Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse.

Healing of diabetic wounds still remains a critical medical problem. Polydeoxyribonucleotide (PDRN), a compound having a mixture of deoxyribonucleotide polymers, stimulates the A2 purinergic receptor with no toxic or adverse effect. We studied the effects of PDRN in diabetes-related healing defect using an incisional skin-wound model produced on the back of female diabetic mice (db+/db+) and their normal littermates (db+/+m).

Simvastatin enhances VEGF production and ameliorates impaired wound healing in experimental diabetes.

Statins have different effects beyond cholesterol reduction and stimulate angiogenesis. We investigated the effect of simvastatin in diabetes-related healing defects. An incisional skin wound model produced on the back of female diabetic mice (db(+)/db(+)) and their normoglycemic littermates (db(+)/(+)m) was used.

Functional mitochondria are required for alpha-synuclein toxicity in aging yeast.

alpha-Synuclein is one of the principal toxic triggers of Parkinson disease, an age-associated neurodegeneration. Using old yeast as a model of alpha-synuclein expression in post-mitotic cells, we show that alpha-synuclein toxicity depends on chronological aging and results in apoptosis as well as necrosis. Neither disruption of key components of the unfolded protein response nor deletion of proapoptotic key players (including the yeast caspase YCA1, the apoptosis-inducing factor AIF1, or the serine protease OMI) did prevent alpha-synuclein-induced cell killing.

Angiopoietin-1 gene transfer improves impaired wound healing in genetically diabetic mice without increasing VEGF expression.

Ang-1 (angiopoietin-1) improves the ineffective angiogenesis and impaired wound healing in diabetes; however, the mechanism underlying this positive effect is still far from being completely understood. In the present study, we investigated whether rAAV (recombinant adeno-associated virus)-Ang-1 gene transfer could improve wound repair in genetically diabetic mice (db+/db+) and the mechanism(s) by which it causes new vessel formation. An incisional skin-wound model in diabetic and normoglycaemic mice was used.

Pharmacokinetics of mycophenolate sodium and comparison with the mofetil formulation in stable kidney transplant recipients.

Background And Objectives: The introduction of mycophenolate mofetil has improved graft survival after organ transplantation; however, its use may be limited by important adverse effects. For overcoming these problems, an enteric-coated formulation of mycophenolate sodium has been developed, but pharmacokinetic data of mycophenolic acid release from this formulation are scanty.

Design, Setting, Participants, & Measurements: Pharmacokinetic studies in 32 kidney transplant recipients who were given the enteric-coated formulation of mycophenolate sodium (n = 12) or mycophenolate mofetil (n = 20) were performed.

Microsurgical arterovenous loops and biological templates: a novel in vivo chamber for tissue engineering.

Background: Microsurgical tissue engineering is an emerging topic in regenerative medicine. Here we describe a new microsurgical model of bioengineering in rats based on the use of an arterovenous loop (AV) implanted into a commercially available crosslinked collagen/glycosaminoglycan template.

Methods: The microvascular loop was created between the femoral artery and vein and covered by the template folded onto itself.

Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a two-year randomized, double-blind, placebo-controlled study.

Context: Genistein, a soy isoflavone, has received wide attention over the last few years because of its potential preventive role for cardiovascular disease.

Objective: Our objective was to assess the effects of genistein administration (54 mg/d) on some predictors of cardiovascular risk in osteopenic, postmenopausal women.

Design And Setting: We conducted a randomized, double-blind, placebo-controlled trial at three Italian university medical centers.

Involvement of mitogen-activated protein kinases (MAPKs) during testicular ischemia-reperfusion injury in nuclear factor-kappaB knock-out mice.

Nuclear factor kappa-B (NF-kappaB), extracellular regulated kinase (ERK 1/2) and c-jun-N terminal kinase (JNK) play an important role in testicular ischemia. We investigated the patterns of ERK1/2, JNK and p38 activation in NF-kappaB knockout (KO) mice subjected to testicular torsion. KO and normal littermate wild-type (WT) animals underwent at 1 h testicular ischemia followed by 24 h reperfusion (TI/R).

Neuroprotection in focal cerebral ischemia owing to delayed treatment with melanocortins.

In gerbils subjected to transient global cerebral ischemia, melanocortin peptides produce long-lasting protection with a broad time window, and through the activation of central nervous system melanocortin MC(4) receptors. Here we aimed to investigate whether melanocortins are neuroprotective also in a rat model of focal cerebral ischemia induced by intrastriatal microinjection of endothelin-1. The vasoconstrictor agent endothelin-1 caused a significant impairment in spatial learning and memory, as well as in sensory-motor orientation and limb use, associated with severe striatal morphological damage including intense neuronal death and an almost complete myelin degradation.

Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial.

Background: Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive.

Objective: To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women.

Design: Randomized, double-blind, placebo-controlled trial.

VEGF overexpression via adeno-associated virus gene transfer promotes skeletal muscle regeneration and enhances muscle function in mdx mice.

Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis. Recently it was reported that the delivery of VEGF using recombinant adeno-associated virus (rAAV) vectors reduces muscle damage and promotes muscle regeneration in different experimental models of muscle necrosis. We demonstrate that intramuscular administration of rAAV-VEGF improved pathophysiology of the mdx mouse, a model of Duchenne muscular dystrophy (DMD).

Raxofelast, (+/-)5-(acetyloxy)-2,3-dihydro-4,6,7-trimethyl-2-benzofuranacetic acid: a new antioxidant to modulate the inflammatory response during ischemia-reperfusion injury and impaired wound healing.

Raxofelast, also named IRFI 016 or (+/-)5-(acetyloxy)-2,3-dihydro-4,6,7-trimethyl-2-benzofuranacetic acid, belongs to a family of novel molecules designed with the aim to maximize antioxidant potency of phenols related to Vitamin E (alpha-tocopherol). This review will focus on the antioxidant and radical scavenging activity of this new promising compound.

Say what? Who? Me? Right here in the trenches? Collaborate on what?--Seeking common ground in regional all-hazards preparedness training.

Heroic responses to the events surrounding September 11, 2001, and Hurricane Katrina in 2005, as well as to other catastrophes, underscore the need for genuine collaboration within communities and among environmental health professionals, public health agencies, first responders from various professions, and other organizations. Because of competing organizational agendas, however, interdisciplinary training is needed to help ensure that communities and various first responders will operate in tandem. This article suggests types of responders who might benefit from such training, lists selected courses from a new curriculum, and shares lessons learned during the development of a regional all-hazards preparedness training program.

Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study.

Objective: To evaluate in a 12-month, prospective, randomized, double-blind, placebo-controlled study whether pure administration of the phytoestrogen genistein (54 mg/d) might reduce the number and severity of hot flushes in postmenopausal women with no adverse effect on the endometrium.

Design: A total of 389 participants met the main study criteria and were randomly assigned to receive the phytoestrogen genistein (n=198) or placebo (n=191). About 40% of participants in both groups did not suffer from hot flushes, and the evaluation was performed in a subgroup of 247 participants (genistein, n=125; placebo, n=122).

The disaccharide trehalose inhibits proinflammatory phenotype activation in macrophages and prevents mortality in experimental septic shock.

Proinflammatory phenotype activation in macrophages (MPhis) after sepsis orchestrates an inflammatory response leading to multiple organ dysfunction. Trehalose preserves cell viability during exposure to a range of environmental stresses. We investigated whether trehalose may inhibit endotoxin-induced activation of the inflammatory phenotype in MPhis.

Lipid peroxidation activates mitogen-activated protein kinases in testicular ischemia-reperfusion injury.

Purpose: Testicular damage after torsion has been attributed to many mechanisms, of which one is lipid peroxidation of the plasma membrane, which could cause the activation of the mitogen-activated protein kinase family. These proteins are of vital importance for signal transduction pathways and 2 of them, extracellular signal-regulated kinase and c-jun N-terminal kinase, participate in the pathogenesis of testicular ischemia. We investigated whether lipid peroxidation may trigger mitogen-activated protein kinase activation in testicular ischemia-reperfusion.

Activation of the cholinergic anti-inflammatory pathway reduces NF-kappab activation, blunts TNF-alpha production, and protects againts splanchic artery occlusion shock.

The cholinergic anti-inflammatory pathway has not yet been studied in splanchnic artery occlusion (SAO) shock. We investigated whether electrical stimulation (STIM) of efferent vagus nerves suppresses the inflammatory cascade in SAO shock. Animals were subjected to clamping of the splanchnic arteries for 45 min, followed by reperfusion.

Broad therapeutic treatment window of [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone for long-lasting protection against ischemic stroke, in Mongolian gerbils.

Melanocortin peptides have been shown to produce neuroprotection in experimental ischemic stroke. The aim of the present investigation was to identify the therapeutic treatment window of melanocortins, and to determine whether these neuropeptides chronically protect against damage consequent to brain ischemia. A 10-min period of global cerebral ischemia in gerbils, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory (Morris test: four sessions from 4 to 67 days after the ischemic episode), associated with neuronal death in the hippocampus.

Tissue factor expression and activity are not increased in peripheral monocytes isolated from uncomplicated hypertensive patients.

Background: Systemic hypertension is one of the main risk factors for atherothrombosis. Tissue factor (TF) is found in the adventitia of blood vessels and in the lipid core of atherosclerotic plaques, and is specifically expressed on monocyte or macrophage cell membrane surfaces. TF plays a pivotal role in blood clotting physiology and is involved in pro-inflammatory action and atherosclerotic plaque destabilization.

Lipid peroxidation inhibition blunts nuclear factor-kappaB activation, reduces skeletal muscle degeneration, and enhances muscle function in mdx mice.

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease resulting from lack of the sarcolemmal protein dystrophin. However, the mechanism leading to the final disease status is not fully understood. Several lines of evidence suggest a role for nuclear factor (NF)-kappaB in muscle degeneration as well as regeneration in DMD patients and mdx mice.

Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds.

Objective: Erythropoietin interacts with vascular endothelial growth factor (VEGF) and stimulates endothelial cell mitosis and motility; thus it may be of importance in the complex phenomenon of wound healing. The purpose of this study was to investigate the effect of recombinant human erythropoietin (rHuEPO) on experimental burn wounds.

Design: Randomized experiment.

Nuclear factor kappa-B blockade reduces skeletal muscle degeneration and enhances muscle function in Mdx mice.

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease due to a mutation in the dystrophin gene and the consequential protein deficiency in muscle. How the lack of the sarcolemmal protein dystrophin gives rise to the final disease status is still not clear. Several evidences suggest a role of nuclear factor kappa-B (NF-kappaB), a pleiotropic transcription factor, in muscle degeneration and regeneration in DMD patients and mdx mice.

Transforming a Master of Public Health program to address public health practice needs.

The future of the constantly changing public health profession is tied to the development of practice skills through competency-based training. In this article, we describe a program change in the Master of Public Health program at East Stroudsburg University in northeastern Pennsylvania. The first goal of the program transition was to ensure that all program elements included the relevant vision, values, mission, goals, and objectives.

Activation of an efferent cholinergic pathway produces strong protection against myocardial ischemia/reperfusion injury in rats.

Objective: A vagus nerve-mediated, brain cholinergic protective mechanism activated by melanocortin peptides is operative in conditions of circulatory shock; moreover, there is anatomical evidence of dual vagal-cardiac efferent pathways in rats, which could play different roles in controlling heart function. Therefore, we investigated the role and functional mechanism of such vagal efferent pathway(s) in an experimental model of ischemic heart disease.

Design: Randomized experimental study.