长春西汀联合纤溶酶治疗突发性耳聋的临床研究

目的探讨长春西汀注射液联合注射用纤溶酶治疗突发性耳聋的临床疗效。方法选取2017年2月—2018年8月上海市徐汇区中心医院收治的突发性耳聋患者124例作为研究对象,采用随机数表法将所有患者分为对照组和治疗组,每组各62例。对照组静脉滴注注射用纤溶酶,100 U加入到生理盐水100 mL中,30 min内滴完,1次/d。治疗组在对照组治疗的基础上滴注长春西汀注射液,20 mg加入到5%葡萄糖注射液500 mL中,1次/d。两组均连续治疗10 d。观察两组的临床疗效,比较两组的血液流变学指标、凝血功能指标、血小板相关指标、平均听阈。结果治疗后,对照组和治疗组的总有效率分别为69.35%、85.48%,两组比较差异有统计学意义(P0.05)。治疗后,两组全血高切黏度、全血低切黏度、血浆黏度和红细胞压积水平均明显下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组全血高切黏度、全血低切黏度、血浆黏度和红细胞压积水平明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组血浆纤维蛋白原(Fg)水平明显下降,而活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、凝血酶原时间(PT)明显延长,同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组这些观察指标明显优于对照组(P0.05),两组比较差异有统计学意义(P0.05)。治疗后,两组血管性假血友病因子(VWF)、蛋白酶激活受体(PAR)、血小板α颗粒膜糖蛋白(CD62p)、血小板溶酶体膜糖蛋白(CD61)水平均明显下降(P0.05),同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组VWF、PAR、CD62p、CD61明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组平均听阈明显下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组平均听阈明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论长春西汀注射液联合注射用纤溶酶治疗突发性耳聋具有较好的临床疗效,能提高患者的听力水平,改善患者的血液高凝状态和微循环,具有一定的临床推广应用价值。     

银丹心脑通软胶囊联合纤溶酶治疗脑梗死的疗效观察

目的探讨银丹心脑通软胶囊联合注射用纤溶酶治疗脑梗死的临床疗效。方法选取2013年10月—2015年6月天津市北辰医院收治的脑梗死患者80例,按照随机数字表法随机分为对照组和治疗组,每组各40例。对照组静脉滴注注射用纤溶酶,100 U加入到250 m L葡萄糖注射液中,滴注速度50滴/min,1次/d。治疗组在对照组基础上口服银丹心脑通软胶囊,3粒/次,3次/d。两组患者均连续治疗12 d。观察两组的临床疗效,比较两组美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数(BI)评分、血液流变学指标情况。结果治疗后,对照组和治疗组的总有效率分别为67.5%、87.5%,两组比较差异有统计学意义(P0.05)。治疗后,两组NIHSS评分均显著下降,BI评分均显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组全血黏度、血浆黏度和血小板聚集率均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的下降程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论银丹心脑通软胶囊联合注射用纤溶酶治疗脑梗死具有较好的临床疗效,能改善神经功能,提高生活自理能力,改善血液流变学指标,具有一定的临床推广应用价值。     

121例纤溶酶注射剂不良反应报告分析

摘 要 目的：探讨纤溶酶注射剂不良反应（ADR）的特点及其可能的原因,为临床安全用药提供参考。方法：收集浙江省药品不良反应监测中心数据库中2010年1月～2018年4月上报的121例纤溶酶注射剂ADR报告,分别按ADR类型、患者性别、年龄、用药原因、用药情况、累及系统/器官及临床表现、发生时间等进行统计分析。结果：纤溶酶注射剂新的ADR占95.04%,以45岁以上的患者居多(94.20%);ADR累及系统/器官主要为全身性反应,严重的ADR主要表现为胸闷、寒战、过敏样反应、发热、呼吸困难等;ADR主要发生在用药过程中。结论：临床应重视纤溶酶注射剂引起的ADR,尤其是严重过敏反应;生产企业应完善药品说明书安全性信息,以指导临床安全用药。     

Ammodytase, a metalloprotease from Vipera ammodytes ammodytes venom, possesses strong fibrinolytic activity

Ammodytase, a high molecular mass metalloproteinase with fibrinogenolytic and fibrinolytic activities, was purified from long-nosed viper (Vipera ammodytes ammodytes) venom by gel filtration, affinity and ion-exchange chromatographies. The enzyme is a single-chain glycoprotein with apparent molecular mass of 70 kDa and isoelectric point of 6.6. Ammodytase shows very weak hemorrhagic activity, and only at doses higher than 20 μg. Consistent with this, it partially degrades some components of the extracellular matrix in vitro. It cleaves the Aα-chain of fibrinogen preferentially at peptide bonds Glu⁴⁴¹-Leu⁴⁴² and Glu⁵³⁹-Phe⁵⁴⁰. Its preference for bulky and hydrophobic amino acids at the P1′ position in substrates is demonstrated by its hydrolysis of only the Gln⁴-His⁵ and Tyr¹⁶-Leu¹⁷ bonds in the B-chain of insulin. Ammodytase is able to dissolve fibrin clots. It neither activates nor degrades plasminogen and prothrombin, and has no effect on collagen- or ADP-induced platelet aggregation in vitro. LC/MS and MS/MS analyses of its tryptic fragments demonstrated that ammodytase is a P-III class snake venom metalloproteinase composed of metalloproteinase, disintegrin-like and cysteine-rich domains. Its similarity to hemorrhagins from V. a. ammodytes venom, accompanied by very low toxicity, makes ammodytase a promising candidate as an antigen to prepare antisera against these most dangerous components of the viper's venom. Moreover, its ability to degrade fibrin clots suggests its clinical use as an antithrombotic agent.     

纤溶酶治疗急性脑梗死临床观察

目的:观察纤溶酶治疗急性脑梗死的临床疗效。方法:将72例急性脑梗死患者随机分为对照组与治疗组进行对比研究,对照组采用常规内科治疗,治疗组在此基础上加用纤溶酶200u,以生理盐水250mL稀释后静脉点滴,每日一次,连用7d。结果:治疗组显效率和有效率(44%,72%)均明显高于对照组(25%,58%)(P<0.01);治疗组存活患者日常生活活动能力明显优于对照组(P<0.01);治疗组用药后血浆纤维蛋白原(FIB)水平比对照组显著下降(P<0.01),治疗组无增加出血事件及其他副作用。结论:纤溶酶治疗急性脑梗死安全有效。     

纤溶酶联合依达拉奉治疗短暂脑缺血发作的疗效观察

目的：观察纤溶酶联合依达拉奉治疗短暂脑缺血发作的疗效。方法：将80例短暂脑缺血发作患者随机分为试验组（40例）和对照组（40例）,两组均给予拜阿司匹林、阿托伐他汀钙片治疗,治疗组在此基础上给予纤溶酶联合依达拉奉注射液静脉滴注,7d为1个疗程。结果：试验组总有效率明显高于对照组（P〈0.05）。结论：纤溶酶联合依达拉奉治疗短暂脑缺血发作疗效显著。     

Bhalternin: Functional and structural characterization of a new thrombin-like enzyme from Bothrops alternatus snake venom

A serine protease from Bothrops alternatus snake venom was isolated using DEAE-Sephacel, Sephadex G-75 and Benzamidine-Sepharose column chromatography. The purified enzyme, named Bhalternin, ran as a single protein band on analytical polyacrylamide gel electrophoresis (SDS-PAGE) and showed molecular weights of 31,500 and 27,000 under reducing and non-reducing conditions, respectively. Its complete cDNA was obtained by RT-PCR and the 708 bp codified for a mature protein of 236 amino acid residues. The multiple alignment of its deduced amino acid sequence showed a structural similarly with other serine proteases from snake venoms. Bhalternin was proteolytically active against bovine fibrinogen and albumin as substrates. When Bhalternin and bovine fibrinogen were incubated at 37 °C, at a ratio of 1:100 (w/w), the enzyme cleaved preferentially the Aα-chain, apparently not degrading the Bβ and γ-chains. Stability tests showed that the intervals of optimum temperature and pH for the fibrinogenolytic activity were 30-40 °C and 7.0-8.0, respectively. Also, the inhibitory effects of benzamidine on the fibrinogenolytic activity of Bhalternin indicate that it is a serine protease. This enzyme caused morphological alterations in heart, liver, lung and muscle of mice and it was found to cause blood clotting in vitro and defibrinogenation when intraperitoneally administered to mice, suggesting it to be a thrombin-like enzyme. Therefore, Bhaltenin may be of interest as a therapeutic agent in the treatment and prevention of thrombotic disorders.     

纤溶酶治疗全聋型突发性耳聋的疗效观察

目的探讨纤溶酶治疗全聋型突发性耳聋的疗效。方法将87例患者随机分为两组,对照组用低分子右旋糖酐治疗,治疗组在用低分子右旋糖酐的基础上加用纤溶酶,均以10?d为一疗程。结果治疗组与对照组比较,突发性聋症状改善更显著（P<0.05）。结论纤溶酶治疗全聋型突发性耳聋有效、安全。     

颈动脉灌注治疗进展性脑梗死80例临床观察

目的观察舒血宁合剂（舒血宁、纤溶酶、利多卡因）颈动脉灌注治疗进展性脑梗死临床疗效指标及血凝分析。方法将进展性脑梗死病人随机分为治疗组（80例）和对照组（40例），予舒血宁、纤溶酶、利多卡因分别进行动脉灌注（治疗组）和静脉输注（对照组），治疗组舒血宁、纤溶酶为对照组的50％，利多卡因为25％，治疗前后分别测试血凝，进行神经功能缺损评分，判断临床疗效。结果治疗组治愈率和总有效率分别57．5％和100％，明显高于对照组的30％和75％（P〈0．05）。结论舒血宁合剂颈动脉灌注临床疗效明显优于静脉滴注，且颈动脉灌注舒血宁合剂仅为静脉输注剂量的一半。两组对血凝的影响是相当的。     

纤溶酶联合血塞通注射液治疗急性脑梗死临床研究

目的 观察纤溶酶联合血塞通注射液治疗急性脑梗死的疗效.方法 112例急性脑梗死患者完全随机分为2组,每组56例,治疗组用纤溶酶联合血塞通注射液,对照组用复方丹参注射液,均为每日用药1次,共15 d.结果 治疗组凝血指标改善比对照组明显（P＜0.05或P＜0.01）,治疗组的总有效率明显高于对照组（91.1%比69.6%,P＜0.05）,治疗组治疗后神经功能缺损积分为,较治疗前有明显改善[（8.0±7.6）分比（19.6±8.1）分,P＜0.05],且未见明显不良反应.结论 纤溶酶联合血塞通注射液治疗急性脑梗死疗效显著且安全.