During the past 15 years, epidemiological,1- 2 basic biological,3- 5 and experimental studies on atherosclerosis have supported the hypothesis that antioxidants protect against atherosclerosis6- 8 by limiting low-density lipoprotein oxidation in the arterial wall. This mechanism inhibits the pathological accumulation of cholesteryl ester in plaque via the macrophage scavenger receptor, a process that can cause plaque rupture and cardiovascular events.9- 10 Similarly, biological mechanisms have been identified in carcinogenesis that may be blocked by antioxidants.11- 14 In the past decade, a number of prospective, randomized, placebo-controlled, 3- to 6-year clinical trials have been published, testing the effect of vitamin E and other antioxidant vitamins or their combinations on clinical manifestations of cardiovascular disease and cancer.15- 21 These trials have surprisingly yet consistently shown that commonly used antioxidant vitamin regimens (vitamins E, C, beta carotene, or a combination) do not significantly reduce overall cardiovascular events or cancer.
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The nuclear receptor heterodimer RXR-LXR modulates the expression of key gene products (apolipoproteins, transporters, or enzymes) affecting lipid metabolism, via an upstream hormone response element DR4. RXR is activated by 9-cis retinoic acid and LXR by certain nuclear oxysterols.34 By affecting these sites of gene regulation, antioxidants could alter lipoprotein metabolism and lipid levels as has been observed.21 For example, isomers of vitamin A (retinoic acid), the breakdown product of beta carotene, could interfere with binding of the specific activator 9-cis retinoic acid to RXR; and antioxidants, including vitamin E, might alter oxysterol levels or their interaction with the LXR nuclear receptor by as yet unproven mechanisms. RXR indicates retinoid x receptor; LXR, liver x receptor; DR, direct repeat; Apo, apolipoprotein; ABC, ATP-binding cassette transmembrane protein; CETP, cholesterol ester transfer protein; SREBP, sterol regulatory element-binding protein.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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