Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation.

AIMS: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress. METHODS AND RESULTS: Hearts from type 2 diabetic and control male Wistar rats were perfused in normoxia, hypoxia and reoxygenation, with the FAT/CD36 inhibitor sulfo-N-succinimidyl oleate (SSO) infused 4 min before hypoxia. SSO infusion into diabetic hearts decreased the fatty acid oxidation rate by 29% and myocardial triglyceride concentration by 48% compared with untreated diabetic hearts, restoring fatty acid metabolism to control levels following hypoxia-reoxygenation. SSO infusion increased the glycolytic rate by 46% in diabetic hearts during hypoxia, increased pyruvate dehydrogenase activity by 53% and decreased lactate efflux rate by 56% compared with untreated diabetic hearts during reoxygenation. In addition, SSO treatment of diabetic hearts increased intermediates within the second span of the Krebs cycle, namely fumarate, oxaloacetate, and the FAD total pool. The cardiac dysfunction in diabetic hearts following decreased oxygen availability was prevented by SSO-infusion prior to the hypoxic stress. Infusing SSO into diabetic hearts increased rate pressure product by 60% during hypoxia and by 32% following reoxygenation, restoring function to control levels. CONCLUSIONS: Diabetic hearts have limited metabolic flexibility and cardiac dysfunction when stressed, which can be rapidly rectified by reducing fatty acid uptake with the FAT/CD36 inhibitor, SSO. This novel therapeutic approach not only reduces fat oxidation but also lipotoxicity, by targeting the primary step in the fatty acid metabolism pathway

Time series analysis of dengue fever and weather in Guangzhou, China

<p>Abstract</p> <p>Background</p> <p>Monitoring and predicting dengue incidence facilitates early public health responses to minimize morbidity and mortality. Weather variables are potential predictors of dengue incidence. This study explored the impact of weather variability on the transmission of dengue fever in the subtropical city of Guangzhou, China.</p> <p>Methods</p> <p>Time series Poisson regression analysis was performed using data on monthly weather variables and monthly notified cases of dengue fever in Guangzhou, China for the period of 2001-2006. Estimates of the Poisson model parameters was implemented using the Generalized Estimating Equation (GEE) approach; the quasi-likelihood based information criterion (QICu) was used to select the most parsimonious model.</p> <p>Results</p> <p>Two best fitting models, with the smallest QICu values, are selected to characterize the relationship between monthly dengue incidence and weather variables. Minimum temperature and wind velocity are significant predictors of dengue incidence. Further inclusion of minimum humidity in the model provides a better fit.</p> <p>Conclusion</p> <p>Minimum temperature and minimum humidity, at a lag of one month, are positively associated with dengue incidence in the subtropical city of Guangzhou, China. Wind velocity is inversely associated with dengue incidence of the same month. These findings should be considered in the prediction of future patterns of dengue transmission.</p

Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis

A time series analysis by Manish Patel and colleagues shows that the introduction of rotavirus vaccination in Brazil is associated with reduced diarrhea-related deaths and hospital admissions in children under 5 years of age

Seroprevalence and factors associated with herpes simplex virus type 2 among HIV-negative high-risk men who have sex with men from Rio de Janeiro, Brazil: a cross-sectional study

Submitted by Frederico Azevedo ([email protected]) on 2010-11-04T17:19:23Z No. of bitstreams: 1 seroprevalence_and_factors.pdf: 273577 bytes, checksum: 742e51b14ff9ef765bf31b52f3fc8f1a (MD5)Made available in DSpace on 2010-11-04T17:19:23Z (GMT). No. of bitstreams: 1 seroprevalence_and_factors.pdf: 273577 bytes, checksum: 742e51b14ff9ef765bf31b52f3fc8f1a (MD5) Previous issue date: 2009Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Comunicação e Informação Científica e Tecnológica em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Background: Herpes simplex virus type 2 (HSV-2) is the leading cause of genital ulcer disease in developing countries, including Brazil, and is especially prevalent among men who have sex with men (MSM). HSV-2 infection represents a risk factor for the acquisition and transmission of other sexually transmitted diseases. The goal of the present cross-sectional study was to estimate HSV- 2 seroprevalence and to determine the factors associated with HSV-2 seropositivity in HIVnegative high-risk MSM from Rio de Janeiro, Brazil. Methods: Stored sera were tested to estimate HSV-2 seroprevalence, while socio-demographic and sexual behavior data were used to measure associations between risk factors and HSV-2 seropositivity. Using the Poisson regression model with robust variance, prevalence ratios (PR) were used to estimate de degree of association between risk factors and HSV-2 seropositivity in bivariate and multivariate analyses. Results: Seroprevalence of HSV-2 was of 45.7% (184 out of 403). Factors independently associated with HSV-2 seroprevalence in the multivariate model were: older age (≥ 26 years, PR: 1.41 95% Confidence Interval: 1.11–1.78), non-white race (PR: 1.32 95%CI: 1.06–1.64), positive serology for syphilis (PR: 1.65 95%CI: 1.33–2.05), positive serology for hepatitis B (PR: 1.25 95%CI: 0.99–1.57), stable male partner in the past 6 months (PR: 1.42 95%CI: 1.12–1.79), and unprotected anal sex with a stable female partner (PR: 1.46 95%CI: 1.05–2.04) in the 6 months preceding the crosssectional assessment. Conclusion: The present study made evident a high prevalence of HSV-2 infection in a sample of HIV-negative high-risk MSM from Rio de Janeiro. This finding indicates the need and urgency for implementing integrated programs for the prevention of HSV-2 and other sexually transmitted diseases, and, in particular, programs targeting high-risk MSM

The Neural Basis of Decision-Making and Reward Processing in Adults with Euthymic Bipolar Disorder or Attention-Deficit/Hyperactivity Disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD