The Effect of Itraconazole on the Vaginal Candidiasis under Different Immunity Conditions in Mice

To study the effect of itraconazole on the vaginal candidiasis caused by Candida under different immunity conditions, the fungal vaginitis model was established in female ICR mice by in- travaginal inoculation of suspension of C. albicans after the animal had been pretreated with estradiol or dexamethasone. Mice were divided at random into different groups and then treated with itracona- zole or IFN-γ given by gastrogavage. The burden of the fungus in the vaginal lavage fluids in the mice of the different groups was measured dynamically at different time points after the beginning of the drug treatment. The difference in the effect of itraconazole on the vaginal candidiasis between normal immune system group (group A) and control group (group D) was statistically significant (P<0.01). The difference in the efficacy of itraconazole among immunosuppressed group (group E), immuno-regulated group (group F) and the control group (group G) was statistically significant (P<0.01). But on the 5th, 6th, 7th, 9th, 11th day after the inoculation the average level of colony forming unit (CFU) of groups A, E and F showed no statistically significant difference (P>0.05). It is concluded that the efficacy of itraconazole in the treatment of the vaginal candidiasis under different immunity conditions (groups A, E and F) in mice were all good, but there was no difference in the anti-fungal effect of itraconazole among the three groups.     

Local Expression of Vaginal Th1 and Th2 Cytokines in Murine Vaginal Candidiasis under Different Immunity Conditions

To investigate the expression of vaginal Th1 and Th2 cytokines in rats with experimental vaginal candidiasis under different immune conditions, ICR murine vaginal candidiasis model was established and immno-suppressed murine models of vaginal cadidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls. The mRNA level of Th1 （IL-2）/Th2 （IL-4, IL-10, TGF-β1） cytokines in murine vaginal tissues was determined by RT-PCR. The cykotine in local tissues was increased to different extent under normal immune condition. IL-2 mRNA was increased during early stage of infection, while IL-10 was increased transiently during late stage of infection. TGF-β1 production was found to be increased persistently. At same time, the expression of IL-2 mRNA was suppressed in immno-suppressed group, and the level of IL-4, IL-10, and TGF-β1 were higher than the normal immunity group to different degree during infection. The high level of IL-2 mRNA during early stage of infection was associated with clearance of mucosal Candidia albicans （C. albicans）, and its expression suppressed leading to decreased clearance of mucosal C. albican in immuno-suppression. The over-expression of IL-4 and IL-10 could significantly enhance the susceptibility to C. albicans infection in mice.     

苦参凝胶治疗阴道假丝酵母病的药效学研究

目的：在动物模型上进行苦参凝胶治疗阴道假丝酵母病的药效学研究。方法建立阴道假丝酵母病BALB/c小鼠模型,分成模型组、空白凝胶组、苦参凝胶组和酮康唑乳膏组,每天阴道内给药1次,连续7 d,于治疗前和给药后第4、7天取阴道分泌物涂片染色观察。阴道冲洗液在体外培养白色假丝酶母。第7次给药后处死动物,取阴道组织进行病理检查。结果与模型组和空白凝胶组比较,苦参凝胶和酮康唑乳膏两组均可使阴道白色假丝酵母菌落数显著减少。苦参凝胶可增加阴道有益菌-乳杆菌数量,而酮康唑不增加。阴道冲洗液体外培养和计数结果表明,苦参凝胶和酮康唑乳膏可抑制白色假丝酵母生长（P＜0.01）。苦参凝胶还能抑制阴道黏膜水肿及炎性增生。结论苦参凝胶通过抑制白色假丝酵母生长、促进乳杆菌增殖、抑制阴道黏膜炎性增生等机制治疗白色假丝酵母阴道炎。     

不同条件下小鼠白念珠菌性阴道炎易感性的研究

目的研究不同条件下小鼠阴道粘膜对白念珠菌的易感性。方法建立免疫系统正常小鼠(雌激素化)与免疫抑制小鼠模型,建立初发与复发白念珠菌性阴道炎模型,对比观察不同干预措施下小鼠的一般生长情况、阴道灌洗液涂片细胞学检查结果、阴道组织病理学改变并测定其阴道灌洗液真菌载量。结果免疫抑制组各时点平均CFU水平均高于雌激素化组,且峰值后移,自第4天起两组相比有显著性差异(P<0.05)。雌激素化组、免疫抑制组各时点平均CFU分别与正常对照组相比均显示极显著性差异(P<0.01)。结论处于免疫抑制状态的小鼠阴道粘膜对白念珠菌更具有易感性;再次感染与初次感染不存在易感性差异。     

Local IL-23 Expression in Murine Vaginal Candidiasis and Its Relationship with Infection and Immune Status

IL-12 is a heterodi meric cytokine which con-sist of p40 and p35 and plays a key role in the dif-ferentiation of T helper1 ( Th1)cells[1].Its func-tions in murine vaginal candidiasis have beenrepor-ted[2 ,3].IL-23 is a new member inthe IL-12 familyof heterodi meric cytokines which is composed ofp40 and p19[4]. IL-23 shares some features withIL-12 but they also differ ,functionally and struc-turally . Many of its biological features ,such as itsroleinthe development of murine vaginal candid…     

The effect of itraconazole on the vaginal candidiasis under different immunity conditions in mice

Summary To study the effect of itraconazole on the vaginal candidiasis caused by Candida under different immunity conditions, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animal had been pretreated with estradiol or dexamethasone. Mice were divided at random into different groups and then treated with itraconazole or IFN-γ given by gastrogavage. The burden of the fungus in the vaginal lavage fluids in the mice of the different groups was measured dynamically at different time points after the beginning of the drug treatment. The difference in the effect of itraconazole on the vaginal candidiasis between normal immune system group (group A) and control group (group D) was statistically significant (P<0.01). The difference in the efficacy of itraconazole among immunosuppressed group (group E), immuno-regulated group (group F) and the control group (group G) was statistically significant (P<0.01). But on the 5th, 6th, 7th, 9th, 11th day after the inoculation the average level of colony forming unit (CFU) of groups A, E and F showed no statistically significant difference (P>0.05). It is concluded that the efficacy of itraconazole in the treatment of the vaginal candidiasis under different immunity conditions (groups A, E and F) in mice were all good, but there was no difference in the anti-fungal effect of itraconazole among the three groups. This project was supported by grants from the Science Research Foundation of Health Department of Hubei Province (No. JXIB048) and the Janssen Research Foundation.     

北京市昌平地区外阴阴道假丝酵母菌病的流行病学研究

目的探讨外阴阴道假丝酵母菌病的临床特征和相关危险因素。方法采用前瞻性研究方法,对945例阴道假丝酵母菌培养阳性者及945例真菌培养阴性者,进行病例对照研究。采用多因素Logistic回归分析外阴阴道假丝酵母菌病的影响因素。结果外阴阴道假丝酵母菌病以白色假丝酵母菌感染最为常见,占80.42%,25-35岁发病率最高。多因素Logistic回归分析显示：非月经期使用护垫（OR=3.457,95%CI：1.379-5.865）、抗生素应用（OR=3.279,95%CI：1.222-4.753）、1年内性伴侣数≥2个（OR=2.865,95%CI：1.467-3.456）、人工流产≥2次（OR=1.645,95%CI：0.964-3.563）是外阴阴道假丝酵母菌病发病的危险因素。结论外阴阴道假丝酵母菌病主要发生于性活跃期育龄妇女,以白色假丝酵母菌感染最为常见,非月经期使用护垫、抗生素应用、1年内性伴侣数≥2个、人工流产≥2次是外阴阴道假丝酵母菌病发病的高危因素。     

老年患者白假丝酵母菌基因分型与药敏试验分析

目的了解老年慢性阻塞性肺炎（COPD）患者白假丝酵母菌基因分型及药敏结果差异。方法对320株白假丝酵母菌进行25SrDNA基因分型,用ATB Fungus3进行药敏实验。结果320株白假丝酵母菌分成了A、B、C3型。A型对5-氟胞嘧啶耐药率高于B型和C型;C型对两性霉素全都敏感,敏感率高于A型和B型;C型对氟康唑、伊曲康唑的耐药率高于A型和B型;B型对伏立康唑耐药率高于A型和C型。结论白假丝酵母菌PCR分型法有较强的特异性,且快速简便;白假丝酵母菌基因型别对不同药物的敏感率有影响。     

复发性外阴阴道假丝酵母菌病患者阴道微生物的动态变化

目的 探究复发性外阴阴道假丝酵母菌病(RVVC)患者阴道菌群的动态变迁.方法 不同时间点采集RVVC患者(6例)以及正常对照女性(5例)阴道分泌物,分别对每个样本进行细菌总基因组DNA提取、16S rRNA V4区基因扩增及采用Illumina高通量测序技术对扩增的PCR产物进行测序等步骤,然后通过BIPES、TSC、GAST等程序,分析比较两组阴道菌群物种丰度和结构以及菌群动态变化.结果 正常对照女性阴道菌群以乳酸杆菌为主,其中惰性乳杆菌和卷曲乳杆菌比例相当,同时存在少量加德纳菌属、普氏菌属和其它菌属;或者以加德纳菌属、普氏菌属、奇异菌属、纤毛菌属等为主要菌属;而RVVC患者阴道菌群丰富度明显降低,以惰性乳杆菌为优势菌属,卷曲乳杆菌含量明显减少.正常对照女性阴道菌群随月经周期的变化出现波动,其中在月经期的波动最为明显,其优势菌属在月经周期中呈现相互交替或保持绝对优势的变化模式;而RVVC患者阴道菌群的波动性减弱,不随月经周期的变化而变化,且在疾病发作期和间歇期的菌群结构相似.结论 RVVC患者阴道菌群结构不随月经周期发生变化,在疾病发作期和间歇期相似.诱导卷曲乳杆菌产生或抑制惰性乳杆菌定植,从而恢复阴道菌群比例,可能可以治愈RVVC.     

兔肺白念珠菌病CT表现与病理变化的关系

目的:通过动物实验探讨急性期肺白念珠菌病CT表现与病理学改变的关系。方法:24只新西兰大白兔随机分为实验组(n=21)及对照组(n=3),实验组通过经皮气管穿刺法建立兔肺念珠菌病模型,对照组用同样方法注入生理盐水。于接种后每隔1 d行胸部CT扫描,观察CT表现,并与病理改变进行对照。结果:成功建立13例兔肺念珠菌病模型,首次CT阳性表现出现于接种后2~10 d,包括实变影10例：其中小叶性分布6例,病理表现为肺泡炎性渗出;叶段性分布4例,病理表现为肺组织坏死或出血性渗出。磨玻璃影6例,多与其他征象并发,病理表现为出血或炎性渗出;结节影3例,聚集于支气管血管束周围,病理表现为肉芽肿性炎症。结论:原发性肺白念珠菌病急性期CT表现以实变影最多见,其次为磨玻璃影和结节影,各种征象可并发,不具特征性。     

阴道分泌物念珠菌感染检测方法对比分析

目的 分析常规镜检、荧光PCR核酸扩增法和真菌显色培养法在阴道分泌物真菌检测结果的相关性.方法 选取2014-2016年于该院就诊的疑似阴道炎患者,收集镜检阴道分泌物真菌阳性和阴性标本各500例,用荧光PCR核酸扩增法鉴定念珠菌类型,并将100份荧光PCR核酸扩增法检测结果阳性标本进行真菌微生物培养,验证分型结果的正确率.结果 荧光PCR核酸扩增法和常规镜检一致性检验Kappa值为0.632,二者一致性差.500例患者阴道分泌物常规镜检阳性标本,荧光PCR核酸扩增法测得白色念珠菌感染382例(76.4％),光滑假丝酵母菌感染73例(14.6％),热带假丝酵母菌感染10例(2.0％),白色念珠菌合并光滑假丝酵母菌感染3例(0.6％),其他真菌感染32例(6.4％).500例患者阴道分泌物常规镜检阴性标本,荧光PCR核酸扩增法鉴定阳性共152例,其中白色念珠菌130例,光滑假丝酵母菌16例,热带假丝酵母菌6例.荧光PCR核酸扩增法与CHROMAgar快速显色法检测结果比较,差异无统计学意义(x2 =0.131,P=0.936).结论 对于有临床表现而镜检阴性的患者,建议行荧光PCR核酸扩增快速分型鉴定或真菌培养鉴定.     

阴道白假丝酵母菌基因型与体外药物敏感性研究

目的 研究不同基因型阴道假丝酵母菌对克霉唑、咪康唑和制霉菌素的体外药物敏感性.方法 以特异引物PCR法(INT-PCR)对151株致病白假丝酵母菌进行基因分型,参考美国临床和实验室标准协会(CLSI)抗真菌药敏实验标准(M27-A方案)以微量稀释法检测不同基因型菌株的药物敏感性.结果 根据扩增条带中是否存在450 bp和840 bp片段可将白假丝酵母菌分为A、B、C 3种基因型;克霉唑和咪康唑对A基因型菌株的最小抑菌浓度(MIC)值明显高于C基因型菌株,差异有统计学意义(P＜0.05);制霉菌素对不同基因型菌株的MIC值间差异无统计学意义(P＞0.05).结论 不同基因型白假丝酵母菌株对抗真菌药物的敏感性有明显差异,这种差异可能是临床上假丝酵母菌性外阴阴道炎治疗效果存在个体差异的原因之一.     

耳念珠菌不同条件下生长特性及体内毒性

目的 探讨耳念珠菌在不同条件下的生长特性、代谢特点及体内毒性特征。方法 以白色念珠菌为参照,测定并比较耳念珠菌与白色念珠菌在常规培养条件、不同pH值和不同盐含量下的生长情况;利用微量生化反应管测定两种念珠菌糖醇发酵情况;以四周龄裸鼠为实验动物,用随机数字表法分为3组,耳念珠菌感染组、白色念珠菌感染组和生理盐水对照组,5只/组。耳念珠菌感染组和白色念珠菌感染组取0.3 mL已调至5×109 cfu/mL菌液,对裸鼠进行灌胃处理,建立胃肠道感染模型,对照组用等量生理盐水灌胃,取肝脏、肾脏、肠、粪便和血液等标本,通过真菌培养和组织病理学变化分析耳念珠菌的体内分布和毒性特征。结果 耳念珠菌的对数生长期约为8~24 h,约在24 h后进入生长稳定期,最适生长的pH值范围为5~7,生长模式与白色念珠菌相同;耳念珠菌在浓度为5%和10%的NaCl培养基中生长情况优于白色念珠菌,能发酵葡萄糖、蔗糖、海藻糖和山梨醇;从裸鼠的粪便、血液、肝脏和肾脏组织中分离出耳念珠菌,肝脏载菌量最多为5.7 log10 cfu/g,其可造成肝组织和肠组织病理学改变,但病变程度比白色念珠菌弱。结论 耳念珠菌在弱酸或中性条件下最适宜生长,具有高耐盐性,在免疫抑制状态下感染机体后,存在突破肠屏障入血及随血流播散并导致组织病变的可能。     

治疗复发性外阴阴道假丝酵母菌病临床观察

目的观察根据药敏试验选择敏感抗真菌药口服联合氯喹那多-普罗雌烯阴道片治疗复发性外阴阴道假丝酵母菌病（RVVC）的疗效。方法将59例RVVC患者随机分为两组,采用强化和巩固治疗,观察组30例口服敏感药物,阴道放置氯喹那多-普罗雌烯阴道片,对照组29例口服氟康唑,阴道放置氯喹那多-普罗雌烯阴道片,治疗3个月。治疗后1个月、3个月复查。结果治疗后1个月观察总有效率,观察组100％,对照组69．0％（P〈0．01）,治疗后3个月观察复发率,观察组3．7％,对照组42．1％（P〈0．01）。结论治疗RVVC应进行真菌培养及药敏试验,选择敏感药物口服联合氯喹那多-普罗雌烯阴道片治疗调整菌群,改善阴道微环境可提高治愈率,减少复发。     

The Expression of Toll-like Receptor 2 and 4 mRNA in Local Tissues of Model of Oropharyngeal Candidiasis in Mice

Oropharyngealcandidiasis,commonlycalledthrush,wasaninfectiousdiseaseoccurringchieflyinprematurebirthordystrophicinfants.Adultcaseswerealmostconfinedtotheimmunosuppressedsubjects.Previousstudieshadconfirmedtheinnateimmunityisaveryimportanthostdefensemechan…     

白念珠菌和新生隐球菌系统感染裸小鼠模型的建立

目的建立白念珠菌和新生隐球菌系统感染裸小鼠模型。方法采用对裸小鼠腹部注射白念珠菌及隐球菌菌悬液的方法,观察记录1～2d内裸小鼠的毒性反应情况和死亡分布,并进行病理检查。根据寇氏法设计测定半数致死量(LD50),并检测感染前后脾脏自然杀伤(NK)细胞活性的变化。结果分别观察白念珠菌和新生隐球菌菌悬液对裸小鼠的急性毒性;检测到裸小鼠腹腔注射白念珠菌菌悬液的LD50为1.6×107cfu/ml,注射新生隐球菌菌悬液的LD50为2.0×107cfu/ml。白念珠菌、新生隐球菌感染裸小鼠时,脾脏组织NK细胞的活性下降。结论建立了白念珠菌和新生隐球菌系统感染裸小鼠模型,为讨论在T细胞为主的细胞免疫缺失的情况下,以B细胞NK细胞为主的体液免疫系统如何应对白念珠菌和新生隐球菌感染提供了一个极好的实验动物模型。     

Comparison of the Effects of Three Different Anti-fungus Drugs on Candida Albicans of Murine Vaginal Mucosa

To compare the therapeutic effects of three different anti-fungal drugs (i.e., terbinafine, fluconazole and intraconazole) in the treatment of experimental vaginitis caused by Candida albicans (C. albicans) in mice, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animal had been pretreated with estradiol. Mice were divided at random into different groups and then respectively treated with terbinafine, flucona- zole and intraconazole given by gastrogavage. The burden of the fungus in the vaginal lavage fluids in the mice of the different groups was measured dynamically at different time points after the begin- ning of the drug treatment. The fungal burdens in the vaginal lavage fluids taken at different time points from the mice treated with terbinafine were significantly higher than those taken at corre- sponding time points from mice treated with fluconazole or itraconazole (P<0.01). The fungal bur- dens in the vaginal lavage fluids taken from mice 1 week after the beginning of the treatment with terbinafine remained at a relatively high level. A dramatic drop in the fungal burden was noted in the vaginal lavage fluids taken on the 2nd day of the treatment from mice treated with itraconazole or flu- conazole group and the fungal burden on the 3rd day of the treatment in these mice were at a very low level, suggesting that fluconazole or itraconazole were highly effective for the treatment. How- ever, the difference in the therapeutic effect between the two drugs was not significant (P>0.05). Itraconazole or fluconazole, but not terbinafine, is very effective for the treatment of fungal vaginitis caused by C. albicans in mice.     

635例阴道分泌物涂片检测结果分析

[目的]探讨阴道分泌物涂片作为女性妇科常规筛查指标在正常人群健康体检中的意义。[方法]选取大连医科大学女性职工635人,由体检中心妇科医生采取阴道分泌物标本直接涂片,干燥后由专业医检人员采用多功能染色液做染色检查,由显微镜在一张涂片上同时作滴虫、念珠菌、纤毛菌、线索细胞、阴道清洁度等检查。[结果]清洁度（Ⅲ～Ⅳ度）检出298例（47%）;念珠菌检出18例（3%）,线索细胞检出77例（11%）;滴虫未检出;混合感染4例（0.6%）。清洁度（Ⅰ～Ⅱ度）组与清洁度（Ⅲ～Ⅳ度）组比较,念珠菌检测结果后者明显高于前者,差异有非常显著性意义（P〈0.005）;线索细胞检出结果后者高于前者,差异有显著性意义（P〈0.05）;混合感染后者高于前者,差异无显著性意义（P〉0.05）。清洁度（Ⅲ～Ⅳ度）检出数25～50岁组与51～89岁组比较,前者明显高于后者,差异有非常显著性意义（P〈0.005）,而比较两组念珠菌及线索细胞检出数前者高于后者,但差异无显著性意义（P〉0.05）。[结论]女性阴道分泌物涂片作为妇科常规体检项目,有利于及时发现疾病和早期治疗,对成年女性定期进行体检是非常有必要的。     

Study on the role of interleukin-4 in experimental murine systemic candidiasis

Candida albicans is the most common oppor-tunistic fungal pathogen,and systemic Candidiasis isgetting increasingly dangerous to patients with im-mune dysfunctions[1] . Interleukin- 4(IL- 4) ,mainlysecreted by activated CD 4T cells,can enhance thedifferentiation from Th0 cells to Th2 cell[2 ] ,inhibitthe differentiation from Th0 cells to Th1cells and theability of neurtrophils and macrophages to phagocy-tose or kill Candida albicans[3 ,4 ] . The detection ofthe level of IL- 4secreted by i…