辛伐他汀加omega-3脂肪酸治疗冠心病及其等危症合并混合性血脂异常随机双盲对照研究

目的评价辛伐他汀与国产omega-3脂肪酸合用在冠心病及其等危症合并混合性血脂异常患者调脂治疗中的疗效和安全性。方法用随机双盲安慰剂平行对照的试验方法,冠心病及其等危症合并混合性血脂异常患者经6-12周辛伐他汀10或20mg治疗后,低密度脂蛋白胆固醇已达标(LDL-C<2.6mmol·L-1)或接近达标(LDL-C<3.4 mmol·L-1),但甘油三酯(TG)水平在2.26-5.64 mmol·L-1,加用omega-3脂肪酸每日3g或安慰剂,治疗2月,40例患者完成试验,每组患者20名。结果Omega-3脂肪酸组治疗后,TG、总胆固醇(TC)、非高密度脂蛋白胆固醇(Non-HDL-C)较基线分别显著降低1.06±O,74(31.1％),0.35±0.58(6.3％),0.44±0.58 mmol·L-1(10.4％)(P<0.05);Omega-3脂肪酸组较安慰剂组TG降低更明显(P<0.05)。加用Omega-3脂肪酸组治疗2个月后,较基线单用辛伐他汀显著增加30％的Non-HDL-C达标率(P<0.05)及25％的全面达标率(P<0.05)。Omega-3脂肪酸组TG基线值与TG下降幅度呈显著正相关(P<0.05)。两组间药物不良反应无统计学差异。结论辛伐他汀加用国产omega-3脂肪酸调脂治疗冠心病及其等危症合并混合性血脂异常患者安全、有效。     

高脂血症患者细胞色素P450 3A4~* 18B基因多态性对辛伐他汀稳态血药浓度及其对降脂疗效的影响

目的分析高脂血症患者细胞色素P450 3A4~*18B(CYP3A4~*18B)基因多态性对辛伐他汀稳态血药浓度及其对降脂疗效的影响。方法 115名高脂血症患者均予以辛伐他汀每次20 mg,qd,口服,连续用药4周。在治疗前和治疗后,分别抽取空腹外周静脉血2 mL,用聚合酶链反应-限制性片段长度多态性分析法分析CYP3A4~*18B的等位基因,用全自动生化分析仪测定血总胆固醇、低密度脂蛋白胆固醇等。在最后一次服药前0.5 h内,抽取外周静脉血4 mL,用HPLC法测定血中辛伐他汀的稳态药物浓度。结果 115名高血脂症患者中,CYP3A4~*18B基因型分布符合Hardy-Weinberg遗传平衡(P>0.05),CYP3A4~*18B等位基因突变率为41.74%。CYP3A4~*1/~*1、CYP3A4~*1/~*18B和CYP3A4~*18B/~*18B的辛伐他汀稳态血药浓度分别为(4.88±0.44),(4.90±0.38)和(4.71±0.36)ng·mL^-1,总胆固醇分别为(5.78±0.47),(5.84±0.47)和(5.82±0.52)mmol·L^-1,低密度脂蛋白胆固醇分别为(2.63±0.04),(2.60±0.08)和(2.58±0.12)mmol·L^-1,差异均无统计学意义(均P>0.05)。结论 CYP3A4~*18B基因多态性对辛伐他汀稳态血药浓度及降脂疗效无明显影响。     

辛伐他汀在冠心病二级预防中的作用及其安全性的初步研究

目的探讨辛伐他汀在冠心病二级预防中的作用及其安全性。方法采用辛伐他汀(20mg/d)治疗冠心病合并高脂血症患者,并进行临床随访研究。分别于服药后1、3、6、12、24个月复查血脂、肝功能、肌酸激酶,观察临床症状如心绞痛发作次数及再住院治疗情况、心肌梗死(MI)、病死率及各种不良反应例数、次数。对照组给予安慰剂。结果辛伐他汀治疗后能降低冠心病患者总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)水平,各组高密度脂蛋白胆固醇(HDL-C)水平均有逐渐增高趋势,甘油三酯(TG)均有逐渐降低趋势。结论辛伐他汀具有显著调脂作用,是一种安全有效的冠心病二级预防药物。     

辛伐他汀联用多烯康与两药单独应用治疗混合性血脂异常临床观察(附103例分析)

目的 评价辛伐他汀联用多烯康及两药单用治疗混合性血脂异常患者的疗效与安全性。方法 103例混合性血脂异常患者随机分为三组。辛伐他汀＋多烯康组33例，给予辛伐他汀20mg／d，多烯康4．05g／d；辛伐他汀组42例，给予辛伐他汀20mg／d；多烯康组28例，给予多烯康4．05g／d；治疗12周，观察降脂疗效和不良反应。结果 辛伐他汀＋多烯康组，总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）均显著降低（P〈0．01），高密度脂蛋白胆固醇（HDL-C）升高（P〈0．01）；辛伐他汀组TC、LDL—C显著降低（P〈0．01），HDL—C升高（P〈0．05）；多烯康组TG下降明显（P〈0．01），TC及LDL—C下降、HDL-C升高不明显（P〉0．05）。结论 辛伐他汀＋多烯康组降低TC、TG、LDL—C明显，升高HDL—C明显；辛伐他汀组降低TC、LDL—C及升高HDL-C明显；多烯康组降低TG明显。辛伐他汀＋多烯康组与单用辛伐他汀组不良反应轻微，多烯康组无明显不良反应。提示对混合性血脂异常患者两药联用疗效好而副作用轻微。     

曲美他嗪联合美托洛尔治疗老年冠心病合并心力衰竭的临床研究

目的研究曲美他嗪联合美托洛尔治疗老年冠心病合并心力衰竭的临床效果。方法将老年冠心病合并心衰患者随机分为对照组和试验组,每组59例。对照组采用常规治疗;在此基础上,试验组口服盐酸曲美他嗪片20 mg,tid+口服酒石酸美托洛尔片6.25 mg,bid。2组均治疗12周。用彩色多普勒超声仪测定心肌重塑指标,用免疫层析法及酶联免疫吸附法测定血液指标,随访治疗效果和观察药物不良反应(ADR)发生情况。结果治疗后,对照组的改善率为77.97%,低于试验组的改善率91.52%;试验组与对照组的左室射血分数分别是(55.17±6.85)%,(48.93±6.37)%;这2组的N端脑钠肽前体含量分别是(2078.96±307.28),(2415.62±321.47)pg·m L^-1;这2组的血清高敏-C反应蛋白含量分别是(4.11±2.27),(6.53±2.48)mg·L^-1。试验组的上述指标与对照组比较,差异均有统计学意义(均P<0.05)。对照组和试验组的ADR发生率分别为10.17%(6例/59例),8.47%(5例/59例),组间比较差异无统计学意义(P>0.05)。结论曲美他嗪联合美托洛尔对老年冠心病合并心力衰竭患者的治疗效果确切,能延缓心肌重塑和心肌损伤,降低炎症反应。     

辛伐他汀两种剂量治疗冠心病血脂异常患者的疗效与安全性

目的探讨辛伐他汀两种剂量治疗冠心病血脂异常患者的疗效与安全性。方法我院治疗的冠心病血脂异常患者90例,平均分为高剂量组和低剂量组各45例。高剂量组患者给予辛伐他汀20mg,低剂量组患者给予辛伐他汀10mg,口服治疗。结果用药90d和180d后,两组患者的TC和LDL-C检测结果与治疗前相比,均有明显的降低(P<0.05),而两组患者的HDL-C和TG,治疗后与治疗前相比,差异均不具有统计学意义(P>0.05)。但两组患者不同时期的TC和LDL-C检测结果相比,差异均无统计学意义(P>0.05)。高剂量组患者药物的降TC作用和降LDL-C作用明显优于低剂量组(P<0.05)。而药物的升HDL-C作用和降TG作用,两组患者相比,差异无统计学意义(P>0.05)。高剂量组患者降低TC和降低LDL-C的达标率明显高于低剂量组患者(P<0.05)。但在两个时段之间的达标率比较,差异均不具有统计学意义(P>0.05)。结论辛伐他汀用药剂量10mg及20mg均具有良好的调节冠心病血脂异常的作用,并且具有很好的安全性,同时20mg的作用效果更佳。     

辛伐他汀、普伐他汀治疗原发性高胆固醇血症的疗效比较

目的:观察辛伐他汀(Sim)、普伐他汀(Pra)治疗原发性高胆固醇血症的疗效及安全性.方法:采用随机分组、平行对照的方法.81例患有原发性高胆固醇血症病人.随机分成2组,Sim组39例.Pra组42例.结果:经过12wk治疗,Sim组TC、TG、LDL-C分别由(7.42±1.33).(2.23±1.16),(4.60±1.18)mmol/L下降到(5.69±1.17),(1.65±0.75),(3.07±0.94)mmol/L(P<0.01).HDL-C治疗前后分别为(1.30±0.28).(1.28±0.49)mmol/L下降了1.5%(P>0.05);Pra组TC、TG、LDL-C分别由(7.14±1.20),(2.32±1.30),(4.64±1.37)mmol/L下降到(5.76±1.13),(1.88±1.07),(3.28±1.30)mmol/L(P<0.01),HDL-C治疗前后分别为(1.27±0.24),(1.31±0.29)mmol/L(P>0.05);2组血脂改变程度、疗效及不良反应经统计学处理无差异(P>0.05).结论:Sim 5mg/d,Pra 10mg/d对原发性高胆固醇血症的病人可获得较好的疗效.且使用方便.     

阿魏酸哌嗪分散片联合氯吡格雷治疗冠心病的临床研究

目的观察阿魏酸哌嗪分散片联合氯吡格雷治疗冠心病的疗效。方法选择本院2015年至2016年收治的88例冠心病患者作为研究对象,按随机数表法将患者分为对照组和试验组,每组44例。对照组予以氯吡格雷治疗,于术前接受氯吡格雷75mg,qd,持续治疗6个月;在对照组基础上,试验组予以阿魏酸哌嗪分散片治疗,口服阿魏酸哌嗪分散片100 mg,tid,持续治疗1个月。比较2组的临床疗效和血清同型半胱氨酸(HCY)、超敏C反应蛋白(Hs CRP)、髓过氧化物酶(MPO)、缺血修饰清蛋白(IMA)水平,并观察药物不良反应(ADR)发生情况。结果试验组和对照组总有效率分别为90.90%(40例/44例)和72.72%(32例/44例),组间比较差异有统计学意义(P<0.05)。治疗后,试验组和对照组的血清HCY分别为(12.48±1.91),(16.36±2.02)μmol·L^-1;这2组的Hs CRP分别为(1.34±0.17),(3.82±0.56)mg·L^-1;这2组的MPO分别为(17.36±2.88),(23.26±4.26)mmol·L^-1;这2组的IMA分别为(20.10±2.44),(24.91±3.53)μg·L^-1,组间比较差异均有统计学意义(均P<0.05)。试验组和对照组的ADR发生率分别为25.00%(11例/44例),20.45%(9例/44例),组间比较差异无统计学意义(P>0.05)。结论阿魏酸哌嗪分散片联合氯吡格雷治疗冠心病的疗效优于单用氯吡格雷,能够降低血清HCY、Hs CRP、MPO、IMA水平,减缓病情。     

氯吡格雷联合依折麦布对冠心病心绞痛患者内皮功能及脂代谢的影响

目的观察氯吡格雷联合依折麦布对冠心病心绞痛患者内皮功能及脂代谢的影响。方法将100例冠心病心绞痛患者,按随机数字表法分为对照组、试验组,各50例。对照组给予依折麦布,每次10 mg,每天1次,每晚服用;试验组在对照组的基础上给予氯吡格雷,每次75 mg,每天1次,每晚服用。2组均连续治疗12周。检测2组治疗前后内皮功能指标及血脂水平。结果治疗后,对照组与试验组血清一氧化氮(NO)水平分别为(62.26±5.43),(79.55±6.82)μmol·L^-1,血清内皮素-1(ET-1)水平分别为(82.54±9.34),(52.19±10.63)pg·L^-1,血清血管内皮细胞生长因子(VEGF)水平分别为(110.68±15.26),(192.65±19.37)ng·L^-1,血清总胆固醇(TC)水平分别为(4.34±0.23),(3.68±0.35)mmol·L^-1,血清三酰甘油(TG)水平分别为(2.09±0.21),(1.74±0.14)mmol·L^-1,血清高密度脂蛋白(HDL-C)水平分别为(1.19±0.32),(1.30±0.19)mmol·L^-1,血清低密度脂蛋白(LDL-C)水平分别为(3.39±0.27),(2.87±0.39)mmol·L^-1,差异均有统计学意义(均P<0.05)。试验组出现恶心2例,腹痛1例,过敏1例,药物不良反应发生率为8.00%;对照组出现恶心3例,呕吐2例,过敏2例,腹痛2例,药物不良反应发生率为18.00%。2组药物不良反应发生率比较,差异无统计学意义(P>0.05)。结论氯吡格雷联合依折麦布治疗冠心病心绞痛有良好的疗效,可显著改善内皮功能指标,还能调节血脂紊乱,且安全性好。     

氨氯地平联合阿托伐他汀钙治疗高血压合并冠心病患者的临床研究北大核心CSCD

目的观察氨氯地平联合阿托伐他汀钙对高血压合并冠心病患者血管内皮功能、血脂及血清Apelin的影响。方法将120例高血压合并冠心病患者用随机数字法分为对照组(n=60)和试验组(n=60)。对照组给予氨氯地平5 mg,每天1次,口服;试验组在对照组的基础上给予阿托伐他汀钙20 mg,每天1次,口服。2组均连续治疗12个月。比较2组患者的临床疗效、血脂水平[总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、Apelin水平、Salusin-β水平、内皮功能、动脉硬化相关指标[血管内皮素-1(ET-1)、一氧化氮(NO)、动脉中层厚度(IMT)]和药物不良反应发生情况。结果对照组和试验组总有效率分别为83.33%,95.00%,差异有统计学意义(P<0.05)。治疗后,对照组和试验组的HDL-C分别为(1.30±0.52),(1.92±0.46)mmol·L^(-1);LDL-C分别为(4.40±0.52),(2.21±0.37)mmol·L^(-1);TC分别为(3.53±0.61),(2.69±0.23)mmol·L^(-1);Apelin分别为(1.67±0.52),(1.99±0.63)μg·L^(-1);Salusin-β分别为(4.50±0.71),(3.73±0.49)mg·L^(-1);ET-1分别为(56.46±7.03),(45.38±6.57)mg·L^(-1);NO分别为(90.68±14.89),(114.36±15.47)mg·L^(-1);IMT分别为(0.91±0.06),(0.74±0.05)mm,差异均有统计学意义(均P<0.05)。对照组和试验组的药物不良反应率分别为6.67%和10.00%,差异无统计学意义(P>0.05)。结论氨氯地平联合阿托伐他汀钙治疗高血压合并冠心病患者可有效调节血脂及炎症反应,改善内皮功能及冠状动脉硬化情况,疗效显著。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.