EFFECTS OF INHALED FLORIDA RED TIDE BREVETOXINS

佛罗里达赤潮是所有有害藻华（HAB）中最臭名昭著的一种，几乎每年都发生沿着佛罗里达的墨西哥湾沿岸。被指控的腰鞭毛虫，短裸藻，沿着德克萨斯海岸，亚拉巴马，路易斯安那州的部分地区和新西兰开花。佛罗里达的赤潮会引起严重的动物流行病，当甲藻在蛤蜊和牡蛎中过滤积累时，会产生有毒的贝类，当海浪条件动荡时，会释放刺激性有毒物质到空气中。有证据表明，短鞭金藻毒素是神经毒素，它们抑制细胞介导的免疫过程，它们是有效的支气管收缩剂。人们对人类呼吸道暴露于海雾中的毒素和风干的有毒颗粒的毒性后遗症知之甚少。短音符。具体内容是：设施核心1“毒素探针和测定”，提供超过4000 L的连续培养G。生产40毫克/周的标准化天然毒素。还将生产合成的短吻蝮蛇毒素代谢物和阳光修饰的毒素衍生物。将提供放射免疫、酶联免疫和免疫荧光试验，以增强突触体结合和HPLC分析，用于毒素的可溶性和组织固定定量和定位。设施核心2“免疫组织化学”将提供一个定性测量毒素积累在细胞，组织，和其他生物材料来自4个研究项目。将开始开发定量“接触生物标志物”。研究计划一“赤潮气溶胶的特性分析”将在实验室及野外，研究风及海雾的物理及化学特性，以及毒素的浓度。研究项目2“吸入性短尾寒毒：健康影响和毒理学”将研究标记短尾寒毒在动物模型中的摄取、分布、代谢和清除。将使用单次给药和重复给药。研究项目3，“过敏性和非过敏性气道中Brevetoxin诱导的支气管和鼻反应的机制”将是对Brevetoxin激发反应的气道收缩性的绵羊模型研究。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。研究计划4“赤潮毒素气溶胶对人体呼吸系统影响的研究”“将收集人的喉咙和鼻腔拭子来测量短尾丝虫毒素。生物标志物数据将与流行病学和临床数据一起收集，以更好地确定暴露的急性和慢性影响。这项研究将有助于建立气溶胶化赤潮毒素对动物和人类健康影响的模型。

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.