ADEGHATE ERNEST , BENEDICT SHEELA , FAHIM MOHAMED , ADEM ABDU
Published: December 2006

Abstract:  Diabetes mellitus (DM) shows a markedly increased incidence of cardiovascular pathology that leads to hypertension, endothelial macro‐ and microangiopathy, diabetic nephropathy, and myocardial infarction. Atrial natriuretic peptide (ANP), is a 28 amino acid peptide hormone synthesized mainly by the heart atria and ventricles. It has potent diuretic and natriuretic properties. In this article the effect of long‐term DM on blood plasma, kidney, and heart atrial and ventricular ANP concentrations were evaluated in streptozotocin (STZ)‐induced 8‐month diabetic and control rats by using radioimmunoassay (RIA). Moreover, ANP receptors in STZ‐induced, 8‐month diabetic rat kidneys were studied by receptor autoradiography. In addition, the expression of ANP concentrations in the kidney of diabetic and control rats was evaluated by means of immunohistochemistry. Body weight loss and increased blood glucose levels were used as indices of DM in the STZ‐induced diabetic rats. Our results showed significantly higher ANP concentrations in diabetic plasma (

P

< 0.05), kidney (

P

< 0.01), heart atria (

P

< 0.05), and ventricles (

P

< 0.01) compared to controls. We also demonstrated a significant decrease in ANP receptors in the outer cortex (

P

< 0.05), juxtaglomerular medulla (

P

< 0.05), and papilla (

P

< 0.05) of 8‐month diabetic rat kidneys compared to controls. The observed increase in ANP levels in plasma and kidney could play a role in the development of diabetic nephropathy: probably by reducing the levels of ANP receptors in diabetic kidney. Furthermore, the role of ANP in the STZ‐induced diabetic heart merits additional study.
Characterization of the Proapoptotic Intracellular Mechanisms Induced by a Toxic Conformer of the Recombinant Human Prion Protein Fragment 90–231
Authors: VILLA VALENTINA , CORSARO ALESSANDRO , THELLUNG STEFANO , PALUDI DOMENICO , CHIOVITTI KATIA , VENEZIA VALENTINA , NIZZARI MARIO , RUSSO CLAUDIO , SCHETTINI GENNARO , ACETO ANTONIO , FLORIO TULLIO
Published: December 2006

Abstract:  Prion diseases comprise a group of fatal neurodegenerative disorders that affect both animals and humans. The transition of the prion protein (PrP) from a mainly α‐structured isoform (PrPC) to a prevalent β‐sheet‐containing protein (PrPSc) is believed to represent a major pathogenetic mechanism in prion diseases. To investigate the linkage between PrP neurotoxicity and its conformation, we used a recombinant prion protein fragment corresponding to the amino acidic sequence 90–231 of human prion protein (hPrP90–231). Using thermal denaturation, we set up an experimental model to induce the process of conversion from PrPC to PrPSc. We report that partial thermal denaturation converts hPrP90–231 into a β‐sheet‐rich isoform, displaying a temperature‐ and time‐dependent conversion into oligomeric structures that share some physico‐chemical characteristics with brain PrPSc. SH‐SY5Y cells were chosen to characterize the potential neurotoxic effect of hPrP90–231 in its different structural conformations. We demonstrated that hPrP90–231 in β‐conformation, but not when α‐structured, powerfully affected the survival of these cells. hPrP90–231 β‐structured caused DNA fragmentation and a significant increase in caspase‐3 proteolytic activity (maximal effects + 170%), suggesting the occurrence of apoptotic cell death. Finally, we investigated the involvement of MAP kinases in the regulation of β‐hPrP90–231‐dependent apoptosis. We observed that the p38 MAP kinase blocker SB203580 prevented the apoptotic cell death evoked by hPrP90–231, and Western blot analysis revealed that the exposure of the cells to the peptide induced p38 phosphorylation. In conclusion, we demonstrate that the hPrP90–231 elicits proapoptotic activity when in β‐sheet‐rich conformation and that this effect is mediated by p38 and caspase‐3 activation.
Effect of Vitamin C on Liver and Kidney Functions in Normal and Diabetic Rats
Authors: SHAMSI MARIAM AL , AMIN AMR , ADEGHATE ERNEST
Published: December 2006

Abstract:  Diabetes mellitus (DM) is recognized as one of the leading causes of morbidity and mortality in the world. About 5–6% of the world population suffers from this disease and the number of people diagnosed with diabetes is rapidly increasing. Diabetes has been demonstrated to be associated with oxidative stress and hyperglycemia, one of the most important indictors of oxidative stress. The endogenous mechanisms of enzymes and antioxidants are able to destroy the reactive species and create a balance between antioxidant and free radicals. In diabetes, the oxidative stress is increased because of the deficiency in the antioxidant defense. The intake of antioxidants, such as vitamin C, may reduce the oxidative stress associated with diabetes and hence help to restore the antioxidant defense system. The aim of this article was to investigate the effect of different doses of vitamin C on the biochemical parameters of normal and streptozotocin (STZ)‐induced diabetic rats. Biochemical analysis was used to study the effect of this vitamin on the biochemical parameters of normal and diabetic rats. Liver and kidney enzymes were elevated after the onset of diabetes. Moderate doses of vitamin C significantly (P < 0.0008) reduced plasma gamma‐glutamyl level in diabetic rats. Moreover, vitamin C significantly (P < 0.01) reduced the blood urea nitrogen level of diabetic rats. The plasma level of electrolytes, such as calcium and sodium, also changed significantly (P < 0.00001) after oral administration of vitamin C. Antioxidants, such as vitamin C, may ameliorate the biochemical parameters of diabetic rats.
Vitamin E Decreases the Hyperglucagonemia of Diabetic Rats
Authors: AL SHAMSI MARIAM , AMIN AMR , ADEGHATE ERNEST
Published: December 2006

Abstract:  Vitamin E has the ability to scavenge a wide spectrum of free radicals, including singlet oxygen, superoxide, and hydroxyl radicals. It has beneficial effects against several other disorders, such as atherosclerosis and ischemic heart disease, because it acts as a transcriptional regulator for gene expression via a transcription factor TAP. The beneficial effect of vitamin E on plasma insulin and glucagon levels was examined using radioimmunoassay technique. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at a dose of 60 mg/kg body weight. Vitamin E was given at a dose of either 0.2 mg, 0.4 mg, or 0.8 mg per animal 10 days before and after the onset of diabetes. Vitamin E significantly (

P

< 0.05) increased plasma insulin levels in normal rats but failed to increase the plasma insulin level in diabetic rats. In contrast, vitamin E caused a significant (

P

< 0.05) reduction in plasma glucagon level in rats treated before and after the onset of diabetes. Vitamin E may ameliorate some diabetic complication via reduction in the level of circulating glucagon.
Effect of High‐Calorie Diet on the Prevalence of Diabetes Mellitus in the One‐Humped Camel (Camelus dromedarius)
Authors: ALI M. AL HAJ , NYBERG FRED , CHANDRANATH S.I. , PONERY A.S. , ADEM A. , ADEGHATE E.
Published: December 2006

Abstract: The one‐humped camel is a typical desert animal. It has the capability of withstanding the harsh climatic changes and the scarcity of food and water, in addition to the high‐ambient temperature. The prevalence of diabetes mellitus in two different groups of the one‐humped camel, group (A) control (n= 102) camels and group (B) high‐calorie diet‐fed camels (n= 103), in Al‐Ain region (UAE) was studied using biochemical and radioimmunoassay techniques. In this article, 7% of the control camels have diabetes mellitus (blood glucose level: ≥140 mg/dL) compared to 21% of the high‐calorie‐fed camels. Plasma insulin level was significantly (P< 0.05) lower in group B compared to group A. The low insulin level in camels consuming high‐caloric diet could be a sign of exhaustion of pancreatic beta cells. The hematological parameters were nearly similar in both groups and no significant differences were seen. Liver and kidney enzymes were normal in both groups. Iron and copper were significantly (P< 0.005) higher in the high‐calorie‐fed camels compared with the control. Our study indicates that high‐caloric feed consumption in camels is associated with the development of disorders in glucose metabolism leading to diabetes mellitus.
Predicting the Development of Macrovascular Disease in People with Type 1 Diabetes
Authors: SIBAL LATIKA , LAW HUONG NAI , GEBBIE JANICE , DASHORA UMESH K , AGARWAL SHARAD C , HOME PHILIP
Published: December 2006

Abstract:  The aim of the article was to use prospectively collected data on people with type 1 diabetes to assess which routinely collected clinical measures predict the development of macrovascular disease in people with type 1 diabetes. Data have been collected in a structured format at an annual review since 1985. For this study, all people with type 1 diabetes in the database in both 1992 and 2001 were ascertained. Data were extracted for a diagnosis of coronary artery disease, stroke, and peripheral vascular disease (macrovascular complications). Presence of other microvascular complications was also ascertained. Forty‐one of 404 (10.1%) people had macrovascular disease at the index visit in 1992 and 61 others developed macrovascular complications during follow‐up. People who developed macrovascular complications were older (48 ± 12 versus 36 ± 11 [SD] years; P= 0.000), had longer duration of diabetes (28 ± 12 versus 18 ± 11 years; P= 0.000), higher BMI (26.7 ± 4.6 versus 25.4 ± 3.6 kg/m2; P= 0.041), higher base line serum cholesterol (5.9 ± 1.7 versus 5.2 ± 1.1 mmol/L, P= 0.007), higher median base line triglyceride levels (1.5 [IQ range 0.9–2.6] versus 1.1 [0.8–1.7] mmol/L; P= 0.002), higher systolic BP (145 ± 21 versus 129 ± 20 mmHg; P= 0.000), and higher serum creatinine (102 ± 57 versus 86 ± 17 μmol/L; P= 0.038) than those who did not. We found no significant difference in the base line glycated hemoglobin in the two groups. The multivariate model showed that age, duration of diabetes, systolic BP, and serum cholesterol and creatinine levels predicted the development of macrovascular complications, which were also associated with the later development of microalbuminuria. Macrovascular complications developed in 16.8% of people with type 1 diabetes over a 9‐year follow‐up, and were predicted by potentially modifiable factors including higher BP, BMI, and serum triglyceride and cholesterol levels.
The Relative Contributions of Aging, Health, and Lifestyle Factors to Serum Testosterone Decline in Men
Authors: Travison Thomas G. , Araujo Andre B. , Kupelian Varant , O’Donnell Amy B. , McKinlay John B.
Published: December 2006

Context: Although it is known that serum testosterone (T) concentrations decline with age, the relative contributions of changes in health and lifestyle to that decline have not been adequately assessed.

Objective: The objective of this study was to establish the relative importance of aging, health, and lifestyle in contributing to male T decline.

Design: A prospective cohort study of health and endocrine functioning in randomly selected men with a baseline visit (T1, 1987–1989) and two follow-up visits (T2, 1995–1997; T3, 2002–2004) was conducted.

Setting: An observational study of men residing in greater Boston, Massachusetts, was conducted.

Participants: Participants included 1667 men aged 40 to 70 at baseline; follow-up was conducted on 947 (57%) and 584 (35%) at T2 and T3, respectively.

Main Outcome Measures: Main outcome measures included total serum T, calculated free T (FT), and SHBG.

Results: There were substantial declines in total serum T and FT levels associated with aging alone. However, many health and lifestyle changes were associated with accelerated decline. A 4- to 5-kg/m2 increase in body mass index or loss of spouse was associated with declines in total serum T comparable to that associated with approximately 10 yr of aging. Results were similar for FT, but fewer factors were associated with SHBG after age was taken into account.

Conclusions: Both chronological aging and changes in health and lifestyle factors are associated with declines in serum T. Comorbidities and lifestyle influences may be as strongly associated with declining T levels as is aging itself over the short- to midterm. These results suggest the possibility that age-related hormone decline may be decelerated through the management of health and lifestyle factors.
Focal adhesion signaling and actin stress fibers are dispensable for progression through the ongoing cell cycle
Authors: Margadant Coert , van Opstal Angelique , Boonstra Johannes
Published: December 2006

Prevention of cell spreading or disruption of actin filaments inhibits growth factor stimulated cell cycle re-entry from quiescence, mainly because of a failure to induce cyclin D expression. Ectopic cyclin D expression overrules anchorage-dependency, suggesting that cell spreading per se is not required as long as cyclin D is otherwise induced. We investigated whether cyclin D expression in cells exiting mitosis is sufficient to drive morphology-independent cell cycle progression in continuously cycling (i.e. not quiescent) cells. Disruption of post-mitotic actin reorganization did not affect substratum reattachment but abolished the formation of filopodia, lamellipodia and ruffles, as well as stress fiber organization, focal adhesion assembly and cell spreading. Furthermore, integrin-mediated focal adhesion kinase (FAK) autophosphorylation and growth factor stimulated p42/p44 mitogen activated protein kinase (MAPK) activation were inhibited. Despite a progressive loss of cyclin D expression in late G1, cyclin E and cyclin A were normally induced. In addition, cells committed to DNA synthesis and completed their entire cycle. Our results demonstrate that post-mitotic disruption of the actin cytoskeleton allows cell cycle progression independent of focal adhesion signaling, cytoskeletal organization and cell shape, presumably because pre-existing cyclin D levels are sufficient to drive cell cycle progression at the M-G1 border.
UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles
Authors: Campalans Anna , Amouroux Rachel , Bravard Anne , Epe Bernd , Radicella J. Pablo
Published: December 2006

The DNA glycosylase hOGG1 initiates base excision repair (BER) of oxidised purines in cellular DNA. Using confocal microscopy and biochemical cell fractionation experiments we show that, upon UVA irradiation of human cells, hOGG1 is recruited from a soluble nucleoplasmic localisation to the nuclear matrix. More specifically, after irradiation, hOGG1 forms foci colocalising with the nuclear speckles, organelles that are interspersed between chromatin domains and that have been associated with transcription and RNA-splicing processes. The use of mutant forms of hOGG1 unable to bind the substrate showed that relocalisation of hOGG1 does not depend on the recognition of the DNA lesion by the enzyme. The recruitment of hOGG1 to the nuclear speckles is prevented by the presence of antioxidant compounds during UVA irradiation, implicating reactive oxygen species as signals for the relocalisation of hOGG1. Furthermore, APE1, the second enzyme in the BER pathway, is also present in nuclear speckles in UVA-irradiated cells. The recruitment of DNA repair proteins to nuclear speckles after oxidative stress implicates these organelles in the cellular stress response.
Specific and conserved sequences inD. melanogasterandC. eleganslamins and histone H2A mediate the attachment of lamins to chromosomes
Authors: Mattout Anna , Goldberg Michal , Tzur Yonatan , Margalit Ayelet , Gruenbaum Yosef
Published: December 2006

The intimate association between nuclear lamins and chromatin is thought to regulate higher order chromatin organization. Previous studies have mapped a region between the rod domain and the Ig fold in the tail domain of Drosophila melanogaster lamin Dm0, which binds chromatin in vitro via the histone H2A/H2B dimer. This region contains an evolutionarily conserved nuclear localization signal (NLS) KRKR, and a sequence composed of the amino acids TRAT. Here we show that binding of lamin Dm0 to chromatin requires both NLS and TRAT sequences. Substituting either of the threonine residues in the TRAT sequence with negatively charged residues decreases the binding of lamin Dm0 to chromatin, indicating that this binding could be regulated by phosphorylation. Both lamin Dm0 and C. elegans Ce-lamin bind directly to histone H2A in vitro and this binding requires the NLS. The amino and carboxyl tail domains of histone H2A are each essential, but not sufficient, for binding to lamin Dm0; only a polypeptide containing both histone H2A tail domains binds efficiently to lamin Dm0. Taken together, these results suggest that specific residues in lamin Dm0 and histone H2A mediate the attachment of the nuclear lamina to chromosomes in vivo, which could have implications on the understanding of laminopathic diseases.
Terlipressin: Vasopressin Analog and Novel Drug for Septic Shock
Authors: Pesaturo Adam B , Jennings Heath R , Voils Stacy A
Published: December 2006

Objective:

To review and assess available literature on chemistry, pharmacology, pharmacodynamics, pharmacokinetics, clinical studies, adverse events, drug interactions, and dosing and administration of terlipressin in septic shock.

Data Sources:

A literature search of MEDLINE (1966–September 2006), International Pharmaceutical Abstracts (1970–September 2006), and Cochrane database (third quarter 2006) was conducted, using key terms of terlipressin, lypressin, triglycyl-lysine vasopressin, hemodynamic support, septic shock, vasopressor, and V1 receptor agonist. Bibliographies of relevant articles were reviewed for additional references.

Study Selection and Data Extraction:

Available English-language literature, including abstracts, animal studies, preclinical studies, clinical trials, and review articles, were examined.

Data Synthesis:

Because of potentially favorable pharmacokinetics versus vasopressin and limited availability of vasopressin in some countries, the effects of terlipressin, a vasopressin analog, have been studied recently for the treatment of septic shock. When administered as a 1–2 mg intravenous dose in patients with septic shock, terlipressin increases mean arterial pressure, urine output, systemic vascular resistance index, pulmonary vascular resistance index, and left and right ventricular stroke work index while decreasing heart rate, cardiac output, lactate, and oxygen delivery and consumption index. It is unclear whether lower doses of terlipressin would produce a similar vasopressor response with fewer cardiopulmonary effects and whether the effects of the drug on oxygen transport indices are detrimental.

Conclusions:

Terlipressin is a promising investigational medication for treatment of septic shock. Small trials have shown terlipressin to have favorable effects on hemodynamics in patients with septic shock refractory to conventional vasopressor treatment. It should be used with extreme caution in patients with underlying cardiac or pulmonary dysfunction. Further studies are needed to verify safety, efficacy, and dosing of terlipressin in patients with septic shock, and its use cannot be recommended in lieu of vasopressin at this time.
Automatic versus User-Controlled Methods of Briefly Interrupting Telephone Calls
Authors: Katz Robert B.
Published: December 2006

Some future telephone services will require that ongoing calls be interruptedbriefly so that one of the parties can receive data transmitted over the voice path. For example, the new service Caller ID on Call Waiting (CIDCW) will allow subscribers who are off-hook and engaged in conversation to receive data indicating the name and telephone number of a new caller, but the data transmission will produce a break of approximately 1s. The question arises, then, as to what method should be used to interrupt calls to transmit data. In an automatic form ofCIDCW, data would be sent without user control once there is a new call, producing an unexpected break in ongoing conversations. In a user-controlled form, users would hear a tone when there is a new call and initiate the data transmission by pressing a button. Astudy was conducted to examine how subjects would react to breaks in their telephone conversations and to determine which form of CIDCW was more favorable. Subjects acting as CIDCW subscribers liked both forms of the service, but they preferred the automatic form, which was also rated as more acceptable and easier to use. Furthermore, compared with the user-controlled form, automatic CIDCW resulted in quick, error-free performance. Subjects acting as the far-end party also favored the automatic form, provided that they heard silence during the interruptions rather than a tone. Generally the automatic approach was found to be the better way to introduce a I-s break into telephone calls.
Self-Selected Manual Lifting Technique: Functional Consequences of the Interjoint Coordination
Authors: Burgess-Limerick Robin , Abernethy Bruce , Neal Robert J. , Kippers Vaughan
Published: December 2006

The pattern of movement self-selected by 39 subjects to lift light loads from 9 cm above the ground is described in kinematic and electromyographic terms. Hamstring length changes were estimated from hip and knee angular kinematics. Subjects adopted a posture at the start of the lift intermediate between stoop and full-squat postures. A consistent coordination between knee, hip, and lumbar vertebral joints during lifting was described through calculation of the relative phase between adjacent joints and found to be exaggerated with increases in load mass. During the early phase of lifting, knee extension leads hip extension, which in turn leads extension of the lumbar vertebral joints. Early in the lifting movement, when load acceleration is greatest, the erectores spinae are thus relatively long and shortening slowly. Both of these factors produce greater back extensor strength. Rapid hamstring shortening is also delayed, which enhances their strength, and coactivation of the monoarticular knee extensors and biarticular hamstrings observed early in the lifting movement suggested that the knee extensors contribute to hip extension through a tendinous action of the hamstrings.
SHORT NOTE Evaluation of Alternative Media Used with a Groupware Editor in a Simulated Telecommunications Environment
Authors: Green Charles A. , Williges Robert C.
Published: December 2006

Writing efficiency using a groupware editor was evaluated in six configurations by factorially combining three communication media (audio only, audio plus video, and face-to-face) each with and without groupware editing in a within-subjects design. Twelve subjects familiar with journalistic writing were matched into dyads and wrote news articles based on sets of questions about video clips shown to them. The quality of the writing task products was consistently high and showed no differences among conditions. Results indicated that face-to-face conditions resulted in significantly less time to complete the task than did other communication conditions. When groupware editing was used, however, all communication media were equally efficient. The results were discussed in terms of the benefits of using the groupware editor to increase efficiency when face-to-face communication is not practical. Methodological procedures were discussed as a means of reducing team variability in evaluating groupware using telecommunications.
Spatial and Spectral Release from Masking in Three-Dimensional Auditory Displays
Authors: Doll Theodore J. , Hanna Thomas E.
Published: December 2006

The extent to which simultaneous sounds in three-dimensional (3D) auditory displays mask one another was examined as a function of their spectral proximity and spatial separation. A tonal signal of either 0.5 or 4 kHz was presented at 0 deg azimuth in the horizontal plane of the listener's head. Spectral proximity was varied by centering a notched-noise masker on the signal frequency and varying the notch width. The masker was presented at an azimuth of 0, 20, or 40 deg, and the listener's head was immobilized. Detection levels decreased with both masker notch width and spatial separation. Analysis of the results shows that spatial separation produces both a broadening of the band over which masking is effective and a decrease in the minimum signal-to-noise ratio needed to detect the signal at all notch widths. Both effects were greater at 0.5 kHz than at 4 kHz. Additional experiments showed that these mechanisms are disrupted when two maskers are positioned symmetrically around the signal and head. The results are interpreted in terms of the effects of spatial separation on binaural processing and the listener's ability to resolve the signal and masker in frequency.
Information-Processing Slope Scores Can Be Reliable!
Authors: Damos Diane L. , Carter Robert C.
Published: December 2006

Several recently published articles imply that slope and difference scores may be unreliable. We present data from a mental rotation experiment that demonstrate high test-retest reliabilities for slope scores. We develop a formula that may be used to estimate intersession reliabilities for slope scores and discuss practical steps to ensure that high reliabilities may be obtained.
Rear Light Arrangements for Cars Equipped with a Center High-Mounted Stop Lamp
Authors: Theeuwes Jan , Alferdinck Johan W. A. M.
Published: December 2006

The present study investigated the influence of layout factors on the effectiveness of the center high-mounted stop lamp (CHMSL) during day and night conditions. In particular, the study evaluated the effect of a vertical separation between the CHMSL and the horizontal plane of conventional stop lamps and the effect of a single strip of lamps extending across the rear of the car (one extended stop lamp). While performing a laboratory tracking task, subjects responded to brake lights by depressing a brake pedal. Reaction time measures (speed and accuracy) indicated that a high CHMSL, located away from the horizontal plane of the other rear lights, results in better performance than a CHMSL located adjacent to that horizontal plane. In addition, performance with a configuration consisting of a strip of stop lamps plus a high or low CHMSL is as good as that with two separate rear stop lamps and a high CHMSL.
Technology Usability and Utility Issues in a State Government Voice Mail Evaluation Survey
Authors: Caldwell Barrett S. , Uang Shiaw-Tsyr
Published: December 2006

This paper summarizes results of a user evaluation survey of computer-based telephone messaging ("voice mail") technologies. A mail survey of the population of voice mail users in state government agencies (approximately 3000 users) yielded 1072 user responses. Survey analyses tested hypotheses regarding how voice mail evaluations are influenced by user characteristics, system use and experience, task and situation factors, and differences in organizational context and operations. Highlights of the results include findings relating both endogenous (age and gender) and exogenous (reported length of experience and average weekly use) user characteristics to ratings of the voice mail interface. Participating organizations reported mean differences in ratings of the interface and situation-based voice mail appropriateness. The findings emphasize the importance of a systems approach to integrate user-centered design and functional, situational, and organizational contexts in order to enhance the success of implementing voice mail and other telecommunications technologies.
SHORT NOTE Relative Effects of Age and Compromised Vision on Driving Performance
Authors: Szlyk Janet P. , Seiple William , Viana Marlos
Published: December 2006

The aim of this study was to determine the relative effects of age and compromised vision on driving-related skills and on-road accidents. A total of 107 subjects were tested. They represented four groups that varied in age and visual status, as follows: (1) a younger, normally sighted group; (2) an older, normally sighted group; (3) a younger, visually compromised group; and (4) an older, visually compromised group. Driving performance was assessed by self-reported and state-recorded accident frequency and by an evaluation of performance on an interactive driving simulator. The older groups had poorer driving-related skills, as measured with our interactive driving simulator, than had the younger groups, but they did not have significantly higher on-road accident rates than the younger groups. The older subjects and those with compromised vision had reduced risk-taking scores, as measured with a self-report questionnaire. In addition, all older drivers had increased eye movements and had slower simulator driving speeds, which suggests that behavioral compensation is made for visuocognitive/motor deficits. Regression analyses showed that compromised vision and visual field loss predicted real-world accidents in our study population.
Effects of a Laser-Induced Temporary Scotoma on Target Acquisition Performance
Authors: Kosnik William
Published: December 2006

Lasers commonly used in industry and the military are increasingly being recognized as possible hazards to vision and visually guided tasks. This study examined the effects of laser-induced visual loss on target acquisition performance. An argon laser was used to produce a temporary central scotoma. Observers searched for variable-contrast aircraft that were embedded in backgrounds of differing complexity. The laser exposures increased acquisition times 2 to 12 times over baseline levels, indicating that the degree of visual deficit was task dependent. Acquisition time increased as background complexity increased and target contrast decreased. However, target motion facilitated acquisition performance and mitigated the laser effect. Although contrast had a systematic effect on acquisition performance, it was clear that factors other than contrast contributed to target visibility. Other factors that may have affected visibility included distractors and masking effects introduced by the structured backgrounds.
Increasing the Usability of Interactive Voice Response Systems: Research and Guidelines for Phone-Based Interfaces
Authors: Schumacher Robert M. , Hardzinski Mary L. , Schwartz Amy L.
Published: December 2006

Thousands of applications-from airline reservations to zoo schedules-use phonebased interfaces to provide information to callers and to request input. The dramatic increase in the number of these applications has led to wide variability in the quality of the interface design. Most users have no choice but to grudgingly accept these systems; experience with poorly designed phone-based interfaces has led to widespread dissatisfaction. We believe that the lack of published guidelines for interface design for these systems contributes to the variability in quality and thus to user antipathy. In this paper we propose guidelines for construction of phone-based interfaces to interactive voice response systems. These guidelines are a compilation of information from the best of current practices, empirical research where available, and the wisdom of the industry. We see this collection as a starting point for further discussion and standardization that will ultimately lead to optimally usable interactive voice response systems.
Neuronal Pentraxin 1 Contributes to the Neuronal Damage Evoked by Amyloid-β and Is Overexpressed in Dystrophic Neurites in Alzheimer's Brain
Authors: Abad Maria A. , Enguita Marta , DeGregorio-Rocasolano Nuria , Ferrer Isidre , Trullas Ramon
Published: December 2006

Accumulation of amyloid-β (Aβ) is thought to play a central role in the progressive loss of synapses, the neurite damage, and the neuronal death that are characteristic in brains affected by Alzheimer's disease. However, the mechanisms through which Aβ produces such neurotoxicity remain unclear. Because Aβ depresses synaptic activity, we investigated whether the neurotoxicity of Aβ depends on the expression of NP1, a protein involved in excitatory synapse remodeling that has recently been shown to mediate neuronal death induced by reduction in neuronal activity in mature neurons. We found that treatment of cortical neurons in culture with Aβ produces a marked increase in NP1 protein that precedes apoptotic neurotoxicity. Silencing NP1 gene expression by RNA interference (short hairpin RNA for RNA interference) prevents the loss of synapses, the reduction in neurite outgrowth, and the apoptosis evoked by Aβ. Transgene overexpression of NP1 reproduced these neurotoxic effects of Aβ. Moreover, we found that NP1 was increased in dystrophic neurites of brains from patients with sporadic late-onset Alzheimer's disease. Dual immunohistochemistry for NP1 and tau showed that NP1 colocalizes with tau deposits in dystrophic neurites. Furthermore, NP1 colocalized with SNAP-25 (synaptosomal-associated protein of 25 kDa) in the majority of dystrophic neurites surrounding amyloid deposits. NP1 was also increased in cell processes surrounding amyloid plaques in the cerebral cortex and hippocampus of APP/PS1 (mutant amyloid precursor protein/presenilin 1) transgenic mice. These findings show that NP1 is a key factor for the synapse loss, the neurite damage, and the apoptotic neuronal death evoked by Aβ and indicate that Aβ contributes to the pathology of Alzheimer's disease by regulating NP1 expression.
GGA1 Is Expressed in the Human Brain and Affects the Generation of Amyloid β-Peptide
Authors: Wahle Tina , Thal Dietmar R. , Sastre Magdalena , Rentmeister Andrea , Bogdanovic Nenad , Famulok Michael , Heneka Michael T. , Walter Jochen
Published: December 2006

The β-amyloid peptide (Aβ) is a major component of Alzheimer disease (AD)-associated senile plaques and is generated by sequential cleavage of the β-amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. BACE1 cleaves APP at the N terminus of the Aβ domain, generating a membrane-bound C-terminal fragment (CTF-β) that can be subsequently cleaved by γ-secretase within the transmembrane domain to release Aβ. Because BACE1 initiates Aβ generation, it represents a potential target molecule to interfere with Aβ production in therapeutic strategies for AD. BACE1 interacts with Golgi-localized, γ-ear-containing, ADP ribosylation factor-binding (GGA) proteins that are involved in the subcellular trafficking of BACE1. Here, we show that GGA1 is preferentially expressed in neurons of the human brain. GGA1 was also detected in activated microglia surrounding amyloid plaques in AD brains. Functional analyses with cultured cells demonstrate that GGA1 is implicated in the proteolytic processing of APP. Overexpression of GGA1 or a dominant-negative variant reduced cleavage of APP by BACE1 as indicated by a decrease in CTF-β generation. Importantly, overexpression of GGA1 reduced, whereas RNAi-mediated suppression of GGA1 increased the secretion of Aβ. The modulation of APP processing by GGA1 is independent of a direct interaction of both proteins. Because total cellular activity of BACE1 was not affected by GGA1 expression, our data indicate that changes in the subcellular trafficking of BACE1 or other GGA1-dependent proteins contribute to changes in APP processing and Aβ generation. Thus, GGA proteins might be involved in the pathogenesis of AD.
Perceptual-Learning Evidence for Separate Processing of Asynchrony and Order Tasks
Authors: Mossbridge Julia A. , Fitzgerald Matthew B. , O'Connor Erin S. , Wright Beverly A.
Published: December 2006

Normal perception depends, in part, on accurate judgments of the temporal relationships between sensory events. Two such relative-timing skills are the ability to detect stimulus asynchrony and to discriminate stimulus order. Here we investigated the neural processes contributing to the performance of auditory asynchrony and order tasks in humans, using a perceptual-learning paradigm. In each of two parallel experiments, we tested listeners on a pretest and a posttest consisting of auditory relative-timing conditions. Between these two tests, we trained a subset of listeners ∼1 h/d for 6–8 d on a single relative-timing condition. The trained listeners practiced asynchrony detection in one experiment and order discrimination in the other. Both groups were trained at sound onset with tones at 0.25 and 4.0 kHz. The remaining listeners in each experiment, who served as controls, did not receive multihour training during the 8–10 d between the pretest and posttest. These controls improved even without intervening training, adding to evidence that a single session of exposure to perceptual tasks can yield learning. Most importantly, each of the two groups of trained listeners learned more on their respective trained conditions than controls, but this learning occurred only on the two trained conditions. Neither group of trained listeners generalized their learning to the other task (order or asynchrony), an untrained temporal position (sound offset), or untrained frequency pairs. Thus, it appears that multihour training on relative-timing skills affects task-specific neural circuits that are tuned to a given temporal position and combination of stimulus components.