一种蒺藜甾体皂苷对人工诱导耐药的红色毛癣菌体外抗菌活性研究

目的 研究蒺藜的甾体皂苷成分TTS-12对于耐药皮肤癣菌的抗真菌作用。方法 用含体外浓度递增法对真菌进行培养,分别诱导红色毛癣菌对氟康唑和酮康唑的耐药性,用微量液基稀释法评价菌株的耐药性、稳定性及对TTS-12的敏感度。结果 经过诱导后,耐氟康唑菌株对氟康唑的最小抑菌浓度(MIC)＞128 μg·mL^-1,耐酮康唑菌株对酮康唑的最小抑菌浓度＞64 μg·mL^-1,且传代三次后耐药性相对稳定,TTS-12对氟康唑耐药菌株的最小抑菌浓度范围在4～16 μg·mL^-1,对酮康唑耐药菌株的最小抑菌浓度范围在4～8 μg·mL^-1。结论 经过浓度递增方式的培养能够成功诱导红色毛癣菌耐氟康唑和酮康唑的菌株,并且TTS-12对两种耐药菌株有良好的生长抑制作用。     

顶空气相色谱法测定几丁糖酯中溶剂残留

目的 :建立顶空气相色谱法分析几丁糖酯中溶剂残留。方法 :采用水溶液顶空和固体顶空 2种气相色谱法 ,用AC -2 0石英毛细管色谱柱 ,以正丙醇为内标进行定量。结果 :水溶液顶空气相色谱法乙醇的线性范围为 8～ 192 μg·mL-1,丙酮的线性范围为 2～ 6 4μg·mL-1;方法的回收率为乙醇 10 3 3% ,丙酮 95 71% ,RSD均为 4 2 % ;最低检测限溶液中乙醇为 4μg·mL-1,丙酮为 1μg·mL-1。固体顶空气相色谱法乙醇的线性范围为 0 16～ 2 4μg·mL-1,丙酮的线性范围为 0 16～ 1 6 μg·mL-1;方法的回收率为乙醇 96 32 % ,丙酮 10 2 1% ,RSD分别为 3 5 %和 2 6 % ;最低检测限乙醇为 0 12 μg·g-1,丙酮为 0 0 6 μg·g-1。结论 :此 2种方法简单 ,准确 ,灵敏度高 ,经显著性检验二者无显著性差异。     

1-(1H-1,2,4-三唑-1-基)-(2,4-二氟苯基)-3-[N-环丙基-N-(4-取代苄基)]-2-丙醇的合成及抗真菌活性

目的：以氟康唑为先导化合物,设计合成新的三唑醇类化合物,并研究其抗真菌活性。方法：引入4位羧酸酯取代的苄基侧链结构,合成一系列目标化合物,所有化合物结构均经MS、^1H-NMR等谱确证;选择8种真菌为实验菌株,测定其体外抗真菌活性。结果：合成了15个未见文献报道的目标化合物;所有化合物对所选真菌均表现出了一定的抑菌活性,其中化合物（1）,（2）和（3）对除薰烟曲霉菌外的7种菌都表现出了较好的抑菌活性。结论：4位羧酸酯取代的苄基侧链结构的引入对目标化合物的抗菌活性有一定的影响,侧链越短．抑菌活性越好.     

次氯酸钙抗真菌的体外实验与临床应用

目的探讨次氯酸钙的抗真菌作用及机制.方法采用琼脂双倍稀释法及中和剂悬液法培养对6种常见致病性真菌进行抑菌实验;观察最小抑菌浓度作用下,3种致病真菌的超微结构变化;随机分组比较次氯酸钙与克霉唑、制霉菌素治疗皮肤浅部真菌病的临床疗效.结果次氯酸钙对红色毛癣菌、石膏样小孢子菌、羊毛状小孢子菌、絮状表皮癣菌有抑制和杀灭作用,其最低抑菌稀释度为1∶400;对白色念珠菌和孢子丝菌均有抑制作用,最低抑菌稀释度分别为1∶100,1∶50;能破坏红色毛癣菌、石膏样小孢子菌及白色念珠菌的细胞壁,使细胞质、细胞核空泡化,细胞器变性;随机分组对比治疗皮肤浅部真菌病,其效果与对照组相似(P＞0.05).结论次氯酸钙具有抗真菌作用,能杀灭常见浅部致病真菌,抑制常见深部致病真菌.临床应用效果确切,副作用小,安全.     

3种中药方剂逆转大肠杆菌耐药性的实验观察

目的研究三黄汤、黄连解毒汤和五味消毒饮3种方剂使产超广谱β-内酰胺酶大肠杆菌部分或全部恢复对抗生素敏感性的作用。方法用纸片扩散法和双纸片协同法筛选产超广谱β-内酰胺酶大肠杆菌,用试管二倍稀释法确定3种中药的最低抑菌质量浓度,以低于最低抑菌不同浓度,在不同时间下培养耐药大肠杆菌,比较各中药的逆转效果。结果三黄汤在0.2g·mL-1,24h;黄连解毒汤在0.4g·mL-1,12h;五味消毒饮在0.3g·mL-1,36h或0.4g·mL-1,48h的逆转效果最佳,与阳性对照克拉维酸比较有显著性差异(P<0.05)。结论3种中药有逆转细菌耐药性的作用,逆转作用与中药质量浓度及培养时间有关。     

1-(1 H-1, 2, 4-三唑-1-基)-2-(2, 4-二氟苯基)-3-[N-异丙基-N-(4-取代苄基)]-2-丙醇的合成及抗真菌活性

目的研究具有异丙基结构的氮唑类化合物的抗真菌活性。方法引入4位羧酸酯取代的苄基侧链结构,合成一系列目标化合物,所有化合物结构均经MS、1H-NMR等谱确证;选择8种真菌为实验菌株,测定其体外抗真菌活性。结果合成了14个未见文献报道的目标化合物;所有化合物对所选真菌均表现出了一定的抑菌活性,其中化合物(1)和(2)对除薰烟曲霉菌外的7种菌都表现出了较好的抑菌活性。结论 4位羧酸酯取代的苄基侧链结构的引入对目标化合物的抗菌活性有一定的影响,侧链越短,抑菌活性越好。     

盐酸左氧氟沙星体内外抗菌作用研究

［摘要］目的评价盐酸左氧氟沙星对临床常见致病菌的体内外抗菌活性。方法采用试管二倍稀释法测定最低抑菌浓度（MIC）， 并对其影响因素进行测定，同时与对照药左氧氟沙星、氧氟沙星进行对比。结果盐酸左氧氟沙星对金黄色葡萄球菌（金葡菌）、表皮葡萄球菌、肺炎球菌等革兰阳性菌有较强的抗菌活性，MIC50为 0.16～0.62 μg·mL-1；对肠杆菌科细菌如变形杆菌、大肠埃希菌、肺炎克雷白杆菌等革兰阴性菌也有较强的抗菌活性，MIC50为 0.31～1.25 μg·mL-1；盐酸左氧氟沙星在酸性条件下抗菌活性降低，随着血清浓度及细菌接种量的提高，盐酸左氧氟沙星的MIC值增大2～4倍；盐酸左氧氟沙星对金葡菌、大肠埃希菌感染小鼠有明显的保护作用，其ED50分别为4.54，1.21 mg·kg-1，盐酸左氧氟沙星的作用与左氧氟沙星相似，但明显强于氧氟沙星。结论盐酸左氧氟沙星对临床常见致病菌有良好的抗菌作用。     

两种预防新生儿眼炎的药物体外抗菌活性的比较

目的：测定并比较预防新生儿眼炎的硝酸银滴眼液、聚维酮碘滴眼液的体外抗菌活性。方法：采用肉汤二倍稀释法测定最低抑菌浓度和最低杀菌浓度。结果：硝酸银滴眼液对致新生儿眼炎常见的金黄色葡萄球菌、肺炎球菌的MIC50分别为4，8 μg·mL 1，MBC90分别为8，32 μg·mL 1；聚维酮碘滴眼液对该两菌的MIC50分别为64，128 μg·mL 1，MBC90均为256 μg·mL 1。结论：硝酸银滴眼液和聚维酮碘滴眼液对新生儿眼炎常见致病菌都具有抑菌和杀菌作用，但硝酸银滴眼液更适用于对新生儿眼炎预防。     

鬼箭锦鸡儿中紫檀烷类化合物抗真菌活性研究

目的研究鬼箭锦鸡儿中紫檀烷类化合物的抗真菌活性。方法在生物活性指导下,利用聚酰胺、硅胶常规色谱和制备型高效液相色谱方法进行化合物分离,采用波谱技术和化学方法鉴定化合物的结构。最低抑菌浓度(MIC)测定参照美国国家临床实验室标准化委员会(NCCLS)推荐的M27-A方案中的微量肉汤稀释法。结果鬼箭锦鸡儿整株植物氯仿部分显示好的抗真菌活性,活性追踪分离得到五个紫檀烷类化合物,分别是3-甲氧基高丽槐素(1)、高丽槐素(2)、3-甲氧基-9羟基紫檀烷(3)、3,9-二甲氧基紫檀烷(4)和3-甲氧基-4,9二羟基紫檀烷(5),其中化合物2面对三种念珠菌菌株,显示出潜在的抗真菌活性,最低抑菌浓度范围为6.25～25 μg·mL-1。结论所有化合物均为首次从该植物分离得到,并且生物活性结果确认紫檀素类化合物是有效的抗真菌成分。     

国产头孢拉宗钠对临床分离致病菌的体内外抗菌作用研究

目的 研究国产注射用头孢拉宗钠(CFB)的体内外抗菌效果.方法 体外实验采用琼脂二倍稀释法计算细菌的最低抑菌浓度(MIC),体内实验用临床分离大肠埃希菌和金黄色葡萄球菌,小鼠腹腔注射最小致死量菌液造成全身感染,静脉注射不同剂量的受试药物,观察7d或14 d内小鼠的死亡情况,用NDST程序的Bliss法计算ED50.结果 CFB对G-菌中的大肠埃希菌、肺炎克雷伯菌抗菌作用良好,MIC50为0.25～0.5 μg·mL-1,对G+菌中的金黄色葡萄球菌、表皮葡萄球菌呈强抗菌作用,MIC50均为0.5 μg· mL-1,对不动杆菌和铜绿假单胞菌无抗菌活性,体内保护实验显示:国产CFB对大肠埃希菌、金黄色葡萄球菌的ED50为5.71、45.00 mg·kg-1.结论 国产注射用CFB对体外多数G+菌效果良好,对金黄色葡萄球菌有强抗菌作用,对G-菌大肠埃希菌、肺炎克雷伯菌有较强抗菌作用.对腹腔感染大肠埃希菌、金黄色葡萄球菌的小鼠也有显著抗菌效果.     

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.