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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：
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
项目类别：
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

项目摘要

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.

酒精滥用和酗酒仍然是非常严重的社会问题。一个重要的问题是没有能力