碳青霉烯类抗生素多尼培南的体外抗菌活性

多尼培南是新的注射用碳青霉烯类广谱抗生素。它是1β-甲基碳青霉烯，由日本大阪的Shionogi等最先发现。该药目前在美国进行临床试验研究。Yigong等测定了多尼培南对临床分离株的体外抗菌活性，并与其他几种碳青霉烯类抗生素(厄他培南、亚胺培南、美罗培南)、头孢菌素(头孢吡肟、头孢曲松)和哌拉西林／三唑巴坦对381株革兰阴性菌和434株革兰阳性菌进行了体外抗菌活性比较。     

三种碳青霉烯类抗生素的体外抗菌作用

为评价亚胺培南、帕尼培南与美罗培南的体外抗菌作用 ,以琼脂对倍稀释法测定三者对 2 2 5株临床分离菌的最低抑菌浓度 (MIC) ,并与相关抗菌药物进行比较。结果 ,三种碳青霉烯类抗生素对肠杆菌科细菌具高度抗菌活性 ,对铜绿假单胞菌、不动杆菌属、粪肠球菌等亦具良好抗菌作用。帕尼培南与亚胺培南体外抗菌作用相仿 ,两者对肺炎克雷伯氏菌、肠杆菌属等革兰氏阴性菌作用略逊于美罗培南。三种碳青霉烯类抗生素体外抗菌作用优于头孢他啶、β-内酰胺类抗生素与β-内酰胺酶抑制剂合剂、氟喹诺酮类等其它受试药物。结果表明 ,碳青霉烯类抗生素是治疗多重耐药菌所致院内感染、免疫缺陷者感染和严重需氧菌与厌氧菌混合感染的适用药物。     

五种碳青霉烯类抗生素对大肠埃希菌和铜绿假单胞菌的体外抗菌活性比较

目的 观察五种碳青霉烯类抗生素对大肠埃希菌和铜绿假单胞菌的体外抗菌活性.方法 采用琼脂稀释法检测5种碳青霉烯类抗生素对55株铜绿假单胞菌、49株产ESBLs的大肠埃希菌的最低抑菌浓度(minimalinhibitoryconcentration,MIC).结果 对抗铜绿假单胞菌活性以美洛培南和比阿培南显示最佳,亚胺培南次之,帕尼培南逊于亚胺培南,厄他培南明显逊于其他四种碳青霉烯类抗生素.对产ESBLs的大肠埃希菌厄他培南的活性明显高于其他几种碳青霉烯类抗生素,而其他几种活性基本相当.结论 铜绿假单胞菌对五种碳青霉烯类抗生素耐药性均较高,而五种碳青霉烯类抗生素对产ESBLs的大肠埃希菌均敏感.     

美罗培南的体外抗菌活性研究

目的 评价国产美罗培南对产β-内酰胺酶细菌的体外抗菌活性。方法 琼脂稀释法测定美罗培南对110株产β-内酰胺酶临床分离菌的最低抑菌浓度(MIC)。并与相关抗菌药物进行比较。结果 碳青霉烯类抗生素对产β-内酰胺酶菌株具有高度抗菌活性，国产美罗培南作用略强于亚胺培南。碳青霉烯类抗生素体外抗菌作用优于头霉素、第四代头孢菌素、β-内酰胺类抗生素与β-内酰胺酶抑制剂合剂、喹诺酮类和氨基糖苷类药物。结论 国产美罗培南是治疗产β-内酰胺酶细菌所致感染的理想药物。     

国内城市医院碳青霉烯类抗生素用药情况

碳青霉烯类抗生素具有抗菌谱广、抗菌活性强的特点,在控制耐药菌、产酶菌感染和免疫缺陷者感染中起着重要作用,是销售增长较快的抗感染药物类别之一。自上世纪80年代中期亚胺培南进入临床应用后,碳青霉烯类抗生素现已发展到含有亚胺培南、美罗培南、帕尼培南、法罗培南、厄他培南、多尼培南和比阿培南这7个药物组成的培南类药物系列品种。目前全球碳青霉烯类抗生素市场超过16亿美元,而活跃在我国城市医院市场上的有5个品种。     

五种碳青霉烯类抗生素对大肠埃希菌和铜绿假单胞菌的体外抗菌活性比较

目的观察五种碳青霉烯类抗生素对大肠埃希菌和铜绿假单胞菌的体外抗菌活性。方法采用琼脂稀释法检测5种碳青霉烯类抗生素对55株铜绿假单胞菌、49株产ESBLs的大肠埃希菌的最低抑菌浓度（minimalinhibitoryconcentration,MIC）。结果对抗铜绿假单胞菌活性以美洛培南和比阿培南显示最佳,亚胺培南次之,帕尼培南逊于亚胺培南,厄他培南明显逊于其他四种碳青霉烯类抗生素。对产ESBLs的大肠埃希菌厄他培南的活性明显高于其他几种碳青霉烯类抗生素,而其他几种活性基本相当。结论铜绿假单胞菌对五种碳青霉烯类抗生素耐药性均较高,而五种碳青霉烯类抗生素对产ESBLs的大肠埃希菌均敏感。     

我院2011年碳青霉烯类抗生素用药频度与鲍曼不动杆菌对其耐药率的相关性研究

目的:分析我院碳青霉烯类抗生素用药频度(DDDs)与鲍曼不动杆菌对其耐药率的相关性,为临床合理用药提供依据。方法:采用K-B纸片扩散法测定抗菌药物敏感性,SPSS16.0软件进行数据分析;采用世界卫生组织推荐的限定日剂量(DDD)法分析常用抗菌药物的DDDs。结果:我院2011年4个季度碳青霉烯类抗生素的总DDDs逐季度减少,第4季度比第1季度下降9.74%,其中同期亚胺培南、帕尼培南分别下降了73.91%和95.22%,美罗培南的DDDs无明显变化;而鲍曼不动杆菌对碳青霉烯类抗生素的耐药率同期下降33.6%。结论:鲍曼不动杆菌的耐药率与碳青霉烯类抗生素总DDDs呈正相关(r=0.996,P<0.05),与亚胺培南、帕尼培南DDDs呈正相关(r分别为0.947、0.895,P均<0.05),与美罗培南DDDs无显著相关(r=-0.485,P>0.05)。     

上碳青霉烯类抗生素的体外抗菌作用

为评价亚胺培南、帕尼培南与美罗培南的体外抗菌作用，以琼脂对倍稀释法测定三者对２２５株临床分离菌的最低抑菌浓度（ＭＩＣ），并与相关抗菌药物进行比较。结果，三种碳青霉烯类抗生素对脾性杆菌细菌具高度抗菌活性，对铜绿假单胞菌，不动杆菌属、粪肠球菌等亦具良好抗菌作用。帕尼同与亚胺培南体外扩展菌作用相仿，两者对肺炎克雷伯氏菌、肠杆菌属等革兰氏阴笥菌作用略逊于我培南。三种碳青霉烯类抗生素体外抗菌作用 地头孢他啶     

青霉烯类及碳青霉烯类抗生素的结构特点与分级管理建议

目的:为抗菌药物的临床分级管理提供建议,促进青霉烯类和碳青霉烯类抗生素的合理使用.方法:检索国内外文献,对已经上市的青霉烯类和碳青霉烯类抗生素的结构、药理学和药动学特性、抗菌谱及临床应用等进行阐述,分析和比较不同品种的特点,提出分级管理建议.结果 和结论:厄他培南具有半衰期长、对产超广谱β-内酰胺酶(ESBLs)肠杆菌...     

美洛培南治疗老年呼吸道感染的临床疗效分析

美洛培南(meropenem MEPM)属于碳青霉烯类(carbapenems)抗生素,其结构特点为1-β位有甲基,2位有二甲基氨基甲烯吡咯烷,该药具有广谱强效抗菌作用和对肾脏脱氢酶的稳定性,成为碳青霉烯类抗生素中一个新品种[1],本研究通过应用美洛培南治疗老年呼吸道感染30例,以评价美洛培南药效学和细菌学效果及安全性,现将结果报告如下.     

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.