长期饮酒对急性中毒大鼠死后体液内MDMA再分布的影响

目的研究长期饮酒对急性中毒大鼠体液中亚甲基二氧甲基苯丙胺(MDMA)死后再分布的影响。方法 SD雄性大鼠360只,随机均分为A、B、C、D 4组;A、B组以白酒,C、D组以双蒸水为饮用液体,4周后各组按150mg/kg MDMA剂量灌胃,处死后分置于25℃、4℃条件下;以VARIAN CP-3800气相色谱仪分别检测处死时血乙醇含量和0～10d内体液样品中MDMA浓度。结果 0～10d不同条件下,大鼠血液、玻璃体液及尿液中MDMA的PMR浓度变化趋势均为先升高、后降低;各时间点A、B组和C、D组大鼠各体液样本MDMA浓度较0h均有显著性差异(P<0.05),各时间点A与C组、B与D组之间体液样本MDMA浓度有显著性差异(P<0.05);A与B组、C与D组之间体液样本MDMA浓度有显著性差异(P<0.05)。结论长期饮用乙醇会降低MDMA在体液样品中的再分布,其影响程度高低依次为血液、尿液及玻璃体液;低温也可减少体液中MDMA的再分布。     

温度对硬膜外麻醉致死犬体内布比卡因死后再分布的影响

目的建立布比卡因在硬膜外麻醉犬体内死后再分布动物模型,观察温度对其死后再分布规律的影响。方法雄性杂种犬18只,盐酸布比卡因（5mg/kg）硬膜外麻醉致死,随机分3组,分别置于室温（20～23℃）、4℃和-20℃,于死后0、2、4、8、24、48、72、96、120h同一尸体提取心血、周围血、肝和大脑,GC-NPD、GC-MS法检测其中布比卡因含量,比较其各组含量变化。结果室温时心血、周围血和大脑的死后再分布现象较明显且复杂．4℃时死后再分布现象较室温下弱且缓慢。-20℃时4种检材中布比卡因的再分布现象进一步减弱。结论布比卡因在硬膜外麻醉致死犬体内可发生死后再分布．低温保存可延缓或阻止其发生。     

利多卡因及MEGX在蛛网膜下腔麻醉致死犬体内死后再分布

目的研究利多卡因及其代谢产物单乙基甘氨酰二甲苯胺(MEGX)在蛛网膜下腔麻醉致死犬体内的死后再分布规律。方法犬6只随机分为A、B两组,分别经蛛网膜下腔注射0.5倍(6.34mg/kg)和5倍(63.35mg/kg)硬膜外麻醉极量的盐酸利多卡因,于死后0h、12h、24h、36h、72h取心血、外周血、肝、脑等,采用高效液相色谱法(HPLC)检测其中利多卡因及MEGX的含量。结果 A组犬死后72h,心血、外周血和脑中利多卡因含量与死亡当时的比值(Ct/C0)分别为4.74,14.87,7.67,均呈上升趋势(P0.05),MEGX含量与死亡当时含量差异无统计学意义(P0.05);B组犬死后72h,心血中利多卡因含量Ct/C0值为0.36,呈下降趋势(P0.05),脑中为3.48(P0.05)呈升高的趋势,肝中MEGX含量与死亡当时相比差异无统计学意义(P0.05)。结论蛛网膜下腔不同剂量麻醉致死犬体内利多卡因均会发生死后再分布,MEGX未发生死后再分布。     

兔死后尸血pH值和气体成份的变化

本文报道30只家兔死后尸血 pH 值和气体成份的变化与死后时间的关系。死后0～2小时,尸血 pH 值下降很快,pCO_2迅速上升,pO_2变化很明显,O_2SAT 降低也很显著。死后2小时以后,上列各项变化逐渐变小。死后0～3小时,由于尸血 pH 值迅速降低引起尸血 HCO~-_3浓度的降低,BE 浓度变化也很大,死后3小时后,尸血 HCO_3浓度、BE 浓度变化逐渐变小。人死后,尸血 pH 值和气体成份很可能也有上述的变化,有待进一步研究,以应用于推断死亡时间。     

家兔玻璃体液2种酶活性变化与死亡时间的相关性

目的探讨死后家兔玻璃体液胆碱脂酶(CHE)和谷草转氨酶(GOT)活性与死后经过时间(PM I)的相关性。方法应用光度法检测在25~30℃和10~15℃下死后即刻至54h之间玻璃体液CHE和GOT活性。结果死后即刻至54h之间,ChE、GOT活性分别由约850U/L、220U/L逐步降解趋于零。死后6h内,两种酶活性降解存在平台期。统计分析,得出相应的单元和多元回归方程,相关系数或决定系数均在0.896以上,P<0.01。结论两种酶活性的降解规律可作为较为客观的推断PM I的参考指标。     

尿中MDMA及其代谢物的GC和GC／MS分析

考察MDMA在人体内的代谢以及建立尿中MDMA和体内主要代谢物MDA的分析方法。尿样水解后经液-液提取处理,用GC／MS（EI、PCI）和GC／FID法分析。人摄入MDMA后尿中MDA和原体MDMA比约为0．10～0．14。GC／MS／SIM和GC／FID法的最低检出限为2ng／ml和50ng／ml,回收率大于85％,变异系数小于10％。该法简便快速、灵敏度高、结果可靠,可用于MDMA滥用者的尿样鉴定。MDA／MDMA浓度比可作为评判毒分结果的参考指标。     

利用肌原纤维小片化指数推断死亡时间

目的研究死后机体骨骼肌肌原纤维小片化指数(MFI)与死亡时间之间的关系。方法双缩脲法测定室温下不同死后时间家兔骨骼肌全蛋白浓度,分光光度法测定540nm处0.5mg/mL蛋白浓度下的骨骼肌肌原纤维小片化指数。结果在死后早期,肌原纤维小片化指数随着时间延长逐步增高。结论肌原纤维小片化指数可用于早期死亡时间的推断。     

氯胺酮在家兔死后体内的弥散研究

目的研究氯胺酮在大白兔体内死后弥散过程和再分布机制。方法 48只实验大白兔随机分为8组,采用缺氧处死后以150mg/kg氯胺酮灌胃,尸体仰卧位于室温下放置;在0~96h内分8个时间点各解剖1组,提取体液和脏器组织样品;采用GC/MS法定性结合GC-NPD法定量检测样品中氯胺酮含量,并计算心血/外周血中氯胺酮含量的比值。结果大白兔死后氯胺酮灌胃尸体放置96h内,脑、尿液、玻璃体液、左上/下肢肌肉样本中均未检测到氯胺酮,心血、外周血、心肌、脾、肾、肝、肺、胆汁中氯胺酮含量随死后时间呈动态升高的变化;其中距离胃较近的组织(如脾)较早检测到含量较高的氯胺酮,而距离较远的组织或体液中氯胺酮含量较低且较晚检测到;心血/外周血中氯胺酮含量比值为1.73。结论氯胺酮在家兔体内存在死后再分布,从胃到器官组织、心血顺浓度梯度弥散是主要机制。脑、玻璃体液、尿液、肢体肌肉不受死后弥散的影响,可作为生前服毒与死后染毒氯胺酮的鉴别依据。     

MDMA心肌毒性的法医毒理学研究进展

3,4-亚甲基二氧基甲基苯丙胺(MDMA)是近年来在全世界,特别是亚洲地区公共娱乐场所流行性滥用的"摇头丸"的主要药物成分。MDMA主要作用于人体神经系统从而表现出各种神经系统症状。目前的实验研究发现,MDMA对人体多个系统具有毒性作用,其中对心血管系统的毒性损害作用较为显著。本文就近年来针对MDMA心肌毒性机制的法医毒理学研究进展进行综述,为进一步深入研究提供理论信息。     

MDMA对原代培养乳鼠脑皮质神经元的损伤机制

目的探讨3,4-亚甲双氧甲基安非他明(MDMA)对原代培养乳鼠脑皮质神经元的损伤机制。方法应用ATP酶测试盒法、荧光分光光度法和高效液相色谱法,分别检测神经细胞线粒体内ATP酶活性、细胞培养上清液中去甲肾上腺素(NA)和多巴胺(DA)含量;电镜下观察MDMA对神经元细胞表面和内部超微结构的组织形态学影响。结果与正常对照组同步比较,培养8d后加入MDMA后继续培养1d,MDMA(50~2000μmol/L)组显示ATP酶活性剂量依赖性降低,但在加入MDMA的细胞培养上清中未检出NA和DA,MDMA(2000μmol/L)组观察到了显著的病理组织形态学改变。结论MDMA对原代培养乳鼠脑皮质神经元有直接损伤作用,该损伤作用非NA和DA介导,与抑制ATP酶活性密切相关。     

Disopyramide and Mianserin Intoxication: A Unique Fatal Case – Review of the Literature

Lethal occurrence is exceptional after disopyramide or mianserin poisoning. A case of intentional lethal intoxication with these drugs was reported, as well as a review of the literature. Pre‐ and postmortem blood concentrations of disopyramide or mianserin were assessed in a woman who died from acute cardiac failure after ingestion. The premortem blood concentration of disopyramide alone was considered lethal, and a toxic premortem concentration of mianserin was observed that may have increased cardiovascular failure induced by disopyramide because the metabolism of both drugs is mediated via cytochrome P450. Moreover, it was shown that the postmortem redistribution of disopyramide was limited, as pre‐ and postmortem concentrations were 48 and 65 mg/L, respectively. As regards mianserin, redistribution was observed after death with pre‐ and portmortem concentrations at 0.23 and 0.79 mg/L, respectively. This case illustrates that if postmortem blood concentration of disopyramide is known, the premortem concentration can be deduced.     

Postmortem redistribution of fentanyl in the rabbit blood

Postmortem redistribution of fentanyl in the rabbit was investigated after application of the 50-μg/h Durogesic pain patch. Patches were applied for 48 hours. Two cycles of patch administration were used before characterization of the postmortem redistribution. Fentanyl showed marked redistribution into the femoral and pulmonary veins of the rabbit through 48 hours after the animals were humanely killed and the pain patches removed. The plasma concentration of 2.34 ng/mL in the femoral blood before killing the animals increased 5.6-fold by 48 hours after patch removal to 13.2 ng/mL. This postmortem concentration is approximately 3-fold the C(max) determined during antemortem pharmacokinetic analysis, 4 ng/mL, which was achieved 24 hours after the application of the second 50-μg/h Durogesic pain patch. After blood sampling for 48 hours after animal termination with patch removal compared with sampling for 48 hours from animals not terminated and with patch removal, the exposure ratios in the terminated animals were approximately 30-fold, indicating that between the postmortem redistribution of fentanyl and the cessation of hepatic clearance of fentanyl in the rabbit, the postmortem redistribution of fentanyl leads to an elevated measures of postmortem blood concentrations relative to antemortem blood concentrations.     

Postmortem redistribution of morphine and its metabolites

The postmortem redistribution of morphine, morphine-3-glucuronide, morphine-6-glucuronide and total morphine was assessed in 40 heroin-related deaths. In blood taken from subclavian, heart, and femoral regions, concentrations of morphine and its metabolites were similar. While there was a trend for higher concentrations in heart blood, when compared with femoral or subclavian blood, this was not significant. There was also no significant difference in concentrations between admission and autopsy blood in which the postmortem interval was on average 59 h. From our observations, significant postmortem redistribution of morphine and its metabolites seems unlikely.     

Interpretation of a 3,4-methylenedioxymethamphetamine (MDMA) blood level: discussion by means of a distribution study in two fatalities

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy" is a currently used or abused designer drug and fatalities are frequently encountered in forensic practice. However, the question remains open whether an MDMA blood level can be toxic or even potentially lethal. In order to provide insight in the interpretation of a detected MDMA concentration, the distribution of MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) in various body fluids and tissues was studied and discussed in two different fatalities. Apart from peripheral blood samples (such as femoral and subclavian blood), various blood samples obtained centrally in the human body and several body fluids (such as vitreous humour) were examined. In addition, various tissues such as cardiac muscle, lungs, liver, kidneys, and brain lobes were analysed. In contrast to the peripheral blood levels, high MDMA and MDA levels were found in cardiac blood and the majority of the organs, except for the abdominal adipose tissue. The high concentrations observed in all lung lobes, the liver and stomach contents indicate that post-mortem redistribution of MDMA and MDA into cardiac blood can occur and, as a result, blood sampled centrally in the body should be avoided. Therefore, our data confirm that peripheral blood sampling remains "the golden standard". In addition, a distinct difference in peripheral blood MDMA concentrations in our two overdose cases was established (namely 0.271 and 13.508 microg/ml, respectively). Furthermore, our results suggest that, if a peripheral blood sample is not available and when putrefaction is not too pronounced, vitreous humour and iliopsoas muscle can be valuable specimens for toxicological analysis. Finally, referring to the various mechanisms of death following amphetamine intake, which can result in different survival times (e.g. cardiopulmonary complications versus hyperthermia), the anatomo-pathological findings and the toxicological results should be considered as a whole in arriving at a conclusion.     

Experimental Study on the Postmortem Redistribution of the Substituted Phenethylamine, 25B‐NBOMe

2‐(4‐Bromo‐2,5‐dimethoxyphenyl)‐N‐(2‐methoxybenzyl)ethanamine (25B‐NBOMe) is a substituted phenethylamine, which has become highly prevalent worldwide since 2014. Recently, in an autopsy case involving fatal 25B‐NBOMe intoxication, we found the postmortem increase of 25B‐NBOMe concentration in the cardiac blood approximately 2 days after death. The aim of this study was to investigate the distribution of 25B‐NBOMe and reproduce the postmortem redistribution using a rat model. Sprague‐Dawley rats were killed 30 min after intraperitoneal injection of 25B‐NBOMe (0.5 mg/kg) and left for 0, 3, 6, 9, 15, or 24 h (six rats at each time point). Postmortem 25B‐NBOMe concentrations in the cardiac blood increased by more than 10‐fold at 6‐h postmortem. 25B‐NBOMe accumulated primarily in the lung. Moreover, this postmortem redistribution occurred even in rats that had died 1 week following the 25B‐NBOMe administration. These findings indicate that attention should be paid to sample collection and data interpretation in the toxicological analysis of 25B‐NBOMe.     

An Examination of the Postmortem Redistribution of Fentanyl and Interlaboratory Variability,

Fentanyl is a synthetic opioid agonist used for pain control. Often administered as a transdermal patch, it is an interesting drug for study of postmortem redistribution. We hypothesized that fentanyl concentrations would increase over time after death, as measured in blood drawn on the day prior to autopsy and in blood drawn at the time of autopsy in ten cases where fentanyl patches were identified at the scene. Concentrations were compared, and heart blood to femoral blood ratios were calculated as markers of postmortem redistribution. Fentanyl concentrations measured in peripheral blood drawn the day of autopsy (peripheral blood 2 [PB2]) were higher than those drawn the day prior to autopsy (peripheral blood 1 [PB1]) with a mean ratio (PB2/PB1) of 1.80. The ratio of heart blood concentrations (HB) to femoral blood concentrations drawn at autopsy (PB2) had a mean ratio (HB/PB2) of 1.08. Some cases had blood from the same source analyzed at two different laboratories, and concentrations of fentanyl in those samples showed inter‐ and intralaboratory differences up to 25 ng/mL. Postmortem fentanyl concentrations may be affected by antemortem factors, postmortem redistribution, and laboratory variability. Forensic pathologists must use caution in interpreting fentanyl levels as part of death investigation.     

Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam,Methadone, and Morphine

Postmortem redistribution (PMR) refers to the site‐ and time‐related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution.     

阿维菌素在急性中毒死家兔体内的再分布研究

目的考察阿维菌素在急性中毒死家兔体内的再分布。方法按最小致死量一次性灌胃250mg/kg阿维菌素,HPLC法检测家兔死后0h、24h、48h和72h中阿维菌素的含量。结果给家兔一次性灌胃250mg/kg阿维菌素的临床死亡时间为120.6±9.2min(±s,n=10);测定了阿维菌素的致死血浓度和致死组织浓度;家兔死后0h~72h心血和各主要脏器组织中阿维菌素含量存在体内再分布现象;确定肝、肾、肺为最佳组织检材。结论阿维菌素在急性中毒死家兔体内的再分布数据,对法医办理此类案件具有重要参考价值。