Lesions oxidative

In addition to LPL, macrophages secrete oxygen-free radicals, proteases, and Apo E, all of which affect lipoprotein accumulation (350,353). In the ARIC study, Apo E epsilon 2/3 was associated with carotid atherosclerosis, probably through delayed clearance of TG-rich lipoproteins (367). Apo E-deficient mice develop hyperlipidemia and atherosclerosis, and the lipoprotein oxidation occurs in macrophage-rich areas in early lesions. However, in necrotic areas of advanced lesions oxidation occurs diffusely in the extracellular areas (368). Physiologic levels of Apo E in the vessel wall are antiatherogenic in conditions of severe hyperlipidemia, and can affect later stages of plaque development (369). 

Probucol. Probucol is an antioxidant that is effective in lowering LDL cholesterol. Whereas probucol was known to lower cholesterol after relatively simple clinical trials (160), its mechanism of action as an antioxidant in the treatment of atherosclerosis is quite novel. Probucol has been shown to have the abiUty to produce regression of atherosclerotic lesions in animal models (161). Probucol therefore represents a novel class of pharmaceutical agent for the treatment of atherosclerosis. This effect occurs mechanistically, in part, by preventing oxidation of LDL, a necessary step in foam cell formation. This antioxidant activity has been shown in laboratory experiments and its activity in lowering LDL cholesterol in human studies is well documented (162). 

Oxidant Stipple small brown or black interveinal necrotic lesions on the adaxial surface of leaf tissue that can be attributed to exposure to ozone. 

Tissue-Specific Expression. In adult rodents, PPAR.a is expressed in liver, kidney, intestine, heart, skeletal muscle, retina, adrenal gland, and pancreas. In adult human, PPARa is expressed in the liver, heart, kidney, large intestine, skeletal muscle (mostly slow-twitch oxidative type I fibers), and in cells of atherosclerotic lesions (endothelial cells, smooth muscle cells, and monocytes/macrophages). Therefore, regardless of... 

Although Mg is generally considered non-toxic, the inhalation of fumes of freshly sublimed Mg oxide may cause metal fume fever. There is no evidence that Mg produces, true systemic poisoning. Particles of metallic Mg or Mg alloy which perforate the skin of gain entry thru cuts and scratched rilay produce a severe local lesion characterized by the evolution of gas and acute inflammatory reaction, frequently with necrosis. The condition Has been called a chemical gas gangrene . Gaseous blebs may develop within 24 hrs of the injury. The lesion is very slow to heal (Ref 23)... 

Histopathological examination shows the typical corelike lesions in a high proportion of muscle fibers in older patients this may amount to 100%. Most typically the cores are large and centrally-placed, but multiple cores may occur in the same fiber cross section. Most older patients show a striking predominance of type 1 (slow twitch oxidative) fibers and virtually all fibers with cores are type 1. Sometimes younger family members have more normal proportions of type 1 and type 2 fibers but, again, the cores are confined to the type 1 fibers. It is well established that muscle fiber types can interconvert due to altered physiological demands, and it is likely that fibers with cores convert to a basically slow twitch-oxidative metabolism to compensate for the fact that up to 50% of their cross sectional area may be devoid of mitochondria. 

Br Riboflavin Coenzyme in oxidation and reduction reactions prosthetic group of flavoproteins Lesions of corner of mouth, lips, and tongue seborrheic dermatitis... 

Injury to cells and tissues may enhance the toxicity of the active oxygen species by releasing intracellular transition metal ions (such as iron) into the surrounding tissue from storage sites, decompartmentalized haem proteins, or metalloproteins by interaction with delocalized proteases or oxidants. Such delocalized iron and haem proteins have the capacity to decompose peroxide to peroxyl and alkoxyl radicals, exacerbating the initial lesion. 

LDL extracted from atherosclerotic lesions is in an oxidized state (Yla-Herttuala et al., 1989). 

Antibodies that recognize oxidized LDL but not native LDL show positive reactivity in human or animal atherosclerotic lesions, but not the normal arterial wall (Haberland etal., 1988 Palinski et al., 1989, 1990 Rosenfeld etal., 1990). 

Rosenfeld, M.E., Palinski, W., Yla-Herttuala, S., Butler, S. and Witztum, J.L. (1990). Distribution of oxidation-specific lipid oxidation adducts and apo lipoprotein B in atherosclerotic lesions of varying severity from WHHL rabbits. Arteriosclerosis 10, 336-349. 

Although atherosclerosis and rheumatoid arthritis (RA) are distinct disease states, both disorders are chronic inflammatory conditions and may have common mechanisms of disease perpetuation. At sites of inflammation, such as the arterial intima undergoing atherogen-esis or the rheumatoid joint, oxygen radicals, in the presence of transition-metal ions, may initiate the peroxidation of low-density lipoprotein (LDL) to produce oxidatively modified LDL (ox-LDL). Ox-LDL has several pro-inflammatory properties and may contribute to the formation of arterial lesions (Steinberg et /., 1989). Increased levels of lipid peroxidation products have been detected in inflammatory synovial fluid (Rowley et /., 1984 Winyard et al., 1987a Merry et al., 1991 Selley et al., 1992 detailed below), but the potential pro-inflammatory role of ox-LDL in the rheumatoid joint has not been considered. We hypothesize that the oxidation of LDL within the inflamed rheumatoid joint plays a pro-inflammatory role just as ox-LDL has the identical capacity within the arterial intima in atherosclerosis. 

Yla-Herttuala, S., Witztum, J.L. and Steinberg, D. (1989). Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions rabbit and man. J. Clin. Invest. 84, 1086-1095. 

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