Platelets Mediating Alcohol and HIV Damage

描述（由申请人提供）：本研究的设计考虑到全球范围内饮酒和艾滋病毒感染的同时发生正在不断升级，而最令人担忧的是，艾滋病毒感染者在其生产力较高的时期，其免疫反应和认知能力会受到严重损害。认识到免疫系统参与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（即血清素、PAF、BDNF）对免疫和认知功能障碍的作用来研究其作用。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) HIV 和饮酒都会影响血小板和血小板相关因子，并受血小板和血小板相关因子的影响，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 HIV 疾病进展有关，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，我们在不同种族的临床样本中评估了酗酒和艾滋病毒感染对神经免疫系统的有害影响。拟议的应用程序将建立在我们之前的研究的基础上。使用基于观察性临床的纵向研究，我们将评估四组的血小板、血小板相关因子、免疫和认知功能：危险和非危险饮酒的 HIV 感染受试者以及危险和非危险饮酒的 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统计、医疗、营养、饮酒和艾滋病毒药物治疗史。纵向跟踪的生物测量（即酒精水平、血小板计数、血清素、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、TNF 病毒载量、营养状况、生化特征）将补充评估。将使用认知测试组在基线、6、12 和 18 个月时评估认知功能，该测试组纳入了 NIMH HIV 神经心理学评估方法工作组的建议。然后，我们将按研究组建立血小板系统测量、认知表现和临床状态之间的横断面和纵向受试者内关系。我们的长期目标是扩展与介导酒精/艾滋病毒损害机制相关的生物医学知识。巨细胞减少症与血小板相关因素的观察。公共健康相关性：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。通过加深对与血小板减少症在艾滋病毒发病机制中的作用相关的新机制的了解，科学家可以操纵它们以获得治疗优势。

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.