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      Neutrophil Elastase Inhibitor Increases Flap Survival in Experimental Degloving Injuries

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          Abstract

          Objectives:

          Degloving hand injuries have generally been viewed as among the most difficult of injuries to manage due to the extensive nature of associated damage. The traditional approach to the circumferentially degloved segment of problematic flap viability has been to resuture the flap and to wait and see. However, the waiting period or the specific hemorheological protocol remains uncertain. This study aims to acknowledge if Sivelestat, known to ameliorate ischemia-reperfusion injury, enhances the survival of avulsed flaps in a hind limb degloving model of rats and to compare Sivelestat’s effects to Pentoxifylline.

          Methods:

          In this study, total flap area (cm 2), area of necrosis in the flap (cm 2), and the ratio between the necrotic and total areas (percentage) were determined. Angiogenesis among the groups was documented with CD31, anti-PECAM staining. TUNEL assay was performed to allow the visualization of cell nuclei containing fragmented DNA, a typical feature of apoptosis.

          Results:

          The findings obtained in this study showed that Sivelestat administered at 10 mg/kg/hour dosage will inhibit the ischemia-reperfusion injury more pertinently than Pentoxifylline, which exerts only hemorheological effects.

          Conclusion:

          The anti-inflammatory effects of Sivelestat will be beneficial for decreasing the early complications of degloving injury, such as inflammation, sepsis, and edema, better than Pentoxifylline, which exerts only hemorheological effects.

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          Most cited references27

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          Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity.

          The promotion of post-ischaemic motor recovery remains a major challenge in clinical neurology. Recently, plasticity-promoting effects have been described for the growth factor erythropoietin in animal models of neurodegenerative diseases. To elucidate erythropoietin's effects in the post-acute ischaemic brain, we examined how this growth factor influences functional neurological recovery, perilesional tissue remodelling and axonal sprouting of the corticorubral and corticobulbar tracts, when administered intra-cerebroventricularly starting 3 days after 30 min of middle cerebral artery occlusion. Erythropoietin administered at 10 IU/day (but not at 1 IU/day), increased grip strength of the contralesional paretic forelimb and improved motor coordination without influencing spontaneous locomotor activity and exploration behaviour. Neurological recovery by erythropoietin was associated with structural remodelling of ischaemic brain tissue, reflected by enhanced neuronal survival, increased angiogenesis and decreased reactive astrogliosis that resulted in reduced scar formation. Enhanced axonal sprouting from the ipsilesional pyramidal tract into the brainstem was observed in vehicle-treated ischaemic compared with non-ischaemic animals, as shown by injection of dextran amines into both motor cortices. Despite successful remodelling of the perilesional tissue, erythropoietin enhanced axonal sprouting of the contralesional, but not ipsilesional pyramidal tract at the level of the red and facial nuclei. Moreover, molecular biological and histochemical studies revealed broad anti-inflammatory effects of erythropoietin in both hemispheres together with expression changes of plasticity-related molecules that facilitated contralesional axonal growth. Our study establishes a plasticity-promoting effect of erythropoietin after stroke, indicating that erythropoietin acts via recruitment of contralesional rather than of ipsilesional pyramidal tract projections.
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            Hyperbaric oxygen attenuates apoptosis and decreases inflammation in an ischemic wound model.

            The molecular mechanisms whereby hyperbaric oxygen (HBO) improves ischemic wound healing remain elusive. In this study, a rat model of wound ischemia was used to test the hypothesis that HBO enhances wound healing by modulating hypoxia-inducible factor-1alpha (HIF-1alpha) signaling. Male Sprague-Dawley rats underwent creation of a previously validated ischemic flap. Three groups underwent daily treatment: HBO (90 minutes, 2.4 atm); systemic administration of the free radical scavenger, N-acetylcysteine (NAC 150 mg kg(-1) intraperitoneal); control (neither HBO nor NAC). HBO treatment improved healing of the ischemic wounds. Analysis of ischemic wound tissue extracts demonstrated significantly reduced expression of HIF-1alpha, p53, and BNip3. Additionally, HBO increased expression of Bcl-2 while decreasing cleaved caspase-3. DNA fragmentation was abolished and the number of TUNEL-positive cells was reduced compared to the other groups. Vascular endothelial growth factor, cyclooxygenase-2, and neutrophil infiltration were reduced in ischemic wounds treated with HBO. These results indicate that HBO improves ischemic wound healing by downregulation of HIF-1alpha and subsequent target gene expression with attenuation of cell apoptosis and reduction of inflammation.
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              Classification of soft-tissue degloving in limb trauma.

              Compressive, tortional and abrasive deforming forces are translated to the limbs during high energy trauma. The long bones may be fractured in many patterns with a varying extent of fragmentation and comminution but the soft-tissues appear to absorb the forces in a predictable way. We retrospectively reviewed a series of 79 complex limb injuries treated in a dedicated centre where the clinical notes and photo-documentation were meticulously kept and where the outcomes were known. The soft-tissue injuries were then described and revealed four patterns of injury: abrasion/avulsion, non-circumferential degloving, circumferential single plane and circumferential multi-plane degloving. These patterns occurred either in isolation or occasionally in combination. Resuturing of degloved skin was only successful in non-circumferential (pattern 2) cases. Radical excision of devitalised tissue followed by soft-tissue reconstruction in a single procedure was successful in all patterns apart from pattern 4 (circumferential multi-plane degloving). In pattern 4 we recommend serial wound excision prior to reconstruction. Copyright © 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Sisli Etfal Hastan Tip Bul
                Sisli Etfal Hastan Tip Bul
                The Medical Bulletin of Sisli Etfal Hospital
                Kare Publishing (Turkey )
                1302-7123
                1308-5123
                2020
                25 July 2018
                : 54
                : 2
                : 169-175
                Affiliations
                [1 ]Department of Plastic Reconstructive and Aesthetic Surgery, Kirikkale Yuksek Ihtisas Hospital, Kirikkale, Turkey
                [2 ]Department of Plastic Reconstructive and Aesthetic Surgery, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
                [3 ]MVK Aesthetic Clinic, Istanbul, Turkey
                [4 ]Department of Plastic Reconstructive and Aesthetic Surgery, Bezmialem Foundation University, Istanbul, Turkey
                [5 ]Department of Plastic Reconstructive and Aesthetic Surgery, Trakya University Faculty of Medicine, Edirne, Turkey
                Author notes
                Address for correspondence: Erkan Yuce, MD. Kirikkale Yuksek Ihtisas Hastanesi, Plastik Rekonstruktif ve Estetik Cerrahi Klinigi, Kirikkale, Turkey Phone: +90 530 285 02 30 E-mail: drerkanyuce@ 123456gmail.com
                Article
                MBSEH-54-169
                10.14744/SEMB.2018.45077
                7326670
                32617053
                5ee3dabb-1729-4ed6-a027-6b467f86ee96
                Copyright: © 2020 by The Medical Bulletin of Sisli Etfal Hospital

                This is an open access article under the CC BY-NC license ( http://creativecommons.org/licenses/by-nc/4.0/).

                History
                : 19 July 2018
                : 24 July 2018
                Categories
                Original Research

                degloving injury,neutrophil elastase inhibitor,ischemia reperfusion injury

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