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）：本修订后的项目竞争性更新的重点是揭示实验室模型中佛罗里达州赤潮毒素暴露后的作用机制，并为暴露在海滩上的人类提供相关信息。由短卡伦虫引起的佛罗里达赤潮每年都会在美国墨西哥湾海岸线发生，并向水和空气中释放 12 种刺激性天然环境聚醚短毒素，产生有毒结果。毒素拮抗剂也被释放。 研究人员表明，在头 5 年中，短尾毒素会在吸入暴露的人类和动物模型中引起神经毒性、免疫和肺部影响。 研究者应进一步确定吸入暴露于赤潮气雾化、沉积在职业、娱乐和易感人类和动物群体中的复杂物质混合物的特征。 作用和预防机制以及治疗方法是实验室和现场的重点关注点。要素包括： 行政核心；设施核心 1“毒素探针和测定”提供 QA/QC 毒素、衍生物和拮抗剂、分析支持和测定开发； ;设施核心 2“现场后勤和部署”优化生物和海水的环境监测，部署空气采样器和计量设备，并为研究项目 4 提供后勤服务。研究项目 1“赤潮气溶胶的表征”将水华动态与大小、成分相关联和气溶胶效力，并将气象建模添加到数据集中。 研究项目 2“吸入 PbTx：健康影响和机制”探索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”探讨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“对人类的气溶胶赤潮 PbTx”收集修订后的队列的暴露前/后数据（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。 简单摘要：佛罗里达赤潮通过赤潮期间产生的生物活性化学物质在空气中的释放而导致人类疾病。 该项目采用跨学科方法，采用实验室研究和海滨工作来了解接触雾化毒素对人类造成的后果，探索中毒疗法，并利用赤潮生物活性材料开发新药。