Oxidative stress defines an imbalance in production of oxidizing chemical species and their effective removal by protective antioxidants and scavenger enzymes. Evidence of massive oxidative stress is well established in adult critical illnesses characterized by tissue ischemia-reperfusion injury and by an intense systemic inflammatory response such as during sepsis and acute respiratory distress syndrome. Oxidative stress could exacerbate organ injury and thus overall clinical outcome. We searched MEDLINE databases (January 1966 to June 2005). For interventional studies, we accepted only randomized trials. Several small clinical trials have been performed in order to reduce oxidative stress by supplementation of antioxidants alone or in combination with standard therapies. These studies have reported controversial results. Newer large multicenter trials with antioxidant supplementation should be performed, considering administration at an early stage of illness and a wider population of critically ill patients.
CorrectionsPHARMACOLOGY. For the article ''Beneficial effects of antioxidants and L-arginine on oxidation-sensitive gene expression and endothelial NO synthase activity at sites of disturbed shear stress,'' by Filomena de Nigris, Lilach O. Lerman, Sharon Williams Ignarro, Giacomo Sica, Amir Lerman, Wulf Palinski, Louis J. Ignarro, and Claudio Napoli, which appeared in issue 3, February 4, 2003, of Proc. Natl. Acad. Sci. USA (100, 1420-1425 first published January 13, 2003; 10.1073͞pnas.0237367100), the authors should have noted that Louis J. Ignarro developed and markets Niteworks, a dietary supplement of L-arginine, L-citrulline, vitamin E, and vitamin C. Dr. Ignarro is also a member of the Scientific Advisory Board of Herbalife, the distributor of Niteworks. The pathogenic mechanisms by which physical exercise influences atherosclerotic lesion formation remain poorly understood. Because vigorous physical training increases oxidative stress, this study tested the hypothesis that graduated and moderate physical exercise together with metabolic intervention (L-arginine and antioxidants) may contribute to increased vascular protection. Exercise training in mice was induced by graduated swimming. In hypercholesterolemic male mice on an atherogenic high-cholesterol diet, graduated and moderate exercise lowered plasma cholesterol and decreased atherosclerotic lesions compared with sedentary control mice. Antioxidants (1.0% vitamin E added to the chow and 0.05% vitamin C added to the drinking water) and L-arginine (6% in drinking water) supplementation to exercising hypercholesterolemic mice further and synergistically reduced atherosclerosis compared with untreated exercised mice. Arterial oxidation-specific epitopes and systemic oxidative stress were reduced by metabolic intervention. Graduated chronic exercise elicited an increase in production of nitric oxide through increased endothelial nitric oxide synthase expression and ameliorated scavenger activities. Thus, metabolic intervention with L-arginine and antioxidants together with graduated and moderate exercise training reduce atherosclerotic lesion formation.catalase ͉ nitric oxide synthase ͉ vitamin E ͉ oxidative stress ͉ low-density lipoprotein P hysical exercise is a deterrent of cardiovascular disease and atherogenesis in animal models (1-5). Exercise can also positively influence classical risk factors that are associated with coronary heart disease such as diabetes, hypertension, obesity, dyslipidemias, and endothelial dysfunction (6-8). The higher respiration rate during severe physical exercise leads to the generation of more free radicals than the endogenous antioxidant systems can scavenge (9), whereas moderate intensity aerobic exercise enhances endothelium dependent vasodilation in humans (10), and attenuates exercise-induced peroxidation (11) and cardiovascular mortality (12) in the elderly. Moreover, there is an inverse association between intensity of physical activity and the risk of coronary heart disease events (13). A metaanalysis of 51 con...
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