Showing papers by "Gayle M. Gordillo published in 2010"

Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice.

Abstract: Background Chronic inflammation is a characteristic feature of diabetic cutaneous wounds. We sought to delineate novel mechanisms involved in the impairment of resolution of inflammation in diabetic cutaneous wounds. At the wound-site, efficient dead cell clearance (efferocytosis) is a pre-requisite for the timely resolution of inflammation and successful healing. Methodology/Principal Findings Macrophages isolated from wounds of diabetic mice showed significant impairment in efferocytosis. Impaired efferocytosis was associated with significantly higher burden of apoptotic cells in wound tissue as well as higher expression of pro-inflammatory and lower expression of anti-inflammatory cytokines. Observations related to apoptotic cell load at the wound site in mice were validated in the wound tissue of diabetic and non-diabetic patients. Forced Fas ligand driven elevation of apoptotic cell burden at the wound site augmented pro-inflammatory and attenuated anti-inflammatory cytokine response. Furthermore, successful efferocytosis switched wound macrophages from pro-inflammatory to an anti-inflammatory mode. Conclusions/Significance Taken together, this study presents first evidence demonstrating that diabetic wounds suffer from dysfunctional macrophage efferocytosis resulting in increased apoptotic cell burden at the wound site. This burden, in turn, prolongs the inflammatory phase and complicates wound healing.

Nox-4-dependent nuclear H2O2 drives DNA oxidation resulting in 8-OHdG as urinary biomarker and hemangioendothelioma formation.

Abstract: Hemangioendotheliomas are classified as endothelial cell tumors, which are the most common soft tissue tumors in infants. In a murine model of hemangioendothelioma, we previously showed th...

Prevalence of obstructive sleep apnea in patients with chronic wounds.

Abstract: Chronic non-healing wounds are a major health problem with steadily increasing importance.1 The prevalence of chronic leg ulcers is 3%–5% in the population over 65 years of age, with an increase of up to 12% in the population over 70 years of age.2 The most prevalent forms of chronic wounds are leg ulcers caused by chronic venous insufficiency(CVI)3–6 accounting for 70%-90% of ulcers found on the lower leg,7 followed by diabetic foot ulcers.8 Despite significant advances in knowledge, management of chronic wounds continues to involve frequent visits to wound centers and repeated interventions imposing significant burden on patients and society.3,9,10 Chronic wound ulcers are commonly associated with delayed healing requiring an average of 4-6 months, with a substantial number of patients failing to heal.11,12 The burden of chronic wounds is expected to be increasing in coming years with the increased aging and obesity of the population.2 Obstructive sleep apnea (OSA) is a disorder of intermittent hypoxia13–18 and severe vascular complications including hypertension, coronary disease, and stroke.19,22 OSA is present in 5%-10% of the middle-aged population and probably increasing in incidence due to the increasing obesity and age of the population.23 These are also the risk factors of chronic non-healing wounds.2 Therefore, it is very likely that patients with chronic wounds would have higher prevalence of OSA than the general population. We endeavored to characterize the risk factors for OSA in patients of academic wound center and to determine the actual prevalence of OSA in this population. BRIEF SUMMARY Current Knowledge/Study Rationale: Patients with non-healing wounds have high prevalence of cardiovascular disease and significant rate of healing failure. The prevalence of obstructive sleep apnea is unknown in this population. Study Impact: The study identifies a new population with very high pre-test probability for obstructive sleep apnea. Wound healing in this population may stand to benefit from expedited surveillance and treatment strategies for OSA.

Dual-mode Imaging of Cutaneous Tissue Oxygenation and Vascular Function

Abstract: Accurate assessment of cutaneous tissue oxygenation and vascular function is important for appropriate detection, staging, and treatment of many health disorders such as chronic wounds. We report the development of a dual-mode imaging system for non-invasive and non-contact imaging of cutaneous tissue oxygenation and vascular function. The imaging system integrated an infrared camera, a CCD camera, a liquid crystal tunable filter and a high intensity fiber light source. A Labview interface was programmed for equipment control, synchronization, image acquisition, processing, and visualization. Multispectral images captured by the CCD camera were used to reconstruct the tissue oxygenation map. Dynamic thermographic images captured by the infrared camera were used to reconstruct the vascular function map. Cutaneous tissue oxygenation and vascular function images were co-registered through fiduciary markers. The performance characteristics of the dual-mode image system were tested in humans.