比阿培南对501株临床分离致病菌的体外抗菌活性研究

目的:评价比阿培南对501株临床分离致病菌的体外抗菌活性。方法:采用刃天青微孔板稀释法测定比阿培南和对照品(美罗培南、亚胺培南、头孢吡肟、头孢他啶、头孢哌酮/舒巴坦、环丙沙星、苯唑西林、万古霉素)对501株临床分离致病菌的体外抗菌活性。结果:比阿培南对大肠埃希菌、克雷伯菌属、产气肠杆菌、阴沟肠杆菌、志贺菌属、沙门菌属、变形杆菌属、沙雷菌属、柠檬酸菌属、不动杆菌属和铜绿假单胞菌的MIC50分别为0.06,0.13,0.25,0.13,0.03,0.03,1.00,0.50,0.13,0.13,0.50μg/mL;MIC90分别为0.13,0.13,0.50,0.50,0.03,0.06,1.00,0.50,0.25,0.25,4.00μg/mL。结论:比阿培南对临床分离致病菌的最低抑菌浓度MIC50、MIC90低于对照品。     

院内常见革兰氏阴性杆菌耐药性监测

目的 了解本院常见的革兰氏阴性杆菌的耐药性,以及大肠埃希氏菌和肺炎克雷伯氏菌超广谱β－内酰胺酶（ESBLs)菌株的发生率。方法 纸片扩散法,ESBLs菌株用头孢他啶／克拉维酸、头孢噻肟／克拉维酸进行确证。结果 482株革兰氏阴性杆菌有67株ESBLs菌株,其中大肠埃希氏菌46株,肺炎克雷伯氏菌21株,分别占该种菌的38．9％、29．2％。药敏检测结果显示,大肠埃希氏菌和肺炎克雷伯氏菌中产ESBLs菌株敏感率由高到低排列为美罗培南100％、亚胺培南100％、头孢匹肟67％、哌拉西林／三唑巴坦66％;不产ESBLs菌株敏感率由高到低排列为美罗培南和亚胺培南均为100％、头孢他啶90％、头孢曲松85％、头孢匹肟84％、头孢噻肟、氨曲南、阿米卡星均为82％、哌拉西林／三唑巴坦73％。阴沟肠杆菌中除美罗培南、亚胺培南的敏感率均为100％外,其它抗生素敏感率低于60％。不动杆菌敏感率由高到低排列为亚胺培南85％、氧氟沙星81％、美罗培南75％、阿米卡星73％、环丙沙星64％。铜绿假单胞菌敏感率较高的有美罗培南90％、亚胺培南82％、头孢匹肟78％、头孢他啶77％、哌拉西林／三唑巴坦73％、环丙沙星68％、妥布霉素63％、哌拉西林61％。结论 本院产ESBLs菌株以大肠埃希氏菌多见。革兰氏阴性杆菌中除嗜麦芽黄单胞菌外,对美罗培南、亚胺培南、哌拉西林／三唑巴坦等的敏感率较高。     

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。     

亚胺培南与四种头孢类抗生素对148株革兰阴性杆菌的体外抗菌活性比较

目的　比较亚胺培南与头孢类抗生素对革兰阴性 (G- )杆菌的体外抗菌活性。方法　运用 Mi-croscan walkaway- 4 0全自动细菌鉴定、药敏分析仪对临床分离的 14 8株常见 G- 杆菌进行亚胺培南和有代表性的三种三代头孢类抗生素 (头孢曲松、头孢他啶、头孢噻肟 )以及一种四代头孢类抗生素 (头孢吡肟 )的药敏分析。结果　亚胺培南对临床常见的 G-杆菌敏感率为 81% ,明显高于头孢噻肟 (2 7% )头孢他啶 (45 .3% )头孢曲松 (2 8.4 % )和头孢吡肟 (36 .5 % ) ,对产 ESBL s的肺炎克雷伯菌和大肠埃希氏菌的敏感率为 80 %。结论　亚胺培南对 G- 杆菌抗菌活性明显优于头孢菌素 ,为治疗常见 G-菌特别是耐头孢类抗生素的 G-菌感染的较为理想的药物     

帕尼培南/倍他米隆的体外抗菌活性研究

为评价帕尼培南的体外抗菌作用，采用琼脂二倍稀释法测定帕尼培南／倍他米隆对247例临床分离菌的最低抑菌浓度（MIC），并与其它5种抗菌药物进行比较，结果表明，帕尼培与亚胺培南体外抗菌作用相仿，但帕尼培南对流感嗜血杆菌，金黄色葡萄球菌包括耐甲氧西林金葡萄球菌（MRSA）和大肠埃希氏菌体外胺培南对肺炎克雷伯氏菌、大肠埃希氏菌等革兰氏阴性菌作用略逊于美罗培南，帕尼培南体外抗菌 于头孢他啶，头孢哌酮／舒巴坦，苯唑西林等其它受试药物。帕尼培南的体外抗菌活性受接种菌量，培养基PH值和血清浓度影响。结果表明，帕尼培南是治疗多重耐药菌所致院内感染和严重需氧菌与厌氧菌混合感染的适用药物。     

头孢吡肟与其它广谱β-内酰胺类抗生素体外抗菌活性比较

测定头孢吡肟对１００株临床分离菌的最低抑菌浓度（ＭＩＣ）,并与头孢他啶,头孢曲松,亚胺培南,头孢哌酮／舒巴坦等广谱β－内酰胺类抗生素体外抗菌活性进行比较。结果：头孢吡肟对革兰氏阴性杆菌有良好抗菌活性;对铜绿假单胞菌亦有较强的抗菌活性,其ＭＩＣ５０为３ｍｇ／Ｌ,和头孢他啶相当,苯唑青霉素敏感的葡萄球菌对头孢吡肟也较敏感,ＭＩＣ９０≤４ｍｇ／Ｌ。表明头孢吡肟较第三代头孢菌素抗菌谱更广,抗菌活性更强。     

2009―2011年本院多重耐药革兰阴性菌的耐药性变迁及对多黏菌素B的体外敏感性

目的分析重庆医科大学附属第一医院2009―2011年多重耐药革兰阴性菌的耐药性变迁并测定多黏菌素B及临床常用抗菌药物对其的体外抗菌活性,为临床制定合理的用药方案提供实验室依据。方法采用K-B法筛选出155株临床分离的多重耐药革兰阴性菌(53株鲍曼不动杆菌、50株肺炎克雷伯菌、52株铜绿假单胞菌),以琼脂稀释法测定其对多黏菌素B、亚胺培南等13种药物的敏感性及MIC值,数据采用Whonet 5.6及SPSS 18.0进行分析。结果琼脂稀释法与K-B纸片法得出的三种多重耐药革兰阴性菌的耐药率无显著差异(P>0.05)。鲍曼不动杆菌对亚胺培南、美罗培南耐药率为58.3%⁶8.2%,对其他抗菌药物耐药率为48.5%68.2%,对其他抗菌药物耐药率为48.5%¹00%。肺炎克雷伯菌对亚胺培南、美罗培南耐药率小于9.4%,对阿米卡星、哌拉西林-他唑巴坦耐药率为8.6%100%。肺炎克雷伯菌对亚胺培南、美罗培南耐药率小于9.4%,对阿米卡星、哌拉西林-他唑巴坦耐药率为8.6%¹5.9%,对头孢他啶、头孢吡肟耐药率为34.8%15.9%,对头孢他啶、头孢吡肟耐药率为34.8%⁴1.8%,对哌拉西林耐药率为46.3%41.8%,对哌拉西林耐药率为46.3%⁵5.2%。铜绿假单胞菌对头孢他啶、头孢吡肟和亚胺培南耐药率为12.8%55.2%。铜绿假单胞菌对头孢他啶、头孢吡肟和亚胺培南耐药率为12.8%³0.7%。多黏菌素B对3种多重耐药革兰阴性菌保持着96%以上的抗菌活性,MIC50和MIC90均<1 mg·L-1。结论本院多重耐药革兰阴性菌对临床常用抗菌药物的耐药已非常普遍,而多黏菌素B对其仍保持较高的抗菌活性。     

头孢吡肟对质粒介导产AmpCβ-酰胺酶大肠埃希菌的接种效应研究

目的本实验研究了临床分离的质粒介导AmpCβ-酰胺酶大肠埃希菌，在两种接种浓度下（标准浓度10^5CFU／ml和高浓度10^7CFU／mI）测定头孢吡肟、头孢噻肟、头孢他啶、头孢哌酮／舒巴坦和亚胺培南的MIC值。方法19株血培养的质粒介导的AmpC β-内酰胺酶大肠埃希菌，其中10株单产ACT型，5株单产DHA型，4株产ACT＋DHA型。采用琼脂稀释法测定头孢吡肟等5种抗生素在两种接种浓度下的MIC值。高接种浓度下测得的MIC值较标准接种浓度下的MIC值≥8倍时定义为有接种效应。结果在标准接种浓度下，亚胺培南的敏感率为100％，头孢吡肟也有84．2％的高敏感率，头孢哌酮／舒巴坦的敏感率为5．3％，头孢噻肟和头孢他啶的敏感率为0。在两种接种浓度下，头孢吡肟MIC值增加从32倍到100多倍不等，100％有接种效应，而亚胺培南几乎没有接种效应。结论头孢吡肟有明显的接种效应，尽管本文结果为实验室的体外实验结果，但仍建议：头孢吡肟不推荐为临床上治疗由质粒介导AmpC β-内酰胺酶大肠埃希菌引起的严重感染的药物。     

头孢吡肟的体外抗菌作用研究

对第四代头孢菌素头孢吡肟的体外抗菌作用进行评价并与其他８种抗菌药进行比较。以琼脂双倍稀释法测定头孢吡肟等对７５９ 株临床分离菌的最低抑菌浓度（ＭＩＣ）,也测定了该药的最低杀菌浓度（ＭＢＣ）及杀菌曲线。研究结果显示头孢吡肟对肠杆菌科细菌、流感杆菌、甲氧西林敏感葡萄球菌、链球菌属、消化链球菌和丙酸杆菌属具有高度抗菌活性,ＭＩＣ９０在≤０．０６～４ｍ ｇ／Ｌ。该药对铜绿假单胞菌、鲁氏不动杆菌亦具良好抗菌作用,ＭＩＣ９０≤４～８ｍ ｇ／Ｌ。甲氧西林耐药葡萄球菌、肠球菌属、脆弱拟杆菌的大多菌株对头孢吡肟呈现耐药。与其他受试药相比,头孢吡肟对肠杆菌科细菌,尤其是阴沟肠杆菌、产气肠杆菌、聚团肠杆菌、柠檬酸杆菌属、肺炎克雷伯氏菌的抗菌活性明显高于受试的β－内酰胺类抗生素和阿米卡星,但略低于亚胺培南,与环丙沙星大致相仿,其中头孢吡肟对大肠埃希氏菌的抗菌活性远高于环丙沙星。头孢吡肟对假单胞菌属、不动杆菌属和革兰氏阳性球菌的抗菌作用与受试的各有关药物大致相仿。头孢吡肟为一杀菌剂,对肠杆菌科细菌杀菌作用强,其ＭＩＣ值与ＭＢＣ值相仿,对铜绿假单胞菌及金葡菌的杀菌作用弱于对肠杆菌科细菌者。     

头孢吡肟等5种抗生素对革兰阴性杆菌抗菌活性比较

目的研究头孢吡肟等5种抗生素对革兰阴性杆菌抗菌活性。方法用纸片扩散法对临床分离的革兰阴性杆菌进行药敏检测，比较头孢吡肟与其他4种临床常用抗生素的抗菌活性。结果分离出245株革兰阴性杆菌。其中：以不动杆菌（48．2％）和铜绿假单胞菌（11．0％）为主的非发酵菌占65．3％。多数革兰阴性杆菌对头孢类菌素的敏感率为44％～68％；除嗜麦芽窄食单胞菌外，其他革兰阴性杆菌对亚胺培南敏感率最高为93．9％。头孢吡肟对阴沟肠杆菌的抗菌活性优于头孢他啶和头孢哌酮／舒巴坦；而对嗜麦芽窄食单胞菌的抗菌活性明显较低，其他与头孢他啶相近；2004年较2003年，头孢吡肟除对肺炎克雷伯菌抗菌活性略升高外，对其他革兰阴性杆菌均有不同程度降低；而头孢他啶和头孢哌酮／舒巴坦抗菌活性保持稳定。结论第4代头孢菌素头孢吡肟可用于ICU危重病人抗感染治疗。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.