EFFECTS OF INHALED FLORIDA RED TIDE BREVETOXINS

佛罗里达赤潮是所有有害藻华（HABs）中最臭名昭著的一种，几乎每年都会发生在佛罗里达的墨西哥湾沿岸。这种被称为短毛裸子鞭毛虫的动物在德克萨斯州海岸、阿拉巴马州、路易斯安那州部分地区和新西兰大量繁殖。佛罗里达的赤潮引起了主要的动物流行病，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，会向空气中释放刺激性有毒物质。有证据表明，短毒素是神经毒素，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沫和风干的短梭菌有毒颗粒中的毒素所产生的毒理学后遗症知之甚少。设施核心1“毒素探针和测定”，提供超过4000L连续培养短弧菌，产生40毫克/周的标准化天然毒素。还将生产合成的短叶毒素代谢物和日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检测，以增强突触体结合和高效液相色谱分析，用于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”将提供来自4个研究项目的细胞、组织和其他生物材料中积累的毒素的定性测量。将开始开发定量的“暴露生物标志物”。研究项目1“红潮气溶胶的特性”将在实验室和实地确定风和海中毒素的物理和化学特性和浓度。研究项目2“吸入短叶草毒素：健康影响和毒性动力学”将在动物模型中研究标记短叶草毒素的吸收、分布、代谢和清除。单次给药和重复给药均可使用。研究项目3，“brevetoxin诱导的过敏性和非过敏性气道支气管和鼻腔反应机制”将是一个绵羊模型，研究brevetoxin刺激下气道收缩的反应。剂量反应、药物干预、肥大细胞受累以及与现有哮喘或气道多动综合征的协同作用将被研究。研究项目4“雾化红潮毒素对人体的呼吸效应研究”将收集人体咽喉和鼻腔拭子来测量毒素。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。总的来说，这项研究将有助于建立雾化红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.