脉动真空灭菌器B-D试验失败的影响因素分析及对策

目的总结分析B—D试验失败的影响因素，制定相应对策。方法采用回顾性调查，对我院供应室2007年至2012年六年中所做的B—D试验效果进行监测研究。结果共进行B-D试验2163次，其中试验失败为59次，占2．73％。B—D试验失败原因以技术原因为主，占71．18％。结论试验包未按标准制作，棉布巾未清洗干净，试验包包扎过紧，灭菌器进气及排气阀失控，密封圈老化等因素，是导致B—D试验失败的关键，灭菌操作人员应严格执行技术操作规程，维护设备正常运行，可以避免B—D试验失败，提高灭菌质量，确保临床医疗安全。     

平板运动试验对无痛性心肌缺血的评价

目的探讨平板运动试验对痛性心肌缺血的试验评价价值。方法对1300例进行平板运动试验，采用美国CASE800平板仪，按BRUCE或改良BRUCE方案进行同步记录12导联心电图，实验、分析。结果试验表明，平静心电图正常，无典型心绞痛。结论对临床怀疑有冠心病，但又缺乏充足证据确定诊断时，患者可做缺血激发试验，如活动平板运动试验，通过增加心脏的负荷，增加心肌的氧耗，诱发冠脉供血不足的发生。     

代谢物的遗传毒性评价与ICH会议的动向

遗传毒性试验的目标之一，就是预测化学物质的变异原性。但是，遗传毒性试验尤其是invitro试验并不能预测所有的致癌物质。最新报道表明，尽管因试验而异，啮齿类动物致癌试验与遗传毒性试验的结果一致率大约在60％左右。引起这种偏离的原因认为有多个，其中一个就是药物代谢上的差异。     

头孢菌素过敏试验的现状分析

分析头孢菌素过敏试验的现状，确保用药安全。就头孢菌素过敏试验的情况，广泛调查了解全国各级各类医院头孢菌素过敏试验的现状，进行分析和总结。以寻求头孢菌素过敏试验的最佳方法，避免发生过敏反应，保护病人的用药安全。     

经皮给药制剂体外经皮渗透试验技术规范专家共识探讨

体外经皮渗透试验是评价经皮给药制剂的重要试验之一，试验结果对制剂的处方筛选、仿制药和参比制剂的一致性评价具有重要参考价值。该试验操作复杂，影响因素多，导致不同试验的结果无法比较，影响此类制剂的质量、有效性及安全性的评价。为此，亟需规范经皮给药制剂体外经皮渗透试验的操作。基于国际要求和国内实际，世界中医药学会联合会经皮给药专业委员会组织专家对形成经皮给药制剂体外经皮渗透试验技术规范进行多次研讨，形成初步共识，供业界同行及监管部门参考。     

新药临床试验中的桥接试验

目的：介绍新药临床试验中桥接试验的概念和实施策略。方法：本文介绍了ICH E5中提出的桥接试验的概念和亚洲桥接试验的现况，结合实例介绍了桥接策略的具体实施。结果：随着ICH E5的发布以及桥接试验在一些国家和地区的成功实施，桥接试验已经成为新药注册申请的一个重要形式。结论：桥接试验对于外推国外的临床试验数据，判断药品种族差异，减少重复试验。缩短新药审批时间将有重要的意义。     

口腔专科医院药物临床试验机构管理现状的调查

目的 了解口腔专科医院药物临床试验机构现状，分析口腔专科医院临床试验管理问题并提出相应的建议。方法 截至2022年1月，在国家药品监督管理局“药物临床试验机构备案管理信息系统”备案的13家口腔专科医院药物临床试验机构作为调查对象，通过问卷星方式进行调查，对收集的数据进行统计分析，并针对机构管理存在的问题提出建议。结果 共发放问卷13份，回收13份。调查结果显示，各机构均配置专职人员负责临床试验工作，每年承接的药物临床试验均不超过1项，仅1家参与过国际多中心的项目。13家机构依据工作实际选择不同方式管理试验药物，有9家机构建立了临床试验中心药房，但整体面积较小。各机构质控频率均按照试验阶段（试验前、中、后）进行，有11家机构采用三级质量控制体系，实行1人全程负责模式。12家机构临床试验相关人员的培训由机构办公室负责并组织实施。结论 目前口腔专科医院药物临床试验机构在人员架构、试验药品管理、人员培训和质量管理等方面基本符合管理要求。后续应在人员专职化建设、伦理审查结果互认、临床试验全过程信息化、试验药物集中化管理和完善质控体系方面加强，促进口腔专科医院临床试验机构的高质量发展。     

氨苄西林/舒巴坦随机对照加开放临床试验治疗细菌性感染35例

目的评价试验药氨苄西林/舒巴坦的临床疗效与安全性。 方法58例确诊的细菌性感染患者，其中46例（呼吸系统感染10对，泌尿系统感染13对）进行随机对照试验，按病种随机配对，每组23例，试验组和对照组分别给予试验药氨苄西林/舒巴坦和对照药舒他西林静脉滴注，均为每次1.5～3.0 g，每8 h给药1次，疗程7～10 d。另外12例患者进行临床开放试验，给予试验药氨苄西林/舒巴坦静脉滴注，每次1.5～3.0 g，每8 h给药1次，疗程7～10 d。评价试验药和对照药的临床疗效，并评价试验药的安全性。结果随机对照试验中，试验组和对照组的临床有效率分别为95.6%与82.6%，细菌清除率分别为100.0%与90.0%，不良反应发生率分别为8.7%与13.0%。经检验，两组上述结果均差异无显著性(均P＞0.05)。开放临床试验中，试验药氨苄西林/舒巴坦治疗细菌性感染的临床有效率为91.7%，细菌清除率为100.0%，不良反应发生率为25.0%。最小抑菌浓度（MIC）试验结果表明，试验药氨苄西林/舒巴坦对肺炎克雷白杆菌、大肠埃希菌的MIC90分别为氨苄西林的1.60%和1.56%。结论试验药氨苄西林/舒巴坦克服了氨苄西林对β 内酰胺酶不稳定的缺点，增强和扩大了氨苄西林的抗菌活性，可有效治疗对β 内酰胺酶耐药的细菌引起的呼吸系统及泌尿系统感染。     

首都医科大学附属北京潞河医院I期临床试验药房试验用药品管理模式分析与探讨

目的：探讨首都医科大学附属北京潞河医院Ⅰ期临床试验药房试验用药品管理模式，总结经验和分析不足，为其他临床试验机构中心药房管理模式提供参考。方法：本文分析总结了Ⅰ期临床试验药房基本情况、试验用药品管理流程、智能冷链监控系统的使用、药物信息化管理等。结果与结论：首都医科大学附属北京潞河医院Ⅰ期临床试验药房不同存储区域可满足试验用药品不同温度存储要求。采用智能冷链温度监控系统监测24 h环境及仪器设备温度，可及时发现超温情况，能尽早采取措施，将试验风险降到最低。试验用药品的电子化管理可在线动态管理与实时记录，提高数据管理的安全性和可靠性，方便数据溯源，提高数据质量。     

中药新药长期毒性试验及其资料整理中易出现的问题与解决方法

临床前安全性评价在新药的安全性评价中占有重要地位。其中，长期毒性试验资料是临床前安全性评价的主要内容，也是新药审评的重点内容之一。目前，中药新药申报资料中长期毒性试验资料是存在问题较多的部分，应引起新药研究者足够的重视。新药长期毒性试验的研究必须科学，设计应周到合理，并做到合理控制试验条件，尽量排除干扰;观察指标应力求全面并能针对新药的作用特点，突出重点;整理资料应如实反映试验情况，对试验结果作出全面科学的分析;新药资料送审时，审评人员也应结合药物的具体情况加以综合评价。该文就目前中药新药长期毒性试验及其资料整理中存在的问题进行了分析和讨论。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.