The potential usefulness of taurine on diabetes mellitus and its complications

Taurine (2-aminoethanesulfonic acid) is a free amino acid found ubiquitously in millimolar concentrations in all mammalian tissues. Taurine exerts a variety of biological actions, including antioxidation, modulation of ion movement, osmoregulation, modulation of neurotransmitters, and conjugation of bile acids, which may maintain physiological homeostasis. Recently, data is accumulating that show the effectiveness of taurine against diabetes mellitus, insulin resistance and its complications, including retinopathy, nephropathy, neuropathy, atherosclerosis and cardiomyopathy, independent of hypoglycemic effect in several animal models. The useful effects appear due to the multiple actions of taurine on cellular functions. This review summarizes the beneficial effects of taurine supplementation on diabetes mellitus and the molecular mechanisms underlying its effectiveness

Physiological roles of taurine in heart and muscle

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals

Learning from the children : exploring preschool children's encounters with ICT at home

This paper is an account of our attempts to understand preschool children's experiences with information and communication technologies (ICT) at home. Using case study data, we focus on what we can learn from talking directly to the children that might otherwise have been overlooked and on describing and evaluating the methods we adopted to ensure that we maximised the children's contributions to the research. By paying attention to the children's perspectives we have learned that they are discriminating users of ICT who evaluate their own performances, know what gives them pleasure and who differentiate between operational competence and the substantive activities made possible by ICT

Quality and safety issues related to traditional animal medicine: role of taurine

<p>Abstract</p> <p>Background</p> <p><it>Calculus Bovis</it> (:<it>C.Bovis</it>) is one of the most precious and commonly-used medicinal materials in Japan and China. As the natural occurrence is very rare, a source of supply for <it>C. Bovis</it> is far behind the actual need and great efforts have been taken for some substitutes of natural <it>C. Bovis</it>. Unfortunately, very little information is available on the quality and/or clinical efficacy of medication based on <it>C. Bovis</it>. To ensure sustainable use of traditional therapeutic agents derived from <it>C. Bovis</it>, we felt that several issues needed to be addressed: 1) the source of the <it>C. Bovis</it> materials and quality control; 2) the role of taurine in the efficacy of <it>C. Bovis</it>.</p> <p>Methods</p> <p>Nine samples of natural <it>C. Bovis</it> and its substitutes were collected. ICP-MS was used for elemental analysis and the characterization was performed by principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA) as multivariate approaches. The efficacy of <it>C. Bovis</it> was evaluated for morphology, viability and beating pattern on cultured cardiac myocytes and/or fibroblasts.</p> <p>Results</p> <p>PCA and multi-elemental focus was effective in discriminating <it>C. Bovis</it> samples derived from different habitats. A satisfactory classification using SIMCA was obtained among Australia <it>C. Bovis</it>, other habitats and the substitutes. Australian samples had better batch uniformity than other habitats and were composed of fewer elements. We have used Australian<it> C. Bovis</it> for assessment on its bioactive compounds. Rat cardiac cells incubated with <it>C. Bovis</it> extract (0.01-0.1mg/ml) maintained normal morphology, viability and beating pattern. Cardiac myocytes and fibroblasts treated for 48 h with CA (0.5mM) or DCA (0.1mM) caused cell injury, as reflected by changes in appearance and a reduction of viability detected by the MTS assay. In cardiomyocytes, 0.5 h exposure of CA (0.5mM) markedly decreased the velocity ratio of beating, whereas the simultaneous addition of 1 mM taurine largely prevented the decrease.</p> <p>Conclusions</p> <p>The multi-elemental focus provided some references for the quality control and the efficacy of <it>C. Bovis</it>. Taurine partly attenuated the harmful actions of bile acids. It is plausible that the relationship between taurine and the bile acids contributes to therapeutic effect of <it>C. Bovis</it>.</p

Differential effects of taurine treatment and taurine deficiency on the outcome of renal ischemia reperfusion injury

Taurine possesses membrane stabilization, osmoregulatory and antioxidant properties, aspects of relevance to ischemic injury. We tested the hypothesis that body taurine status is a determinant of renal ischemic injury. Accordingly, renal function and structure were examined in control (C), taurine-treated (TT) and taurine deficient (TD) rats that were subjected to bilateral renal ischemia (60 min) followed by reperfusion (IR); sham operated rats served as controls. Baseline urine osmolality was greater in the TD group than in the control and the TT groups, an effect associated with increased renal aquaporin 2 level. The IR insult reduced urine osmolality (i.e., day-1 post insult); the TD/IR group displayed a more marked recovery in urine osmolality by day-6 post insult than the other two groups. Fluid and sodium excretions were lower in the TD/IR group, suggesting propensity to retention. Histopathological examination revealed the presence of tubular necrotic foci in the C/IR group than sham controls. While renal architecture of the TD/IR group showed features resembling sham controls, the TT/IR group showed dilated tubules, which lacked immunostaining for aquaporin 2, but not 1, suggestive of proximal tubule origin. Finally, assessment of cell proliferation and apoptosis revealed lower proliferation but higher apoptotic foci in the TT/IR group than other IR groups. Collectively, the results indicate that body taurine status is a major determinant of renal IR injury

Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice

Taurine, a sulfur-containing β-amino acid, is highly contained in heart and skeletal muscle. Taurine has a variety of biological actions, such as ion movement, calcium handling and cytoprotection in the cardiac and skeletal muscles. Meanwhile, taurine deficiency leads various pathologies, including dilated cardiomyopathy, in cat and fox. However, the essential role of taurine depletion on pathogenesis has not been fully clarified. To address the physiological role of taurine in mammalian tissues, taurine transporter-(TauT-) knockout models were recently generated. TauTKO mice exhibited loss of body weight, abnormal cardiac function and the reduced exercise capacity with tissue taurine depletion. In this chapter, we summarize pathological profile and histological feature of heart and skeletal muscle in TauTKO mice

An Innovative Interactive Modeling Tool to Analyze Scenario-Based Physician Workforce Supply and Demand

Effective physician workforce management requires that the various organizations comprising the House of Medicine be able to assess their current and future workforce supply. This information has direct relevance to funding of graduate medical education. We describe a dynamic modeling tool that examines how individual factors and practice variables can be used to measure and forecast the supply and demand for existing and new physician services. The system we describe, while built to analyze the pathologist workforce, is sufficiently broad and robust for use in any medical specialty. Our design provides a computer-based software model populated with data from surveys and best estimates by specialty experts about current and new activities in the scope of practice. The model describes the steps needed and data required for analysis of supply and demand. Our modeling tool allows educators and policy makers, in addition to physician specialty organizations, to assess how various factors may affect demand (and supply) of current and emerging services. Examples of factors evaluated include types of professional services (3 categories with 16 subcategories), service locations, elements related to the Patient Protection and Affordable Care Act, new technologies, aging population, and changing roles in capitated, value-based, and team-based systems of care. The model also helps identify where physicians in a given specialty will likely need to assume new roles, develop new expertise, and become more efficient in practice to accommodate new value-based payment model

Emergency department visits, ambulance calls, and mortality associated with an exceptional heat wave in Sydney, Australia, 2011: a time-series analysis

<p>Abstract</p> <p>Background</p> <p>From January 30-February 6, 2011, New South Wales was affected by an exceptional heat wave, which broke numerous records. Near real-time Emergency Department (ED) and ambulance surveillance allowed rapid detection of an increase in the number of heat-related ED visits and ambulance calls during this period. The purpose of this study was to quantify the excess heat-related and all-cause ED visits and ambulance calls, and excess all-cause mortality, associated with the heat wave.</p> <p>Methods</p> <p>ED and ambulance data were obtained from surveillance and administrative databases, while mortality data were obtained from the state death registry. The observed counts were compared with the average counts from the same period from 2006/07 through 2009/10, and a Poisson regression model was constructed to calculate the number of excess ED visits, ambulance and deaths after adjusting for calendar and lag effects.</p> <p>Results</p> <p>During the heat wave there were 104 and 236 ED visits for heat effects and dehydration respectively, and 116 ambulance calls for heat exposure. From the regression model, all-cause ED visits increased by 2% (95% CI 1.01-1.03), all-cause ambulance calls increased by 14% (95% CI 1.11-1.16), and all-cause mortality increased by 13% (95% CI 1.06-1.22). Those aged 75 years and older had the highest excess rates of all outcomes.</p> <p>Conclusions</p> <p>The 2011 heat wave resulted in an increase in the number of ED visits and ambulance calls, especially in older persons, as well as an increase in all-cause mortality. Rapid surveillance systems provide markers of heat wave impacts that have fatal outcomes.</p

Discovery of High-Affinity Protein Binding Ligands – Backwards

BACKGROUND: There is a pressing need for high-affinity protein binding ligands for all proteins in the human and other proteomes. Numerous groups are working to develop protein binding ligands but most approaches develop ligands using the same strategy in which a large library of structured ligands is screened against a protein target to identify a high-affinity ligand for the target. While this methodology generates high-affinity ligands for the target, it is generally an iterative process that can be difficult to adapt for the generation of ligands for large numbers of proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a class of peptide-based protein ligands, called synbodies, which allow this process to be run backwards--i.e. make a synbody and then screen it against a library of proteins to discover the target. By screening a synbody against an array of 8,000 human proteins, we can identify which protein in the library binds the synbody with high affinity. We used this method to develop a high-affinity synbody that specifically binds AKT1 with a K(d)<5 nM. It was found that the peptides that compose the synbody bind AKT1 with low micromolar affinity, implying that the affinity and specificity is a product of the bivalent interaction of the synbody with AKT1. We developed a synbody for another protein, ABL1 using the same method. CONCLUSIONS/SIGNIFICANCE: This method delivered a high-affinity ligand for a target protein in a single discovery step. This is in contrast to other techniques that require subsequent rounds of mutational improvement to yield nanomolar ligands. As this technique is easily scalable, we believe that it could be possible to develop ligands to all the proteins in any proteome using this approach

California Men's Health Study (CMHS): a multiethnic cohort in a managed care setting

BACKGROUND: We established a male, multiethnic cohort primarily to study prostate cancer etiology and secondarily to study the etiologies of other cancer and non-cancer conditions. METHODS/DESIGN: Eligible participants were 45-to-69 year old males who were members of a large, prepaid health plan in California. Participants completed two surveys on-line or on paper in 2002 – 2003. Survey content included demographics; family, medical, and cancer screening history; sexuality and sexual development; lifestyle (diet, physical activity, and smoking); prescription and non-prescription drugs; and herbal supplements. We linked study data with clinical data, including laboratory, hospitalization, and cancer data, from electronic health plan files. We recruited 84,170 participants, approximately 40% from minority populations and over 5,000 who identified themselves as other than heterosexual. We observed a wide range of education (53% completed less than college) and income. PSA testing rates (75% overall) were highest among black participants. Body mass index (BMI) (median 27.2) was highest for blacks and Latinos and lowest for Asians, and showed 80.6% agreement with BMI from clinical data sources. The sensitivity and specificity can be assessed by comparing self-reported data, such as PSA testing, diabetes, and history of cancer, to health plan data. We anticipate that nearly 1,500 prostate cancer diagnoses will occur within five years of cohort inception. DISCUSSION: A wide variety of epidemiologic, health services, and outcomes research utilizing a rich array of electronic, biological, and clinical resources is possible within this multiethnic cohort. The California Men's Health Study and other cohorts nested within comprehensive health delivery systems can make important contributions in the area of men's health