Clinical Studies in Nutrition and Metabolism

描述(申请人提供)：心血管疾病是美国发病率和死亡率的主要原因。氧化应激和炎症在动脉粥样硬化形成中起着关键作用。候选人：在资助的K24奖(第4年)中，首席研究人员在生产率(出版物和获得赠款)、指导和加强他的研究计划方面取得了出色的进步。研究计划：在这项旨在进一步加强其面向患者研究的研究计划和指导的建议中，主要研究人员提出了以下研究：1)大剂量补充α-生育酚对冠心病患者氧化应激(OS)、炎症和颈动脉粥样硬化的影响；2)1型糖尿病患者单核细胞功能和炎症反应及其辛伐他汀治疗的调节；3)辛伐他汀治疗对代谢综合征患者单核细胞炎症标志物和hsCRP水平的影响；4)补充番茄红素对OS生物标志物的剂量-反应效应；5)补充α-生育酚和γ-生育酚对代谢综合征患者OS和炎症生物标志物的影响。将分析的OS生物标志物包括尿F2-异前列腺素、低密度脂蛋白氧化敏感性；炎症生物标志物将包括hs-CRP、SAA、血浆可溶性细胞黏附分子、单核细胞超氧阴离子释放、细胞因子释放、与内皮的黏附。指导计划：除了加州大学戴维斯分校提供的教学课程和指导临床研究培训计划外，这些营养和代谢方面的重点和凝聚力的临床研究将为初级教员和临床研究员提供一个以患者为导向的研究领域的良好培训基础。因此，这项建议中概述的研究将明显增强首席研究员的长期目标，因为他的主要兴趣是糖尿病和动脉粥样硬化中的脂蛋白、氧化应激和炎症及其调节。

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Oxidative Stress and Inflammation play a pivotal role in atherogenesis. CANDIDATE: In the funded K24 Award (Year 4), the principal investigator has made excellent progress with respect to productivity (publications and procuring grants), mentoring and enhancing his research program. RESEARCH PLAN: In the present proposal, which aims to further strengthen his research program and mentoring in patient-oriented research, the principal investigator proposes the following studies: 1) The Effect of High dose Alpha tocopherol Supplementation on Oxidative Stress (OS), Inflammation and Carotid Atherosclerosis in Patients with Coronary artery disease ; 2) Monocyte Function and Inflammation in Type 1 Diabetes and its Modulation with Simvastatin therapy; 3) The Effect of Simvastatin Therapy on Monocytic Inflammatory Markers and hsCRP Levels in Patients with the Metabolic Syndrome; 4) A Dose-Response Effect of Lycopene supplementation on Biomarkers of OS; 5) Effect of Alpha tocopherol and Gamma tocopherol Supplementation on Biomarkers of OS and Inflammation in Patients with the Metabolic Syndrome. Biomarkers of OS that will be analyzed include urinary F2-isoprostanes, LDL oxidative susceptibility; biomarkers of inflammation will include hs-CRP, SAA, plasma soluble cell adhesion molecules, monocyte superoxide anion release, cytokine release, adhesion to endothelium. MENTORING PLAN: These focused and cohesive clinical studies in Nutrition and Metabolism, in addition to the didactic courses and Mentored Clinical Research Training Program offered at UC-Davis will provide an excellent training ground for the junior faculty and clinical fellows in the area of patient-oriented research. Thus, studies outlined in this proposal will clearly enhance the long-term objectives of the principal investigator, since his major interest is in the area of lipoproteins, oxidative stress and inflammation in diabetes and atherosclerosis and their modulation.