2012~2014年温州某地区泌尿道感染病原菌分布及耐药性分析

目的分析近3年来温州某地区泌尿道感染病原菌的分布和耐药情况,指导临床合理应用抗生素。方法回顾性分析2012~2014年本院泌尿道感染患者病原菌的分布及耐药性。结果泌尿道感染的病原菌中排在第一的是大肠埃希菌,占47.4%,其次为真菌和凝固酶阴性葡萄球菌,分别占9.8%和6.1%。药敏结果显示,大肠埃希菌对青霉素、头孢唑林、美罗培南、亚胺培南的耐药率分别是100%、85.1%、2.1%和0%。结论泌尿道感染的主要致病菌是大肠埃希菌,其次是真菌和凝固酶阴性葡萄球菌,大肠埃希菌对青霉素和头孢唑林几乎已完全耐药,对美罗培南和亚胺培南最敏感。     

新氨基糖苷类抗生素vertimicin的体内抗菌活性研究

目的 评价新氨基糖苷类抗生素vertimicin（VTM）的体内抗菌活性。方法 采用小鼠全身感染模型，观察VTM对临床分离大肠埃希菌（E．coli）、肺炎克雷伯菌（K．pneumoniae）、铜绿假单胞菌（Ps．aeruginosa）和金葡菌（S．aureus）腹腔感染小鼠的体内疗效；采用兔皮肤烫伤感染模型、小鼠泌尿道上行性感染模型观察VTM对临床分离大肠埃希菌局部感染的体内疗效，并与对照药进行比较。结果 VTM皮下或静脉给药对E．coll96-12、K．pneumonlae93-5、Ps．aeruglnosa94-17和S．aureus93-44腹腔感染小鼠具有相似的体内疗效，皮下给药的ED50值分别为0．67、0．29、2．41和0．99mg／kg，静脉给药的ED50值分别为0．46、0．23、0．99和1．52mg／kg，体内疗效与奈替米星相近。兔皮肤烫伤感染模型中，VTM各剂量组兔皮肤组织活菌落数明显低于对照组（P〈0．05或0．01）。小鼠泌尿道上行性感染模型中，VTM各剂量组肾组织活菌落数明显低于对照组，肾剖面盖印细菌阴性率明显高于对照组（P〈0．01），抗菌活性优于庆大霉素。结论 VTM对全身和局部感染动物均显示较好保护作用，体内疗效与奈替米星相近。     

泌尿道感染大肠埃希菌476株耐药分析

目的：了解医院泌尿道感染的主要病原菌及大肠埃希菌的耐药性,指导临床合理用药。方法对2011年2月至2013年11月该院住院及门诊尿路感染患者尿培养分离出的476株大肠埃希菌进行药敏分析。结果尿路感染476株大肠埃希菌中产ESBLs菌株检出率为62.4%;大肠埃希菌对阿米卡星、美罗培南、亚胺培南、哌拉西林/他唑巴坦和头孢哌酮/舒巴坦耐药率最低,对青霉素类、头孢类及喹诺酮类耐药率较高,产ESBLs 株耐药率明显高于非产ESBLs。结论泌尿道感染中大肠埃希菌分离率最高,且细菌耐药严重,特别是产ESBLs株耐药更为严重,应当加强细菌耐药监测,指导临床合理选用抗菌药物,减缓耐药菌株的产生。     

注射用法罗培南的体内抗菌活性

目的评价注射用法罗培南的体内抗菌活性。方法建立小鼠腹膜炎模型,比较注射用法罗培南及厄他培南对产酶的大肠埃希菌、肺炎克雷伯菌及对甲氧西林敏感的金黄色葡萄球菌、耐万古霉素的粪肠球菌感染小鼠的体内抗菌活性。结果注射用法罗培南对产超广谱β内酰胺酶(ESBLs)的大肠埃希菌、肺炎克雷伯菌和对甲氧西林敏感的金黄色葡萄球菌有较强的体内和体外抗菌活性,其ED_(50)分别为10.96、9.12和7.07 mg·kg~(-1),厄他培南则为14.84、12.58和10.16 mg·kg~(-1)。法罗培南对耐万古霉素的粪肠球菌体外敏感,而厄他培南显示耐药。法罗培南对耐万古霉素的粪肠球菌的ED_(50)比厄他培南低66.77%,分别为10.75和32.35 mg·kg~(-1)。结论注射用法罗培南和厄他培南对产ESBLs的大肠埃希菌、肺炎克雷伯菌和对甲氧西林敏感的金黄色葡萄球菌有较强的体内和体外抗菌活性,两者作用相似。法罗培南对耐万古霉素的粪肠球菌感染可能有治疗作用,效果优于厄他培南。     

注射用多尼培南体内抗菌活性研究

目的:评价注射用多尼培南的体内抗菌活性.方法:建立小鼠腹腔感染模型,以注射用美罗培南为对照药,观察注射用多尼培南的体内抗菌活性.结果:注射用多尼培南对大肠埃希菌DC01、DC02和甲氧西林敏感的金黄色葡萄球菌JP02有良好的体内抗菌活性,其ED50分别为4.5、1.0和2.0 mg/kg,美罗培南为15.9、10.6和17.3 mg/kg.阴性对照对感染小鼠无保护作用.结论:注射用多尼培南对大肠埃希菌和甲氧西林敏感的金黄色葡萄球菌所致的小鼠腹腔感染具有良好的治疗作用,其体内抗菌活性优于同类对照药.     

体外诱导大肠埃希菌对厄他培南敏感性降低及机制研究

目的 体外诱导获得对厄他培南敏感性降低的大肠埃希菌,并分析可能的产生机制.方法 将厄他培南敏感大肠埃希菌经厄他培南体外诱导后分离突变株;药敏试验测定MIC(无或含PAβN); PFGE检测同源性;SDS-PAGE及Real-time PCR检测外膜蛋白表达;MALDI-TOF/TOF鉴定差异蛋白;并对外膜蛋白基因进行测序.结果 厄他培南处理得到的两个突变株(大肠埃希菌08-1E及大肠埃希菌08-3E)除对厄他培南敏感性显著降低外,对美罗培南、头孢西丁及头孢吡肟等β-内酰胺类药物敏感性也呈现不同程度的降低.PFGE显示突变株与亲本株同源,进一步的研究发现突变株对厄他培南敏感性降低与外排泵无关,而与基因的插入失活等机制引起的外膜蛋白(OmpC、NmpC、LamB、OmpF)缺失或表达降低有关.结论 体外诱导大肠埃希菌对厄他培南敏感性降低与外膜蛋白缺失或表达降低紧密相关.     

119株泌尿道感染大肠埃希菌的耐药性分析

目的了解我院泌尿道感染大肠埃希菌耐药现状,为临床治疗提供参考。方法对笔者医院2011年1月至2013年12月门诊和住院的尿路感染患者进行尿培养分离的119株大肠埃希菌耐药性进行统计分析。结果分离出的119株大肠埃希菌中,共有产ESBLs株52株,检出率为43.69%;大肠埃希菌对亚胺培南和美罗培南耐药率为0.0%,其次为阿米卡星和哌拉西林/他唑巴坦,产ESBLs株耐药率明显高于非产ESBLs株。结论泌尿道感染大肠埃希菌的耐药率越来越严重,临床治疗时应参考药敏试验结果合理选用抗菌药物,防止耐药菌株的产生和传播。     

老年患者大肠埃希菌尿路感染现状及耐药性分析

目的了解老年患者大肠埃希菌尿路感染的感染现状及耐药性特征,为临床治疗及合理使用抗菌药物提供理论依据。方法收集我院2013年1月至2015年12月65岁及以上住院患者送检的中段清洁尿标本,从中培养出444株大肠埃希菌,采用回顾性分析方法进行感染现状及耐药性分析。结果美罗培南及厄他培南耐药率最低,亚胺培南其次,耐药率高于70%的抗生素分别为哌拉西林、氨苄西林、加替米星、头孢唑林、头孢唑喃钠、头孢噻吩、环丙沙星、罗米沙星、左氧氟沙星、左旋氧氟沙星、氨苄西林/舒巴坦。结论老年患者大肠埃希菌尿路感染现状较为严峻,从尿液标本中分离出的大肠埃希菌耐药率较高,应根据药敏试验结果合理使用抗菌药物。     

2015～2016年我院感染科产ESBLs大肠埃希菌感染抗生素使用情况分析

目的:分析2015～2016年我院感染科产超广谱β-内酰胺酶(ESBLs)大肠埃希菌感染抗生素使用情况.方法:选取我院2015年1月～2016年12月感染科各类临床标本308个,进行细菌培养及药敏试验.统计产ESBLs大肠埃希菌检出率及药敏试验结果.结果:本组308个临床标本,共分离大肠埃希菌314株,产ESBLs大肠埃希菌检出率为37.26％(117/314);产ESBLs大肠埃希菌对头孢噻肟、哌拉西林、左氧氟沙星耐药率较高,且对亚胺培南、美罗培南耐药率较低.结论:产ESBLs大肠埃希菌对头孢噻肟、哌拉西林、左氧氟沙星耐药率较高,对美罗培南、亚胺培南等碳青霉烯类抗生素耐药率较低,但临床应合理使用此类药物,以防其耐药性升高.     

产 ESBLs 大肠埃希菌和肺炎克雷伯菌的耐药性分析及分布

目的：了解医院临床分离的产超广谱β内酰胺酶（ESBLs）大肠埃希菌和肺炎克雷伯菌的临床分布特点及耐药状况,为临床合理用药提供参考依据。方法收集2014年医院临床分离的925株大肠埃希菌和363株肺炎克雷伯菌。使用法国生物－梅里埃 ATB 细菌鉴定系统,应用药敏测试仪及配套微生物检测试剂进行细菌鉴定和药敏试验。结果925株大肠埃希菌中分离出产 ESBLs 菌657株（占71．0％）;363株肺炎克雷伯菌中分离出产 ESBLs 菌150株（占41．32％）。产 ESBLs 大肠埃希菌来自尿标本266株（占40．49％）,产 ESBLs 肺炎克雷伯菌来自痰标本89株（占59．33％）。产 ESBLs 株的耐药率均普遍高于 ESBLs 阴性株;与产 ESBLs 肺炎克雷伯菌相比,产 ESBLs 大肠埃希菌对氟喹诺酮类抗生素耐药率较高;且二者对青霉素类、一到三代头孢菌素类抗生素耐药率均较高,而对厄它培南、亚胺培南、美罗培南等药高度敏感。结论某院产 ESBLs 大肠埃希菌主要引起泌尿道感染,产 ESBLs 肺炎克雷伯菌主要引起呼吸道感染。临床应高度重视产 ESBLs 菌的检测和药敏试验,根据药敏结果合理选择抗生素,减缓细菌耐药的发生,尤其要控制 ESBLs 菌的产生和爆发流行。     

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.