Regional distribution of cocaine in postmortem brain of chronic human cocaine users

We measured concentrations of cocaine and its major metabolites (benzoylecgonine, ecgonine methylester, norcocaine, and cocaethylene) in 15 autopsied brain regions of 14 human chronic cocaine users. Only slight differences were observed in concentrations of cocaine and its metabolites amongst the examined brain areas. Although it is likely that some postmortem redistribution of the drug must have occurred, our data are consistent with the possibility that behaviorally relevant doses of cocaine are widely distributed throughout the brain of humans who use the drug on a chronic basis. Consideration should therefore be given to the possible pharmacological and toxicological actions of cocaine in both striatal and extra-striatal brain areas in human users of the drug.     

Determination of chronic methamphetamine abuse by hair analysis

A 30-year-old male truck driver, known to be asthmatic, was found dead at the roadside lying near his car. A nebulizer bottle of Berotec (fenoterol hydrobromide) was found near his hand. The anatomic cause of death was suspected to be asthma. Toxicological screening of urine using Triage demonstrated the presence of methamphetamine. The blood concentration of methamphetamine was 0.4 microg/ml, and fenoterol was not detected. Hair analysis clearly indicated chronic methamphetamine abuse and medium dependency during the 2 months before death. We conclude that death might have been induced by the interaction of fenoterol and methamphetamine.     

Structural alterations in the human brain in chronic alcohol intoxication

Different brain samples were studied in 23 male alcoholics and 14 healthy victims who had died of heart and major vessels wounds to determine histological changes in the brain and quantitative relations between its tissue structures. The complex of histological, stereo- and morphometric examinations has shown that the brain of alcoholics is characterized by sclerosis and hyalinosis of the vascular branches as well as dystrophic, atrophic and hypertrophic changes of neurocytes. Moreover, there were calcinated petrificates and the cysts, foci of demyelination, diffuse microglyosis. These alterations are accompanied with impairment of quantitative correlations between tissue brain structures. The diameter of cerebral capillaries narrows with resultant lessening of vascular bed capacity and chronic brain ischemia. The concentration of nervous cells decreased because of their progressive atrophy and death while the indices of the glyal component development rose. The findings are important for tanatogenesis and postmortem forensic-medical diagnosis of alcoholism.     

CI-mass fragmentographic analysis of methamphetamine and amphetamine in human autopsy tissues after acute methamphetamine poisoning

A 22-year-old male methamphetamine abuser was put under police protection owing to his abnormal state of excitation, but died 1 h later. Distribution of methamphetamine and amphetamine in the body was analyzed by the chemical ionization mass fragmentographic method. Amphetamine/methamphetamine concentrations (μmol/100 g) were $\text{0.24}\text{5.59}$ in blood, $\text{0.41}\text{9.43}$ in liver, $\text{0.41}\text{10.02}$ in brain, $\text{0.37}\text{9.80}$ in kidney, $\text{0.18}\text{4.57}$ in muscle, $\text{0.02}\text{0.63}$ in subcutaneous fat and $\text{1.87}\text{1464}$ in gastric contents. Total amount of methamphetamine hydrochloride in stomach contents was about 54 mg. Amphetamine concentrations in tissues ranged from 3.2% to 4.3% of methamphetamine, and was 0.1% in stomach contents. Amphetamine in tissues seems to be a metabolite of methamphetamine, and amphetamine in gastric contents is presumed to result from gastric mucous excretion. The blood concentration of methamphetamine was at a fatal level, and the total amount of the drug in gastric contents indicates that fatal poisoning occurred by ingestion.     

甲基苯丙胺在豚鼠毛发中分布及转化的初步研究

目的对甲基苯丙胺在豚鼠毛发中分布及转化机制进行初步研究。方法利用GC/MS,GC/NPD法,测定单次及多次给药豚鼠毛发中MAP、AP的含量变化过程,考察给药剂量与毛发中MAP、AP的含量间的关系,并研究毛发颜色对染毒豚鼠毛发中MAP、AP含量的影响。结果单次及多次给药豚鼠毛发中代谢产物AP均高于原体MAP,给药时间及给药剂量与毛发中MAP、AP的含量显著相关,同体豚鼠黑色毛发中的MAP、AP含量均明显高于棕色、白色毛发。结论给药方式、给药剂量及毛发颜色对豚鼠毛发中MAP、AP的含量均有显著影响。     

甲基苯丙胺及其代谢产物在急性中毒豚鼠体内的分布

目的研究甲基苯丙胺 (MAP)及其代谢产物苯丙胺 (AP)在急性中毒豚鼠体内的含量分布。方法应用GC/NPD技术 ,以 4 苯基丁胺 (4 PBA)为内标 ,样品经水解后碱化或直接碱化至pH >11,环已烷混旋提取 ,三氟乙酸酐 (TFA)微波衍生化 ,测定MAP急性中毒豚鼠体液和组织中MAP及AP的含量。结果急性中毒死亡豚鼠体内各器官和体液中MAP及AP含量最高为肺 ;其次为肝、脑、肾、脾、肠、心、血 ;再次为胃、胆汁 ;最少是尿。结论MAP在动物体内代谢迅速 ,组织或体液中MAP和AP浓度的比值与豚鼠给药后存活时间有关     

A high selective screening test for methamphetamine in human urine

A high selective screening test (Ad-Tip method) for methamphetamine in human urine has been devised. The method involves a brief extraction from a urine sample with an Ad-Tip (ODS-silica minicolumn), washing, eluting with modified Simon's reagent, and coloration with carbonate buffer. Detection limit of methamphetamine in urine is 1 microgram/ml and the test takes within 3 min/sample. The results of the Ad-Tip method were almost identical to those of laboratory analyses.     

Use of MDA (the "love drug") and methamphetamine in Toronto by unsuspecting users of ecstasy (MDMA)

It has recently been reported that purity of illicit tablets of ecstasy (MDMA) is now high. Our objective was to confirm whether hair of drug users, who request only ecstasy from their supplier, contains MDMA in the absence of other drugs. GC-MS analysis of scalp hair segments disclosed the presence of MDMA in 19 of 21 subjects and amphetamine/methamphetamine in eight subjects. Surprisingly, seven subjects had hair levels of the MDMA metabolite, MDA, equal to or greater than those of MDMA, suggesting use of MDA in addition to that of MDMA. These amphetamine derivatives might be included by clandestine laboratories to enhance effects of the drug cocktail or because of a perception that MDA synthesis might be simpler than that of MDMA. Drug users and investigators examining possible brain neurotoxic effects of MDMA need to consider that "ecstasy" tablets can contain MDA and methamphetamine despite no demand for the drugs.     

Report documents human rights abuses of drug users in Thailand

A violent, state-sponsored "war on drugs" is jeopardizing Thailand's long struggle to become one of Southeast Asia's leading rights-respected democracies. This is one of the findings of a report released by Human Rights Watch (HRW) on the eve of the XV International AIDS Conference in Bangkok, Thailand in July 2004.     

甲基苯丙胺在家兔体内的毒物代谢动力学研究

目的研究甲基苯丙胺及其代谢物苯丙胺在家兔体内的毒物代谢动力学行为。方法GC/MS法测定家兔灌胃甲基苯丙胺后不同时间点血、尿中甲基苯丙胺和代谢物苯丙胺浓度,采用3P97程序进行房室模型拟合以及毒物代谢动力学参数计算。结果甲基苯丙胺和苯丙胺在家兔体内的毒物代谢动力学过程均呈一级动力学特征,符合二室开放模型。甲基苯丙胺在家兔体内Cm ax为1.457 mg/L±0.094 mg/L,Tm ax为1.557h±0.078h,t1/2 ka、t1/2α和t1/2β分别为0.384h±0.052h、1.614h±0.036h和3.007h±0.430h,CL为1.769 L/h/kg±0.114 L/h/kg。甲基苯丙胺的毒物代谢动力学方程为:C t=2.767 e-0.746 t+1.454 e-0.234 t+4.119 e-1.746 t。结论甲基苯丙胺在家兔体内吸收、消除和代谢都较快。建立的甲基苯丙胺毒物代谢动力学方程和参数可为甲基苯丙胺分析的合理取样、从血药浓度推断服毒时间以及甲基苯丙胺滥用的法医学鉴定提供理论依据。     

Assessment of edema fluid distribution in the brain

The technique is proposed allowing quantitation of brain edema and typing of liquor distribution in different parts of brain tissue. In combination with other assays this test can determine a variant of tanatogenesis, detect cause of death and duration of the terminal period. The method application is illustrated by the study of brain hydration in mechanical strangulation asphyxia. It is shown that this death is associated with hypohydration of cerebral structures, especially pronounced in the cortical compartments.     

On-column derivatization for determination of amphetamine and methamphetamine in human blood by gas chromatography-mass spectrometry

A simple determination method of amphetamine (AP) and methamphetamine (MA) in human blood was developed using on-column derivatization and gas chromatography-mass spectrometry (GC-MS). AP and MA were adsorbed on the surface of Extrelut and then derivatized the N-propoxycarbonyl derivatives using propylchloroformate. Pentadeuterated MA was used as an internal standards. The recoveries of AP and MA from the spiked blood were 89.7 and 90.3%, respectively. The calibration curves showed linearity in the range of 12.5-2000 ng/g for AP and MA in blood. The coefficients of variation of intraday and interday were 0.42-4.58%. Furthermore, this proposed method was applied to some medico-legal cases of MA intoxication. MA and its metabolite AP were detected in the blood samples, and the correlation of the blood level of amphetamines and the behaviors of the victims was in good agreement with the criteria proposed by Nagata [Jpn. J. Legal Med. 37 (1983) 513].     

Interaction of 3,4-methylenedioxymethamphetamine and methamphetamine during metabolism by in vitro human metabolic enzymes and in rats

Illicit amphetamine-type stimulant (ATS) tablets commonly contain one or more active ingredients, which have hallucinogenic and/or stimulant effects. Because components such as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MA) in ATS tablets have similar chemical structures, they could be metabolized by common metabolic enzymes. To investigate potential metabolic interactions of ATS tablet components, we studied the in vitro metabolism of MDMA and MA using human metabolic enzymes. MDMA and MA were mainly metabolized by cytochrome P450 2D6 (CYP2D6) and mutually inhibited the production of their main metabolites. In vivo experiments were also performed using intravenous administration of MDMA, MA, or their mixture to rats. The plasma concentrations of MDMA and MA after co-administration were higher than those after administration of MDMA or MA alone. The results in this study imply that multiple components in ATS tablets can interact to mutually inhibit their metabolism and potentially enhance the toxicity of each component.     

Determination of manganese in human brain samples

A method is presented for the determination of manganese (Mn) in human tissue samples (especially brain) by graphite furnace atomic absorption spectrophotometry (GFAAS). After complete digestion by a mixture of concentrated nitric acid (HNO₃)/concentrated perchloric acid (HClO₄) (50:50, v/v), the samples are assayed on a Perkin-Elmer 5100 PC apparatus, equipped with transversal graphite tubes and a Mn-specific hollow cathode lamp. The furnace conditions are as follows (for each step: temperature (°C)/ramp (s)/duration (s)) dry 120/1/40; char 1200/5/10; atomization 2250/0/4; pyrolysis 2400/1/1. Zeeman correction is employed. The method is linear over the range 0.05 to 5.00 μg/g wet tissue, and the limit of detection for Mn is about 0.01 μg/g wet tissue. This simple and rapid method may be of value for the post-mortem assessment of Mn accumulation in brain structures due to occupational or iatrogenic exposure. An application is presented in which elevated levels of Mn were determined in the brain samples of a 63-year-old female deceased after long-term total parenteral nutrition involving Mn supplementation.     

Human plague in New Mexico: report of three autopsied cases

Plague is a deadly disease of obvious concern to individuals, communities, and public health officials. The rapid recognition of plague victims is of paramount importance in saving the lives of the victims and in the protection of contacts. Three autopsied plague cases have been presented and the pathological features have been discussed.     

Markers of chronic alcohol use in hair: comparison of ethyl glucuronide and cocaethylene in cocaine users

Two direct ethanol metabolites, namely ethyl glucuronide (EtG) and cocaethylene (CE), in the hair of cocaine (COC) users were compared in this study. Hair samples (n=68) were submitted to the determination of EtG (by liquid chromatography-electrospray-tandem mass spectrometry) and of COC and metabolites, including CE (by gas chromatography-mass spectrometry). Quantitative and qualitative results were compared. No quantitative correlation was found between EtG and CE, as well as between EtG and the cocaethylene concentration divided by the concentration of COC and its metabolites (benzoylecgonine and ecgonine methylester, as COC equivalents). Nevertheless, many factors are supposed to affect the amount of the two substances incorporated in the hair matrix, such as the subject's habits in ethanol and COC use, genetic variability in the metabolism of both substances, and the different chemical and physical properties of EtG and CE. When establishing a cut-off of 4 pg/mg for EtG and of 200 pg/mg for CE, 47 samples tested positive for EtG and 41 samples tested positive for CE; 12 samples out of the 47 EtG-positives tested negative for CE (25%), whereas 6 samples out of the 41 CE-positives tested negative for EtG (15%). According to these data, EtG appears to be a more sensitive and specific marker of non-moderate alcohol users than CE.     

Immunohistochemical detection of methadone in the human brain

To develop a method of detecting methadone in the human brain by immunohistochemistry, brain tissue of frontal cortex, cerebellum, hippocampus, basal ganglions and brain stem from victims of a lethal methadone overdose was examined. The staining was performed with a monoclonal anti-methadone antibody from the mouse, originally developed for immunochemichal purposes (ELISA). With the help of the DAKO((R)) Catalyzed Signal Amplification (CSA) System, a specific positive immunoreaction was obtained in the neurons of the frontal cortex and hippocampus, as compared with specimen from deaths without exposition to methadone. Thus, along with metamphetamine, phenobarbital, morphine and insulin, immunohistochemical detection is also possible for methadone and the intake of this medicament can now be proven morphologically.     

生物检材中甲基苯丙胺及苯丙胺的分析研究进展

对近几年国内外22篇有关生物检材中甲基苯丙胺及苯丙胺测定的文献进行了综述。介绍了血、尿、毛发等生物检材的收集与预处理方法,比较了生物检材中甲基苯丙胺及苯丙胺的液-液萃取(LLE)、固相萃取(SPE)、固相微萃取(SPME)和顶空固相微萃取(HS-SPME)等提取方法,以及内标的选取、不同的衍生化方法和包括免疫、GC/MS、GC/NPD、GC/ECD、GC/FID、HPLC、HPCE在内的各种检测方法。最后,对分析结果的评定进行了讨论。