Treatment of atopic dermatitis based on control of microorganisms colonized skin surfface

1.用非培养的方法对特应性皮炎(AD)患者和健康人皮肤表面的嗜脂性马拉色菌进行了分析。结论：1.阿尔茨海默病患者为球形马拉色菌和限制性马拉色菌。建立了实时荧光定量聚合酶链式反应方法。与躯干或四肢相比，马拉色菌在头部和颈部的定殖率高出7到12倍，在任何身体部位，球形分枝杆菌和限制分枝杆菌的定殖量约占所有马拉色菌定殖量的80%。我们用琼脂稀释法检测了目前被接受的11个马拉色菌种中的125个菌株。11种马拉色菌对两种唑类药物均高度敏感，最低抑菌浓度为0.016~0.25MICg/m L。他克莫司对半数菌株有抗真菌活性，最低抑菌浓度为16~32微克/毫升。唑类药物与他克莫司联合应用对马拉色菌…有协同作用更多的分离物基于分数抑制指数(FIX)0.245至0.378。我们的结果提示ITC或KTZ联合他克莫司可能是减少AD4患者皮肤表面马拉色菌细胞定植数量的有效疗法。已经确定了几种马拉色菌特应性过敏原。其中，Mala f6(一种亲环素同系物)被认为是主要的过敏原，因为在AD患者的血清中检测到高水平的IgE抗体。本研究探讨了钙调神经磷酸酶抑制剂他克莫司对马拉色菌特应性变应原基因表达的影响。在他克莫司存在的情况下，马拉色菌的Mala f6基因的表达与对照相比受到抑制，而在类固醇(戊酸倍他米松)的存在下，其表达没有改变。这表明，他克莫司除了具有良好的抗炎作用外，还可能通过抑制马拉色菌特应性变应原基因的表达而有助于湿疹皮损的改善。较少

1. Lipophilic Malassezia species colonized on skin surface in atopic dermatitis (AD) patients and healthy subjects was analayzed by culture-independent method. The patient with AD was controlled under the specific genotypic strain of Malassezia globosa and M. restricta.2. Real-time PCR assay was established. Seven to 12 times more Malassezia colonized the head and neck compared to the trunk or limbs, and the species M. globosa and M. restricta accounted for approximately 80% of all Malassezia colonization at any body site.3. We examined 125 strains of the eleven currently accepted Malassezia species using the agar dilution method. All strains of the eleven Malassezia species were very susceptible to both azole agents with minimum inhibitory concentrations (MIC) ranging from 0.016 to 0.25 μg/mL. Tacrolimus had antifungal activities against half of the strains, with MICs ranging from 16 to 32 ug/mL. A combination of azole agents and tacrolimus had a synergistic effect against Malassezia … More isolates based on a fractional inhibitory index (FIX) of 0.245 to 0.378. Our results suggest that a combination of ITC or KTZ with tacrolimus might be an effective therapy for reducing the number of Malassezia cells colonizing the skin surface in patients with AD.4. Several Malassezia atopic allergens have been identified. Of these, Mala f6 (a cyclophilin homolog) is considered major atopic allergen because high levels of IgE antibodies against it is detected in the serum of patients with AD. This study investigated the influence of the calcineurin inhibitor tacrolimus on the expression of Malassezia atopic allergen genes. In the presence of tacrolimus, the expression of the Mala f6 gene of Malassezia was suppressed compared with the control expression, whereas their expression was not changed in the presence of the steroid (betamethasone valerate). This suggests that tacrolimus may contribute to the improvement of eczematous lesions via the suppression of Malassezia atopic allergen gene expression, in addition to its well-characterized anti-inflammatory effect. Less