Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of pravastatin (CAS 81131-70-6) on serum lipid levels in 91 type 2 diabetic patients with mean glycosylated hemoglobin of 8.5% was investigated up to 12 weeks. Oral administration of 10 to 20 mg/d of pravastatin significantly decreased total cholesterol by 18.4 +/- 1.5% after 4 weeks. When analyzed separately in type IIa and IIb hyperlipidemia, the reduction of total cholesterol by pravastatin was more prominent in the former. Low-density lipoprotein cholesterol were also significantly decreased 22.2 +/- 2.7% after 4 weeks. The effect of pravastatin in reducing triglyceride was more prominent in patients with higher triglyceride compared to those with lower triglyceride before the administration of the drug. High-density lipoprotein cholesterol showed a slight but significant increase by 4.2 +/- 1.9% after 4 weeks. Among the apolipoproteins examined, apolipoprotein B was significantly decreased after 4 weeks. Atherogenic index and apolipoprotein B/apolipoprotein A-I ratio were also significantly decreased after 4 weeks. The efficacy of pravastatin was also observed after 12 weeks to the same extent as after 4 weeks. No major side effects or abnormalities of laboratory parameters have been observed. These data lead to the conclusion that pravastatin is useful for the treatment of hyperlipidemia in type 2 diabetic patients with poor glycemic control without major adverse effects.
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PMID:Clinical efficacy of pravastatin for hyperlipidemia in patients with type 2 diabetes mellitus. 764 75

1. The preventive effects of atherosclerosis and hyperlipidemia of monatepil ([(+-)-N-(6,11-dihydrodibenzo [b,e]thiepin-11-yl)-4-(4-fluorophenyl)-1-piperazine-butanamide+ + +]monomaleate , AJ-2615, CAS 103377-41-9), a new antihypertensive drug with potent calcium antagonistic and alpha 1-adrenoceptor blocking activities, were investigated in Japanese monkeys (Macaca fuscata) fed with a cholesterol-rich diet (2% cholesterol + 6% corn oil) and compared with those of prazosin. 2. The dose of monatepil selected (30 mg/kg/d, p.o., 6 months) was the plasma concentration dose level of antihypertensive therapy and that of prazosin (2 mg/kg twice daily, p.o., 6 months) was the dose where hypolipidemic effect in cholesterol-fed monkeys has been reported. 3. In the cholesterol diet control group (n = 7), plasma levels of total cholesterol and low-density lipoprotein (LDL) significantly increased and that of high-density lipoprotein-cholesterol (HDL-C) decreased compared with the normal diet group (n = 5). In the monatepil group (n = 5), these changes were significantly suppressed. In the prazosin group (n = 5), these changes were also inhibited but the inhibitory effect was weaker than in the monatepil group. 4. The cholesterol content and sudanophilic area in the aorta indicating atheromatous lesions in the cholesterol-diet fed control group were significantly higher than those in the normal diet control group. In the monatepil group, these changes were significantly suppressed whereas in the prazosin group these changes were partially inhibited. 5. In the histological study, aortic lesions characterized by aggregations of foam cells were observed in the cholesterol-diet control group, while there was little change in the monatepil group. The anti-atherogenic effect of prazosin was weaker than that of monatepil. 6. Coronary atheromatous lesions were found in 4 out of the 7 animals in the cholesterol-diet control group and 3 out of the 5 animals in prazosin group. In contrast, no coronary atheromatous lesion was found in the monatepil group. 7. The treatment with monatepil did not influence food consumption, body weight, physical signs or blood biochemistry. 8. The anti-atherosclerotic and plasma lipid-lowering effects of monatepil may in part be attributable to its calcium antagonistic, alpha 1-adrenoceptor blocking, and anti-lipid peroxidation activities. 9. In conclusion, monatepil is a new class of antihypertensive agent that possesses anti-atherogenic properties and the ability to reduce plasma lipid levels, a main risk factor for atherosclerosis.
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PMID:Anti-atherosclerotic and plasma lipid lowering effects of the novel calcium blocker with alpha 1-adrenoceptor antagonistic activity, monatepil, in high cholesterol diet-fed Japanese Macaca fuscata monkeys. 819 92

Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low density lipoprotein) remnant metabolism display hyperlipidaemia and atherosclerosis. In the present study, these mice were used for testing the hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5) and gemfibrozil (CAS 25812-30-0) as well as a novel compound, SB 204990 (the 5-ring lactone of +/-(3R*,5S*) 3-carboxy-11-(2,4-dichlorophenyl)-3,5-dihydroxyundecanoic acid, CAS 154566-12-8), a potent inhibitor of cholesterol and fatty acid synthesis at the level of ATP-citrate lyase. APOE*3-Leiden mice were fed a saturated fat and cholesterol-rich diet supplemented with either 0.05 or 0.1% w/w of lovastatin, 0.1 or 0.2% w/w of gemfibrozil or 0.1 or 0.2% w/w of SB 204990. Lovastatin showed a dose-related decrease in plasma cholesterol levels (up to -20%) due to a lowering of LDL and HDL (low density resp. high density lipoprotein)-cholesterol (-20 and -18%, respectively), while plasma triglyceride levels were unaffected. Gemfibrozil had no effect on plasma total cholesterol levels but gave significant dose-dependent decreases in plasma (VLDL) triglyceride levels (up to -53%). SB 204990 resulted in a dose-dependent reduction of plasma cholesterol (up to -29%) by lowering VLDL, LDL and HDL-cholesterol (-50, -20 and -20%, respectively). In addition, a strong dose dependent reduction of plasma (VLDL) triglycerides up to -43% was observed with this compound. Although the effects of gemfibrozil and SB 204990 were not simply explained by changes in a single determinant of VLDL metabolism--no effects of these drugs were seen on post-heparin plasma lipoprotein lipase activity, in vivo rate of VLDL synthesis or hepatic apoC-III mRNA levels--APOE*3-Leiden mice were found to give robust hypolipidaemic responses to these test compounds. The responsiveness to hypolipidaemic therapy combined with a clear relationship between aortic lesion size and plasma cholesterol exposure, as demonstrated previously, makes this mouse an attractive model for the testing of anti-atherosclerotic properties of hypolipidaemic drugs.
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PMID:Apolipoprotein E*3-Leiden transgenic mice as a test model for hypolipidaemic drugs. 960 83

The triglyceride (TG)-lowering effect of pitavastatin (CAS 147526-32-7), a potent 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, was investigated in a guinea pig model of post-prandial lipemia. Plasma TG levels started to rise 2 h after the fat load, reached the maximum at 8 h and then gradually decreased. A 14-day dose of pitavastatin at 3 mg/kg decreased the 8 h plasma TG levels by 59%, and the 0-12 h area under the curve (AUC) of TG levels above the initial levels, by 77%. This effect was also shown with 30 mg/kg of atorvastatin (CAS 134523-00-5), and the same dose of simvastatin (CAS 79902-63-9). The intensity of the action was equivalent for pitavastatin and atorvastatin, but weaker with simvastatin. In order to clarify the mechanism of this action, the effect of pitavastatin exerted on the activity of microsomal triglyceride transfer protein (MTP), which participates in the secretion to the lymph vessel of chyromicron (CM)-TG in the small intestine, and the activity of lipoprotein lipase (LPL), which is the hydrolysis enzyme of the very low density lipoprotein (VLDL)-TG and CM-TG, was examined. However, an influence on the activity of MTP or LPL by pitavastatin was not shown. These results suggested that pitavastatin lowered the postprandial TG levels in guinea pigs by accelerating the remnant clearance, probably through the enhancement of the low density lipoprotein (LDL) receptor. This effect is expected to improve postprandial lipemia.
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PMID:Triglyceride-lowering effect of pitavastatin in a guinea pig model of postprandial lipemia. 1270 69

Although patients with medically treated vasospastic angina have a good outcome, few data exist regarding the role of underlying lesion severity associated with or without hyperlipidemia in the prognosis. Therefore, the aim of the present study was to assess the relationship between the long-term outcome of vasospastic angina and the factors influencing its prognosis. A total of 256 patients (219 men, 37 women; mean age, 54.1+/-9.2) who had coronary spasm with or without underlying lesions and were being treated with calcium channel antagonists were enrolled and followed for 13.6+/-3.7 years. Cardiac events consisted of cardiac death and ischemic events, which included acute myocardial infarction and unstable angina. Cox analysis selected coronary artery stenosis (CAS, >/=50%) and risk factors such as age, hypertension, diabetes mellitus, low-density lipoprotein-cholesterol (LDL-C), sex and smoking. There were 19 cases of cardiac death (7.4%) and 58 of ischemic events (22.7%) during the follow-up period. The presence of significant CAS was an independent predictor of event-free survival (hazard ratio (HR) =2.84, 95% confidence interval (CI) =1.79-4.52, p<0.0001). In 193 patients without significant CAS, there were 10 cases of cardiac death (5.2%, p<0.05) and 34 of ischemic events (17.6%, p<0.01). In that group, high LDL-C was the independent predictor of event-free survival (HR = 3.89, 95% CI = 1.20-12.6, p=0.02). Kaplan-Meier survival analysis revealed significantly lower event-free survival in patients with than in those without lesions (p<0.0001 by log-rank test). These results demonstrate that the most important factor for long-term prognosis of vasospastic angina treated with calcium channel antagonists is significant CAS. High LDL-C, which might alter the underlying coronary endothelial function and/or accelerate atherosclerotic lesions, could also contribute to the occurrence of cardiac events, particularly in patients without significant CAS.
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PMID:Lesion severity and hypercholesterolemia determine long-term prognosis of vasospastic angina treated with calcium channel antagonists. 1463 19

Hyperlipidemia is considered one of the key factors for cardiovascular diseases. Based on earlier work on a series of 5-alkyl-4-aryl-3-mercapto-(4H)-1,2,4-triazoles, for further lead modification, a series of 4-(substituted)amino-5-substituted-3-mercapto-(4H)-1,2,4-triazoles was designed. Target compounds were synthesized by the well known Hoggarth synthesis of substituted 1,2,4-triazoles. Synthesized compounds were screened for lipid lowering activity using the "Poloxamer 407 induced hyperlipidemia in rats" model at a dose of 100 mg/kg p.o. Compounds were found to alter serum lipid levels significantly. Most of the compounds significantly reduced serum cholesterol and triglyceride levels. Some of the compounds were found to reduce triglycerides and elevate high density lipoprotein (HDL) levels more than the standard drug atorvastatin (CAS 134523-03-8). Compounds with chloro substitution on aryl rings were found more active in reducing serum lipid levels than other substitutions.
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PMID:Synthesis and antihyperlipidemic activity of some novel 4-(substitutedamino)-5-substituted-3-mercapto- (4H)-1,2,4-triazoles. 2195 Jan 49