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991.
Yuji Yasunobu Kozo Hayashi Tetsuji Shingu Katsuhiko Nomura Yoshifumi Ohkura Kouichi Tanaka Yoshio Kuga Syu-ichi Nomura Harumi Ohtani Takaharu Nishimura Hideo Matsuura Goro Kajiyama 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1997,11(4):567-574
The effects of cerivastatin sodium (BAY w 6228), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
reductase, on plasma cholesterol concentrations and the induction of hepatic LDL receptors were investigated with beagle dogs
and Hep G2 cells. Oral administration of cerivastatin (0.01, 0.03, and 0.1 mg/kg per day) for 3 weeks reduced plasma total
and very low-density lipoprotein plus low-density lipoprotein (VLDL + LDL) cholesterol concentrations and increased hepatic
LDL receptor binding activity in dogs. Scatchard plot analysis revealed a 1.9-fold increase in the maximum binding capacity
of hepatic LDL receptors in cerivastatin-treated animals. Similar results were obtained by administration of pravastatin (1.0
and 5.0 mg/kg/day) for 3 weeks. Binding activity of the LDL receptor, as well as receptor mRNA and protein concentrations,
were increased in a dose-dependent manner (0.01–1.0 μM) by exposure of Hep G2 cells to cerivastatin. The results suggest that
cerivastatin reduces plasma cholesterol concentrations by increasing hepatic LDL receptor expression. The mechanism of lowering
cholesterol concentration by cerivastatin was the same as with the other previously examined HMG-CoA reductase inhibitors,
but the effects with cerivastatin were apparent at doses much lower than the effective doses of the other drugs. Cerivastatin,
therefore, shows potential for clinical use as a potent and efficacious plasma cholesterol-lowering drug.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
992.
S. HÖRKKÖ † K. HUTTUNEN K. KERVINEN † Y. ANTERO KESÄNIEMI † 《European journal of clinical investigation》1994,24(2):105-113
Abstract. Low-density lipoprotein (LDL) was in vitro carbamylated with potassium cyanate and the clearance was studied in man. A minor carbamylation of LDL decreased the clearance of LDL by 41% (94% of amino groups free) and by 18% (90% of amino groups free). When LDL was extensively carbamylated its clearance was substantially accelerated. Moreover, the clearance of LDL isolated from 14 haemodialysis patients (uremic-LDL) was studied in rabbits. Uraemic-LDL, injected into rabbits simultaneously with the LDL of a healthy control subject, was cleared more slowly than the control-LDL (difference in fractional catabolic rate –6·5%, P = 0·02). We also examined the lipid peroxidation of the carbamylated LDL by measuring the amount of thiobarbituric-acid reactive substances (TBARS) and formation of conjugated dienes during exposure of carbamylated LDL to 5 μ M Cu2+ . The carbamylated and native LDL had similar lipid peroxidation and propensity for oxidation. In summary, both the uraemic-LDL and minimally carbamylated LDL had a decreased clearance in vivo , which may contribute to the accelerated atherosclerosis in uraemic patients. 相似文献
993.
目的测定冠状动脉粥样硬化(AS)患者血中氧化型低密度脂蛋白(OX-LDL)、丙二醛(MDA)和总抗氧化能力(TAOC)水平并探讨其与AS之间的关系。方法分别用ELISA法、硫代巴比妥法和Fe3+/Fe2+化学法对52例AS患者及30例对照组血中OX-LDL、MDA和TAOC进行检测,并与其冠脉造影结果比较。结果AS患者血中OX-LDL、MDA水平明显高于对照组(P<0.05),且多支冠脉病变患者高于单支病变,冠脉狭窄程度高患者二项指标更高;TAOC浓度明显低于对照组(P<0.05),且多支冠脉病变患者低于单支病变,冠脉狭窄程度高者TAOC浓度更低。OX-LDL、MDA浓度与TAOC浓度呈显著负相关(r1=-0.71,r2=-0.67,P<0.05)。结论OX-LDL、MDA明显升高与AS的发生与病变程度和范围有关,TAOC的检测可为AS抗氧化治疗提供重要依据。 相似文献
994.
Recent studies have shown that one cause of primary moderate hypercholesterolaemia is familial defective apolipoprotein B-100 (FDB), a condition in which a mutation in apolipoprotein B-100 (apo B-100) causes low-density lipoproteins (LDL) to bind poorly to LDL receptors. One specific mutation, a glutamine-for-arginine transformation at position 3500 of apo B-100, has been reported to produce FDB. However, other mutations in apo B-100 might also cause FDB. The present study was designed to determine whether some patients with hypercholesterolaemia, who do not have the 3500 defect, may have a slowly cleared subfraction of LDL compatible with other forms of FDB. It was postulated that slowly removed LDL should accumulate excess cholesterol ester and hence be less dense than normal LDL. If so, in patients who are heterozygous for FDB, two forms of LDL might be separable by ultracentrifugation. To test this hypothesis, less-dense (d = 1.030 g ml-1) and more-dense (d = 1.040 g ml-1) subfractions of LDL were isolated from a patient with proven FDB (3500 mutation); the two forms of LDL were labelled with different isotopes of radioiodine and re-injected into the patient. The less-dense form was removed much more slowly (0.285 pools day-1) than more-dense LDL (0.570 pools day-1). This finding appeared to confirm the validity of the approach. The same procedure was then applied to 18 other patients having elevated LDL cholesterol but not the 3500 mutation. In 13 patients, the two forms of LDL were removed at essentially identical rates, suggesting that they did not have an abnormal form of LDL. In the other five, less-dense LDL were removed at a significantly slower rate than more-dense LDL; this finding suggests that a significant portion of patients with moderate hypercholesterolaemia have an abnormal LDL species, which is not the 3500 mutation, but delays clearance of LDL from the circulation. 相似文献
995.
血清抗氧化低密度脂蛋白抗体水平对冠心病患者预后的评估价值 总被引:4,自引:0,他引:4
目的:观察分析血清抗氧化低密度脂蛋白(ox-LDL)抗体水平对冠心病患者预后的评估价值。方法:用酶联免疫吸附法(ELISA)检测100例冠心病患者及31例正常健康者血清抗ox-LDL抗体水平;用31例正常健康者血清抗ox-LDL抗体水平平均值作为标准,将这100例患者分为高水平组和低水平组,并对这两组患者进行随访,观察两组患者在随访期间心血管事件的发生率。结果:血清抗ox-LDL抗体水平高水平组(1.42±0.53)明显高于低水平组(0.64±0.14,P<0.01)。在随访期间,高水平组有21例发生心血管事件,发生率为32.31%;低水平组有1例发生心血管事件,发生率为3.33%;经X2检验两组心血管事件发生率差异有显著性意义(P<0.01)。同时,Logistic回归分析显示:血清抗ox-LDL抗体水平(P<0.01)与患者预后密切相关。结论:血清抗ox—LDL抗体水平对冠心病患者预后有一定的评价意义。 相似文献
996.
Resveratrol (3,4′,5‐trihydroxy‐trans‐stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that at low doses (such as consumed in the common diet) resveratrol may have cardioprotective activity. In this article we describe recent in vitro and in vivo studies in animal models. The results of these studies suggest that resveratrol modulates vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation and reduces myocardial damage during ischemia‐reperfusion. Although the reported biological data indicate that resveratrol is a highly promising cardiovascular protective agent, more studies are needed to establish its bioavailability and in vivo cardioprotective effects, particularly in humans. 相似文献
997.
998.
胆红素对兔实验性动脉粥样硬化形成的预防作用 总被引:1,自引:0,他引:1
目的 探讨体内的强抗氧化剂—血清胆红素防止动脉粥样硬化 (AS)的作用及机制。 方法 在新西兰兔食饵性 AS模型上 ,观察胆红素治疗性给药对氧化修饰低密度脂蛋白 (Ox L DL)、胆固醇 (TC)、甘油三酯 (TG)、低密度脂蛋白 (L DL )等水平变化及主动脉壁 AS斑块形成的影响。血清胆红素采用重氮法测定 ,Ox L DL采用EL ISA法测定 ,TC、TG采用酶法测定 ,高密度脂蛋白 (HDL)采用选择性抑制法测定 ,L DL 通过 Friedward公式计算。 结果 AS模型组的血清胆红素较正常对照组及胆红素处理组降低 (P<0 .0 5 ) ,胆红素处理组的 Ox L DL较对照组增高但低于 AS模型组 (P<0 .0 1 ) ,胆红素处理组与 AS模型组的 TC、TG、L DL 等水平差异无显著性 (P>0 .0 5 )。 结论 适当提高体内胆红素浓度以增加体内抗氧化能力 ,有利于抑制 L DL 氧化形成 Ox L DL,防止泡沫细胞形成 ,可能是防治 AS的又一重要途径 相似文献
999.
S. D. Hobbs M. W. C. Claridge C. R. G. Quick N. E. Day A. W. Bradbury A. B. M. Wilmink 《European journal of vascular and endovascular surgery》2003,26(6):618-622
OBJECTIVE: To examine the relationship between serum lipids and abdominal aortic aneurysms (AAA). METHODS: Two hundred and six males (>50 years) with AAA (> or =30 mm) detected in a population based screening programme were compared with 252 age-matched male controls in a nested case-control study. Smoking status, previous medical and family histories, height, weight, blood pressure, ankle brachial pressure index (ABPI) and non-fasting lipid profile were recorded. RESULTS: Cases were found to have significantly higher LDL cholesterol than controls. LDL cholesterol was an independent predictor of the risk for aneurysms in a logistic regression model adjusting for smoking status, family history of AAA, history of ischaemic heart disease, presence of peripheral vascular disease, use of lipid lowering medication and treatment for hypertension. There was a linear effect with increased levels of LDL cholesterol increasing the risk of having a small aneurysm (test for trend p=0.03). CONCLUSION: The highly significant association between LDL cholesterol and small aneurysms suggests that LDL, possibly acting via inflammatory mediated matrix degeneration, could be an initiating factor in the development of AAA. The ability of statin therapy to prevent AAA formation requires further investigation. 相似文献
1000.
Rabbits were fed with normal (group 1 and 2) and cholesterol rich diets (group 3 and 4) concomitantly to a daily peroral administration of 50 mg/kg procyanidolic oligomers (PCO) to groups 2 and 4. After 10 weeks, the cholesterol content of the blood serum and the excised aortic intima-media were significantly higher in groups 3 and 4 than in groups 1 and 2.The DNA, hydroxyproline, uronic acid contents were similar in aortic dry weight basis in all four groups.The intima-media samples were extracted successively with 0.15 M NaCl, 0.02 M sodium phosphate pH 7.4 (NaCl extract) and with 4M guanidinium chloride, 0.05 M sodium acetate pH 5.8 prior (G1 extract) and following (G2 extract) hydrolysis of the collagen with collagenase.The cholesterol contents of G1 extracts were higher in groups 2 and 4 than in groups 1 and 3.The cholesterol content of aortic elastin increased with cholesterol feeding (group 3). With simultaneous administration of cholesterol and PCO the cholesterol content of aortic elastin in group 4 was significantly lower than in group 3.The uronic acid contents increased in G1 extracts and in the collagenase digest with PCO treatment of both normal and hypercholesterolemic rabbits. The ratio of dermatan-sulphate to chondroitinsulphate decreased with hypercholesterolemia (group 3) and with PCO (group 2 and 4). The parallelism between increased cholesterol and uronic acid contents and modified glycosaminoglycan composition in Gl extract, indicate that the interaction of cholesterol with macromolecules of the aorta can be modulated by PCO. This drug modifies the extractibility of aortic cholesterol and glycosaminoglycans and reduces the association of cholesterol to elastin. 相似文献