Drug-related deaths with evidences of body packing: Two case reports and medico-legal issues

Body packing is a general term used to indicate the internal transportation of drug packages, mainly cocaine, heroin, amphetamines, and methamphetamine, within the gastrointestinal tract. We described two cases of accidental drug intoxication, observed over the last year period, with evidence of intracorporeal drug concealment. The first case concerned a body packer transporting 69 drug packages of heroin adulterated with piracetam. The second body packer transported 16 drug packages of cocaine adulterated with levamisole. For both cases, forensic examination and toxicological analysis of drug packages and biological samples were carried out. Authors also wants to highlight the main medico-legal issues that commonly arise in cases of suspected or ascertained body packers.     

莫西沙星阴道泡腾片的毒理学研究

目的研究莫西沙星阴道泡腾片（MVET）对豚鼠的毒性作用。方法对豚鼠分别采用单次及多次阴道给药，进行急性毒性和刺激性试验，观察其全身状态有无异常及阴道组织有无红斑和水肿等。结果豚鼠给药前、后全身状态无明显变化，刺激反应评分为0分。结论MVET对豚鼠安全，未见明显毒性。     

Expression profiling of heat stress effects on mice fed ergot alkaloids.

Fescue toxicosis affects wild and domestic animals consuming ergot alkaloids contained in tall fescue forage infected with the endophytic fungus, Neotyphodium coenophialum. When animals are consuming infected fescue (E+) forage during periods of elevated ambient temperatures (summer), a range of phenotypic disorders collectively called summer slump is observed. It is characterized by hyperthermia, with an accompanying decrease in feed intake, growth, milk yield, and reproductive fitness. Laboratory mice also exhibit symptoms of fescue toxicosis at thermoneutral (TN) temperature, as indicated by reduced growth rate and reproductive fitness. Our goal was to characterize the differences in gene expression in liver of mice exposed to summer-type heat stress (HS) and E+ when compared to mice fed E+ at TN temperature. Mice were fed E+ diet under HS (34 +/- 1 degrees C; n = 13; E+HS) or TN conditions (24 +/- 1 degrees C; n = 14; E+TN) for a period of 2 weeks between 47 and 60 days of age. Genes differentially expressed between E+HS versus E+TN were identified using DNA microarrays. Forty-one genes were differentially expressed between treatment groups. Expressions of eight genes were measured using quantitative real-time PCR. Genes coding for phase I detoxification enzymes were upregulated in E+HS mouse liver. This detoxification pathway is known to produce reactive oxidative species. We observed an upregulation of genes involved in the protection against reactive oxidative species. Key genes involved in de novo lipogenesis and lipid transport were also upregulated. Finally, genes involved in DNA damage control and unfolded protein responses were downregulated.     

组织芯片技术及其在新药毒理学研究中的应用

组织芯片(tissue microarray,TMA)也称组织微阵列,是将数十个甚至上千个微小组织标本整齐排列在一张载玻片上制成的高通量微阵列,是基因芯片的延伸和发展,可以同时进行多个标本的同一个指标的研究,具有体积小、耗材少、快速、含生物学信息量大等优点,该技术还可以与免疫组化(immunohistochemistry,ICH)、荧光核酸原位杂交(fluorescence in situ hybridization,FISH)、RNA原位杂交(RNA in situ hybridization,RNA-ISH)等技术相结合,在基因、转录和表达产物的不同表达分子水平进行研究。本文结合组织芯片技术的特点,对其在新药毒理学研究中的应用进行初步探讨。     

四氟苯菊酯的合成与毒理学及生物学特征

目的分析四氟苯菊酯的毒理学和生物学特征。方法通过喂食、涂敷、喷雾等方法，对埃及伊蚊、家蝇等进行直接测试。结果在试验浓度范围内，四氟苯菊酯的急慢性毒性极低，致畸、致癌性未观测到，对埃及伊蚊、家蝇、德国小蠊、幕衣蛾击倒速度快，用量小。结论四氟苯菊酯毒性低，适合用于卫生杀虫制品。     

毒理病理学报告的国际GLP规范

毒理病理学报告是一般毒理试验、啮齿类致癌性试验以及生殖发育毒理试验等非临床安全评价试验综合报告的重要组成部分,在GLP管理方面有其特殊的国际规范。现根据美国毒理病理学家学会发布的指导性文件,就完成毒理病理学报告人员、报告形式、报告内容、质量保证等方面对其相关要求进行详细介绍。     

The challenge of reproductive and developmental toxicology under REACH.

The European Union's REACH regulation has explicit requirements for reproductive and developmental toxicity data on all substances manufactured in or imported into the European Union at > or = 10 metric tons/year. Meeting the data requirements with whole-animal testing could result in the use of almost 22 million vertebrate animals for the registration of existing chemicals and cost up to several hundred thousand dollars per registered substance. The requirement for financial and animal resources can be reduced by the use of in vitro testing, quantitative structure-activity relationship models, and grouping of related substances. Although REACH strongly encourages these methods of avoiding vertebrate animal testing, it does not appear that in vitro testing or quantitative structure-activity relationship analysis will be able to replace whole-animal reproductive and developmental toxicity testing. Grouping of related compounds offers the possibility, perhaps in conjunction with in vitro testing and structure-activity analysis, of reducing vertebrate animal testing provided there is sufficient information on the related compounds and sufficient reason to believe that the related compounds will have similar toxicological properties. The designation of a substance as a reproductive or developmental toxicant follows criteria that do not consider the dose level of the substance at which reproductive or developmental effects occur, as long as excessive generalized toxicity does not occur. This method of labeling substances without consideration of effective dose level does not provide information on the actual risk of the chemical. Designation of a substance as a reproductive or developmental toxicant may have important implications under REACH and can be expected to result in the need to obtain authorization for marketing of the substance in the European Union.     

癃开颗粒抗前列腺增生的药理毒理研究

目的:探讨癃开颗粒口服给药抗前列腺增生的药效与毒性作用。方法:给小鼠癃开颗粒,测定正常幼年小鼠和丙酸睾丸素皮下注射或尿生殖窦植入诱发前列腺增生模型动物的前列腺指数、前列腺组织内DNA含量、血清酸性磷酸酶活性、精囊和睾丸湿重;检测单次给药的小鼠最大给药量,考察3个月连续给药的Wistar大鼠或Beagle犬长期毒性反应。结果:癃开颗粒20、40 g/kg(Qd×20 d)能降低正常幼年小鼠前列腺的重量及该组织内DNA的含量,10、20、40 g/kg(Qd×10 d)能抑制丙酸睾丸素引起的小鼠前列腺腹叶的增生,20、40 g/kg(Qd×30 d)能抑制植入胎鼠尿生殖窦引起的小鼠前列腺腹叶的增生;100 g/kg(Qd×13 w)能使大鼠前列腺呈轻度萎缩状态,腺上皮由柱状向扁平移生,腺腔变小,停药4周未见消失;癃开颗粒ig对小鼠的最大给药量为200 g/kg;癃开颗粒给大鼠10、40、100 g/kg或给Beagle犬12、60 g/kg(Qd×13周),未发现有明显的毒性反应。结论:癃开颗粒口服给药能抑制前列腺增生且无明显毒性反应。     

马钱子药理毒理研究回顾及安全性研究展望

2005年版《中国药典》记载，马钱子又名苦实、番木鳖，味苦有大毒，一般需炮制后入药，归肝、脾经；马钱子功能散结消肿、通络止痛，中医主治风湿顽痹、麻木瘫痪和跌打损伤等。临床上常于成药、复方中配伍应用．治疗风湿和类风湿性关节炎、中风偏瘫、痴呆、视网膜病变以及骨伤科、外科等疾病。其临床应用已有近千年的历史，也取得了很好的临床疗效。但近年来有关马钱子毒性的病例报道不断增多，影响马钱子及其成药的临床安全使用及国际准入，因此，急需开展有关马钱子及其成药的安全性研究工作以制定国内外公认的保证其质量和安全的控制标准。马钱子含有多种生物碱比。     

Toxicological safety evaluation of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar despite differing plasmid backbones or gene-inserts.

The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies were performed to screen for potential toxicities (intrinsic and immunotoxicities). All treatment-related toxicities identified in these repeated-dose toxicology studies have been confined primarily to the sites of injection and seem to be the result of both the delivery method (as they are seen in both control and treated animals) and the intended immune response to the vaccine (as they occur with greater frequency and severity in treated animals). Reactogenicity at the site of injection is generally seen to be reversible as the frequency and severity diminished between doses and between the immediate and recovery termination time points. This observation also correlated with the biodistribution data reported in the companion article (Sheets et al., 2006), in which DNA plasmid vaccine was shown to remain at the site of injection, rather than biodistributing widely, and to clear over time. The results of these safety studies have been submitted to the Food and Drug Administration to support the safety of initiating clinical studies with these and related DNA plasmid vaccines. Thus far, standard repeated-dose toxicology studies have not identified any target organs for toxicity (other than the injection site) for our DNA plasmid vaccines at doses up to 8 mg per immunization, regardless of disease indication (i.e., expressed gene-insert) and despite differences (strengths) in the promoters used to drive this expression. As clinical data accumulate with these products, it will be possible to retrospectively compare the safety profiles of the products in the clinic to the results of the repeated-dose toxicology studies, in order to determine the utility of such toxicology studies for signaling potential immunotoxicities or intrinsic toxicities from DNA vaccines. These data build on the biodistribution studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications.