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: 7645755
• 负责人: Daniel G Baden
• 金额: $ 146.61万
• 依托单位: UNIVERSITY OF NORTH CAROLINA WILMINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-10 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7645755
• 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）：本修订后的计划项目竞争性更新的重点是揭示佛罗里达赤潮毒素暴露在实验室模型中的作用机制，并为暴露在海滩上的人类提供相关信息。沿着美国墨西哥湾每年发生一次由短凯伦藻引起的佛罗里达赤潮，并向水体和空气中释放12种具有刺激性的天然环境聚醚短链藻毒素。也释放毒素拮抗剂。 研究人员在前5年的研究中发现，在吸入暴露的人类和动物模型中，短尾孢毒素会引起神经毒性、免疫学和肺部效应。 调查人员应进一步描述吸入暴露于从赤潮中雾化的复杂混合物的特征，这些混合物沉积在职业、娱乐和易感的人类和动物群体中。 作用机制和预防以及治疗方法是实验室和现场的重点。要素包括：行政核心;设施核心1“毒素探针和分析”提供毒素、衍生物和拮抗剂的质量保证/质量控制、分析支持和分析开发;设施核心2“现场后勤和部署”优化生物体和海水的环境监测，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”将水华动力学与尺寸，成分和气溶胶效力相关联，并将气象模型添加到数据集。 研究项目2“吸入PbTxs：健康影响和机制”探讨啮齿动物的肺和免疫毒性机制。 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，粘膜纤毛清除，治疗和预防。 研究项目4“人体吸入的赤潮PbTx”为修订的队列以及预防/干预试验收集暴露前/暴露后数据（化学和生理标准）。 利用过去5年优化的研究项目和设施核心协同作用，研究人员将评估PbTx对人类和动物的急性和慢性免疫和肺部影响，以及预防和干预。 简要介绍：佛罗里达赤潮通过空气中释放的生物活性化学物质引起人类疾病。 使用跨学科的方法，该计划项目采用实验室研究和海滨工作，以了解暴露于气溶胶毒素的人类后果，探索中毒的治疗方法，并开发利用赤潮生物活性材料的新药。