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. ? ?
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