Overall Application: Trauma Primes Cells

描述(由申请人提供)：我们的全球假设是，人类核心(存储临床数据库和患者样本)与炎症信号机制研究之间的双向交换将有助于我们设计创伤启动细胞的治疗方法。自1993年首次提供资金以来，我们的财政部数据库大幅增长，对(I)失血性休克、(Ii)、输血(Iii)、抗炎复苏机制等固有的基本问题产生了新的见解。这些项目仍然高度依赖于彼此，并邀请人类核心进一步测试假设。项目。我的重点是失血性休克后肠系膜淋巴的细胞毒特性引起的肺损伤，推测是由于二十烷类化合物的代谢所致。在这项建议中，我们详细阐述了这种淋巴的潜在生物活性，即其毒性所必需的条件，并剖析了其成分。项目。II对血液产品中积累的脂质和蛋白质进行详细分析，重点是创伤的急性凝血障碍，目的是通过适当的血液复苏将死亡率降至最低。项目。ILL研究了通过高渗溶液调节转录因子激活来减轻炎症的机制，并试图应用吸入高渗盐水来减轻动物和人类的肺部炎症。为了验证这些想法，人类核心负责提供标本，收集数据，并更新创伤MOF数据库，同时保持严格的法规遵从性。一个充满活力的细胞、成像和蛋白质组学核心将为每个项目提供常用的人类细胞、设备和专业知识，以使用抗体和先进的MS蛋白质组学执行先进的分子共定位和细胞测量。这些努力得到了经验丰富的管理核心的支持，该管理核心寻求进一步加强我们的三个机构(丹佛健康医疗中心、百丽邦菲尔斯血液中心、科罗拉多大学健康科学中心)发布创伤研究和改善患者护理的能力。

DESCRIPTION (provided by applicant): Our global hypothesis is that two-way exchanges between Human Core (housing clinical databases and patient samples) with mechanistic studies of inflammatory signaling will help us devise THERAPY FOR TRAUMA PRIMED CELLS. Since initial funding in 1993, our MOF databases have grown substantially to yield novel insights into fundamental problems inherent to (I) hemorrhagic shock, (II), transfusion (III), mechanisms of anti-inflammatory resuscitation. The projects remain highly dependent on each other, and invite the Human Core to further test hypotheses. Project. I focuses on lung injury induced by the cytotoxic properties of mesenteric lymph that occur after hemorrhagic shock, presumably due to eicosanoid metabolism. In this proposal we expand on the potential bioactivity of this lymph, the condition necessary for its toxicity, and dissect its components. Project. II undertakes a detailed analysis of lipids and proteins accruing in blood products, focusing on the acute coagulopathy of trauma with the aim of minimizing mortality by proper blood resuscitation. Project. Ill examines mechanism of reducing inflammation by regulating transcription factor activation with hypertonic solution and seeks to apply inhaled hypertonic saline to reduce lung inflammation in animals and humans. To validate these ideas, the Human Core is charged with supplying specimens, gathering data, and updating the Trauma MOF database while remaining in strict regulatory compliance. A vigorous Cell, Imaging & Proteomics Core will provide each project with commonly used human cells, equipment and expertise to perform advanced molecular colocalization and cytometry using antibodies as well and advanced MS proteomics . These efforts are supported by a seasoned Administrative Core that seeks to further the prowess of our three institutions (Denver Health Medical Center, Belle Bonfils Blood Center, University of Colorado Health Sciences Center) to promulgate Trauma Research and improve patient care.