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苯硝唑治疗:时间和剂量依赖性因菌株而异。

Benznidazole Treatment: Time- and Dose-Dependence Varies with the Strain.

作者信息

Fonseca Kátia da Silva, Perin Luísa, de Paiva Nívia Carolina Nogueira, da Silva Beatriz Cristiane, Duarte Thays Helena Chaves, Marques Flávia de Souza, Costa Guilherme de Paula, Molina Israel, Correa-Oliveira Rodrigo, Vieira Paula Melo de Abreu, Carneiro Cláudia Martins

机构信息

Laboratory of Immunopathology, Nucleus of Biological Sciences Research, Federal University of Ouro Preto, Ouro Preto 35400-000, Brazil.

Laboratory of Morphopathology, Department of Biological Sciences, Nucleus of Biological Sciences Research, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35400-000, Brazil.

出版信息

Pathogens. 2021 Jun 9;10(6):729. doi: 10.3390/pathogens10060729.

Abstract

As the development of new drugs for Chagas disease is not a priority due to its neglected disease status, an option for increasing treatment adherence is to explore alternative treatment regimens, which may decrease the incidence of side effects. Therefore, we evaluated the efficacy of different therapeutic schemes with benznidazole (BNZ) on the acute and chronic phases of the disease, using mice infected with strains that have different BNZ susceptibilities. Our results show that the groups of animals infected by VL-10 strain, when treated in the chronic phase with a lower dose of BNZ for a longer period of time (40 mg/kg/day for 40 days) presented better treatment efficacy than with the standard protocol (100 mg/kg/day for 20 days) although the best result in the treatment of the animals infected by the VL-10 strain was with100 mg/kg/day for 40 days. In the acute infection by the Y and VL-10 strains of , the treatment with a standard dose, but with a longer time of treatment (100 mg/kg/day for 40 days) presented the best results. Given these data, our results indicate that for BNZ, the theory of dose and time proportionality does not apply to the phases of infection.

摘要

由于恰加斯病处于被忽视疾病的状态,开发治疗该病的新药并非优先事项,因此,提高治疗依从性的一个选择是探索替代治疗方案,这可能会降低副作用的发生率。因此,我们使用感染了对苯硝唑(BNZ)敏感性不同菌株的小鼠,评估了不同苯硝唑治疗方案对该病急性期和慢性期的疗效。我们的结果表明,感染VL-10菌株的动物组,在慢性期用较低剂量的苯硝唑治疗较长时间(40毫克/千克/天,持续40天),比采用标准方案(100毫克/千克/天,持续20天)呈现出更好的治疗效果,尽管治疗感染VL-10菌株的动物的最佳结果是100毫克/千克/天,持续40天。在Y和VL-10菌株的急性感染中,采用标准剂量但治疗时间更长(100毫克/千克/天,持续40天)的治疗呈现出最佳效果。基于这些数据,我们的结果表明,对于苯硝唑来说,剂量和时间成正比的理论不适用于感染阶段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b494/8229751/53532b030871/pathogens-10-00729-g001.jpg

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