TOPICAL RETINOIDS FOR DIABETIC FOOT ULCERS

局部用维A酸治疗糖尿病足溃疡

• 批准号: 6635342
• 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 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635342
• 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.

说明(改编自应用程序) 糖尿病仍然是导致截肢的主要原因之一，是一种 在超过55,000例截肢中，高达70%的截肢是促成因素 每年一次。在大多数糖尿病受试者中， 导致最终截肢的原因是糖尿病足溃疡。总目标 这一应用的目的是确定局部维甲酸治疗的能力 诱导糖尿病患者的皮肤发生变化，从而减少 溃疡形成的发生率，并在伤口确实发生时改善愈合。 我们从最近的研究中得知，外用维甲酸治疗可以改善 年龄和/或皮肤损伤的组织结构和生化功能 过度暴露在太阳辐射下。由于糖尿病皮肤表现出 与老年人皮肤相同的萎缩性变化，可能会得到改善 糖尿病皮肤的结构和功能也是如此。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，如 皮肤(理论上)对溃疡形成的抵抗力更强，而且会愈合。 如果真的发生了伤人就更好了。提出了一个由三个部分组成的方法来实现 此应用程序的总体目标。我们将在特定的目标上评估成纤维细胞 生长、结缔组织合成、基质金属蛋白酶 精制、血管发育、反应性和氧化指数 糖尿病患者髋部皮肤的压力，包括那些有 微血管病变并发症，并评价局部应用视黄醇的效果 对这些参数的处理。在具体目标2中，目标将是评估 成纤维细胞生长、结缔组织合成、基质金属蛋白酶精制、血管 糖尿病皮肤氧化应激的发生、反应及指标 利用器官培养易发生溃烂 技巧。视黄醇治疗对这些参数的影响将是 评估过了。《特定目标3》将使用一种糖尿病的啮齿动物模型。在这里我们 将确定外用视黄醇对皮肤的影响 链脲佐菌素糖尿病(STZ-D)大鼠的结构/功能及磨损比较 正常大鼠、STZ-D大鼠和STZ-D大鼠伤口的形成和愈合 已经用外用视黄醇进行了预处理。

项目成果

Human skin organ culture for assessment of chemically induced skin damage.

• DOI: 10.1586/edm.12.24
• 发表时间: 2012-06-01
• 期刊: Expert review of dermatology
• 作者: Varani J

Antagonism of epidermal growth factor receptor tyrosine kinase ameliorates the psoriatic phenotype in organ-cultured skin.

表皮生长因子受体酪氨酸激酶的拮抗作用可改善器官培养皮肤的银屑病表型。

• DOI: 10.1159/000084909
• 发表时间: 2005
• 期刊: Skin pharmacology and physiology.
• 作者: Varani,J;Lateef,H;Fay,K;Elder,JT
• 通讯作者: Elder,JT

Retinoid-induced epidermal hyperplasia in human skin organ culture: inhibition with soy extract and soy isoflavones.

• DOI: 10.1016/j.yexmp.2004.08.003
• 发表时间: 2004-12
• 期刊: Experimental and molecular pathology
• 影响因子: 3.6
• 作者: J. Varani;E. Kelley;P. Perone;Huma Lateef

Activity of MDI-301, a novel synthetic retinoid, in xenografts.

MDI-301（一种新型合成类维生素A）在异种移植物中的活性。

• DOI: 10.1097/00001813-200411000-00009
• 发表时间: 2004
• 期刊: Anti-cancer drugs
• 影响因子: 2.3
• 作者: Appleyard,VirginiaCL;O'Neill,MaryA;Murray,KarenE;Bray,SusanE;Thomson,George;Kernohan,NeilM;Varani,James;Zhang,Jian;Thompson,AlastairM
• 通讯作者: Thompson,AlastairM