Serum Biomarkers of Alcohol Self-Administration in Non-Human Primates

非人类灵长类动物自我饮酒的血清生物标志物

• 批准号: 7547094
• 负责人: KENT E VRANA
• 金额: $ 32.91万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7547094
• 关键词: Acute; Address; Adolescent; Adult; Albumins; Alcohol abuse; Alcohol consumption; Alcoholism; Alcohols; Animals; Archives; Biological; Biological Assay; Biological Markers; Blinded; Clinical; Cluster Analysis; Data; Diagnosis; Diagnostic; Diagnostic Sensitivity; Diet; Disease; Dose; Drug usage; Enzyme-Linked Immunosorbent Assay; Enzymes; Ethanol; Female Adolescents; Fluorescence; Funding; General Population; Goals; Haptoglobins; Health; Heavy Drinking; Human; Immunoblotting; Immunoglobulins; Individual; Institution; Intake; Interdisciplinary Study; Life; Measurement; Methods; Modeling; Monkeys; Pathology; Pattern; Population; Predictive Value; Pregnancy; Probability; Process; Productivity; Protein C Inhibitor; Proteins; Proteomics; Recording of previous events; Relapse; Research Personnel; Resources; Sampling; Screening procedure; Self Administration; Self-Administered; Sensitivity and Specificity; Serum; Serum Proteins; Source; Specificity; Study Subject; Talents; Testing; Training; Transferrin; Two-Dimensional Gel Electrophoresis; Validation; animal resource; behavior observation; chronic alcohol ingestion; cohort; design; drinking; gel electrophoresis; health care delivery; high risk; high risk drinking; indexing; male; nonhuman primate; problem drinker; protein expression; research clinical testing; research study; tool

Ethanol abuse and alcoholism remain very serious societal problems. A significant problem is the inability to diagnose alcohol abuse either in the general population or within selected groups of individuals such as adolescents and the recovering alcoholic. Accordingly, this proposal seeks to develop diagnostic biomarker signatures of acute and chronic alcohol consumption for diagnosing high-risk drinking, detecting relapse to drinking, disclosing recent drinking and in high risk situations such as pregnancy. To this end, studies are proposed to examine serum proteins and protein patterns for potential signatures in a powerful non-human primate model that is not encumbered by problems of comorbid drug use, inadequate diet and unreliable assessments of drinking history. In these NIAAA-funded, ongoing, within-subject studies, monkeys have been induced to voluntarily drink large amounts of alcohol. In the course of the studies (encompassing over 100 individual animals covering years of behavior and observation), serum samples have routinely been collected and archived. Experiments are proposed to screen these samples for potential biomarkers that can then be taken forward into the human population. Serum samples from a long-standing nonhuman primate self-administration study will be used as a training set for biomarker identification using high throughput proteomics. Samples will be processedto deplete the most abundant, obscuring proteins and then subjected to 2-DIGE (2-D Fluorescence Difference In-Gel Electrophoresis) for quantitative fluorescence identification of altered serum protein expression followed by MALDI-ToF/ToF identification of protein species. Statistical validation will be conducted, in a blinded fashion, using a test set of samples from an independent colony of self-administering monkeys, which will also contain data on adolescent vulnerability. The key criteria of any putative biomarkers will be sensitivity (percentage of positive scores among drinkers) and specificity (percentage of false positives in a non-drinking population). In addition, these studies will provide initial indices of positive and negative predictive values for biomarker signatures. A clinical test for ethanol abuse and alcoholism would have many potential uses. To discover protein biomarkers of ethanol abuse and alcoholism, serum from a controlled non-human primate population self- administering ethanol will be examined by quantitative proteomic methods.

乙醇滥用和酒精中毒仍然是非常严重的社会问题。一个重要的问题是无法 诊断一般人口或选定的个体群体中的酗酒 青少年和康复的酒精。因此，该建议旨在开发诊断生物标志物 急性和长期饮酒的特征，用于诊断高危饮酒，检测到复发 饮酒，披露最近的饮酒以及诸如怀孕之类的高风险情况。为此，研究是 提议检查强大非人类的潜在特征的血清蛋白质和蛋白质模式 不受合并药物使用问题，饮食不足和不可靠问题所束缚的灵长类动物模型 评估饮酒史。在这些NIAAA资助的，正在进行的受试者内研究中，猴子有 被诱使自愿喝大量酒精。在研究过程中（涵盖 涵盖了多年行为和观察的100种单个动物）通常是血清样品 收集和存档。提出了实验以筛选这些样品的潜在生物标志物可以 然后被带入人口。长期存在的非人类灵长类动物的血清样品 自我管理研究将用作使用高吞吐量的生物标记识别的训练集 蛋白质组学。样品将被处理以耗尽最丰富，遮盖的蛋白质，然后受到。 至2-DIGE（2-D荧光差异凝胶电泳），以定量荧光鉴定 血清蛋白表达改变，然后是蛋白质物种的MALDI-TOF/TOF鉴定。统计 验证将以盲目的方式使用来自独立群体的样本进行测试集 自我管理的猴子，这也将包含有关青少年脆弱性的数据。任何关键标准 推定的生物标志物将是敏感性（饮酒者的正分数百分比）和特异性 （在不喝酒的人群中的假阳性百分比）。此外，这些研究将提供初始 生物标志物特征的正和阴性预测值的指标。 对乙醇滥用和酗酒的临床测试将有许多潜在用途。发现蛋白质 乙醇滥用和酗酒的生物标志物，来自受控非人类灵长类动物人群的血清 施用乙醇将通过定量蛋白质组学方法检查。