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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of nicotinic acid was investigated in Rhesus monkeys. Subcutaneous injections of nicotinic acid lower the plasma very low density lipoprotein (VVLDL) and low density lipoprotein (HDL) concentration. The fall in LDL concentration is not accompained by any change in the lipid or protein composition of either lipoprotein. Analysis by Sephadex gel chromatography and polyacrylamide-gel electrophoresis showed that the proteins of monkey VLDL and LDL are qualitatively similar to those of human VLDL and LDL, although there are differences in the proportions of the various proteins present in the two species. Subcutaneous injections of nicotinic acid diminish the maximum incorporation of 14C from [14C]threonine into VLDL and LDL apoproteins, but have no effect on incorporation into albumin or HDL apoprotein. Peak incorporations into the apo-B and apo-C of VLDL are diminished to about equal extents by nicotinic acid. Comparison of the amount of 14C lost from apo-B of VLDL after the peak of incorporation, with that gained by apo-B of LDL during the same period, suggests that some of the circulating apo-B of LDL IS DERIVED FROM SOURCES OTHER THAN CIRCULATING VLDL.
Atherosclerosis
PMID:The effect of nicotinic acid on the metabolism of the plasma lipoproteins of rhesus monkeys. 16 24

In epididymal adipose tissue from rats, human serum antagonizes inhibition of basal lipolysis by nicotinic acid in vitro. Under similar conditions caffeine-stimulated lipolysis was unaffected by the presence of human serum. Very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins were all found to antagonize the action of nicotinic acid on basal lipolysis. VLDL also antagonized prostaglandin E1 (PGE1)-inhibition of basal lipolysis in vitro. The fat cell membrane was suggested as the site at which human serum lipoproteins antagonize nicotinic acid or PGE1 antilipolytic action on basal lipolysis in vitro.
Atherosclerosis 1976 Oct
PMID:Modification of nicotinic acid and prostaglandin E1 antilipolytic action in vitro. 18 78

VLDL of fasting serum was fractionated into 4 fractions of decreasing particle size by preparative ultracentrifugation in a density gradient from a patient with massive type V hyperlipoproteinaemia before and after treatment with 12 g daily of nicotinic acid. Serum triglycerides fell from 58 to 9 mmol/1 in response to treatment due particularly to reduction of larger VLDL particles. Total, insoluble (apoprotein B) and soluble protein of all VLDL fractions also fell but the ratio of these 3 protein fractions to triglyceride rose particularly in the smaller VLDL fractions. The relative amount of apolipoprotein CII increased in all fractions and the ratio apo CII to triglycerides increased by 60--90% in all VLDL fractions. The relative amounts of apo CI, apo CII-2 and apo E appeared also to increase. The results are consistent with the hypothesis that low amounts of apo CII may play a role for the development of hypertriglyceridaemia.
Atherosclerosis 1978 Sep
PMID:Relative increase in apolipoprotein CII content of VLDL and chylomicrons in a case with massive type V hyperlipoproteinaemia by nicotinic acid treatment. 21 88

The hypolipidemic and antiatherogenic effects of different nicotinic acid derivatives were studied. Five rabbit groups maintained on an atherogenic diet were given simultaneously various nicotinic acid derivatives (50 mg/kg body weight/day): nicotinic acid, Xantinol-nicotinate, beta-pyridylcarbinol or Pirozadil (bis-3,4,5-trimethoxybenzoate, 2,6-pyridindiyldimethylene). All 4 compounds showed a clear hypocholesterolemic and antiatherogenic effect, as measured by serum cholesterol, and by planimetric evaluation of the aortic lesions in terms of percent surface area affected in the aortas and coronary lumen. The simultaneously observed elevation of the HDL/LDL cholesterol ratio of the aortic tissue possibly indicates an antiatherogenic effect of these changes.
Atherosclerosis 1978 Dec
PMID:Efficacy of hypolipidemic treatment in inhibition of experimental atherosclerosis: the effect of nicotinic acid and related compounds. 21 72

This report describes the effects of pharmacologic doses (3 g/d) of nicotinic acid on the plasma distribution and chemical composition of the high density lipoprotein (HDL) subfractions HDL(2) and HDL(3) and examines the influence of the drug on the metabolism of the major HDL apoproteins, apolipoproteins A-I (ApoA-I) and A-II (Apo-II). The drug lowered plasma cholesterol (15%, P < 0.05) and triglyceride (27%, P < 0.01); the former effect a result of a fall in the amount of cholesterol associated with very low density lipoproteins (31%, P < 0.02) and low density lipoproteins (36%, P < 0.02). Conversely, it raised plasma HDL cholesterol (23%, P < 0.05) and increased (by 345%) the plasma HDL(2):HDL(3) ratio. The latter derived from an absolute increment (646%) in circulating HDL(2), coupled with a fall (47%) in HDL(3). This change was not associated with major alterations in the overall cholesterol (free and esterified), triglyceride, phospholipid, or protein content of the subfractions; however, it was accompanied by substantial changes in their protein composition. In particular, the molar ratio of ApoA-I:ApoA-II in HDL(3) declined from 2.7:1 to 2.1:1 during nicotinic acid treatment.Significant perturbations of ApoA-I and ApoA-II metabolism accompanied the drug-induced HDL subfraction redistribution. Specifically, the plasma concentration of ApoA-I rose by 7% (P < 0.05) because of a decrease in its fractional catabolic rate. Moreover, whereas before treatment 6 and 94% of the plasma ApoA-I circulated with HDL(2) and HDL(3), after commencement of nicotinic acid therapy this distribution became 49 and 51% in HDL(2) and HDL(3), respectively. ApoA-II was found mainly in HDL(3), both before and during nicotinic acid treatment. Administration of the drug caused a 14% reduction in its plasma concentration (P < 0.05), which derived principally from a fall (22%, P < 0.01) in its synthetic rate. These data suggest that the effects of nicotinic acid on the HDL subfraction distribution may be mediated via (a) net transfer of ApoA-I from HDL(3) to HDL(2) and (b) a reduction in ApoA-II synthesis. Our present understanding of the association between HDL and atherosclerosis indicates that such changes may have prophylactic value in the prevention of coronary artery disease.
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PMID:Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. 22 31

In cardiovascular diseases with potential atherosclerosis, the serum concentration of HDL cholesterol as determined by a precipitation method with dextran sulfate and Mg++ was lower while that of total cholesterol was normal or elevated. Treatment with a daily dose of 1,200 mg of Nicomol, a derivative of nicotinic acid, for 1 to 3 months increased the mean HDL cholesterol level by 3 to 5 mg/dl and reduced the total cholesterol level by 14 to 15 mg/dl and total/HDL cholesterol ratio by 0.8 (3 months) to 0.9 (1 month, p less than 0.05). Similar decreases in HDL cholesterol concentration were also found in parenchymal and obstructive liver diseases with normal total cholesterol values except in fulminant hepatitis and intrahepatic cholestasis.
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PMID:Effect of nicomol on HDL cholesterol level. 22 32

The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.
Atherosclerosis 1979 Aug
PMID:Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease. 22 84

Healthy fasted volunteers were subjected to an acute oral ethanol load over 12 h after a diet of 3 days with high linolenic acid content. Free fatty acids, triglycerides, glycerol, phospholipids, cholesterol and insulin, as well as the fatty acid pattern of triglycerides in the plasma, were determined during the test. The test was repeated with nicotinic acid added. The lipid values obtained and the comparisons of fatty acid composition both indicate that the predominant role of peripheral lipolysis in the genesis of acute ethanol-induced hypertriglyceridemia, in spite of the possibility of enhanced synthesis of palmitic acid in the liver.
Atherosclerosis 1978 Jan
PMID:Plasma lipids, triglyceride/fatty acid pattern, and plasma insulin in fasted healthy volunteers during continuous ingestion of ethanol. Influence of lipolysis inhibited by nicotinic acid. 62 23

Four patients heterozygous for familial hypercholesterolaemia were treated by repeated plasma exchange with or without lipid-lowering drugs. Repeated plasma exchange without drug therapy in 3 patients was associated with a significant 18--28% decrement in plasma cholesterol level, comparing control with plateau values observed 3 weeks after exchange. Further decrements in plateau values followed the addition of lipid-lowering drugs used in combination, clofibrate--nicotinic acid or clofibrate--nicotinic acid--cholestyramine (range of total decrement 39--50%). Plasma exchange was associated with an increased excretion of endogenous faecal steroids, but this increase was completely abolished by the subsequent administration of clofibrate--nicotinic acid. This therapy prevented any increase in bile acid excretion with concomitant use of cholestyramine resin. Plasma exchange with drug therapy was associated with a sustained rise in plasma cholesterol specific radioactivity. In a fourth patient, clofibrate--nicotinic acid was administered prior to plasma exchange and led to a 24% fall in plasma cholesterol. Subsequent plasma exchange in this patient produced no sustained change in plasma cholesterol plateau level. In two patients, withdrawal of drugs allowed plasma cholesterol to return to pre-exchange control levels. These observations suggest that plasma exchange probably produced an increase in endogenous cholesterol synthesis and a mobilisation of tissue cholesterol. In relation to plateau cholesterol values 3 weeks after an exchange, the data suggested that the reduction in plasma cholesterol level with plasma exchange and drug therapy could have been achieved by intensive drug therapy alone.
Atherosclerosis 1978 Oct
PMID:The effects of plasma exchange on cholesterol metabolism. 72 37

In an ongoing study 558 consecutive survivors of myocardial infarction below 70 years, mean age 59 years, were randomly allocated 4 months after the acute episode into a control group or a chemotherapy group from December 1972 to April 1976. Both groups were given moderate advice about diet and the chemotherapy group was prescribed clofibrate, 1 g twice daily, and nicotinic acid 1 g three times daily. Serum cholesterol and triglycerides were lowered around 15-20% and 30% respectively in the chemotherapy group while only insignificant reductions were observed in the control group. Until December 1976 total mortality and mortality from IHD has been the same in the two groups. The number of non-fatal myocardial infarctions has been 38 in the control and 19 in the chemotherapy group, a statistically significant reduction (P less than 0.01).
Atherosclerosis 1977 Sep
PMID:Reduction of myocardial reinfarction by the combined treatment with clofibrate and nicotinic acid. 91 71


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