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硝唑尼特对细粒棘球绦虫原头节和中绦期幼虫的体外作用

In vitro effects of nitazoxanide on Echinococcus granulosus protoscoleces and metacestodes.

作者信息

Walker Mirjam, Rossignol Jean François, Torgerson Paul, Hemphill Andrew

机构信息

Institute of Parasitology, Faculties of Veterinary Medicine and Medicine, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Swizerland.

出版信息

J Antimicrob Chemother. 2004 Sep;54(3):609-16. doi: 10.1093/jac/dkh386. Epub 2004 Jul 28.

Abstract

OBJECTIVES

Infection of humans and domestic ruminants with the larval stage (metacestode) of Echinococcus granulosus results in cystic echinococcosis (CE). The metacestode causes a space-occupying lesion in visceral organs, most commonly in the liver. Benzimidazole carbamate derivatives, such as mebendazole and albendazole, are currently used for chemotherapeutic treatment of CE. In human patients, benzimidazoles have to be applied in high doses for extended periods of time, and adverse side effects are frequently observed. In order to evaluate alternative treatment options, the in vitro efficacy of nitazoxanide, a broad-spectrum drug used against intestinal parasites and bacteria, was investigated.

METHODS

Freshly isolated E. granulosus protoscoleces were subjected to nitazoxanide treatment (1, 5 and 10 microg/mL), and the effects on parasite viability were monitored by Trypan Blue staining and scanning electron microscopy. Protoscolex cultures were maintained further, until metacestode development took place. Metacestodes were then subjected to nitazoxanide treatment (10 microg/mL), and corresponding effects were visualized by scanning and transmission electron microscopy.

RESULTS

Dose-dependent protoscolex death within a few days of nitazoxanide treatment was observed. Subsequent in vitro culture of drug-treated protoscoleces confirmed the non-viability of parasites, while further cultivation of non-treated protoscoleces for a period of at least 3 months resulted in stage conversion and the formation of small metacestodes 3-4 mm in diameter. Nitazoxanide had a deleterious effect on these metacestodes, which was comparable to that of albendazole.

CONCLUSIONS

Our study indicates a potential for nitazoxanide as an alternative treatment option against CE.

摘要

目的

细粒棘球绦虫幼虫期(原头蚴)感染人类和家养反刍动物会导致囊型包虫病(CE)。原头蚴在内脏器官中形成占位性病变,最常见于肝脏。苯并咪唑氨基甲酸酯衍生物,如甲苯咪唑和阿苯达唑,目前用于CE的化疗。在人类患者中,苯并咪唑必须高剂量长时间应用,且经常观察到不良反应。为了评估替代治疗方案,研究了一种用于治疗肠道寄生虫和细菌的广谱药物硝唑尼特的体外疗效。

方法

将新鲜分离的细粒棘球绦虫原头蚴用硝唑尼特处理(1、5和10微克/毫升),通过台盼蓝染色和扫描电子显微镜监测对寄生虫活力的影响。原头蚴培养物进一步维持,直到原头蚴发育为幼虫。然后将幼虫用硝唑尼特处理(10微克/毫升),通过扫描和透射电子显微镜观察相应的效果。

结果

在硝唑尼特处理后的几天内观察到原头蚴死亡呈剂量依赖性。随后对经药物处理的原头蚴进行体外培养,证实寄生虫无活力,而对未处理的原头蚴进一步培养至少3个月会导致阶段转化并形成直径3-4毫米的小幼虫。硝唑尼特对这些幼虫有有害作用,与阿苯达唑相当。

结论

我们的研究表明硝唑尼特作为CE替代治疗方案具有潜力。

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