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Research of the Death from Drug Induced Anaphylactic Shock

药物性过敏性休克死亡的研究

基本信息

批准号：
63480186
负责人：
KASHIMURA Seiichi
金额：
$ 3.07万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480186/
关键词：
Anaphylaxis Death from shock Postmortem blood Histamine Postmortem change Compound 48 80 IgE Compound 48 アナフィラキシーショック死体血液脱顆粒反応

项目摘要

This study was undertaken for the purposes of the certifying drug-induced anaphylaxis from postmortem materials. The findings were as follows :1. Administrating Compound 48/80, a degranulating agent of mast cells, is a convenient and useful method in the field of forensic medicine, for creating an experimental animal model of death from anaphylaxis instead of using the usual immunological method.2. Whole blood must be used as the postmortem sample for blood. This is because neither plasma nor serum can be clearly separated because of clotting, hemolysis and degeneration due to postmortem changes.3. Deproteinization, extraction and purification with cation-exchange cellulose were needed for the determination of Histamine (HA), one of the most important shock mediators, and 1-Methylhistamine (MHA), one of the metabolites of HA, levels in dog's blood after death, using high-performance liquid chromatography with a fluorometric detector without interfering substances.4. HA levels in blood were tremendously increased about 24 hours after death, even without a release of HA into the blood just before death. MHA levels were considerably increased after death, only when a lot of HA had been present just before death.5. In vitro immunoglobulin E (IgE) antibody responses in blood were stable for 3 days at 20ﾟC. Even in cases when blood could not be obtained from the cadaver, it was possible to measure the hapten specific IgE antibody responses for up to 3 days after death using the supernatant of the visceral homogenates.This study, however, is not directly applicable to humans, because the situations and conditions both before and after death concerning, for example, disease and emergency etc, were completely different. However, these findings, especially concerning the experimental animal model and the stability of IgE antibody, suggest the possibility of being able to certify death from anaphylaxis.

进行本研究的目的是从尸检材料中证明药物诱导的过敏反应。研究结果如下：1.给予肥大细胞脱粒剂化合物48/80，在法医学领域是一种方便和有用的方法，用于建立过敏性死亡的实验动物模型，而不是使用通常的免疫学方法.全血必须用作血液的死后样本。这是因为血浆和血清由于死后变化而发生凝血、溶血和变性，不能清楚地分离。采用高效液相色谱荧光检测器，在无干扰物质的条件下，测定犬死后血液中最重要的休克介质之一组胺（HA）及其代谢产物1-甲基组胺（MHA）的含量，需要用阳离子交换纤维素进行脱蛋白、提取和纯化.血液中的HA水平在死亡后约24小时显著增加，即使在死亡前没有HA释放到血液中。死亡后MHA水平显著增加，只有在死亡前存在大量HA时。血液中的体外免疫球蛋白E（IgE）抗体应答在20 ℃下稳定3天。即使在不能从尸体中获得血液的情况下，也可以使用内脏匀浆的上清液测量死亡后长达3天的半抗原特异性IgE抗体应答。然而，这项研究并不直接适用于人类，因为死亡前和死亡后的情况和条件，例如疾病和紧急情况等，是完全不同的。然而，这些发现，特别是关于实验动物模型和IgE抗体的稳定性，表明有可能证明过敏性反应导致死亡。