白假丝酵母菌阴道炎小鼠模型的构建

摘 要 目的：构建白假丝酵母菌阴道炎小鼠模型,探索最佳成模条件,以提供经济实用的白假丝醇母菌性阴道炎动物模型。方法: 采用昆明雌性小鼠,预先连续灌胃给予低、中、高剂量（0.001 5,0.015,0.15 mg/10 g）的戊酸雌二醇7 d后接种白假丝酵母菌建立阴道炎模型,并进行阴道灌洗液真菌载量和阴道组织病理观察。结果: 戊酸雌二醇低、中、高剂量组阴道灌洗液的菌落计数分别为124.67±19.01、217.67±22.50、282.00±27.87,高剂量组与中、低剂量组比较差异有统计学意义（P<0.05或P<0.01）。HE染色和PAS染色结果显示,戊酸雌二醇高剂量组有较多多形核粒细胞（PMNs）浸润及紫红色线状菌丝。结论: 戊酸雌二醇高剂量组造模方式为昆明小鼠白假丝酵母菌阴道炎模型的最佳造模条件。     

门诊外阴阴道假丝酵母菌病菌株调查和药敏分析

目的探讨外阴阴道假丝酵母菌病(VVC)致病菌株分布和药敏情况。方法对2005年12月至2008年12月在孝感市中心医院妇科门诊以阴道炎症状就诊者中,阴道分泌物真菌培养阳性的260例患者进行菌株调查和药敏分析。结果VVC致病菌株白假丝酵母菌占89.6%(233/260),非白假丝酵母菌占10.4%,白假丝酵母菌菌株与非白假丝酵母菌菌株药敏无明显差异,两性霉素B药敏率98.87%。结论VVC致病菌株仍以白假丝酵母菌占优势,非白假丝酵母菌对两性霉素耐药率无增加。     

美廉净凝胶的抗炎、镇痛及抗瘙痒作用研究

目的 研究美廉净凝胶抗炎、镇痛及抗瘙痒的作用.方法 通过蛋清液致小鼠足肿胀试验,羧甲基纤维素钠(carboxymethylcellulose sodium,CMC-Na)致小鼠皮下气囊白细胞游走试验,棉球致小鼠肉芽肿试验考察美廉净凝胶的抗炎作用;通过醋酸致小鼠扭体反应试验考察美廉净凝胶的镇痛作用;通过右旋糖酐-40致小...     

假丝酵母菌性阴道炎的菌种分类及耐药性

目的分析假丝酵母菌性阴道炎患者病原性真菌的菌种分布及其耐药性,为临床合理选用抗真菌药物提供依据。方法严格按照《全国临床检验操作规程》,采用常规方法以念珠菌显色培养基进行培养,用珠海迪尔公司生产的DL-96细菌鉴定系统进行假丝酵母菌鉴定及药敏检测。结果自239例假丝酵母菌性阴道炎的分泌物中共检出5种假性酵母菌,其中白假丝酵母菌居首位,达到171株（71.5%）,其次为光滑假丝酵母菌29株（12.1%）,热带假丝酵母菌22株（9.2%）,近平滑假丝酵母菌11株（4.6%）,克柔假丝酵母菌6株（2.5%）,5种假丝酵母菌对5-氟尿嘧啶、两性霉素、制霉菌素敏感率均为100.0%,对氟康唑、克霉唑、伊曲康唑、伏立康唑等抗菌药物的耐药率为2.1%～28.6%。结论假丝酵母菌性阴道炎以白色假丝酵母菌感染为主。致病性真菌除对5-氟尿嘧啶、两性霉素、制霉菌素敏感率均为100.0%敏感外,对其它4种常用抗真菌药物已产生了不同程度的耐药性,应重视假丝酵母菌的培养和药敏试验,指导临床合理选择抗真菌药物。     

氟康唑与克霉唑栓联用对白假丝酵母菌性阴道炎患者的临床疗效评价

目的:评价氟康唑与克霉唑栓联用对老年白假丝酵母菌性阴道炎患者的临床疗效。方法:选取医院门诊2016年3月—2017年3月期间诊治的老年白假丝酵母菌性阴道炎患者160例临床资料,将其随机分为治疗组和对照组(每组80例);对照组患者给予氟康唑片口服治疗,治疗组患者在对照组治疗基础上加用克霉唑栓腔内治疗,比较两组患者治疗后的总有效率、症状复常时间,以及治疗后的复发率和生活质量评分值等指标。结果:治疗组患者治疗后的总有效率为97.50%高于对照组为78.75%(P<0.05),症状复常时间明显短于对照组(P<0.05);治疗组患者治疗后3、6和12月的复发率均明显低于对照组(P<0.05),心理、生理以及环境、社会关系领域等生活质量评分值均明显高于对照组(P<0.05)。结论:氟康唑与克霉唑栓联用治疗老年白假丝酵母菌性阴道炎患者的临床疗效优于单用氟康唑,能迅速改善的临床症状,复发率较低。     

我院2009-2011年老年真菌感染菌种分布及其对抗真菌药敏感性分析

目的:探讨临床老年患者标本中所分离的假丝酵母菌属的菌种分布及其对临床常用抗真菌药的敏感性,为老年人使用抗真菌药提供参考。方法:对我院2009-2011年从老年体内分离的213例假丝酵母菌进行回顾性分析,分析其菌种分布情况以及对5种抗真菌药的敏感性。结果:在213株假丝酵母菌中,白假丝酵母菌占42.3%(90/213),非白假丝酵母菌占57.7%(123/213);5-氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑和伏立康唑的总敏感率分别为87.8%、100%、93.2%、85.9%和95.9%;90株白假丝酵母菌对上述5种抗真菌药的敏感率分别为93.3%、100%、95.4%、92.2%和96.3%,123株非白假丝酵母菌分别为83.7%、100%、91.6%、81.3%和95.6%。结论:在老年感染假丝酵母菌中最常见的菌种仍是白假丝酵母菌,但其比例较已报道的非老年感染者比例有所下降;白假丝酵母菌对常用抗真菌药仍有较高的敏感性,非白假丝酵母菌的耐药性则高于白假丝酵母菌。     

255份白假丝酵母菌感染患者的病历分析

目的:分析引起住院患者白假丝酵母菌感染的相关因素,为控制该菌感染提供参考。方法:根据细菌室提供的资料,对我院2005年1～12月255份白假丝酵母菌感染患者的病历进行统计分析。结果:共检出360株白假丝酵母菌,其中抗菌药物的使用率为98.04%,确诊为院内感染的病历为24.31%。结论:白假丝酵母菌感染患者与其使用抗菌药物、体质、年龄、基础病况、病程等均有关系。     

氟康唑与克霉唑阴道片联用对白假丝酵母菌阴道炎患者的疗效与安全性评价

目的:评价氟康唑与克霉唑阴道片联用对白假丝酵母菌阴道炎患者的疗效与安全性。方法:选取2015年1月—2016年7月间收治的白假丝酵母菌阴道炎患者81例临床资料,按入院顺序编号采用随机数表法将其分为对照组(n=40)和观察组(n=41);对照组患者给予单用克霉唑阴道片治疗,观察组患者在对照组基础上加用氟康唑治疗,评价两组患者治疗后的总有效率和不良反应发生的变化情况。结果:观察组患者治疗后的总有效率为95.12%高于对照组为75.00%(P<0.05);两组患者用药期间不良反应的发生率经组间比较其差异无统计学意义(P>0.05),而观察组患者阴道炎的复发率为4.89%低于对照组为25.00%(P<0.05)。结论:采用氟康唑与克霉唑阴道片联用治疗白假丝酵母菌阴道炎患者的疗效优于单用克霉唑阴道片的治疗,且"安全性好、不易复发"等优势。     

克霉唑阴道片治疗妊娠合并外阴阴道假丝酵母菌病疗效观察

外阴阴道假丝酵母菌病(VVC)是一种常见的阴道炎,多见于生育年龄的妇女,而妊娠妇女比非妊娠期患病率高10～20倍.妊娠期阴道炎可引起胎膜炎,导致胎膜早破,甚至早产,对胎儿及新生儿可发生假丝酵母菌感染.     

社区感染中白假丝酵母菌的药敏结果分析

目的了解社区感染中白假丝酵母菌的药敏情况,以指导临床合理用药。方法收集医院2007年1月至2010年12月住院患者社区感染的送检标本(3202例)中的白假丝酵母菌培养标本,进行药敏结果分析。结果共分离出白假丝酵母菌菌株244株,平均分离率7.6%。药敏结果显示,两性霉素B药物敏感率最高>94.9%,其次为五氟胞嘧啶,药物敏感率>86.8%。结论两性霉素B和五氟胞嘧啶对社区感染中白假丝酵母菌的敏感率最高,两性霉素B和五氟胞嘧啶联合应用是治疗白假丝酵母菌感染理想的首选。     

肤鲜洗剂对急性湿疹小鼠T细胞介导的细胞免疫调节作用研究

目的: 观察肤鲜洗剂对小鼠变应性接触性皮炎(allergic contact dermatitis,ACD)的影响。方法: 采用BALB/c小鼠40只,适应性喂养3 d后随机分为4组,每组10只,分别为空白对照组、模型对照组、肤鲜洗剂组、阳性药物对照组,除空白对照组外,均采用1% 2,4-二硝基氟苯(2,4-dinitrofluorobenzene,DNFB)丙酮橄榄油溶液致敏和激发小鼠皮肤,建立小鼠ACD模型,激发后12 h开始用药,连续2 d,每天给药2次。在激发后48 h分别对小鼠耳厚度及耳变应反应程度进行测量评分,计数1 min内小鼠搔抓耳部次数,小鼠耳部皮损以HE染色,观察皮肤炎性细胞浸润等病理变化情况。采用ELISA检测血清中γ干扰素(interferon gamma,IFN-γ)、白细胞介素-4(interleukin-4,IL-4)、白细胞介素-17(interleukin-17,IL-17)及白细胞介素-35(interleukin-35,IL-35)水平。结果: 与空白对照组比较,模型对照组小鼠耳厚度、耳变应反应评分、搔抓指数、血清中IL-4、IL-17水平显著升高(P＜0.05),IFN-γ、IL-35水平显著降低(P＜0.05),出现明显的ACD病理改变。与模型对照组比较,肤鲜洗剂可有效减轻小鼠的耳廓肿胀程度,降低耳变应反应评分,同时明显降低血清中IL-4、IL-17水平(P＜0.05),升高IFN-γ、IL-35水平(P＜0.05),显著改善耳部组织的病理形态。结论: 肤鲜洗剂对急性湿疹小鼠T细胞介导的细胞免疫具有一定的调节作用,可达到治疗急性湿疹的作用。     

Candida albicans cellular internalization: a new pathogenic factor?

The preliminary results of a study to show the possibility that Candida albicans can internalize into epithelial cells are reported. The study was performed on buccal, vaginal and HeLa cells. Buccal and vaginal cells, at a concentration of 5×10⁴ cells/ml and HeLa monolayers were incubated for 2, 3 and 4 h with 10⁵ colony forming units of a Candida albicans isolate. After incubation, non-internalised yeasts were eliminated and samples were processed for examination by Scanning Electron Microscopy. Results suggest that receptor-mediated endocytosis could be involved in the pathogenesis of recurrent oral and vaginal infections. This phenomenon could represent an interesting experimental model to testing drug interference in the development of therapeutic strategies against C. albicans infections.     

类叶升麻苷对APP/PS1双转基因小鼠抗炎及抗氧化作用的研究

目的：探讨类叶升麻苷（Acteoside，AS）对APP/PS1双转基因小鼠炎症因子及氧化应激因子变化的影响。方法：健康APP/PS1转基因小鼠90只，对照B6C3雄鼠16只，雌雄各半，连续90 d灌胃给药，给药76 d进行Morris水迷宫实验，87 d进行跳台实验，解剖后检测血清、海马和皮层中炎症及氧化应激相关因子。结果：模型组小鼠血清中IL6、TNF-α含量显著高于正常组，模型组小鼠海马中IL1-β、IL6、IFN-γ、ROS含量显著高于正常组，模型组小鼠皮层中IL1-β、ROS含量显著高于正常组，IL6、TNF-α、IFN-γ含量与正常组无明显差异。AS可显著降低皮层中IL1-β、IL6、IFN-γ、ROS含量。结论：AS可通过降低痴呆小鼠致炎因子含量以抑制炎症反应，从而对机体产生免疫调节作用，保护神经细胞并改善脑部损伤，进而发挥其神经保护及改善学习记忆的作用。同时，AS可显著降低ROS含量，说明AS可通过抑制氧化应激损伤达到改善小鼠学习记忆功能的作用。     

Teasaponin induces reactive oxygen species-mediated mitochondrial dysfunction in Candida albicans

Candida albicans is the most prevalent commensal fungus and readily causes invasive fungal infection in immunocompromised individuals. Teasaponin (TS), a natural product generally regarded as safe, has been reported to inhibit filamentation of C. albicans. This study found that TS could exert moderate fungicidal activity against C. albicans, and the mode of action was further explored. The minimum fungicidal concentration (MFC) was determined by the broth microdilution method. The colony counting method was used to determine the time-killing curve of TS against C. albicans in every 2 h. The effect of TS on the content of intracellular reactive oxygen species (ROS) in C. albicans was analyzed by 2′,7′-dichlorofluorescin diacetate (DCFH-DA) staining, and the mitochondrial membrane potential (mtΔψ) was determined by rhodamine123 (RH123) staining. An ATP assay kit was utilized to determine the intracellular ATP levels after TS treatment. Results showed that TS-induced ROS accumulation and mitochondrial dysfunction contributed to the death of C. albicans cells. Further research demonstrated that VC could reinforce the fungicidal ability of TS. On the contrary, VE could antagonize the function of TS against C. albicans, which might guide the clinical application of TS. The results preliminarily elucidated the potential mechanisms of TS against C. albicans and might provide a potential option for the treatment of clinical Candida.     

基于P38MAPK信号通路探讨加味黄连膏对小鼠湿疹模型的影响

目的：基于P38MAPK信号通路探讨加味黄连膏对湿疹模型小鼠模型的治疗效果。方法：BALB/c小鼠60只,采用二硝基氯苯（1-chloro-24-dinitrochloro-benzene,DNCB）建立皮肤湿疹模型,随机分为6组,分别为空白对照组、空白基质（模型对照组）、复方醋酸地塞米松软膏（阳性对照组）及高、中、低剂量组（加味黄连膏治疗组）,对湿疹部位皮肤连续涂抹给药11d,以HE染色实验结果评价皮肤中炎症细胞浸润情况;Western Blot检测小鼠皮肤组织中p-p38和p38蛋白表达;qRT-PCR法检测皮肤组织中p38MAPKmRNA的表达;ELISA法检测血清中促炎细胞因子白细胞介素-6（interleukin 6,IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）、白细胞介素-2（interleukin 2,IL-2）、干扰素（IFN-γ）的水平。结果：药物治疗组与模型对照组相比,小鼠皮肤肿胀明显减轻;与模型对照组比较,血清中细胞因子（IL-2,IL-6,TNF-α和IFN-γ）的水平,加味黄连膏治疗组各组细胞因子水平均低于模型组（P<0.05,P<0.01）;且与模型组相比,加味黄连膏治疗组皮肤组织中p-p38MAPK蛋白水平明显下降,p-p38MAPK mRNA表达降低（P<0.05,P<0.01）。结论：加味黄连膏可以通过抑制p38MAPK信号通路的激活,抑制炎症反应,有效治疗皮炎湿疹。     

Antifungal activity of a new benzothiazole derivative against Candida in vitro and in vivo

The antifungal activity of 6-amino-2-n-pentylthiobenzothiazole (APB) against 26 strains of the genus Candida in vitro was studied. Susceptibility of 17 strains was IC₅₀ ≤ 40 μmol/ml, of 7 strains IC₅₀ = 40−80 μmol/ml and of 2 strains IC₅₀ = 80−200 μmol/ml. Generalized candidosis of mice was treated with APB (doses 50, 100, 250 mg/kg) and ketoconazole (KET, 50 mg/kg of body weight). The optimal dose of APB was shown to be 100 mg/kg; 25% of mice survived after 14 days as compared to control animals. C. albicans was not found in the kidney of the sacrificed mice. 80% of mice survived after KET therapy. However, C. albicans was present in the kidney in an amount of 10⁵−10⁶ CFU/g of tissue. C. albicans did not reappear in the kidney 7 days after the discontinuation of APB treatment, but it was found there after KET therapy.     

克班宁透皮贴剂对佐剂性关节炎大鼠的抗炎作用

目的：考察克班宁制备成透皮贴剂后对佐剂性关节炎大鼠的抗炎作用。方法：将60只雄性Wistar大鼠随机分为6组,分别为正常组、模型组、甲氨蝶呤（MTX）组、克班宁贴剂低、中、高剂量组,每组10只。除正常组外,其余大鼠右后足趾皮下注射0.1 mL弗氏完全佐剂（CFA）造模,给药组于腹部脱毛区域给予克班宁透皮贴剂,MTX组腹腔注射给予甲氨蝶呤,正常组、模型组给予空白透皮贴剂,隔天给药1次,连续给药20 d。观察各组大鼠体质量、关节肿胀度、关节炎指数和免疫器官指数的变化,检测血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）水平,苏木素伊红（HE）染色观察大鼠踝关节病理变化情况。结果：与正常组相比,模型组体质量增长较慢,关节炎指数明显升高,右后肢关节严重肿胀,血清TNF-α、IL-1β和IL-6水平显著升高（P<0.01）,踝关节可见严重滑膜炎症、软骨侵蚀及骨破坏。与模型组相比,各给药组大鼠体质量增加较快,关节肿胀度降低（P<0.01）、关节炎指数降低（P<0.01）,血清中TNF-α、IL-1β、IL-6水平降低（P<0.01）,踝关节炎细胞浸润减轻,软骨破坏减弱。结论：克班宁透皮贴剂能明显改善佐剂性关节炎大鼠关节炎症和病理损伤,降低血清中炎症因子水平,说明克班宁透皮贴剂对佐剂性关节炎具有一定的治疗作用。     

Thymol inhibits Candida albicans biofilm formation and mature biofilm

Candida albicans has a high propensity to develop biofilms that are resistant to traditional antifungal agents. Thymol is credited with a series of pharmacological properties including antimicrobial and antifungal effects. As C. albicans biofilms are known to be important factors underlying its virulence and pathogenicity, the aim of this study was to investigate whether thymol can interfere with biofilm formation as well as acting on mature biofilms. Tests of C. albicans strains ATCC 3153A and ATCC MYA 2876 showed that thymol interferes with the starting phases of biofilm production as well as with mature C. albicans biofilms. The metabolic activity of sessile cells was reduced by >90% at twice the minimum inhibitory concentration of planktonic cells. As biofilm is a multifactorial phenomenon, the multiple mechanisms of thymol (terpenes) could act on different steps in the evolution of mature biofilm.     

Antifungal susceptibility of candida isolates at the American University of Beirut Medical Center

For the first time from Lebanon, the antifungal susceptibility patterns of 70 consecutive clinical candida isolates (each from one patient) representing 48 C. albicans, 12 C. tropicalis, 6 C. parapsilosis, 2 C. kruseii, and 2 C. (Torulopsis) glabrata were studied against amphotericin B (AP), 5-fluorocytosine (FC), ketoconazole (KE), fluconazole (FL), and itraconazole (IT) using the Epsilometer test (E-test; AB Biodisk, Solna, Sweden). The MIC₉₀ (and MIC range, mg/l) determined, at 24 h incubation, for each antifungal agent against C. albicans were: AP 0.032 (≤0.002–0.064), FC 0.75 (0.023–2), KE 0.064 (0.002–>32), FL 2 (0.064–>256), and IT 0.19 (0.012–2), against C. tropicalis were: AP 0.016 (<0.002–0.047), FC 0.125 (0.023–0.19), KE 0.094 (0.012–0.19), FL 2 (0.5–2), and IT 0.5 (0.047–1) and against C. parapsilosis were: AP<0.002 (<0.002–0.002), FC 0.047 (0.003–0.5), KE 0.004 (0.002–0.004), FL 0.125 (0.032–0.19), and IT 0.004 (<0.002–0.004). Based on the NCCLS established MICs breakpoints, resistance was found among C. albicans to FL (MIC ≥6 mg/l) and IT (MIC ≥1 mg/l) in 6 and 4%, respectively, and among C. tropicalis to IT in 17% of the isolates. The susceptibility dependent upon dose (S-DD) was noted only to IT (MIC 0.25–0.5 mg/l) among C. albicans (8%) and C. tropicalis (58%). MICs determination at 48 h incubation were higher, showed more resistance rates and more endpoint trailing particularly with the azoles drugs. The small numbers of C. kruseii and C. glabrata preclude providing meaningful results. Thus, this study indicates that the antifungal susceptibility by E-test can be conveniently incorporated and performed in a hospital-based clinical laboratory. Despite the uniform susceptibility to AP and FC, resistance to azoles drugs is encountered in a range of 4–17% among candida isolates in this country.     

Effect of neonatal exposure to des in fas and BCL-2 expression in the adult mouse vagina and approach to the DES syndrome

Neonatal exposure to a synthetic estrogen, diethylstilbestrol (DES), induces the ovary-independent persistent proliferation of vaginal epithelium in mice. Mouse vagina at the estrous stage in the normal estrous cycle shows 10 to 15 layers of epithelium with superficial keratinized layers, and ovariectomy induces a decrease of these epithelial cell layers and lymphocyte infiltration. Thus, cell proliferation and regression of vaginal epithelium are ovary dependent. Neonatally DES-treated mouse vagina showed the same phenotype as normal mouse vagina at the estrous stage, but ovariectomy did not induce a decrease of epithelial cell layers or a lymphocyte infiltration, and there was persistent proliferation of vaginal epithelium even after ovariectomy. In addition, apoptotic cell death characterized by oligonucleosomal DNA fragmentation, Fas expression, and Bcl-2 downregulation were induced after ovariectomy in normal mouse vagina, but not in DES-treated mouse vagina. These results suggest that neonatal DES-exposure in mice prevents vaginal Fas-mediated apoptosis following the downregulation of Bcl-2, and these abnormalities in expression are involved in persistent proliferation of the vaginal epithelium.