Platelets Mediating Alcohol and HIV Damage

血小板介导酒精和艾滋病毒损伤

• 批准号: 8080465
• 负责人: Maria-Jose Miguez
• 金额: $ 34.64万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-10 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8080465
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Alcohol abuse; Alcohol consumption; Alcoholism; Alcohols; Apoptosis; Area; Behavioral Mechanisms; Binding; Biochemical; Biological; Blood - brain barrier anatomy; Blood Platelets; Brain; Brain-Derived Neurotrophic Factor; CD8B1 gene; Caring; Clinic; Clinical; Cognition; Cognitive; Complement; Data; Dementia; Development; Disease; Disease Progression; Drops; Drug user; Equation; Evaluation; Grant; Growth; HIV; HIV Infections; HIV Seropositivity; Health; Heavy Drinking; Hemostatic function; High Prevalence; Homosexuals; Host Defense Mechanism; Human; Immune; Immune System Diseases; Immune response; Immune system; Immunomodulators; Impaired cognition; Impairment; In Vitro; Individual; Inflammation; Inflammatory; Knowledge; Longitudinal Studies; Maintenance; Measures; Mediating; Mediator of activation protein; Medical; Memory; Modeling; Moods; National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; Neurocognitive; Neurologic; Neurons; Neurotransmitters; Nutritional; Oxidative Stress; Participant; Pathogenesis; Patients; Performance; Peripheral; Persons; Pharmaceutical Preparations; Platelet Activation; Platelet Count measurement; Population; Predisposition; Prevalence; Publishing; Questionnaires; Recommendation; Recording of previous events; Reporting; Research; Risk; Risk Factors; Role; Sampling; Scientist; Serotonin; Source; Staging; Syndrome; System; TNF gene; Testing; Therapeutic; Therapeutic Intervention; Thrombocytopenia; Time; Tumor Necrosis Factor-alpha; United States; United States National Institutes of Health; Variant; Viral Load result; Visit; Woman; World Health Organization; aged; alcohol effect; alcohol measurement; alcohol related problem; base; case control; cell injury; clinically significant; cofactor; cognitive function; cytokine; design; drinking; follow-up; global health; immune function; immunoregulation; in vivo; information processing; innovation; insight; interest; men; mood regulation; multidisciplinary; neurobiological mechanism; neuropsychological; nutrition; processing speed; response; secondary outcome

DESCRIPTION (provided by applicant): This study has been designed with the recognition that the concurrence of alcohol use and HIV infection are escalating worldwide, and of critical concern is the significantly impairing immune responses and cognitive performance among those HIV infected individuals in their more productive years. Recognizing the involvement of the immune system in the neurobiological mechanisms that underlie cognitive impairment, we will also investigate its action, through the evaluation of platelets and platelet associated factors (i.e. serotonin, PAF, BDNF) on both immune and cognitive dysfunction. Support for this potential mechanism is based upon our preliminary findings and evidence that 1) both HIV and alcohol use affect and are affected by platelets and platelet associated factors, 2) platelets are a source of neurotransmitters and immunomodulators; 3) platelet drops have been associated with HIV disease progression and 4) platelets have been proof a good peripheral model to study CNS compromise. Over the past six years, we have evaluated the deleterious effects of combined alcohol abuse and HIV infection over the neuroimmune system, in an ethnically diverse clinical sample. The proposed application will build upon our previous studies. Using an observational clinic based longitudinal study we will evaluate platelets, platelet associated factors, immune and cognitive function in four groups: hazardous and non-hazardous alcohol consuming HIV-infected subjects and hazardous and non-hazardous alcohol consuming HIV sero-negative subjects (n=540). Using standard questionnaires, a detailed sociodemographic, medical, nutritional, alcohol use and HIV medication history will be obtained. Biological measures (i.e. alcohol levels, platelet counts, serotonin, brain derived neurotrophic factors, platelet activator factor, CD4, CD8, markers or apoptosis, TNF viral load, nutrition status, biochemical profile) followed longitudinally will complement the evaluation. Cognitive function will be evaluated at baseline, 6, 12 and 18 months using a cognitive test battery that incorporates recommendations from the NIMH Workgroup on Neuropsychological Assessment Approaches in HIV. We will then establish cross-sectional and longitudinal within-subject relationships among platelets system measures, cognitive performance, and clinical status by study groups. Our long-term objectives are to extend biomedical knowledge related to mechanism mediating alcohol/HIV damage. magebocytopenia and platelet associated factors on the observations. PUBLIC HEALTH RELEVANCE: Collectively, this information will broaden the scope of therapeutic interventions that might be used to enhance or restore host defense mechanisms and neuroimmune modulation that have been altered as a result of HIV infection and drinking. By increasing understanding of the new mechanistic insights related to the role of thrombocytopenia in the pathogenesis of HIV, scientist can manipulate them to therapeutic advantage.

描述(由申请人提供)：这项研究是在认识到酒精使用和艾滋病毒感染在全球范围内不断升级的情况下设计的，特别令人担忧的是，艾滋病毒感染者在其生产力较高的年龄段对免疫反应和认知能力造成了严重损害。认识到免疫系统参与了认知障碍的神经生物学机制，我们还将通过评估血小板和血小板相关因子(即5-羟色胺、PAF、BDNF)在免疫和认知功能障碍中的作用。对这一潜在机制的支持是基于我们的初步发现和证据，即1)艾滋病毒和酒精使用都会影响血小板和血小板相关因子，2)血小板是神经递质和免疫调节剂的来源；3)血小板下降与艾滋病毒疾病的进展有关，4)血小板已被证明是研究中枢神经系统损害的良好外周模型。在过去的六年里，我们在一个不同种族的临床样本中评估了酒精滥用和艾滋病毒感染对神经免疫系统的有害影响。拟议的申请将建立在我们之前的研究基础上。采用观察性临床纵向研究，我们将评估四组患者的血小板、血小板相关因子、免疫和认知功能：危险和非危险饮酒HIV感染者和危险和非危险饮酒HIV血清阴性受试者(n=540)。使用标准问卷，将获得详细的社会人口、医疗、营养、酒精使用和艾滋病毒用药史。随后的纵向生物学测量(即酒精水平、血小板计数、5-羟色胺、脑源性神经营养因子、血小板激活因子、CD4、CD8、标记物或细胞凋亡、肿瘤坏死因子病毒载量、营养状况、生化图谱)将补充评估。认知功能将在基线、6个月、12个月和18个月时使用认知测试组合进行评估，其中纳入了NIMH工作组关于艾滋病毒神经心理评估方法的建议。然后，我们将通过研究小组在血小板系统测量、认知表现和临床状态之间建立横断面和纵向的受试者内关系。我们的长期目标是扩展与酒精/艾滋病毒损伤机制相关的生物医学知识。对巨噬细胞减少症和血小板相关因子进行观察。公共卫生相关性：总的来说，这些信息将扩大治疗干预的范围，这些干预措施可能用于增强或恢复因艾滋病毒感染和饮酒而改变的宿主防御机制和神经免疫调节。通过增加对与血小板减少在艾滋病毒发病机制中的作用相关的新机制的了解，科学家可以将其操纵为治疗优势。

项目成果

Heavy alcohol use hinders HIV therapy: study.

研究表明，大量饮酒会阻碍艾滋病毒治疗。

• 发表时间: 2001
• 期刊: AIDS alert
• 作者: Shor-Posner,G;Miguez,MJ
• 通讯作者: Miguez,MJ

Cholesterol as a Mediator of Alcohol-Induced Risks for Respiratory Disease Hospitalizations among People Living With HIV.

• DOI: 10.4172/2155-6113.s1-001
• 发表时间: 2011
• 期刊: Journal of AIDS & clinical research
• 作者: M. Míguez;R. Rosenberg;X. Burbano;R. Malow

The effect of alcohol use on IL-6 responses across different racial/ethnic groups.

• DOI: 10.2217/fvl.12.3
• 发表时间: 2012-02
• 期刊: Future virology
• 影响因子: 3.1
• 作者: Míguez MJ;Rosenberg R;Burbano-Levy X;Carmona T;Malow R
• 通讯作者: Malow R

Hypocalcaemia, alcohol drinking and viroimmune responses in ART recipients.

ART 接受者的低钙血症、饮酒和病毒免疫反应。

• DOI: 10.1016/j.alcohol.2012.07.004
• 发表时间: 2012
• 期刊: Alcohol (Fayetteville, N.Y.)
• 作者: Míguez,MaríaJosé;Burbano-Levy,Ximena;Carmona,Talita;Quiros,Clery;Thompson,Michelle;Lewis,JohnE;Asthana,Desharatan;Rodríguez,Allan;Valiathan,Ranjini;Malow,Robert
• 通讯作者: Malow,Robert