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.     

多尼培南药理作用与临床应用

多尼培南（doripenem）为新型碳青霉烯类抗菌药物,作用机制与其他β-内酰胺类抗菌药物相同,抗菌谱广,抗菌活性强,对多种革兰阳性（G⁺）菌（包括对甲氧西林敏感和耐药的金黄色葡萄球菌、表皮葡萄球菌等）和革兰阴性（G^－）菌（包括大肠埃希菌、肺炎克雷白杆菌、奥克西托克雷白杆菌、奇异变形杆菌等）均有很强的抗菌活性,对G^＋菌的抗菌活性强于美罗培南和比阿培南,对G^－菌的抗菌活性强于亚胺培南和比阿培南,其中对铜绿假单胞菌有着很强的抗菌活性. 多项临床试验 结果 表明,多尼培南对复杂性尿道感染的疗效与左氧氟沙星相当,对复杂性腹腔内感染的疗效与美罗培南相当. 该文对其作用机制、抗菌活性、药动学、临床研究及药物不良反应等进行综述.     

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。     

新型广谱碳青霉烯类抗菌药物——多尼培南

多尼培南（Doripenem）是由美国强生公司研发,于2007年10月15日被美国FDA批准的广谱碳青霉烯类抗菌药物,其结构特点是具有1β-甲基和C-2被氨磺酰氨甲基吡咯烷硫代基团取代。其通过抑制细胞壁合成,显示出广谱、高效的抗菌活性,特别对铜绿假单胞菌的活性强于现有碳青霉烯抗生素;其对革兰阳性菌的活性比美罗培南强,对革兰阴性菌的活性比亚胺培南强,尤其是抗绿脓杆菌活性有所增强。     

碳青霉烯类抗生素—多尼培南

多尼培南（Doripenem，S-4661）是由日本盐野义制药株式会社（Shionogi＆Co,Ltd）开发的碳青霉烯类新广谱抗生素，具有抗菌谱广、对绝大多数β-内酰胺酶稳定的特点。本品注射剂于2005年在日本上市，现在美国进行临床试验，已完成Ⅲ期临床研究。多尼培南已经获得美国FDA的快速审批待遇，用于治疗医院获得性肺炎，包括呼吸器相关性肺炎。其吸入剂正在进行Ⅰ期临床研究，用于囊性纤维化患者的肺部感染。目前国内正在研究开发。     

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特点及临床应用

亚胺培南、帕尼培南、美罗培南均为碳青霉烯类抗生素,属于β -内酰胺抗生素之一,具有超广谱的抗菌活性,覆盖了多数临床常见的需氧G+、G -菌及厌氧菌,因而成为治疗严重感染的一线经验性治疗药物.亚胺培南是第一代产品,帕尼培南、美罗培南是第二代产品,二者比亚胺培南具有更多的优点.下面就三种碳青霉烯类抗生素的化学结构、作用方式、抗菌活性、药代学、药效学、临床应用等特点作一简要介绍.     

多尼培南的药理和临床研究

多尼培南（doripenem，S-4661）是新型碳青霉烯类抗生素，抗菌谱广，抗菌活性强，对多种G^＋和G^-菌均有很强的抗菌活性。现对其作用机制、抗菌活性、药动学、临床应用及药物不良反应做一综述。     

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。     

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。     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

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.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

盐酸达泊西汀中甲磺酸甲酯、甲磺酸乙酯及甲磺酸异丙酯的顶空毛细管GC-ECD法测定

建立了衍生化顶空毛细管气相色谱-电子捕获检测器(ECD)法测定盐酸达泊西汀中的甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS).应用碘化钠衍生技术,使用PW-5毛细管柱,载气为氮气,ECD检测,程序升温.MMS、EMS和IMS分别在0.03～0.30、0.05～0.50和0.05～0.50 μg/ml浓度范围内线性关系良好,平均回收率分别为63.5％、100.3％和96.2％,最低检测限分别为0.30、0.50和0.50 ng/ml.     

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.