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免疫识别与中和毒液的商业抗毒液生产在哥伦比亚。

Immunorecognition and Neutralization of Venom by a Commercial Antivenom Produced in Colombia.

机构信息

Programa de Biología, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.

Grupo de Investigación en Toxinología, Alternativas Terapéuticas y Alimentarias, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia, Medellín 050010, Colombia.

出版信息

Toxins (Basel). 2022 Mar 25;14(4):235. doi: 10.3390/toxins14040235.

Abstract

In Colombia, on average 2.9% of the nearly 5600 snakebite events that occur annually involve the rattlesnake . The envenomation by this snake is mainly characterized by neurotoxicity and the main toxin is crotoxin (~64.7% of the total venom). The Instituto Nacional de Salud (INS) produces a polyvalent antivenom aimed at the treatment of bothropic, crotalid, and lachesic envenomations; nonetheless, its immune reactivity profile and neutralizing capacity over biological activities of the venom has been poorly evaluated. In this sense, the study aims: (1) to describe an in-depth exploration of its immunoreactivity through second-generation antivenomics and HPLC fraction-specific ELISA immunoprofiles; and (2) to evaluate the neutralization pattern of the rattlesnake venom in vitro and in vivo biological activities. The results obtained showed a variable recognition of crotoxin subunits, in addition to a molecular mass-dependent immunoreactivity pattern in which the disintegrins were not recognized, and snake venom metalloproteinases and L-amino acid oxidases were the most recognized. Additionally, a high neutralization of proteolytic and coagulant activities was observed, but not over the PLA activity. Further, the median effective dose against venom lethality was 962 μL of antivenom per mg of venom. In conclusion, (1) the antivenom recognition over the crotoxin and the disintegrins of the should be improved, thus aiming upcoming efforts for the exploration of new techniques and approaches in antivenom production in Colombia, and (2) the neutralization activity of the antivenom seems to follow the molecular mass-dependent recognition pattern, although other explanations should be explored.

摘要

在哥伦比亚,每年近 5600 起蛇伤事件中,平均有 2.9%涉及响尾蛇。这种蛇的中毒主要表现为神经毒性,主要毒素是响尾蛇毒素(约占总毒液的 64.7%)。Instituto Nacional de Salud(INS)生产了一种多价抗蛇毒血清,旨在治疗 Bothropic、Crotalid 和 Lachesic 蛇咬伤;然而,其免疫反应谱和中和能力对毒液的生物活性的评估一直很差。在这种情况下,研究的目的是:(1)通过第二代抗蛇毒血清学和 HPLC 分级特异性 ELISA 免疫谱深入探讨其免疫反应性;(2)评估抗响尾蛇毒液在体外和体内生物活性中的中和模式。研究结果表明,响尾蛇毒素的 crotoxin 亚单位具有可变的识别性,此外,还存在一种依赖于分子量的免疫反应模式,其中不识别 disintegrins,而 snake venom metalloproteinases 和 L-amino acid oxidases 是最被识别的。此外,观察到对水解和凝血活性具有很高的中和作用,但对 PLA 活性没有中和作用。此外,抗响尾蛇毒液的半数有效剂量为每毫克毒液 962 μL 的抗血清。总之,(1)应改进抗蛇毒血清对 crotoxin 和 响尾蛇毒素 disintegrins 的识别,从而为哥伦比亚即将进行的探索抗蛇毒血清生产新技术和方法的努力提供指导,(2)抗蛇毒血清的中和活性似乎遵循分子量依赖性的识别模式,尽管应探索其他解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/9025410/f393a9317d29/toxins-14-00235-g001.jpg

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