Mercury as a hapten: A review of the role of toxicant-induced brain autoantibodies in autism and possible treatment considerations

BackgroundMercury has many direct and well-recognized neurotoxic effects. However, its immune effects causing secondary neurotoxicity are less well-recognized. Mercury exposure can induce immunologic changes in the brain indicative of autoimmune dysfunction, including the production of highly specific brain autoantibodies. Mercury, and in particular, Thimerosal, can combine with a larger carrier, such as an endogenous protein, thereby acting as a hapten, and this new molecule can then elicit the production of antibodies.MethodsA comprehensive search using PubMed and Google Scholar for original studies and reviews related to autism, mercury, autoantibodies, autoimmune dysfunction, and haptens was undertaken. All articles providing relevant information from 1985 to date were examined. Twenty-three studies were identified showing autoantibodies in the brains of individuals diagnosed with autism and all were included and discussed in this review.ResultsResearch shows mercury exposure can result in an autoimmune reaction that may be causal or contributory to autism, especially in children with a family history of autoimmunity. The autoimmune pathogenesis in autism is demonstrated by the presence of brain autoantibodies (neuroantibodies), which include autoantibodies to: (1) human neuronal progenitor cells; (2) myelin basic protein (MBP); (3) neuron-axon filament protein (NAFP); (4) brain endothelial cells; (5) serotonin receptors; (6) glial fibrillary acidic protein (GFAP); (7) brain derived neurotrophic factor (BDNF); (8) myelin associated glycoprotein (MAG); and (9) various brain proteins in the cerebellum, hypothalamus, prefrontal cortex, cingulate gyrus, caudate putamen, cerebral cortex and caudate nucleus.ConclusionRecent evidence suggests a relationship between mercury exposure and brain autoantibodies in individuals diagnosed with autism. Moreover, brain autoantibody levels in autism are found to correlate with both autism severity and blood mercury levels. Treatments to reduce mercury levels and/or brain autoantibody formation should be considered in autism.     

Human Variation and Risk Assessment: Microarray and Other Studies Utilizing Human Hepatocytes and Human Liver Subcellular Preparations

The new paradigms proposed for human health risk assessment stress the need for the use of human and human‐derived cell lines, and this review summarizes the use of primary human hepatocytes and hepatocyte subcellular preparations for the investigation of the metabolism and metabolic interactions of environmental chemicals. This includes interactions based on inhibition, induction, and activation. The role of cytotoxicity is also considered. The use of hepatocytes and hepatocyte preparations provides especially important information for the investigation of human variation and is summarized. This area is, at present, relatively neglected but will in the future be essential for accurate assessment of human health risk. A detailed summary of an initial attempt to utilize microarray technology for the study of genome‐wide effects is included.     

Toxicity assessment of compounds in soil using a simple respirometric technique

A laboratory procedure using a simple respirometric technique was evaluated to determine the microbial toxicity in soil of three toxicant compounds: two pesticides, chlorpyrifos and glyphosate; and diesel oil. The microbial toxicity was tested using the specific oxygen uptake rate (SOUR) method, evaluating the soil samples for both the reduction in maximum SOUR (SOUR_max) and the cumulative oxygen demands after 20 h (OD₂₀). Consumption rate curves were produced for the lowest concentrations assessed: diesel (2460 ppm), chlorpyrifos (62.5 ppm), and glyphosate (250 ppm) (limiting amounts considered as local soil contamination). In comparison with the control, these showed drastic reductions in SOUR_max, demonstrating the high sensitivity of this SOUR method. The SOUR_max provides a better indication of the microbial toxicity of these contaminants compared to the OD₂₀ because of the different effects of these toxic compounds on microbial communities in the soil. Increasing concentrations of these toxic compounds resulted in different responses, evaluated as percentage inhibition by these different xenobiotic compounds. For these reasons, the microbial toxicity of xenobiotic compounds can be better recognized with SOUR_max as compared to other respirometric methodologies.     

太湖流域水质状况与土地利用格局的相关性

为探索异质景观内不同土地利用格局与水质之间的相关关系,以太湖流域为对象,根据地形条件、土地利用状况及主要水系的流向,将太湖流域分为13个水文生态单元,并对各水文生态单元内主要土地利用/覆盖类型的相对面积占比与水质等级之间的相关性进行了研究.结果表明:各水文生态单元水质等级2006年的变异系数与其林地面积占比呈正相关,与农田和聚落用地的面积占比呈负相关,其中与聚落用地占比在非汛期时具有显著性,体现了不同土地利用方式对水质改善能力不同,林地对水质改善能力较强,而农田和聚落用地相对较弱;各水文生态单元水质等级与农田、聚落用地的相对面积占比呈正相关,并分别在汛期和非汛期表现出显著性;与林地面积占比呈负相关,与各单元湿地面积占比在非汛期时呈弱负相关,汛期和全年为弱正相关;4类主要土地利用方式对水质等级改善的效应在汛期为林地>湿地>聚落用地>农田,非汛期为林地>农田>湿地>聚落用地.林地对水质的正贡献最大;农田和聚落用地分别对汛期和非汛期水质负贡献最大.     

以毒性鉴别评价法评价化工废水处理效果的研究

江苏省某化工厂废水处理设施进、出水经大型Sou（Daphnia magna）急性毒性试验的结果表明,废水在处理前、后均显示毒性。采用毒性鉴别评价的试验程序,对处理设施的进、出水进行了关键毒物的鉴别和评价。发现进水中存在的关键毒物为金属铜离子并共存多种金属和极性有机毒物,而出水中存在的毒物为酸性条件下易被氧化的有毒有机物。该废水处理工艺对废水毒性去除率为77.6%。由此可见,该处理工艺对金属离子有较好的去除,而对有毒有机化合物的去除效果不甚理想,因此,该厂生产工艺和废水处理工艺还有待进一步改进。     

具毒物影响和中立型时滞两种群竞争系统的周期正解

讨论了一类具毒物影响的中立型时滞两种群竞争系统,利用重合度理论和分析技巧建立了该系统正周期解全局存在的充分条件。     

生态毒理试验中的连续流系统设计及控制

长期连续流试验中,毒物浓度波动主要归因于毒物稀释系统的故障。为了提高毒性数据质量,毒物浓度水平监控是必不可少的.本文对现有连续流试验系统中的毒物稀释器作了改进,采用计量泵输送毒物和稀释水,提高毒物稀释系统的精确度。同时,在连续流试验系统中配置了实时监控系统(RTMS).RTMS由泵、样品室、分析仪器、记录仪等组成.在56d试验中,RTMS随时提供毒物稀释器运行的最新情况,各级毒物浓度变异系数在2.16%-6.13%之间。系统的运行成功为规范中、长期毒性试验提供了技术保证.       

具有毒素影响的二维Kolmogorov模型的持续生存和绝灭

研究了具有毒素影响的二维Kolmogorov模型,给出了该系统持续生存与绝灭的充分条件.