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一种治疗蛇咬伤中毒的新疗法的设计。

Design of a new therapy to treat snake envenomation.

作者信息

Shahidi Bonjar Leyla

机构信息

Department of Pharmacology, College of Pharmacy, Kerman University of Medical Sciences, International Campus, Kerman, Iran.

出版信息

Drug Des Devel Ther. 2014 Jun 18;8:819-25. doi: 10.2147/DDDT.S65395. eCollection 2014.

Abstract

The prospective removal of snake venoms from the blood of snake-bitten patients is discussed here. Opportune neutralization of killer antigens from the blood of poisoned victims is a vital treatment step. Delays may lead to death, or cripple the patient permanently. The present procedure describes the elimination of venom antigens of a wide range of snakes from the blood of such patients. Compared to conventional treatments, the treatment is administrable in the lack of proper antivenoms, expected to be more effective with less side effects, covers a vast range of snake venoms, minimizes contact of venoms with internal tissues and organs, is applicable in patients sensitive to serum injections, has a high chance of effectiveness because there is no need to identity the snake involved to administer its specific antibody, and is capable of universal application. The principal component to this approach is a "polyvalent venom antibody column" (PVAC), which selectively traps venom antigens from blood in an extracorporeal circuit while detoxified blood returns back to the patient's body. The PVAC is intended for removal of numerous snake venom antigens in a relatively simple procedure. Detoxification is performed under the supervision of trained personnel using simple blood-circulating machines in which blood circulates from patient to PVAC and back to the patient aseptically. The device acts as a biological filter that selectively immobilizes harmful venom antigens from poisoned blood. For effective neutralization, the PVAC provides a large contact surface area with blood. The PVAC's reactive sites would consist of carbon nanotubes, on which a vast spectra of venoms' antibodies are bonded to. In this extracorporeal detoxification process, nocent antigens conjugate with their antibodies and become immobilized, and are eliminated from the poisoned patient blood. Detoxification resuscitation is expected to take 2-3 hours, when the titers of venom antigens in the blood reach harmless levels, as confirmed by sampling of the blood and appropriate serological evaluations. If conventional antivenoms do not cover the entire spectrum of venom antigens in blood, rehabilitation would be a matter of a longer period; whilst the PVAC covers the widest range of antibodies to remove the broadest range of venom antigens, the rehabilitation period would be shorter since venom antigens have been removed from the body in a few hours duration. PVACs are to be biotechnologically engineered against a wide spectra of antigens present in the venoms of the dominant poisonous snakes for a defined geographical zone; ie, a country, part of a continent, or an entire continent. As a polyvalent column, the PVAC bears a sufficient amount of venom antibodies of all snakes that pose a threat in the region. PVAC treatment would have high applicability in cases where the patient is unconscious and/or the snake identity is not clear for administration of related antivenom medication. For opportune administration, research on the use of PVACs in emergency ambulances should receive special attention. Starting in situ detoxification, such ambulances would provide more efficient resuscitations to envenomed patients.

摘要

本文讨论了从被蛇咬患者血液中前瞻性去除蛇毒的方法。及时中和中毒受害者血液中的致命抗原是至关重要的治疗步骤。延误可能导致死亡,或使患者永久致残。目前的方法描述了从这类患者血液中清除多种蛇毒抗原的过程。与传统治疗方法相比,该治疗方法在没有合适抗蛇毒血清的情况下也可实施,预计效果更佳且副作用更少,能涵盖多种蛇毒,最大限度减少毒液与体内组织和器官的接触,适用于对血清注射敏感的患者,因无需确定所涉蛇种即可施用其特异性抗体,故有很高的有效几率,并且能够普遍应用。该方法的主要成分是“多价蛇毒抗体柱”(PVAC),它在体外循环中选择性地从血液中捕获蛇毒抗原,同时将解毒后的血液回输到患者体内。PVAC旨在通过相对简单的程序去除多种蛇毒抗原。解毒过程在经过培训的人员监督下,使用简单的血液循环机器进行,血液在无菌条件下从患者流向PVAC再回到患者体内。该装置充当生物过滤器,选择性地固定中毒血液中的有害蛇毒抗原。为实现有效中和,PVAC为血液提供了较大的接触表面积。PVAC的反应位点由碳纳米管组成,上面结合了大量不同蛇毒的抗体。在这个体外解毒过程中,有害抗原与其抗体结合并被固定,然后从中毒患者的血液中清除。预计解毒复苏过程需要2至3小时,届时通过血液采样和适当的血清学评估确认血液中蛇毒抗原的滴度达到无害水平。如果传统抗蛇毒血清不能涵盖血液中所有种类的蛇毒抗原,恢复过程将会更长;而PVAC涵盖了最广泛的抗体,能去除最广泛的蛇毒抗原,由于蛇毒抗原在数小时内就已从体内清除,因此恢复周期会更短。PVAC将通过生物技术针对特定地理区域(即一个国家、一个大陆的一部分或整个大陆)中主要毒蛇毒液中存在的多种抗原进行设计。作为一种多价柱,PVAC含有该区域内所有构成威胁的蛇的足量蛇毒抗体。PVAC治疗在患者昏迷和/或不清楚蛇的种类而无法施用相关抗蛇毒血清药物的情况下具有很高的适用性。为了及时施用,在紧急救护车上使用PVAC的研究应受到特别关注。从现场开始解毒,这类救护车将为中毒患者提供更有效的复苏治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c045/4069039/3d803735755f/dddt-8-819Fig1.jpg

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