Effects of Inhaled Florida Red Tide Brevetoxins

吸入佛罗里达赤潮短尾毒素的影响

• 批准号: 7902982
• 负责人: Daniel G Baden
• 金额: $ 80万
• 依托单位: UNIVERSITY OF NORTH CAROLINA WILMINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7902982
• 关键词: Effects; Inhaled; Florida; Red; Tide

DESCRIPTION (provided by applicant): This amended Program Project competitive renewal is focused on revealing mechanisms of action following Florida red tide toxin exposure in laboratory models, and at providing relevant information for humans exposed on beaches. Florida red tides caused by Karenia brevis occur annually along the U.S. Gulf of Mexico coastline, and release 12 irritating natural environmental polyether brevetoxins into water and air with toxic results. Toxin antagonists are also released. The investigators have shown during the first 5 years that brevetoxins elicit neurotoxic, immunologic, and pulmonary effects in inhalation-exposed humans and animal models. The investigators shall further characterize inhalation exposure to the complex mixture of materials aerosolized from red tide, depositing in occupational, recreational, and susceptible human and animal populations. Mechanisms of action and prevention, and therapeutics are intensified foci in laboratory and field alike. Elements include: Administrative Core; Facility Core 1 "Toxin Probes & Assays" provides QA/QC toxins, derivatives and antagonists, analytical support and assay development; ; Facility Core 2 "Field Logistics & Deployment" optimizes environmental monitoring of organism and seawater, deploys air samplers and meterologic gear, and provides logistics for Research Project 4. Research Project 1 "Characterization of Red Tide Aerosols" correlates bloom dynamics with the size, composition, and aerosol potency, and adds meteorlogic modeling to data sets. Research Project 2 "Inhaled PbTxs: Health Effects & Mechanisms" explores pulmonary and immunotoxic mechanisms in rodents. Research Project 3 "Mechanism of PbTx-lnduced Responses" explores inhaled effects in a sheep model, including inflammation, mucociliary clearance, therapeutics and prevention. Research Project 4 "Aerosolized Red Tide PbTx on Humans" collects pre/post exposure data (chemical and physiological criteria) for a revised cohort, as well as prevention/intervention trials. Using the Research Projects and Facility Cores synergy optimized over the past 5 years, the investigators will evaluate acute and chronic immune and pulmonary PbTx effects on humans and animals, as well as prevention and intervention. Lay summary: Florida red tides cause human illness through the airborne release of bioactive chemicals produced during a bloom. Using an interdisciplinary approach, this Program Project employs both laboratory studies and beachside work to understand the human consequences of exposure to aerosolized toxins, to explore therapies for intoxication, and to develop new drugs exploiting red tide bioactive materials.

描述(由申请人提供)：这项修订计划项目竞争更新的重点是揭示佛罗里达州赤潮毒素在实验室模型中暴露后的作用机制，并为暴露在海滩上的人类提供相关信息。由短小卡氏杆菌引起的佛罗里达州赤潮每年发生在美国墨西哥湾的海岸线上，并向水和空气中释放12种刺激性的自然环境聚醚短杆菌毒素，导致有毒结果。毒素拮抗剂也会被释放。研究人员表明，在最初的5年中，短杆菌毒素在吸入暴露的人类和动物模型中引起神经毒性、免疫学和肺部影响。调查人员应进一步确定吸入赤潮物质的复杂混合物的特征，这种物质沉积在职业、娱乐和易受影响的人和动物群体中。作用机制、预防机制和治疗方法都是实验室和现场研究的重点。内容包括：管理核心；设施核心1“毒素探测器和化验”提供QA/QC毒素、衍生物和拮抗剂、分析支持和化验开发；设施核心2“现场后勤和部署”优化对生物和海水的环境监测，部署空气采样器和气象设备，并为研究项目4提供后勤。研究项目1“赤潮气溶胶的特征”将水华动力学与大小、组成和气溶胶效力联系起来，并为数据集增加气象模拟。研究项目2“吸入PbTxs：健康影响和机制”探索了啮齿动物的肺部和免疫毒性机制。研究项目3“PBTX诱导反应的机制”探索了绵羊模型中的吸入效应，包括炎症、粘液纤毛清除、治疗和预防。研究项目4“人体上的气雾化赤潮PBTX”为修订的队列收集暴露前/暴露后的数据(化学和生理标准)，以及预防/干预试验。利用过去5年优化的研究项目和设施核心协同效应，研究人员将评估急性和慢性免疫和肺PBTX对人和动物的影响，以及预防和干预。 莱文摘要：佛罗里达赤潮通过在水华期间产生的生物活性化学物质在空气中释放，导致人类疾病。该计划项目采用跨学科的方法，利用实验室研究和海边工作，了解暴露在气雾化毒素中对人类的影响，探索中毒的治疗方法，并开发利用赤潮生物活性物质的新药。