妊娠期妇女外阴阴道念珠菌病的病原学和治疗研究

目的 调查孕妇外阴阴道念珠菌病(vulvovaginal candidiasis，VVC)的发病率，对检出的VVC进行病原学和治疗研究。方法 连续对产科门诊1000例孕妇进行VVC发病情况调查。对分离的念珠菌进行体外抗真菌药物敏感试验。对66例VVC患者应用咪康唑栓治疗，400mg／d，6d为一疗程。结果 孕妇VVC的发病率为12．7％(127／1000)。37．4％(374／1000)的孕妇以往有VVC病史，0．6％的孕妇为复发性VVc。127例VVC中，白念珠菌、光滑念珠菌、热带念珠菌和克柔念珠菌分别占87．1％、9．9％、1．5％和1．5％。有4例患者同时感染2种念珠菌。114株白念珠菌对咪康唑、克霉唑、氟康唑、伊曲康唑、制霉菌素耐药率依次为10．5％、2．6％、6．1％、7．9％和0。13株光滑念珠菌对咪康唑和制霉菌素均敏感，对克霉唑、伊曲康唑和氟康唑均敏感或剂量依赖敏感。应用咪康唑栓治疗的患者在治疗完成后1～2周及4～6周的病原学治愈率分别为84．8％和80．3％。结论 VVC是孕妇的常见病，白念珠菌仍然是主要致病菌，其次为光滑念珠菌。常用抗真菌药物对引起VVC的念珠菌存在不同程度的耐药率，应用咪康唑栓治疗孕妇VVC效果满意。     

Biochemical and ultrastructural alterations produced by miconazole and econazole in Trypanosoma cruzi

Miconazole and econazole, two fungicide imidazole derivatives, completely inhibited growth of Trypanosoma cruzi (Tulahuen strain) at concentrations of about 20 muM. Culturing of T. cruzi in the presence of lower doses of imidazole derivatives produced: decrease of 5,7-diene sterol content in epimastigotes (including ergosterol); disappearance of the nuclear chromatin, vacuolization and decrease in the electron density of the cytoplasm; selective surface alterations as revealed by an increased response to wheat-germ- and phytohemagglutinin. At variance with the effect of miconazole on Candida (De Nollin et al. (1977) Antimicrobial. Agents Chemother. 11, 500-513), miconazole and econazole, under the experimental conditions used, did not increase the rate of hydrogen peroxide generation by T. cruzi.     

Polymeric versus lipid nanocapsules for miconazole nitrate enhanced topical delivery: in vitro and ex vivo evaluation

Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(ε-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and in vitro drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and ex vivo permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi’s diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less ex vivo permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 µg/cm²) than LNCs (12.7 ± 1.52 µg/cm²). The antifungal activity of the PNCs was high 19.07 mm compared to 11.4 mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections.     

4厂家硝酸咪康唑乳膏的体外透皮性比较

目的:比较不同厂家(ZH、CZ、SD、FJ)硝酸咪康唑乳膏的体外透皮速度大小。方法:采用Franz扩散池收集样品,用高效液相色谱法测定24h内单位面积的累积体外透皮量,并计算透皮速率。结果:透皮速度依次为ZH>CZ>SD>FJ,且最高与最低相差9.7倍。结论:采用不同基质制备的同一制剂,其透皮性有差异。     

HPLC测定硝酸咪康唑尿素乳膏中硝酸咪康唑的含量

目的 建立高效液相色谱法测定硝酸咪康唑尿素乳膏中硝酸咪康唑的含量.方法Agilent TC-C18(4.6mm×150 mm,5μm)色谱柱;流动相0.5%醋酸铵溶液·乙腈和甲醇(11)混合液(16.583.5);流速1.0 mL·min-1;检测波长230 nm.结果硝酸咪康唑在0.192 8～1.928 4 mg·mL-1的浓度内线性关系良好(r=0.999 1),平均回收率为98.21%.RSD=1.41%(n=9).结论 此法操作简便、结果准确、精密度好,可用于硝酸咪康唑尿素乳膏的质量控制.     

复发性念珠菌外阴阴道炎发病的相关因素及不同的治疗方法

目的 探讨复发性念珠菌外阴阴道炎发病的相关因素并观察微生态制剂对其治疗效果的影响.方法 将复发性念珠菌性外阴阴道炎576例通过问卷调查、化验检查得出：滥用抗生素、合并其他病原菌感染、经常阴道冲洗各占发病因素30%、25%和19.1%;同时对其中226例随机分为对照组（单独抗真菌治疗）与治疗组（抗真菌治疗联合微生态制剂）.治疗前、后1周、1个月、2个月进行临床、真菌学疗效分析.结果 经抗真菌治疗后,临床、真菌学疗效较好.治疗后2个月,治疗组有效率明显高于对照组（x^2=16.61,P＜0.01）,复发率低.结论 联合微生态制剂治疗复发性念珠菌性外阴阴道炎效果良好.     

Reduced glutathione, dithiothreitol and cytochrome P-450 inhibitors do not influence hypoxic chemosensory responses in the rat carotid body

Glomus cells and carotid sinus afferents are anatomically connected, and the chemical events in the glomus cells are expected to be conveyed reflexly as afferent signals. Accordingly, K(+) channel inhibition of the glomus cell membrane is expected to be followed by excitation of the afferents. In order to test the redox inhibition of K(+) channels of glomus cells by reduced glutathione (GSH), dithiothreitol (DTT) and by cytochrome P-450 inhibitors (clotrimazole and miconazole), we measured the carotid sinus nerve (CSN) discharge using an in vitro perfused adult rat carotid body (CB) in the presence and absence of these chemicals which are expected to excite the afferents. Our findings were that these agents did not stimulate the CSN activities during normoxia and kept the hypoxic responses intact. These results led us to conclude that the redox modulation of glomus cells was not conveyed to the afferents, and this functional disconnection did not support the redox hypothesis of O(2) chemoreception in the whole carotid body.     

达克宁霜剂用于小儿尿布皮炎的观察

目的：探讨达克宁霜剂用于尿布皮炎的护理与防治。方法：将52例尿布皮炎患儿按1：1随机分组,分为治疗组（达克宁霜剂组）和对照组（鞣酸软膏组）。治疗组采用每次更换尿布后,温水清洗臀部,达克宁霜剂涂擦,均匀覆盖在患处皮肤;对照组采用鞣酸软膏涂擦患处。两组分别在治疗护理7日后观察疗效。结果：统计学分析,卡方检验P〈0.05,两组患儿的疗效和恢复时间均有显著差异;达克宁霜剂组总有效率好于鞣酸软膏组。结论：应用达克宁霜剂涂擦患处,在促进患儿康复、减轻痛苦、缩短病程、简单适用等方面,优于传统方法。     

The contraceptive vaginal ring, NuvaRing, and antimycotic co-medication

We investigated the effect of antimycotic co-medication on the systemic exposure to etonogestrel (ENG) and ethinylestradiol (EE) released from the contraceptive vaginal ring, NuvaRing. Different formulations of miconazole nitrate and single as well as multiple dosing were investigated during two separate randomized, open-label, crossover studies. The first study recruited 12 women to compare the effects of co-use of NuvaRing and a single dose of antimycotic to NuvaRing alone. The second study recruited 14 women to compare the effects of multiple doses of an antimycotic vaginal suppository to an antimycotic vaginal cream equivalent. Co-administration of all three antimycotic formulations resulted in a slight increase in systemic exposure to ENG and EE over time, with suppositories having a more pronounced effect than a cream formulation in the multiple-dosing study. The increases in serum levels observed with the different antimycotic formulations are not expected to compromise NuvaRing's contraceptive efficacy or tolerability.     

Influence of the roll compactor parameter settings and the compression pressure on the buccal bio-adhesive tablet properties

Miconazole buccal tablets were prepared via a dry granulation process. By applying a factorial design (2⁴), the roll compactor parameters (compaction force, gap between the rolls, type of the rolls (smooth, ribbed) and the sieve aperture) were optimised for the tablet strength. The compaction force and the roll type significantly affected the tablet strength. Afterwards, a quarter fractional factorial design (2^5-2) was applied, consisting of the four compactor parameters and additionally the compression pressure, in order to optimise these parameters for the dissolution profile and the buccal bio-adhesion characteristics (bio-adhesive force and energy). In order to evaluate the dissolution profiles properly, the similarity factor between sample and a zero-order release reference profile was used. The compression pressure and the roll type significantly affected the dissolution profile. The sieve aperture had a significant effect on the buccal adhesion properties and the compaction force had a significant effect on the dissolution profile and the bio-adhesive energy. The gap between the rolls affected the bio-adhesive force significantly.