埃索美拉唑及其光学异构体的亲和毛细管电泳手性拆分

以牛血清白蛋白为手性添加剂,建立埃索美拉唑对映体杂质检查的亲和毛细管电泳方法,并采用荧光光谱、圆二色光谱法,通过研究埃索美拉唑及光学异构体与牛血清白蛋白作用的热力学参数、焓熵驱动过程及蛋白构象变化对其拆分机理进行探讨。建立的电泳分离条件为:未涂层石英毛细管柱(50 cm×50 μm,有效长度41.5 cm),以pH 8.0的20 mmol/L磷酸二氢钠-磷酸氢二钠缓冲液(含250 μmol/L牛血清白蛋白和7%正丙醇)作为运行缓冲液,正向运行电压30 kV,柱温25 ℃,检测波长302 nm,压力进样(5 kPa,5 s)。在优化的实验条件下,埃索美拉唑与其对映体的分离度大于1.8,对映体杂质的最低检测限和定量限分别为0.8和2.0 μg/mL,在2~20 μg/mL浓度范围内线性关系良好;平均回收率为100.4%,RSD小于2.0%。该方法可用于埃索美拉唑原料药的对映体杂质检查。     

阿莫西林克拉维酸钾联合方案与阿莫西林联合方案对消化性溃疡及根除HP疗效比较

目的比较阿莫西林克拉维酸钾联合治疗方案与阿莫西林联合治疗方案对消化性溃疡及根除幽门螺旋杆菌的疗效。方法选取我院门诊经胃镜及病理学检查确诊为消化性溃疡患者,经碳呼气试验确诊幽门螺旋杆菌感染385例,男224例,女161例,年龄17～74岁,平均年龄（34.8±14.4）岁,随机分为两组：治疗组193例,男115例,女78例;年龄18～74岁（平均35.2±14.7）岁。治疗方案为：埃索美拉唑20 mg,2次/d,克拉霉素500 mg,2次/d及阿莫西林克拉维酸钾分散片1 125 mg,2次/d,7 d后继续埃索美拉唑20 mg,2次/d,21 d。对照组192例,男109例,女83例;年龄17～65岁（平均34.5±13.6）岁。对照组为：埃索美拉唑20 mg,2次/d,克拉霉素500 mg,2次/d及阿莫西林1 000 mg,2次/d,7 d后继续埃索美拉唑20 mg,2次/d,21 d。结果治疗组和对照组的症状缓解率分别为97.9%和92.2%,溃疡愈合率分别为90.2%和85.4%,HP根除率分别为90.7%和82.3%。经比较均无统计学差异（P〉0.05）。主要不良反应均是轻微可接受的。结论虽然阿莫西林克拉维酸钾联合治疗方案在症状缓解率、溃疡愈合率、HP根除率优于对照组,但是差异无统计学意义（P〉0.05）。故是否应用阿莫西林克拉维酸钾代替阿莫西林根除HP尚有待进一步研究。     

质子泵抑制剂市场前景看好

目的：消化性溃疡是一种常见病和多发病,质子泵抑制剂是目前治疗消化性溃疡病抑制胃酸分泌最强的药物,质子泵抑制剂市场的现状和进展是人们关注的热点。方法：调查近年来长江流域上海、杭州、南京、武汉、成都和重庆六城市样本医院质子泵抑制剂品种用药金额、排序、份额、增长率及临床评价。结果：常用品种为奥美拉唑、泮托拉唑、埃索美拉唑、雷贝拉唑和兰索拉唑,其中用药金额名列第1是奥美拉唑,第2是泮托拉唑。结论：质子泵抑制剂市场前景看好。     

埃索美拉唑对幽门螺杆菌诱导胃上皮细胞表达细胞因子的影响

目的探讨埃索关拉唑对幽门螺杆菌（Hp）感染的胃上皮细胞的体外抗炎效应。方法体外培养胃上皮细胞系AGS,加入不同浓度埃索美拉唑和培养的Hp感染8或24h。Westernblot检测和实时定量PCR分别检测AGS细胞中红素氧合酶1（HO-1）蛋白和mRNA表达情况;ELISA检测白细胞介素-1β（IL-1β）和IL-8的产生。同时采用RNA干扰HO-1表达后,观察其对Hp诱导IL-1β和IL-8产生的影响。结果埃索美拉唑孵育8h后,能显著抑制Hp诱导的IL—1β和IL-8表达。同时,埃索美拉唑能在转录翻译水平分别调控HO-1mRNA和蛋白表达。HO-1siRNA沉默HO-1表达后,与Hp组相比,IL-1β和IL-6分泌进一步增高。结论埃索美拉唑可能通过上调HO-1的表达而发挥对胃上皮细胞的抗炎作用。     

Aspirin and esomeprazole are superior to clopidogrel in preventing recurrent ulcer bleeding

Although low-dose aspirin is commonly used as the antiplatelet agent to prevent ischaemic events such as myocardial infarction and stroke, clopidogrel is probably superior at preventing ischaemic events. For patients who cannot tolerate aspirin, adding a proton pump inhibitor or substituting clopidogrel are options. Patients with endoscopy-confirmed ulcer healing were assigned to clopidogrel 75 mg/day or aspirin 80 mg/day and esomeprazole 20 mg b.i.d. for 12 months. There were 14 confirmed cases of recurrent ulcer bleeding, with 13 being from the 161 patients taking clopidogrel and 1 from the 159 patients taking aspirin plus esomeprazole. This trial has clearly shown that the combination of aspirin and esomeprazole is superior to clopidogrel in preventing recurrent ulcer bleeding. A more interesting study may have been to compare the effects of aspirin and clopidogrel in the presence of esomeprazole in patients with a history of ulcers.     

Interaction between clopidogrel and proton-pump inhibitors

The American Heart Association/American College of Cardiology guidelines recommend initiating a proton-pump inhibitor (PPI) to prevent gastrointestinal bleeding if patients are receiving concomitant therapy with clopidogrel and aspirin. Recently, concern has been raised regarding the ability of PPIs to decrease the antiplatelet activity of clopidogrel. To date, there are 16 studies that evaluated the outcomes of using clopidogrel with a PPI. One of the studies has shown that adding lansoprazole to clopidogrel has no effect on the concentration of clopidogrel’s inactive metabolite. The eight clinical trials that studied the effect of using PPIs and clopidogrel together on platelet function testing have shown differing effects between PPIs. Concurrent omeprazole and clopidogrel use was shown to decrease the antiplatelet effects of clopidogrel in three studies; whereas pantoprazole, lansoprazole and esomeprazole have been shown to have no significant effect on the antiplatelet response to clopidogrel. Six other studies showed that using PPIs and clopidogrel together led to adverse clinical outcomes; however, one study that did a separate analysis on pantoprazole, showed that using pantoprazole with clopidogrel had no significant impact on clinical outcomes. Post hoc analysis from a large randomized trial comparing prasugrel with clopidogrel indicated no clinically significant effects of PPIs in patients treated with either prasugrel or clopidogrel. Preliminary results from a prospective, randomized trial comparing cardiovascular clinical outcomes between omeprazole and placebo in clopidogrel-treated patients have been reported and suggest no interaction. However, the study was stopped prematurely secondary to loss of funding and follow-up limited to a median of 133 days so no firm conclusions were drawn. The data currently available regarding concurrent clopidogrel and PPI use are limited, so further studies are needed to provide a definite conclusion. Until additional prospective studies are available, the use of clopidogrel with a PPI should be avoided, if possible, and a H₂-receptor antagonist be selected instead. Prasugrel may be administered safely with a PPI as there is currently no evidence of a pharmacokinetic, pharmacodynamic or adverse clinical effects.     

内镜止血联合埃索美拉唑治疗急性非静脉曲张性上消化道出血的临床分析

目的评价内镜下止血联合埃索美拉唑治疗急性非静脉曲张性上消化道出血的临床效果。方法对比分析内镜联合埃索美拉唑治疗组(68例)与单用埃索美拉唑治疗组(70例)的止血时间、再出血率、剖腹手术率、平均输血量、住院时间等。结果内镜联合药物组的止血时间、再出血率、剖腹手术率、平均输血量及住院时间均少于单用药物组(P<0.01),且内镜下止血未发生医源性穿孔病例。结论内镜下止血联合埃索美拉唑治疗急性非静脉曲张性上消化道出血安全可靠,值得临床推广。     

氩离子凝固术联合埃索美拉唑治疗Barrett食管的近期疗效观察

目的探讨内镜下氩离子凝固术(APC)联合埃索美拉唑治疗对Barrett食管(BE)的临床疗效。方法选择经内镜及病理证实的52例BE患者,在内镜下行APC治疗,再给予埃索美拉唑抑酸40 mg/d口服8周。术后进行内镜、病理随访12个月。结果 52例均完成治疗,其中需要1次治疗者40例,2次者10例,3次者2例。49例达到完全的鳞状上皮再生(94.2%),3例再生的鳞状上皮间混有岛状的柱状上皮(5.8%)。12个月后共有6例出现内镜下可见的复发。结论内镜下APC联合埃索美拉唑治疗BE简单、安全、有效,但有一定比例的残留和复发。