Characterization of cocaine induced signaling pathways that enhances HIV transcription

标题：评估可卡因和艾滋病毒对加速衰老过程的影响 尽管高效的抗逆转录病毒治疗有效，但加速衰老是艾滋病毒感染的并发症 (HAART或ART)。这在一定程度上是由于艾滋病毒相关的神经疾病(手)，主要是由 通过中枢神经系统中持续的免疫激活和炎症。有相当多的证据表明 可卡因对HIV患者神经认知功能障碍持续时间和严重程度的相加或协同作用 被感染的病人。因此，滥用毒品，如可卡因、艾滋病毒感染、 神经退化和加速衰老是特别令人感兴趣的。 拟议调查的总体目标是了解可卡因通过 使用可进一步加速HIV感染者的衰老过程，这是通过增强免疫活性和 发炎。醋栗抗艾滋病毒疗法无法限制艾滋病毒蛋白质的生产。某些HIV蛋白是 有毒，特别是对中枢神经系统，因为它们刺激促炎细胞因子和免疫激活。可卡因 进一步提高艾滋病毒蛋白产量。本申请书中提出的调查将确定 可卡因通过比较感染了艾滋病毒的可卡因和未治疗的人加速衰老过程 淋巴样细胞和髓样细胞。结果将在HIV感染者的PBMC中得到确认，无论是否有 接触可卡因。 提出以下目标，以确认和量化可卡因在促进过早衰老方面的影响： 目的1A：分析免疫激活和炎症的细胞表面标志物，选择性地由 可卡因 目的1B：研究可卡因暴露对细胞衰老的潜在影响 目的1C：确定可卡因对细胞耗竭的影响 目的2：确定可卡因使用后免疫激活和炎症的血浆标志物 目的3：研究可卡因对端粒长度、端粒酶转录本、蛋白质和活性的影响。 本申请中提议的调查将确定可卡因通过以下方式加速衰老过程 比较使用可卡因的艾滋病毒感染者和不使用可卡因的人。

TITLE: Assessing the impact of cocaine and HIV in accelerating aging process Accelerated aging is a complication of HIV infection despite the effectiveness of highly active antiretroviral therapy (HAART or ART). This is due, in part, to HIV-associated neurological disorders (HAND) which are caused mainly by the ongoing immune activation and inflammation in the CNS. There is considerable evidence that suggests an additive or synergistic effect of cocaine on the persistence and severity of neurocognitive dysfunction in HIV- infected patients. Therefore, the relationship between drugs of abuse, such as cocaine, HIV infection, neurodegeneration and accelerated aging is of particular interest. Overall goal of the proposed investigation is to understand the underlying mechanisms through which cocaine use further accelerates the aging process in HIV infected individuals by enhancing immune activation and inflammation. Currant anti-HIV therapy is unable to restrict HIV protein production. Certain HIV proteins are toxic, especially to the CNS, as they stimulate pro-inflammatory cytokines and immune activation. Cocaine further enhance HIV protein production. The investigation proposed in this application will establish that cocaine accelerates the aging process by comparing cocaine treated and untreated HIV-infected both lymphoid and myeloid cells. Results will be confirmed in PBMCs of HIV-infected subjects with or without cocaine exposure. The following aims are proposed to confirm and quantify the impact of cocaine in promoting premature aging: Aim 1A: Analysis of cell surface markers of immune activation and inflammation, selectively triggered by cocaine Aim 1B: Investigate the potential impact of cocaine exposure on cell senescence Aim 1C: Determine the cocaine effect on cell exhaustion Aim 2: Define the plasma markers of immune activation and inflammation following cocaine use Aim 3: Examine the impact of cocaine on telomere length, telomerase transcript, protein and activity. The investigation proposed in this application will establish that cocaine accelerates the aging process by comparing cocaine-using HIV infected subjects with those not using cocaine.