Antimycotic Ciclopirox Olamine in the Diabetic Environment Promotes Angiogenesis and Enhances Wound Healing

Diabetic wounds remain a major medical challenge with often disappointing outcomes despite the best available care. An impaired response to tissue hypoxia and insufficient angiogenesis are major factors responsible for poor healing in diabetic wounds. Here we show that the antimycotic drug ciclopirox olamine (CPX) can induce therapeutic angiogenesis in diabetic wounds. Treatment with CPX in vitro led to upregulation of multiple angiogenic genes and increased availability of HIF-1α. Using an excisional wound splinting model in diabetic mice, we showed that serial topical treatment with CPX enhanced wound healing compared to vehicle control treatment, with significantly accelerated wound closure, increased angiogenesis, and increased dermal cellularity. These findings offer a promising new topical pharmacologic therapy for the treatment of diabetic wounds

Mesenchymal stromal cells : a new tool against graft-versus-host disease ?

Mesenchymal stromal cells (MSCs) represent a heterogeneous subset of multipotent cells that can be isolated from several tissues including bone marrow and fat. MSCs exhibit immunomodulatory and anti-inflammatory properties that prompted their clinical use as prevention and/or treatment for severe graft-versus-host disease (GVHD). Although a number of phase I-II studies have suggested that MSCs infusion was safe and might be effective for preventing or treating acute GVHD, definitive proof for their efficacy remains lacking thus far. Multicenter randomized studies are ongoing to more precisely assess the impact of MSCs infusion on GVHD prevention/treatment, whereas further research is performed in vitro and in animal models with the aims of determining the best way to expand MSCs ex vivo as well as the most efficient dose and schedule of MSCs administration. After introducing GVHD, MSC biology, and results of MSCs infusion in animal models of allogeneic hematopoietic cell transplantation, this article reviews the results of the first clinical trials investigating the use of MSCs infusion as prevention or treatment of GVHD.Peer reviewe

Pre-Hospital Decision Process and Prognosis in Men and Women with Coronary Heart Disease

The overall aim of this thesis was to describe experiences, strategies and actions in the prehospital phase among patients with a first acute myocardial infarction and to examine long-term trends in survival among patients with coronary heart disease. The thesis consists of two qualitative and two quantitative studies. Interviews were conducted with 21 men and 17 women, experiencing symptoms from a first acute myocardial infarction (AMI) and analyzed with Grounded Theory. Two national prospective cohort studies were performed by using the Swedish Inpatient register (IPR). From this, prognosis for 37,276 adult patients 18 years who underwent a first coronary artery bypass (CABG) 1987-2006 could be estimated. During the decision process, various spectra of bodily changes were described in both men and women, sometimes over an extended period before submission to hospital. Intermittent, vague and insidious symptoms caused confusion about how to act. Vague symptoms sometimes experienced by the men did not match their preconception of typical symptoms in a myocardial infarction. To come to an understanding they compared with their past experiences which led to an awareness of the abnormality, the severity and the need for contact medical attention. The women usually attributed their symptoms to harmless conditions and struggled to continue with their responsibilities in their daily lives. Intensified symptoms made the women unable to perform their daily task and they could no longer maintain earlier explanations for their discomfort which contributed to an understanding for the need of professional help. Sometimes, when men and women sought medical attention for their discomfort, and had no objective signs of an AMI they were dismissed, with no diagnosis, which caused a hesitation to contact medical care once again. This emphasizes that health care professionals have to pay more attention to the patient’s narrative. In the quantitative part of the thesis younger men with a first AMI had a 2 to 4-fold risk for mortality compared to men in the same age in the general population while women had a 6 to 14-fold risk during the last study period (2002-2006). Survival increased during the study period in men. In women there was a favorable trend in survival until the last period 2002-2006 but survival then reverted to that in the second period (1992-1996) in the last period. Men and women ≥55 years surviving the first 30 days after CABG (coronary artery bypass grafting) showed a lower mortality risk than those in the general population and showed a decreasing trend in mortality during the study period. Women below the age of 55 showed no significant improvement in survival and had a 4-fold risk for mortality compared to women in the same age in the general population. Men <55 displayed improved survival, which was higher than that for men in the general population

Adipose-derived Stromal Cells Overexpressing Vascular Endothelial Growth Factor Accelerate Mouse Excisional Wound Healing

Angiogenesis is essential to wound repair, and vascular endothelial growth factor (VEGF) is a potent factor to stimulate angiogenesis. Here, we examine the potential of VEGF-overexpressing adipose-derived stromal cells (ASCs) for accelerating wound healing using nonviral, biodegradable polymeric vectors. Mouse ASCs were transfected with DNA plasmid encoding VEGF or green fluorescent protein (GFP) using biodegradable poly (β-amino) esters (PBAE). Cells transfected using Lipofectamine 2000, a commercially available transfection reagent, were included as controls. ASCs transfected using PBAEs showed enhanced transfection efficiency and 12–15-fold higher VEGF production compared with cells transfected using Lipofectamine 2000 (*P < 0.05). When transplanted into a mouse wild-type excisional wound model, VEGF-overexpressing ASCs led to significantly accelerated wound healing, with full wound closure observed at 8 days compared to 10–12 days in groups treated with ASCs alone or saline control (*P < 0.05). Histology and polarized microscopy showed increased collagen deposition and more mature collagen fibers in the dermis of wound beds treated using PBAE/VEGF-modified ASCs than ASCs alone. Our results demonstrate the efficacy of using nonviral-engineered ASCs to accelerate wound healing, which may provide an alternative therapy for treating many diseases in which wound healing is impaired.ISSN:1525-0016ISSN:1525-002