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胺碘酮和伊曲康唑可提高五价锑剂治疗实验性皮肤利什曼病的疗效。

Amiodarone and itraconazole improve the activity of pentavalent antimonial in the treatment of experimental cutaneous leishmaniasis.

机构信息

Programa de Pós-Graduação em Medicina Tropical e Infectologia, Universidade Federal do Triângulo Mineiro, Av Getúlio Guarita S/N, Abadia, 38001-970, Uberaba, Minas Gerais, Brazil; Núcleo de Ciências Biomédicas, Centro de Laboratório Regional de Bauru, Instituto Adolfo Lutz, R Rubens Arruda, Qd 6, Centro, 17015-110, Bauru, São Paulo, Brazil.

Programa de Pós-Graduação em Medicina Tropical e Infectologia, Universidade Federal do Triângulo Mineiro, Av Getúlio Guarita S/N, Abadia, 38001-970, Uberaba, Minas Gerais, Brazil.

出版信息

Int J Antimicrob Agents. 2017 Aug;50(2):159-165. doi: 10.1016/j.ijantimicag.2017.06.007. Epub 2017 Jun 28.

DOI:10.1016/j.ijantimicag.2017.06.007
PMID:28668672
Abstract

Leishmaniasis affect millions of people, causing morbidity and mortality, especially in developing tropical and subtropical countries. Unfortunately, the possibilities of treatment for these infections are still quite limited and most of the available drugs present serious side effects. The objective of this paper was to evaluate the therapeutic role of amiodarone and itraconazole in the treatment of cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis. In order to perform this evaluation, hamsters were infected with 1 × 10 metaciclic promastigotes of the parasite in the hind footpad and, after the onset of the lesions, were treated with glucantime, amiodarone, itraconazole, glucantime and amiodarone, glucantime and itraconazole or amiodarone and itraconazole. The treatments' efficacy was evaluated per analysis of the size of the cutaneous lesions and by parasitic investigation of the infected foot (by histopathological examination and PCR) and possible side effects were analyzed taking into account the weight of the animals and some biochemical and metabolic parameters (glucose, urea, creatinine, AST, ALT and ALP). The results have shown that, in hamsters, amiodarone and itraconazole, either used isolated or in combination, are unable to stop the development of cutaneous lesions caused by L. (L.) amazonensis, but improve the activity of glucantime in the treatment of these lesions and seem to present no evident side effects. More studies are necessary in order to investigate the clinical potential of these combinations, so there can be the possibility of broadening the therapeutic options available, especially in resistant cases.

摘要

利什曼病影响了数百万人,导致发病率和死亡率,尤其是在发展中热带和亚热带国家。不幸的是,这些感染的治疗可能性仍然相当有限,而且大多数可用的药物都存在严重的副作用。本文的目的是评估胺碘酮和伊曲康唑在治疗由 Leishmania (Leishmania) amazonensis 引起的皮肤利什曼病中的治疗作用。为了进行这种评估,仓鼠在后脚垫中感染了 1×10 个代谢期前鞭毛体寄生虫,在病变出现后,用葡萄糖胺、胺碘酮、伊曲康唑、葡萄糖胺和胺碘酮、葡萄糖胺和伊曲康唑或胺碘酮和伊曲康唑进行治疗。通过分析皮肤损伤的大小、对受感染足部的寄生虫调查(通过组织病理学检查和 PCR)以及考虑动物体重和一些生化和代谢参数(葡萄糖、尿素、肌酐、AST、ALT 和 ALP)来评估治疗的疗效。结果表明,在仓鼠中,胺碘酮和伊曲康唑,无论是单独使用还是联合使用,都不能阻止由 L.(L.) amazonensis 引起的皮肤损伤的发展,但能提高葡萄糖胺治疗这些损伤的活性,并且似乎没有明显的副作用。为了研究这些组合的临床潜力,需要进行更多的研究,以便有可能扩大现有的治疗选择,特别是在耐药病例中。

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