离体和在体消毒方法相关性的初步研究

目的:探索建立以猪皮和仿真皮作为载体代替人手的离体消毒模拟现场试验方法。方法:以金黄色葡萄球菌、铜绿假单胞菌,大肠埃希菌,粘质沙雷氏菌为试验菌,参照《消毒技术规范》方法,采用消毒剂对皮肤消毒模拟现场试验方法进行试验研究。结果:离体模型中,仿真皮消毒模拟现场试验结果和皮肤消毒模拟现场试验结果的细菌杀灭对数值均大于3.0,猪皮消毒模拟现场试验结果的细菌杀灭对数值均大于2.0,离体仿真皮消毒模拟现场试验结果与人手消毒模拟现场试验的结果一致,离体猪皮消毒模拟现场试验细菌减少率相对较低,但与在体试验结果有较好的相关性。结论:离体仿真皮消毒模拟试验与在体皮肤试验结果相近,同时仿真皮之间结果重复性良好,操作简单可控,省时,对防止交叉感染有重要意义,在消毒产品的效果评估中可以替代在体皮肤模拟现场试验。     

猪离体不停跳心脏模型建立和应用

目的 研究不停跳技术在猪离体心脏实验模型的应用.方法 7只实验用猪,戊巴比妥钠麻醉后常规开胸,在不停跳的情况下游离血管,建立体外循环管道连接,利用体外循环机保证冠脉灌注.在心脏不停跳情况下进行心脏离体手术,离体后心脏置无菌塑料袋于恒温水箱(37℃)保存,左心耳置引流管.灌注血液温度37℃,流量控制在300 ml/min左右.观察离体后心脏跳动情况,离体后每隔1小时取左心耳组织测定丙二醛(MDA)、超氧化歧酶(SOD),6小时后取心尖部心肌行电镜检测.结果 7只动物除一只因左心反流胀停失败,其余均成功建立离体不停跳模型.MDA及SOD在离体6h内变化不明显,心肌超微结构保持良好.结论 在体外循环系统支持下可以保证心脏在离体及体外过程中不停跳,避免了缺血再灌注损伤,为大型动物的体外心脏实验提供了良好的模型.     

离体胎盘灌注模型应用的研究进展

离体胎盘灌注模型是一种模拟生理环境建立胎盘循环的体外模型,是目前应用最广泛的药物胎盘转运研究模型。随着技术进一步发展,其也被应用于研究疾病发生发展机制、治疗方案、毒物经胎盘转运等其他方面。该模型与细胞培养模型、质膜囊泡模型、胎盘绒毛外植体模型等体外模型相比,拥有完整胎盘结构,使得其成为进行胎盘相关研究的最理想模型之一。本文就离体胎盘灌注模型的应用进行综述。     

人群有机氯化合物暴露和体负荷的研究

1990年在江苏无锡市进行的有机氯化合物人体暴露和体负荷的研究,检测了17类环境样品和食物样品,52例受试乳母的膳食和乳汁中六氯苯、666和DDT 的浓度,估算受试乳母日平均六氯苯、666、DDT暴露量分别为0.63μg、9.34μg和43.81μg。婴儿每公斤体重每天自母乳摄入六氯苯、β-666、DDT分别为0.19μg、107μg和94μg。本研究所得到这些有机氯化合物在环境和食物中的浓度分布和污染趋势,为制定环境保护和保护人群健康的对策提供了依据。     

环境铅暴露体荷水平动态预测研究

环境铅暴露体荷水平动态预测研究叶方立，张绪忠（武汉冶金医学高等专科学校，４３００８０）铅暴露者体内总铅负荷水平如何评估，是当前工业毒理学有待研究的一个新领域。作者根据铅在机体内的生物转运特性，建立以血液为中央室的乳头状开室模型，并选用Ｒａｂｉｎｏｗｉ...     

氟化钠对离体培养大鼠心肌细胞内糖原及琥珀酸脱氢酶的影响

目的探讨氟化物对离体培养大鼠心肌细胞的毒性作用机制。方法应用离体培养心肌细胞模型和细胞化学方法研究不同剂量的氟化钠处理后,细胞搏动或停搏与心肌细胞内糖原的水平及琥珀酸脱氢酶(SDH)活力的变化。结果心肌细胞的停搏率与氟离子(F-)剂量间存在明显的正相关关系(r=0.969、P<0.05),F-的半数停搏物质的量浓度为1.92×10-4mol/L。细胞化学研究及图像分析数据表明,对照组心肌细胞内糖原和SDH反应都呈强阳性,实验组停搏的心肌细胞这2种反应随着F-剂量增加而减弱,呈负相关关系(r分别为-0.917 3,-0.960 3),且不同剂量组间差异都有统计学意义(P<0.05)。结论氟化钠可使心肌细胞内糖原的合成受阻及SDH活力被抑制,导致搏动的心肌细胞因能量供应不足而停搏,呈明显的剂量-反应关系。     

外泌体与外泌体microRNAs在糖尿病周围神经病变发生发展中的研究进展

糖尿病周围神经病变(diabetic peripheral neuropathy, DPN)是糖尿病神经损害的慢性并发症之一, 也是导致慢性伤口及致残的主要原因。外泌体(exosomes)与外泌体microRNAs(miRNAs)与DPN密切相关, 通过介导细胞间通讯, 参与周围神经系统的信号转导及蛋白表达。但在高糖环境中, 外泌体与外泌体miRNAs引起DPN发生发展的具体作用和机制尚不完全清楚, 本文就高糖环境中外泌体与外泌体miRNAs在抑制轴突生长、促进炎症反应和诱导血管损伤方面促进DPN发生和发展进行阐述。     

二烷基磷酸酯类有机磷农药降解产物在暴露评估中的应用研究进展

大多数有机磷农药(OP)通常都有相似结构,在环境或动植物体内能通过水解和氧化途径等降解转化为六种二烷基磷酸酯类化合物(DAPs)中的一种或一种以上,它们常被用作人群农药暴露评估的生物标志物。该文综述了OP在环境中的主要降解机制、DAPs在生物监测中的应用进展,分析了食品中OP及DAPs残留对生物监测的影响,提出了新的OP暴露评估策略。     

纳米材料氧化石墨烯的细胞毒性机制研究进展

氧化石墨烯是一种新型二维碳纳米材料,可对职业暴露人群构成潜在的健康风险。本文从氧化应激、物理损伤和酶活性紊乱等分子机制综述了氧化石墨烯及其衍生物的细胞毒性研究进展,讨论当前细胞毒性减轻机制的研究热点,以期为我国石墨烯材料职业健康风险防控和生物安全性评估提供参考依据。     

离体眼球体内环境模拟装置的研制

本文所述的离体眼球体内环境模拟装置利用仿生学原理,在体外模拟眼球的体内环境,以维持离体眼球的正常形态及其对刺激物的反应能力。评价实验证明该装置可以稳定的维持角膜的形态,满足离体眼球实验的需要。     

Exposure science and the U.S. EPA National Center for Computational Toxicology

The emerging field of computational toxicology applies mathematical and computer models and molecular biological and chemical approaches to explore both qualitative and quantitative relationships between sources of environmental pollutant exposure and adverse health outcomes. The integration of modern computing with molecular biology and chemistry will allow scientists to better prioritize data, inform decision makers on chemical risk assessments and understand a chemical's progression from the environment to the target tissue within an organism and ultimately to the key steps that trigger an adverse health effect. In this paper, several of the major research activities being sponsored by Environmental Protection Agency's National Center for Computational Toxicology are highlighted. Potential links between research in computational toxicology and human exposure science are identified. As with the traditional approaches for toxicity testing and hazard assessment, exposure science is required to inform design and interpretation of high-throughput assays. In addition, common themes inherent throughout National Center for Computational Toxicology research activities are highlighted for emphasis as exposure science advances into the 21st century.     

Occupational and environmental medicine: moving the factory fence or hedging our bets?

Occupational and environmental medicine evolved out of concern for the effect of work hazards on health. The experienced gained in considering such hazards has been extended to understanding general risks in the environment. As we look toward the future, classical occupational and environmental hazards such as over exposure to lead, asbestos and mercury are waning and being replaced by concerns around sustainable development, toxicology testing and exposure information for high production volume chemicals, development of better approaches for setting workplace and community exposure limits, environmental justice and many others. The opportunities for the future exist in overcoming these new challenges.     

新愿景下毒性测试方法的发展与变革

随着全球化学品产量增加, 人群暴露及健康风险加重, 对化学品毒性测试和安全性评价提出更高的要求。21世纪毒性测试愿景和策略的提出大力推动了毒性测试的变革。新时代毒性测试通过运用新模型、新方法和新策略, 结合交叉学科和高新技术优势, 得到了长足发展。提高化学物毒性测试效率的同时, 也实现了更全面、多层次、高质量的数据获取和毒性评价, 为毒作用模式、毒作用机制和毒性通路的探索提供有力支持。本期重点号围绕当前毒性测试替代新方法, 邀请多位学者对高内涵分析、3D细胞培养技术、Ex vivo试验、单细胞测序、斑马鱼实验方法进行介绍和阐述, 以期为推动我国化学物毒性测试评估实现跨越发展开拓崭新思路。     

A Search for Guidance: Examining Prenatal Substance Exposure Protocols

Objectives: To describe key elements of a set of hospital prenatal substance exposure protocols, and to relate variations in protocol content to the state legislative environment and hospital characteristics. Methods: Nurse managers and hospital administrators with responsibility for perinatal care were asked to provide their hospital's prenatal substance exposure protocol. Using a structured coding form, two independent coders read and abstracted information from the 87 protocols received. Hospital and patient characteristics and the state's legal environment were cross-tabulated. Results: Only half of coded protocols included an implementation date; 37% lacked any goal or statement of purpose. Most covered the key components of prenatal substance exposure management, such as precipitants and guidelines for toxicology screening, but failed to present their contents clearly. Only a few discussed whether specific maternal consent is required for a maternal or a newborn toxicology screen. Protocols from states that had made some legislative response to prenatal substance exposure were more likely to provide reporting guidelines and a discussion of consent for a toxicology screen for mothers and newborns. Protocols were more likely to be found in larger hospitals and were more detailed in hospitals serving more affluent and less minority patient populations. Conclusions: More attention needs to be devoted to the development of prenatal substance exposure protocols, as their lack of clarity precludes most from meeting protocol development goals, such as encouraging standardized care. Associations between hospital characteristics, state legislative environment and protocol features suggest that legislative mandates could shape their development and features.     

Perinatal Toxicology: Its Recognition and Fundamentals

Perinatal toxicology is the study of aberrant or toxic responses to environmental agents when exposure occurs from conception through the neonatal period. The current increased interest in perinatal toxicology reflects the concern of both society and the individual in the resultant deficits induced by exposure to agents in the workplace, home. environment and by therapeutic intervention during early development. Not only is differentiation during organogenesis (the first eight weeks in human gestation) a highly susceptible period to the induction of malformations, but the fetal/neonatal developmental phases are just as sensitive for certain developmental deficits. Long-term postnatal evaluations are in most instances critical for the documentation of fetal/neonatal functional defects, which include carcinoogenesis, behavioral impairment, endocrine and immune dysfunction, Ethylnitrosource, estrogens (diethylstilbestrol), and cadmium are discussed in relationship to specificity of their fetal effects, long-term follow-up, and possible mechanisms of toxic action.     

Could pesticide toxicology studies be more relevant to occupational risk assessment?

Pesticide toxicology study design has evolved from concern for oral exposure via food residues. The emphasis on the oral route does not generally apply to workers that are exposed primarily via the dermal route either handling pesticides or re-entering treated fields. As a result numerous assumptions about how oral toxicology results relate to dermal exposure must be made when conducting worker risk assessments. These assumptions introduce a high degree of uncertainty. Alternative toxicology study designs are suggested to reduce uncertainty when assessing risk. Because the dermal route is so important to characterizing occupational risk, methods to improve the accuracy of dermal absorption estimates are suggested, including the use of human subjects to study dermal absorption. Additional suggestions include tailoring dermal, oral and inhalation kinetic study designs to reflect worker exposure dosages. Suggestions are made to routinely conduct a single dose toxicity study patterned after the neurotoxicity study design to distinguish single dose effects and NOAELs from those resulting from multiple doses. Finally, interspecies pharmacokinetics studies are proposed to determine which toxicology study regimen of dosing best reflects intermittent worker exposure.     

Recent applications of DNA microarray technology to toxicology and ecotoxicology

Gene expression is a unique way of characterizing how cells and organisms adapt to changes in the external environment. The measurements of gene expression levels upon exposure to a chemical can be used both to provide information about the mechanism of action of the toxicant and to form a sort of "genetic signature" for the identification of toxic products. The development of high-quality, commercially available gene arrays has allowed this technology to become a standard tool in molecular toxicology. Several national and international initiatives have provided the proof-of-principle tests for the application of gene expression for the study of the toxicity of new and existing chemical compounds. In the last few years the field has progressed from evaluating the potential of the technology to illustrating the practical use of gene expression profiling in toxicology. The application of gene expression profiling to ecotoxicology is at an earlier stage, mainly because of the the many variables involved in analyzing the status of natural populations. Nevertheless, significant studies have been carried out on the response to environmental stressors both in model and in nonmodel organisms. It can be easily predicted that the development of stressor-specific signatures in gene expression profiling in ecotoxicology will have a major impact on the ecotoxicology field in the near future. International collaborations could play an important role in accelerating the application of genomic approaches in ecotoxicology.     

微阵列技术在毒理学研究中的应用

毒理基因组学是一门研究与环境因素所致健康危险性有关的人类基因组的新学科。这是毒理学和基因组技术结合所产生的一门新的学科分技。微阵列技术即基因芯片技术包括芯片制备、待检样品制备、探针杂交、检测和数据处理。微阵列技术在毒理学主要应用于可疑毒物的鉴定、作用机制的研究、剂量-反应关系的评价、化学混合物中交互反应的鉴定、暴露的生物标记和易感性的生物标记。例如微阵列技术已用于研究人膀胱癌的生物标记以及氯化镉、苯并（a）芘和三氯乙烯相关基因调控的指纹。还介绍了一种全自动、多用途、新型的分子生物学工作站NanoChip分子生物系统。     

Behavioral toxicology: from historical background to future trends

In the 1960's and 70's some investigators started to use behavioral tests in toxicology, realizing that classical toxicological methods were inadequate to describe the negative effects on workers health caused by workplace neurotoxic exposures. Among the first publications were those of Helena H?nninen, who reported on exposure to CS2 (24, 22). In clinical examinations, these workers presented severe functional changes to the central nervous system (CNS), although there were no observable signs of frank brain damage. In experimental studies of effects from acute exposures to various chemicals, methods from classical toxicology were definitely not useful. Such investigations were performed with exposure to carbon monoxide and to different solvents. Studies were carried out in the US, Sweden, and Germany, and reported by Richard Stewart (53), Francesco Gamberale (15, 16), and Gerhard Winneke (63). Rapid development followed. Scientists active in behavioral toxicology gathered at various meetings, and in 1982 an international symposium dedicated solely to the use and development of behavioral testing techniques in toxicology was organized by Renato Gilioli. He then used the Scientific Committee of Neurotoxicology and Psychophysiology of the International Commission on Occupational Health as a platform for a series of triennal symposia. The 9th meeting was held in Korea 2005, and the 10th will be organized in Costa Rica 2008. By providing a basis for the exchange of scientific knowledge and ideas, these symposia have been successful in further advancing the development and application of behavioral techniques in toxicology. This history is presented in some more detail, and a few possibilities for further development of the area will be discussed.     

Multiple exposure to pesticides and impacts on health: a cross-section study of 102 rural workers, Nova Friburgo, Rio de Janeiro State, Brazil

A cross section study was carried out in a farming community from Nova Friburgo, Rio de Janeiro state, Brazil, to examine epidemiological, clinical and laboratory aspects of multiple exposure to pesticides in a representative sample of 102 small farmers. Both males and females were submitted to an extensive protocol which included an occupation questionnaire, biological sample collection for toxicology analysis and clinical - general and neurological - evaluation. The toxicology test results showed light to moderate episodes of acute intoxication by organophosphorates either described by the farmers or observed during clinical examination. Thirteen cases of delayed neuropathies (12,8%) as well as 29 cases of neural behavioral syndromes and psychiatric disorders associated to the continued use of pesticides were diagnosed. These results indicate recurrent multiple overexposures to high concentrations of different chemicals, with serious damage to vital functions, especially considering their young age (average 35 +/- 11 years old) and the productive period in their lifetime. These results show how important it is to monitor multiple exposure to pesticides - a chain of events that may have major impacts on public health and the environment.