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体外指甲感染作为一种有效的临床前方法,用于筛选新的局部抗真菌药物。

Ex vivo nail infection as an effective preclinical method for screening of new topical antifungals.

机构信息

Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

出版信息

J Mycol Med. 2020 Jun;30(2):100938. doi: 10.1016/j.mycmed.2020.100938. Epub 2020 Feb 9.

Abstract

Onychomycosis are fungal nail infections comprising of about 50% of onychopathies and are commonly caused by dermatophytes. The treatment of this dermatomycosis requires a long period of time and is associated with high rates of recurrence. In view of the need to evaluate the antifungal performance of promising preclinical compounds, we developed, in this study, a practical and accessibleex vivo model for establishing a Trichophyton rubrum onychomycosis framework using porcine hooves. This model has as its main advantage the similar structural and three-dimensional characteristics that the porcine hooves have with the human nail. The proposed model allowed to evaluate the antifungal activity of a new antifungal compound and a reference drug (terbinafine), both already incorporated into a nail lacquer for topical use. Treatments with compound 3-selenocyanate-indole (Se4a) and with terbinafine incorporated into this nail lacquer completely inhibited fungal growth, corresponding to the profile of in vitro activity observed against T. rubrum. This study concludes that the ex vivo porcine hoof model is an effective alternative method for preclinical screening of drugs or new topical compounds developed to combat onychomycosis. Further studies are needed to compare the permeability of porcine hooves with human nails permeability.

摘要

甲真菌病是由真菌引起的指甲感染,约占甲病的 50%,通常由皮肤癣菌引起。这种皮肤真菌病的治疗需要很长时间,且复发率很高。鉴于需要评估有前途的临床前化合物的抗真菌性能,我们在本研究中开发了一种实用且易于获得的体外模型,使用猪蹄来建立红色毛癣菌甲真菌病模型。该模型的主要优点是猪蹄与人类指甲具有相似的结构和三维特征。所提出的模型允许评估一种新的抗真菌化合物和一种参考药物(特比萘芬)的抗真菌活性,这两种药物都已被纳入一种局部用指甲油中。用化合物 3-硒氰酸吲哚(Se4a)和特比萘芬制成的指甲油进行治疗完全抑制了真菌的生长,这与体外观察到的对红色毛癣菌的活性一致。本研究得出结论,体外猪蹄模型是一种有效的替代方法,可用于筛选药物或新的局部化合物,以对抗甲真菌病。需要进一步的研究来比较猪蹄和人指甲的渗透性。

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