TOPICAL RETINOIDS FOR DIABETIC FOOT ULCERS
局部用维A酸治疗糖尿病足溃疡
基本信息
- 批准号:6635342
- 负责人:
- 金额:$ 34.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 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
项目摘要
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
期刊论文数量(13)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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:
- 影响因子:0
- 作者:Varani J
- 通讯作者: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:
- 影响因子:0
- 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:
- 影响因子:3.6
- 作者:J. Varani;E. Kelley;P. Perone;Huma Lateef
- 通讯作者: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:
- 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
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JAMES VARANI其他文献
JAMES VARANI的其他文献
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