Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Since the emergence of highly active antiretroviral therapy (HAART), human immunodeficiency virus-1 (HIV-1)-infected patients have demonstrated dramatic decreases in viral burden and opportunistic infections, and an overall increase in life expectancy. Despite these positive HAART-associated outcomes, it has become increasingly clear that HIV-1 patients have an enhanced risk of developing cardiovascular disease over time. Clinical studies are instrumental in our understanding of vascular dysfunction in the context of HIV-1 infection. ⋯ We analyze recent in vitro and in vivo studies examining endothelial toxicity in response to HIV-1 proteins or in response to the various classes of antiretroviral drugs. Furthermore, we discuss the multiple mechanisms by which HIV-1 proteins and HAART injure the vascular endothelium in HIV-1 patients. By understanding the molecular mechanisms of HIV-1 protein- and antiretroviral-induced cardiovascular disease, we may ultimately improve the quality of life of HIV-1 patients through better drug design and the discovery of new pharmacological targets.
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The peroxisome proliferator-activated receptor (PPAR) gamma is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Thiazolidinediones, pharmacological ligands for PPARgamma, are currently used in the management of type 2 diabetes. ⋯ Furthermore, thiazolidinedione PPARgamma ligands reduced pulmonary hypertension and vascular remodeling in several experimental models of pulmonary hypertension. This report reviews current evidence that PPARgamma may represent a novel therapeutic target in pulmonary hypertension and examines studies that have begun to elucidate mechanisms that underlie these potential therapeutic effects.
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Adenovirus is a common infectious pathogen in both children and adults. It is a significant cause of morbidity in immunocompetent people living in crowded living conditions and of mortality in immunocompromised hosts. ⋯ The initial innate immune response is associated with the severe acute manifestations of adenovirus infection and also plays a significant role in acute toxicity owing to adenovirus vector exposure. This review discusses the innate immune response primarily during wild-type adenovirus infection because this serves as the basis for understanding the response during both natural infection and exposure to adenovirus vectors.
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Reviewed are data on gluconeogenesis (GNG) and glycogenolysis (GL) obtained in healthy volunteers and diabetic patients with newer, quantitative methods. Specifically addressed are effects of overnight and prolonged fasting, of acute changes in serum insulin and plasma free fatty acid (FFA) levels, as well as acute changes of combined FFA and insulin levels on GNG and GL in nondiabetic subjects and of abnormalities in GNG and GL in patients with type 1 and type 2 diabetes.