Clinical Investigations in Infectious and Autoimmune Diseases

免疫功能低下的患者表现出各种各样的特发性皮肤和粘膜损害，包括皮炎、胃肠道和生殖道溃疡以及复发性口腔炎。这项研究的目标之一是评估与免疫失调相关的粘膜炎症的发病机制，这些炎症与HIV感染的口疮患者有关。一项使用局部使用沙利度胺的随机对照临床试验被启动，作为一种工具，旨在研究口腔口疮的发病机制和治疗。口腔口疮是一种原因不明的自发性复发性粘膜溃疡，在艾滋病毒/艾滋病患者中持续存在并使人虚弱。除了粘膜损伤，皮肤损伤也可能成为慢性和衰弱的，新的努力集中在治疗干预慢性不可愈合的伤口。以中性粒细胞占优势和弹性酶过多为特征的老年人的延迟愈合反应，可以在去卵巢的啮齿动物和分泌性白细胞蛋白酶抑制物(SLPI)基因敲除小鼠的动物模型中模拟。使用这些模型，局部应用雌激素或具有抗炎和抗弹性酶特性的SLPI可以逆转延迟愈合。在局部应用雌激素成功逆转人类不可愈合创面的基础上，将评估其他抑制炎症部位持续的白细胞募集和过多的弹性蛋白酶释放的新方法在促进愈合过程中的效果。

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. In addition to mucosal lesions, cutaneous lesions may also become chronic and debilitating, and new efforts are focusing on therapeutic intervention in chronic nonhealing wounds. The delayed 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, delayed healing can be reversed by the topical application of estrogen or by SLPI which has anti-inflammatory and anti-elastase properties. Based on the successful application of estrogen topically in reversing human nnnonhealing 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.