基因多态性、饮酒种类与乙醇代谢的相关性CSCD

目的探索ADH1B和ALDH2基因多态性以及饮酒种类对乙醇代谢的影响,为司法鉴定实践中涉及乙醇代谢结果解释或对血乙醇含量回推的案件提供数据支持。方法筛选出81名志愿者,通过多重SNa Pshot分型方法获得ADH1B、ADH1C和ALDH2的基因型。饮酒剂量为1.0 g/kg,在饮酒前以及饮酒后30 min、45 min、1 h、1.5 h、2 h、3 h、4 h、5 h、6 h、7 h和8 h静脉采血1 m L,通过顶空气相色谱法检测血中乙醇和乙醛的浓度,计算血乙醇达峰时间(T_(max))、乙醇峰值质量浓度(C_(max))、乙醇曲线下面积(area under curve,AUC_(乙醇))、AUC_(乙醛)和乙醇消除斜率(β)。为排除ADH1C基因多态性的干扰,选择携带ADH1C*1/*1基因型的个体,根据ADH1B和ALDH2的基因型分组,对各组上述参数进行单因素方差分析,并运用最小显著差异法进行组间比较,基因间的相互作用关系采用双因素方差分析。对3种饮酒种类(白酒、红酒和啤酒)组间的各参数进行随机区组设计方差分析。结果不同ADH1B和ALDH2基因型组间T_(max)和C_(max)差异无统计学意义,部分基因型组间AUC_(乙醇)、β和AUC_(乙醛)差异有统计学意义。个体饮相同剂量不同种类酒时,各组间各参数差异均无统计学意义。结论乙醇代谢受相关基因多态性影响较大,基本不受饮酒种类的影响。     

基因多态性、饮酒种类与乙醇代谢的相关性

目的探索ADH1B和ALDH2基因多态性以及饮酒种类对乙醇代谢的影响,为司法鉴定实践中涉及乙醇代谢结果解释或对血乙醇含量回推的案件提供数据支持。方法筛选出81名志愿者,通过多重SNa Pshot分型方法获得ADH1B、ADH1C和ALDH2的基因型。饮酒剂量为1.0 g/kg,在饮酒前以及饮酒后30 min、45 min、1 h、1.5 h、2 h、3 h、4 h、5 h、6 h、7 h和8 h静脉采血1 m L,通过顶空气相色谱法检测血中乙醇和乙醛的浓度,计算血乙醇达峰时间(T_(max))、乙醇峰值质量浓度(C_(max))、乙醇曲线下面积(area under curve,AUC_(乙醇))、AUC_(乙醛)和乙醇消除斜率(β)。为排除ADH1C基因多态性的干扰,选择携带ADH1C*1/*1基因型的个体,根据ADH1B和ALDH2的基因型分组,对各组上述参数进行单因素方差分析,并运用最小显著差异法进行组间比较,基因间的相互作用关系采用双因素方差分析。对3种饮酒种类(白酒、红酒和啤酒)组间的各参数进行随机区组设计方差分析。结果不同ADH1B和ALDH2基因型组间T_(max)和C_(max)差异无统计学意义,部分基因型组间AUC_(乙醇)、β和AUC_(乙醛)差异有统计学意义。个体饮相同剂量不同种类酒时,各组间各参数差异均无统计学意义。结论乙醇代谢受相关基因多态性影响较大,基本不受饮酒种类的影响。     

乙醇、乙醛慢代谢与酒后驾车肇事

在体内乙醇代谢过程中起重要作用的酶有乙醇脱氢酶（ADH）、乙醛脱氢酶（ALDH）和细胞色素P4502E1酶（CYP2E1）,它们均具有基因多态性,不同基因型个体对乙醇的耐受性存在差别,表现为酒后的行为反应能力不同。司机若为慢代谢型,乙醇、乙醛代谢速率低下,即使少量饮酒,酒后开车也可造成交通肇事。通过对ADH、ALDH和CYP2E1基因多态性与乙醇、乙醛代谢能力的关系进行综述。     

血中乙醇质量浓度与神经行为能力的关系

目的 研究血中乙醇质量浓度与神经行为能力的关系。方法 采用中文第三版计算机化神经行为测试评价系统（NES-C3）,通过自身对照的方式,对233名饮酒者进行神经行为能力的测试。结果 当血中乙醇质量浓度I〉0．157mg／mL时,视简单反应时和数字筛选能力指数有显著性下降;当血中乙醇质量浓度I〉0．204mg／mL时,心算、视觉保留、线条判断能力指数有显著性下降。结论 神经行为能力随着血中乙醇质量浓度的升高而下降,然后随着乙醇的不断代谢,血中乙醇质量浓度的降低,神经行为能力逐渐恢复。     

GC法检测血液和尿液中甲基苯丙胺和咖啡因

目的建立同时测定血、尿中甲基苯丙胺和咖啡因含量的方法。方法应用GC／NPD技术,以4-苯基丁胺为内标,直接碱化,用氯仿提取,三氟乙酸酐衍生化,8CB熔融石英毛细管柱（30m×0．25mm×0．25μm）分析。结果生物样品中甲基苯丙胺与咖啡因在0．012—7．5μg/mL浓度范围内线性关系良好,检测限（S／N=3）依次为1．2ng／mL,0．6ng／mL（血）;1．6ng／mL,0．8ng／mL（尿）。苯丙胺在0．017—10．0μg／mL浓度范围内线性关系良好,检测限为1．6mg／mL（血）,3．2ng／mL（尿）。所有样本回收率均大于85％。结论本方法准确、灵敏,适用于血、尿中甲基苯丙胺及其代谢物苯丙胺的三氟乙酸酐衍生化物和咖啡因的同时检测,为判定滥用毒品种类、追查毒品来源以及研究生物体内甲基苯丙胺和咖啡因的交互影响提供了检测手段。     

藿香正气水中中药成分对大鼠体内乙醇代谢的影响

目的研究服用藿香正气水后,大鼠体内乙醇含量及药代动力学参数的变化。方法将大鼠随机分为3组,分别按3.0 m L/kg剂量灌胃白酒、低浓度中药酒和高浓度中药酒,于给药前(0 min)和给药后5 min、10 min、15 min、30 min、1 h、2 h、3 h、4 h、5 h、6 h、8 h断尾采血,用顶空-气相色谱法测定大鼠血液中的乙醇含量,用DAS 2.0软件计算乙醇的药代动力学参数,SPSS 17.0软件对药代动力学参数进行分析。结果高浓度中药酒组与白酒组最大血药浓度相比,差异有统计学意义(P0.05);其他药代动力学参数在三组间差异均无统计学意义(P0.05)。结论藿香正气水中中药成分对大鼠体内乙醇代谢和消除无明显影响。本研究对涉及饮用藿香正气水导致的交通案(事)件的定性判定和处理以及药物间的相互作用研究具有参考意义。     

生物检材中阿维菌素的HPLC—MS／MS分析

目的建立生物检材包括血、肝组织、胃组织中阿维菌素（Avermectins）的HPLC—MS／MS分析方法。方法采用Oasis HLB固相萃取柱进行提取,以XTerra^TM RP18柱（2．1mm×100mm,3．5μm）色谱柱分离,以甲醇-0．1％冰醋酸水溶液（75：25）为流动相,流速为0．2mL／min。结果线性范围10ng／mL～3μg／mL,最小检出限为0．1ng／mL。结论本方法准确、快速,可用于生物检材血中阿维菌素的定性定量分析,肝及胃组织中阿维菌素的定性分析。     

酒的种类对乙醇代谢动力学的影响

目的乙醇代谢动力学受诸多因素影响，关于酒的种类对其影响少见报道。方法本研究让志愿者在相同的饮酒时间内，饮用舍相同乙醇量的啤酒、白酒。将所得数据用药代动力学计算程序DAS Ver1．0进行处理。结果乙醇的体内过程符合一级吸收、非线性消除、一室模型，权重为1。啤酒与白酒相比，吸收速度快，峰浓度高。达峰时间旱，消除速度快。结论酒的种类对乙醇代谢动力学有影响，如果根据乙醇的代谢动力学规律来推测饮酒个体某一时刻的BAC。或根据BAC推测实际饮酒量，应该充分考虑到酒的种类对乙醇代谢动力学的影响。     

酒精在人体内的代谢动力学研究

将16名健康男性志愿者随机分为两组，分别按含酒精0．65g／kg和0．80g／kg体重的剂量给予酒精饮料，于酒后不同时间点采取静脉血样。用乙醇脱氨酶（ADH）氧化分析法测血样酒精浓度（BAC），所得浓度-时间数据经用药代动力学软件分析拟合。结果表明，酒精在人体内的代谢符合非线性消除伴一级吸收的一室开放模型。据此，作者建立了描述酒精在人体内动态变化规律的数学模型。经验证，该模型符合度良好，可用于司法实践。     

腐败血液中乙醇的顶空气相色谱分析

目的分析血液腐败后产生的乙醇及其他物质并探讨腐败血液中乙醇的检测及计算方法。方法以正常人空白血液制作腐败血样,采用1,4-二氧六环为内标物,通过顶空气相色谱进行定性及定量分析。结果血中乙醇在0.0625～1mg/mL范围内线性关系良好（r^2=0.9996）,各质量浓度组的变异系数（CV%）〈2%,血中乙醇的最低检出限为1μg/mL（S/N≥3）。腐败血样所产生乙醇与正丙醇的比例大致为25：1。结论检验方法简便、准确。为法医毒化检验相关工作提供了依据。     

Fatal acute alcohol intoxication in an ALDH2 heterozygote: a case report

On an evening in November, a 25-year-old man was found dead in his bedroom. There were many empty snap-out sheets for flunitrazepam tablets in the trash at his bedside. He had been beaten by a gang of young people earlier in the morning of the same day. At the medico-legal autopsy, although there were many bruises and/or abrasions on the whole body, only slight subdural hemorrhage was observed, and none of them was thought to be the cause of death. Flunitrazepam and its metabolites were not detected in his body fluid by gas chromatography-mass spectrometry (GC-MS). Marked lung edema and a severe congestion of organs were observed. His blood alcohol concentration from the femoral vein was 2.00 mg/ml. Fatal cases of acute alcohol intoxication usually have shown higher alcohol concentration (2.25-6.23 mg/ml). Although the genotype of aldehyde dehydrogenase 2 (ALDH2) has not previously been mentioned as a contributing factor in determining the cause of death, in this case the genotype of ALDH2 was ALDH2*1/2 and thus is important. Those who possess the ALDH2*2 gene show high concentrations of acetaldehyde (AcH) at even comparatively lower alcohol levels. Consequently, the cause of death was considered to be acute alcohol intoxication including AcH poisoning.     

Suicidal Fatality from Azide Ingestion

A 35-year-old man ingested an unknown amount of sodium azide and died within 2 h. The postmortem interval was 3 days. No alcohol or drugs were found in the blood and urine. Azide was derivatized in the peripheral blood, urine, and vitreous fluid with propionic anhydride. A portion of the headspace was injected onto a gas chromatograph with a nitrogen–phosphorus detector. Azide was quantitated in the peripheral blood (1.1 μg/mL), urine (7.5 μg/mL), and vitreous (43 μg/mL). The vitreous appears to be a better fluid for azide screening because of slower degradation.     

UPLC-MS/MS法同时检测全血中16种除草剂

目的建立全血中16种除草剂的超高效液相色谱-串联质谱(UPLC-MS/MS)同时检测方法,为除草剂中毒案事件及其他刑事案件血液中该16种除草剂的检验鉴定提供依据。方法取200μL的血液,加入800μL乙腈-水(体积比80/20),进行蛋白沉淀后,采用Acquity BEH C18(2.1mm×100mm,1.7μm)色谱柱,以水(5mmol/L的甲酸铵,0.1%的甲酸)-乙腈为流动相进行梯度洗脱,采用电喷雾离子源(ESI)、多反应监测(MRM)正离子模式对16种化合物进行检测。结果在1~200ng/mL范围内线性关系良好,R2均大于0.996;基质效应(ME%)为85.2%~104.4%,相对标准偏差(RSD%)为0.72%~4.84%;仪器检出限(IDLs)为0.2~2 ng/mL(信噪比S/N≥3),方法检出限(MDLs)为0.5~3ng/mL(信噪比S/N≥3),最低定量限(LOQs)为1~7ng/mL(信噪比S/N≥10)。结论本实验建立的全血中16种除草剂同时检验方法,前处理简便快捷、回收率高、精密度好、方法检出限低,可作为该16种除草剂中(投)毒案件的检验方法。     

Determination of Acetamiprid and IM‐1‐2 in PostMortem Human Blood,Liver, Stomach Contents by HPLC‐DAD

An HPLC‐DAD method was developed to detect and quantify a neonicotinoid insecticide acetamiprid (ATP) and its metabolite IM‐1‐2 in autopsy samples of a fatal intoxication case. The postmortem blood and tissue distribution of ATP and IM‐1‐2 was determined for the first time. The method showed acceptable precisions and recoveries with relative standard deviations of <10% for ATP level and 1.38 % for IM‐1‐2. The detection and quantification limits for ATP were 0.015 μg/mL and 0.030 μg/mL for blood and were 0.035 μg/g and 0.050 μg/g for liver samples, respectively. The mean contents of ATP were 0.79 μg/g in the liver, 47.35 μg/g in the stomach contents and 2.7 μg/mL in the blood. IM‐1‐2 content was 17.0 μg/g in the stomach contents. ATP and IM‐1‐2 were not detected in the urine. The presence of ATP and IM‐1‐2 in the samples was confirmed by GC‐MS. The method can be exploited in future forensic casework.     

HPLC-MS/MS方法检验血液中可待因

目的 采用HPLC-MS/MS方法对血液中可待因进行定性、定量检验.方法 以Clean Screen DAU混合阳离子交换固相萃取柱提取血样,应用HPLC色谱法分离,MS/MS检测分析.结果 该方法回收率高于70％,线性范围0.01～2 μg/mL,检测限0.1ng(S/N≥3).结论 本文方法快速、灵敏、准确,可用于血液中可待因的定性、定量分析检验.     

Genetically-induced variability of alcohol metabolism and its effect on drinking behavior and predisposition to alcoholism

Alcoholism is one of the most challenging current health problems in the Western countries with far-reaching medical, social, and economic consequences. There are a series of factors that interact in predisposing or protecting an individual against alcoholism and alcohol-related disorders. This article surveys the state of our knowledge concerning the biochemical and genetic variations in alcohol metabolism and their implications in alcohol sensitivity, alcohol drinking habits, and alcoholism in different racial/ethnic groups. The major pathway for the degradation of ethanol is its oxidation to hydrogen and acetaldehyde--to which many of the toxic effects of ethanol can be attributed. Variations in alcohol and acetaldehyde metabolism via genetically determined polymorphisms in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) seem to play an important role in individual and racial differences in acute and chronic reactions to alcohol, alcohol drinking habits, as well as vulnerability to organ damage after chronic alcohol abuse. Alcohol sensitivity and associated discomfort symptoms accompanying alcohol ingestion may be determinental for the significantly low incidence of alcoholism among the Japanese, Chinese and other Orientals of Mongoloid origin. An abnormal ALDH isozyme has been found to be widely prevalent among individuals of the Mongoloid race and is mainly responsible for the acute sensitivity to alcohol commonly observed in this race. Persons sensitive to alcohol by virtue of their genetically controlled ALDH isozyme deficiency may be discouraged from drinking large amounts of alcohol in their daily life due to the initial adverse reaction experienced after drinking alcohol. Indeed, a significantly low incidence of the mitochondrial ALDH isozyme deficiency has been observed in alcoholics as compared to psychiatric patients, drug dependents and healthy controls in Japan. How far any variation in ADH and/or ALDH activity among individuals of Caucasian origin will have similar effects has yet to be studied.     

HPLC-UVD/FLD法测定血中氟乙酸类杀鼠剂

目的采用水相催化衍生化-液相色谱-紫外/荧光检测分析法,检测血中氟乙酸类杀鼠剂。方法血样经乙腈沉淀蛋白后,加入衍生化试剂4-溴甲基-7-甲氧基香豆素、催化剂四丁基溴化铵,在80℃水浴中衍生化反应120min,衍生产采用液相色谱-紫外/荧光检测分析。结果紫外检测法:氟乙酸根浓度在0.38～38.50μg/mL之间线性关系良好,最低检出限为0.10μg/mL;荧光检测法:氟乙酸根浓度在0.15～15.40μg/mL之间线性关系良好,最低检出限为0.050μg/mL。结论水相催化衍生化-液相色谱-紫外/荧光检测分析方法具有较好的灵敏度、准确性和精密度,可用于实际案例检测。     

HS-SPME-GC/MS联用法测定生物检材中的百草枯

目的建立检测生物检材中百草枯的顶空固相微萃取-气相色谱-质谱联用（HS-SPME-GC/MS）的分析方法。方法尿样中加乙基百草枯作为内标,在氯化镍作催化剂的条件下,用硼氢化钠在碱性条件下进行还原,HS-SPME萃取,提取物经GC/MS分析。全血需先离心,沉淀血细胞提取上清液,再用甲醇沉淀蛋白。最终得到的上清液加内标乙基百草枯,以下操作同尿样。结果尿样和血样中的百草枯的还原产物在1.0μg/mL~100μg/mL范围内线性关系良好,回归方程分别为y=0.0957x-0.0163,r=0.9974（n=6）;y=0.1096x＋0.0871,r=0.9964（n=6）。尿样、血样低、中、高三个质量浓度,RSD值均小于7%。回收率分别为尿样85.49%~100.83%,血样94.72%~99.68%。结论本法操作简便易行、灵敏度高、快速准确。为检测生物检材中的百草枯提供了有效的方法。