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对转染绿色荧光蛋白[pIR3(-)-eGFP]的新大陆利什曼原虫物种进行抗利什曼原虫药物的体外感染性和敏感性研究。

Studies in vitro on infectivity and sensitivity to antileishmanial drugs in New World Leishmania species transfected with the green fluorescent protein [pIR3(-)-eGFP].

作者信息

Palacios Genesis, Parodi Adriana, Upegui Yulieth A, Montoya Andres, Pulido Sergio, Vélez Iván D, Robledo Sara M

机构信息

PECET-Facultad de Medicina,Universidad de Antioquia,Medellin,Colombia.

出版信息

Parasitology. 2017 Nov;144(13):1718-1725. doi: 10.1017/S0031182017000671. Epub 2017 Aug 23.

Abstract

Current chemotherapeutic agents for leishmaniasis have several disadvantages interfering with the effective treatment and therefore more and better antileishmanial drugs are needed. Discovery of candidates for leishmaniasis treatment requires not only accurate and precise methodologies but also well-known biological system to measure infectivity of parasites and antileishmanial activity of the new compounds. Significant variation in the in vitro and in vivo infectivity and sensitivity to established and experimental drugs in Leishmania strains are reported. This work reports the in vitro biological behavior and antileishmanial drugs sensitivity of different green fluorescent protein transfectant Leishmanias strains. The in vitro growth kinetic and infectivity to U937 cells vary slightly in the Leishmania transfectant strains in comparison with their correspondant wild-type. However, the insertion of the pIR3(-)-eGFP may affect the sensitivity of the parasites to meglumine antimoniate (MA) and miltefosine but not to amphotericin B (AMB) and pentamidine isethionate. In consequence, AMB or pentamidine isethionate but not MA or miltefosine should be used as antileishmanial control drugs during in vitro assays of antileishmanial activity. Furthermore, is recommended to test compounds against more than one Leishmania strain in order to verify that the antileihmanial activity of these compound is similar among species.

摘要

目前用于治疗利什曼病的化疗药物存在几个缺点,影响了有效治疗,因此需要更多更好的抗利什曼病药物。发现利什曼病治疗候选药物不仅需要准确精确的方法,还需要知名的生物系统来测量寄生虫的感染性和新化合物的抗利什曼病活性。据报道,利什曼原虫菌株在体外和体内的感染性以及对现有药物和实验药物的敏感性存在显著差异。这项工作报道了不同绿色荧光蛋白转染的利什曼原虫菌株的体外生物学行为和抗利什曼病药物敏感性。与相应的野生型相比,利什曼原虫转染菌株对U937细胞的体外生长动力学和感染性略有不同。然而,pIR3(-)-eGFP的插入可能会影响寄生虫对葡甲胺锑酸盐(MA)和米替福新的敏感性,但不会影响对两性霉素B(AMB)和乙磺半胱氨酸戊烷脒的敏感性。因此,在抗利什曼病活性的体外试验中,应使用AMB或乙磺半胱氨酸戊烷脒而不是MA或米替福新作为抗利什曼病对照药物。此外,建议针对不止一种利什曼原虫菌株测试化合物,以验证这些化合物在不同物种中的抗利什曼病活性是否相似。

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