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病变，包括皮炎、胃肠道和生殖道溃疡以及复发性口疮性口炎。 本研究项目的目的之一是评估与免疫失调相关的粘膜炎症的发病机制，在艾滋病毒感染的口疮病变患者。 开始了一项使用局部沙利度胺的随机对照临床试验，该试验作为几种调查途径的载体，旨在研究口腔阿弗他溃疡的发病机制和治疗，阿弗他溃疡是自发的、复发性粘膜溃疡，病因不明，在HIV/AIDS患者中持续存在并使人衰弱。 除了粘膜病变，皮肤病变也可能成为慢性和衰弱，新的努力集中在慢性不愈合伤口的治疗干预。老年人的延迟愈合反应，其特征在于中性粒细胞和过量弹性蛋白酶的优势，可以在动物模型中模拟，包括卵巢切除啮齿动物和分泌性白细胞蛋白酶抑制剂（SLPI）基因敲除小鼠。 使用这些模型，延迟愈合可以通过局部应用雌激素或通过具有抗炎和抗弹性蛋白酶性质的SLPI来逆转。基于局部应用雌激素成功逆转人类nnnonhealing伤口，其他新的方法，抑制持续白细胞募集和过度丰富的弹性蛋白酶释放在炎症部位将评估其在促进愈合过程中的疗效。

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. 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.