49 research outputs found

    Some Thoughts About Appealing Directions for the Future of Fuzzy Theory and Technologies Along the Path Traced by Lotfi Zadeh

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    The quoted text is an interesting instance of a fuzzy object: it is currently known in slightly diversified forms, each rather different from the quoted one, which corresponds to the first known appearance in English of this adage

    Compartment-Specific Gene Regulation of the CAR Inducer Efavirenz In Vivo

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    Nuclear receptors such as the constitutive androstane receptor (CAR) are central factors that link drug exposure to the activities of drug metabolism and elimination. In order to determine the in vivo effects of efavirenz, a CAR activator, the expression of target genes was determined in duodenal biopsies obtained from 12 healthy volunteers before treatment and after 10 days of treatment with efavirenz; concomitant administration of the cholesterol inhibitor ezetimibe produced no significant difference. However, in in vitro studies, efavirenz significantly increased CYP2B6 expression in several cell types, suggesting that the drug transactivates CAR. This hypothesis is supported by our findings that there is significant induction of CAR target genes in in vivo peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers treated with multiple doses of efavirenz. The impact of efavirenz on hepatic metabolism in vivo was confirmed by significant changes in plasma 4β-hydroxycholesterol and bilirubin levels and the area under the curve (AUC) of efavirenz. induction of CYP2B6 mRNA expression correlated with the decrease in the AUC of efavirenz (r = 0.61; P = 0.036). Taken together, our results provide evidence that efavirenz exerts compartment-specific inductive capacity in vivo

    Prevalence of Helicobacter Pylori Infection and Its Link to Coronary Risk Factors in Japanese Patients With Acute Myocardial Infarction

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