HCV NS3 N末端部分氨基酸缺失对NS3/NS3与NS3/NS4A分子间相互作用的影响

目的旨在弄清ＮＳ３参与分子间相互作用的确切区段，为研究针对ＮＳ３的抗ＨＣＶ寡肽小分子药物的设计提供依据。方法参照ＨＣＶ中国河北株序列设计ＮＳ３引物，将其Ｎ末端的前１５个和前３０个氨基酸分别缺失掉。然后用酵母双杂交系统检测ＮＳ３／ＮＳ３及ＮＳ３／ＮＳ４Ａ分子间相互作用强度在缺失前后的变化，从而判明ＮＳ３Ｎ末端氨基酸在分子间相互作用中的意义。核苷酸序列分析采用ＡｐｐｌｉｅｄＢｉｏｓｙｓｔｅｍ３７３Ａ型自动测序仪。结果ＮＳ３Ｎ末端氨基酸缺失前后，ＮＳ３／ＮＳ３分子间及ＮＳ３／ＮＳ４Ａ分子间相互作用的强度相差有显著性（Ｐ＜０．０１），但缺失１５个氨基酸和缺失３０个氨基酸对上述相互作用强度的影响差异无显著性（Ｐ＞０．０５）。结论ＮＳ３Ｎ末端的１～３０个氨基酸在ＮＳ３／ＮＳ３及ＮＳ３／ＮＳ４Ａ分子间相互作用中有一定意义，其Ｎ末端前１５个氨基酸（ＡＰＩＴＡＹＳＱＱＴＲＧＬＬＧ）对于分子间相互作用更为关键。本研究结果将为抗ＮＳ３丝氨酸蛋白酶活性的寡肽抑制物的研究打下基础，并为抗ＨＣＶ的寡肽小分子药物的设计提供依据     

Human immunodeficiency virus and fungal infections

The discovery of HIV was largely due to the presence of Pneumocystis pneumonia (PCP) in young patients that did not have the usual known causes of immune deficiencies in the early 1980s. Currently, treatment with highly active anti-retroviral therapy (HAART) and the use of prophylaxis for PCP have lowered the frequency of fungal infections; however, these infections continue to cause morbidity and mortality in those patients that fall out or are not in care. The frequency of specific fungal diseases in HIV patients will depend on the prevalence of fungi in the particular geographic location. Nowadays, superficial and invasive Candida infections, PCP, and cryptococci are the most frequent fungal infections seen in HIV positive patients worldwide. The role of pathology in diagnosing fungal infections is crucial because a lesion may be biopsied without obtaining mycology cultures, certain organisms may take several weeks to grow, or the sample sent to the mycology laboratory may not have the organism. Following we will describe fungal infections that are particularly frequent in HIV infected patients and their key pathological features.     

大蒜素、氟康唑对医院感染酵母菌的体外抗菌活性研究

目的研究大蒜素、氟康唑对临床分离酵母菌的体外抗菌活性,比较中西药对酵母菌的耐药现状.方法286株酵母菌由住院患者各类感染标本中分离,菌种采用全自动微生物鉴定仪VITEK YBC卡鉴定,用琼脂稀释法测定大蒜素和氟康唑对酵母菌的最低抑菌浓度(MIC),比较大蒜素和氟康唑对酵母菌的MIC50、MIC90.结果经鉴定临床分离的酵母菌中,白色假丝酵母菌最常见,占67.6%,其次为热带假丝酵母菌17.5%、光滑假丝酵母菌8.4%、近平滑假丝酵母菌3.5%等;大蒜素对各类酵母菌均有抑菌作用;氟康唑对白色假丝酵母菌、热带假丝酵母菌及近平滑假丝酵母菌的敏感率较高.结论医院深部酵母真菌感染及耐药性呈上升趋势,提示临床在不明确何种酵母菌感染的情况下,中西药联合使用,可能得到好的疗效.     

氟康唑纸片扩散法和E-test法检测酵母菌体外药敏试验相关性研究

目的对比研究酵母菌氟康唑纸片扩散法和E-test法的相关性,以期确立一种简便可靠的酵母菌体外药物敏感试验方法。方法分别应用纸片扩散法和E-test法检测151株临床分离的酵母菌对氟康唑的敏感性,采用BOMIC仪自动读取培养板上的抑菌环直径,记录试验结果并对质控数据进行核实,使用WHONET-5.4软件分析结果并进行比较。结果两种体外药敏试验方法的一致率可达84.7%,极重要误差率为0.7%,重大误差率为2.0%,次要误差率为12.6%;对于光滑假丝酵母菌两种方法的检测结果有较大差异。结论应用WHO-NET-5.4软件分析得出氟康唑纸片扩散法和E-test法对于检测大多数酵母菌具有非常好的一致性,但对于部分菌株需要进一步应用常量肉汤法确定其最低抑菌浓度值。     

Diversity of Salmonella spp. and fungi in northern Greek rivers and their correlation to fecal pollution indicators

The prevalence and diversity of Salmonella spp., filamentous fungi, and yeasts and their correlation with fecal pollution indicators (total coliforms, fecal coliforms, enterococci) and total heterotrophic bacteria counts were investigated in 95 water samples from the northern Greek rivers Aliakmon and Axios. Salmonella spp. were isolated in 27.4% of the samples and a total of 19 serotypes were identified. The frequency of Salmonella isolation was higher in the Axios (36.8%) than in the Aliakmon (21.0%) river. Significantly (P<0.001) more Salmonella spp. were recovered during warm (41.4%) than cold (5.4%) months. Salmonella-positive samples showed significantly higher counts of total heterotrophic bacteria and coliforms. Filamentous fungi were isolated from 98.9% and yeasts from 17.9% of the samples with respective mean counts of 2.36 x 10(3) and 1.28 x 10(2)cfu/100mL. Totals of 23 genera of filamentous fungi and 3 genera of yeasts were identified. The most frequent filamentous fungi were Penicillium and Aspergillus, while Candida was the most prevalent yeast. A significant (P<0.001) positive correlation of the fecal pollution indicators was demonstrated only for filamentous fungi. The results of this study indicate that these rivers may be potential pathways for human and other animal contamination with Salmonella spp., filamentous fungi, and yeasts, which contribute to the pollution of marine waters and the surrounding environment.     

氟康唑和伏立康唑对酵母菌抗菌活性的研究

目的 :研究氟康唑和伏立康唑对 2 14株酵母菌的体外抗菌活性。方法 :酵母菌收集自 2 0 0 0年 1月至 2 0 0 1年 12月住院患者提供的标本。采用酵母菌纸片扩散法敏感试验 ,Mueller Hinton琼脂中补充 2 %葡萄糖和 0 .5mg/L美蓝 ,其他类似于美国国家临床实验室标准委员会 (NCCLS)M2 A6细菌药敏试验法。采用BIOMIC仪自动读取平皿抑菌环直径、解释和记录试验结果及核对质控数据。结果 :白念珠菌最常见 ,占 5 4 .7% ,其次为热带念珠菌占 18.7% ,光滑念珠菌占 12 .1% ,近平滑念珠菌占 4 .7% ,克柔念珠菌占 3.7%和新型隐球菌占 3.7%。白念珠菌、热带念珠菌和近平滑念珠菌对氟康唑的敏感率为 92 .5 %～10 0 .0 % ,MIC90 均在敏感范围内 (<3～ 8mg/L) ,伏立康唑对白念珠菌、热带念珠菌、光滑念珠菌和近平滑念珠菌的MIC90 为 0 .0 6 4～ 1.5mg/L。结论 :氟康唑对白念珠菌、热带念珠菌和近平滑念珠菌有较好的抗菌活性 ,伏立康唑比氟康唑对白念珠菌、热带念珠菌、光滑念珠菌和近平滑念珠菌有更高的抗菌活性 ,有较低的MIC值