Bone Manganese as a Biomarker for Early Diagnosis of Manganese Neurotoxicity in O

描述(由申请人提供)：涉及焊接、冶炼、采矿和电池生产的工人职业性接触锰。仅在美国，数百万工人，包括30多万名焊工，就面临着过量接触锰的高风险。接触锰与许多类型的疾病有关，最令人担忧的是神经系统疾病。在其最后阶段，锰中毒表现为一种神经紊乱，称为 锰中毒，这与帕金森氏症非常相似。慢性锰中毒的症状一旦确立，就会逐渐发展并不可逆转。因此，建立一种生物标志物来评估累积锰暴露和早期诊断锰神经毒性是至关重要的。在这个项目中，一个潜在的有价值的长期累积接触锰的生物标志物将在一个有已知锰暴露历史的公认的工人群体中进行测试。这一生物标记物涉及在活体内测量人类骨骼中的锰。在过去的四年里，这项技术已经在PI的实验室中得到了开发和验证，现在它已经准备好在人类群体中进行测试。在这项建议中，我们的中心假设是，骨锰(MnBn)是长期累积锰暴露评估和锰神经毒性早期诊断的可靠生物标志物。我们将从中国一个成熟的冶炼厂队列中招募30家冶炼厂和30名匹配的对照组，对这些受试者进行MnBn非侵入性测量，使用现有的暴露模型估计累积锰暴露，并建立MnBn与估计的累积锰暴露之间的关系。我们还将对招募的受试者进行神经认知和神经行为测试，并确定暴露组和对照组中MnBn浓度与神经行为测试分数之间的关系。在该项目完成后，我们将能够确定锰是否可以作为累积锰暴露的良好生物标志物，并用于锰神经毒性的早期诊断。使用一种新的生物标记物来了解接触锰的神经毒性效应对数百万接触锰的工人来说至关重要，原因有两个。首先，神经障碍是这些工人的主要健康问题之一；其次，神经损伤降低了工人的生产力，是与工作有关的伤害的主要原因。PHS 398/2590(06/09版)页面续格式页面

DESCRIPTION (provided by applicant): Occupational exposure to manganese (Mn) occurs among workers involved in welding, smelting, mining, and battery production. In the US alone, millions of workers, including over 300,000 welders, are at high risk of excessive Mn exposure. Mn exposure is associated with many types of diseases, and the most concerned is neurological disorders. In its final stage, Mn toxicity manifests as a neurological disorder termed manganism, which closely resembles Parkinson's disease. The symptoms of chronic Mn toxicity, once established, become progressive and irreversible. Hence, a biomarker for the assessment of cumulative Mn exposure and early diagnosis of Mn neurotoxicity is crucial. In this project, a potential valuable biomarker for long term cumulative Mn exposure will be tested among a well-established workers population with a known history of Mn exposure. This biomarker involves measuring Mn in human bone in vivo. This technology has been developed and validated in the PI's laboratory for the past four years and it's now ready to be tested in a human population. Our central hypothesis to be tested in this proposal is that bone Mn (MnBn) is a reliable biomarker for long- term cumulative Mn exposure assessment and for early diagnosis of Mn neurotoxicity. We will recruit 30 smelters and 30 matched controls from a well-established smelter cohort in China, perform noninvasive MnBn measurement on these subjects, estimate cumulative Mn exposure using an existing exposure model, and establish the relationship between MnBn and estimated cumulative Mn exposure. We will also conduct neurocognitive and neurobehavioral tests on the recruited subjects and determine the relationship between MnBn concentrations and neurobehavioral test scores among the exposed and control groups. At the completion of the project, we will be able to determine whether Mn can be used as a good biomarker for cumulative Mn exposure and for early diagnosis of Mn neuro-toxicity. The use of a new biomarker to understand the neurotoxic effects of exposure to Mn is critical to millions of workers who have been exposed to Mn for two reasons. First, neurological disorder is one of the main health issues for these workers; second, neurological impairment reduces the workers' productivity and is a major cause for work related injuries. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page