烟酰胺及联合伊曲康唑体外抗烟曲霉活性研究CSCD

目的检测烟酰胺及联合伊曲康唑的抗烟曲霉活性。方法采用CLSI推荐的M38-A2肉汤稀释法及棋盘式微量液基稀释法检测烟酰胺与伊曲康唑对15株烟曲霉的最低抑菌浓度(MIC)和协同指数(FICI),通过荧光定量PCR检测加药后烟曲霉的相关基因表达水平。结果烟酰胺对烟曲霉具有抑制作用,MIC为12.8~25.6 mg/mL;烟酰胺与伊曲康唑具有协同抗菌作用,协同指数<0.5;膜蛋白相关基因与外排泵相关基因在烟酰胺单用及联合用药下,表达下调。结论烟酰胺具有抑制烟曲霉及增强伊曲康唑抗烟曲霉的作用,抑菌及增效作用与下调烟曲霉膜蛋白基因和外排泵基因表达有关。     

伊曲康唑治疗胃部真菌感染1例

患者因患陈旧性心肌梗死、脑梗塞,长期服药致胃黏膜损伤,同时合并糖尿病,引发胃部真菌感染,经口服伊曲康唑200mg,2次／d,治疗3周后痊愈。     

伊曲康唑治疗花斑癣52例疗效观察

我们从1999年4月～2000年3月用伊曲康唑治疗花斑癣52例,获得满意疗效,现将结果报告如下 1材料与方法 1.1临床资料门诊选择经临床和真菌镜检确诊的花斑癣共52例.     

伊曲康唑治疗甲真菌病的疗效观察

本组于2000年3月～2005年6月对128例甲真菌病患者给予口服伊曲康唑胶囊（商品名：斯皮仁诺）治疗,采用间歇冲击疗法,治疗结果报告如下。 1 资料与方法 1．1 临床资料 128例患者均为门诊患者,男性73例,女性55例,年龄17～72岁,平均年龄36．5岁,病程2个月～45年。其中指甲真菌感染者32例（病甲48个）,趾甲真菌感染者72例（病甲377个）,指甲、趾甲均真菌感染者24例（病指甲35个,病趾甲103个）。近端甲下真菌病37例,远端甲下真菌病61例,白色甲下真菌病30例。其中32例伴有手癣,67例伴发足癣,19例伴发甲沟炎,2例伴有股癣。真菌直接镜检,镜下均可见菌丝及孢子。     

国产伊曲康唑在中国10年的应用

目的：概述国产伊曲康唑（商品名“美扶”）在国内10 a 的应用情况,为其在国内临床规范、合理应用提供循证学证据。方法检索复习10 a 来国产伊曲康唑在国内应用的各类文章。结果共计检索筛选获得48篇文献,手足体股癣10篇,共计治疗手足癣451例,总有效率为90.91℅;花斑癣6篇,共治疗340例,总有效率为92.94℅;糠秕孢子菌毛囊炎5篇,共治疗238例,单疗程单用国产伊曲康唑总有效率为71.05℅;头癣2篇,总有效率为80.00℅;甲真菌病6篇,治疗指甲甲真菌病患者2疗程法总治愈率为78.95℅（135例/171例）,3疗程法治愈率为82.60℅（19例/23例）,治疗趾甲真菌病患者总治愈率为79.94℅（275例/344例）;生殖器念珠菌病21篇,共治疗念珠菌性外阴阴道炎2260例,总治愈率为94.32℅,有效率为97.27℅,男性念珠菌病409例,总痊愈率75.04℅;头皮脂溢性皮炎2篇,总痊愈率为81.18℅（69例/85例）;小儿皮肤真菌病1篇,痊愈率68.2℅（30例/44例）;真菌性眼炎1篇,56例患者全部有效。主要不良反应为胃肠道不适,其次为头晕头痛、乏力、食欲下降、可逆性肝酶升高等,总不良反应发生率为6.95℅。结论国产伊曲康唑在多种真菌病有效率高,不良反应小。     

五环三萜类柴胡皂苷单体对白念珠菌伊曲康唑耐药株活性研究

目的 从柴胡中提取具有抗真菌活性的五环三萜类单体Bp3,研究该单体对伊曲康唑耐药白念珠菌菌株的作用及其与伊曲康唑的相互作用.方法 参照CLSI标准,采用棋盘微量稀释法,测定单用Bp3、伊曲康唑及两者联合使用时对20株伊曲康唑耐药白念珠菌菌株的MIC,计算部分抑菌浓度指数(FIC),判定两药相互作用.结果 单独用药时Bp3及伊曲康唑对伊曲康唑耐药白念珠菌菌株MIC的几何均数值(GM值)分别为1.941 μg/mL和1.008 μg/mL.联合用药时Bp3和伊曲康唑的GM值分别降低为1.189 μg/mL和0.346 μg/mL.2种药物单用和联合使用时MIC值差异均有统计学意义(P＜0.05),联用时在20株耐药株均表现为协同或相加作用.结论 五环三萜类单体Bp3对白念珠菌伊曲康唑耐药株有一定的抑制作用,且与伊曲康唑有协同或相加作用.     

口服伊曲康唑治疗婴儿泛发性皮肤黏膜念珠菌病1例

随着低体重儿存活率的提高以及抗生素的广泛应用,婴儿皮肤、黏膜念珠菌病的患病率在逐年上升.本院1例9个月男婴,因喂养不当而诱发泛发性皮肤、黏膜念珠菌病,采用口服伊曲康唑100 mg隔日1次,治疗14 d后痊愈.     

伊曲康唑治疗严重烧伤患者真菌感染的疗效分析

目的 评价伊曲康唑治疗严重烧伤患者真菌感染的疗效及其安全性。方法 采用开放、随机研究单组评估设计,治疗前2d：伊曲康唑注射液2次／d,间隔12h,200mg／次。此后1次／d,剂量200mg,间隔24h,1疗程14d。试验结束后口服伊曲康唑口服液维持治疗至少4周,2次／d,200mg／次。结果 伊曲康唑治疗23例严重烧伤患者总有效率为60．87％;本组86．96％的患者临床疗效为改善;63．64％的患者真菌学疗效为真菌清除;8．70％和52．17％的患者综合疗效分别为痊愈和显效,未发生不良反应。结论 伊曲康唑治疗严重烧伤患者真菌感染有良好的疗效、不良反应少。     

伊曲康唑胶囊上市16周年安全性资料回顾

伊曲康唑（斯皮仁诺,西安杨森制药有限公司）属于三唑类抗真菌药物,其作用机制和其他唑类药物一样,主要干扰真菌细胞膜麦角固醇的生物合成。但伊曲康唑对真菌细胞色素P450酶系统亲和力强,选择性强,而对人类细胞色素P450酶系统亲和力差,故毒性较低,且没有对内分泌的影响。伊曲康唑目前有3种制剂可供临床使用,如胶囊、口服液和静脉注射液,多数临床研究显示对浅部和深部真菌感染有良好效果,     

不同剂量伊曲康唑口服联合外用抗真菌药物治疗足癣的疗效观察

目的比较伊曲康唑200mg／d与400ne／d口服联合外用复方酮康唑乳膏治疗足癣的疗效。方法36例非角化型足癣患者随机分为2组,分别采用不同剂量伊曲康唑口服联合外用复方酮康唑乳膏治疗1周,比较停药2周时两组患者的治疗有效率和真菌清除率。结果200mg组治疗有效率为83．3％（15／18）,痊愈率为55．6％（10／18）,真菌清除率为66．7％（12／18）;400mg组治疗有效率为88．9％（16／18）,痊愈率为55．6％（10／18）,真菌清除率为77．8％（14／18）;统计学分析两组之间差异无显著性。结论伊曲康唑200mg／d口服即可有效治疗非角化型足癣,增加伊曲康唑口服剂量至400mg/d并不能提高治疗效果。     

伊曲康唑联合特比萘芬治疗孢子丝菌病疗效及其对病原真菌体外抗菌活性研究

目的 初步探讨伊曲康唑和特比萘芬联合治疗孢子丝菌病的疗效,评价两药体外联合对申克孢子丝菌菌丝相和酵母相的抗菌活性.方法 口服伊曲康唑200mg/d和特比萘芬250mg/d治疗孢子丝菌病;体外联合药敏试验采用棋盘微量稀释法,计算分数抑菌浓度(FIC)指数判定两药相互作用具有协同、拮抗或无关作用.结果 伊曲康唑和特比萘芬联...     

Comparison of in vitro antioxidant and antiradical activities of L-tyrosine and L-Dopa

Summary. Phenolic compounds are interesting because of their antioxidant properties. In the present study, the antioxidant properties of L-tyrosine as a monophenolic and L-Dopa as a diphenolic amino acid were investigated by using different antioxidant assays: (i) 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^•) scavenging; (ii) 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation decolorization assay; (iii) total antioxidant activity by ferric thiocyanate method; (iv) ferric ions (Fe³⁺) reducing power; (v) superoxide anion radical (O₂ ^•−) scavenging; (vi) hydrogen peroxide (H₂O₂) scavenging, and (vii) ferrous ions (Fe²⁺) chelating activities. Butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol and trolox, a water-soluble analogue of tocopherol, were used as the reference antioxidant compounds. At the same concentration (20 μg/mL), L-tyrosine and L-Dopa showed 30.6 and 67.9% inhibition of lipid peroxidation of linoleic acid emulsion, respectively. On the other hand, BHA, BHT, α-tocopherol and trolox indicated inhibitions of 74.4, 71.2, 54.7 and 20.1% on the peroxidation of linoleic acid emulsion, respectively, at the above-mentioned concentration. In addition, L-tyrosine and L-Dopa had an effect on DPPH radical scavenging, ABTS radical scavenging, superoxide anion radical scavenging, H₂O₂ scavenging, total ferric ions reducing power and metal chelating on ferrous ions activities.     

In vitro activities of voriconazole, fluconazole, itraconazole and amphotericin B against non Candida albicans yeast isolates

Antifungal susceptibility testing was performed on 197 yeast isolates from the BCCM/IHEM biomedical fungi and yeasts collection (Belgian Co-ordinated Collections of Micro-organisms / IPH-Mycology) to study the in vitro activity of voriconazole against fluconazole, itraconazole and amphotericin B. MICs of the four antifungal agents were determined by an adapted NCCLS M27-A microdilution reference method. MIC readings were visually and spectrophotometrically determined. Optical density data were used for calculation of the MIC endpoints. For amphotericin B, the MIC endpoint was defined as the minimal antifungal concentration that exerts 90% inhibition, compared to the control growth. The azoles endpoints were determined at 50% inhibition of growth. The MIC distribution of voriconazole susceptibilities showed that 193 isolates had a MIC < or = 2 microg/ml and 185 a MIC < or = 1 microg/ml. Cross-tabulation of voriconazole, fluconazole, and itraconazole MICs indicated that voriconazole MICs raised with fluconazole and itraconazole MICs. The in vitro data obtained in this study suggest that voriconazole may also be effective treating yeast infection in patients infected with fluconazole or itraconazole resistant isolates.     

Comparison of the in vitro transforming activities of human papillomavirus types.

The association of certain human papillomavirus (HPV) types with the majority of human cervical carcinomas suggests a role for the virus in the development of this type of cancer. In this paper, we have examined the transforming properties of several HPV types where the early region genes of the virus are under the control of a strong heterologous promoter and show that major differences exist between the HPV types in their ability to transform primary rat kidney epithelial cells in conjunction with an activated ras oncogene. Those HPV types most commonly found in carcinomas--types 16, 18, 31 and 33--are capable of co-operating with ras to transform primary cells, but those types most commonly found in benign lesions--types 6 and 11--are not. We further demonstrate that the E7 gene of HPV16 by itself is sufficient to co-operate with activated ras to produce transformed cells which are tumorigenic in immunocompetent animals.     

Comparison between in vivo and in vitro enzyme activities in continuous and batch fermentations of Clostridium acetobutylicum

Summary In vitro activities of key enzymes and related parameters (ATP and ADP concentrations, intracellular pH (pH _i ), cell volume and the transmembrane pH) in various continuous and batch fermentations of Clostridium acetobutylicum were studied in order to investigate the regulation (genetic vs. enzyme level) of the solventogenesis process. In vitro activities varied significantly among an acidogenic (glucose limited) and three solventogenic (an iron limited, a CO gassed and a biomass recycle) continuous fermentations. However, in vitro enzyme activities did not correlate with in vivo specific production rates in continuous cultures indicating that solvent formation is regulated primarily at the enzyme level. Carbon monoxide (CO) gassing of an acidogenic continuous culture resulted in butyrate uptake without acetone formation due to inactivation of the acetoacetate decarboxylase by CO. In continuous, and to some extent in batch cultures, butyrate can be taken up via the reversal of the butyrate kinase and phosphotransbutyrylase pathway. Solvent formation in batch fermentations is both a result of enzyme induction and regulation. Acetone formation and the induction of acetoacetate decarboxylase occur simultaneously whereas both alcohol dehydrogenases are induced several hours before initiation of alcohol production. Finally, the levels of intracellular and related cell parameters (pH _i , pH, ATP and ADP concentrations) are discussed and related to the possible mechanisms of solventogenesis.     

In vitro susceptibility of fungal and yeast clinical isolates to itraconazole and voriconazole

The interest on the in vitro susceptibility to itraconazole has recently increased due the availability of the intravenous formulation. In this study, comparative MICs of this antifungal with voriconazole were carried out in 62 clinical isolates of filamentous fungi and 100 yeasts isolates using the NCCLS microbroth methods described in M38-A and M27-A2 documents. A MIC90 of 0.125 micrograms per ml was observed for itraconazole and voriconazole against Aspergillus fumigatus. Higher susceptibility to itraconazole was found for the filamentous form of Sporotrhix schenckii (p = 0.001). Voriconazole was more effective against Scedosporium apiospermium while Scedosporium prolificans isolates were resistant to both azoles. Some isolates of Rhizopus stolonifer were susceptible to itraconazole and resistant to voriconazole, but without statistical significance. Susceptibility of nine species of Candida was similar for both triazoles used in this study. However, Candida glabrata was more susceptible to voriconazole. Some fluconazole-resistant Candida albicans isolates were susceptible to itraconazole and / or voriconazole. Cryptococcus neoformans was more susceptible to itraconazole than to voriconazole. Itraconazole and voriconazole showed very close in vitro activity against the tested fungal isolated, except against S. schenckii. In spite of this, there were some differences in susceptibility among isolates within the same fungal species.     

Comparison of lipolytic and antilipolytic activities of lower vertebrate growth hormones on chicken adipose tissue in vitro

Mammalian and avian growth hormones (GH) (pituitary derived or biosynthetic) exert two effects on chicken adipose tissue explants in vitro. They (i) increase the basal rate of glycerol release a lipolytic effect) and (ii) inhibit glucagon-stimulated glycerol release (an antilipolytic effect). The ability of lower vertebrate GH preparations to exert lipolytic and antilipolytic effects was examined and biological activity was compared to differences in amino-acid residue sequences and to predicted structure. Irrespective of species origin (blue shark, sturgeon, bonito, yellow tail, salmon, bullfrog, sea turtle), all lower vertebrate GH preparations showed very weak (less than 5% the potency of bovine GH), if any, lipolytic activity, but retained strong antilipolytic activity. The present data indicate that the structural requirements for lipolytic and antilipolytic activities of GH differ in chicken adipose tissue. Despite the high sequence homology (88%) between chicken and sea turtle GH, the latter preparation did not stimulate lipolysis. It is suggested that Pro132, conserved only in lipolytically active GH species (human, bovine, and chicken), represents a major determinant of lipolytic activity in chicken adipose tissue. The structural determinants for antilipolytic activity may comprise any or all of residues 3, 17, 64, 108, 109, and 152.     

Zinc-finger recombinase activities in vitro

Zinc-finger recombinases (ZFRs) are chimaeric proteins comprising a serine recombinase catalytic domain linked to a zinc-finger DNA binding domain. ZFRs can be tailored to promote site-specific recombination at diverse 'Z-sites', which each comprise a central core sequence flanked by zinc-finger domain-binding motifs. Here, we show that purified ZFRs catalyse efficient high-specificity reciprocal recombination between pairs of Z-sites in vitro. No off-site activity was detected. Under different reaction conditions, ZFRs can catalyse Z-site-specific double-strand DNA cleavage. ZFR recombination activity in Escherichia coli and in vitro is highly dependent on the length of the Z-site core sequence. We show that this length effect is manifested at reaction steps prior to formation of recombinants (binding, synapsis and DNA cleavage). The design of the ZFR protein itself is also a crucial variable affecting activity. A ZFR with a very short (2 amino acids) peptide linkage between the catalytic and zinc-finger domains has high activity in vitro, whereas a ZFR with a very long linker was less recombination-proficient and less sensitive to variations in Z-site length. We discuss the causes of these phenomena, and their implications for practical applications of ZFRs.     

Hydrocortisone, prednisolone and dexamethasone act on Aspergillus fumigatus in vitro susceptibility to itraconazole

In a previous in vitro investigation from the same laboratory a therapeutic level of hydrocortisone enhanced the itraconazole susceptibility of a single strain of Aspergillus fumigatus. In the present work, the influence of therapeutic levels of hydrocortisone (1 microM), prednisolone (0.125 microM 0.25 microM and 0.5 microM) and dexamethasone (0.25 microM and 0.5 microM) on the itraconazole susceptibility of four A. fumigatus strains, was determined. A. fumigatus conidia were germinated either in the absence or in the presence of a glucocorticoid. The germinated conidia were then spread onto plates and grown either in the presence or in the absence of a glucocorticoid, together with increasing concentrations of itraconazole. The mean colony forming units (CFU) were measured. Two factor analyses of variance showed that hydrocortisone significantly (p <0.001) potentiated the action of itraconazole. The cytotoxic effect of prednisolone on the fungal strains added significantly to the effect of itraconazole (p <0.001). Dexamethasone was also cytotoxic to the fungus but, when used in conjunction with itraconazole, it effectively increased (p <0.01) the number of CFU. This study showed a direct effect of glucocorticoids, currently in use for patient therapy, on in vitro A. fumigatus susceptibility to itraconazole.