30例甲巯咪唑致胰岛素自身免疫综合征的文献分析

目的 分析甲巯咪唑致胰岛素自身免疫综合征（IAS）临床特点与发生规律,为适宜人群筛查及合理用药提供参考。方法 检索PubMed、EBSCO、中国知网（CNKI）、万方医学网及维普中文期刊（VIP）等数据库中有关甲巯咪唑致胰岛素自身免疫综合征（IAS）的个案报道,并对相关指标进行统计分析和关联性评价。检索时间为建库至2022年9月。结果 共得到27篇个案报道,中文19篇,英文8篇,文献质量评价均较高;发生IAS共计30例,其中女性风险高于男性（80.00% vs 20.00%）,41～60岁年龄层（36.67%）、自由职业者（42.10%）发生占比最高,其次患者有过治疗中断或停药史也会影响IAS的发生;诱导期以21～30 d为主,占比37.04%,且相较于联合用药,单次给药差异有显著性（63.33% vs 23.33%）;关联性评价肯定4例（13.33%）,很可能20例（66.67%）,可能6例（20.00%）。结论 药学门诊或临床医生在对甲亢患者开具甲巯咪唑时,开展必要的药物流行病学问询可有效降低患者服用甲巯咪唑致IAS的发生风险。     

24例甲巯咪唑致胆汁淤积性肝损伤文献分析

目的 分析甲巯咪唑致胆汁淤积性肝损伤发生特点与规律,为防治及临床安全用药提供参考。方法 检索国内外文献数据库中有关甲巯咪唑致胆汁淤积性肝损伤（黄疸）的个案报道,并进行计量学分析。结果 获8篇个案报道,共计24例患者,其中男性1例,女性23例;年龄48~58岁共8例,均为女性,占33.33%;其次为37~47岁共7例,均为女性,占29.17%。合并用药与甲巯咪唑单次给药相比,致胆汁淤积性肝损伤发生率未见差异（25.00% vs 25.00%,P>0.05）;诱导期以21~35 d为主,占比58.33%,其次为7~21 d,占比37.50%。药物与不良事件因果关系诺氏（Naranjo''s）评分肯定4例（16.67%）,很可能20例（83.33%）。结论 中年女性甲亢患者为甲巯咪唑致胆汁淤积性肝损伤的高危人群,宜对其进行中短期用药监护,权衡利弊,尽量避免和减少药源性胆汁淤积性肝损伤发生。     

261例骨瓜提取物注射剂致不良反应/事件监测数据分析

摘 要 目的:分析骨瓜提取物注射剂致不良反应的特点,为临床合理用药提供参考。方法：对山东省药品不良反应监测中心2012年1月～2014年6月收到的261例骨瓜提取物注射剂致不良反应病例报告进行统计分析。结果：骨瓜提取物注射剂所致ADR多集中于40～49岁患者,男性多于女性。不良反应临床主要表现为皮肤及附件损害、全身性系统损害。55.17%的病例在用药30 min内发生,为速发型过敏反应;经停药及对症治疗后全部病例预后良好。结论：骨瓜提取物注射剂引起的不良反应不容忽视,临床使用时要密切监测其不良反应,及时处理。     

曲马多致5-羟色胺综合征的危险因素分析

摘 要 目的：了解曲马多引起5 羟色胺综合征的临床特征与危险因素,以促进临床合理使用该药。方法: 检索国外Pubmed、Embase、中国知网全文数据库（CNKI）及万方数据库建库至2016年曲马多致5 羟色胺综合征的文献报道,对获得的病例资料进行不良反应（ADR）关联性评价与分级、患者性别与年龄、药物应用的情况、发生5 羟色胺综合征的时间、临床表现、处理方法与转归等方面的统计分析。结果: 检索获得曲马多所致5 羟色胺综合征的文献报道共21例,其中19例为合并用药,合并使用选择性5 羟色胺再摄取抑制药有12例。关联性评价为很可能2例,可能19例;严重ADR10例,一般的ADR11例。1例患者测定CYP2D6基因型（CYP2D*1/*4）,对曲马多的代谢能力减弱,发生5 羟色胺综合征的易感性更高。5 羟色胺综合征在用药剂量改变或联合用药后24 h内发生的比例占28.6%。经停药及对症治疗后大部分病例完全恢复,通常少于1周的时间。结论: 在使用曲马多时,临床医务工作者需警惕曲马多合并使用5 羟色胺能药物时可能存在的药物相互作用、药物基因多态性的影响而发生5 羟色胺综合征的风险,应注意密切观察患者,以减少药物不良反应的危害。     

41例热毒宁注射液不良反应分析

摘 要 目的:分析41例热毒宁注射液不良反应（ADR）病例,探讨ADR发生的相关因素方法：提取惠州市2013年1月～2014年9月药品不良反应网络管理平台中41例热毒宁注射液ADR病例报告,分别统计患者性别、年龄、原患疾病,ADR累及的系统 器官及临床表现等并作分析。结果：41份ADR报告中,不良反应集中在儿童组,以变态反应居多,主要累及皮肤及其附件损害（53.8%）;78.1%的ADR发生在用药30 min内;82.9%的关联性评价结果为很可能;均为单独用药后发生的ADR。结论：医务人员应该重视热毒宁注射液的不良反应,加强临床使用过程的主动监测,分析ADR的发生特点,尽量减少或避免ADR的发生,确保临床用药安全。     

长春西汀注射液临床使用调查

摘 要 目的：调查长春西汀注射液临床使用及不良反应发生情况。方法: 统计分析某院神经内科2013年12月～2014年12月住院患者中长春西汀注射液的使用情况。检索关于长春西汀注射液不良反应的相关文献并做统计分析。结果: 363例患者使用长春西汀注射液输注浓度均大于0.06 mg·mL^-1 ,发生不良反应3例,主要表现为皮疹及药物热。检索获得28篇文献中使用长春西汀注射液浓度高于0.06 mg·mL^-1的有19篇,8篇文献出现了不同程度的不良反应。结论:临床医生在临床用药过程中应重视说明书的应用,提高药物的安全合理应用。     

葛根素注射液致心血管系统不良反应的Meta分析

摘 要 目的：评价葛根素注射液对于心血管系统的安全性。方法：计算机检索CNKI,VIP,WanFang Data,SinoMed,Medline,EMbase,CENTRAL,PubMed,Web of Science数据库公开发表的有关葛根素注射液致心血管系统不良反应的临床研究文献,根据纳入和排除标准收集资料,采用RevMan 5.3软件对葛根素注射液致心血管系统不良反应发生情况进行Meta分析。结果：符合标准并纳入分析的文献共17篇。Meta分析结果显示,与未使用葛根素注射液的对照组相比,葛根素注射液致心血管系统不良反应发生风险较高,两组差异有统计学意义[RR=2.81,95%CI（1.50,5.24）,P=0.001]。亚组分析显示：冠心病心绞痛亚组,剂量≥400 mg·d-1亚组、疗程≥14 d亚组中,葛根素注射液致心血管系统不良反应发生风险均高于对照组（P＜0.05）;而剂量＜400 mg·d-1亚组、疗程＜14 d亚组、脑梗死亚组、其他疾病亚组中,葛根素注射液致心血管系统不良反应发生风险与对照组的差异均无统计学意义（P＞0.05）。结论：葛根素注射液致心血管系统不良反应发生率较高,当治疗冠心病心绞痛且使用剂量≥400 mg·d-1、疗程≥14 d时,临床医师需要注意用药安全性,降低心血管不良反应的发生风险。     

氯化铵甘草口服溶液致不良反应6例分析

摘 要 目的：探讨氯化铵甘草口服溶液不良反应的特点,为临床安全用药提供参考。方法：对本院2014年1月～2016年3月上报的6例氯化铵甘草口服溶液不良反应监测报告进行回顾性分析,对6例患者的年龄、性别、原患疾病,药物使用情况,ADR 发生时间、临床表现、治疗与转归,ADR的类型与关联性评价等项目进行统计分析。结果：氯化铵甘草口服溶液不良反应多发生于老年患者;发生时间主要在用药8h内;以累及系统呼吸系统和皮肤为主;6例患者均痊愈,未出现后遗症或导致死亡。6例ADR中一般的ADR 2例, 新的一般的ADR 2例,新的严重ADR 2例;关联性评价为可能4例,很可能2例。结论：临床上应重视氯化铵甘草口服溶液的不良反应,应密切观察患者,保证用药安全。     

头孢哌酮/舒巴坦致神经系统不良反应影响因素分析

摘 要 目的：探讨注射用头孢哌酮/舒巴坦致神经系统不良反应的影响因素,为临床安全用药提供参考。方法：收集我院2011～2012年1 141例应用头孢哌酮/舒巴坦患者中发生神经系统不良反应的病例33例,采用回顾性分析方法对神经系统不良反应的病例的患者基本信息、用药情况、不良反应临床表现等相关因素进行调查分析。 结果：33例患者中男22例,女11例;60岁以上患者30例,占90.9%。患者中原患神经内科和肾内科疾病患者27例,占81.8%。33例神经系统不良反应多发生在应用常规剂量头孢哌酮/舒巴坦治疗6～15 d,其次为用药大于15 d。33例患者中2例联用左氧氟沙星,1例联用头孢哌酮。神经系统不良反应的临床表现以抽搐、不自主抖动为主,与癫痫症状相似。 结论：性别、年龄、基础疾病、给药时间、联合用药等因素对头孢哌酮/舒巴坦致神经系统不良反应可能产生影响。     

康艾注射液上市后医院集中监测

摘 要 目的：对康艾注射液上市后临床应用情况进行评价,为规范和指导临床合理用药提供依据。方法：采用医院集中监测的方法,以本院2016年11月～2017年3月入院并使用康艾注射液的住院患者为研究对象,记录患者基本情况、用药情况和药品不良反应发生情况,并评价用药合理性。 结果：共观察病例1 000例,其中超适应证用药占2.5%,用药剂量不足占2.1%,超疗程用药占0.8%,溶媒剂量不足占0.5%。1例患者发生药品不良反应,发生率为0.1%。结论：康艾注射液临床应用欠规范,提示临床用药应严格按照说明书规定适应证、疗程和用法用量,并密切监护患者有无不良反应发生等。     

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.     

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.