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Novel Treatments of Chlorine Induced Injury to the Cardio-Respiratory Systems-U54

氯引起的心肺系统损伤的新疗法-U54

基本信息

批准号：
8270066
负责人：
Sadis Matalon
金额：
$ 21.24万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8270066
关键词：
Acetylcysteine Adrenergic Agents Adrenergic Agonists Adult Advisory Committees Aerosols Affect Afferent Neurons Agonist Air Albumins Alveolar American Anatomy Animals Anions Anti-Inflammatory Agents Anti-inflammatory Antioxidants Area Ascorbic Acid Asthma Biochemical Biological Blood Vessels Books Breathing Bronchial Spasm Caring Cells Centers of Research Excellence Chemicals Child Chlorine Committee Members Communities Complex Consult Core Facility Cyclic AMP Data Deferoxamine Deferoxamine Methanesulfonate Diagnosis Disease Documentation Dose Effectiveness Elderly Electronic Mail Ensure Epithelial Epithelial Cells Epithelium Equipment Exposure to FDA approved Fertilization Free Radicals Functional disorder Gases Glutathione Disulfide Goals Grant High Pressure Liquid Chromatography Homeostasis Human Human Resources Hypersensitivity Hypochlorous Acid Hypoxemia Hypoxia In Vitro Inbred BALB C Mice Indium Individual Infant Inflammation Inflammatory Inflammatory Response Influenza Injection of therapeutic agent Injury Institution Instruction Intervention Ion Channel Irritants Laboratories Life Link Liquid substance Lower Respiratory Tract Infection Lung Lung diseases Measurement Measures Modeling Morbidity - disease rate Mucous body substance Mus Names Neurons Nitric Oxide Nitric Oxide Donors Nitrites Obstruction Operations Research Organ Ovalbumin Ovum Oxygen Pain Panic Pathologic Patients Perfusion Peritoneal Physiological Play Pneumonia Population Postdoctoral Fellow Publishing Rattus Reagent Recovery Reduced Glutathione Relative (related person)Reporting Research Research Personnel Resistance Respiratory Syncytial Virus Infections Respiratory System Respiratory syncytial virus Rest Review Committee Rodent Role Seminal Series Services Signal Pathway Signal Transduction Sodium Sodium Channel Stimulus Structure Structure of parenchyma of lung Structure of respiratory epithelium Talents Techniques Telephone Testing Therapeutic Therapeutic Agents Time Tissues Toxic effect Treatment Efficacy United States National Institutes of Health Ventilatory Depression Viral Load result Virus Diseases Work abstracting airway epithelium alveolar epithelium antioxidant therapy ascorbate base cell injury combat constriction cytokine efficacy testing epithelial Na+ channel experience high risk human NOS3 protein in vivo indexing innovation lung injury meetings member mortality novel patient population prevent protective effect pulmonary agents pulmonary function receptor research study respiratory response sensor sodium channel proteins stem surfactant web site

项目摘要

This Research Center of Excellence (RCE) entitled: "Novel Treatments of Chlorine Induced Injury to the Cardio-Respiratory Systems" consists of three projects and two cores. The unifying theme spanning all projects is that exposure of animals to C12 results in the formation of reactive intermediates which deplete ascorbate and reduced glutathione in the lung epithelial fluids, damage key components of the respiratory and alveolar epithelial [such as transient receptor protein (TRP) and epithelial sodium channels (ENaC)] and then, via inhibition of eNOS signaling compromise seminal functions of the pulmonary and systemic vasculatures. Furthermore, we propose that these toxic effects of C12 will be heightened in animals infected with respiratory syncytial virus or challenged with ova albumin. In our first series of experiments we will perform a number of state of the art biochemical, biophysical, physiological and morphometric measurements in RSV infected and ova albumin challenged mice as well as normal rats prior to and following C12 exposure to document the onset and progression of injury to lung epithelia and pulmonary and systemic vasculature. We will then treat them with antioxidants, TRP antagonists, B2 agonists and nitrite administered at various intervals post C12 exposure either intra-tracheally or via aerosolization or intraperitoneally (antioxidants and nitrite) and quantify recovery by specific functional measurements. Strong points of the RCE include the diverse talents of the investigators, the unique facilities, and the novelty of the preliminary data. The three projects (two of which build on novel findings generated by existing UO1 grants) are supported by an administrative core and the exposure core, which play key roles by both providing essential functions (such as exposure of animals to C12) and helping to integrate the team into a cohesive entity.

这个卓越的研究中心（RCE）题为：“氯引起的呼吸系统损伤的新疗法”由三个项目和两个核心组成。涵盖所有项目的统一主题是，动物暴露于C12导致形成活性中间体，其消耗肺上皮液中的抗坏血酸盐和还原型谷胱甘肽，损害呼吸和肺泡上皮的关键组分[如瞬时受体蛋白（TRP）和上皮钠通道（ENaC）]，然后，通过抑制eNOS信号传导损害肺和全身血管的精液功能。此外，我们认为C12的这些毒性作用在呼吸道合胞病毒感染或卵清蛋白攻击的动物中会增强。在我们的第一系列实验中，我们将在暴露于C12之前和之后，在RSV感染和卵白蛋白攻击的小鼠以及正常大鼠中进行许多最先进的生物化学、生物物理学、生理学和形态测量，以记录肺上皮和肺及全身血管系统损伤的发生和进展。然后，我们将用抗氧化剂、TRP拮抗剂、B2激动剂和亚硝酸盐在C12暴露后的不同时间间隔进行治疗，气管内或通过雾化或腹膜内（抗氧化剂和亚硝酸盐），并通过特定的功能测量来量化恢复。RCE的优点包括调查人员的多样性，独特的设施和初步数据的新奇。这三个项目（其中两个基于现有UO 1赠款产生的新发现）得到了行政核心和暴露核心的支持，这两个核心通过提供基本功能（如动物暴露于C12）和帮助将团队整合为一个有凝聚力的实体来发挥关键作用。