缩宫素在中枢神经系统疾病中的研究进展

缩宫素是一种肽类激素，由垂体后叶分泌，经下丘脑的室旁核和视上核合成。缩宫素具有促进妊娠子宫平滑肌收缩和乳腺肌上皮收缩(排乳)的功能。近年来，缩宫素与脑内缩宫素受体结合产生的生理作用在中枢神经系统疾病领域受到广泛关注。该文回顾并总结缩宫素在中枢神经系统疾病中的研究进展及缩宫素类似物的应用，以期为缩宫素临床应用及新药研究开发提供参考。     

抗肿瘤多肽蜂毒素的固相合成

目的 合成具有抗肿瘤活性的二十六肽蜂毒素.方法 采用Fmoc固相逐步化学合成,确立了以Wang树脂为固相载体,HOBt/ DCC为缩合剂的合成工艺.结果 通过本法能够顺利合成得到二十六肽蜂毒素,收率达32％.结论 该合成方法具有可行性强、操作简便、总收率高等特点,适用于长链多肽的合成.     

缩宫素引产的临床体会

缩宫素是由下丘脑室旁核中合成后从垂体后叶分泌的一种环八肽。它与颗粒内的后叶素运载蛋白（neyrophysin）结合,沿下丘脑神经元的神经轴运送至垂体后叶储存。对子宫平滑肌有较强的兴奋作用,可引起子宫收缩。子宫对缩宫素的反应在妊娠过程中逐渐增加,足月时达高峰。在妊娠早期应用缩宫素需要很大剂量才可引起子宫收缩,到妊娠晚期只需稀释后缓慢静脉点滴小量即可。本院在产科引产方法中,常用缩宫素,尤其是晚期妊娠诱发宫缩及产程进展缓慢或停滞时,使用缩宫素更为多见。     

缩宫素联合米索前列醇防治子宫收缩乏力性产后出血临床效果观察

目的:探讨缩宫素联合米索前列醇防治子宫收缩乏力性产后出血临床效果观察.方法:随机选取本院在2014年1月～2015年8月收治的200例临盆产妇,随机分为A和B两组,每组100例.A组给予缩宫素与米索前列醇联合用药防治,B组单纯给予缩宫素治疗.A组与B组进行治疗效果比较.结果:A组产妇子宫收缩乏力性产后出血率仅为2.0％,B组产妇子宫收缩乏力性产后出血率高达7.0％.结论:选用缩宫素联合米索前列醇能提高临盆产妇子宫收缩能力,对防治产妇产后出血具有较好的效果.可将缩宫素联合米索前列醇大力推广.     

0．9％氯化钠溶液缓解肌内注射缩宫素所致疼痛的效果观察

目的为肌内注射缩宫素寻找一种可减轻疼痛的有效治疗方法。方法对两组患者肌内注射缩宫素时分别采用原液和加用0．9％氯化钠溶液稀释，对两组患者注射后疼痛反应和局部反应进行观察。结果采用0．9％氯化钠溶液稀释缩宫素比用缩宫素原液肌内注射时疼痛明显减轻，差异有统计学意义（P〈0．01）。结论采用0．9％氯化钠溶液稀释缩宫素肌内注射能有效缓解患者疼痛，且安全可靠，不影响药物疗效。     

缩宫素预防产后出血的高风险因素Meta分析

目的 分析缩宫素预防产后出血使用中的风险归属和高风险因素排序.方法 检索2009年1月至2013年7月中国知网（CNKI）以及CNKI网络资源共享平台中资源总库中的源数据库公开发表的期刊论文及学位论文中关于缩宫素预防产后出血的临床回顾性研究文献,采用RevMan 5.1软件,按照用药剂量、用药途径及合并用药分别对缩宫素使用中的不良反应发生率进行Meta分析,对不能进行Meta分析的文献进行描述性分析,得出缩宫素使用中的风险归属.结果 符合标准的35篇文献纳入研究,其中与用药剂量相关的1篇,与用药途径相关的2篇,与合并用药相关的32篇.Meta分析结果显示,大剂量（剂量＞10 U）使用缩宫素风险性较高[比值比（OR）=0.20,95％置信区间（CI）：0.08～0.48,P=0.00],合并用药（OR=1.65,95％ CI：0.97 ～2.79）,P=0.07）和静脉给药（OR =0.18,95％ CI：0.01 ～3.16,P=0.27）增加缩宫素使用风险的差异无统计学意义.缩宫素与卡前列甲酯、卡前列素氨丁三醇、益母草、葡萄糖酸钙、地诺前列酮联合使用过程中,可在一定程度上降低药物不良反应的发生.米索前列醇与缩宫素联合使用,很大程度上增加了药物不良反应的发生率（OR =2.87,95％ CI：1.38 ～5.96,P=0.00）,文献异质性分析差异无统计意义（P＜0.01）.结论 缩宫素在预防产后出血使用中的高风险因素排序为用药剂量高于合并用药,合并用药高于用药途径.缩宫素在预防产后出血使用中大剂量（剂量＞10 U）使用时,药物不良反应发生率较高;米索前列醇联合缩宫素使用时,可增加用药风险.     

卡前列素氨丁三醇注射液联合缩宫素预防产后出血的疗效观察

目的观察卡前列素氨丁三醇注射液联合缩宫素预防产后出血的临床效果。方法将50例宫缩乏力性产后出血高危因素产妇随机分为观察组和对照组各25例。观察组胎儿娩出后予缩宫素20U宫体注射,卡前列素氨丁三醇注射液0．25mg肌内注射。对照组予缩宫素20U宫体注射,缩宫素20U静脉滴注。应用称重法计算2组产后2h及24h出血量、出血率和不良反应。结果观察组产后2h及24h出血量明显少于对照组,差异均有统计学意义（P〈0．05）。观察组产后出血率为16．0％（4／25）低于对照组的56．0％（14／25）,差异均有统计学意义（P〈0．05）。结论卡前列素氨丁三醇注射液联合缩宫素治疗宫缩乏力性产后出血较单独使用缩宫素疗效显著,具有临床意义。     

长效催产素受体激动剂卡贝缩宫素的药理作用与临床应用

卡贝缩宫素是一种合成的具有激动剂性质的长效催产素九肽类似物,用于选择性硬膜外或腰麻下剖腹产术后,以预防子宫收缩乏力和产后出血。本文综述了卡贝缩宫素的化学结构、药理毒理、药动学、临床应用、最大耐受量、安全性等,供临床参考,以促进临床安全合理用药。     

西曲瑞克的固相合成

目的 优化西曲瑞克的固相合成条件及纯化方法。方法 采用Fmoc固相合成法,以Rink Amide-AM Resin为固相载体,以DIC/HOBt或DIC/HOAt为缩合剂,采用制备型反相高效液相色谱法进行纯化。 结果 合成西曲瑞克粗肽,粗品纯度为94.8%。粗肽经制备型反相高效液相色谱纯化,所得精肽的纯度高达99%,总收率为62%。结论 该合成方法简单易行,产品纯度及收率都很高,适合用于西曲瑞克的工业化生产。     

缩宫素催产280例临床分析

目的：探讨缩宫素静脉滴注在产程中的应用效果。方法：对280例产妇应用缩宫素静脉滴注。结果：催产效果良好，成功率达90％。结论：缩宫素在产科上的应用效果良好，缩短了产程，达到加速分娩及提高自然分娩的目的并降低了剖宫产率及围生儿病死率。     

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.

     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

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.