EFFECTS OF INHALED FLORIDA RED TIDE BREVETOXINS

吸入佛罗里达赤潮短叶藻毒素的影响

• 批准号: 7127106
• 负责人: Daniel G Baden
• 金额: $ 17.5万
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127106
• 关键词: environmental health; environmental toxicology; marine toxins

Florida red tide is one of the most notorious of all Harmful Algal Blooms (HABs), occurring on a virtually annual basis along Florida's Gulf coast. The incriminated dinoflagellete, Gymnodinium breve, blooms along the Texas coast, Alabama, parts of Louisiana, and New Zealand. Florida red tide causes major epizootics, produces toxic shellfish when the dinoflagellate is filter-accumulated in clams and oysters, and releases in irritating toxicant into the air when surf conditions are turbulent. There is evidence that brevetoxins are neurotoxins, that they inhibit cell-mediated immunological processes, and they are potent bronchoconstrictors. Very little is known about the toxicological sequelae that accompany human respiratory exposure to toxins in seaspray and wind-dried toxic particles of G. breve. The specific elements are: Facilities Core 1 "Toxins Probes and Assays", provides over 4000L of continuous culture G. breve for producing 40 mg/week standardized natural toxins. Synthetic brevetoxin metabolites and sunlight-modified toxin derivatives will also be produced. Radioimmuno-, enzyme-linked immuno- and immuno- fluorescent assays will be provided to augment synaptosome binding and HPLC analysis for soluble and tissue-fixed quantification and localization of toxin. Facilities Core 2 "Immunohistochemistry" will provide a qualitatively measure of toxin accumulated in cells, tissu8es, and other biological materials derived from the 4 research projects. Development of a quantitative "biomarker of exposure" will be initiated. Research Project 1 "Characterization of Red Tide Aerosols" will seek to determine, in the lab and field, the physical and chemical character, and concentration of toxins in wind and seaspray. Research Project 2 "Inhaled Brevetoxins: Health Effects and Toxicokinetics" will investigate the uptake, distribution, metabolism, and clearance of labeled brevetoxin in animal models. Both single dose and repeat administration will be used. Research Project 3, "Mechanism of Brevetoxin-Induced Bronchial and Nasal Responses in Allergic and Non-Allergic Airways" will be a sheep model investigation of airway contractility in response to brevetoxin challenge. Dose response, drug intervention, mast cell involvement, and synergy with existing asthma or hyperactive airway syndromes will be studied. Research Project 4 "Respiratory Effect Study of Aerosolized Red Tide Toxins on Human..." will collect human throat and nasal swabs to measure brevetoxin. Biomarker data will be collected in conjunction with epidemiologic and clinical data, to better define the acute and chronic effects of exposure. The research overall will contribute to the model of animal and human health effects of aerosolized red tide toxins.

佛罗里达赤潮是所有有害藻华 (HAB) 中最臭名昭著的一种，几乎每年都会在佛罗里达州墨西哥湾沿岸发生。受罪的甲藻（Gymnodinium breve）在德克萨斯州海岸、阿拉巴马州、路易斯安那州部分地区和新西兰盛开。佛罗里达赤潮会引起主要的动物流行病，当甲藻在蛤和牡蛎中过滤积累时，会产生有毒的贝类，当海浪汹涌时，会向空气中释放刺激性有毒物质。有证据表明短尾毒素是神经毒素，它们抑制细胞介导的免疫过程，并且是有效的支气管收缩剂。人们对人类呼吸道接触海喷雾中的毒素和短G. breve风干有毒颗粒所产生的毒理学后遗症知之甚少。具体要素是： 核心设施 1“毒素探针和测定”，提供超过 4000L 的连续培养短短杆菌，用于每周生产 40 毫克标准化天然毒素。合成的短尾毒素代谢物和阳光改性的毒素衍生物也将被生产。将提供放射免疫、酶联免疫和免疫荧光测定，以增强突触体结合和 HPLC 分析，以实现可溶性和组织固定的毒素定量和定位。设施核心 2“免疫组织化学”将对 4 个研究项目中衍生的细胞、组织和其他生物材料中积累的毒素进行定性测量。将启动定量“暴露生物标志物”的开发。研究项目1“赤潮气溶胶的表征”将寻求在实验室和现场确定风和海浪中毒素的物理和化学特征以及浓度。研究项目2“吸入短尾藻毒素：健康影响和毒代动力学”将研究动物模型中标记的短尾藻毒素的摄取、分布、代谢和清除。将使用单剂量和重复给药。研究项目 3“过敏性和非过敏性气道中短尾藻毒素诱导的支气管和鼻腔反应机制”将是绵羊模型研究响应短尾藻毒素挑战的气道收缩性。将研究剂量反应、药物干预、肥大细胞参与以及与现有哮喘或气道过度活跃综合征的协同作用。研究项目4“气溶胶赤潮毒素对人体呼吸影响的研究……”将收集人体咽喉和鼻拭子来测量短尾藻毒素。生物标志物数据将与流行病学和临床数据结合收集，以更好地确定暴露的急性和慢性影响。总体而言，该研究将有助于建立雾化赤潮毒素对动物和人类健康影响的模型。