In this study, we evaluated the cognitive performance of mice submitted to a model of hypercholesterolemia, as well as its relationship with mitochondrial dysfunction and oxidative
stress, two key events involved in AD pathogenesis. Wildtype C57bI/6 or low density lipoprotein receptor (LDLr)-deficient mice were fed with either standard or cholesterol-enriched diet for a 4-week period and tested for spatial learning and memory in the object location learn more task. LDLr-/- mice displayed spatial learning and memory impairments regardless of diet. Moreover, LDLr-/- mice fed cholesterol-enriched diet presented a significant decrease in the mitochondrial complexes I and II activities in the cerebral cortex, which were negatively correlated with respective blood cholesterol levels. Additionally, hypercholesterolemic LDLr-/- mice presented a significant decrease in glutathione levels, about 40% increase in the thiobarbituric acid-reactive substances levels, as well as an imbalance between the peroxide-removing-related enzymes glutathione peroxidase/glutathione reductase activities in the cerebral cortex. These findings indicate a significant relationship between hypercholesterolemia, cognitive impairment, and cortico-cerebral mitochondrial dysfunctional/oxidative stress. Because of the involvement of such alterations
in AD patients, our data render this mouse model of hypercholesterolemia a useful approach to comprehend the molecular events mediating AD pathogenesis. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Background In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy Mocetinostat solubility dmso against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy.
Methods In our randomised, double-blind, placebo-controlled trial we enrolled adults
infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months’ open-label isoniazid followed by 30 months’ masked placebo (control IPI-549 price group) or 6 months’ open-label isoniazid followed by 30 months’ masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per mu L. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281.
Findings Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3.