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米替福新能否用作治疗弓形虫病的药物?

Could miltefosine be used as a therapy for toxoplasmosis?

作者信息

Eissa Maha M, Barakat Ashraf M A, Amer Eglal I, Younis Layla K

机构信息

Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Department of Zoonotic Diseases, National Research Centre, Cairo, Egypt.

出版信息

Exp Parasitol. 2015 Oct;157:12-22. doi: 10.1016/j.exppara.2015.06.005. Epub 2015 Jun 23.

Abstract

Toxoplasmosis is a zoonotic protozoal disease affecting more than a billion people worldwide. The shortfalls of the current treatment options necessitate the development of non-toxic and well-tolerated, efficient alternatives especially against the cyst form. The current study was undertaken to investigate, for the first time, the potential potency of miltefosine against Toxoplasma gondii infection in acute and chronic experimental toxoplasmosis. Results showed that there is no evidence of anti-parasitic activity of miltefosine against T. gondii tachyzoites in acute experimental toxoplasmosis. However, anti-parasitic activity of miltefosine against T. gondii cyst stage in chronic experimental toxoplasmosis could not be excluded as demonstrated by significant reduction in brain cyst burden. Moreover, considerable morphological changes in the cysts were revealed by light and electron microscopy study and also by amelioration of pathological changes in the brain. Future studies should focus on enhancement of anti-toxoplasma activity of miltefosine against chronic toxoplasmosis using formulation based nanotechnology. To the best of our knowledge, this is the first study highlighting efficacy of miltefosine against chronic toxoplasmosis, thus, increasing the list of diseases that can be targeted by this drug.

摘要

弓形虫病是一种人畜共患的原生动物疾病,全球有超过10亿人受其影响。当前治疗方案存在不足,因此有必要开发无毒、耐受性良好且有效的替代方案,尤其是针对包囊形式的治疗方案。本研究首次探讨了米替福新在急性和慢性实验性弓形虫病中对刚地弓形虫感染的潜在效力。结果表明,在急性实验性弓形虫病中,没有证据表明米替福新对刚地弓形虫速殖子具有抗寄生虫活性。然而,在慢性实验性弓形虫病中,米替福新对刚地弓形虫包囊期的抗寄生虫活性不能排除,因为脑内包囊负担显著减轻。此外,通过光学显微镜和电子显微镜研究以及脑内病理变化的改善,揭示了包囊中有相当大的形态变化。未来的研究应集中在利用基于纳米技术的制剂增强米替福新对慢性弓形虫病的抗弓形虫活性。据我们所知,这是第一项强调米替福新对慢性弓形虫病疗效的研究,因此,增加了可被该药物靶向治疗的疾病清单。

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