TOPICAL RETINOIDS FOR DIABETIC FOOT ULCERS

局部用维A酸治疗糖尿病足溃疡

• 批准号: 6517861
• 负责人: JAMES VARANI
• 金额: $ 34.65万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6517861
• 关键词: adult human (21+); angiogenesis; cell proliferation; chemoprevention; collagenase; connective tissue development; diabetes mellitus; fibroblasts; foot; hip; histology; human subject; human therapy evaluation; in situ hybridization; laboratory rat; morphometry; organ culture; oxidative stress; patient oriented research; retinoids; skin disorder chemotherapy; skin ulcer; topical drug application; western blottings; wound healing

DESCRIPTION (adapted from the application) Diabetes remains one of the leading causes of lower limb amputation and is a contributing factor in up to 70 percent of the greater than 55,000 amputations annually. In the majority of diabetic subjects, the underlying factor which contributes to eventual amputation is the diabetic foot ulcer. The overall goal of this application is to determine the capacity of topical retinoid treatment to induce changes in the skin of diabetic patients that would reduce the incidence of ulcer formation and improve healing of wounds when they did occur. We know from recent studies that topical retinoid treatment improves histological structure and biochemical function of skin damaged by age and/or excessive exposure to solar radiation. Since diabetic skin demonstrates the same atrophic changes seen in aged human skin, it might be possible to improve structure and function in diabetic skin with the same approach. If one can improve the structure and function of diabetic skin in a similar fashion, such skin would be (in theory) more resistant to ulcer formation, and would heal better if wounding did occur. A three-part approach is proposed to achieve the overall goal of this application. We will in Specific Aim I assess fibroblast growth, connective tissue synthesis, matrix metalloproteinase (MMP) elaboration, vascular development and reactivity and indices of oxidative stress in hip skin from diabetic patients, including those with microangiopathic complications, and evaluate the effects of topical retinol treatment on these parameters. In Specific Aim 2, the goal will be to assess fibroblast growth, connective tissue synthesis, MMP elaboration, vascular development and reactivity and indices of oxidative stress in diabetic skin predisposed to the development of ulceration utilizing organ culture techniques. The effects of retinol treatment on these parameters will be assessed. Specific Aim 3 will make use of a rodent model of diabetes. Here we will determine the effects of topical retinol treatment on dermal structure/function in streptozotocin diabetic (STZ-D) rats and compare abrasion wound formation and healing in control rats, STZ-D rats and STZ-D rats that have been pretreated with topical retinol.

描述（根据应用程序改编） 糖尿病仍然是下肢截肢的主要原因之一，是 贡献高达55,000多个截肢的70％ 每年。在大多数糖尿病患者中，是基本因素 最终截肢的贡献是糖尿病足溃疡。总体目标 此应用的是确定局部视网膜类似治疗的能力 引起糖尿病患者皮肤的变化，以减少 确实发生溃疡的发生率并改善伤口的愈合。 从最近的研究中我们知道，局部类维生素性治疗可改善 年龄和/或受损的皮肤的组织学结构和生化功能 过度暴露于太阳辐射。由于糖尿病皮肤证明了 在老年人皮肤中看到的同样的萎缩变化，可能有可能改善 具有相同方法的糖尿病皮肤的结构和功能。如果可以的话 以类似的方式改善糖尿病皮肤的结构和功能 皮肤（理论上）对溃疡形成更具耐药性，并且会治愈 如果确实发生了伤害，更好。提出了三部分的方法来实现 该应用程序的总体目标。我们将以特定的目的评估成纤维细胞 生长，结缔组织合成，基质金属蛋白酶（MMP） 详细，血管发育和反应性以及氧化指标 糖尿病患者的髋关节皮肤压力，包括 微血管病并发症，并评估局部视网膜的影响 这些参数的处理。在特定目标2中，目标是评估 成纤维细胞生长，结缔组织合成，MMP阐述，血管 糖尿病皮肤中氧化应激的反应性和反应性和指标 利用器官培养的溃疡发展易于发展 技术。视黄醇处理对这些参数的影响将是 评估。具体的目标3将利用糖尿病的啮齿动物模型。我们在这里 将确定局部视黄醇处理对皮肤的影响 链蛋白酶糖尿病（STZ-D）大鼠的结构/功能，并比较磨损 控制大鼠，STZ-D大鼠和STZ-D大鼠的伤口形成和愈合 已预处理局部视黄醇。