药物洗脱球囊制备工艺探讨

以尼龙-12球囊导管为材料,采用直接涂覆的方式制备紫杉醇药物洗脱球囊导管,考察了胶黏剂溶液浓度、紫杉醇溶液浓度、风干时间和风速对紫杉醇载药量的影响。结果表明,制备药物洗脱球囊的最佳反应条件为:胶黏剂溶液浓度为60 mg/m L,紫杉醇的浓度为12.5 mg/m L,风速为5 m/s,风干时间为35 s。     

药物洗脱球囊制备工艺探讨

以尼龙-12球囊导管为材料,采用直接涂覆的方式制备紫杉醇药物洗脱球囊导管,考察了胶黏剂溶液浓度、紫杉醇溶液浓度、风干时间和风速对紫杉醇载药量的影响。结果表明,制备药物洗脱球囊的最佳反应条件为:胶黏剂溶液浓度为60 mg/m L,紫杉醇的浓度为12.5 mg/m L,风速为5 m/s,风干时间为35 s。     

应用国产雷帕霉素药物洗脱支架治疗支架内再狭窄病变临床结果初步分析

目的评价国产雷帕霉素洗脱支架(LEPU MEDICAL公司,Partner支架)在支架内再狭窄病变(ISR)中应用的安全性及近期疗效。方法分析24例植入Partner支架的ISR病人的一般临床资料、手术操作技巧、手术前后影像学结果、住院期间主要不良心性事件(MACEs,死亡、非致死性心梗、心绞痛复发等)发生、出院后随访等结果。结果该组患者中75%表现为急性冠脉综合征;70%以上的患者病变位于LAD;病变平均内径由术前0.40mm增加到了术后3.14mm;所有患者住院期间无MACEs发生;平均随访(9.5±3.23)个月(1～11个月),无死亡病例,MACEs事件为0%,2例患者术后7个月复查冠脉造影,原支架内未见明显狭窄。结论 Partner支架在ISR病变中的应用近期内是安全、有效的。     

钴铬合金生物降解涂层雷帕霉素药物洗脱支架微观结构及在体植入研究

药物洗脱支架植入术是目前冠心病介入治疗的重要手段之一.药物洗脱支架通过包被于金属支架表面的聚合物涂层携带药物,药物从聚合物中缓慢释放,在局部发挥药理作用,从而改善支架术后疗效,降低支架内再狭窄发生率.传统316L不锈钢非降解涂层支架的远期安全性特别是支架血栓作为冠心病介入治疗的主要致命不良事件受到高度关注.发生支架内血栓事件的原因可能与以下因素有关,首先,传统的316L不锈钢支架金属平台管壁较厚,导致内皮细胞覆盖缓慢;其次,不可降解的聚合物涂层在局部造成炎症反应;第三、非降解聚合物涂层内残留药物未被洗脱或延迟洗脱,造成内皮延迟愈合.鉴于上述原因,采用生物可降解聚合物涂层及钴铬合金支架平台的药物洗脱支架是近年来的重点研究课题之一.本研究通过以钴铬合金支架平台优化设计、生物降解多级涂层涂敷技术、钴铬金支架平台表面预处理和径向分级压握等技术手段改善药物洗脱支架的微观结构,并通过在体动物植入实验观察其炎症反应等生物相容性指标及抑制新生内膜增生的情况,以验证其安全性及有效性.     

邻甲苯基苯甲腈的合成及其在心血管药物中的应用与前景

介绍了邻甲苯基苯甲腈的合成方法及其在新型血管紧张素Ⅱ拮抗体药物中的应用，以邻甲苯基苯甲腈为基础中间体开发的几种产品的合成，邻甲苯基苯甲腈的发展前景。     

酶工程药物及中间体研发进展与应用前景

1医药用酶的研发进展与应用前景 1．1酶在疾病诊断方面的研发进展与应用前景 人类疾病的治疗效果好坏与否，在很大程度上决定于诊断的准确性。疾病诊断的方法很多，其中酶学诊断特别引人注目。由于酶具有专一性强、催化效率高、作用条件温和等显著的催化特点，酶学诊断已经发展成为可靠、简便又快捷的诊断方法，具有广阔的应用前景。     

药物洗脱支架植入与冠状动脉旁路移植术治疗多支冠状动脉病变临床疗效的对比研究

目的评价与比较多支冠脉病变行冠状动脉旁路移植术(CABG)与药物洗脱支架(SES)植入的近期与中期治疗效果。方法采用病历回顾的方法入选2004年7月至2007年6月在吉林省人民医院行血运重建的多支冠状动脉病变的患者。排除急性心肌梗死行原发性支架术(primary stenting)、既往行CABG、或CABG与其他心脏外科手术同期进行的患者。根据血运重建方式的不同,将患者分为二组,冠状动脉搭桥组(CABG组),156例;药物洗脱支架组(SES组),251例。记录住院期间死亡、新发心肌梗死、卒中和再次血运重建事件。以电话询问的方式,对患者出院后上述临床事件的发生情况进行回顾性随访。采用Kaplan-Meier方法分析无事件生存率,采用Logistic多元逐步回归分析不同血运重建方式对临床结果的相对影响。结果:随访时间的中位数为779天(29.3月)。随访成功率92.1%。CABG组84.1%患者使用了乳内动脉。SES组53.2%的患者植入了2个以上支架。CABG组与SES组比较,CABG组三支病变、前降支近段病变、左主干病变和慢性完全闭塞病变,及既往陈旧性心肌梗死(OMI)患者明显多于SES组。SES组糖尿病和ST段抬高心肌梗死(STEMI)的患者较多。结果CABG组主要心脑血管事件(MACE)的发生率高于SES组(4.8%比1.2%,多因素分析:CABG与SES植入相比OR4.7,95%CI1.1-19.8,P=0.035);CABG组的死亡率高于SES组(3.8%比0.8%,多因素分析:CABG与SES植入相比OR 4.2,95%CI0.9-17.2,P=0.06),但未达到显著性水平。随访临床结果的多因素Logistic逐步回归分析显示,累积MACE、卒中和心肌梗死(MI)的发生两组差异无显著性,CABG组累积死亡率高于SES组(7.6%比3.1%,多因素分析:CABG与SES植入相比OR 2.9,95%CI1.3-6.5,P=0.012),SES组的累积血运重建率高于CABG组(8.4%比1.5%,多因素分析:SES植入与CABG比较OR6.8,95%CI3.1-15.2,P<0.001)。采用Kaplan-Meier分析显示CABG组累积生存率低于SES组,两组间差异有显著性(P=0.017),无MACE生存率两组间差异无显著性(P=0.732)。以30天为分期分析,CABG组30天生存率低于SES组(95.4%比98.8%,P=0.017),两组30天后生存率差异无显著性(97.2%比98.3%,P=0.476)。结论CABG组的30天死亡率高于SES组,30天后死亡率无差异。多支冠脉病变SES植入组的中期血运重建率高于CABG组。     

预洗脱技术在组氨酸提纯工艺中的应用研究

在离子交换法提纯组氨酸的工艺中,引入预洗脱技术,通过选择适宜的预洗液浓度和预洗脱速度实现高纯度组氨酸的提取。     

新型传质分离装置在洗脱苯中的应用

传质分离装置的选型关系着粗苯回收工段的关键设备洗苯塔、脱苯塔的效率、能耗等。评述了各种常见的传质分离装置的优缺点及选择依据,分析了在洗苯和脱苯工艺过程中的传质分离特点。结合工艺参数介绍了新型高效CJST塔板,该塔板具有气液相表面积大、液相中分子传递速率快、通过气液相高速碰撞湍流可加强相界面更新等特点,并指出在操作中要注意控制脱苯塔富油进塔温度。实践证明,CJST塔内件的使用,提高了粗苯回收率。     

纳米生物技术在药物发现中的应用进展

纳米生物技术在诊断学和药物运送中有重要作用,文章主要解释了几种技术包括纳米技术和纳米装置如纳米生物传感器和纳米生物芯片是怎样应用于提高药物发现和发展过程的。在体内应用纳米粒子会有一些安全方面的考虑,一些研究正在试验这些物质的天然和扩大的不良反应。应用纳米技术于健康护理及个体化药物的前景十分广阔。     

平板运动试验与冠状动脉造影诊断冠心病的对照分析

目的探讨活动平板运动试验(TET)对冠心病(CHD)的诊断价值。方法对200例拟诊为冠心病患者先后行平板运动试验和冠状动脉造影检查(CAG)。根据冠状动脉造影结果将患者分成冠心病组和非冠心病组,并对运动试验结果进行对比分析。结果200例患者中确诊为冠心病者149例,其中平板运动试验阳性127例(85.23%),阴性22例(14.77%);非冠心病者51例,平板运动试验阳性14例(27.45%),阴性37例(72.55%)。运动试验诊断冠心病的敏感性为85.23%,特异性为72.55%,阳性预测值为90.08%,阴性预测值为62.71%。平板运动试验对冠心病患者多支血管病变及左主干病变检出率明显高于单支血管病变(P<0.01)。结论平板运动试验诊断冠心病敏感度和特异度较高,尤其对多支血管和左主干病变患者,是一种较理想的无创性的检查方法。     

Bioresorbable Drug-Eluting Magnesium-Alloy Scaffold for Treatment of Coronary Artery Disease

The introduction of metallic drug-eluting stents has reduced the risk of restenosis and widened the indications of percutaneous coronary intervention in treatment of coronary artery disease. However, this medical device can induce hypersensitive reaction that interferes with the endothelialization and healing process resulting in late persistent or acquired malapposition of the permanent metallic implant. Delayed endotheliaization and malapposition may lead to late and very late stent thrombosis. Bioresorbable scaffolds (BRS) have been introduced to potentially overcome these limitations, as they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage. Magnesium is an essential mineral needed for a variety of physiological functions in the human body and its bioresorbable alloy has the strength-to-weight ratio comparable with that of strong aluminum alloys and alloy steels. The aim of this review is to present the new developments in Magnesium BRS technology, to describe its clinical application and to discuss the future prospects of this innovative therapy.     

新型生物标志物在冠心病中的研究进展

近年来,冠心病的生物标志物的研究逐渐引起人们的重视.大量研究发现冠心病生物标志物参与冠心病发生发展的各个阶段,在冠心病的发生发展中起着十分重要的作用.目前生物标志物已成为诊治冠心病不可缺少的一种手段.本文就亲环素A、心型脂肪酸结合蛋白、正五聚蛋白3、核苷酸结合寡聚化结构域样受体蛋白3炎性小体这四种新型生物标志物在冠心病...     

Factor XIII B Subunit Polymorphisms and the Risk of Coronary Artery Disease

The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.     

A Genetic Polymorphism in RBP4 Is Associated with Coronary Artery Disease

Insulin resistance and obesity is influenced by the retinol binding protein 4 (RBP4) adipokine. This study aims to determine if genetic polymorphisms in RBP4 are associated with the risk of coronary artery disease (CAD) in Chinese patients. RBP4 polymorphisms were analyzed by high resolution melting (HRM) analysis in a case-control study of 392 unrelated CAD patients and 368 controls from China. The Gensini score was used to determine the severity of CAD. The genotypic and allelic frequencies of RBP4 single-nucleotide polymorphisms were evaluated for associations with CAD and severity of disease. The A allele frequency was significantly higher in CAD case groups compared to control groups (16.7% vs. 8.8%) at the RBP4 rs7094671 locus. Compared to the G allele, this allele was associated with a higher risk of CAD (OR = 2.07 (1.50–2.84)). Polymorphisms at rs7094671 were found to associate with CAD using either a dominant or recessive model (OR, 95% CI: 1.97, 1.38–2.81; 3.81, 1.53–9.51, respectively). Adjusting for sex, history of smoking, serum TC, TG, LDL-c, and HDL-c, the risk of CAD for carriers remained significantly higher in both dominant and recessive models (OR, 95% CI: 1.68, 1.12–2.51; 2.74, 1.00–7.52, respectively). However, this SNP was not significantly associated with severity of CAD using angiographic scores in multivariable linear regression models (p = 0.373). The RBP4 rs7094671 SNP is associated with CAD; however, our results do not indicate that this locus is associated with clinical severity of CAD or the extent of coronary lesions.     

In Vitro Simultaneous Transfer of Lipids to HDL in Coronary Artery Disease and in Statin Treatment

The exchange of lipids with cells and other lipoproteins is a crucial process in HDL metabolism and for HDL antiatherogenic function. Here, we tested a practical method to quantify the simultaneous transfer to HDL of phospholipids, free-cholesterol, esterified cholesterol and triacylglycerols and to verify the lipid transfer in patients with coronary artery disease (CAD) or undergoing statin treatment. Twenty-eight control subjects without CAD, 27 with CAD and 25 CAD patients under simvastatin treatment were studied. Plasma samples were incubated with a donor nanoemulsion prepared by ultrasonication of the constituent lipids and labeled with radioactive lipids; % lipids transferred to HDL were quantified in the HDL-containing supernatant after chemical precipitation of non-HDL fractions and the nanoemulsion. The assay was precise and reproducible. Increase of temperature (4–37 °C), of incubation period (5 min to 2 h), of HDL-cholesterol concentration (33–244 mg/dL) and of mass of nanoemulsion lipids (0.075–0.3 mg/μL) resulted in increased lipid transfer from the nanoemulsion to HDL. In contrast, increasing pH (6.5–8.5) and albumin concentration (3.5–7.0 g/dL) did not affect lipid transfer. There was no difference between CAD and control non-CAD with regard to the lipid transfer, but statin treatment reduced the transfer to HDL of all four lipids. The test herein described is a valid and practical tool for exploring an important aspect of HDL metabolism.     

Risk-Association of DNMT1 Gene Polymorphisms with Coronary Artery Disease in Chinese Han Population

Recently, a significant epigenetic component in the pathogenesis of Coronary Artery Disease (CAD) has been realized. Here, we evaluated the possible association of candidate Single Nucleotide Polymorphisms (SNPs) in the epigenetic-regulatory gene, DNA methyltransferase 1 (DNMT1), with CAD in Chinese Han population. Five tag SNPs (rs16999593, rs2336691, rs2228611, rs4804494, rs7253062) were analyzed by High Resolution Melt (HRM) method in 476 CAD patients and 478 controls. Overall, there were significant differences in the genotype and allele distributions of rs2228611 and rs2336691, between patients and controls. The minor A allele of rs2228611 was associated with a lower risk of CAD (p = 0.034); modest effect in the additive analysis but also marginal significance was found in the recessive model [OR_additive = 0.404 (0.184, 0.884), p = 0.023 and OR_recessive = 0.452 (0.213, 0.963), p = 0.040] after adjusting for confounders. While the rs2336691 A allele were associated with a higher risk of developing CAD (p = 0.037); borderline significant association in both additive and dominant models [OR_additive = 1.632 (1.030, 2.583), p = 0.037 and OR_dominant = 1.599 (1.020, 2.507), p = 0.040]. In conclusion, these data provide the first evidence that occurrence of CAD may be moderated by genetic variation in the gene involved in the epigenetic machinery.     

Essential Polyunsaturated Fatty Acids in Blood from Patients with and without Catheter-Proven Coronary Artery Disease

Coronary artery disease (CAD) is the leading cause of death worldwide. Statins reduce morbidity and mortality of CAD. Intake of n-3 polyunsaturated fatty acid (n-3 PUFAs), particularly eicosapentaenoic acid (EPA), is associated with reduced morbidity and mortality in patients with CAD. Previous data indicate that a higher conversion of precursor fatty acids (FAs) to arachidonic acid (AA) is associated with increased CAD prevalence. Our study explored the FA composition in blood to assess n-3 PUFA levels from patients with and without CAD. We analyzed blood samples from 273 patients undergoing cardiac catheterization. Patients were stratified according to clinically relevant CAD (n = 192) and those without (n = 81). FA analysis in full blood was performed by gas chromatography. Indicating increased formation of AA from precursors, the ratio of dihomo-gamma-linolenic acid (DGLA) to AA, the delta-5 desaturase index (D5D index) was higher in CAD patients. CAD patients had significantly lower levels of omega-6 polyunsaturated FAs (n-6 PUFA) and n-3 PUFA, particularly EPA, in the blood. Thus, our study supports a role of increased EPA levels for cardioprotection.     

Macadamia Nut Consumption Modulates Favourably Risk Factors for Coronary Artery Disease in Hypercholesterolemic Subjects

Macadamia nuts are rich source of monounsaturated fats (oleic and palmitoleic acids) and contain polyphenol compounds, therefore, their consumption can be expected to impart health benefits to humans. This study was conducted to examine the effects of consuming macadamia nuts in hypercholesterolemic male individuals on plasma biomarkers of oxidative stress, coagulation and inflammation. Seventeen hypercholesterolemic male subjects were given macadamia nuts (40–90 g/day), equivalent to 15% energy intake, for a period of 4 weeks. As expected, monounsaturated fatty acids (16:1n-7, 18:1n-9 and 20:1n-9) were elevated in the plasma lipids of all volunteers following intervention with macadamia nuts. Plasma markers of inflammation (leukotriene, LTB₄) and oxidative stress (8-isoprostane) were significantly lower (1,353 ± 225 vs. 1,030 ± 129 pg/mL and 876 ± 97 vs. 679 ± 116 pg/mL, respectively) within 4 weeks following macadamia nut intervention. There was a non-significant (23.6%) reduction in the plasma TXB₂/PGI₂ ratio following macadamia nut consumption. This study demonstrates, for the first time, that short-term macadamia nut consumption modifies favourably the biomarkers of oxidative stress, thrombosis and inflammation, the risk factors for coronary artery disease, despite an increase in dietary fat intake. These data, combined with our previous results on cholesterol-lowering effects of macadamia nuts, suggest that regular consumption of macadamia nuts may play a role in the prevention of coronary artery disease.