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

Some patients with familial hypercholesterolemia (FHC, type II) are highly responsive to the cholesterol-lowering effect of clofibrate, while others are not only resistant to this effect but may even show an increase in plasma beta-lipoproteins. In an attempt to find an explanation for these striking differences, we have studied the pharmacokinetics of clofibrate in FHC patients at both extremes of responsiveness. The results disclosed several major differences between the two groups. Plasma clofibric acid (CPIB) measured during the chronic administration of the drug was significantly higher in the responders than in the non-responders, whether all patients in each group or only those with tendon xanthomas were considered. Plasma CPIB concentrations were negatively correlated with body weight in the responders but not in CPIB-resistant patients. They were also inversely proportional to decreases in plasma beta-lipoprotein cholesterol after chronic clofibrate administration in the responsive group, but directly proportional to increases in the non-responders. Increasing the dose of clofibrate from 2 to 3 g/day in CPIB-resistant patients always resulted in an increase in plasma CPIB levels, but this was followed in some patients by a decrease and in others by an increase in plasma beta-lipoprotein cholesterol concentrations, so that the overall effect was not statistically significant. The half-life of plasma CPIB was measured over 48 h after a single 1-g dose of clofibrate in patients who had not received this drug for at least 3 weeks. Half-life was significantly longer in the responsive patients. In addition, the bioavailability and the rate of absorption of clofibrate tended to be higher in this group than in the resistant patients. We suspect that both groups differ not only in the metabolic handling of clofibrate but also in some aspect of their beta-lipoprotein cholesterol metabolism.
Atherosclerosis 1977 Apr
PMID:Pharmacokinetics of clofibrate in familial hypercholesterolemia. 19 24

Groups of male rats were fed various doses of clofibrate and diosgenin, both alone and in combination for 1 week. Clofibrate suppressed the diosgenin-induced increase in hepatic cholesterol synthesis but did not alter the effectiveness of diosgenin in reducing cholesterol absorption. Diosgenin did not affect the bioavailability of CPIB. Clofibrate reduced the diosgenin induced increase in biliary levels of cholesterol; none of the regimens altered biliary bile acids. The combination produced greater decreases in LDL cholesterol than did either compound alone; the diosgenin-induced elevation in HDL cholesterol was partially reversed by clofibrate. The data provide a basis for the combined use of clofibrate and diosgenin in the control of hyperlipoproteinemia.
Atherosclerosis 1978 Mar
PMID:Combined effects of clofibrate and diosgenin on cholesterol metabolism in rats. 20 86

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

Chronic administration of ethyl 2-methyl-2(4-chlorophenoxy)-propionate [clofibrate, CPIB], ethyl 6-cyclohexylchroman-2carboxylate, and ethyl 6-phenylchroman-2-carboxylate to normolipemic rats, in vivo, reduced serum cholesterol levels and inhibitid the activiry of hepatic 3-hydroxy-3methyl-glutaryl Coenzyme A. Only clofibrate was found to lower liver cholesterol content after pretreatment for 4 or 18 days. The cyclic analogs, ethyl 6-cholorochromone-2-carboxylate and 9-chloro-2,3-dihydro-5H-1,4-dioxepino [6,5-b] benzofuran were inaffective as cholesterol lowering agents in normolipemic rats. These findings indicate that appropriate modification of clofibrate can lead to the development of compounds which are selective and equally effective to clofibrate as potential hypocholesterolemic agents. Results obtained in these studies are also discussed in terms of the known structural requirements of biological activity for this series of cyclic analogs in the Triton WR-1339 hyperlipemic rat model and modes of action of the parent compound.
Atherosclerosis 1977 May
PMID:Comparison of hypocholesterolemic activity for cyclic analogs of clofibrate in normolipemic rats. 85 13

The influence of the efficacy of triglyceride and cholesterol correction on cardiovascular complications and mortality was analysed in a follow-up study with 260 patients with primary HLP (triglycerides before entry greater than 2.9 mmol/l and/or cholesterol greater than 7.8 mmol/l). The follow-up time was 67.4 +/- 27 months. It was hypothesised that reduction of elevated levels of triglycerides and/or cholesterol influenced favourably the incidence of angina pectoris, MI, stroke and total mortality. For ethical reasons, it was not possible to carry out the investigations with a control group. Therefore, we performed an internal comparison of 3 categories of lipid correction achieved during the trial (effective, moderate, insufficient). A substantial improvement of the lipid disorder was obtained by individualizing the therapy. Triglycerides and cholesterol decreased on average by 50% and 20%, respectively. The incidence of MI was 10 times higher than in the general population. With respect to the type of HLP, hypertriglyceridemia revealed a significantly higher incidence of MI compared with hypercholesterolemia and mixed HLP. The therapy variant was only of importance with respect to gallstone diseases accumulating in the CPIB-treated subgroups. We found a majority of cases with newly manifested angina pectoris and stroke in the group with moderate correction of both triglycerides and cholesterol. Patients with effective triglyceride and cholesterol correction suffered less frequently from MI than those with insufficient correction. This was also the case with secondary prevention in cases with MI prior to entry. There was no significant difference in the distribution of lipid categories at entry between those with and without recurrent infarction. In the group without reinfarction, however, the percentage with insufficient control diminished significantly. Associated risk factors such as hypertension, diabetes, smoking and obesity were of minor or no significance. In subjects with effective triglyceride correction, the total mortality was 0.97/1000 treatment months vs. 3.63 in insufficiently treated patients. The figures for MI mortality were 0.36 and 1.91, respectively.
Atherosclerosis 1984 Oct
PMID:Reduced incidence of cardiovascular complications and mortality in hyperlipoproteinemia (HLP) with effective lipid correction. The Dresden HLP study. 649 44

The efficacy of clofibrate (CPIB) and nicotinic acid (NA) in the treatment of type III hyperlipoproteinemia was evaluated in 5 male subjects in a randomized cross-over study with clofibrate 1 g b.i.d. and NA 3 g/day (given either b.i.d. or t.i.d.). Following a baseline period of 6 weeks, each drug was given for 12 weeks with samples for lipid and lipoprotein determinations obtained at 6, 9, and 12 weeks. Both clofibrate and NA resulted in a significant reduction from baseline of total cholesterol (23% and 28%), VLDL cholesterol (49% and 56%), total triglycerides (40% and 43%), and VLDL triglycerides (46% and 48%), as well as a significant increase in HDL cholesterol (22% and 28%) and HDL/LDL ratio (31% and 62%). The HDL/LDL ratio was higher on NA than clofibrate (0.47 +/- 0.19 vs. 0.38 +/- 0.09, P less than 0.05). Four subjects were continued in the study and treated sequentially with NA 3.0 g/day (alternate to the previous schedule) and gemfibrozil 1.2 g/d in divided doses. Each of the 4 regimens resulted in a significant change from baseline of each of the measured lipid and lipoprotein determinations except LDL cholesterol. Comparison among the treatment regimens revealed no differences except for significantly higher HDL cholesterol and HDL/LDL ratio with NA given t.i.d.
Atherosclerosis
PMID:Treatment of type III hyperlipoproteinemia with four different treatment regimens. 658 75

Serial liver biopsies were carried out in 67 patients with HLP and/or fatty liver before, during short- and long-term therapy with CPIB and after termination of therapy. Results (1) Decrease of liver glycogen from 4.17% to 2.69% (wet weight, P less than 0.02). (2) Insignificant changes of liver triglyceride content. (3) Significant decrease of manganese, while the concentrations of zinc and copper in the liver biopsy specimens remained unchanged. (4) No signs of liver intoxication or cancerogeneous effects of light-microscopic pictures. (5) Significant increases in numbers of mitochondria and cristae as well as a hypertrophy of endoplasmic reticulum with longer lasting therapy. (6) Striking focal proliferation of cristae mitochondriales in 3 cases on longterm treatment. (7) Regression of the mitochondrial alterations after termination of the CPIB therapy. Our findings suggest that an increased number of mitochondria and of their inner membranes in the liver cells induced by CPIB could play an important role in the hypolipidemic action of the drug.
Atherosclerosis 1980 Jun
PMID:Effects of p-chlorophenoxyisobutyric acid (CPIB) on the human liver. 740 47

Fibrates are a standard in the treatment impaired lipid metabolism, in particular in combined disorders. The classical Helsinki trial provided evidence of a decreased incidence of IHD in the treated group as compared with the group on placebo. Moreover there is some recent work which proved by statistical methods regression of atherosclerosis after fibrate administration, e.g. the angiographic study BECAIT with bezafibrate. The objective of the present study was to test the effectiveness of bezafibrate (Regadrin B, 200 mg tablets, Berlin-Chemie, FRG) in patients with combined familial hyperlipidaemia. The total cholesterol concentration dropped by 12.7% the LDL-cholesterol concentration by 8.8%. There was a significant drop of triacylglycerols by 37% and a rise of HDL-cholesterol by 24.2%. The apoB concentration declined by 11.3% and apo A-1 increased by 19.6%. The fibrinogen value dropped significantly by 15.2%, the Lp(a) value did not change significantly. The body weight in the two groups did not change significantly. The achieved results resemble those of work published abroad. In the authors opinion it is a positive feature that it proved possible to engage the patients in regular aerobic physical activity. Bezafibrate, Regadrin B was well tolerated by the patients, neither clinical nor laboratory tests revealed significant undesirable effects.
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PMID:[Bezafibrate in the treatment of familial combined hyperlipidemia and its effect on certain parameters of lipid metabolism, particularly fibrinogen]. 982 67