国产环丙氟哌酸的体外抗菌活性研究

本文测定了国产环丙氟哌酸对临床分离的883株需氧菌与58株厌氧菌的抗菌作用。金葡球菌的 MIC_(90) 为1mg/L,除沙雷菌的 MIC_(90)为0.25mg/L外,其他肠杆菌科细菌的 MIC_(90)≤0.06mg/L,绿脓杆菌和不动杆菌属的 MIC_(90)分别为1mg/L和0.125～0.5mg/L,90％以上的耐Ceftazidime和庆大霉素的革兰氏阴性菌对环丙氟哌酸仍敏感。对淋球菌的MIC_(90)≤0.0075mg/L,环丙氟哌酸与氧哌嗪青霉素联合对绿脓杆菌和肠球菌、环丙氟哌酸与庆大霉素联合对耐甲氧西林金葡球菌50％呈协同和相加作用,均未出现拮抗现象。     

口服丙氟哌酸治疗骨、关节和软组织感染

丙氟哌酸是对肠杆菌科(MIC_(90)≤1.0μg/ml),绿脓杆菌(MIC_(90)≤1.0μg/ml)和金葡菌(MIC_(90)≤0.8μg/ml)均具有强大抗菌活性的喹诺酮羧酸抗菌药.本品耐药突变比氨基糖苷类抗生素低,并具有口服吸收良好和半衰期长等优点.本品对52例骨、关节和软组织感染进行临床和细菌评价.治疗方案为口服500mg20例,750mg41例,12小时一次,疗程为5～181日,在治疗期间混合耐药菌感染者联用其他抗菌剂.临床治疗结果表明,在研究期间的分离病原菌包括肠杆菌37株、金葡菌30株和绿脓杆菌21株等在内共92株均清除,分离菌88株(96%)对本品敏感.29例骨髓炎病例,14例经随访一年未见复发;20例皮肤软组织感染中,治愈18(90%),2例分别由于C族链球菌和绿脓杆菌混合耐甲氧西林的金葡菌重复感染而失败;3例关节感染病例中,1例经     

罗美沙星体外抗菌活性研究

罗美沙星是由日本北陆公司于1985年开始研制的新喹诺酮类抗菌药物,上海医药工业研究院于1990年研制成功,本文测定了国产罗美沙星对临床分离的966株需氧菌与93株厌氧菌的抗菌作用,并与进口品及8种有关抗菌药物进行比较。对非产酶金葡球菌和产酶但对甲氧西林敏感金葡球菌(MSSA)的MIC_(50)为0.5～1mg/L;对β-溶血性链球菌的MIC_(50)为2mg/L;对肠杆菌科细菌的MIC_(50),除雷极氏杆菌为64mg/L外,其他均在0.5mg /L以下;对流感杆菌的MIC_(50)和MIC_(90)均为≤0.06mg/L;对绿脓杆菌和不动杆菌属的MIC_(50)为0.25mg/L。罗美沙星对淋球菌的MIC_(50)和MIC_(90)分别为≤0.06mg/L和0.5mg/L。     

国产氧氟沙星体外抗菌活性研究

本文报道国产氧氟沙星对临床分离的632株致病菌的体外抗菌作用研究结果,并与日本进口氧氟沙星进行比较。结果表明国产品与进口品对632株细菌的MIC_(50)、MIC_(90)和MIC范围基本相同。国产氧氟沙星对金葡菌敏感(MIC_(50)为0.125mg/L,MIC_(90)为0.25mg/L),对肠道不同菌株均显示明显抗菌活性,对痢疾杆菌其MIC_(90)为0.06mg/L,对沙门氏菌MIC_(90)为0.25mg/L。对大肠杆菌、产气杆菌和哈夫尼亚菌MTC_(90)为0.25～0.5mg/L,而对绿脓杆菌和沙雷氏菌抗菌作用略差。对产β-内酰胺酶阳性和阴性的细菌的抗菌活性一致,与日本产物亦一致。     

新一代β—内酰胺类抗生素对脆弱拟杆菌抗菌作用的比较

1986年1月到1986年12月,从7个临床中心共分离到557株脆弱拟杆菌组细菌,药敏结果表明,抗菌作用最强者为 Imipenem,MIC_(50)和 MIC90分别为<0.06和1μg/ml,替卡西林-克拉维酸次之,MIC_(50)和 MIC_(90)分别为1和16μg/ml,两者的耐药率分别为0.2%和1.7%,头孢西丁的 MIC_(50)和 MIC_(90)分别为8和16μg/ml,耐药率为11%,Moxalactam的 MIC_(50)和 MIC_(90)分别为4和128μg/ml,耐药率为23%,哌拉西林,头孢替坦,头孢唑肟     

国产利福喷丁治疗急性肺部感染32例

国产利福喷丁(Rifapentine,DL-473)是一个新的利福霉素衍生物,由四川抗菌素工业研究所研制成功,除对抗酸杆菌有较强的抗菌活性外,还对革蓝氏阳性球菌有很强的抗菌活性。对金色葡萄球菌的MIC_(90)为0.2～0.5mg/L,肺炎链球菌的MIC_(90)为0.2mg/L,但对革蓝氏阴性杆菌抗菌作用较差,对大肠杆菌的MIC_(90)为64mg/L。利福喷丁对小鼠感染金葡菌,A群化脓性链球菌,肺炎链球菌有卓越的保护作用。我们试用国产利福喷丁治疗32例急性肺部感染病人,以观察其疗效和副作用,同时进行了病人的血药浓度测定,兹报告如下。     

交沙霉素的抗菌作用及临床治疗各种细菌感染34例

本文测定了交沙霉素的体外抗菌作用。43株表皮葡萄球菌(表葡菌)和金黄色葡萄球菌(金葡菌)对交沙霉素和红霉素敏感率分别为81％和54％。交沙霉素对26株厌氧葡萄球菌(消化球菌)、消化链球菌和28株类杆菌的MIC_(50)分别为0.5和2mg/L。交沙霉素对34例口腔、五官及皮肤的感染全部有效,其中显效(痊愈)占88％。31例获细菌33株,细菌转阴率为97％。治疗中仅3例出现头晕和轻度消化道反应。     

麦迪霉素与乙酰螺旋霉素治疗104例感染随机对照观察

应用麦迪霉素和乙酰螺旋霉素随机对照治疗革兰阳性球菌和厌氧菌感染104例,包括口腔感染、耳鼻喉感染、呼吸系感染和皮肤软组织感染等,临床有效率各为90.6％和90.2％,细菌清除率各为89.4％和90.7％;临床应用中两组不良反应均低微。上述结果统计学处理皆无显著差异,提示西药的疗效和安全性相仿。麦迪霉素和乙酰螺旋霉素对本系列24株葡萄球菌的MIC_(50)分别为2mg/L和32mg/L,敏感率分别为67％和46％;纸片法药敏结果显示,37株临床分离厌氧菌对两药呈现敏感者分别为30株和31株。     

一种新的头孢菌素——头孢匹罗

Qadri等采用标准的琼脂稀释法就头孢匹罗对临床分离的肠杆菌科(478株)、绿脓杆菌(91株)、嗜麦芽黄杆菌(27株)、不动杆菌(36株)、嗜水气单胞菌属(28株)、Weeksella(1株)、葡萄球菌(361株)和肠球菌(50株)的体外活性与其它广谱的抗生素进行了比较。头孢匹罗对肠杆菌科、不动杆菌和嗜水气单胞菌显示出极好的抗菌活性,MIC_(50)<0.03～2.0 mg/L,MIC_(90)为0.12～4.0mg/L。对87％绿脓杆菌的MIC为4.0～16.0 mg/L。对Rahnella,哈夫尼菌和Weeksella三种菌中每一菌株的抑菌浓度≤4.0mg/L。在对亚胺培南耐药的大肠杆菌和肠杆     

CEFTAZIDIME的协同抗菌作用及对细菌形态学影响

采用琼脂稀释棋盘法,应用多点接种仪分别对Ceftazidime(CTD)单用或合用时抗菌活性进行测定。结果表明CTD对60株绿脓杆菌的抗菌活性最强,其MIC_(50)和MIC_(90)均为1μg/ml,对50株大肠杆菌的MIC_(50)为0.125μg/ml,MIC(90)为0.25μg/ml,优于实验中其它六种抗生素。 联合抗菌作用结果表明,CTD与妥布拉霉素及丁胺卡那霉素联合对20株绿脓杆菌,其协同率分别为15％、10％。CTD与哌拉西林联合协同率亦为15％,和CTD与妥布拉霉素联合时相同。CTD与丁胺卡那霉素联合对20株大肠杆菌也具有一定的协同作用(5％)。 形态学观察结果表明,光镜、电镜结果基本一致。 CTD2μg/ml(2MIC)作用4小时后,菌体拉长呈丝状,不见横膈形成; 20μg/ml(20MIC)作用后,细菌呈丝状及不规则型,胞壁、胞膜结构不完整,出现断裂和缺损。 CTD与哌拉西林各2MIC联合作用 4小时后,细菌呈多形性改变,胞壁破坏明显,胞内空泡形成。CTD与妥布拉霉素各2MIC联合作用4小时后,细菌形态以短小为主,可以见到收缩期横膈。 CTD与妥布拉霉素各20MIC联合作用后,细菌呈不规则形,有的可见菌体松解,有的则又浓缩变小,多数细菌胞壁结构不完整。     

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.     

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.     

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.     

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.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.