PATHOGENESIS OF ORAL ULCERS IN HIV INFECTED INDIVIDUALS

HIV 感染者口腔溃疡的发病机制

• 批准号: 2545670
• 负责人: THOMAS B. ALBRECHT
• 金额: $ 24.58万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2545670
• 关键词: HIV infections; Herpes simplex disease; cytomegalovirus; human subject; immunocytochemistry; opportunistic infections; oral pharyngeal disorder; pathologic process; polymerase chain reaction; saliva; tissue /cell culture; ulcer; virus cytopathogenic effect

Oral ulcerative lesions are an important cause of morbidity among HIV- infected individuals, often causing serious difficulties in complying with therapeutic regimens and sufficient nutrient and fluid intake. Some of these ulcers represent aphthous stomatitis which usually responds well to corticosteroid treatment, while data from a number of laboratories suggest that human cytomegalovirus (HCMV), and possibly herpes simplex virus (HSV), are involved in the pathogenesis of other persistent oral ulcerations. In addition, necrotizing stomatitis, gingivitis and periodontitis are ulcerative lesions that not only have a bacterial component but also may demonstrate concurrent infection with HCMV and HSV. Unfortunately, the reports of these persistent oral ulcers, published to date, have involved relatively small numbers of patients. The research proposed in this project will attempt to determine the role of HCMV and other factors (e.g., HSV) in the development and progression of persistent oral ulcers. Sections from surgical specimens of chronic oral ulcerations which have not responded to empirical drug therapy will be examined for virus-induced cytopathic changes and the presence of virus-specific components by immunohistochemical methods, in situ hybridization, and the multiplex polymerase chain reaction (PCR) to identify the specific cell types and virus(es) that are involved in these lesions. Saliva from individuals afflicted with persistent oral lesions and from those without these lesions will be monitored for human herpesviruses by culture and by quantitative PCR. Individuals with demonstrated involvement of HCMV in their persistent oral ulcers will be treated with ganciclovir to evaluate the potential of this therapeutic approach to manage these lesions. The contribution of several mechanisms of cellular injury associated with HCMV infection to the development and progression of persistent oral ulcers will be examined in an effort to begin to better characterize the pathogenesis of these lesions.

口腔溃疡性病变是艾滋病毒感染者发病的重要原因， 受感染的个人，往往造成严重的困难，在遵守 治疗方案和充足的营养和液体摄入。一些 这些溃疡的代表阿弗他口炎，通常反应良好 皮质类固醇治疗，而来自一些实验室的数据 提示人巨细胞病毒（HCMV），可能还有单纯疱疹 病毒（HSV），参与其他持续性口腔溃疡的发病机制 溃疡此外，坏死性口腔炎、牙龈炎和 牙周炎是一种溃疡性病变，不仅有细菌感染， 但也可能表现出并发HCMV感染， HSV。不幸的是，这些持续性口腔溃疡的报告， 迄今为止发表的文献涉及的患者数量相对较少。 本项目提出的研究将试图确定 HCMV和其他因素（例如，HSV）在发展和进展中的作用 持续性口腔溃疡。慢性胰腺炎手术标本切片 经验性药物治疗无效的口腔溃疡将 检查病毒诱导的细胞病变和是否存在 原位免疫组织化学法检测病毒特异性成分 杂交和多重聚合酶链反应（PCR）， 确定参与这些的特定细胞类型和病毒 病变患有持续性口腔病变的个体的唾液 从那些没有这些病变将监测人类 通过培养和定量PCR检测疱疹病毒。人士 证明HCMV参与他们的持续性口腔溃疡， 更昔洛韦治疗，以评估这种治疗的潜力， 方法来管理这些病变。若干机制的贡献 与HCMV感染相关的细胞损伤对发育和 将检查持续性口腔溃疡的进展， 开始更好地描述这些病变的发病机制。