CORE--ANALYTICAL

直接测量活性物质的研究数量有限， 氧化应激在ARDS患者中的作用。一个主要限制 测量活性物质的最大障碍是它们在生物体内的半衰期很短， 系统.由于活性物质会改变生物分子， 蛋白质、脂质和DNA，对修饰靶点的测量提供了 用于检测和定量的实验工具。蛋白 羰基是通过氨基酸残基的直接氧化衍生的，或 醛类的共轭是由不饱和的氧化形成的 脂质或糖。总体血浆蛋白羰基表明 氧化剂。蛋白质酪氨酸残基的硝化导致 形成3-硝基酪氨酸。之前我们发现 过氧硝酸盐与CO2的混合物提供了必要的硝化剂， 解释了血浆蛋白3-硝基酪氨酸的形成。过氧硝酸盐是 由一氧化氮的几乎扩散限制反应形成， 过氧化物。尿异前列腺素是由反应性物质攻击产生的 对脂双层中花生四烯酸的影响，是选择性和敏感的指示剂 脂质过氧化反应。因此，分析的主要功能 化学核心（核心C）是测量修饰的血浆水平， 蛋白质（羰基和3-硝基酪氨酸）和尿异前列腺素 三号计划的人体样本蛋白质羰基也将被测量， 细胞裂解物、肺组织、灌注液和血浆 项目4。核心C还将作为中央处理、存储和 在项目3中收集的样品的分配设施。的 分析化学将设在环境研究所 药核心C的优势包括： 临床标本的采集、处理和保存， 研究人员测量这些生物标志物， 了解这些生物标志物的生化起源。

Limited number of studies that directly measure reactive species or oxidative stress in patients with ARDS are presently. A major limitation for measuring reactive species is their short half life in biological systems. Since reactive species modify biological molecules such as proteins, lipids and DNA, measurement of the modified targets provide the experimental tools for their detection and quantification. Protein carbonyls are derived by the direct oxidation of amino acid residues or conjugation of aldehydes that are formed by the oxidation of unsaturated lipids or sugars. Overall plasma protein carbonyls indicate the formation of oxidants. Nitration of protein tyrosine residues results in the formation of 3-nitrotyrosine. Previous we found that the reaction of peroxynitrate with C02 provides the necessary nitrating agent that explains the formation of plasm protein 3-nitrotyrosine. Peroxynitrate is formed by the nearly diffusion limited reaction of nitric oxide and superoxide. Urinary isoprostanes are generated by reactive species attack on arachidonate in lipid bilayers and is selective and sensitive indicator of lipid peroxidation. Therefore, the main function of the analytical chemistry core (Core C) is to measure the levels of modified plasma proteins (carbonyls and 3-nitrotyrosine) and urinary isoprostanes in the human samples for Project 3. Protein carbonyls will be also measured in cell lysates, lung tissue, perfusate and plasma in samples generated in Project 4. Core C will also function as a central processing, storage and distribution facility for the samples collected in Project 3. The analytical chemistry will be located at the Institute for Environmental Medicine. Strengths of Core C include the established protocols for clinical specimen collection, processing and storage, the experience of the investigators with measuring these biological markers and the understanding of the biochemical origin of these biological markers.