Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BR-931 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)-acetamide], a new hypolipidemic agent of low toxicity, was evaluated in several tests of lipolysis and hyperlipidemia in rats, and in the cholesterol-induced atherosclerosis in rabbits. Significant hypolipidemic activity was observed in rats with doses of the agent at 12.5--50 mg/kg. In the Triton-induced hyperlipidemia, 50 mg BR-931 per kg was equieffective as 200 mg of clofibrate (CPIB) per kg. In contrast with CPIB, BR-931 exerted a powerful antilipolytic activity against epinephrine, ACTH, nicotine and cold exposure. BR-931 was particularly effective in diet-induced hyperlipidemias. Ethanol lipemia was totally prevented by the agent at 100 mg/kg. With Nath's diet, doses as low as 25 mg/kg significantly reduced hypercholesterolemia and hypertriglyceridemia. In these last two tests, the distribution of lipoprotein cholesterol was also determined. CPIB did not affect HDL cholesterol levels that had been decreased by the diets; in contrast, BR-931, already at doses of 50 mg/kg, brought the HDL/total cholesterol ratio back toward normal. A significant HDL cholesterol increase, together with some reduction of atheromatosis, was also observed in cholesterol-fed rabbits. BR-931, a potent inducer of liver peroxisones and of mitochondrial carmitine acetyltransferase, appears to be a hypolipidemic agent of high efficacy and low toxicity for the clinical treatment of hyperlipidemias and atherosclerosis.
Atherosclerosis 1978 May
PMID:Pharmacological profile of BR-931, a new hypolipidemic agent that increases high-density lipoproteins. 20 96

Tests on 100 alcoholic patients revealed increased lipoprotein levels in 24%. Type IV was the most frequently ecountered (80%), followed by type II or V. The average plasma triglyceride level of the alcoholic group was significantly increased in comparison with a control population. The causal mechanism of alcoholic hyperlipoproteinemia remains poorly understood. The combination of a genetic defect of lipid metabolism, nutritional factors and acute alcohol excess may have an essential bearing on the incidence of hyperlipoproteinemia. Acute excessive intake of alcohol was significantly increased in comparison with alcoholic subjects wihtout hyperlipoproteinemia. The critical dose may be a daily ethanol consumption of about 200 gm. There appeared to be no correlation between acute pancreatic injury or active liver disease and serum lipid elevation. On the other hand, the observation was confirmed that alcoholic patients with hepatic cirrhosis usually do not develop hyperlipoproteinemia. Ethanol-induced hyperlipoproteinemia may be a risk factor for the development of atherosclerosis and pancreatitis.
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PMID:[Alcohol-induced hyperlipoproteinemia]. 91 92

Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day (p less than 0.05 and p less than 0.01, respectively). The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lowering of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers. Ethanol intake may be added to the short list of factors that affect the quite stable, genetically determined Lp(a) concentrations in the plasma.
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PMID:A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men. 182 57

The influence of chronic ethanol intoxication upon vitamin D-induced damage of cardiovascular system in rats was examined. Eighty rats, divided into 16 groups according to sex and age, were intoxicated with ethanol as the only source of liquid. Control rats drank water only. After 6 months of ethanol intoxication, part of ethanol and part of water-drinking rats received 3 x 100,000 IU vitamin D/rat, in order to induce atherosclerosis and heart muscle necrosis. The results of the described experiment revealed that the degree of circulatory system damage after chronic ethanol intoxication and vitamin D treatment was dependent on the age of the animals at the beginning of the experiment. Ethanol intoxication intensified vitamin D-dependent heart muscle necrosis in young individuals. In old rats chronic alcohol intoxication diminished atherosclerosis induced by vitamin D.
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PMID:Effects of ethanol on the development of experimental atherosclerosis and cardionecrosis in rats. 239 Feb 5

Rats of the atherosclerosis-prone JCR:LA-corpulent strain were subjected to long-term low (0.5% wt/vol) or high (4% wt/vol) consumption of ethanol from 1 to 12 months of age. The corpulent rats are hyperphagic, obese, and insulin-resistant; exhibit a marked very low density lipoprotein hyperlipidemia; and develop both vascular and myocardial lesions while eating a normal rat chow. The total lipid profile of the rat sera showed only limited changes with ethanol consumption. There were also no significant effects on high density lipoprotein lipids. Ethanol consumption was associated with elevated fasting glucose concentrations in both lean and corpulent rats and a strong decrease in fasting insulin levels and pancreatic B-cell volume density in the hyperinsulinemic corpulent rats. The relative frequency of myocardial nodules of chronic inflammatory cells was increased in the ethanol-consuming rats, both lean and corpulent. In contrast, old organized lesions (scars) were absent in the ethanol-consuming corpulent rats. Thus, ethanol consumption had no major effect on serum lipids or lipoproteins in the corpulent rat but was associated with a reduction in insulin resistance and islet cell hyperplasia, with an associated decreased incidence of myocardial lesions.
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PMID:Effects of chronic ethanol consumption in atherosclerosis-prone JCR:LA-corpulent rat. 264 22

The effect of variable doses of ethanol on plasma lecithin: cholesterol acyltransferase (LCAT) activity was examined in male, atherosclerosis-susceptible squirrel monkeys over a 12-month period. Primates were divided into three groups: 1) Controls fed isocaloric liquid diet; 2) Low Ethanol monkeys given liquid diet with vodka substituted isocalorically for carbohydrate at 12% of calories; and 3) High Ethanol animals fed diet plus vodka at 24% of calories. There were no significant differences between the treatments in serum glutamate oxaloacetate transaminase (SGOT), a measure of liver function. However, plasma LCAT activity (% esterification/min) measured in vitro was significantly reduced in High Ethanol monkeys while cholesterol esterification was elevated in the Low Ethanol group and intermediate in Controls. Similarly, the in vivo appearance of radiolabeled cholesteryl ester in high density lipoproteins (HDL) following the intravenous injection of 3H mevalonolactone was highest in the Low Ethanol primates, intermediate in Controls and significantly lower in monkeys fed the high alcohol diet. In vitro measurement of LCAT enzyme efficiency was similar for the three groups while substrate efficiency was lower in the High Ethanol treatment. Although LCAT activator (apoprotein A-I) was not markedly altered by dietary ethanol and the concentration of LCAT substrates (HDL free cholesterol and phosphatidyl choline) was significantly elevated in the High Ethanol group, subtle modifications in substrate-product composition may account for the observed reduction in cholesterol esterification. These include potential substrate and/or product LCAT inhibition resulting from increased concentrations of plasma free cholesterol, HDL lysophosphatidyl choline, and higher HDL2/HDL3 subfraction ratios, as well as alterations in HDL phospholipid fatty acid profiles in the High Ethanol group. Results from this study provide the first evidence of an anomalous enhancement in LCAT activity in nonhuman primates fed ethanol at 12% of calories and a marked depression in cholesterol esterification at the 24% dose which may be due to substrate alterations and product inhibition prior to overt biochemical evidence of liver dysfunction.
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PMID:Effect of ethanol on lecithin:cholesterol acyltransferase (LCAT) activity. 399 6

Ethanol (88-880 mmol/l) inhibited the formation of proaggregatory, vasoconstricting thromboxane A2 (TxA2) during whole blood clotting and during thrombin-induced aggregation of platelet rich plasma. This inhibition was counteracted by the addition of exogenous arachidonic acid, which suggested that ethanol suppressed the liberation of arachidonic acid, evidently by inhibiting phospholipase A2. Ethanol had no effect on the formation of prostacyclin (PGI2, epoprostenol), the endogenous antagonist of TxA2, by human lung. Thus our results suggest that ethanol may shift the balance between TxA2 and PGI2 to the dominance of antiaggregatory, vasodilating PGI2 by suppressing the release of arachidonic acid in platelets. This finding might partly explain why ethanol protects against atherosclerosis and also the increased risk of subarachnoidal haemorrhage after heavy ethanol intake.
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PMID:Ethanol inhibits platelet thromboxane A2 production but has no effect on lung prostacyclin synthesis in humans. 636 50

Male Macaca nemestrina were studied in an experiment with a 2 x 2 factorial design. Diets contained low vs high cholesterol levels (0.3 vs 1.0 mg/Kcal) and no ethanol or ethanol, as 36% of the calories substituted isocalorically for carbohydrate. After receiving their diets for 18 months, the monkeys had blood samples drawn for lipoprotein analyses, and then were killed for evaluation of the extent of atherosclerosis. Ethanol-fed groups had significantly increased concentrations of serum cholesterol, triglycerides, low density lipoprotein, and high density lipoprotein. The molecular weight of the low density lipoprotein particles was lower in ethanol-fed animals and the cholesterol esters of low density lipoprotein and high density lipoprotein contained relatively more cholesteryl linoleate and less cholesteryl oleate. Dietary cholesterol had the effect of increasing the concentration of low density lipoprotein (primarily via increasing the low density lipoprotein molecular weight) and decreasing the concentration of high density lipoprotein. Significant interactions were found between the effects of ethanol and cholesterol on high density lipoprotein and low density lipoprotein. Ethanol significantly decreased the cholesterol-induced atherosclerosis found in the aorta and coronary arteries. Highly significant correlations between coronary artery atherosclerosis and low density lipoprotein cholesterol ester pattern were found. In contrast, low density lipoprotein molar concentration (number of low density lipoprotein particles per liter of plasma) was not significantly correlated with coronary artery atherosclerosis. Different relationships with aortic atherosclerosis were found; low density lipoprotein molecular weight and cholesterol ester pattern were highly correlated, while high density lipoprotein concentration was not. The high correlations found between lipoprotein characteristics and atherosclerosis severity have been mediated through its effects on the plasma lipoproteins.
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PMID:Dietary ethanol-induced modifications in hyperlipoproteinemia and atherosclerosis in nonhuman primates (Macaca nemestrina). 729 89

Free radicals are involved in the formation of both atherosclerosis and thrombosis. Therefore, considerable interest has recently been aroused by their role in the development of ischemic cerebral injury. Experimental observations suggest that antioxidants could reduce cerebral arterial vasospasm, reduce infarct size and prevent the development of both atherosclerosis and thrombosis. However, clinical evidence for these beneficial effects is still lacking. Alcohol can act as an antioxidant and an oxidant, and its intake seems to exert both beneficial and untoward effects on stroke, depending on drinking habits. Light-to-moderate regular alcohol intake has been suggested to protect against internal carotid artery atherosclerosis, a major cause of ischemic stroke. Ethanol metabolism in human blood vessel walls could antagonize the oxidation of LDL and thereby prevent the development of atherosclerosis. In addition, ethanol and the phenolic compounds of wine could decrease platelet aggregation and thromboxane formation and also prevent thrombus formation. Whether the effects are clinically significant remains to be proved. On the other hand, recent heavy drinking has been observed to worsen vasospastic ischemia caused by subarachnoid bleeding. Whether a lack of antioxidants is responsible for this effect also remains to be proved. Future stroke research should focus on solving these problems.
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PMID:Oxidants, antioxidants, alcohol and stroke. 1047 72

It has been reported in the epidemiological literature that cataract, stroke, and atherosclerosis risk is reduced by 50% in people consuming one alcoholic drink per day. Peroxide has been implicated as a causative agent in cataractogenesis, and LDL oxidation appears to play a role in atherosclerosis. The antioxidant activity of alcohol was measured by: (i) use of a luminescent assay developed in our laboratory, confirmed as appropriate; (ii) electron spin resonance (ESR) spin-trapping; and (iii) copper-catalysed oxidation of LDL and VLDL from hamsters fed 6% ethanol in their drinking water. Ethanol reduced the luminescent counts/min from peroxide and superoxide. It significantly reduced the spin-trapped signal of hydroxyl radical, but not the superoxide signal. Other alcohols also showed large reductions in counts from hydrogen peroxide. Plasma from hamsters fed 6% ethanol had lower lipid peroxides and the oxidizability of LDL and VLDL was significantly reduced compared to controls. These data provide a possible explanation for the effect of beverages containing ethanol in the reduction of cataract and atherosclerosis risk observed in human population studies.
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PMID:Is ethanol an important antioxidant in alcoholic beverages associated with risk reduction of cataract and atherosclerosis? 1049 11


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