Oxidative stress induces in endothelial cells a quick and transient coactivation of both stress-activated protein kinase-2/p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases. We found that inhibiting the ERK pathway resulted, within 5 min of oxidative stress, in a misassembly of focal adhesions characterized by mislocalization of key proteins such as paxillin. The focal adhesion misassembly that followed ERK inhibition with the mitogen-activated protein kinase kinase (MEK) inhibitor PD098059 (2'-amino-3'-methoxyflavone) or with a kinase negative mutant of ERK in the presence of H(2)O(2) resulted in a quick and intense membrane blebbing that was associated with important damage to the endothelium. We isolated by two-dimensional gel electrophoresis a PD098059-sensitive phosphoprotein of 38 kDa that we identified, by mass spectrometry, as tropomyosin-1. In fact, H(2)O(2) induced a time-dependent phosphorylation of tropomyosin that was sensitive to inhibition by PD098059 and UO126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butanediane). Tropomyosin phosphorylation was also induced by expression of a constitutively activated form of MEK1 (MEK(CA)), which confirms that its phosphorylation resulted from the activation of ERK. In unstimulated cells, tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation of ERK by H(2)O(2) or by expression of MEK(CA). We propose that phosphorylation of tropomyosin-1 downstream of ERK by contributing to formation of actin filaments increases cellular contractility and promotes the formation of focal adhesions. Incidentally, ML-7 (1-[5iodonaphthalene-1-sulfonyl]homopiperazine, HCl), an inhibitor of cell contractility, inhibited phosphorylation of tropomyosin and blocked the formation of stress fibers and focal adhesions, which also led to membrane blebbing in the presence of oxidative stress. Our finding that tropomyosin-1 is phosphorylated downstream of ERK, an event that modulates its interaction with actin, may lead to further understanding of the role of this protein in regulating cellular functions associated with cytoskeletal remodeling.
The results of this study reinforce postoperative radiotherapy as effective management for keloids. Specifically, brachytherapy was the most effective of the currently used radiation modalities.
Background: Several surgical techniques exist for treatment of cubital tunnel syndrome. Endoscopic cubital tunnel release (ECTuR) has been recently reported as a promising minimally invasive technique. This study aims to compare outcomes and complications of open cubital tunnel release (OCTuR) and ECTuR in the treatment of idiopathic cubital tunnel syndrome. Methods: A systematic review of the literature identified 118 citations. Studies including adults with idiopathic cubital tunnel treated exclusively by ECTuR or OCTuR were included. Outcomes of interest were postoperative grading, complications, number of reoperations, and the need for intraoperative conversion to another technique. Postoperative outcomes were combined into a uniform scale with 4 categories: "excellent," "good," "fair," and "poor." Results: Twenty studies met the inclusion criteria (17 observational and 3 comparative), representing 425 open and 556 endoscopic decompressions. In the open group, 79.8% experienced "good" or "excellent" results with 12% complication rate and 2.8% reoperation rate. In the endoscopic group, 81.8% experienced "good" or "excellent" results with 9% complication rate and 1.6% reoperation rate. Meta-analysis of 3 comparative studies demonstrated a significantly lower overall complication rate with ECTuR. Subgroup analysis of complications revealed a significantly higher incidence of scar tenderness and elbow pain with OCTuR. Conclusions: The current study demonstrates similar effectiveness between the endoscopic (ECTuR) and open (OCTuR) techniques for treatment of idiopathic cubital tunnel syndrome with similar outcomes, complication profiles, and reoperation rates.
Background Dupuytren's disease is described as a thickening of the palmar fascia. It typically affects men of Northern European descent in their fifties. The disease process starts as a nodule at the distal palmar crease that progressively gives rise to a cord invading distally toward the finger. Historically, different treatments have been described. Our purpose was to perform a meta-analysis of the evidence published on the percutaneous fasciotomy (PCF) treatment. Methods We searched Medline, PubMed, and the Cochrane Library for articles evalu ating the use of PCF for Dupuytren's disease. No study was excluded based on quality. Results The search yielded nine studies. Because of their different methodologies, a meta-analysis could not be performed. However, we were able to extract common qualitative conclusions. PCF is an effective treatment modality for patients in whom general anesthesia is contraindicated, with a good outcome especially at the metacarpophalangeal joint, a low recurrence rate in the short term, and few complications. Conclusions Similar conclusions were reached by all the articles under study. Nevertheless, there remains the need for a prospective study with a higher statistical power and standardized clinical evaluation and surgical methods in order to achieve more objective quantitative results. It would also be pertinent to compare the outcomes and complication rates of PCF with the new collagenase treatment.
Background Open dorsal metacarpophalangeal joint dislocations are rare. We report the case of a 62-year-old man who fell from a height of 10 m onto his left outstretched hand and presented to us with four open dorsal metacarpophalangeal joint dislocations. We review the literature and present our case to elucidate the best treatment protocol for open dorsal metacarpophalangeal joint dislocations. Methods A systematic review was conducted using MEDLINE, Embase, and PubMed from 1946 to present. Publications were found using key terms and crossreferencing. Detail on patient demographic, presentation, mechanism of injury, injury management, and outcome were collected. Results A total of 102 articles of metacarpophalangeal joint dislocation (excluding thumb dislocations) were identified. Of these, only four were of open dorsal metacarpophalangeal joint dislocation involving the four long fingers. Open dislocation of the metacarpophalangeal joint in these studies showed no hand predominance, nor association with hand dominance. Conclusion Open dorsal metacarpophalangeal joint dislocations of the four long fingers are unusual. Based on the available case reports and our experience, we suggest addressing this injury intraoperatively with minimal delay. Most cases will be associated with volar plate injury, and we encourage its repair with figure-of-eight stitches. Postoperatively, we suggest a dorsal blocking splint for 2 weeks followed by occupational therapy consisting of passive and active range of motion (ROM) exercises and adjunctive therapies to control edema and optimize scar tissue. Inadequate management of such injuries could be highly detrimental to hand function.
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