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Baltzis D.,Joslin Beth Israel Deaconess Foot Center and Microcirculation Laboratory | Eleftheriadou I.,Joslin Beth Israel Deaconess Foot Center and Microcirculation Laboratory | Veves A.,Beth Israel Deaconess Medical Center
Advances in Therapy | Year: 2014

Diabetic foot ulcers (DFUs) are one of the most common and serious complications of diabetes mellitus, as wound healing is impaired in the diabetic foot. Wound healing is a dynamic and complex biological process that can be divided into four partly overlapping phases: hemostasis, inflammation, proliferative and remodeling. These phases involve a large number of cell types, extracellular components, growth factors and cytokines. Diabetes mellitus causes impaired wound healing by affecting one or more biological mechanisms of these processes. Most often, it is triggered by hyperglycemia, chronic inflammation, micro- and macro-circulatory dysfunction, hypoxia, autonomic and sensory neuropathy, and impaired neuropeptide signaling. Research focused on thoroughly understanding these mechanisms would allow for specifically targeted treatment of diabetic foot ulcers. The main principles for DFU treatment are wound debridement, pressure off-loading, revascularization and infection management. New treatment options such as bioengineered skin substitutes, extracellular matrix proteins, growth factors, and negative pressure wound therapy, have emerged as adjunctive therapies for ulcers. Future treatment strategies include stem cell-based therapies, delivery of gene encoding growth factors, application of angiotensin receptors analogs and neuropeptides like substance P, as well as inhibition of inflammatory cytokines. This review provides an outlook of the pathophysiology in diabetic wound healing and summarizes the established and adjunctive treatment strategies, as well as the future therapeutic options for the treatment of DFUs. © 2014, Springer Healthcare. Source


Dushay J.R.,Beth Israel Deaconess Medical Center | Tecilazich F.,Joslin Beth Israel Deaconess Foot Center and Microcirculation Laboratory | Kafanas A.,Joslin Beth Israel Deaconess Foot Center and Microcirculation Laboratory | Magargee M.L.,Joslin Beth Israel Deaconess Foot Center and Microcirculation Laboratory | And 4 more authors.
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System | Year: 2015

Objective: The objective of this paper is to study the effect of aliskiren on metabolic parameters and micro- and macrovascular reactivity in individuals diagnosed with or at high risk for developing type 2 diabetes mellitus (T2DM). Research design and methods: We studied 47 T2DM and 41 at-risk individuals in a randomized, double-blinded, placebocontrolled trial. All subjects were treated with 150 mg aliskiren or placebo daily for 12 weeks. Twenty-six (55%) of T2DM and four (8%) at-risk subjects were also treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers. Results: Aliskiren treatment was associated with improvement in systolic and diastolic blood pressure and endotheliumindependent vasodilation at the skin microcirculation in those with T2DM but not in those at risk. There were no incidences of hypotension and no significant changes in serum potassium or creatinine levels with aliskiren treatment in either study group. Conclusions: Aliskiren improves blood pressure and vascular smooth muscle function in the skin microcirculation of T2DM patients. © 2015 The Author(s). Source

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