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...     

In Candida albicans, resistance to flucytosine and terbinafine is linked to MAT locus homozygosity and multilocus sequence typing clade 1

A panel of 637 isolates of Candida albicans that had been typed by multilocus sequence typing (MLST) and tested for susceptibility to amphotericin B, caspofungin, fluconazole, flucytosine, itraconazole, ketoconazole, miconazole, terbinafine and voriconazole was the material for a statistical analysis of possible associations between antifungal susceptibility and other properties. For terbinafine and flucytosine, the greatest proportion of low-susceptibility isolates, judged by two resistance breakpoints, was found in MLST clade 1 and among isolates homozygous at the MAT locus, although only three isolates showed cross-resistance to the two agents. Most instances of low susceptibility to azoles, flucytosine and terbinafine were among oropharyngeal isolates from HIV-positive individuals. Statistically significant correlations were found between terbinafine and azole minimal inhibitory concentrations (MICs), while correlations between flucytosine MICs and azole MICs were less strong. It is concluded that a common regulatory mechanism may operate to generate resistance to the two classes of agent that inhibit ergosterol biosynthesis, terbinafine and the azoles, but that flucytosine resistance, although still commonly associated with MAT homozygosity, is differently regulated.     

Sporotrichosis Successfully Treated with Terbinafine and Potassium Iodide: Case Report and Review of the Literature

Sporotrichosis is rare in Turkey. We report a 40-year-old woman who had subcutaneous sporotrichosis caused by sporothrix schenckii that was successfully treated with terbinafine (250 mg, twice a day) for a period of 6 months. She received a saturated solution of potassium iodide orally for two months. Terbinafine and potassium iodide are suggested to be the agents of choice for treatment of subcutaneous sporotrichosis.     

口服特比萘芬联合外用联苯苄唑乳膏治疗足癣长期临床研究

目的 为足癣治疗提供较理想的方案.方法 盐酸特比萘芬250 mg,口服1次/d;1%联苯苄唑乳膏,外用1次/d.250例足癣患者随机入组.A组口服1周加外用1周,B组口服1周加外用2周,C组口服2周加外用1周,D组口服2周加外用2周,E组单独外用4周.在治疗结束时、治疗结束后4周、24周、40周、56周、72周时对各组的疗效、复发率进行评价.结果 在停药后第24周时,A、B、C、D组与E组疗效比较差异有统计学意义.在停药后第40周、56周、72周时,D组与A、B组疗效比较差异也出现统计学意义.在停药后24周、40周时,A、B、C、D组真菌学疗效与E组比较差异有统计学意义.在停药56周、72周时,D组与A、B组真菌学疗效比较差异也出现统计学意义.在停药40周时,A、B、C、D组与E组复发率比较差异有统计学意义.在停药56周、72周时,D组与A、B组复发率比较差异也出现统计学意义.结论 口服特比萘芬2周联合外用1%联苯苄唑乳膏2周治疗足癣的有效率和真菌学疗效最高,复发率最低.     

Comparative study between synthetic and phospholipids of natural origin: effect of phospholipid selection on the behavior of a topical liposomal dosage form incorporating terbinafine

Selection of excipients used is a critical step in the design of a pharmaceutical dosage form as it affects its behavior upon application, as during storage. The purpose of the present study is to evaluate and compare the behavior of six liposomal formulations intended for topical application composed of two widely used phospholipids 1,2-diacyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine with and without incorporation of cholesterol. Liposomal hydrogels made of hydroxyethylcellulose 3% and incorporating the anti-fungal agent terbinafine hydrochloride (E)-N-(6,6-dimethyl-2-hepten-4-inyl)-N-methyl-1-naphthalene-methanamine (-hydrochloride) were prepared, their viscosity was measured and in vitro drug release was studied. Moreover, physical stability and drug retention during storage at two different temperatures (2–8?°C and RT) were examined over time. The results showed differences in the behavior between the two phospholipids while incorporation of cholesterol at the studied concentrations was found to be of minor importance. Drug release was found to be favorable from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomal hydrogels and drug retention was found to be higher at lower storage temperature for all batches. Original physicochemical properties of all batches were found to be retained at least for a week.     

误诊2年的左上臂难辨认体癣1例

报道1例由须癣毛癣菌引起的难辨认体癣。患者女,45岁,左臂伸侧多处红斑、丘疹伴脱屑、瘙痒2a余。曾多次就医诊断不明,患处皮损取活检做病理检查倾向于＂银屑病＂但疗效不佳。刮取皮屑镜检见真菌菌丝,小培养见葡萄串状小分生孢子及螺旋菌丝,尿素酶试验阳性,毛发穿孔试验阳性,鉴定为须癣毛癣菌。经内服特比萘芬和外用萘替芬酮康唑乳膏治疗28d后皮损消退,复查真菌阴性。     

须癣毛癣菌致成人眉区脓癣1例

报告1例由须癣毛癣菌引起的眉毛区域脓癣。患者女性,46岁,左眉部周围红斑1个月。致病菌株经真菌学鉴定为须癣毛癣菌。给予盐酸特比萘芬250mg/d口服,硝酸舍他康唑软膏外用,治疗1个月后皮损完全愈合。     

不同方法口服特比萘芬片治疗趾甲甲真菌病的疗效观察

目的评价不同方法口服特比萘芬片治疗趾甲甲真菌病的疗效。方法将入选患者随机分成两组,A组口服特比萘芬片0.25 g/d连续12周,B组前4周0.25 g/d,第5周开始隔天服0.25 g至16周,分别于治疗开始前、16周及26周对观察指标进行记录、分析。结果共入选1 001例,其中A组512例,16周、26周临床有效率分别是83.01%、95.31%,B组489例,16周、26周临床有效率分别是81.12%、93.86%,两组对应观察期有效率经χ2检验,差异无统计学意义,26周时有效率比16周有进一步提高。结论 4周后隔日服药疗法在减少服用14片特比萘芬片的情况下可以达到与常规治疗组近似的疗效,患者依从性较高,特比萘芬片治疗甲真菌病具有明显的后效应。     

球形孢子丝菌致婴儿固定型孢子丝菌病1例及相关实验研究

报道1例由球形孢子丝菌所致的婴儿固定型孢子丝菌病。患儿女,3个月,因左眼下内侧皮损2个月就诊,皮损脓液标本进行真菌培养,对培养获得菌株进行形态学、生理学和分子生物学鉴定,并进行药物敏感性检测。真菌培养阳性,镜下可见典型的套袖样菌丝。钙调蛋白基因序列分析鉴定为球形孢子丝菌。药敏试验显示特比萘芬和伊曲康唑对该菌株的菌丝相最低抑菌浓度（minimal inhibitorycon centration,MIC）分别为0．5μg／mL和0．5μg／mL;对该菌株的酵母相的MIC值分别为0．25μg／mL和0．5μg／mL。给予患者口服特比萘芬32．5mg／d治疗10周后皮损消退呈瘢痕化修复。依据临床及实验室检查确诊该病例为球形孢子丝菌所致固定型孢子丝菌病,特比萘芬治疗本病例显示较好疗效。     

Involvement of the JNK activation in terbinafine‐induced p21 up‐regulation and DNA synthesis inhibition in human vascular endothelial cells

Previously, we demonstrated that the extracellular signal‐regulated kinase (ERK)‐mediated pathway contributes to the terbinafine (TB)‐induced increases of p21 and p53 protein level as well as decrease of DNA synthesis in human umbilical venous endothelial cells (HUVEC). The aim of this study is to examine the involvement of c‐Jun NH2‐terminal kinase (JNK) in the TB‐induced increase of p21 protein level and DNA synthesis inhibition. Western blot analysis and kinase assay demonstrated that TB treatment increased both the protein level and the kinase activity of JNK1/2 in HUVEC. Transfection of HUVEC with JNK1 dominant negative (DN‐JNK1) prevented the TB‐induced increases of p21 and p53 protein level and decrease of DNA synthesis, suggesting that JNK1/2 activation is involved in the TB‐induced cell cycle arrest in HUVEC. Moreover, over‐expression of mitogen‐activated protein kinase (MEK)‐1 prevented the TB‐induced increase of JNK1/2 protein levels, suggesting that MEK‐1 is an upstream inhibitor of JNK. Transfection of HUVEC with DN‐JNK1 prevented the TB‐induced inhibition of ERK phosphorylation, suggesting that JNK1/2 might serve as a negative regulator of ERK. Taken together, our results suggest that JNK activation is involved in the TB‐induced inhibition of ERK phosphorylation, p53 and p21 up‐regulation and DNA synthesis inhibition in HUVEC. J. Cell. Biochem. 108: 860–866, 2009. © 2009 Wiley‐Liss, Inc.