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碳酸酐酶作为实验性旋毛虫病的潜在治疗靶点。

Carbonic anhydrase enzyme as a potential therapeutic target for experimental trichinellosis.

作者信息

Saad Abeer E, Ashour Dalia S, Abou Rayia Dina M, Bedeer Asmaa E

机构信息

Department of Medical Parasitology, Faculty of Medicine, Tanta University, Tanta, Gharbiya, Egypt.

Department of Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

Parasitol Res. 2016 Jun;115(6):2331-9. doi: 10.1007/s00436-016-4982-9. Epub 2016 Mar 16.

DOI:10.1007/s00436-016-4982-9
PMID:26979731
Abstract

Trichinellosis is a globally distributed helminthic infection. There is a considerable interest in developing new anti-helminthic drugs affecting all the developmental stages of Trichinella. Acetazolamide (carbonic anhydrase (CA) inhibitor) involves a novel mechanism of action by inhibiting such an essential enzyme for parasite metabolism. This work aimed to study the effect of acetazolamide against different stages of T. spiralis in experimental animals. Mice were divided into three groups: group I: infected and treated with acetazolamide on day 2 post infection (P.I.), group II: infected and treated with acetazolamide on day 12 P.I., and group III: infected non-treated. From each group, small intestine and muscles were removed for histopathological and immunohistochemical studies. Also, total adult and muscle larval count were estimated. We found that acetazolamide was effective in reduction of both adult and muscle larval counts. When given early, the effect was more pronounced on the adults (62.7 %). However, the efficacy of the drug against muscle larvae was increased when given late (63 %). Improvement of the intestinal histopathological changes was observed in all the treated groups. Degeneration of encysted larvae with minimal pathologic changes of infected skeletal muscle was observed in the treated groups. Expression of matrix metalloproteinase-9 showed a statistically significant decrease in the intestinal and muscle tissues in all treated groups as compared to the control group. In conclusion, the present study revealed that acetazolamide, carbonic anhydrase inhibitor, could be a promising drug against both adults and larvae of T. spiralis.

摘要

旋毛虫病是一种全球分布的蠕虫感染。开发影响旋毛虫所有发育阶段的新型抗蠕虫药物备受关注。乙酰唑胺(碳酸酐酶(CA)抑制剂)通过抑制寄生虫代谢所必需的这种酶,涉及一种新的作用机制。这项工作旨在研究乙酰唑胺对实验动物体内旋毛虫不同阶段的影响。将小鼠分为三组:第一组:感染后第2天感染并用乙酰唑胺治疗;第二组:感染后第12天感染并用乙酰唑胺治疗;第三组:感染但未治疗。从每组中取出小肠和肌肉进行组织病理学和免疫组织化学研究。此外,还估计了成虫和肌幼虫的总数。我们发现乙酰唑胺在减少成虫和肌幼虫数量方面是有效的。早期给药时,对成虫的效果更明显(62.7%)。然而,晚期给药时该药物对肌幼虫的疗效增加(63%)。在所有治疗组中均观察到肠道组织病理学变化有所改善。在治疗组中观察到包囊幼虫退化,感染的骨骼肌病理变化最小。与对照组相比,所有治疗组的肠道和肌肉组织中基质金属蛋白酶-9的表达均有统计学意义的下降。总之,本研究表明,碳酸酐酶抑制剂乙酰唑胺可能是一种有望对抗旋毛虫成虫和幼虫的药物。

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Serine proteases of parasitic helminths.寄生蠕虫的丝氨酸蛋白酶
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Identification of metal dithiocarbamates as a novel class of antileishmanial agents.鉴定二硫代氨基甲酸盐金属盐为一类新型抗利什曼原虫药物。
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Characterization of a novel pyruvate kinase from Trichinella spiralis and its participation in sugar metabolism, larval molting and development.旋毛虫新型丙酮酸激酶的特性及其在糖代谢、幼虫蜕皮和发育中的作用。
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Mitigation of -induced ileitis by infection pinpointing immunomodulation.通过感染确定免疫调节来减轻诱导性回肠炎。 (注:原文中“-induced ileitis”前面似乎缺失关键信息,翻译可能不太准确,建议补充完整准确的原文内容以便更精准翻译。)
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