他汀类药物治疗缺血性脑卒中的临床研究

目的观察他汀类药物对缺血性脑卒中复发的预防作用。方法观察100例动脉粥样硬化性脑梗死患者,随机分为常规组与治疗组,每组50例。治疗组在常规组治疗基础上加用他汀药物治疗,治疗2周后比较两组患者的TC、LDL-C、HDL-C、hs-CRP水平及神经功能缺损评分。结果常规组与治疗组两组在治疗前TC、LDL-C、HDL-C、hs-CRP、NHSS水平差异均无统计学意义(P>0.05);治疗2周后,两组血清TC、LDL-C、hs-CRP、NHSS水平均较治疗前下降,HDL-C均较治疗前上升。阿托伐他汀钙片治疗组较常规组TC、LDL-C、HDL-C、hs-CRP、NHSS下降明显,HDL-C升高显著,差异有统计学意义(P<0.05)。结论他汀类药物能有效降低脑卒中血脂水平,控制炎症,从而改善患者神经功能。     

匹伐他汀钙的合成

2-环丙基-4-（4-氟苯基）-喹啉-3-羧酸乙酯经KBH4／ZnCl2还原、溴化、制得膦叶立德后，与（3R，5S）-6-氧代-3，5-二羟基-3，5．0-亚异丙基己酸叔丁酯进行Wittig-Homor反应、脱保护并内酯化、水解成盐制得HMG CoA还原酶抑制剂类降血脂药物匹伐他汀钙，总收率约31％。     

早期与延迟他汀治疗对急性缺血性卒中患者血清超敏C-反应蛋白及预后的影响

目的 探讨早期与延迟他汀治疗对急性缺血性卒中（AIS）患者血清超敏C-反应蛋白（hs-CRP）和预后的影响。方法 选择2016年10月至2018年1月安徽省立医院神经内科住院的AIS患者267例,采用随机数字表法分为早期他汀治疗组（n=134）与延迟他汀治疗组（n=133）。两组患者分别于发病24 h内和第7天开始接受他汀治疗。采用美国国立卫生研究院卒中量表评价入院时和发病第7天患者神经功能缺损情况;使用改良Rankin量表（mRS）评定第90天临床预后;通过胶乳增强免疫比浊法测定患者发病24 h内、第7天、第90天的hs-CRP水平。比较两组患者血清hs-CRP的变化、急性期神经功能的改善及90天预后良好比例,并分析延迟他汀治疗与预后不良的相关性。结果 早期他汀治疗组患者第7天hs-CRP水平较发病24 h内下降[（5.02±0.65）mg/L vs（6.45±0.59）mg/L],差异有统计学意义（P<0.05）。早期他汀治疗组患者90天mRS评分预后良好的比例高于延迟他汀治疗组[48.51%vs 36.09%],差异有统计学意义（P<0.05）。logstics回归分析显示,第7天hs-CRP水平、延迟治疗是预后不良的影响因素（P<0.05）。结论 早期他汀治疗可降低AIS患者急性期血清hs-CRP浓度,并可改善预后。     

氟伐他汀钠的合成

氟苯和氯乙酰氯经付-克酰化、与N-异丙基苯胺缩合后环合，得3-（4-氟苯基）-1-异丙基-1H-吲哚，再经Vilsmeier-Haack反应、与乙酰乙酸甲酯缩合、选择性还原后水解成盐得HMG CoA还原酶抑制剂类降血脂药氟伐他汀钠，总收率约26％。     

Changes in Lp(a) lipoprotein levels during the treatment of hypercholesterolaemia with simvastatin

Summary Thirty-six patients with total serum cholesterol levels above 6.5 mmol/l and Lipoprotein(a) levels above 100 mg · 1^–1 were evaluated in a 24 week double-blind, placebo controlled, cross-over study to assess the possible changes in Lp(a) during treatment with the HMG CoA reductase inhibitor simvastatin.The median plasma Lp(a) increased from 359 to 464 mg·l^–1 during simvastin treatment as compared to placebo (not significant). Individual changes in Lp(a) varied. In a multivariate linear regression analysis the individual change in Lp(a) was correlated with the baseline Lp(a) (r = 0.64), the change in serum triglycerides (r = 0.48) and the baseline apolipoprotein B (r = 0.36). Differences between the Lp(a) phenotypes may explain some of the varied Lp(a) responses. It appears that the effect of simvastatin on the Lp(a) level in individuals is usually insignificant, but in patients with a high Lp(a) simvastatin may further increase it.     

The effect of statins on the development of new-onset type 2 diabetes: a meta-analysis of randomized controlled trials

ABSTRACT

Objective: To determine the ability of statins to prevent the development of new-onset type 2 diabetes mellitus through a meta-analysis of randomized, controlled trials.

Research design and methods: A systematic literature search through November 6, 2007 was conducted to identify randomized, placebo-controlled trials of statins that reported data on the incidence of new-onset diabetes mellitus. Incidence of new-onset type 2 diabetes mellitus was treated as a dichotomous variable. Weighted averages were reported as relative risk (RR) with associ­ated 95% confidence intervals (CI). A random-effects model was used.

Results: Five prospective, randomized controlled trials (n?=?39?791) were identified. Upon meta-analysis, the use of a statin did not significantly alter a patient's risk of developing new-onset type 2 diabetes mellitus (relative risk, 1.03; 95% confidence interval 0.89–1.19). Subgroup and sensitivity analyses did not significantly change the results. There was statistical heterogeneity that stemmed from pravastatin's tendency towards a reduction in risk and the other statins showing an increase in risk. The funnel plot could not rule out publication bias.

Conclusions: Statins, as a class, do not demonstrate a statistically significant positive or negative impact on a patient's risk of developing new-onset type 2 diabetes mellitus.     

急性心肌梗死院前急救临床效果观察

目的探讨院前急救对急性心肌梗死患者的影响。方法将80例急性心肌梗死患者随机分为观察组和对照组各40例。对照组实施一般治疗,观察组实施院前急救。观察2组患者梗死部位和抢救情况。结果 2组梗死部位比较差异无统计学意义(P>0.05);观察组抢救成功率为95.0%显著高于对照组的77.5%,差异有统计学意义(P<0.05)。结论院前急救能显著提高急性心肌梗死的抢救成功率,降低患者病死率,急救效果显著。     

The actions of lovastatin on platelet function and platelet eicosanoid receptors in type II hypercholesterolaemia

Summary We have studied the effects of 12 weeks of lovastatin (20 mg per day) on platelet function and thromboxane formation in 18 patients with type II hypercholesterolaemia in a double-blind, placebo-controlled, prospective study.Lovastatin significantly reduced total serum and LDL-cholesterol by 20% and 25% respectively. Washed platelets of lovastatin-treated patients had significantly reduced collagen-induced aggregation and thromboxane formation ex vivo. There was no change in ADP-induced platelet aggregation, but a significant increase in prostacyclin (iloprost)-stimulated platelet cyclic AMP concentrations in lovastatin-treated patients. This was associated with a significant increase in the number of prostacyclin receptors in platelet membranes prepared from lovastatin-treated patients. There was also an increase in platelet thromboxane receptors. There were no such changes in the placebo group.These data confirm our original observation of normalization of platelet function in hypercholesterolaemia by HMGCoA reductase inhibitors and suggest changes in platelet membrane composition at the megakaryocyte level as a possible site of action.     

应激性高血糖对非糖尿病急性心肌梗死患者预后的影响

目的 评估应激性高血糖对非糖尿病急性心肌梗死(AMI)患者预后的影响和意义.方法 将138例AMI患者以空腹血糖水平分为应激性高血糖组(98例)和无应激性高血糖组(40例),比较2组患者的临床特点、并发症及病死率等.结果 AMI后应激性高血糖组严重心律失常、心力衰竭、心源性休克、大面积梗死、冠状动脉2支及3支病变发生率及病死率高于无应激性高血糖组[39.8%(39/98)比12.5%(5/40)、32.7%(32/98)比10.0%(4/40)、37.8%(37/98)比12.5%(5/40)、48.0%(47/98)比15.0%(6/40)、42.9%(42/98)比15.0%(6/40)、45.9%(45/98)比12.5%(5/40)、18.4%(18/98)比5.0%(2/40),均P＜0.05].应激性高血糖组肌酸激酶水平明显高于无应激性高血糖组[(521±116)U/L比(334±134)U/L,P＜0.05].应激性高血糖组的左冠状动脉前降支近段、左冠状动脉回旋支近段、右冠状动脉近段的梗死面积均明显大于无应激性高血糖组[(5.10±0.88)cm2 比(3.70±1.14)cm2,(3.40±0.65)cm2比(1.20±0.54)cm2,(4.50 ±1.20)cm2比(1.80±0.91)cm2,均P＜0.05].结论 应激性高血糖是AMI患者住院期间预后不良的独立预测因子和危险因素,对AMI患者应积极控制血糖水平,早发现、早处理高血糖,降低心血管事件的发生危险,以提高患者生活质量、改善其预后.

Abstract：

Objective To evaluate the influence and significance of stress-hyperglycemia on prognosis in non-diabetic patients with acute myocardial infarction(AMI). Methods All 138 AMI patients were divided, according to fasting blood glucose level, into stress-hyperglycemia group (n = 98) and non-stress-hyperglycemia group (n=40). Clinical features,complications and mortalities were compared between 2 groups. Results There was significant difference in severe arrhythmias,heart failure,cardiogenic shock,mortality and lesion incidence in 2 or 3 coronary arteries between 2 groups[(39. 8% (39/98) vs 12. 5% (5/40), 32. 7% (32/98) vs 10. 0% (4/40), 37.8% (37/98) vs 12.5% (5/40), 48. 0% (47/98) vs 15. 0% (6/40), 42. 9% (42/98) vs 15. 0% (6/40), 45.9%(45/98) vs 12.5% (5/40), 18.4%(18/98) vs5.0%(2/40), P＜0.05]. Fasting blood glucose and creatine phosphokinase were higher in stress-hyperglycemia group than in non-stress-hyperglycemia group. Proximal (left anterior descending artery, circumflex artery and right coronary artery) were higher in stress-hyperglycemia group than in non-stress-hyperglycemia group[(5.10 ±0.88)cm2 vs (3.70 ±1.14)cm2 ,(3.40 ±0.65)cm2 vs (1.20± 0.54)cm2,(4.50±1.20)cm2 vs (1.80±0.91)cm2,P＜0.05]. Conclusions Stress-hyperglycemia is the independent predictor and the risk factor for poor prognosis in patients with acute myocardial infarction during hospitalization. Active control of blood glucose is of importance for preventing and controling of complication and lowing of mortality.     

血尿酸对急性心肌梗死预后的影响

目的 探讨血尿酸水平对急性心肌梗死(AMI)预后的影响.方法 对198例急性心肌梗死患者的血尿酸水平及其肌酸激酶同工酶(CK-MB)峰值,梗死后心绞痛、心律失常、心源性休克、心力衰竭的发生率和病死率的相关关系进行分析比较.结果 198例中正常血尿酸133例,高血尿酸65例.高血尿酸组CK-MB峰值较高,梗死后心绞痛、心律失常、心力衰竭的发生率和病死率均高于正常血尿酸组(P＜0.01或P＜0.05).结论 高血尿酸与AMI预后不良有关.     

Comparative effects of simvastatin and cholestyramine in treatment of patients with hypercholesterolaemia

Summary The efficacy and safety of 20 mg simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) and of 16 g cholestyramine daily in the treatment of 34 hypercholesterolaemic patients have been compared after dietary treatment and stratified randomization. The effect of combined treatment with the two drugs was studied in 5 patients with severe hypercholesterolaemia.After 6 weeks of treatment the simvastatin group showed a significantly greater (p<0.05) decrease in the mean total plasma cholesterol concentration from 7.88 to 5.48 mmol/l than in the cholestyramine group in whom there was a fall from 7.82 to 6.73 mmol/l. Simvastatin decreased the mean plasma LDL cholesterol concentration from 6.07 to 3.76 mml/l and cholestyramine decreased it from 6.16 to 4.46 mmol/l. Simvastatin also reduced the mean plasma total triglycerides by 24%, VLDL triglycerides by 20% and VLDL cholesterol by 36%, while cholestyramine led to increases in these parameters by 64%, 85% and 63%, respectively. Mean plasma HDL cholesterol concentration and the subfractions HDL₂ and HDL₃ cholesterol were significantly increased by simvastatin. Simvastatin and cholestyramine reduced the mean plasma apolipoprotein B concentration by 28% and 13%, respectively.The mean plasma apolipoprotein A–I concentration was significantly higher only on simvastatin treatment.Simvastatin did not cause any subjective or objective side effects, while cholestyramine caused gastrointestinal problems in 31% of patients. Small increases in serum alanine aminotransferase (S-ALT) activity were seen with both drugs. Cholestyramine significantly raised the serum alkaline phosphatase (S-ALP) although to a level still within the normal range.It is concluded that 20 mg simvastatin was more effective than 16 g cholestyramine in the treatment of hypercholesterolaemia. Simvastatin was also better tolerated and it is more convenient for patients to take.     

瑞舒伐他汀对内皮细胞中组织因子途径抑制物表达的影响

目的探讨瑞舒伐他汀对组织因子途径抑制物(TF-PI)表达的调节作用及机制。方法培养人脐静脉内皮细胞(HUVECs),给予多种剂量的瑞舒伐他汀和(或)肿瘤坏死因子-α(TNF-α)、磷酸腺苷激活的蛋白激酶(AMPK)抑制剂与激活剂处理细胞,利用实时定量PCR、Western blot技术检测内皮细胞中TFPI表达的变化。结果 TNF-α下调内皮细胞中TFPI的的表达水平,而这一作用被瑞舒伐他汀所阻断。而且,瑞舒伐他汀呈时间及剂量依赖性上调TFPI的mRNA与蛋白水平。AMPK抑制剂———Compoud C则可逆转瑞舒伐他汀对TFPI表达的上调作用,而AMPK激动剂———Aicar则具有与瑞舒伐他汀相似的上调TFPI的作用。结论瑞舒伐他汀通过激活AMPK途径上调血管内皮细胞中TFPI的表达。     

观察倍他乐克对心肌梗塞患者院外治疗临床疗效

目的：探讨对心肌梗塞的患者采用倍他乐克的院外治疗效果。方法：选择69例在病情稳定之后出院接受治疗的心肌梗塞患者,将患者随机分作考察组40例与治疗组29例,考察组采用常规吸氧、止痛及溶栓等治疗方法,治疗组在常规治疗基础上加倍他乐克口服治疗,对比两组治疗半年后的临床疗效。结果：治疗组患者的有效治愈率明显比考察组高,再次发病率明显比考察组低（P＜0.05）。结论：对于心肌梗塞的患者在院外治疗中采用倍他乐克疗效显著,能够提高治愈率,降低复发率,从而提高患者的生活质量。     

国产氯吡格雷与进口氯吡格雷治疗ST段抬高型心肌梗死的疗效比较

目的：比较国产氯吡格雷与进口氯吡格雷治疗ST段抬高型心肌梗死的临床疗效。方法选取2013年11月—2014年11月泾县人民医院收治的87例ST段抬高型心肌梗死患者,按照随机数字表法分为对照组44例和治疗组43例。两组均给予溶栓、抗凝、调脂、抗心肌缺血治疗,治疗组同时给予阿司匹林联合国产氯吡格雷治疗,对照组给予阿司匹林联合进口氯吡格雷治疗。近期观察心肌梗死患者疾病进展情况、检测患者的心肌酶谱及血小板功能,远期记录患者心肌梗死再发情况。结果急性期随访21d两组心血管事件联合终点发生率、总有效率比较,差异无统计学意义（ P>0.05）。远期随访12个月,两组心脑血管事件联合终点发生率、心肌梗死再发率比较,差异无统计学意义（ P>0.05）。随访7d,两组心肌钙蛋白（ cTnI）、肌酸激酶同工酶（ CK-MB）异常持续时间、血小板聚集率比较,差异无统计学意义（ P>0.05）。两组患者出血反应、胃肠道不良反应、神经系统反应、粒细胞或血小板减少发生率比较,差异无统计学意义（ P>0.05）,两组无法坚持12个月服用药物比例比较,差异有统计学意义（ P<0.05）。结论国产氯吡格雷近期应用可减轻心肌损伤,降低心肌梗死死亡风险,长期应用可预防心肌梗死再发,其临床疗效与安全性与进口氯吡格雷无明显差异。     

Effect of ketanserin tartrate on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts

In man ketanserin tartrate reduces plasma LDL cholesterol. To clarify the mechanism of this effect the effect of ketanserin on 3-hydroxy-3-methylglutaryl (HMG) CoA reductase and LDL receptor activity in cultured human skin fibroblasts has been examined. After incubation with ketanserin for 14 h HMG CoA reductase activity was decreased in a dose-dependent manner up to 300 ng/ml (550 nM) without changing the free cholesterol content in the cells. Ketanserin increased specific binding and specific internalization of 125I-LDL dose-dependently. There was a significant inverse relationship between the percentage changes in HMG CoA reductase and LDL receptor activity. It appears that ketanserin induces up-regulation of LDL receptor activity by direct suppression of HMG CoA reductase, and this may be one mechanism by which plasma LDL-cholesterol is reduced by ketanserin.     

Effects of a secondary prevention combination therapy with an aspirin,an ACE inhibitor and a statin on 1-year mortality of patients with acute myocardial infarction treated with a beta-blocker. Support for a polypill approach

Abstract

Objective:

Large randomized clinical trials have shown the efficacy of aspirin, ACE (angiotensin converting enzyme) inhibitors and statins as secondary prevention measures in patients after an acute coronary syndrome with and without ST elevations. Therefore we aimed to determine the effect of a combination therapy with these three drugs on 1-year mortality after acute myocardial infarction (AMI).     

Effects of gender and moderate smoking on the pharmacokinetics and effects of the CYP1A2 substrate tizanidine

Objective We studied the effects of gender and smoking on the pharmacokinetics and effects of the cytochrome P450 (CYP) 1A2 substrate tizanidine. Methods Seventy-one healthy young volunteers (male and female nonsmokers, male smokers) ingested 4 mg tizanidine. Plasma concentrations and pharmacodynamics of tizanidine were measured, and a caffeine test was performed. Results Among nonsmokers, the peak concentration (C_max) and area under concentration-time curve from 0 to infinity [AUC(0-∞)] of tizanidine did not differ significantly between females and males. However, the half-life (t_1/2) was 9% shorter in female nonsmokers than in male nonsmokers (P < 0.05). In male smokers, the t_1/2 was 10% shorter and the weight-adjusted AUC(0-∞) 33% smaller than in male nonsmokers (P < 0.05). The caffeine/paraxanthine ratio was 35–40% smaller (P = 0.001) in male smokers than in nonsmoking males or females, but did not differ between males and females. Tizanidine lowered blood pressure and caused drowsiness significantly (P < 0.05) more in females than in either male groups. The effects on blood pressure were smallest in male smokers (P < 0.05). Conclusions Gender by itself seems to have no clinically significant effect on the pharmacokinetics of tizanidine, whereas smoking reduces plasma concentrations and effects of tizanidine. Any possible effect of gender and smoking is largely outweighed by individual variability in CYP1A2 activity due to genetic and environmental factors and in body weight. Careful dosing of tizanidine is warranted in small females, whereas male smokers can require higher than average doses. This study was supported by grants from the Helsinki University Central Hospital Research Fund, the National Technology Agency, and the Sigrid Jusélius Foundation, Finland.     

急性心肌梗死患者自体骨髓干细胞移植治疗效果随访

目的:研究急性心肌梗死(Acute myocardial infarction,AMI)患者自体骨髓间质干细胞(Mesenchymal stem cells,MSCs)冠脉内注射治疗的安全性以及对心功能的改善作用,并探讨其可能机制.方法:20例急性心肌梗死患者(治疗组)经皮冠状动脉介入(PCI)术后抽取骨髓分离、培养、扩增后12～14 d行冠脉内注射,另选取20例PCI术后拒绝行细胞治疗的急性心肌梗死患者作为对照组,PCI术后1周及1年进行临床随访、超声心动图及18氟-脱氧葡萄糖单光子心肌断层显像(18 F-FDG-SPECT).结果:治疗组未见与移植有关的体温升高及恶性心律失常发生.与对照组比较,1年后治疗组超声心动图心脏收缩、舒张功能指标及SPECT代谢缺损指标有明显改善,差异具有统计学意义(P＜0.05).结论:急性心肌梗死患者自体骨髓间质干细胞冠脉内注射安全有效,可以改善患者心功能及远期预后;骨髓来源的心肌细胞生成及血管新生可能为其机制.     

性别对罗库溴铵药效的影响

目的探讨性别对罗库溴铵起效时间、无反应期和恢复指数的影响。方法择期行全身麻醉手术患者60例,根据性别将患者分为男性组和女性组,各30例。5s内静脉推注罗库溴铵0．9mg／kg,记录从推药到T1达0％的时间（起效时间）、无反应期（T1为0％的时间）和恢复指数（T1由25％至75％的时间）。结果男性组和女性组的起效时间分别为（69±20）和（70±17）s,无反应期分别为（40±12）和（45±11）min,恢复指数分别为（22q-6）和（23±4）rain,2组的起效时间、无反应期和恢复指数的组间比较差异无统计学意义（P〉0．05）。结论按0．9mg／kg罗库溴铵给药,性别对其起效时间、无反应期和恢复指数无影响。