阿糖胞苷神经损害事件原因的动物实验研究

只猴均于给药后12～15 d死亡.Beagle犬实验显示,事件有关阿糖胞苷40 mg组4只犬和事件无关阿糖胞苷40 mg加长春新碱16 μg组2只犬于用药后9～13 d出现行走困难;事件无关阿糖胞苷40 mg加长春新碱160 μg组2只犬在用药后6～7 d处于濒死;长春新碱160 μg组3只犬于给药后4～12 d处于濒死.生理盐水组和事件无关阿糖胞苷组均未出现神经损害症状.结论:含长春新碱的阿糖胞苷制品鞘内(椎管内)注射能致神经损害.     

维生素K1注射液致过敏性休克45例分析

目的了解维生素K1注射液致过敏性休克的特点与规律,为临床合理用药提供参考。方法检索国内有关数据库,下载原始病例报告,然后对这些病例报告进行整理与分析。结果维生素K1注射液所致的过敏性休克45例,涉及肌内注射、静脉注射和静脉滴注3个给药途径,其中以静脉滴注给药,60岁以下的成年人多见,30min以内发生者较多,有6例是重复用药发生的过敏性休克。1例死亡。结论建议临床医务人员尽量使用肌内注射给药途径,重视与维生素K1注射液有关的不良反应。     

配制乳酸钠林格注射液应注意的几个问题

乳酸钠林格注射液是临床上用于体液、电解质、酸碱平衡调节的常用药。由于处分中乳酸钠是以药用稀乳酸加氢氧化钠溶液中和而成的［刁，其pH值、含量、杂质限量均较难控制，不仅造成制剂配制上的困难，而且使乳酸钠林格注射液的质量及稳定性受到影响。根据以往的教训和体会，我们认为，在配制过程中应注意下列问题：IN减应：市售乳酸钠原料的标示浓度为40％（yg）左右。在贮存、生产过程中，乳酸钠容易发生聚合或脱水成乳酸研是使其注射液PH值不稳定的主要原因，故造成其灭菌前后的PH值发生很大变化。我们的体会是，在配制时，应先将市售…     

乳酸钠林格注射液配制方法

乳酸钠林格注射液，既能保持病人的水和电解质平衡状态，又可防止或纠正酸中毒，一度广泛用于临床，有“白色血液”之称。因乳酸钠原料不易购得，通常在配制乳酸钠林格液前用乳酸、氢氧化钠中和制取。用下述方法一步直接配制乳酸钠林格注射液，产品PH稳定，各项质量标准符合规定。1配制原理乳酸钠由乳酸与氢氧化钠中和而成：反应中，乳酸酐水解为慢反应’‘’。根据活化分子理论[2]，当增加反应物浓度，反应加快。若此反应为二级反应，那么，速度定律表示式为：V＝K[乳酸酐][OH-]因此，为了使反应短时完成，特于反应体系中加入过量的氢氧…     

鞘内注射抗菌药物引起不良反应的国内文献回顾

目的：调查鞘内注射抗菌药物引起不良反应的病例报告,分析引起该类不良反应的相关因素,为临床安全用药提供参考。方法：检索国内医学文献数据库,收集1979～2009年有关鞘内注射抗菌药物引起不良反应的病例报告20例,对患者性别、年龄、原发疾病、用药种类、给药速度、给药次数及发生不良反应的临床表现、处理、预后等进行分析。结果：共纳入20例病例,其中18岁以下儿童2例,占10%;从抗菌药物的种类看,氨基糖苷类17例,占85%;第1次鞘内注射后出现不良反应的10例,占50%;有12例不良反应的表现为双下肢肌力0级,腱反射消失,占60%;经治疗后恢复正常的有12例,占60%。结论：患者的年龄、药物的种类、鞘内注射的次数和给药速度等都是鞘内注射抗菌药物引起不良反应的相关因素。     

安痛定致过敏性休克死亡抢救护理教训

目的重视安痛定药物的不良反应,高度警惕过敏性反应的发生。方法通过2例肌内注射安痛定致过敏性休克窒息死亡病例分析。结果 2例患者救治无效死亡,其教训深刻。结论用药前详细询问病史。能口服用药不要行肌内或静脉注射。     

香丹注射液与乳酸钠林格注射液的配伍稳定性研究

目的 考察香丹注射液与乳酸钠林格注射液配伍的稳定性，为临床安全用药提供参考。方法 按临床用药配伍使用量，制备香丹注射液与乳酸钠林格注射液的配伍溶液，考察配伍溶液的外观、pH值、不溶性微粒、紫外光谱及丹参素钠、原儿茶醛、咖啡酸、紫草酸、丹酚酸B和丹酚酸A的多指标含量。结果 香丹注射液与乳酸钠林格注射液配伍6 h内，溶液性状、pH值、紫外光谱均无显著变化，不溶性微粒呈下降趋势，丹参素钠、原儿茶醛、咖啡酸和丹酚酸B的含量无显著性变化（<3%），紫草酸含量下降了17.41%，丹酚酸A的含量下降了78.64%。结论 香丹注射液与乳酸钠林格注射液在配伍6 h内部分有效成分含量下降，建议减少配伍或配伍后尽快输注，以提高输液的有效性与安全性。     

醋酸钠林格液用于围术期容量治疗的随机对照临床研究

目的评价醋酸钠林格液用于围术期容量治疗的有效性和安全性。方法本研究为随机、对照、双盲研究。选择需要输液的择期手术患者80例,ASAⅠ～Ⅱ级,年龄18～65岁,随机分为2组(n=40),醋酸钠林格液组(AR组)和乳酸钠林格液组(LR组),病人建立静脉通路后2 h内输注试验药或对照药2 L,作为血容量补充剂。观察生命体征的稳定性、血管活性药物的使用频次、酸碱和离子平衡以及血尿常规、肝肾功能和凝血功能等指标。结果各时间点收缩压、舒张压和心率,两组间比较差异无统计学意义(P>0.05);两组的血管活性药物的使用频次差异无统计学意义(P>0.05);治疗结束时两组收缩压稳定律的比较差异无统计学意义(P>0.05);给药后两组pH值与实际碱剩余(ABE)值变化差异有统计学意义(P<0.05)。结论醋酸林格注射液能有效用于围术期容量治疗,与乳酸钠林格注射液相比,其在维持血流动力学稳定及电解质平衡方面无显著性差异,但输注后pH值与ABE值高于乳酸钠林格液,用于治疗乳酸血症、酸中毒和缺氧或氧代谢异常者应更有优势。     

尼莫地平不同给药途径防治蛛网膜下腔出血脑血管痉挛效果分析

目的探讨尼莫地平不同给药途径防治蛛网膜下腔出血脑血管痉挛的临床效果。方法选择40例蛛网膜下腔出血患者使用尼莫地平鞘内注射,并与40例使用静脉注射的蛛网膜下腔出血患者比较,比较两组患者治疗后发生的不良反应并统计治疗的临床效果。结果鞘内组发生低血压、心率增快和头痛比率均为2．5％,静脉注射组发生低血压、心率增快和头痛比率为15．0％、17．5％和15．0％,鞘内注射组低血压、心率增快和头痛比率低于静脉注射组（P〈0．05）,鞘内组发生颅内血管痉挛的比率仅为2．5％,静脉组为17．5％,鞘内注射组低于静脉注射组（P〈0．05）。结论鞘内注射尼莫地平能有效预防网膜下腔出血后脑血管痉挛,改善临床治疗效果。     

甲氨蝶呤过量致危及生命不良反应救治的药学监护

甲氨蝶呤是一种可用于卵巢肿瘤、头颈部肿瘤、肺癌、乳腺癌、宫颈癌、某些白血病及淋巴瘤等疾病的抗肿瘤药物,其免疫抑制作用明显,有时亦可对银屑病、类风湿性关节炎进行治疗。近年来甲氨蝶呤用于医院各科领域单次大剂量或多次小剂量的保守治疗均取得不错的疗效,但同时由于甲氨蝶呤是一种不论口服给药、静脉注射、肌内注射、鞘内注射等,均可能出现危及患者生命安全不良反应的临床用药,实施对症的药学监护较为关键,就此本文作如下综述。     

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.

---

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.     

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.     

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.