氟康唑治疗阴道念珠菌病

目的：探讨国产氟康唑对阴道念珠菌的疗效。方法：对９０例阴道念珠菌病人（年龄３３±ｓ５ａ）分离的９０株菌株进行药敏比较，随机分为３组（每组３０例）。国产和进口氟康唑组分别用国产和进口氟康唑注射液２００ｍｇ，ｉｖ，ｑｄ，连用２ｄ；制霉菌素组用制霉菌素０．５ＭＵ，放入阴道，ｑｄ，连用７ｄ。结果：念珠菌对国产氟康唑的敏感率及治疗有效率均达９７％，与进口氟康唑无差异，Ｐ＞０．０５，２药治疗有效率均非常明显优于制霉菌素（Ｐ＜０．０１）。结论：国产氟康唑抗真菌作用与进口氟康唑疗效相同，并优于制霉菌素。     

氟康唑阴道缓释片的制备及体外释放的研究

目的：制备氟康唑阴道缓释片,选择最优缓释片处方,为下一步体内药动学实验和其它各项研究奠定基础。方法：以氟康唑为主药,采用三因素三水平,正交试验设计方法考察MCC,HPMC,Carbopol对氟康唑缓释片释放的影响。应用紫外分光光度法测定药物片剂的释放度和片剂中氟康唑的含量。结果：确定处方FCZ50mg Carbopol 100mg MCC 150mg。HPMC 90mg淀粉210mg为最佳处方,片重0.6g。HPMC为该片剂缓释作用的主要影响因素,卡波姆影响作用次之。结论：该制剂有望成为治疗阴道真菌感染的有效制剂。     

三唑类抗真菌药物致急性胰腺炎不良反应文献分析

目的 探讨三唑类抗真菌药物致急性胰腺炎不良反应的临床特点、发生机制及防治措施,为临床合理用药提供参考。方法 检索三唑类抗真菌药物自上市以来国内外发表的关于其引起急性胰腺炎不良反应的文献,按照患者性别、年龄、饮酒史、用药情况、不良反应发生的时间、临床表现及处理方法等进行统计分析。结果 共纳入8篇文献,涉及11例患者,18岁以下儿童所占比例最高（36.36%）。不良反应发生时间最短的为用药12 h,最长的为用药10周后,停药或减量或更换药品后不良反应症状可痊愈或好转。结论 三唑类抗真菌药物致急性胰腺炎不良反应需引起医务人员重视,尤其是应用于儿童时。建议临床在应用三唑类抗真菌药物时,严格按照说明书的推荐剂量和疗程给药,并密切监测患者是否出现急性胰腺炎的症状。     

反相高效液相色谱法测定氟康唑搽剂中氟康唑含量

目的建立测定氟康唑搽剂含量的反相高效液相色谱（RP—HPLC）法。方法色谱柱为Diamonsil C18柱（250mm×4．6mm,5μm）,流动相为磷酸盐缓冲液（pH=7．0）-甲醇（55：45）,检测波长为261nm。结果氟康唑进样量的线性范围为1．2～6．0μg,平均回收率为99．73％,RSD=0．30％（n=6）。结论该法简便、准确、重现性好,可用于氟康唑搽剂的含量测定。     

薄层色谱扫描法检测氟康唑对真菌麦角固醇生物合成的影响

目的：用薄层色谱扫描法检测抗真菌药物氟康唑对真菌麦角固醇生物合成的影响。方法：真菌与不同浓度氟康唑温育24h后计数、称量、皂化,提取真菌中难皂化脂,薄层层析,扫描测定其中的麦角固醇和羊毛固醇含量。结果：随着氟康唑浓度的增加,真菌中的麦角固醇含量逐渐减少,而羊毛固醇含量迅速增加。当抑制85％的麦角固醇生物合成时,真菌生长繁殖的受抑率也在85％左右。结论：薄层色谱扫描法能准确测定真菌中的麦角固醇和羊毛固醇含量,可用于考察抗真菌药物对真菌麦角固醇生物合成的影响,为新化合物的体外抗真菌活性筛选和作用机制研究提供了新方法。     

Die In-vitro-Empfindlichkeitsprüfung von Candida-Species gegenüber Fluconazol im Mikrodilutionstest unter Einsatz von Alamar Blue

ZUSAMMENFASSUNG. Die Fluconazoltestung von Candida -Spezies erfolgte im Mikrodilutionstest mit supplementiertem HR-Medium. Zur Verbesserung der visuellen MHK-Bestim-mung wurde der Redox-Indikator Alamar Blue 10%ig dem Testmedium zugesetzt. Die gute Reproduzierbarkeit des Testverfahrens konnte mit Kontrollstümmen und Patientenstämmen nachgewiesen werden. Die Eignung dieser Methode in der Routinediagnostik zeigte sich bei der In-vitro-Empfindlichkeitsprüfung von 279 Candida -Isolaten von Patienten mit einer massiven Candida -Kolonisierung bzw. einer Endomykose.
Die Candida -Spezies variierten in ihrer Empfindlichkeit gegenüber Fluconazol. Während 96% der. C.-albi-cans -Isolate sensibel waren, fanden wir bei 55% der C.-glabrata -Stämme eine verminderte Empfindlichkeit, und 26% dieser Spezies waren resistent (MHK > 25 μg/ml). Neun der elf isolierten C.-krusei -Stämme waren Fluconazol-resistent.
Summary. The investigation of susceptibility of Candida species to fluconazole was performed in microdilution to a supplemented HR-medium. The sufficient reproducibility of the test was verified using special control isolates and isolates of patients. The excellent applicability of the method in routine diagnostics was evaluated by in vitro testing of susceptibility of 279 Candida isolates from patients being colonised or suffering from endomycoses. The Candida species showed different suceptibility against fluconazole: 96% of the C. albicans isolates were sensitive, 55% of the C. glabrata isolates had a reduced sensitivity, and 26% were resistant against fluconazole (MIC > 25 μg/ml). C. krusei isolates were highly resistant (9 of 11 strains).     

白色假丝酵母菌耐药性与耐药基因表达及蛋白酶的关系

目的研究呼吸道白色假丝酵母菌耐药性与耐药相关基因表达及细胞外蛋白水解酶的关系。方法用NCCLSM27-A方案中的微量液基稀释法检测99株呼吸道分离的白色假丝酵母菌对氟康唑和伊曲康唑的最小抑菌浓度(MIC),RT-PCR半定量检测耐药相关基因CDR1和MDR1的表达,牛血清清蛋白平板法检测细胞性蛋白酶活力。结果99株菌对氟康唑的耐药率为4%,对伊曲康唑的耐药率为12.1%,CDR1的表达在氟康唑的剂量依赖性敏感组高于敏感组和耐药组(P<0.05),蛋白酶的活力在氟康唑剂量依赖性敏感组高于敏感组(P<0.05)。结论菌株的耐药性除与CDR1的过表达有关外,还与其他耐药机制有关,耐药程度不同的菌株细胞性蛋白酶活力有差别,提示菌株的耐药性与毒力之间可能有关联。     

Anti-Candida,docking studies,and in vitro metabolism-mediated cytotoxicity evaluation of Eugenol derivatives

The high morbidity and mortality rates of Candida infections, especially among immunocompromised patients, are related to the increased resistance rate of these species and the limited therapeutic arsenal. In this context, we evaluated the anti-Candida potential and the cytotoxic profile of eugenol derivatives. Anti-Candida activity was evaluated on C. albicans and C. parapsilosis strains by minimum inhibitory concentration (MIC), scanning electron microscopy (SEM), and molecular docking calculations at the site of the enzyme lanosterol-14-α-demethylase active site, responsible for ergosterol formation. The cytotoxic profile was evaluated in HepG2 cells, in the presence and absence of the metabolizing system (S9 system). The results indicated compounds 1b and 1d as the most active ones. The compounds have anti-Candida activity against both strains with MIC ranging from 50 to 100 μg ml⁻¹. SEM analyses of 1b and 1d indicated changes in the envelope architecture of both C. albicans and C. parapsilosis like the ones of eugenol and fluconazole, respectively. Docking results of the evaluated compounds indicated a similar binding pattern of fluconazole and posaconazole at the lanosterol-14-α-demethylase binding site. In the presence of the S9 system, compound 1b showed the same cytotoxicity profile as fluconazole (1.08 times) and compound 1d had 1.23 times increase in cytotoxicity. Eugenol and other evaluated compounds showed a significant increase in cytotoxicity. Our results suggest compound 1b as a promising starting point candidate to be used in the design of new anti-Candida agent prototypes.