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Evaluation of methylene blue, pyrimethamine and its combination on an in vitro Neospora caninum model

机译:亚甲基蓝,吡米甲胺及其对体外Neospora Caninum模型的影响

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摘要

Neospora caninum is an apicomplexan parasite strongly related to reproductive problems in cattle. The neosporosis control is not well established and several fronts are under development, predominantly based on immune protection, immunomodulation and chemotherapy. The use of anti-malarial drugs as therapeutic sources has, in theory, considerable potential for any apicomplexan. Drugs such as methylene blue (MB) and pyrimethamine (Pyr) represent therapeutic options for malaria; thus, their use for neosporosis should be assessed. In this work, we tested the effects of MB and Pyr on N. caninum proliferation and clearance, using LacZ-tagged tachyzoites. The drugs inhibited at nanomolar dosages and its combination demonstrated an antagonistic interaction in proliferation assays, according to the Chou and Talalay method for drug combination index. However, the drug combination significantly improved the parasite in vitro clearance. The repositioning of well-established drugs opens a short-term strategy to obtain low-cost therapeutics approaches against neosporosis.
机译:Neospora caninum是一种与牛中生殖问题有关的Apicomplexan寄生虫。新孢子症控制尚未确定,几个前沿正在开发,主要是基于免疫保护,免疫调节和化疗。理论上,使用抗疟疾药物作为治疗来源的任何apicomplexan的潜力相当大。亚甲基蓝(MB)和吡米甲胺(Pyr)等药物代表疟疾的治疗选择;因此,应评估它们对新孢子症的用途。在这项工作中,我们使用Lacz标记的Tachyzoites测试了Mb和Pyr对N. caninum增殖和间隙的影响。根据药物组合指数的呼吸和塔拉勒方法,纳摩尔剂量抑制的药物抑制在纳摩尔剂量及其组合中表明了增殖测定中的拮抗相互作用。然而,药物组合在体外清除的情况下显着改善了寄生虫。既定良好的药物重新定位开辟了短期策略,以获得针对新孢子症的低成本治疗方法。

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