Clinical Investigations In Infectious And Autoimmune Dis

免疫功能低下的患者表现出多种特发性皮肤和粘膜病变，包括皮炎、胃肠道和生殖道溃疡以及复发性口腔炎。本研究计划的目的之一是评估与免疫失调相关的粘膜炎症在hiv感染的口腔病变患者中的发病机制。一项使用局部沙利度胺的随机对照临床试验被启动，该试验作为几条调查线的载体，旨在调查口腔溃疡的发病机制和治疗，口腔溃疡是一种病因不明的自发性、复发性粘膜溃疡，在HIV/AIDS患者中持续存在并使人虚弱。剂量相关愈合反应局部沙利度胺无不良反应。基于令人印象深刻的愈合反应，局部沙利度胺似乎是口服沙利度胺治疗艾滋病感染患者口腔溃疡的有效替代方法。除了粘膜病变，颞下颌关节疾病和皮肤病变也可能成为慢性和衰弱，努力集中在表征潜在的发病机制。老年人皮肤愈合反应的延迟，以中性粒细胞和多余弹性蛋白酶为主，可以在动物模型中模拟，包括卵巢切除的啮齿动物和分泌白细胞蛋白酶抑制剂（SLPI）敲除小鼠。使用这些皮肤和口腔伤口模型，局部应用TNF拮抗剂、SLPI和合成纤维连接蛋白肽可以逆转延迟愈合。基于这些药物和其他药物在逆转人类不愈合伤口方面的成功局部递送，其他抑制炎症部位持续白细胞募集和过多弹性蛋白酶释放的新方法将被评估其促进愈合过程的功效。

Immunocompromised patients demonstrate a wide variety of idiopathic cutaneous and mucosal lesions including dermatitis, gastrointestinal and genital tract ulcerations, and recurrent aphthous stomatitis. One objective of this research program is to evaluate the pathogenesis of mucosal inflammation associated with immune dysregulation in HIV-infected patients with aphthous lesions. A randomized, controlled clinical trial using topical thalidomide was initiated which serves as a vehicle for several lines of inquiry directed towards investigating the pathogenesis and treatment of oral aphthous ulcers, which are spontaneous, recurrent mucosal ulcerations of unknown etiology, and which are persistent and debilitating in persons with HIV/AIDS.Dose related healing in response to topical thalidomide without adverse effects. Based on the impressive healing response, topical thalidomide appears to be an effective alternative to oral thalidomide treatment for aphthous ulcers in pateints with HIV infection. In addition to mucosal lesions, temporomandibular joint disease and cutaneous lesions may also become chronic and debilitating, and efforts are focusing on characterizing the underlying pathogenesis. The delayed cutaneous healing response in the aged, characterized by a predominance of neutrophils and excess elastase, can be mimicked in animal models including ovariectomized rodents and secretory leukocyte protease inhibitor(SLPI) knockout mice. Using these models of cutaneous and oral wounds, delayed healing can be reversed by the topical application of TNF antagonists, SLPI and synthetic fibronectin peptides. Based on the successful topical delivery of these and other agents in reversing human nonhealing wounds, other novel approaches for inhibiting the persistent leukocyte recruitment and overabundant elastase released at the inflammatory site will be evaluated for their efficacy in facilitating the healing process.