EFFECTS OF INHALED FLORIDA RED TIDE BREVETOXINS

佛罗里达赤潮是所有有害藻华中最臭名昭著的一种，几乎每年都会发生在佛罗里达州的墨西哥湾沿岸。被牵连的短裸甲藻在德克萨斯州海岸、阿拉巴马州、路易斯安那州的部分地区和新西兰大量繁殖。佛罗里达州的赤潮会导致主要的家畜流行病，当甲藻通过过滤积累在蛤和牡蛎中时，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，短杆菌毒素是一种神经毒素，它们抑制细胞介导的免疫过程，并且它们是强有力的支气管收缩因子。人们对人类呼吸道暴露于海藻和风干有毒颗粒中的毒素的毒理学后遗症知之甚少。具体要素是：设施核心1“毒素检测和分析”，提供超过4000升的连续培养G.Brive，用于生产每周40毫克的标准化天然毒素。还将生产合成的短杆菌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分析以增强突触体结合，并提供高效液相分析以用于可溶性和组织固定的毒素的定量和定位。设施核心2“免疫组织化学”将提供从4个研究项目中获得的细胞、组织和其他生物材料中积累的毒素的定性测量。将开始开发一种定量的“暴露生物标记物”。研究项目1“赤潮气溶胶的特征”将寻求在实验室和现场确定风和海绵中毒素的物理和化学性质以及浓度。研究项目2“吸入短杆菌毒素：对健康的影响和毒物动力学”将调查标记的短杆菌毒素在动物模型中的摄取、分布、代谢和清除。单次给药和重复给药都将使用。研究项目3，“Brevetoxin在过敏性和非过敏性呼吸道中引起的支气管和鼻腔反应的机制”将是一个绵羊模型，研究对短杆菌毒素攻击的呼吸道收缩能力的反应。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高活动性呼吸道综合征的协同作用。研究项目4“雾化赤潮毒素对人体的呼吸效应研究”。将收集人类咽喉和鼻部拭子来检测短杆菌毒素。生物标记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。总体来说，这项研究将有助于建立气雾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.