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

基本信息

批准号：
7187483
负责人：
KENT E VRANA
金额：
$ 35.71万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-01 至 2009-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7187483
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 Medical Surveillance 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 Risk Sampling Score 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 alcoholism/alcohol abuse animal resource behavior observation chronic alcohol ingestion cohort design drinking gel electrophoresis health care delivery high risk drinking indexing male nonhuman primate problem drinker protein expression research clinical testing research study tool

项目摘要

DESCRIPTION (provided by applicant): 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 processed to 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.

描述（由申请人提供）：滥用乙醇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，无法诊断普通人群中的酗酒，或者在青少年和康复的酗酒者等人群中诊断滥用。因此，该提案旨在开发急性和长期饮酒的诊断生物标志物特征，以诊断高危饮酒，检测到饮酒的复发，披露最近的饮酒以及在高风险情况下（例如怀孕）。为此，提出了研究，以检查强大的非人类灵长类动物模型中潜在特征的血清蛋白质和蛋白质模式，该模型并非被合并药物使用，饮食不足和对饮酒史的不可靠评估所困扰。在这些NIAAA资助的，持续的受试者内部研究中，猴子被诱导自愿喝大量的酒精。在研究过程中（包含100多种单独的动物，涵盖了多年的行为和观察），经常收集和存档血清样品。提出了实验来筛选这些样品的潜在生物标志物，然后将其前进到人群中。长期非人类灵长类动物自我管理研究的血清样品将用作使用高吞吐量蛋白质组学的生物标志物鉴定的训练集。样品将被处理以耗尽最丰富，模糊的蛋白质，然后经过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，然后通过MALDI-TOF/TOF/TOF鉴定蛋白质物种。统计验证将以盲目的方式使用来自自我管理猴子的独立菌落的样本进行测试集，该样本还将包含有关青少年脆弱性的数据。任何推定的生物标志物的关键标准都将是敏感性（饮酒者的正分数百分比）和特异性（不饮用的人群中假阳性的百分比）。此外，这些研究将为生物标志性特征提供正面和阴性预测值的初始指数。对乙醇滥用和酗酒的临床测试将有许多潜在用途。为了发现乙醇滥用和酒精中毒的蛋白质生物标志物，将通过定量蛋白质组学方法检查来自受控非人类灵长类动物种群自我管理乙醇的血清。