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The paraspecific neutralisation of snake venom induced coagulopathy by antivenoms

机译:抗蛇毒血清对蛇毒诱发的凝血病的亚种中和

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摘要

Snake envenoming causes several potentially lethal pathologies. The specific pathology is dictated by the toxin composition of venom, which varies by species, geography and ontogeny. This variation severely restricts the paraspecific efficacy of antivenoms used to treat snakebite victims. With a view to devising pathology-specific snakebite treatments, we assessed the procoagulant activity of 57 snake venoms and investigated the efficacy of various antivenoms. We find that procoagulant venoms act differentially on key steps of the coagulation cascade, and that certain monospecific antivenoms work in a previously unrecognised paraspecific manner to neutralise this activity, despite conventional assumptions of congener-restricted efficacy. Moreover, we demonstrate that the metal chelator EDTA is also capable of neutralising venom-induced lethality in vivo. This study illustrates the exciting potential of developing new, broad-spectrum, toxin-targeting antivenoms capable of treating key snakebite pathologies, and advocates a thorough re-examination of enzyme inhibiting compounds as alternative therapies for treating snakebite victims.
机译:蛇毒化会导致几种潜在的致命病态。具体病理由毒液的毒素组成决定,毒液的组成因物种,地理和个体发育而异。这种变化严重限制了用于治疗蛇咬受害者的抗蛇毒血清的超特异功效。为了设计特定于病理学的蛇咬疗法,我们评估了57种蛇毒的促凝血活性,并研究了各种抗蛇毒的功效。我们发现促凝血毒液在凝血级联反应的关键步骤上有不同的作用,尽管常规假设限制了同类药物的功效,但某些单特异性抗蛇毒草以以前无法识别的亚种方式中和该活性。此外,我们证明了金属螯合剂EDTA也能够中和毒液诱导的体内致死性。这项研究说明了开发能够治疗关键蛇咬病的新型,广谱,靶向毒素的抗蛇毒药物的令人兴奋的潜力,并主张彻底重新检查酶抑制化合物,作为治疗蛇咬病受害者的替代疗法。

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