Short term supplementation of dietary antioxidants selectively regulates the inflammatory responses during early cutaneous wound healing in diabetic mice

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Park Na-Young

2011-11-01

Full Text Available Abstract Background Diabetic foot ulcers are serious complications for diabetic patients, yet the precise mechanism that underlines the treatment of these diabetic complications remains unclear. We hypothesized that dietary antioxidant supplementation with vitamin C, combined either with vitamin E or with vitamin E and NAC, improves delayed wound healing through modulation of blood glucose levels, oxidative stress, and inflammatory response. Methods Diabetes was induced by administration of alloxan monohydrate. Mice were divided into 4 groups; CON (non-diabetic control mice fed AIN 93 G purified rodent diet, DM (diabetic mice fed AIN 93 G purified rodent diet, VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet, and Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E, and 2.5% NAC supplemented diet. After 10 days of dietary antioxidant supplementation, cutaneous full-thickness excisional wounds were performed, and the rate of wound closure was examined. TBARS as lipid peroxidation products and vitamin E levels were measured in the liver. Expression levels of oxidative stress and inflammatory response related proteins were measured in the cutaneous wound site. Results Dietary antioxidant supplementation improved blood glucose levels and wound closure rate and increased liver vitamin E, but not liver TBARS levels in the diabetic mice as compared to those of the CON. In addition, dietary antioxidant supplementation modulated the expression levels of pIκBα, HO-1, CuZnSOD, iNOS and COX-2 proteins in the diabetic mice. Conclusions These findings demonstrated that delayed wound healing is associated with an inflammatory response induced by hyperglycaemia, and suggests that dietary antioxidant supplementation may have beneficial effects on wound healing through selective modulation of blood glucose levels, oxidative stress, and inflammatory response.

Efficient Healing Takes Some Nerve: Electrical Stimulation Enhances Innervation in Cutaneous Human Wounds.

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Emmerson, Elaine

2017-03-01

Cutaneous nerves extend throughout the dermis and epidermis and control both the functional and reparative capacity of the skin. Denervation of the skin impairs cutaneous healing, presenting evidence that nerves provide cues essential for timely wound repair. Sebastian et al. demonstrate that electrical stimulation promotes reinnervation and neural differentiation in human acute wounds, thus accelerating wound repair. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Clinically relevant doses of lidocaine and bupivacaine do not impair cutaneous wound healing in mice.

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Waite, A; Gilliver, S C; Masterson, G R; Hardman, M J; Ashcroft, G S

2010-06-01

Lidocaine and bupivacaine are commonly infiltrated into surgical cutaneous wounds to provide local anaesthesia after surgical procedures. However, very little is known about their effects on cutaneous wound healing. If an inhibitory effect is demonstrated, then the balance between the benefits of postoperative local anaesthesia and the negatives of impaired cutaneous wound healing may affect the decision to use local anaesthesia or not. Furthermore, if a difference in the rate of healing of lidocaine- and bupivacaine-treated cutaneous wounds is revealed, or if an inhibitory effect is found to be dose-dependent, then this may well influence the choice of agent and its concentration for clinical use. Immediately before incisional wounding, we administered lidocaine and bupivacaine intradermally to adult female mice, some of which had been ovariectomized to act as a model of post-menopausal women (like post-menopausal women, ovariectomized mice heal wounds poorly, with increased proteolysis and inflammation). Day 3 wound tissue was analysed histologically and tested for expression of inflammatory and proteolytic factors. On day 3 post-wounding, wound areas and extent of re-epithelialization were comparable between the control and local anaesthetic-treated animals, in both intact and ovariectomized groups. Both tested drugs significantly increased wound activity of the degradative enzyme matrix metalloproteinase-2 relative to controls, while lidocaine also increased wound neutrophil numbers. Although lidocaine and bupivacaine influenced local inflammatory and proteolytic factors, they did not impair the rate of healing in either of two well-established models (mimicking normal human wound healing and impaired age-related healing).

Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro.

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Bussche, Leen; Harman, Rebecca M; Syracuse, Bethany A; Plante, Eric L; Lu, Yen-Chun; Curtis, Theresa M; Ma, Minglin; Van de Walle, Gerlinde R

2015-04-11

The prevalence of impaired cutaneous wound healing is high and treatment is difficult and often ineffective, leading to negative social and economic impacts for our society. Innovative treatments to improve cutaneous wound healing by promoting complete tissue regeneration are therefore urgently needed. Mesenchymal stromal cells (MSCs) have been reported to provide paracrine signals that promote wound healing, but (i) how they exert their effects on target cells is unclear and (ii) a suitable delivery system to supply these MSC-derived secreted factors in a controlled and safe way is unavailable. The present study was designed to provide answers to these questions by using the horse as a translational model. Specifically, we aimed to (i) evaluate the in vitro effects of equine MSC-derived conditioned medium (CM), containing all factors secreted by MSCs, on equine dermal fibroblasts, a cell type critical for successful wound healing, and (ii) explore the potential of microencapsulated equine MSCs to deliver CM to wounded cells in vitro. MSCs were isolated from the peripheral blood of healthy horses. Equine dermal fibroblasts from the NBL-6 (horse dermal fibroblast cell) line were wounded in vitro, and cell migration and expression levels of genes involved in wound healing were evaluated after treatment with MSC-CM or NBL-6-CM. These assays were repeated by using the CM collected from MSCs encapsulated in core-shell hydrogel microcapsules. Our salient findings were that equine MSC-derived CM stimulated the migration of equine dermal fibroblasts and increased their expression level of genes that positively contribute to wound healing. In addition, we found that equine MSCs packaged in core-shell hydrogel microcapsules had similar effects on equine dermal fibroblast migration and gene expression, indicating that microencapsulation of MSCs does not interfere with the release of bioactive factors. Our results demonstrate that the use of CM from MSCs might be a promising

Delayed Cutaneous Hypersensitivity Reactions to Antibiotics: Management with Desensitization.

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McNulty, Caitlin M G; Park, Miguel A

2017-11-01

Successful desensitization to mild to moderate delayed cutaneous adverse reaction to antibiotics has been described in a limited number of antibiotics and found to be safe. However, there are ample opportunities to standardize protocols for delayed cutaneous adverse reactions to antibiotics. Copyright © 2017 Elsevier Inc. All rights reserved.

Platelet Rich Plasma: New Insights for Cutaneous Wound Healing Management

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Deborah Chicharro-Alcántara

2018-01-01

Full Text Available The overall increase of chronic degenerative diseases associated with ageing makes wound care a tremendous socioeconomic burden. Thus, there is a growing need to develop novel wound healing therapies to improve cutaneous wound healing. The use of regenerative therapies is becoming increasingly popular due to the low-invasive procedures needed to apply them. Platelet-rich plasma (PRP is gaining interest due to its potential to stimulate and accelerate the wound healing process. The cytokines and growth factors forming PRP play a crucial role in the healing process. This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process.

Platelet Rich Plasma: New Insights for Cutaneous Wound Healing Management

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Chicharro-Alcántara, Deborah; Damiá-Giménez, Elena; Carrillo-Poveda, José M.; Peláez-Gorrea, Pau

2018-01-01

The overall increase of chronic degenerative diseases associated with ageing makes wound care a tremendous socioeconomic burden. Thus, there is a growing need to develop novel wound healing therapies to improve cutaneous wound healing. The use of regenerative therapies is becoming increasingly popular due to the low-invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining interest due to its potential to stimulate and accelerate the wound healing process. The cytokines and growth factors forming PRP play a crucial role in the healing process. This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process. PMID:29346333

Effect of astaxanthin on cutaneous wound healing

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Meephansan J

2017-07-01

Full Text Available Jitlada Meephansan,1 Atiya Rungjang,1 Werayut Yingmema,2 Raksawan Deenonpoe,3 Saranyoo Ponnikorn3 1Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand; 2Laboratory Animal Centers, Thammasat University, Pathum Thani, Thailand; 3Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand Abstract: Wound healing consists of a complex series of convoluted processes which involve renewal of the skin after injury. ROS are involved in all phases of wound healing. A balance between oxidative and antioxidative forces is necessary for a favorable healing outcome. Astaxanthin, a member of the xanthophyll group, is considered a powerful antioxidant. In this study, we investigated the effect of topical astaxanthin on cutaneous wound healing. Full-thickness dermal wounds were created in 36 healthy female mice, which were divided into a control group and a group receiving 78.9 µM topical astaxanthin treatment twice daily for 15 days. Astaxanthin-treated wounds showed noticeable contraction by day 3 of treatment and complete wound closure by day 9, whereas the wounds of control mice revealed only partial epithelialization and still carried scabs. Wound healing biological markers including Col1A1 and bFGF were significantly increased in the astaxanthin-treated group since day 1. Interestingly, the oxidative stress marker iNOS showed a significantly lower expression in the study. The results indicate that astaxanthin is an effective compound for accelerating wound healing. Keywords: astaxanthin, wound healing, reactive oxygen species, antioxidant 

Injectable Polyurethane Composite Scaffolds Delay Wound Contraction and Support Cellular Infiltration and Remodeling in Rat Excisional Wounds

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Adolph, Elizabeth J.; Hafeman, Andrea E.; Davidson, Jeffrey M.; Nanney, Lillian B.; Guelcher, Scott A.

2011-01-01

Injectable scaffolds present compelling opportunities for wound repair and regeneration due to their ability to fill irregularly shaped defects and deliver biologics such as growth factors. In this study, we investigated the properties of injectable polyurethane biocomposite scaffolds and their application in cutaneous wound repair using a rat excisional model. The scaffolds have a minimal reaction exotherm and clinically relevant working and setting times. Moreover, the biocomposites have mechanical and thermal properties consistent with rubbery elastomers. In the rat excisional wound model, injection of settable biocomposite scaffolds stented the wounds at early time points, resulting in a regenerative rather than a scarring phenotype at later time points. Measurements of wound width and thickness revealed that the treated wounds were less contracted at day 7 compared to blank wounds. Analysis of cell proliferation and apoptosis showed that the scaffolds were biocompatible and supported tissue ingrowth. Myofibroblast formation and collagen fiber organization provided evidence that the scaffolds have a positive effect on extracellular matrix remodeling by disrupting the formation of an aligned matrix under elevated tension. In summary, we have developed an injectable biodegradable polyurethane biocomposite scaffold that enhances cutaneous wound healing in a rat model. PMID:22105887

Early induction of NRF2 antioxidant pathway by RHBDF2 mediates rapid cutaneous wound healing.

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Hosur, Vishnu; Burzenski, Lisa M; Stearns, Timothy M; Farley, Michelle L; Sundberg, John P; Wiles, Michael V; Shultz, Leonard D

2017-04-01

Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. In humans, a gain-of-function mutation in the RHBDF2 gene accelerates cutaneous wound healing in an EGFR-dependent manner. Likewise, a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2 cub/cub ) shows a regenerative phenotype (rapid ear-hole closure) resulting from constitutive activation of the EGFR pathway. Because the RHBDF2-regulated EGFR pathway is relevant to cutaneous wound healing in humans, we used Rhbdf2 cub/cub mice to investigate the biological networks and pathways leading to accelerated ear-hole closure, with the goal of identifying therapeutic targets potentially effective in promoting wound healing in humans. Comparative transcriptome analysis of ear pinna tissue from Rhbdf2 cub/cub and Rhbdf2 +/+ mice at 0h, 15min, 2h, and 24h post-wounding revealed an early induction of the nuclear factor E2-related factor 2 (NRF2)-mediated anti-oxidative pathway (0h and 15min), followed by the integrin-receptor aggregation pathway (2h) as early-stage events immediately and shortly after wounding in Rhbdf2 cub/cub mice. Additionally, we observed genes enriched for the Fc fragment of the IgG receptor IIIa (FCGR3A)-mediated phagocytosis pathway 24h post-wounding. Although cutaneous wound repair in healthy individuals is generally non-problematic, it can be severely impaired due to aging, diabetes, and chronic inflammation. This study suggests that activation of the NRF2-antioxidant pathway by rhomboid protein RHBDF2 might be beneficial in treating chronic non-healing wounds. Copyright © 2017 Elsevier Inc. All rights reserved.

Cutaneous wound healing: Current concepts and advances in wound care

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Kenneth C Klein

2014-01-01

Full Text Available A non-healing wound is defined as showing no measurable signs of healing for at least 30 consecutive treatments with standard wound care. [1] It is a snapshot of a patient′s total health as well as the ongoing battle between noxious factors and the restoration of optimal macro and micro circulation, oxygenation and nutrition. In practice, standard therapies for non-healing cutaneous wounds include application of appropriate dressings, periodic debridement and eliminating causative factors. [2] The vast majority of wounds would heal by such approach with variable degrees of residual morbidity, disability and even mortality. Globally, beyond the above therapies, newer tools of healing are selectively accessible to caregivers, for various logistical or financial reasons. Our review will focus on the use of hyperbaric oxygen therapy (HBOT, as used at our institution (CAMC, and some other modalities that are relatively accessible to patients. HBOT is a relatively safe and technologically simpler way to deliver care worldwide. However, the expense for including HBOT as standard of care for recognized indications per UHMS(Undersea and Hyperbaric Medical Society may vary widely from country to country and payment system. [3] In the USA, CMS (Centers for Medicare and Medicaid Services approved indications for HBOT vary from that of the UHMS for logistical reasons. [1] We shall also briefly look into other newer therapies per current clinical usage and general acceptance by the medical community. Admittedly, there would be other novel tools with variable success in wound healing worldwide, but it would be difficult to include all in this treatise.

Cutaneous wound healing: Current concepts and advances in wound care

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Klein, Kenneth C; Guha, Somes Chandra

2014-01-01

A non-healing wound is defined as showing no measurable signs of healing for at least 30 consecutive treatments with standard wound care.[1] It is a snapshot of a patient's total health as well as the ongoing battle between noxious factors and the restoration of optimal macro and micro circulation, oxygenation and nutrition. In practice, standard therapies for non-healing cutaneous wounds include application of appropriate dressings, periodic debridement and eliminating causative factors.[2] The vast majority of wounds would heal by such approach with variable degrees of residual morbidity, disability and even mortality. Globally, beyond the above therapies, newer tools of healing are selectively accessible to caregivers, for various logistical or financial reasons. Our review will focus on the use of hyperbaric oxygen therapy (HBOT), as used at our institution (CAMC), and some other modalities that are relatively accessible to patients. HBOT is a relatively safe and technologically simpler way to deliver care worldwide. However, the expense for including HBOT as standard of care for recognized indications per UHMS(Undersea and Hyperbaric Medical Society) may vary widely from country to country and payment system.[3] In the USA, CMS (Centers for Medicare and Medicaid Services) approved indications for HBOT vary from that of the UHMS for logistical reasons.[1] We shall also briefly look into other newer therapies per current clinical usage and general acceptance by the medical community. Admittedly, there would be other novel tools with variable success in wound healing worldwide, but it would be difficult to include all in this treatise. PMID:25593414

Excisional wound healing is delayed in a murine model of chronic kidney disease.

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Akhil K Seth

Full Text Available BACKGROUND: Approximately 15% of the United States population suffers from chronic kidney disease (CKD, often demonstrating an associated impairment in wound healing. This study outlines the development of a surgical murine model of CKD in order to investigate the mechanisms underlying this impairment. METHODS: CKD was induced in mice by partial cauterization of one kidney cortex and contralateral nephrectomy, modifying a previously published technique. After a minimum of 6-weeks, splinted, dorsal excisional wounds were created to permit assessment of wound healing parameters. Wounds were harvested on postoperative days (POD 0, 3, 7, and 14 for histological, immunofluorescent, and quantitative PCR (qPCR. RESULTS: CKD mice exhibited deranged blood chemistry and hematology profiles, including profound uremia and anemia. Significant decreases in re-epithelialization and granulation tissue deposition rates were found in uremic mice wounds relative to controls. On immunofluorescent analysis, uremic mice demonstrated significant reductions in cellular proliferation (BrdU and angiogenesis (CD31, with a concurrent increase in inflammation (CD45 as compared to controls. CKD mice also displayed differential expression of wound healing-related genes (VEGF, IL-1β, eNOS, iNOS on qPCR. CONCLUSIONS: These findings represent the first reported investigation of cutaneous healing in a CKD animal model. Ongoing studies of this significantly delayed wound healing phenotype include the establishment of renal failure model in diabetic strains to study the combined effects of CKD and diabetes.

Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

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Zhao, Pan; Sui, Bing-Dong; Liu, Nu; Lv, Ya-Jie; Zheng, Chen-Xi; Lu, Yong-Bo; Huang, Wen-Tao; Zhou, Cui-Hong; Chen, Ji; Pang, Dan-Lin; Fei, Dong-Dong; Xuan, Kun; Hu, Cheng-Hu; Jin, Yan

2017-10-01

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Wound healing delays in α-Klotho-deficient mice that have skin appearance similar to that in aged humans - Study of delayed wound healing mechanism.

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Yamauchi, Makoto; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Matsumoto, Yoshitaka; Yamashita, Ken; Kayama, Musashi; Sato, Noriyuki; Yotsuyanagi, Takatoshi

2016-05-13

Skin atrophy and delayed wound healing are observed in aged humans; however, the molecular mechanism are still elusive. The aim of this study was to analyze the molecular mechanisms of delayed wound healing by aging using α-Klotho-deficient (kl/kl) mice, which have phenotypes similar to those of aged humans. The kl/kl mice showed delayed wound healing and impaired granulation formation compared with those in wild-type (WT) mice. The skin graft experiments revealed that delayed wound healing depends on humoral factors, but not on kl/kl skin tissue. The mRNA expression levels of cytokines related to acute inflammation including IL-1β, IL-6 and TNF-α were higher in wound lesions of kl/kl mice compared with the levels in WT mice by RT-PCR analysis. LPS-induced TNF-α production model using spleen cells revealed that TNF-α production was significantly increased in the presence of FGF23. Thus, higher levels of FGF23 in kl/kl mouse may have a role to increase TNF-α production in would lesion independently of α-Klotho protein, and impair granulation formation and delay wound healing. Copyright © 2016 Elsevier Inc. All rights reserved.

Topical application of dressing with amino acids improves cutaneous wound healing in aged rats.

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Corsetti, Giovanni; D'Antona, Giuseppe; Dioguardi, Francesco Saverio; Rezzani, Rita

2010-09-01

The principal goal in treating surgical and non-surgical wounds, in particular for aged skin, is the need for rapid closure of the lesion. Cutaneous wound healing processes involve four phases including an inflammatory response with the induction of pro-inflammatory cytokines. If inflammation develops in response to bacterial infection, it can create a problem for wound closure. Reduced inflammation accelerates wound closure with subsequent increased fibroblast function and collagen synthesis. On the contrary, prolonged chronic inflammation results in very limited wound healing. Using histological and immunohistochemical techniques, we investigated the effects of a new wound dressing called Vulnamin that contains four essential amino acids for collagen and elastin synthesis plus sodium ialuronate (Na-Ial), compared with Na-Ial alone, in closure of experimental cutaneous wounds of aged rats. Our results showed that the application of Vulnamin dressings modulated the inflammatory response with a reduction in the number of inflammatory cells and inducible nitric oxide synthase (iNOS) immunolocalisation, while increasing endothelial nitric oxide synthase (eNOS) and transforming growth factor-beta1 (TGF-beta1) immunolocalisation. Furthermore, the dressing increased the distribution density of fibroblasts and aided the synthesis of thin collagen fibers resulting in a reduction in healing time. The nutritive approach using this new wound dressing can provide an efficacious and safe strategy to accelerate wound healing in elderly subjects, simplifying therapeutic procedures and leading to an improved quality of life. 2009 Elsevier GmbH. All rights reserved.

Paracrine action of mesenchymal stromal cells delivered by microspheres contributes to cutaneous wound healing and prevents scar formation in mice.

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Huang, Sha; Wu, Yan; Gao, Dongyun; Fu, Xiaobing

2015-07-01

Accumulating evidence suggests that mesenchymal stromal cells (MSCs) participate in wound healing to favor tissue regeneration and inhibit fibrotic tissue formation. However, the evidence of MSCs to suppress cutaneous scar is extremely rare, and the mechanism remains unidentified. This study aimed to demonstrate whether MSCs-as the result of their paracrine actions on damaged tissues-would accelerate wound healing and prevent cutaneous fibrosis. For efficient delivery of MSCs to skin wounds, microspheres were used to maintain MSC potency. Whether MSCs can accelerate wound healing and alleviate cutaneous fibrosis through paracrine action was investigated with the use of a Transwell co-culture system in vitro and a murine model in vivo. MSCs cultured on gelatin microspheres fully retained their cell surface marker expression profile, proliferation, differentiation and paracrine potential. Co-cultures of MSCs and fibroblasts indicated that the benefits of MSCs on suppressing fibroblast proliferation and its fibrotic behavior induced by inflammatory cytokines probably were caused by paracrine actions. Importantly, microspheres successfully delivered MSCs into wound margins and significantly accelerated wound healing and concomitantly reduced the fibrotic activities of cells within the wounds and excessive accumulation of extracellular matrix as well as the transforming growth factor-β1/transforming growth factor-β3 ratio. This study provides insight into what we believe to be a previously undescribed, multifaceted role of MSC-released protein in reducing cutaneous fibrotic formation. Paracrine action of MSCs delivered by microspheres may thus qualify as a promising strategy to enhance tissue repair and to prevent excessive fibrosis during cutaneous wound healing. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Impaired cutaneous wound healing in mice lacking tetranectin

DEFF Research Database (Denmark)

Iba, Kousuke; Hatakeyama, Naoko; Kojima, Takashi

2009-01-01

disruption of the tetranectin gene to elucidate the biological function of tetranectin. In this study, we showed that wound healing was markedly delayed in tetranectin-null mice compared with wild-type mice. A single full-thickness incision was made in the dorsal skin. By 14 days after the incision......, the wounds fully healed in all wild-type mice based on the macroscopic closure; in contrast, the progress of wound healing in the tetranectin null mice appeared to be impaired. In histological analysis, wounds of wild-type mice showed complete reepithelialization and healed by 14 days after the incision....... However, those of tetranectin-null mice never showed complete reepithelialization at 14 days. At 21 days after the injury, the wound healed and was covered with an epidermis. These results supported the fact that tetranectin may play a role in the wound healing process....

Smad4 disruption accelerates keratinocyte reepithelialization in murine cutaneous wound repair.

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Yang, Leilei; Li, Wenlong; Wang, Shaoxia; Wang, Lijuan; Li, Yang; Yang, Xiao; Peng, Ruiyun

2012-10-01

Keratinocyte reepithelialization is a rate-limiting event in cutaneous wound repair, which involves the migration and proliferation of keratinocytes to cover the denuded dermal surface. Transforming growth factor-β1 (TGF-β1) has the ability to induce epithelial cell migration while inhibiting proliferation, and controversial results have been generated regarding the effect of TGF-β signaling on reepithelialization. In this study, full-thickness skin wounds were made in keratinocyte-specific Smad4 knockout and the control mice. The wound closure, reepithelialization, keratinocyte proliferation, myofibroblast numbers and collagen deposition of were assessed. The results showed that the proliferation of keratinocytes increased, which accelerated the reepithelialization, and led to faster wound repair in the epidermis of Smad4 mutant mice. Upregulation of keratin 17, 14-3-3 sigma and phosphorylated AKT in the hyperproliferative epidermis may be correlated with the accelerated reepithelialization. We conclude that Smad4 plays an inhibitory role in the keratinocyte-mediated reepithelialization of wound healing.

Delayed wound healing after forefoot surgery in patients with rheumatoid arthritis.

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Ishie, Shinichiro; Ito, Hiromu; Azukizawa, Masayuki; Furu, Moritoshi; Ishikawa, Masahiro; Ogino, Hiroko; Hamamoto, Yosuke; Matsuda, Shuichi

2015-05-01

To elucidate the systemic and local risk factors and the effect of surgical procedures for delayed wound healing after forefoot surgery in patients with rheumatoid arthritis (RA). Fifty forefoot surgeries were performed in 39 patients using resection arthroplasty or a joint-preserving procedure (25 feet for each procedure). The associations between the occurrence of delayed wound healing and clinical variables, radiological assessment, or surgical procedures were analyzed. Delayed wound healing was recorded in nine feet of eight patients. The duration of RA was significantly longer in the delayed healing group than that in the healed group. Age, sex, smoking history, concomitant diabetes, and RA medication did not differ between the groups. Radiological evaluation showed significant differences between groups in metatarsophalangeal dorsal flexion angle. The shortened length of the fourth and the fifth metatarsal bones affected the occurrence of the complication. The joint-preserving procedure had significantly less delayed wound healing compared with resection arthroplasty. Preoperative dorsoplantar deformity and perioperative tissue damage can cause delayed wound healing after forefoot surgery in RA patients.

Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

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Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

2016-01-01

Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. Copyright © 2015

Wound healing potential of adipose tissue stem cell extract.

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Na, You Kyung; Ban, Jae-Jun; Lee, Mijung; Im, Wooseok; Kim, Manho

2017-03-25

Adipose tissue stem cells (ATSCs) are considered as a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using stem cells, intercellular molecule exchange by stem cell secretory factors showed beneficial effects by reducing tissue damage and augmentation of endogenous repair. Delayed cutaneous wound healing is implicated in many conditions such as diabetes, aging, stress and alcohol consumption. However, the effects of cell-free extract of ATSCs (ATSC-Ex) containing secretome on wound healing process have not been investigated. In this study, ATSC-Ex was topically applied on the cutaneous wound and healing speed was examined. As a result, wound closure was much faster in the cell-free extract treated wound than control wound at 4, 6, 8 days after application of ATSC-Ex. Dermal fibroblast proliferation, migration and extracellular matrix (ECM) production are critical aspects of wound healing, and the effects of ATSC-Ex on human dermal fibroblast (HDF) was examined. ATSC-Ex augmented HDF proliferation in a dose-dependent manner and migration ability was enhanced by extract treatment. Representative ECM proteins, collagen type I and matrix metalloproteinase-1, are significantly up-regulated by treatment of ATSC-Ex. Our results suggest that the ATSC-Ex have improving effect of wound healing and can be the potential therapeutic candidate for cutaneous wound healing. Copyright © 2017 Elsevier Inc. All rights reserved.

Antioxidant Sol-Gel Improves Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats

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Lee, Yen-Hsien; Chang, Jung-Jhih; Chien, Chiang-Ting; Yang, Ming-Chien; Chien, Hsiung-Fei

2012-01-01

We examined the effects of vitamin C in Pluronic F127 on diabetic wound healing. Full-thickness excision skin wounds were made in normal and diabetic Wistar rats to evaluate the effect of saline, saline plus vitamin C (antioxidant sol), Pluronic F127, or Pluronic F127 plus vitamin C (antioxidant sol-gel). The rate of wound contraction, the levels of epidermal and dermal maturation, collagen synthesis, and apoptosis production in the wound tissue were determined. In vitro data showed that after 6 hours of air exposure, the order of the scavenging abilities for HOCl, H2O2, and O2  − was antioxidant sol-gel > antioxidant saline > Pluronic F127 = saline. After 7 and 14 days of wound injury, the antioxidant sol-gel improved wound healing significantly by accelerated epidermal and dermal maturation, an increase in collagen content, and a decrease in apoptosis formation. However, the wounds of all treatments healed mostly at 3 weeks. Vitamin C in Pluronic F127 hastened cutaneous wound healing by its antioxidant and antiapoptotic mechanisms through a good drug delivery system. This study showed that Pluronic F127 plus vitamin C could potentially be employed as a novel wound-healing enhancer. PMID:22919368

Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain.

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Zhu, Qi; Mangukiya, Hitesh Bhagavanbhai; Mashausi, Dhahiri Saidi; Guo, Hao; Negi, Hema; Merugu, Siva Bharath; Wu, Zhenghua; Li, Dawei

2017-09-01

Anterior gradient 2 (AGR2), a member of protein disulfide isomerase (PDI) family, is both located in cytoplasm and secreted into extracellular matrix. The orthologs of AGR2 have been linked to limb regeneration in newt and wound healing in zebrafish. In mammals, AGR2 influences multiple cell signaling pathways in tumor formation and in normal cell functions related to new tissue formation like angiogenesis. However, the function of AGR2 in mammalian wound healing remains unknown. This study aimed to investigate AGR2 expression and its function during skin wound healing and the possible application of external AGR2 in cutaneous wound to accelerate the healing process. Our results showed that AGR2 expression was induced in the migrating epidermal tongue and hyperplastic epidermis after skin excision. Topical application of recombinant AGR2 significantly accelerated wound-healing process by increasing the migration of keratinocytes (Kera.) and the recruitment of fibroblasts (Fibro.) near the wounded area. External AGR2 also promoted the migration of Kera. and Fibro. in vitro in a dose-dependent manner. The adhesion domain of AGR2 was required for the formation of focal adhesions in migrating Fibro., leading to the directional migration along AGR2 gradient. These results indicate that recombinant AGR2 accelerates skin wound healing through regulation of Kera. and Fibro. migration, thus demonstrating its potential utility as an alternative strategy of the therapeutics to accelerate the healing of acute or chronic skin wounds. © 2017 Federation of European Biochemical Societies.

Enhanced Cutaneous Wound Healing In Vivo by Standardized Crude Extract of Poincianella pluviosa.

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Fernanda Giacomini Bueno

Full Text Available Wound healing is a complex process that involves several biological events, and a delay in this process may cause economic and social problems for the patient. The search continues for new alternative treatments to aid healing, including the use of herbal medicines. Members of the genus Caesalpinia are used in traditional medicine to treat wounds. The related species Poincianella pluviosa (DC. L.P. Queiroz increases the cell viability of keratinocytes and fibroblasts and stimulates the proliferation of keratinocytes in vitro. The crude extract (CE from bark of P. pluviosa was evaluated in the wound-healing process in vivo, to validate the traditional use and the in vitro activity. Standardized CE was incorporated into a gel and applied on cutaneous wounds (TCEG and compared with the formulation without CE (Control for 4, 7, 10, or 14 days of treatment. The effects of the CE on wound re-epithelialization; cell proliferation; permeation, using photoacoustic spectroscopy (PAS; and proteins, including vascular endothelial growth factor (VEGF, superoxide dismutase 2 (SOD-2 and cyclooxygenase 2 (COX-2 were evaluated. The TCEG stimulated the migration of keratinocytes at day 4 and proliferation on the following days, with a high concentration of cells in metaphase at 7 days. Type I collagen formed more rapidly in the TCEG. PAS showed that the CE had permeated through the skin. TCEG stimulated VEGF at day 4 and SOD-2 and COX-2 at day 7. The results suggest that the CE promoted the regulation of proteins and helped to accelerate the processes involved in healing, promoting early angiogenesis. This led to an increase in the re-epithelialized surface, with significant mitotic activity. Maturation of collagen fibers was also enhanced, which may affect the resistance of the extracellular matrix. PAS indicated a correlation between the rate of diffusion and biological events during the healing process. The CE from P. pluviosa appears promising as an aid in

Adenoviral gene delivery to primary human cutaneous cells and burn wounds.

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Hirsch, Tobias; von Peter, Sebastian; Dubin, Grzegorz; Mittler, Dominik; Jacobsen, Frank; Lehnhardt, Markus; Eriksson, Elof; Steinau, Hans-Ulrich; Steinstraesser, Lars

2006-01-01

The adenoviral transfer of therapeutic genes into epidermal and dermal cells is an interesting approach to treat skin diseases and to promote wound healing. The aim of this study was to assess the in vitro and in vivo transfection efficacy in skin and burn wounds after adenoviral gene delivery. Primary keratinocytes (HKC), fibroblasts (HFB), and HaCaT cells were transfected using different concentrations of an adenoviral construct (eGFP). Transfection efficiency and cytotoxicity was determined up to 30 days. Expression was quantified by FACS analysis and fluorimeter. Cytotoxicity was measured using the trypan blue exclusion method. 45 male Sprague Dawley rats received 2x10(8) pfu of Ad5-CMV-LacZ or carrier control intradermally into either superficial partial thickness scald burn or unburned skin. Animals were euthanized after 48 h, 7 or 14 days posttreatment. Transgene expression was assessed using immunohistochemistry and bioluminescent assays. The highest transfection rate was observed 48 h posttransfection: 79% for HKC, 70% for HFB, and 48% for HaCaT. The eGFP expression was detectable in all groups over 30 days (P>0.05). Cytotoxic effects of the adenoviral vector were observed for HFB after 10 days and HaCaT after 30 days. Reporter gene expression in vivo was significantly higher in burned skin compared with unburned skin (P=0,004). Gene expression decreases from 2 to 7 days with no significant expression after 14 days. This study demonstrates that effective adenoviral-mediated gene transfer of epidermal primary cells and cell-lines is feasible. Ex vivo gene transfer in epithelial cells might have promise for the use in severely burned patients who receive autologous keratinocyte sheets. Transient cutaneous gene delivery in burn wounds using adenoviral vectors causes significant concentrations in the wound tissue for at least 1 week. Based on these findings, we hypothesize that transient cutaneous adenoviral gene delivery of wound healing promoting factors has

Impaired Healing of a Cutaneous Wound in an Inducible Nitric Oxide Synthase-Knockout Mouse

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Takashi Kitano

2017-01-01

Full Text Available Background. We investigated the effects of loss of inducible nitric oxide synthase (iNOS on the healing process of cutaneous excisional injury by using iNOS-null (KO mice. Population of granulation tissue-related cell types, that is, myofibroblasts and macrophages, growth factor expression, and reepithelialization were evaluated. Methods. KO and wild type (WT mice of C57BL/6 background were used. Under general anesthesia two round full-thickness excision wounds of 5.0 mm in diameter were produced in dorsal skin. After specific intervals of healing, macroscopic observation, histology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction (RT-PCR were employed to evaluate the healing process. Results. The loss of iNOS retards granulation tissue formation and reepithelialization in excision wound model in mice. Detailed analyses showed that myofibroblast appearance, macrophage infiltration, and mRNA expression of transforming growth factor b and of collagen 1α2 were all suppressed by lacking iNOS. Conclusions. iNOS is required in the process of cutaneous wound healing. Lacking iNOS retards macrophage invasion and its expression of fibrogenic components that might further impair fibrogenic behaviors of fibroblasts.

Feasibility of speckle variance OCT for imaging cutaneous microvasculature regeneration during healing of wounds in diabetic mice

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Sharma, P.; Kumawat, J.; Kumar, S.; Sahu, K.; Verma, Y.; Gupta, P. K.; Rao, K. D.

2018-02-01

We report on a study to assess the feasibility of a swept source-based speckle variance optical coherence tomography setup for monitoring cutaneous microvasculature. Punch wounds created in the ear pinnae of diabetic mice were monitored at different times post wounding to assess the structural and vascular changes. It was observed that the epithelium thickness increases post wounding and continues to be thick even after healing. Also, the wound size assessed by vascular images is larger than the physical wound size. The results show that the developed speckle variance optical coherence tomography system can be used to monitor vascular regeneration during wound healing in diabetic mice.

Wound healing potential of adipose tissue stem cell extract

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Na, You Kyung; Ban, Jae-Jun; Lee, Mijung; Im, Wooseok; Kim, Manho

2017-01-01

Adipose tissue stem cells (ATSCs) are considered as a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using stem cells, intercellular molecule exchange by stem cell secretory factors showed beneficial effects by reducing tissue damage and augmentation of endogenous repair. Delayed cutaneous wound healing is implicated in many conditions such as diabetes, aging, stress and alcohol consumption. However, the effects of cell-free extract of ATSCs (ATSC-Ex) containing secretome on wound healing process have not been investigated. In this study, ATSC-Ex was topically applied on the cutaneous wound and healing speed was examined. As a result, wound closure was much faster in the cell-free extract treated wound than control wound at 4, 6, 8 days after application of ATSC-Ex. Dermal fibroblast proliferation, migration and extracellular matrix (ECM) production are critical aspects of wound healing, and the effects of ATSC-Ex on human dermal fibroblast (HDF) was examined. ATSC-Ex augmented HDF proliferation in a dose-dependent manner and migration ability was enhanced by extract treatment. Representative ECM proteins, collagen type I and matrix metalloproteinase-1, are significantly up-regulated by treatment of ATSC-Ex. Our results suggest that the ATSC-Ex have improving effect of wound healing and can be the potential therapeutic candidate for cutaneous wound healing. - Highlights: • Topical application of ATSC-Ex results in faster wound closure than normal wound in vivo. • ATSC-Ex enhances dermal fibroblast proliferation, migration and extracellular matrix production. • This study suggests that ATSC-Ex is an effective source to augment wound healing.

Fibroblast-Specific Deletion of Hypoxia Inducible Factor-1 Critically Impairs Murine Cutaneous Neovascularization and Wound Healing.

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Duscher, Dominik; Maan, Zeshaan N; Whittam, Alexander J; Sorkin, Michael; Hu, Michael S; Walmsley, Graham G; Baker, Hutton; Fischer, Lauren H; Januszyk, Michael; Wong, Victor W; Gurtner, Geoffrey C

2015-11-01

Diabetes and aging are known risk factors for impaired neovascularization in response to ischemic insult, resulting in chronic wounds, and poor outcomes following myocardial infarction and cerebrovascular injury. Hypoxia-inducible factor (HIF)-1α, has been identified as a critical regulator of the response to ischemic injury and is dysfunctional in diabetic and elderly patients. To better understand the role of this master hypoxia regulator within cutaneous tissue, the authors generated and evaluated a fibroblast-specific HIF-1α knockout mouse model. The authors generated floxed HIF-1 mice (HIF-1) by introducing loxP sites around exon 1 of the HIF-1 allele in C57BL/6J mice. Fibroblast-restricted HIF-1α knockout (FbKO) mice were generated by breeding our HIF-1 with tamoxifen-inducible Col1a2-Cre mice (Col1a2-CreER). HIF-1α knockout was evaluated on a DNA, RNA, and protein level. Knockout and wild-type mice were subjected to ischemic flap and wound healing models, and CD31 immunohistochemistry was performed to assess vascularity of healed wounds. Quantitative real-time polymerase chain reaction of FbKO skin demonstrated significantly reduced Hif1 and Vegfa expression compared with wild-type. This finding was confirmed at the protein level (p wound closure and vascularity (p wound healing, reduced wound vascularity, and significant impairment in the ischemic neovascular response. These findings provide new insight into the importance of cell-specific responses to hypoxia during cutaneous neovascularization.

Anti‐aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application

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Zhao, Pan; Sui, Bing‐Dong; Liu, Nu; Lv, Ya‐Jie; Zheng, Chen‐Xi; Lu, Yong‐Bo; Huang, Wen‐Tao; Zhou, Cui‐Hong; Chen, Ji; Pang, Dan‐Lin; Fei, Dong‐Dong; Xuan, Kun; Hu, Cheng‐Hu; Jin, Yan

2017-01-01

Summary Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical ad...

Neutrophil depletion in the early inflammatory phase delayed cutaneous wound healing in older rats: improvements due to the use of un-denatured camel whey protein.

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Ebaid, Hossam

2014-03-04

While it is known that advanced age alters the recruitment of neutrophils during wound healing, thereby delaying the wound healing process, little is known about prolonged wound healing in advanced ages. Thus, we investigated the correlation of neutrophil recruitment with healing events, and the impact of whey protein (WP) on neutrophil activation. The animals were allocated into wounded young group, wounded older group and wounded older rats with daily treatment of WP at a dose of 100 mg/kg of body weight. Our results pointed to a marked deficiency in the number of neutrophils in the wounds of older rats, which was accompanied with impairment of the healing process. In the group of older rats, phagocytic activity, as tested by fluorescence microscopy, declined throughout the first 24 hours after wounding. Both the neutrophil number and the phagocytic activity recovered in older rats which received WP supplementation. Interestingly, WP was found to significantly up-regulate the MIP-1α and CINC-1 mRNA expression in old rats. On the other hand, the wound size in older rats was significantly higher than that in younger ones. Blood angiogenesis was also significantly delayed in the older group as opposed to the young rats. WP, however, was found to return these indices to normal levels in the older rats. Proliferation and epidermal migration of the keratinocytes and the collagen deposition were also returned to the normal rates. This data confirms the critical role of neutrophil recruitment in the early inflammatory phase of wound healing in older rats. In addition, WP protein was used to improve neutrophil function in older rats, healing events returned to a more normal profile. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2100966986117779.

Gene expression profiling of cutaneous wound healing

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Wang Ena

2007-02-01

Full Text Available Abstract Background Although the sequence of events leading to wound repair has been described at the cellular and, to a limited extent, at the protein level this process has yet to be fully elucidated. Genome wide transcriptional analysis tools promise to further define the global picture of this complex progression of events. Study Design This study was part of a placebo-controlled double-blind clinical trial in which basal cell carcinomas were treated topically with an immunomodifier – toll-like receptor 7 agonist: imiquimod. The fourteen patients with basal cell carcinoma in the placebo arm of the trial received placebo treatment consisting solely of vehicle cream. A skin punch biopsy was obtained immediately before treatment and at the end of the placebo treatment (after 2, 4 or 8 days. 17.5K cDNA microarrays were utilized to profile the biopsy material. Results Four gene signatures whose expression changed relative to baseline (before wound induction by the pre-treatment biopsy were identified. The largest group was comprised predominantly of inflammatory genes whose expression was increased throughout the study. Two additional signatures were observed which included preferentially pro-inflammatory genes in the early post-treatment biopsies (2 days after pre-treatment biopsies and repair and angiogenesis genes in the later (4 to 8 days biopsies. The fourth and smallest set of genes was down-regulated throughout the study. Early in wound healing the expression of markers of both M1 and M2 macrophages were increased, but later M2 markers predominated. Conclusion The initial response to a cutaneous wound induces powerful transcriptional activation of pro-inflammatory stimuli which may alert the host defense. Subsequently and in the absence of infection, inflammation subsides and it is replaced by angiogenesis and remodeling. Understanding this transition which may be driven by a change from a mixed macrophage population to predominately M2

Cutaneous Nocardia brasiliensis infection in an immunocompetent host after ovarian cystectomy: A case study

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Manideepa SenGupta

2011-11-01

Full Text Available Nocardia brasiliensis is a rare human pathogen that is usually associated with localised cutaneous infections. We report a case of primary cutaneous Nocardia brasiliensis infection causing delayed wound healing that developed after ovarian cystectomy in an otherwise healthy 32-year-old woman. The patient was initially treated with cotrimoxazole, however due to intolerance intravenous amikacin was given and gradually the wound healed. The diagnosis was confirmed by demonstrating the causative organism in exudates, and cultures. Early diagnosis as well as early institution of chemotherapy is effective in most patients, and antimicrobial susceptibility testing of the isolate should be performed to identify the best treatment options.

Cutaneous Nocardia brasiliensis infection in an immunocompetent host after ovarian cystectomy: A case study.

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Soma, Sarkar; Saha, Puranjay; Sengupta, Manideepa

2011-01-01

Nocardia brasiliensis is a rare human pathogen that is usually associated with localised cutaneous infections. We report a case of primary cutaneous Nocardia brasiliensis infection causing delayed wound healing that developed after ovarian cystectomy in an otherwise healthy 32-year-old woman. The patient was initially treated with cotrimoxazole, however due to intolerance intravenous amikacin was given and gradually the wound healed. The diagnosis was confirmed by demonstrating the causative organism in exudates, and cultures. Early diagnosis as well as early institution of chemotherapy is effective in most patients, and antimicrobial susceptibility testing of the isolate should be performed to identify the best treatment options.

Development of an acquisition protocol and a segmentation algortihm for wounds of cutaneous Leishmaniasis in digital images

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Diaz, Kristians; Castañeda, Benjamín; Miranda, César; Lavarello, Roberto; Llanos, Alejandro

2010-03-01

We developed a protocol for the acquisition of digital images and an algorithm for a color-based automatic segmentation of cutaneous lesions of Leishmaniasis. The protocol for image acquisition provides control over the working environment to manipulate brightness, lighting and undesirable shadows on the injury using indirect lighting. Also, this protocol was used to accurately calculate the area of the lesion expressed in mm2 even in curved surfaces by combining the information from two consecutive images. Different color spaces were analyzed and compared using ROC curves in order to determine the color layer with the highest contrast between the background and the wound. The proposed algorithm is composed of three stages: (1) Location of the wound determined by threshold and mathematical morphology techniques to the H layer of the HSV color space, (2) Determination of the boundaries of the wound by analyzing the color characteristics in the YIQ space based on masks (for the wound and the background) estimated from the first stage, and (3) Refinement of the calculations obtained on the previous stages by using the discrete dynamic contours algorithm. The segmented regions obtained with the algorithm were compared with manual segmentations made by a medical specialist. Broadly speaking, our results support that color provides useful information during segmentation and measurement of wounds of cutaneous Leishmaniasis. Results from ten images showed 99% specificity, 89% sensitivity, and 98% accuracy.

[Comparative description and retrospective analisis of modern methods of surgical wounds closure for intraoperative prophylaxis of development of pathologic cutaneous cicatrices].

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Stavyts'kyĭ, S O; Avetikov, D S; Lokes, K P; Rozkolupa, O O; Boĭko, I V

2014-05-01

The experience of application of various methods of closure was presented for the head and neck cutaneous wound surfaces after elective operative interventions. The variant of the postoperative results estimation and optimization of the wounds healing by primary closure was proposed.

Advanced glycation end products delay corneal epithelial wound healing through reactive oxygen species generation.

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Shi, Long; Chen, Hongmei; Yu, Xiaoming; Wu, Xinyi

2013-11-01

Delayed healing of corneal epithelial wounds is a serious complication in diabetes. Advanced glycation end products (AGEs) are intimately associated with the diabetic complications and are deleterious to the wound healing process. However, the effect of AGEs on corneal epithelial wound healing has not yet been evaluated. In the present study, we investigated the effect of AGE-modified bovine serum albumin (BSA) on corneal epithelial wound healing and its underlying mechanisms. Our data showed that AGE-BSA significantly increased the generation of intracellular ROS in telomerase-immortalized human corneal epithelial cells. However, the generation of intracellular ROS was completely inhibited by antioxidant N-acetylcysteine (NAC), anti-receptor of AGEs (RAGE) antibodies, or the inhibitor of NADPH oxidase. Moreover, AGE-BSA increased NADPH oxidase activity and protein expression of NADPH oxidase subunits, p22phox and Nox4, but anti-RAGE antibodies eliminated these effects. Furthermore, prevention of intracellular ROS generation using NAC or anti-RAGE antibodies rescued AGE-BSA-delayed epithelial wound healing in porcine corneal organ culture. In conclusion, our results demonstrated that AGE-BSA impaired corneal epithelial wound healing ex vivo. AGE-BSA increased intracellular ROS generation through NADPH oxidase activation, which accounted for the delayed corneal epithelial wound healing. These results may provide better insights for understanding the mechanism of delayed healing of corneal epithelial wounds in diabetes.

Raman spectroscopy enables noninvasive biochemical identification of the collagen regeneration in cutaneous wound healing of diabetic mice treated with MSCs.

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Yan, Wenxia; Liu, Hanping; Deng, Xiaoyuan; Jin, Ying; Sun, Huimin; Li, Caiyun; Wang, Ning; Chu, Jing

2017-07-01

Mesenchymal stem cells (MSCs) had been reported as a novel therapeutic strategy for non-healing diabetic cutaneous wound mainly by promoting the formation of extracellular matrix (ECM) and neovasculature. Collagen regeneration is one of the key processes of ECM remodeling in wound healing. Accordingly, rapid assessment of the collagen content in a noninvasive manner can promptly provide objective evaluation for MSC therapy of cutaneous wound healing and strength evidence to adjust therapeutic regimen. In the present study, noninvasive Raman microspectroscopy was used for tracing the regeneration status of collagen during diabetic wound healing with MSCs. Wound tissues of normal mice, diabetic mice, and MSC-treated diabetic mice were subjected to Masson trichrome staining assay and submitted to spectroscopic analysis by Raman microspectroscopy after wounding 7, 14, and 21 days. Masson trichrome staining demonstrated that there was more collagen deposition in diabetic + MSCs group relative to diabetic group. The relative intensity of Raman collagen peak positions at 937, 1004, 1321, 1452, and 1662 cm -1 increased in MSC-treated diabetic group compared to diabetic group, although normal mice group had the highest relative intensity of collagen peak bands. Correlation analysis suggested that the spectral bands had a high positive correlation with the collagen intensity detected by Masson trichrome staining in wound tissues of three groups. Our results demonstrate that Raman microspectroscopy has potential application in rapidly and quantitatively assessing diabetic wound healing with MSCs by monitoring collagen variation, which may provide a novel method for the study of skin regeneration.

Consequences of age on ischemic wound healing in rats: altered antioxidant activity and delayed wound closure.

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Moor, Andrea N; Tummel, Evan; Prather, Jamie L; Jung, Michelle; Lopez, Jonathan J; Connors, Sarah; Gould, Lisa J

2014-04-01

Advertisements targeted at the elderly population suggest that antioxidant therapy will reduce free radicals and promote wound healing, yet few scientific studies substantiate these claims. To better understand the potential utility of supplemental antioxidant therapy for wound healing, we tested the hypothesis that age and tissue ischemia alter the balance of endogenous antioxidant enzymes. Using a bipedicled skin flap model, ischemic and non-ischemic wounds were created on young and aged rats. Wound closure and the balance of the critical antioxidants superoxide dismutase and glutathione in the wound bed were determined. Ischemia delayed wound closure significantly more in aged rats. Lower superoxide dismutase 2 and glutathione in non-ischemic wounds of aged rats indicate a basal deficit due to age alone. Ischemic wounds from aged rats had lower superoxide dismutase 2 protein and activity initially, coupled with decreased ratios of reduced/oxidized glutathione and lower glutathione peroxidase activity. De novo glutathione synthesis, to restore redox balance in aged ischemic wounds, was initiated as evidenced by increased glutamate cysteine ligase. Results demonstrate deficiencies in two antioxidant pathways in aged rats that become exaggerated in ischemic tissue, culminating in profoundly impaired wound healing and prolonged inflammation.

Cutaneous squamous cell carcinoma presenting as a wound with discharging sinus tracts in a wild African lion (Panthera leo).

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Mwase, M; Mumba, C; Square, D; Kawarai, S; Madarame, H

2013-11-01

A female wild African lion (Panthera leo) was presented with an 8-month history of a wound with multiple discharging sinus tracts on the left paw. Microscopical examination revealed squamous cell carcinoma (SCC). To the best of our knowledge, this is the first report of cutaneous SCC in an African lion. Cutaneous SCC presenting as discharging sinus tracts lined by neoplastic squamous cells has not been reported previously in animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing

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Henshaw, F. R.; Boughton, P.; Lo, L.; McLennan, S. V.; Twigg, S. M.

2015-01-01

Aims/Hypothesis. Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Methods. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1??g?rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulati...

Mesenchymal stem cells delivered in a microsphere-based engineered skin contribute to cutaneous wound healing and sweat gland repair.

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Huang, Sha; Lu, Gang; Wu, Yan; Jirigala, Enhe; Xu, Yongan; Ma, Kui; Fu, Xiaobing

2012-04-01

Bone-marrow-derived mesenchymal stem cells (BM-MSCs) can contribute to wound healing after skin injury. However, the role of BM-MSCs on repairing skin appendages in renewal tissues is incompletely explored. Moreover, most preclinical studies suggest that the therapeutic effects afforded by BM-MSCs transplantation are short-lived and relatively unstable. To assess whether engrafted bone-marrow-derived mesenchymal stem cells via a delivery system can participate in cutaneous wound healing and sweat-gland repair in mice. For safe and effective delivery of BM-MSCs to wounds, epidermal growth factor (EGF) microspheres were firstly developed to both support cells and maintain appropriate stimuli, then cell-seeded microspheres were incorporated with biomimetic scaffolds and thus fabricated an engineered skin construct with epithelial differentiation and proliferative potential. The applied efficacy was examined by implanting them into excisional wounds on both back and paws of hind legs in mice. After 3 weeks, BM-MSC-engineered skin (EGF loaded) treated wounds exhibited accelerated healing with increased re-epithelialization rates and less skin contraction. Furthermore, histological and immunofluorescence staining analysis revealed sweat glands-like structures became more apparent in BM-MSC-engineered skin (EGF loaded) treated wounds but the number of implanted BM-MSCs were decreased gradually in later phases of healing progression. Our study suggests that BM-MSCs delivered by this EGF microspheres-based engineered skin model may be a promising strategy to repair sweat glands and improve cutaneous wound healing after injury and success in this study might provide a potential benefit for BM-MSCs administration clinically. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

The effect of intravitreal bevacizumab and ranibizumab on cutaneous tensile strength during wound healing

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Christoforidis JB

2013-01-01

Full Text Available John B Christoforidis,1 Jillian Wang,2 Angela Jiang,2 James Willard,5 Cedric Pratt,2 Mahmoud Abdel-Rasoul,3 Sashwati Roy,4 Heather Powell51Department of Ophthalmology and Vision Science, College of Medicine, The University of Arizona, Tucson, AZ, USA; 2Department of Ophthalmology, College of Medicine, The Ohio State University, Columbus, OH, USA; 3Center for Biostatistics, The Ohio State University, Columbus, OH, USA; 4Center Surgery, The Ohio State University, Columbus, OH, USA; 5Department of Materials Science, College of Engineering, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal bevacizumab and ranibizumab on wound tension and by histopathology during cutaneous wound healing in a rabbit model and to compare this effect to placebo intravitreal saline controls 1 and 2 weeks following intravitreal injection.Methods: A total of 120 New Zealand white rabbits were randomly assigned to one of three treatment groups each consisting of 40 rabbits. Each group received intravitreal injections of bevacizumab, ranibizumab, or normal saline. Immediately afterwards, each rabbit underwent four 6 mm full-thickness dermatologic punch biopsies. Twenty rabbits from each agent group underwent wound harvesting on day 7 or day 14. The skin samples were stained for CD34 for vascular endothelial cells on day 7, and maximal wound tensile load was measured on days 7 and 14. Quantitative assessment of mean neovascularization (MNV scores was obtained from 10 contiguous biopsy margin 400× fields of CD34-stained sections by two independent observers.Results: Wound tension reading means (N with standard error and adjusted P-values on day 7 were: saline placebos, 7.46 ± 0.87; bevacizumab, 4.50 ± 0.88 (P = 0.041; and ranibizumab, 4.67 ± 0.84 (P = 0.025. On day 14 these were: saline placebos, 7.34 ± 0.55; bevacizumab, 6.05 ± 0.54 (P = 0.18; and ranibizumab 7.99 ± 0.54 (P = 0.40. MNV scores in CD34 stained sections were

Clinical and histological findings of cutaneous wound healing in the red-eared slider turtle (Trachemys scripta elegans) housed in unheated outdoor enclosures.

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Negrini, Joao; Ginel, Pedro J; Novales, Manuel; Guerra, Rafael; Mozos, Elena

2016-10-01

Cutaneous wounds are common in chelonians. The clinical and histological features of wound healing in these species are not well described and this prevents evaluation of new therapies. To describe clinical and histopathological features of cutaneous wound healing in the red-eared slider turtle (Trachemys scripta elegans). Twenty four healthy adult females housed in outdoor facilities with free access to water and exposed to daily variations in temperature. Full thickness 6 mm skin biopsy punch wounds were created in the rear limbs. The turtles were assigned to Group 1 (n = 12 for clinical evaluation) and Group 2 (n = 12 for microscopic study). Group 1 was photographed on Day 1 and weekly, until 28 days post wounding. Wound retraction was expressed as the percentage of perimeter reduction. For Group 2, three skin wounds were sampled at 2, 7, 14, 21, 28, 42, 60 and 135 days post wounding for histological study. The avidin-biotin-peroxidase (ABC) staining method was used to evaluate five commercial antibodies. Wound contraction was limited; crust persisted at least 28 days. Re-epithelialization was complete by Day 14 in many animals; active inflammation persisted until 28 days; connective tissue re-constitution and remodelling was achieved from 42 to 135 days. Antibodies AE1/AE3, Factor VIII, MAC 387, CD3 and NCL-MSA showed cross reactivity with the cell counterpart in turtle tissues. Second intention wound healing progressed slowly and with an indolent behaviour. Microscopically there was marked overlapping of the inflammatory and proliferative phases over a long time period. © 2016 ESVD and ACVD.

[Cutaneous adverse reactions to tattoos and piercings].

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Mataix, J; Silvestre, J F

2009-10-01

Piercings and tattoos have become very popular in western society in recent decades, particularly among younger generations. Reports of medical complications associated with these decorative techniques have increased in parallel with the rise in their popularity. Due to their high frequency, adverse cutaneous reactions are particularly important among these potential complications. Tattoo-related complications include a number of cutaneous and systemic infections secondary to breach of the epidermal barrier, acute and delayed inflammatory reactions with different histopathological patterns, the appearance of benign and malignant tumors on tattooed areas of skin, and certain dermatoses triggered by isomorphic phenomena. Piercing-related complications are similar, though some, such as pyogenic skin infections, are much more common due to the delayed wound healing after piercing in certain sites. We must differentiate between complications that are independent of the site of piercing, and specific complications, which are closely related to the body area pierced. The rate of complications after performing piercings or tattoos depends on the experience of the artist, the hygiene techniques applied, and the postprocedural care by the customer. However, some of these complications are unpredictable and depend on factors intrinsic to the patient. In this article, we review the most common decorative techniques of body art, with particular focus on the potential cutaneous complications and their management.

Early versus delayed post-operative bathing or showering to prevent wound complications.

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Toon, Clare D; Sinha, Sidhartha; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2015-07-23

Many people undergo surgical operations during their life-time, which result in surgical wounds. After an operation the incision is closed using stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of the surgical procedure and before the patient leaves the operating theatre, the surgeon covers the closed surgical wound using gauze and adhesive tape or an adhesive tape containing a pad (a wound dressing) that covers the surgical wound. There is currently no guidance about when the wound can be made wet by post-operative bathing or showering. Early bathing may encourage early mobilisation of the patient, which is good after most types of operation. Avoiding post-operative bathing or showering for two to three days may result in accumulation of sweat and dirt on the body. Conversely, early washing of the surgical wound may have an adverse effect on healing, for example by irritating or macerating the wound, and disturbing the healing environment. To compare the benefits (such as potential improvements to quality of life) and harms (potentially increased wound-related morbidity) of early post-operative bathing or showering (i.e. within 48 hours after surgery, the period during which epithelialisation of the wound occurs) compared with delayed post-operative bathing or showering (i.e. no bathing or showering for over 48 hours after surgery) in patients with closed surgical wounds. We searched The Cochrane Wounds Group Specialised Register (30th June 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP). We considered all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of

Interactions of methicillin resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in polymicrobial wound infection.

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Irena Pastar

Full Text Available Understanding the pathology resulting from Staphylococcus aureus and Pseudomonas aeruginosa polymicrobial wound infections is of great importance due to their ubiquitous nature, increasing prevalence, growing resistance to antimicrobial agents, and ability to delay healing. Methicillin-resistant S. aureus USA300 is the leading cause of community-associated bacterial infections resulting in increased morbidity and mortality. We utilized a well-established porcine partial thickness wound healing model to study the synergistic effects of USA300 and P. aeruginosa on wound healing. Wound re-epithelialization was significantly delayed by mixed-species biofilms through suppression of keratinocyte growth factor 1. Pseudomonas showed an inhibitory effect on USA300 growth in vitro while both species co-existed in cutaneous wounds in vivo. Polymicrobial wound infection in the presence of P. aeruginosa resulted in induced expression of USA300 virulence factors Panton-Valentine leukocidin and α-hemolysin. These results provide evidence for the interaction of bacterial species within mixed-species biofilms in vivo and for the first time, the contribution of virulence factors to the severity of polymicrobial wound infections.

Ameliorative effect of dietary genistein on diabetes induced hyper-inflammation and oxidative stress during early stage of wound healing in alloxan induced diabetic mice.

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Eo, Hyeyoon; Lee, Hea-Ji; Lim, Yunsook

2016-09-23

Among the diabetic complications, diabetic foot ulcer due to delayed wound healing is one of the most significant clinical problems. Early inflammatory stage is important for better prognosis during wound healing. Thus, regulation of inflammatory response during early stage of wound healing is main target for complete cutaneous recovery. This study investigated the role of genistein supplementation in inflammation and oxidative stress, which are related to NLRP3 inflammasome, NFκB and Nrf2 activation, during cutaneous wound healing in alloxan-induced diabetic mice. Mice with diabetes with fasting blood glucose (FBG) levels > 250 mg/dl were fed diets with AIN-93G rodent diet containing 0%, 0.025% (LG) or 0.1% (HG) genistein. After 2 weeks of genistein supplementation, excisional wounds were made by biopsy punches (4 mm). Genistein supplementation improved fasting glucose levels and wound closure rate. Moreover, genistein supplementation restored NLRP3 inflammasome (NLRP3, ASC and caspase-1) at the basal level and ameliorated both inflammation (TNFα, iNOS, COX2 and NFκB) and antioxidant defense system (Nrf2, HO-1, GPx, and catalase) during early stage of wound healing in diabetic mice. Taken together, genistein supplementation would be a potential therapeutic nutrient in prevention and treatment of delayed wound healing by modulation of inflammation and oxidative stress during inflammatory stage. Copyright © 2016. Published by Elsevier Inc.

Aging-dependent reduction in glyoxalase 1 delays wound healing.

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Fleming, Thomas H; Theilen, Till-Martin; Masania, Jinit; Wunderle, Marius; Karimi, Jamshid; Vittas, Spiros; Bernauer, Rainer; Bierhaus, Angelika; Rabbani, Naila; Thornalley, Paul J; Kroll, Jens; Tyedmers, Jens; Nawrotzki, Ralph; Herzig, Stephan; Brownlee, Michael; Nawroth, Peter P

2013-01-01

Methylglyoxal (MG), the major dicarbonyl substrate of the enzyme glyoxalase 1 (GLO1), is a reactive metabolite formed via glycolytic flux. Decreased GLO1 activity in situ has been shown to result in an accumulation of MG and increased formation of advanced glycation endproducts, both of which can accumulate during physiological aging and at an accelerated rate in diabetes and other chronic degenerative diseases. To determine the physiological consequences which result from elevated MG levels and the role of MG and GLO1 in aging, wound healing in young (≤12 weeks) and old (≥52 weeks) wild-type mice was studied. Old mice were found to have a significantly slower rate of wound healing compared to young mice (74.9 ± 2.2 vs. 55.4 ± 1.5% wound closure at day 6; 26% decrease; p wounds of young mice, decreased wound healing by 24% compared to untreated mice, whereas application of BSA modified minimally by MG had no effect. Treatment of either young or old mice with aminoguanidine, a scavenger of free MG, significantly increased wound closure by 16% (66.8 ± 1.6 vs. 77.2 ± 3.1%; p wound healing in the old mice was restored to the level observed in the young mice. These findings were confirmed in vitro, as MG reduced migration and proliferation of fibroblasts derived from young and old, wild-type mice. The data demonstrate that the balance between MG and age-dependent GLO1 downregulation contributes to delayed wound healing in old mice. Copyright © 2013 S. Karger AG, Basel.

Biostimulative effects of 809 nm diode laser on cutaneous skin wounds

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Solmaz, Hakan; Gülsoy, Murat; Ülgen, Yekta

2015-03-01

The use of low-level laser therapy (LLLT) for therapeutic purposes in medicine has become widespread recently. There are many studies in literature supporting the idea of therapeutic effects of laser irradiation on biological tissues. The aim of this study is to investigate the biostimulative effect of 809nm infrared laser irradiation on the healing process of cutaneous incisional skin wounds. 3-4 months old male Wistar Albino rats weighing 300 to 350 gr were used throughout this study. Lowlevel laser therapy was applied through local irradiation of 809nm infrared laser on open skin incisional wounds of 1 cm length. Each animal had six identical incisions on their right and left dorsal region symmetrical to each other. The wounds were separated into three groups of control, 1 J/cm2 and 3 J/cm2 of laser irradiation. Two of these six wounds were kept as control group and did not receive any laser application. Rest of the incisions was irradiated with continuous diode laser of 809nm in wavelength and 20mW power output. Two of them were subjected to laser irradiation of 1 J/cm2 and the other two were subjected to laser light with energy density of 3 J/cm2. Biostimulation effects of irradiation were studied by means of tensile strength tests and histological examinations. Wounded skin samples were morphologically examined and removed for mechanical and histological examinations at days 3, 5 and 7 following the laser applications. Three of the six fragments of skin incisions including a portion of peripheral healthy tissue from each animal were subjected to mechanical tests by means of a universal tensile test machine, whereas the other three samples were embedded in paraffin and stained with hematoxylin and eosin for histological examinations. The findings of the study show that tissue repair following laser irradiation of 809nm has been accelerated in terms of tissue morphology, strength and cellular content. These results seem to be consistent with the results of many

Comparison of primary and delayed primary closure in dirty abdominal wounds in terms of frequency of surgical site infection

International Nuclear Information System (INIS)

Aziz, O.B.A.; Ahmed, N.; Butt, M.W.U.D.; Saleem, M.R.

2013-01-01

Objective: Objective of this study was to compare primary and delayed primary wound closure for dirty abdominal wounds in terms of frequency of surgical site infection. Study Design: Randomized Controlled Trial. Place and Duration of Study: Combined Military Hospital, Multan. From 16 Sep 2010 to 15 Mar 2011. Patients and Methods: A total of 110 patients were randomly divided into two groups of 55 patients each using random numbers table. Abdominal wounds of one group were closed primarily and of other group were subjected to delayed primary wound closure. The wounds were then checked for surgical site infection for seven post operative days. Results: A higher frequency of surgical site infection was observed in primary closure group (27.3%) as compared to delayed primary closure group (9.1%) which was statistically significant (p=0.013). Conclusion: Delayed primary closure is superior to primary closure in dirty abdominal wounds in terms of frequency of surgical site infection. (author)

Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

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Maria Giovanna Scioli

Full Text Available Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS reduction, inducible nitric oxide synthase (iNOS and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF, placental growth factor (PlGF and reduction of NADPH-oxidase 4 (Nox4 expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and

Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil: Role of COL1A1

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Almeida, Lucas; Oliveira, Joyce; Guimarães, Luiz Henrique; Carvalho, Edgar M; Blackwell, Jenefer M

2015-01-01

Previous studies have demonstrated a role for wound healing genes in resolution of cutaneous lesions caused by Leishmania spp. in both mice and humans, including the gene FLI1 encoding Friend leukaemia virus integration 1. Reduction of Fli1 expression in mice has been shown to result in up-regulation of collagen type I alpha 1 (Col1a1) and alpha 2 (Col1a2) genes and, conversely, in down-regulation of the matrix metalloproteinase 1 (Mmp1) gene, suggesting that Fli1 suppression is involved in activation of the profibrotic gene program. Here we examined single nucleotide polymorphisms (SNPs) in these genes as risk factors for cutaneous (CL) and mucosal leishmaniasis (ML), and leishmaniasis per se, caused by L. braziliensis in humans. SNPs were genotyped in 168 nuclear families (250 CL; 87 ML cases) and replicated in 157 families (402 CL; 39 ML cases). Family-based association tests (FBAT) showed the strongest association between SNPs rs1061237 (combined P=0.002) and rs2586488 (combined P=0.027) at COL1A1 and CL disease. This contributes to our further understanding of the role of wound healing in the resolution of CL disease, providing potential for therapies modulating COL1A1 via drugs acting on FLI1. PMID:25562121

Influence of phytochemicals in piper betle linn leaf extract on wound healing.

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Lien, Le Thi; Tho, Nguyen Thi; Ha, Do Minh; Hang, Pham Luong; Nghia, Phan Tuan; Thang, Nguyen Dinh

2015-01-01

Wound healing has being extensively investigated over the world. Healing impairment is caused by many reasons including increasing of free-radicals-mediated damage, delaying in granulation tissue formation, reducing in angiogenesis and decreasing in collagen reorganization. These facts consequently lead to chronic wound healing. Piper betle Linn (Betle) leaves have been folklore used as an ingredient of drugs for cutaneous wound treatment. However, the effect of betle leaf on wound healing is not yet well elucidated. In this study, we aimed to investigate the healing efficacy of methanol leaf extract of Piper betle Linn on proliferation of fibroblast NIH3T3 cells as well as full-thickness burn and excision wounds in swiss mice. Scratch wound healing assays were conducted to examine the effects of betle leaf extract on healing activity of fibroblast cells. Burn and excision wounds on swiss mouse skins were created for investigating the wound healing progress caused by the betle leaf extract. Malondialdehyde (MDA) was also evaluated to examine the products of lipid hydroperoxide (LPO) under conditions of with or without betle leaf extract treatment. The results of this study showed that Piper betle Linn leaf extract in methanol increased proliferation of NIH3T3 cells and promoted wound healing in vitro and in vivo with both burn wound and excision wound models. In addition, this extract significant decreased level of malondialdehyde (MDA) in liver of treated-mice compared with that in non-treated mice. Our results suggest that Piper betle Linn can be used as an ingredient in developing natural origin drugs for treatment of cutaneous wounds.

Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

International Nuclear Information System (INIS)

Kioka, Noriyuki; Ito, Takuya; Yamashita, Hiroshi; Uekawa, Natsuko; Umemoto, Tsutomu; Motoyoshi, Soh; Imai, Hiroshi; Takahashi, Kenzo; Watanabe, Hideto; Yamada, Masayasu; Ueda, Kazumitsu

2010-01-01

In the process of tissue injury and repair, epithelial cells rapidly migrate and form epithelial sheets. Vinexin is a cytoplasmic molecule of the integrin-containing cell adhesion complex localized at focal contacts in vitro. Here, we investigated the roles of vinexin in keratinocyte migration in vitro and wound healing in vivo. Vinexin knockdown using siRNA delayed migration of both HaCaT human keratinocytes and A431 epidermoid carcinoma cells in scratch assay but did not affect cell proliferation. Induction of cell migration by scratching the confluent monolayer culture of these cells activated both EGFR and ERK, and their inhibitors AG1478 and U0126 substantially suppressed scratch-induced keratinocyte migration. Vinexin knockdown in these cells inhibited the scratch-induced activation of EGFR, but not that of ERK, suggesting that vinexin promotes cell migration via activation of EGFR. We further generated vinexin (-/-) mice and isolated their keratinocytes. They similarly showed slow migration in scratch assay. Furthermore, vinexin (-/-) mice exhibited a delay in cutaneous wound healing in both the back skin and tail without affecting the proliferation of keratinocytes. Together, these results strongly suggest a crucial role of vinexin in keratinocyte migration in vitro and cutaneous wound healing in vivo.

Monoolein-alginate beads as a platform to promote adenosine cutaneous localization and wound healing.

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Ng, Wing Y; Migotto, Amanda; Ferreira, Thamyres Soares; Lopes, Luciana B

2017-09-01

Alginate beads containing the polar lipid monoolein were developed as a strategy to manage wet wounds by providing improved uptake of excess exudate while releasing adenosine locally for promotion of healing. To obtain monoolein-containing beads, the lipid was mixed with almond oil (2:1w/w), and emulsified within the alginate aqueous dispersion, followed by ionotropic gelation in CaCl 2 solution. Compared to alginate-only, monoolein-alginate systems were 1.44-fold larger, their swelling ability was 1.40-fold higher and adenosine cumulative release was approximately 1.30-fold lower (at 24h). Monoolein-alginate beads were considered safe for topical application as demonstrated by the absence of changes on the viability of reconstructed skin equivalents compared to PBS. Smaller amounts of adenosine were delivered by the beads into and across damaged porcine skin (created by an incisional wound) compared to the drug aqueous solution, and cutaneous localization was favored. More specifically, the beads increased the viable skin layer/receptor phase delivery ratio by approximately 4-fold at 12h post-application. Considering the wide range of adenosine physiological effects and the importance of skin localization for its use in wound healing, these results demonstrate the potential of monoolein-containing beads for localized drug delivery and management of wet wounds. Copyright © 2017 Elsevier B.V. All rights reserved.

NETosis Delays Diabetic Wound Healing in Mice and Humans.

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Fadini, Gian Paolo; Menegazzo, Lisa; Rigato, Mauro; Scattolini, Valentina; Poncina, Nicol; Bruttocao, Andrea; Ciciliot, Stefano; Mammano, Fabio; Ciubotaru, Catalin Dacian; Brocco, Enrico; Marescotti, Maria Cristina; Cappellari, Roberta; Arrigoni, Giorgio; Millioni, Renato; Vigili de Kreutzenberg, Saula; Albiero, Mattia; Avogaro, Angelo

2016-04-01

Upon activation, neutrophils undergo histone citrullination by protein arginine deiminase (PAD)4, exocytosis of chromatin and enzymes as neutrophil extracellular traps (NETs), and death. In diabetes, neutrophils are primed to release NETs and die by NETosis. Although this process is a defense against infection, NETosis can damage tissue. Therefore, we examined the effect of NETosis on the healing of diabetic foot ulcers (DFUs). Using proteomics, we found that NET components were enriched in nonhealing human DFUs. In an independent validation cohort, a high concentration of neutrophil elastase in the wound was associated with infection and a subsequent worsening of the ulcer. NET components (elastase, histones, neutrophil gelatinase-associated lipocalin, and proteinase-3) were elevated in the blood of patients with DFUs. Circulating elastase and proteinase-3 were associated with infection, and serum elastase predicted delayed healing. Neutrophils isolated from the blood of DFU patients showed an increased spontaneous NETosis but an impaired inducible NETosis. In mice, skin PAD4 activity was increased by diabetes, and FACS detection of histone citrullination, together with intravital microscopy, showed that NETosis occurred in the bed of excisional wounds. PAD4 inhibition by Cl-amidine reduced NETting neutrophils and rescued wound healing in diabetic mice. Cumulatively, these data suggest that NETosis delays DFU healing. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Matrix metalloproteinase inhibition delays wound healing and blocks the latent transforming growth factor-beta1-promoted myofibroblast formation and function

DEFF Research Database (Denmark)

Mirastschijski, Ursula; Schnabel, Reinhild; Claes, Juliane

2010-01-01

applied topically to full-thickness skin excisional wounds in rats and its ability to inhibit the promotion of myofibroblast formation and function by the latent transforming-growth factor-beta1 (TGF-beta1). BB-94 delayed wound contraction, as well as all other associated aspects of wound healing examined......, including myofibroblast formation, stromal cell proliferation, blood vessel formation, and epithelial wound coverage. Interestingly, BB-94 dramatically increased the level of latent and active MMP-9. The increased levels of active MMP-9 may eventually overcome the ability of BB-94 to inhibit this MMP...... and may explain why wound contraction and other associated events of wound healing were only delayed and not completely inhibited. BB-94 was also found to inhibit the ability of latent TGF-beta1 to promote the formation and function of myofibroblasts. These results suggest that BB-94 could delay wound...

Neutralisation of uPA with a monoclonal antibody reduces plasmin formation and delays skin wound healing in tPA-deficient mice

DEFF Research Database (Denmark)

Jögi, Annika; Rønø, Birgitte; Lund, Ida K

2010-01-01

Proteolytic degradation by plasmin and metalloproteinases is essential for epidermal regeneration in skin wound healing. Plasminogen deficient mice have severely delayed wound closure as have mice simultaneously lacking the two plasminogen activators, urokinase-type plasminogen activator (u......PA) and tissue-type plasminogen activator (tPA). In contrast, individual genetic deficiencies in either uPA or tPA lead to wound healing kinetics with no or only slightly delayed closure of skin wounds....

The effects of different nutritional measurements on delayed wound healing after hip fracture in the elderly.

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Guo, Jiong Jiong; Yang, Huilin; Qian, Haixin; Huang, Lixin; Guo, Zhongxing; Tang, Tiansi

2010-03-01

It has been well recognized that malnutrition causes wounds to heal inadequately and incompletely. Malnutrition is often observed in the elderly, and it appears to be more severe in patients with hip fracture than in the general aging population. Few prospective studies give a detailed account of the identification and classification of nutritional status in the elderly. The objective of this study was to evaluate the effects of different nutritional measurements on wound healing status after hip fracture in the elderly. From September 2002 to December 2007, 207 hip fracture patients older than 60 y treated surgically were reviewed for preoperative nutritional status. There were 81 males and 126 females with an average age of 75.93 y (62-91 y); 131 cases with femoral neck fractures, 76 cases with intertrochanteric fractures. Parameters indicative of nutritional status (serum albumin, serum transferrin, serum pre-albumin, and total lymphocyte count levels) at the time of admission were assessed, along with anthropometric measurements, Rainey MacDonald nutritional index, and MNA tool. Suture removal was performed on postoperative day 14. Delayed wound healing complicated 46 (22.2%) of the 207 cases. The preoperative serum transferring total lymphocyte count levels, MNA total score, and Rainey MacDonald nutritional index were significantly lower for patients who subsequently had delayed wound healing. When all variables were subjected to multivariate analysis, only total lymphocyte count levels and MNA total score showed significant value in predicting which patients would have delayed wound healing. Through prophylactic antibiotics and adherence to strict aseptic precautions, on follow-up, wound healing was normal in all patients. Patients at risk for delayed wound healing problems after hip fracture can be identified using relatively inexpensive laboratory test such as TLC and MNA tool. The clinician must be aware of the risk values of both measurements. We believe

Topically applied connective tissue growth factor/CCN2 improves diabetic preclinical cutaneous wound healing: potential role for CTGF in human diabetic foot ulcer healing.

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Henshaw, F R; Boughton, P; Lo, L; McLennan, S V; Twigg, S M

2015-01-01

Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r = 0.406; P diabetic foot ulcers.

Delayed pneumothorax after stab wound to thorax and upper abdomen: Truth or myth?

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Zehtabchi, Shahriar; Morley, Eric J; Sajed, Dana; Greenberg, Oded; Sinert, Richard

2009-01-01

Stab wounds to the thorax and upper abdomen have the potential to cause pneumothorax (PTX). When a CXR (CXR) obtained during initial resuscitation is negative, a second CXR (CXR-2) is commonly performed with the goal of identifying delayed PTX. To assess the diagnostic yield of the CXR-2 in identifying delayed PTX. Prospective observational study of patients (age >or=13 years) with stab wounds to the thorax (chest/back) and upper abdomen with suspected PTX, in a level 1 trauma centre. Patients were included if they had a negative initial CXR followed by a repeat CXR 3-6h after the initial one. patients who died, were transferred out of the ED, or received chest tubes before the second CXR. The outcome of interest was delayed PTX. All CXR were read by an attending radiologist. To test the inter-observer agreement, another blinded radiologist reviewed 20% of CXR. Continuous data is presented as mean+/-standard deviation and categorical data as percentages with 95% confidence interval (CI). Kappa statistics were used to measure the inter-observer agreement between radiologists. Between January 2003 and December 2006 a total of 185 patients qualified for the enrollment (mean age: 28+/-10 years, age range: 13-65, 94% male). Only 2 patients (1.1%, 95% CI, 0.4- 4.1%) had PTX on the CXR-2. Both patients received chest tubes. The inter-observer agreement for radiology reports was high (kappa: 0.79). Occurrence of delayed PTX in patients with stab wounds to the thorax and upper abdomen and negative triage CXR is rare.

Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production.

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Atiba, Ayman; Nishimura, Mayumi; Kakinuma, Shizuko; Hiraoka, Takeshi; Goryo, Masanobu; Shimada, Yoshiya; Ueno, Hiroshi; Uzuka, Yuji

2011-06-01

Delayed wound healing is a significant clinical problem in patients who have had previous irradiation. This study investigated the effectiveness of Aloe vera (Av) on acute radiation-delayed wound healing. The effect of Av was studied in radiation-exposed rats compared with radiation-only and control rats. Skin wounds were excised on the back of rats after 3 days of local radiation. Wound size was measured on days 0, 3, 6, 9, and 12 after wounding. Wound tissues were examined histologically and the expressions of transforming growth factor β-1 (TGF-β-1) and basic fibroblast growth factor (bFGF) were examined by immunohistochemistry and reverse-transcription polymerase chain reaction. Wound contraction was accelerated significantly by Av on days 6 and 12 after wounding. Furthermore, the inflammatory cell infiltration, fibroblast proliferation, collagen deposition, angiogenesis, and the expression levels of TGF-β-1 and bFGF were significantly higher in the radiation plus Av group compared with the radiation-only group. These data showed the potential application of Av to improve the acute radiation-delayed wound healing by increasing TGF-β-1 and bFGF production. Copyright © 2011 Elsevier Inc. All rights reserved.

Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately.

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Shi, Yan; Shu, Bin; Yang, Ronghua; Xu, Yingbin; Xing, Bangrong; Liu, Jian; Chen, Lei; Qi, Shaohai; Liu, Xusheng; Wang, Peng; Tang, Jinming; Xie, Julin

2015-06-16

Wnt and Notch signaling pathways are critically involved in relative cell fate decisions within the development of cutaneous tissues. Moreover, several studies identified the above two pathways as having a significant role during wound healing. However, their biological effects during cutaneous tissues repair are unclear. We employed a self-controlled model (Sprague-Dawley rats with full-thickness skin wounds) to observe the action and effect of Wnt/β-catenin and Notch signalings in vivo. The quality of wound repair relevant to the gain/loss-of-function Wnt/β-catenin and Notch activation was estimated by hematoxylin-and-eosin and Masson staining. Immunofluorescence analysis and Western blot analysis were used to elucidate the underlying mechanism of the regulation of Wnt and Notch signaling pathways in wound healing. Meanwhile, epidermal stem cells (ESCs) were cultured in keratinocyte serum-free medium with Jaggedl or in DAPT (N-[(3,5-difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl) to investigate whether the interruption of Notch signaling contributes to the expression of Wnt/β-catenin signaling. The results showed that in vivo the gain-of-function Wnt/β-catenin and Notch activation extended the ability to promote wound closure. We further determined that activation or inhibition of Wnt signaling and Notch signaling can affect the proliferation of ESCs, the differentiation and migration of keratinocytes, and follicle regeneration by targeting c-Myc and Hes1, which ultimately lead to enhanced or delayed wound healing. Furthermore, Western blot analysis suggested that the two pathways might interact in vivo and in vitro. These results suggest that Wnt and Notch signalings play important roles in cutaneous repair by targeting c-Myc and Hes1 separately. What's more, interaction between the above two pathways might act as a vital role in regulation of wound healing.

Tight Skin 2 Mice Exhibit Delayed Wound Healing Caused by Increased Elastic Fibers in Fibrotic Skin.

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Long, Kristen B; Burgwin, Chelsea M; Huneke, Richard; Artlett, Carol M; Blankenhorn, Elizabeth P

2014-09-01

Rationale: The Tight Skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of human disease, including tight skin, excessive collagen deposition, alterations in the extracellular matrix (ECM), increased elastic fibers, and occurrence of antinuclear antibodies with age. A tight skin phenotype is observed by 2 weeks of age, but measurable skin fibrosis is only apparent at 10 weeks. We completed a series of wound healing experiments to determine how fibrosis affects wound healing in Tsk2/+ mice compared with their wild-type (WT) littermates. Method: We performed these experiments by introducing four 4 mm biopsy punched wounds on the back of each mouse, ventral of the midline, and observed wound healing over 10 days. Tsk2/+ mice showed significantly delayed wound healing and increased wound size compared with the WT littermates at both 5 and 10 weeks of age. We explored the potential sources of this response by wounding Tsk2/+ mice that were genetically deficient either for the NLRP3 inflammasome (a known fibrosis mediator), or for elastic fibers in the skin, using a fibulin-5 knockout. Conclusion: We found that the loss of elastic fibers restores normal wound healing in the Tsk2/+ mouse and that the loss of the NLRP3 inflammasome had no effect. We conclude that elastic fiber dysregulation is the primary cause of delayed wound healing in the Tsk2/+ mouse and therapies that promote collagen deposition in the tissue matrix in the absence of elastin deposition might be beneficial in promoting wound healing in SSc and other diseases.

The Reparative Abilities of Menstrual Stem Cells Modulate the Wound Matrix Signals and Improve Cutaneous Regeneration

Directory of Open Access Journals (Sweden)

Jimena Cuenca

2018-05-01

expression of VEGF (1.42-fold among other factors, translating an important conversion of the matrix signals in the wound site. Furthermore, histological analysis of the wound tissue from MenSCs-treated group displayed a more mature robust vascular network and a genuinely higher collagen content confirming the pro-angiogenic and reparative effect of MenSCs treatment. In conclusion, the superior clonogenicity, immunosuppressive and migration potential in combination with specific paracrine signature of MenSCs, resulted in an enhanced wound healing and cutaneous regeneration process.

[Aortodigestive fistula and septic wound of the lower leg. A case report].

Science.gov (United States)

Sommier, B; Casoli, V; Gachie, E; Weigert, R; Castède, J-C

2013-06-01

An aortodigestive fistula can be revealed by a peripheral septic wound when patient have aortic endovascular prosthesis. Our clinical case is about a 69-year-old patient with an abscess of the lateral aspect of his left lower limb. He has been treated few years ago for an aorto-abdominal anevrysm by an aortobifemoral prosthesis. In spite of a negative initial assessment for an aortodigestive fistula, anaerobic germs were found into the abscess. The initial treatment associated debridement, negative pressure therapy, dermal substitute and a split thickness skin graft for the loss of cutaneous substance. Months later, in front of an unexplained skin healing delay and fever, we realised new assessment bringing to light an aortodigestive fistula. Furthermore, the local bacterial samples from the wound and the hemocultures found both a lot of Escherichia Coli. The change of the aorto-bifemoral prosthesis and the cure of the aortodigestive fistula allowed the complete healing of the loss of cutaneous substance of the leg. The aortodigestive fistulas have a very high mortality. Because of their difficult diagnosis, their clinical suspicion has to start a complete medical assessment. Every septic wound when patients have vascular prosthesis is suggestive of an aortodigestive fistula. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Intractable Postoperative Wounds Caused by Self-Inflicted Trauma in a Patient with Cutaneous Munchausen Syndrome Presenting as a Pyoderma Gangrenosum-Like Lesion

Directory of Open Access Journals (Sweden)

Keiko Inui

2016-04-01

Full Text Available A 50-year-old Japanese woman consulted the emergency department of our hospital for bleeding due to an intractable postoperative wound on the lower abdomen; the postoperative wound was owing to a laparoscopic cholecystectomy performed 1 year previously for acute cholecystitis. She presented with a painful ulcer on her right lower abdomen. She also presented with multiple scars, skin grafts on the extremities, and a missing left lower leg, the causes for all of which were unexplained. The results of her blood test were normal, except for the hemoglobin level. Histology of the skin biopsy specimen from the ulcer did not show any specific findings. The previous surgeon who had performed the laparoscopic cholecystectomy revealed that surgical wound dehiscence had occurred during her admission. After a body restraint had been applied, the ulcer improved. Medical records indicated that she had been admitted to the department of plastic surgery at our hospital for skin grafting of a leg ulcer. During that admission, she refused to consult with the department of psychiatry, although the staff suspected mental disorders. Therefore, we diagnosed her with cutaneous Munchausen syndrome. After vacuum-assisted closure (VAC therapy had been performed to prevent her from traumatizing the ulcer again, it rapidly became granulated and reepithelialized. Munchausen syndrome is characterized by feigning physical symptoms to seek attention. Patients self-inflict numerous lesions, keep getting admitted to different hospitals, and feign acute illness, usually spectacular diseases. VAC therapy may be effective for preventing patients with cutaneous Munchausen syndrome from traumatizing their wounds.

Intractable Postoperative Wounds Caused by Self-Inflicted Trauma in a Patient with Cutaneous Munchausen Syndrome Presenting as a Pyoderma Gangrenosum-Like Lesion.

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Inui, Keiko; Hanafusa, Takaaki; Namiki, Takeshi; Ueno, Makiko; Igawa, Ken; Yokozeki, Hiroo

2016-01-01

A 50-year-old Japanese woman consulted the emergency department of our hospital for bleeding due to an intractable postoperative wound on the lower abdomen; the postoperative wound was owing to a laparoscopic cholecystectomy performed 1 year previously for acute cholecystitis. She presented with a painful ulcer on her right lower abdomen. She also presented with multiple scars, skin grafts on the extremities, and a missing left lower leg, the causes for all of which were unexplained. The results of her blood test were normal, except for the hemoglobin level. Histology of the skin biopsy specimen from the ulcer did not show any specific findings. The previous surgeon who had performed the laparoscopic cholecystectomy revealed that surgical wound dehiscence had occurred during her admission. After a body restraint had been applied, the ulcer improved. Medical records indicated that she had been admitted to the department of plastic surgery at our hospital for skin grafting of a leg ulcer. During that admission, she refused to consult with the department of psychiatry, al-though the staff suspected mental disorders. Therefore, we diagnosed her with cutaneous Munchausen syndrome. After vacuum-assisted closure (VAC) therapy had been performed to prevent her from traumatizing the ulcer again, it rapidly became granulated and reepithelialized. Munchausen syndrome is characterized by feigning physical symptoms to seek attention. Patients self-inflict numerous lesions, keep getting admitted to different hospitals, and feign acute illness, usually spectacular diseases. VAC therapy may be effective for preventing patients with cutaneous Munchausen syndrome from traumatizing their wounds.

Rapid healing of cutaneous leishmaniasis by high-frequency electrocauterization and hydrogel wound care with or without DAC N-055: a randomized controlled phase IIa trial in Kabul.

Directory of Open Access Journals (Sweden)

Ahmad Fawad Jebran

2014-02-01

Full Text Available Anthroponotic cutaneous leishmaniasis (CL due to Leishmania (L. tropica infection is a chronic, frequently disfiguring skin disease with limited therapeutic options. In endemic countries healing of ulcerative lesions is often delayed by bacterial and/or fungal infections. Here, we studied a novel therapeutic concept to prevent superinfections, accelerate wound closure, and improve the cosmetic outcome of ACL.From 2004 to 2008 we performed a two-armed, randomized, double-blinded, phase IIa trial in Kabul, Afghanistan, with patients suffering from L. tropica CL. The skin lesions were treated with bipolar high-frequency electrocauterization (EC followed by daily moist-wound-treatment (MWT with polyacrylate hydrogel with (group I or without (group II pharmaceutical sodium chlorite (DAC N-055. Patients below age 5, with facial lesions, pregnancy, or serious comorbidities were excluded. The primary, photodocumented outcome was the time needed for complete lesion epithelialization. Biopsies for parasitological and (immunohistopathological analyses were taken prior to EC (1(st, after wound closure (2(nd and after 6 months (3(rd. The mean duration for complete wound closure was short and indifferent in group I (59 patients, 43.1 d and II (54 patients, 42 d; p = 0.83. In patients with Leishmania-positive 2(nd biopsies DAC N-055 caused a more rapid wound epithelialization (37.2 d vs. 58.3 d; p = 0.08. Superinfections occurred in both groups at the same rate (8.8%. Except for one patient, reulcerations (10.2% in group I, 18.5% in group II; p = 0.158 were confined to cases with persistent high parasite loads after healing. In vitro, DAC N-055 showed a leishmanicidal effect on pro- and amastigotes.Compared to previous results with intralesional antimony injections, the EC plus MWT protocol led to more rapid wound closure. The tentatively lower rate of relapses and the acceleration of wound closure in a subgroup of patients with parasite persistence warrant

Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing

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Das, Subhamoy; Baker, Aaron B.

2016-01-01

Wound healing is an intricate process that requires complex coordination between many cell types and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care, the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds, including excessive inflammation, ischemia, scarring, and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or are currently used in clinical practice. PMID:27843895

Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing

Directory of Open Access Journals (Sweden)

Subhamoy Das

2016-10-01

Full Text Available Wound healing is an intricate process that requires complex coordination between many cells and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care; the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds including excessive inflammation, ischemia, scarring and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or currently used in clinical practice.

Early versus delayed dressing removal after primary closure of clean and clean-contaminated surgical wounds.

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Toon, Clare D; Lusuku, Charnelle; Ramamoorthy, Rajarajan; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2015-09-03

Most surgical procedures involve a cut in the skin that allows the surgeon to gain access to the deeper tissues or organs. Most surgical wounds are closed fully at the end of the procedure (primary closure). The surgeon covers the closed surgical wound with either a dressing or adhesive tape. The dressing can act as a physical barrier to protect the wound until the continuity of the skin is restored (within about 48 hours) and to absorb exudate from the wound, keeping it dry and clean, and preventing bacterial contamination from the external environment. Some studies have found that the moist environment created by some dressings accelerates wound healing, although others believe that the moist environment can be a disadvantage, as excessive exudate can cause maceration (softening and deterioration) of the wound and the surrounding healthy tissue. The utility of dressing surgical wounds beyond 48 hours of surgery is, therefore, controversial. To evaluate the benefits and risks of removing a dressing covering a closed surgical incision site within 48 hours permanently (early dressing removal) or beyond 48 hours of surgery permanently with interim dressing changes allowed (delayed dressing removal), on surgical site infection. In March 2015 we searched the following electronic databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched the references of included trials to identify further potentially-relevant trials. Two review authors independently identified studies for inclusion. We included all randomised clinical trials (RCTs) conducted with people of any age and sex, undergoing a surgical procedure, who had their wound closed and a dressing applied. We included only trials that compared

Phototherapy improves healing of cutaneous wounds in nourished and undernourished Wistar rats.

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Pinheiro, Antonio Luiz Barbosa; Meireles, Gyselle Cynthia Silva; de Barros Vieira, Alessandro Leonardo; Almeida, Darcy; Carvalho, Carolina Montagn; dos Santos, Jean Nunes

2004-01-01

A wound represents the interruption of the continuity of tissue that is followed by damage or cellular death. Wound healing occurs due to a competitive mechanism between the synthesis and lysis of collagen. Any factor that increases collagen lysis or reduces its synthesis may result in changes in the healing process, i.e., nutritional deficiencies. Phototherapies have been suggested as an effective method to improve wound healing. This study evaluated, histologically, the differences in the healing of cutaneous wounds in nourished and undernourished rats following laser therapy or illumination by polarized light. Fifty nourished or undernourished Wistar rats had a standardized wound created on the dorsum and were divided into 6 subgroups: Group 1--Control (Standard diet; n=5); Group 2--Control (DBR; n=5); Group 3--Standard diet + laser therapy (lambda635nm; 20J/cm2, n=5; or 40J/cm2, n=5); Group 4--Standard diet + Bioptron (lambda400-2000nm; 20J/cm2, n=5; or 40 J/cm2, n=5); Group 5--DBR + laser therapy (lambda635nm; 20J/cm2, n=5; or 40J/cm2, n=5); Group 6--DBR + Bioptron (lambda400-2000nm; 20J/cm2, n=5; or 40 J/cm2, n=5). The first application of the treatment was carried out immediately after surgery and repeated every 24 h during 7 days. Specimens were routinely processed (wax, cut and stained with H&E and Picrosirius stain) and analyzed under light microscopy. Analysis included re-epithelization, inflammatory infiltrate, and fibroblastic proliferation. Picrosirius stained slides were used to perform descriptive analysis of the collagen fibers. The results showed the best results for nourished and undernourished groups treated with polarized light at a dose of 20J/cm2 and the undernourished groups irradiated with the laser light. It is concluded that the nutritional status influenced the progression of the healing process as well as the quality of the healed tissue and that the use of both modalities of phototherapy resulted in a positive biomodulatory effect in

RIP2: A novel player in the regulation of keratinocyte proliferation and cutaneous wound repair?

International Nuclear Information System (INIS)

Adams, Stephanie; Valchanova, Ralitsa S.; Munz, Barbara

2010-01-01

We could recently demonstrate an important role of receptor interacting protein 4 (RIP4) in the regulation of keratinocyte differentiation. Now, we analyzed a potential role of the RIP4 homolog RIP2 in keratinocytes. Specifically, we demonstrate here that rip2 expression is induced by scratch-wounding and after the induction of differentiation in these cells. Furthermore, serum growth factors and cytokines can induce rip2, with TNF-α-dependent induction being dependent on p38 MAPK. In addition, we demonstrate that scratch-induced upregulation of rip2 expression is completely blocked by the steroid dexamethasone. Since we also show that RIP2 is an important player in the regulation of keratinocyte proliferation, these data suggest that inhibition of rip2 upregulation after wounding might contribute to the reduced and delayed wound re-epithelialization phenotype seen in glucocorticoid-treated patients.

Factors Affecting Wound Healing

OpenAIRE

Guo, S.; DiPietro, L.A.

2010-01-01

Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutane...

Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing.

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Rodriguez-Menocal, Luis; Shareef, Shahjahan; Salgado, Marcela; Shabbir, Arsalan; Van Badiavas, Evangelos

2015-03-13

Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process.

Poly (3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) hydrogel promotes angiogenesis and collagen deposition during cutaneous wound healing in rats.

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Gumel, Ahmad Mohammed; Razaif-Mazinah, Mohd Rafais Mohd; Anis, Siti Nor Syairah; Annuar, Mohamad Suffian Mohamad

2015-07-08

Wound management and healing in several physiological or pathological conditions, particularly when comorbidities are involved, usually proves to be difficult. This presents complications leading to socio-economic and public health burdens. The accelerative wound healing potential of biocompatible poly(3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) (PHA-PCL) composite hydrogel is reported herein. The biosynthesized PHA-PCL macromer was cross-linked with PEGMA to give a hydrogel. Twenty-four rats weighing 200-250 g each were randomly assigned to four groups of six rats. Rats in group I (negative control) were dressed with sterilized gum acacia paste in 10% normal saline while PEGMA-alone hydrogel (PH) was used to dress group II (secondary control) rats. Group III rats were dressed with PHAs-PCL cross-linked PEGMA hydrogel (PPH). For the positive control (group IV), the rats were dressed with Intrasite(®) gel. Biochemical, histomorphometric and immunohistomorphometric analyses revealed a significant difference in area closure and re-epithelialization on days 7 and 14 in PPH or Intrasite(®) gel groups compared to gum acacia or PEGMA-alone groups. Furthermore, wounds dressed with PPH or Intrasite(®) gel showed evident collagen deposition, enhanced fibrosis and extensively organized angiogenesis on day 14 compared to the negative control group. While improvement in wound healing of the PH dressed group could be observed, there was no significant difference between the negative control group and the PH dressed group in any of the tests. The findings suggested that topical application of PPH accelerated the rats' wound healing process by improving angiogenesis attributed to the increased microvessel density (MVD) and expressions of VEGF-A in tissue samples. Thus, PPH has been demonstrated to be effective in the treatment of cutaneous wounds in rats, and could be a potential novel agent in the management and acceleration of wound healing in humans and animals.

Ovariectomy delays alveolar wound healing after molar extractions in rats.

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Pereira, Michele Conceição; Zecchin, Karina Gottardello; Campagnoli, Eduardo Bauml; Jorge, Jacks

2007-11-01

This study was conducted to investigate the morphological effects of the absence of estrogen on alveolar wound healing of young female rats after tooth extraction. A total of 60 4- to 6-week-old female rats underwent bilateral ovariectomy (OVX) or sham operations. Three weeks later, the first mandibular molars were extracted. Subsequently, the animals were killed by cervical dislocation 3, 5, 7, 14, 21, or 28 days after tooth extraction. The mandibles were removed, and serial transversal sections of mesial alveolus of the first mandibular molars were obtained for histometric analysis. OVX sockets showed significant increases in fibroblasts and collagen content 3 and 5 days after the extractions, followed by significant decreases in these parameters in the subsequent periods. In accordance with the decreased collagen content in the latest period of healing, new bone formation was significantly reduced in the OVX animals. These findings suggest that the initial molecular changes observed in the absence of estrogen lead to delayed alveolar wound healing.

Comment on "Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing".

Science.gov (United States)

Li, Hongling; Cao, Cong; Huang, Ai; Man, Yi

2015-01-01

A recent paper in this journal, presented a novel method by topical application of growth factors in stimulating diabetic cutaneous wound healing that caught our attention. We believe that the experimental method in the article is efficient and creative, but it also has some controversies and shortcomings to be discussed. We noted that the authors used "Tegaderm" as a semiocclusive dressing film and stated that it exerted a "splinting effect" on the wound margins and controlled contraction. Indeed, the "Tegaderm" itself can serve as a dressing film to isolate the wound bed with outside environments while the "splinting effect" is mainly achieved by adding silicone splints around the wound. Considering the unique properties of silicone splints and "Tegaderm," our experimental group propose an alternative method named "combined-suturing" technique that is not only suturing the silicone splints but also securing the "Tegaderm" around the wound. The specific reasons and operative procedures are explained in detail in this letter.

Factors Affecting Wound Healing

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Guo, S.; DiPietro, L.A.

2010-01-01

Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

Development of a Porcine Delayed Wound-Healing Model and Its Use in Testing a Novel Cell-Based Therapy

International Nuclear Information System (INIS)

Hadad, Ivan; Johnstone, Brian H.; Brabham, Jeffrey G.; Blanton, Matthew W.; Rogers, Pamela I.; Fellers, Cory; Solomon, James L.; Merfeld-Clauss, Stephanie; DesRosiers, Colleen M.; Dynlacht, Joseph R.; Coleman, John J.; March, Keith L.

2010-01-01

Purpose: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. Methods and Materials: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm 2 wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. Results: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. Conclusions: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

Distal Based Sural Fascio-Cutaneous Flap: A Practical Limb Saviour for Wounds of War and Peace

International Nuclear Information System (INIS)

Tahirkheli, M. U. I.; Ellahi, I.; Dar, M. F.; Sharif, A.

2016-01-01

Objective: To determine the effect of mechanism of injury on wound healing, and on the viability and success of distally based sural flap when used for the coverage of defects of lower leg, ankle and foot. Study Design: Descriptive study. Place and Duration of Study: Department of Surgery, Combined Military Hospital, Peshawar and Khariyan, from January 2012 to December 2014. Methodology: Patients with soft tissue defects over the distal leg, ankle and foot were selected by purposive sampling technique and divided into 2 groups of 19 patients each. Group A(road traffic accidents) and group B (war injuries). Sural fascio-cutaneous flap was the reconstructive tool used in all the cases using single technique by the same surgical team; and time for recipient site preparation, size of the defect, graft survival, its healing time and complications, were studied. Result: The mean age of the 38 patients in the study was 28.2 ±13.4 years. There were 36 male and 2 female patients. The most common site of injury encountered was leg (n=20) followed by foot (n=11) and ankle (n=5). Maximum wound size seen in group A was 10 x 12 cm and in group B was 15 x 38 cm. Recovery was uneventful in 17/19 cases of group Awhile 7/19 in group B and with no graft failure. Superficial epidermolysis was seen in 2 and 8 cases in group A and B respectively while edge necrosis of the flap was observed in group B only (n=4). Healing time on average was 2 to 3 weeks in group A, and 4 to 5 weeks in group B. Conclusion: Soft tissue defects of the distal lower extremity as a result of war injuries and road traffic accidents have different dynamics in terms of wound size, time of wound healing, wound complications and functional outcome; but distal based sural flap has promising Result in both situations. (author)

Complications in skin grafts when continuing antithrombotic therapy prior to cutaneous surgery requiring skin grafting

DEFF Research Database (Denmark)

Jarjis, Reem Dina; Jørgensen, Lone; Finnerup, Kenneth

2015-01-01

Abstract The risk of postoperative bleeding and wound healing complications in skin grafts among anticoagulated patients undergoing cutaneous surgery has not been firmly established. The objective was to examine the literature and assess the risk of postoperative bleeding or wound healing...... complications in skin grafts among anticoagulated patients, compared with patients who discontinue or patients who are not receiving antithrombotic therapy prior to cutaneous surgery requiring skin grafting. A systematic review examining the effect of antithrombotic therapy on cutaneous surgery was performed...... studies were of prospective and retrospective design. Most of the reviewed studies suggest that the use of antithrombotic therapy can increase the risk of bleeding complications in skin grafts. These complications are only wound threatening and not life threatening. Therefore, this is of concern mostly...

Optimizing Wound Bed Preparation With Collagenase Enzymatic Debridement

Science.gov (United States)

McCallon, Stanley K.; Weir, Dorothy; Lantis, John C.

2015-01-01

Difficult-to-heal and chronic wounds affect tens of millions of people worldwide. In the U.S. alone, the direct cost for their treatment exceeds $25 billion. Yet despite advances in wound research and treatment that have markedly improved patient care, wound healing is often delayed for weeks or months. For venous and diabetic ulcers, complete wound closure is achieved in as few as 25%–50% of chronic or hard-to-heal wounds. Wound bed preparation and the consistent application of appropriate and effective debridement techniques are recommended for the optimized treatment of chronic wounds. The TIME paradigm (Tissue, Inflammation/infection, Moisture balance and Edge of wound) provides a model to remove barriers to healing and optimize the healing process. While we often think of debridement as an episodic event that occurs in specific care giver/patient interface. There is the possibility of a maintenance debridement in which the chronic application of a medication can assist in both the macroscopic and microscopic debridement of a wound. We review the various debridement therapies available to clinicians in the United States, and explore the characteristics and capabilities of clostridial collagenase ointment (CCO), a type of enzymatic debridement, that potentially allows for epithelialization while debriding. It appears that in the case of CCO it may exert this influences by removal of the necrotic plug while promoting granulation and sustaining epithelialization. It is also easily combined with other methods of debridement, is selective to necrotic tissue, and has been safely used in various populations. We review the body of evidence has indicated that this concept of maintenance debridement, especially when combined episodic debridement may add a cost an efficacious, safe and cost-effective choice for debridement of cutaneous ulcers and burn wounds and it will likely play an expanding role in all phases of wound bed preparation. PMID:26442207

Predictors of delayed wound healing after endovascular therapy of isolated infrapopliteal lesions underlying critical limb ischemia in patients with high prevalence of diabetes mellitus and hemodialysis.

Science.gov (United States)

Shiraki, T; Iida, O; Takahara, M; Soga, Y; Yamauchi, Y; Hirano, K; Kawasaki, D; Fujihara, M; Utsunomiya, M; Tazaki, J; Yamaoka, T; Shintani, Y; Suematsu, N; Suzuki, K; Miyashita, Y; Tsuchiya, T; Uematsu, M

2015-05-01

Acceptable limb salvage rates underlie the widespread use of endovascular therapy (EVT) for patients with critical limb ischemia (CLI) secondary to isolated infrapopliteal lesions; however, post-EVT delayed wound healing remains a challenge. Predictors of delayed wound healing and their use in risk stratification of EVT in patients with CLI due to isolated infrapopliteal lesions are explored. This was a retrospective multicenter study. 871 consecutive critically ischemic limbs were studied. There was tissue loss in 734 patients (age: 71 ± 10 years old; 71% male) who had undergone EVT between April 2004 and December 2012. The wound healing rate after EVT was estimated by the Kaplan-Meier method. The association between baseline characteristics and delayed wound healing was assessed by the Cox proportional hazard model. Diabetes mellitus and regular dialysis were present in 75% (553/734) and 64% (476/734) of patients, respectively; 67% of limbs (585/871) had Rutherford class 5 CLI; 8% (67/871) of wounds were located in the heel only; 25% (219/871) of limbs had Rutherford 6 (involving not only the heel); and 42% (354/871) of wounds were complicated by infection. The rate of freedom from major amputation at 1 year reached 88%, whereas the wound healing rate was 67%. Median time to wound healing was 146 days. By multivariate analysis, non-ambulatory status (hazard ratio [HR], 1.58; 95% confidence interval [CI] 1.31-1.91) serum albumin wound infection (HR 1.24; 95% CI 1.03-1.50), EVT not based on angiosome concept (HR 1.28; 95% CI 1.06-1.55), and below the ankle (BTA) 0 vessel runoff after EVT (HR 1.45; 95% CI 1.14-1.86) were independent predictors of delayed wound healing. Non-ambulatory status, low albumin level, Rutherford 6 (not only heel), wound infection, indirect intervention, and poor BTA runoff were independent predictors for delayed wound healing after EVT in patients with CLI secondary to infrapopliteal lesions, and their use in risk stratification allows

Topical Erythropoietin Treatment Accelerates the Healing of Cutaneous Burn Wounds in Diabetic Pigs Through an Aquaporin-3-Dependent Mechanism.

Science.gov (United States)

Hamed, Saher; Ullmann, Yehuda; Egozi, Dana; Keren, Aviad; Daod, Essam; Anis, Omer; Kabha, Hoda; Belokopytov, Mark; Ashkar, Manal; Shofti, Rona; Zaretsky, Asaph; Schlesinger, Michal; Teot, Luc; Liu, Paul Y

2017-08-01

We have previously reported that the topical application of erythropoietin (EPO) to cutaneous wounds in rats and mice with experimentally induced diabetes accelerates their healing by stimulating angiogenesis, reepithelialization, and collagen deposition, and by suppressing the inflammatory response and apoptosis. Aquaporins (AQPs) are integral membrane proteins whose function is to regulate intracellular fluid hemostasis by enabling the transport of water and glycerol. AQP3 is the AQP that is expressed in the skin where it facilitates cell migration and proliferation and re-epithelialization during wound healing. In this report, we provide the results of an investigation that examined the contribution of AQP3 to the mechanism of EPO action on the healing of burn wounds in the skin of pigs with experimentally induced type 1 diabetes. We found that topical EPO treatment of the burns accelerated their healing through an AQP3-dependent mechanism that activates angiogenesis, triggers collagen and hyaluronic acid synthesis and the formation of the extracellular matrix (ECM), and stimulates reepithelialization by keratinocytes. We also found that incorporating fibronectin, a crucial constituent of the ECM, into the topical EPO-containing gel, can potentiate the accelerating action of EPO on the healing of the burn injury. © 2017 by the American Diabetes Association.

Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice.

Science.gov (United States)

Demyanenko, Ilya A; Popova, Ekaterina N; Zakharova, Vlada V; Ilyinskaya, Olga P; Vasilieva, Tamara V; Romashchenko, Valeria P; Fedorov, Artem V; Manskikh, Vasily N; Skulachev, Maxim V; Zinovkin, Roman A; Pletjushkina, Olga Yu; Skulachev, Vladimir P; Chernyak, Boris V

2015-07-01

The process of skin wound healing is delayed or impaired in aging animals. To investigate the possible role of mitochondrial reactive oxygen species (mtROS) in cutaneous wound healing of aged mice, we have applied the mitochondria-targeted antioxidant SkQ1. The SkQ1 treatment resulted in accelerated resolution of the inflammatory phase, formation of granulation tissue, vascularization and epithelization of the wounds. The wounds of SkQ1-treated mice contained increased amount of myofibroblasts which produce extracellular matrix proteins and growth factors mediating granulation tissue formation. This effect resembled SkQ1-induced differentiation of fibroblasts to myofibroblast, observed earlierin vitro. The Transforming Growth Factor beta (TGFb) produced by SkQ1-treated fibroblasts was found to stimulated motility of endothelial cells in vitro, an effect which may underlie pro-angiogenic action of SkQ1 in the wounds. In vitro experiments showed that SkQ1 prevented decomposition of VE-cadherin containing contacts and following increase in permeability of endothelial cells monolayer, induced by pro-inflammatory cytokine TNF. Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1. Our findings point to an important role of mtROS in pathogenesis of age-related chronic wounds.

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

Directory of Open Access Journals (Sweden)

Savita Khanna

2010-03-01

Full Text Available 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.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.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.

Delayed wound healing in aged skin rat models after thermal injury is associated with an increased MMP-9, K6 and CD44 expression.

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Simonetti, Oriana; Oriana, Simonetti; Lucarini, Guendalina; Guendalina, Lucarini; Cirioni, Oscar; Oscar, Cirioni; Zizzi, Antonio; Antonio, Zizzi; Orlando, Fiorenza; Fiorenza, Orlando; Provinciali, Mauro; Mauro, Provinciali; Di Primio, Roberto; Roberto, Di Primio; Giacometti, Andrea; Andrea, Giacometti; Offidani, Annamaria; Annamaria, Offidani

2013-06-01

Age-related differences in wound healing have been documented but little is known about the wound healing mechanism after burns. Our aim was to compare histological features and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9), collagen IV, K6 and CD44 in the burn wound healing process in aged and young rats. Following burns the appearance of the wound bed in aged rats had progressed but slowly, resulting in a delayed healing process compared to the young rats. At 21 days after injury, epithelial K6, MMP-9 and CD44 expression was significantly increased in aged rats with respect to young rats; moreover, in the aged rat group we observed a not fully reconstituted basement membrane. K6, MMP-9 and CD44 expression was significantly increased in wounded skin compared to unwounded skin both in young and aged rats. We hypothesise that delayed burn skin wound healing process in the aged rats may represent an age dependent response to injury where K6, MMP-9 and CD44 play a key role. It is therefore possible to suggest that these factors contribute to the delayed wound healing in aged skin and that modulation could lead to a better and faster recovery of skin damage in elderly. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Comment on “Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing”

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Hongling Li

2015-01-01

Full Text Available A recent paper in this journal, presented a novel method by topical application of growth factors in stimulating diabetic cutaneous wound healing that caught our attention. We believe that the experimental method in the article is efficient and creative, but it also has some controversies and shortcomings to be discussed. We noted that the authors used “Tegaderm” as a semiocclusive dressing film and stated that it exerted a “splinting effect” on the wound margins and controlled contraction. Indeed, the “Tegaderm” itself can serve as a dressing film to isolate the wound bed with outside environments while the “splinting effect” is mainly achieved by adding silicone splints around the wound. Considering the unique properties of silicone splints and “Tegaderm,” our experimental group propose an alternative method named “combined-suturing” technique that is not only suturing the silicone splints but also securing the “Tegaderm” around the wound. The specific reasons and operative procedures are explained in detail in this letter.

Acute effects of low-level laser therapy (660 nm) on oxidative stress levels in diabetic rats with skin wounds.

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Denadai, Amanda Silveira; Aydos, Ricardo Dutra; Silva, Iandara Schettert; Olmedo, Larissa; de Senna Cardoso, Bruno Mendonça; da Silva, Baldomero Antonio Kato; de Carvalho, Paulo de Tarso Camillo

2017-09-01

Laser therapy influences oxidative stress parameters such as the activity of antioxidant enzymes and the production of reactive oxygen species. To analyze the effects of low-level laser therapy on oxidative stress in diabetics rats with skin wounds. Thirty-six animals were divided into 4 groups: NDNI: non-diabetic rats with cutaneous wounds that not received laser therapy; NDI: non-diabetic rats with cutaneous wounds that received laser therapy; DNI: diabetic rats with skin wounds who did not undergo laser therapy; DI: rats with diabetes insipidus and cutaneous wounds and received laser therapy. The animals were treated with LLLT (660 nm, 100 mW, 6 J/cm, spot size 0.028 cm). On the day of killing the animals, tissue-wrapped cutaneous wounds were collected and immediately frozen, centrifuged, and stored to analyze malondialdehyde (MDA) levels. Significant difference was observed within the groups of MDA levels (ANOVA, p = 0.0001). Tukey's post-hoc test showed significantly lower values of MDA in irradiated tissues, both in diabetic and non-diabetic rats. ANOVA of the diabetic group revealed a significant difference (p < 0.01) when all groups, except NDI and DI, were compared. LLLT was effective in decreasing MDA levels in acute surgical wounds in diabetic rats.

Age-related aspects of cutaneous wound healing: a mini-review.

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Sgonc, Roswitha; Gruber, Johann

2013-01-01

As the aging population in developed countries is growing in both numbers and percentage, the medical, social, and economic burdens posed by nonhealing wounds are increasing. Hence, it is all the more important to understand the mechanisms underlying age-related impairments in wound healing. The purpose of this article is to give a concise overview of (1) normal wound healing, (2) alterations in aging skin that have an impact on wound repair, (3) alterations in the repair process of aged skin, and (4) general factors associated with old age that might impair wound healing, with a focus on the literature of the last 10 years. Copyright © 2012 S. Karger AG, Basel.

Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing.

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Turk, Harmony F; Monk, Jennifer M; Fan, Yang-Yi; Callaway, Evelyn S; Weeks, Brad; Chapkin, Robert S

2013-05-01

Epidermal growth factor receptor (EGFR)-mediated signaling is required for optimal intestinal wound healing. Since n-3 polyunsaturated fatty acids (PUFA), specifically docosahexaenoic acid (DHA), alter EGFR signaling and suppress downstream activation of key signaling pathways, we hypothesized that DHA would be detrimental to the process of intestinal wound healing. Using a mouse immortalized colonocyte model, DHA uniquely reduced EGFR ligand-induced receptor activation, whereas DHA and its metabolic precursor eicosapentaenoic acid (EPA) reduced wound-induced EGFR transactivation compared with control (no fatty acid or linoleic acid). Under wounding conditions, the suppression of EGFR activation was associated with a reduction in downstream activation of cytoskeletal remodeling proteins (PLCγ1, Rac1, and Cdc42). Subsequently, DHA and EPA reduced cell migration in response to wounding. Mice were fed a corn oil-, DHA-, or EPA-enriched diet prior to intestinal wounding (2.5% dextran sodium sulfate for 5 days followed by termination after 0, 3, or 6 days of recovery). Mortality was increased in EPA-fed mice and colonic histological injury scores were increased in EPA- and DHA-fed mice compared with corn oil-fed (control) mice. Although kinetics of colonic EGFR activation and downstream signaling (PLCγ1, Rac1, and Cdc42) were delayed by both n-3 PUFA, colonic repair was increased in EPA- relative to DHA-fed mice. These results indicate that, during the early response to intestinal wounding, DHA and EPA uniquely delay the activation of key wound-healing processes in the colon. This effect is mediated, at least in part, via suppression of EGFR-mediated signaling and downstream cytoskeletal remodeling.

Remote effects of extracorporeal shock wave therapy on cutaneous microcirculation.

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Kisch, Tobias; Sorg, Heiko; Forstmeier, Vinzent; Knobloch, Karsten; Liodaki, Eirini; Stang, Felix; Mailänder, Peter; Krämer, Robert

2015-11-01

Extracorporeal shock wave treatment (ESWT) has proven its clinical benefits in different fields of medicine. Tissue regeneration and healing is improved after shock wave treatment. Even in the case of burn wounds angiogenesis and re-epithelialization is accelerated, but ESWT in extensive burn wounds is impracticable. High energy ESWT influences cutaneous microcirculation at body regions remote from application site. Eighteen Sprague Dawley rats were randomly assigned to two groups and received either high energy ESWT (Group A: total 1000 impulses, 10 J) or placebo shock wave treatment (Group B: 0 impulses, 0 J), applied to the dorsal lower leg of the hind limb. Ten minutes later microcirculatory effects were assessed at the contralateral lower leg of the hind limb (remote body region) by combined Laser-Doppler-Imaging and Photospectrometry. In Group A cutaneous capillary blood velocity was significantly increased by 152.8% vs. placebo ESWT at the remote body location (p = 0.01). Postcapillary venous filling pressure remained statistically unchanged (p > 0.05), while cutaneous tissue oxygen saturation increased by 12.7% in Group A (p = 0.220). High energy ESWT affects cutaneous hemodynamics in body regions remote from application site in a standard rat model. The results of this preliminary study indicate that ESWT might be beneficial even in disseminated and extensive burn wounds by remote shock wave effects and should therefore be subject to further scientific evaluation. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Wound complications and clinical results of electrocautery versus a scalpel to create a cutaneous flap in thyroidectomy: a prospective randomized trial.

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Uludag, Mehmet; Yetkin, Gurkan; Ozel, Alper; Ozguven, M Banu Yilmaz; Yener, Senay; Isgor, Adnan

2011-08-01

The use of electrocautery for tissue dissection is becoming increasingly popular, despite the associated risk of poor wound healing and excessive scarring. We conducted this study to compare the wound complications and early and late clinical results resulting from electrocautery versus the scalpel to create a cutaneous flap during thyroidectomy. The subjects of this study were 100 patients, randomized prospectively to either a scalpel group (group S, n = 50) or an electrocautery group (group E, n = 50). Thickness of tissue damage, postoperative thickness of the flap, discomfort in the neck 7 days after surgery, and hypoesthesia and paresthesia in the neck 3 months after surgery were significantly higher in group E than in group S. There were no significant differences in overall postoperative wound complications, postoperative pain, satisfaction with the cosmetic result, or overall outcome of the operation between the groups. Although the incidence of seroma was higher in group E (20%) than in group S (8%), the difference was not significant. Although electrocautery was associated with increased histological tissue damage, postoperative flap edema, discomfort, and other complications in the early stage, the clinical and cosmetic results of flaps made using electrocautery or a scalpel were similar and satisfactory 6 months after surgery.

Histopathological and clinical evaluation of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds healing in rats: an experimental study.

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Barati, Fardin; Javanbakht, Javad; Adib-Hashemi, Farajollah; Hosseini, Ehsan; Safaeie, Reyhaneh; Rajabian, Mojtaba; Razmjoo, Mostafa; Sedaghat, Reza; Aghamohammad Hassan, Mehdi

2013-07-17

Kombucha, a fermented tea (KT) is claimed to possess many beneficial properties. The aim of this study was to evaluate clinical and histopathological alterations of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds healing in rat. In present study 24 Wister -albino rats weighing 150-200 g were selected and divided to two treatment groups as Nitrofurazone ointment (0.2%) and Kombucha tea. Subsequently, the anesthesia was exerted by Ketamin hydrochloride 10% (40 mg/kg) and Xylasine (2 mg/kg) through intra muscular (IM) route. Furthermore, upon preparation of dorsal region of the animal for surgery, a piece of full-thickness skin removed (2 × 2 cm). In order to comparing wounds healing clinically and histologically, once every four days from the commencement, the wounds were photographed and the healed surface was measured by Scion image software. The clinical findings indicated that the Kombucha fungus resulted in precipitating healing than Nitrofurazone; however, it was not significant (p > 0.05). In order to pathological comparing of wound healing process, several wound biopsies were taken on 4, 8, 12, 16 and 20th days. Additionally, the histopathological results demonstrated that there was inflammation in Nitrofurazone group through twelveth day, somehow the epithelium was formed and abundant vessels were visible. Although on 16th day and the previous days the healing condition of Kombucha fungus was considered as minimal rate, revealing it is similar to Nitrofurazone group on 20th day. To wrap up. These observations suggest that the Kombucha fungus healing quality was rapid from 12th day to the end of the research, whereas no significant difference was observed. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1107407136102196.

Usefullness of Honey from the Islamic Point of View and Evaluation of Its Effects on Cutaneous Leishmaniasis Wounds in Balb/C Rats Invitro

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J Hossein Zadeh

2007-01-01

Full Text Available Introduction: Honey has been one of the most complete and a delicious edible since ages and there has been a special consideration towards it in Islam. In the Holy Quran, there is a full chapter named “The Bee (Nahl” and there is a verse in it as follows: “And your lord revealed to the bee saying make hives in the mountains and in the trees and in what they build, then eat of all of fruits and walk in the ways of your lord submissively. There comes forth from within it a beverage of many colors, in which there is healing for men, most surely there is a sign in this for a people who reflect.” (2 Honey has been used traditionally in medicine throughout history, for healing chronic wounds resistant to antibiotics and various kinds of burns. Because honey has low humidity, high osmotic pressure and pH, it causes stasis of growth of infectious agents and a sterile layer on sorts. A former survey showed that honey contains 20 types of sugars, 8 types of vitamins, 11 types of mineral substances,16 types of amino acids, a large of enzymes and so on. In this study we surveyed the properties of honey from the Islamic point of view and its effects on cutaneous leishmaniasis wounds in BALB/c rats in the laboratory. Methods: Sufficient natural honey from Golpayegan, a city in Isfahan province renown for its natural, good quality honey and ointment Paramo-U (made in Iran were obtained. 30 BALB/c mice were infected with the parasiteLeishmania(Lmajor[MRHO/IR/75/ER] (Parasitology Dept on Faculty Medicine in Tarbiat Modares University. They were divided into three groups Honey study group, Negative and Positive groups and as soon as the Leishmania lesion was obvious, weight of the mice and size of the lesion were measured in all by using Scale and Coliss(Mettler,Switzerlandweekly until the death of the last mouse in the Negative control group. The data was analyzed using SPSS software. Results: The mean weight of the mice that received honey was not

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing.

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Zheng, Zhong; Zhang, Xinli; Dang, Catherine; Beanes, Steven; Chang, Grace X; Chen, Yao; Li, Chen-Shuang; Lee, Kevin S; Ting, Kang; Soo, Chia

2016-11-01

In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss- and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in late-gestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age-matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-β1 expression and scarless repair, while low Fm levels correlated with increased TGF-β1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FM-TGF-β1 nexus plays in fetal-type scarless skin repair. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Assessment of platelet-derived growth factor using A splinted full thickness dermal wound model in bearded dragons (Pogona vitticeps).

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Keller, Krista A; Paul-Murphy, Joanne; Weber, E P Scott; Kass, Philip H; Guzman, Sanchez-Migallon David; Park, Shin Ae; Raghunathan, Vijay Krishna; Gustavsen, Kate A; Murphy, Christopher J

2014-12-01

Wounds in reptiles are a common reason for presentation to a veterinarian. At this time there is limited information on effective topical medications to aid in wound closure. The objectives of this study were to translate the splinted, full-thickness dermal wound model, validated in mice, to the bearded dragon (Pogona vitticeps) and to determine the effect of topical becaplermin (BP), a platelet-derived growth factor (0.01%), on the rate of wound closure. Ten bearded dragons were anesthetized and two full-thickness cutaneous wounds were made on the dorsum of each lizard. Encircling splints were applied surrounding each wound and subsequently covered by a semi-occlusive dressing. Five lizards had one wound treated with BP and the adjacent wound treated with a vehicle control. Five additional lizards had one wound treated with saline and the second wound treated with a vehicle control. Wounds were imaged daily, and the wound area was measured using digital image analysis. The change in percentage wound closure over 17 days and the time to 50% wound closure was compared among the four treatment groups. There was no significant difference in wound closure rates between BP-treated and saline-treated wounds or in the time to 50% wound closure between any treatments. Vehicle-treated wounds adjacent to saline-treated wounds closed significantly slower than did BP (P dragons. When compared with saline, BP did not have a significant effect on wound closure rates, while the vehicle alone delayed wound closure. Histologic analysis of experimentally created wounds throughout the wound healing process is needed to further evaluate the effects of these treatments on reptile dermal wound healing.

Axolotl cells and tissues enhances cutaneous wound healing in mice

OpenAIRE

DEMIRCAN, Turan; KESKIN, Ilknur; GUNAL, Yalcin; ILHAN, Ayse Elif; KOLBASI, Bircan; OZTURK, Gurkan

2017-01-01

Adult mammalian skin wound repair is defective due to loss of the regulation in balancing the complete epithelial regeneration and excessive connective tissue production, and this repair process commonly results in scar tissue formation. However, unlike mammals, adult salamanders repair the wounds by regeneration compared to scarring. To elucidate the healing capability of a salamander, Axolotl, in a different species, here we addressed this question by treating the wounds in mice with Axolot...

Cutaneous mucormycosis secondary to penetrative trauma.

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Zahoor, Bilal; Kent, Stephen; Wall, Daryl

2016-07-01

Mucormycosis is a rare but serious sequelae of penetrating trauma [1-5]. In spite of aggressive management, mortality remains high due to dissemination of infection. We completed a review of literature to determine the most optimal treatment of cutaneous mucormycosis which occurs secondary to penetrating trauma. We completed a review regarding the management of mucormycosis in trauma patients. We selected a total of 36 reports, of which 18 were case-based, for review. Surgical debridement is a primary predictor of improved outcomes in the treatment of mucormycosis [3,6,7]. Anti-fungal therapy, especially lipid soluble formulation of Amphotericin B, is helpful as an adjunct or when surgical debridement has been maximally achieved. Further research is needed to fully evaluate the impact of topical dressings; negative pressure wound therapy is helpful. An aggressive and early surgical approach, even at the expense of disfigurement, is necessary to reduce mortality in the setting of cutaneous mucormycosis that results from penetrating trauma [4,8,9]. Anti-fungal therapy and negative pressure wound therapy are formidable adjuncts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of laser and LED irradiation on mast cells of cutaneous wounds of rats with iron deficiency anemia

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Becher Rosa, Cristiane; Oliveira Sampaio, Susana C. P.; Monteiro, Juliana S. C.; Ferreira, Maria F. L.; Zanini, Fátima A. A.; Santos, Jean N.; Cangussú, Maria Cristina T.; Pinheiro, Antonio L. B.

2011-03-01

This work aimed to study histologically the effect of Laser or LED phototherapy on mast cells on cutaneous wounds of rats with iron deficiency. 18 rats were used and fed with special peleted iron-free diet. An excisional wound was created on the dorsum of each animal which were divided into: Group I - Control with anemia + no treatment; Group II - Anemia + Laser; Group III - Anemia + LED; Group IV - Healthy + no treatment; Group V - Healthy + Laser; Group VI - Healthy + LED. Irradiation was performed using a diode Laser (λ660nm, 40mW, CW, total dose of 10J/cm2, 4X2.5J/cm2) or a RED-LED ( λ700nm, 15mW, CW, total dose of 10J/cm2). Histological specimens were routinely processed, cut and stained with toluidine blue and mast cell counts performed. No significant statistic difference was found between groups as to the number of degranulated, non-degradulated or total mast cells. Greater mean values were found for degranulated mast cells in the Anemia + LED. LED irradiation on healthy specimens resulted in a smaller number of degranulated mast cells. Our results leads to conclude that there are no significant differences in the number of mast cells seven days after irradiation following Laser or LED phototherapy.

Effect of UV irradiation on cutaneous cicatrices

DEFF Research Database (Denmark)

Due, Eva; Rossen, Kristian; Sorensen, Lars Tue

2007-01-01

The aim of this study was to examine the effect of ultraviolet (UV) irradiation on human cutaneous cicatrices. In this randomized, controlled study, dermal punch biopsy wounds served as a wound healing model. Wounds healed by primary or second intention and were randomized to postoperative solar UV...... postoperatively, UV-irradiated cicatrices healing by second intention: (i) were significantly pointed out as the most disfiguring; (ii) obtained significantly higher scores of colour, infiltration and cicatrix area; and (iii) showed significantly higher increase in skin-reflectance measurements of skin......-pigmentation vs. non-irradiated cicatrices. No histological, immunohistochemical or biochemical differences were found. In conclusion, postoperative UV exposure aggravates the clinical appearance of cicatrices in humans....

Effect of a high-fat diet and alcohol on cutaneous repair: A systematic review of murine experimental models.

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Daiane Figueiredo Rosa

Full Text Available Chronic alcohol intake associated with an inappropriate diet can cause lesions in multiple organs and tissues and complicate the tissue repair process. In a systematic review, we analyzed the relevance of alcohol and high fat consumption to cutaneous and repair, compared the main methodologies used and the most important parameters tested. Preclinical investigations with murine models were assessed to analyze whether the current evidence support clinical trials.The studies were selected from MEDLINE/PubMed and Scopus databases, according to Fig 1. All 15 identified articles had their data extracted. The reporting bias was investigated according to the ARRIVE (Animal Research: Reporting of in Vivo Experiments strategy.In general, animals offered a high-fat diet and alcohol showed decreased cutaneous wound closure, delayed skin contraction, chronic inflammation and incomplete re-epithelialization.In further studies, standardized experimental design is needed to establish comparable study groups and advance the overall knowledge background, facilitating data translatability from animal models to human clinical conditions.

Animal models of chronic wound care

DEFF Research Database (Denmark)

Trøstrup, Hannah; Thomsen, Kim; Calum, Henrik

2016-01-01

on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s), and time...

High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling.

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Qi, Weiwei; Yang, Chuan; Dai, Zhiyu; Che, Di; Feng, Juan; Mao, Yuling; Cheng, Rui; Wang, Zhongxiao; He, Xuemin; Zhou, Ti; Gu, Xiaoqiong; Yan, Li; Yang, Xia; Ma, Jian-Xing; Gao, Guoquan

2015-04-01

Diabetic foot ulcer (DFU) caused by impaired wound healing is a common vascular complication of diabetes. The current study revealed that plasma levels of pigment epithelium-derived factor (PEDF) were elevated in type 2 diabetic patients with DFU and in db/db mice. To test whether elevated PEDF levels contribute to skin wound-healing delay in diabetes, endogenous PEDF was neutralized with an anti-PEDF antibody in db/db mice. Our results showed that neutralization of PEDF accelerated wound healing, increased angiogenesis in the wound skin, and improved the functions and numbers of endothelial progenitor cells (EPCs) in the diabetic mice. Further, PEDF-deficient mice showed higher baseline blood flow in the skin, higher density of cutaneous microvessels, increased skin thickness, improved numbers and functions of circulating EPCs, and accelerated wound healing compared with wild-type mice. Overexpression of PEDF suppressed the Wnt signaling pathway in the wound skin. Lithium chloride-induced Wnt signaling activation downstream of the PEDF interaction site attenuated the inhibitory effect of PEDF on EPCs and rescued the wound-healing deficiency in diabetic mice. Taken together, these results suggest that elevated circulating PEDF levels contribute to impaired wound healing in the process of angiogenesis and vasculogenesis through the inhibition of Wnt/β-catenin signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Topical Application of Aloe vera Accelerated Wound Healing, Modeling, and Remodeling: An Experimental Study.

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Oryan, Ahmad; Mohammadalipour, Adel; Moshiri, Ali; Tabandeh, Mohammad Reza

2016-01-01

Treatment of large wounds is technically demanding and several attempts have been taken to improve wound healing. Aloe vera has been shown to have some beneficial roles on wound healing but its mechanism on various stages of the healing process is not clear. This study was designed to investigate the effect of topical application of A. vera on cutaneous wound healing in rats. A rectangular 2 × 2-cm cutaneous wound was created in the dorsum back of rats. The animals were randomly divided into 3 groups of control (n = 20), low-dose (n = 20), and high-dose (n = 20) A. vera. The control and treated animals were treated daily with topical application of saline, low-dose (25 mg/mL), and high-dose (50 mg/mL) A. vera gel, up to 10 days, respectively. The wound surface, wound contraction, and epithelialization were monitored. In each group, the animals were euthanized at 10 (n = 5), 20 (n = 5), and 30 (n = 10) days post injury (DPI). At 10, 20, and 30 DPI, the skin samples were used for histopathological and biochemical investigations; and at 30 DPI, the skin samples were also subjected for biomechanical studies. Aloe vera modulated the inflammation, increased wound contraction and epithelialization, decreased scar tissue size, and increased alignment and organization of the regenerated scar tissue. A dose-dependent increase in the tissue level of dry matter, collagen, and glycosaminoglycans' content was seen in the treated lesions, compared to the controls. The treated lesions also demonstrated greater maximum load, ultimate strength, and modulus of elasticity compared to the control ones (P vera improved the biochemical, morphological, and biomechanical characteristics of the healing cutaneous wounds in rats. This treatment option may be valuable in clinical practice.

β-Catenin–regulated myeloid cell adhesion and migration determine wound healing

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Amini-Nik, Saeid; Cambridge, Elizabeth; Yu, Winston; Guo, Anne; Whetstone, Heather; Nadesan, Puviindran; Poon, Raymond; Hinz, Boris; Alman, Benjamin A.

2014-01-01

A β-catenin/T cell factor–dependent transcriptional program is critical during cutaneous wound repair for the regulation of scar size; however, the relative contribution of β-catenin activity and function in specific cell types in the granulation tissue during the healing process is unknown. Here, cell lineage tracing revealed that cells in which β-catenin is transcriptionally active express a gene profile that is characteristic of the myeloid lineage. Mice harboring a macrophage-specific deletion of the gene encoding β-catenin exhibited insufficient skin wound healing due to macrophage-specific defects in migration, adhesion to fibroblasts, and ability to produce TGF-β1. In irradiated mice, only macrophages expressing β-catenin were able to rescue wound-healing deficiency. Evaluation of scar tissue collected from patients with hypertrophic and normal scars revealed a correlation between the number of macrophages within the wound, β-catenin levels, and cellularity. Our data indicate that β-catenin regulates myeloid cell motility and adhesion and that β-catenin–mediated macrophage motility contributes to the number of mesenchymal cells and ultimate scar size following cutaneous injury. PMID:24837430

The Effect of Withania Somnifera Root Extract on Open Wound Healing in the Male Rats

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N Ajand

2015-12-01

Full Text Available Introduction: Healing cutaneous wounds is regarded as one of the most important issues in the medicine. Different chemical agents have been used in regard with promoting wound healing, most of which unfortunately present some side effects and defects. Since natural combinations have proposed less disadvantages, this study aimed to investigate the effect of Withania Somnifera root extract on cutaneous wound healing in the male rats. Methods: This study was performed on 36 rats weighing 180-220g that were divided into 6 groups (n=6. First, wounds (2x2 were made on the dorsal skin of the animals. The first group was left without treatment (control group, the second was treated with Eucerin(negative control, the third group received 1% of phenytoin cream and in the other groups, different concentrations of hydroalcoholic extract of Withania Somnifera (20%, 40%, 60% w/w combined with Eucerin base were administrated once per day. The area of wounds was measured by Autocad software every day, from the 2nd day to 14th day. The study data were analyzed via SPSS software (ver.16 at the significant level of P<0.05. Results:The reduction of incisional wound area in the all groups treated with root extract of Withania Somnifera  ointment was significantly higher on the 8th  day. Moreover, dose of 60% and 90% revealed better effects (p<0.001. Conclusion: The findings of the present study demonstrated that Withania Somnifera root, due to its significant reduction in the healing time as well as wound area, can be used as an effective material in regard with the cutaneous wound healing.

The effect of topical minoxidil pretreatment on nonsurgical delay of rat cutaneous flaps: further studies.

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Gümüş, Nazım; Odemiş, Yusuf; Tuncer, Ersin; Yılmaz, Sarper

2013-08-01

The purpose of this study was to determine the effectiveness of topically applied minoxidil in the pharmacological delay phenomenon and to demonstrate the comparable microscopic and macroscopic changes between minoxidil-pretreated flaps and surgically delayed flaps. A modified version of the McFarlane flap was used. Group 1 rats, in which a caudally based dorsal skin flap was raised and sutured back, were the control group. In group II, minoxidil solution was spread over the marked skin flap area for 7 days. On the 7th day, a caudally based dorsal skin flap was elevated and then sutured back. Group III rats underwent a surgical delay procedure alone. On the 7th day after flap elevation, evaluation was done by histologic examination and calculation of the flap survival areas in all groups. The lowest flap survival rate appeared in group I and was statistically different from groups II and III. The mean surviving skin flap area in the minoxidil-pretreated group was significantly larger than that in the control group. After histologic evaluation, moderate angiogenesis was also detected in group II. We also found that surgical delay significantly reduced flap necrosis when compared to the minoxidil pretreatment group. According to our study, minoxidil may be considered an effective vasoactive agent for the stimulation of angiogenesis in rat cutaneous flaps and capable of achieving pharmacological delay and increasing flap survival. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hyperosmotic nanoemulsions: Development and application of a new antimicrobial treatment for wound care

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Connell, Sean

Wound healing is the intricate process that restores function to damaged skin. The process consists of the inflammatory, proliferative and remodeling phases that orchestrate dynamic cellular responses to regenerate the cutaneous barrier. However, microbial contamination of the wound site stimulates a deleterious inflammatory response with the production of endotoxins, exotoxins and proteases that result in secondary injury. The end result is delayed healing, protracted debilitation and increased health care costs. Controlling contamination is critical for proper wound management and reduced burden on the healthcare system. Based on this concern, we developed and applied a new antimicrobial therapeutic that relies on hyperosmotic nanoemulsions (HNE). The biomechanical process consists of a high-energy nanoemulsion component that permeates the protective microbial membrane and a (ii) nonionic hyperosmoticum that facilitates intracellular water extraction to critically dehydrate the pathogen. HNE was shown to be effective against a multitude of pathogens including bacteria, antibiotic-resistant variants, fungi and viruses. Reported non-clinical studies demonstrate that the membrane disrupting nanoemulsion and hyperosmotic component act synergistically to enhance microbicidal activity. Further, results illustrate that pathogen inactivation was rapid as determined by ion and macromolecule leakage assays. Application of HNE in a pre-clinical animal model of wound healing demonstrated the treatment actively promoted healing to reduce treatment times. HNE mitigated wound infection to reduce the inflammatory response and mechanically debrided the wound to facilitate wound closure. Recent work further enhanced the stability of the nanoemulsion component with the addition of surfactant stabilizers using a low-energy spontaneous emulsification process. The refined nanoemulsion composition was stable against physical stressors and long-term storage without disrupting the

Nod-Like Receptor Protein-3 Inflammasome Plays an Important Role during Early Stages of Wound Healing

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Weinheimer-Haus, Eileen M.; Mirza, Rita E.; Koh, Timothy J.

2015-01-01

The Nod-like receptor protein (NLRP)-3 inflammasome/IL-1β pathway is involved in the pathogenesis of various inflammatory skin diseases, but its biological role in wound healing remains to be elucidated. Since inflammation is typically thought to impede healing, we hypothesized that loss of NLRP-3 activity would result in a downregulated inflammatory response and accelerated wound healing. NLRP-3 null mice, caspase-1 null mice and C57Bl/6 wild type control mice (WT) received four 8 mm excisional cutaneous wounds; inflammation and healing were assessed during the early stage of wound healing. Consistent with our hypothesis, wounds from NLRP-3 null and caspase-1 null mice contained lower levels of the pro-inflammatory cytokines IL-1β and TNF-α compared to WT mice and had reduced neutrophil and macrophage accumulation. Contrary to our hypothesis, re-epithelialization, granulation tissue formation, and angiogenesis were delayed in NLRP-3 null mice and caspase-1 null mice compared to WT mice, indicating that NLRP-3 signaling is important for early events in wound healing. Topical treatment of excisional wounds with recombinant IL-1β partially restored granulation tissue formation in wounds of NLRP-3 null mice, confirming the importance of NLRP-3-dependent IL-1β production during early wound healing. Despite the improvement in healing, angiogenesis and levels of the pro-angiogenic growth factor VEGF were further reduced in IL-1β treated wounds, suggesting that IL-1β has a negative effect on angiogenesis and that NLRP-3 promotes angiogenesis in an IL-1β-independent manner. These findings indicate that the NLRP-3 inflammasome contributes to the early inflammatory phase following skin wounding and is important for efficient healing. PMID:25793779

Effect of astaxanthin on cutaneous wound healing

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Meephansan J; Rungjang A; Yingmema W; Deenonpoe R; Ponnikorn S

2017-01-01

Jitlada Meephansan,1 Atiya Rungjang,1 Werayut Yingmema,2 Raksawan Deenonpoe,3 Saranyoo Ponnikorn3 1Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand; 2Laboratory Animal Centers, Thammasat University, Pathum Thani, Thailand; 3Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand Abstract: Wound healing consists of a complex series of convoluted processes which involve renewal of the skin afte...

Study of wound healing potential of Stevia rebaudiana ethanol extract in male rats

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S. Goorani

2018-01-01

Full Text Available Background and objectives: Stevia rebaudiana has been used in medicine as anti-inflammatory, antioxidant, antipyretic, anti-fungal, and antibacterial agent. The present study was conducted to investigate the healing effects of S. rebaudiana ethanol extracts on cutaneous wounds in rats. Methods: Full-thickness excisional wounds (2×2 cm were induced on the back of 32 rats. The rats were divided into four groups as follows; untreated (control and treated with 1 mL basal cream, 1 mL S. rebaudiana ethanol extract 10%, and 1 mL tetracycline (3% for 20 days (short term. Animals of each group were euthanized at 20 day post-injury and wounds were assessed through macroscopic and microscopic analyses. Results: During the experiment, S. rebaudiana indicated a significant reduction in the wound area compared to other groups. Parameters such as arrangement of the healing tissue, re-epithelilization and epithelial formation demonstrated considerable changes when compared to the control. In addition, treatment with S. rebaudiana decreased the total number of cells, fibrocytes/fibroblasts ratio, neutrophils, and lymphocytes and enhanced the number of blood vessels and fibroblasts at 20 day. Conclusion: The present study demonstrated the wound healing activity of S. rebaudiana, lending credence to the folkloric use in the treatment of cutaneous wounds.

Multifunctional skin-like electronics for quantitative, clinical monitoring of cutaneous wound healing.

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Hattori, Yoshiaki; Falgout, Leo; Lee, Woosik; Jung, Sung-Young; Poon, Emily; Lee, Jung Woo; Na, Ilyoun; Geisler, Amelia; Sadhwani, Divya; Zhang, Yihui; Su, Yewang; Wang, Xiaoqi; Liu, Zhuangjian; Xia, Jing; Cheng, Huanyu; Webb, R Chad; Bonifas, Andrew P; Won, Philip; Jeong, Jae-Woong; Jang, Kyung-In; Song, Young Min; Nardone, Beatrice; Nodzenski, Michael; Fan, Jonathan A; Huang, Yonggang; West, Dennis P; Paller, Amy S; Alam, Murad; Yeo, Woon-Hong; Rogers, John A

2014-10-01

Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here, an electronic sensor platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing is reported. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of "epidermal" electronics system in a realistic clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Initial Management of Traumatic Wounds.

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Devriendt, Nausikaa; de Rooster, Hilde

2017-11-01

When traumatic wounds are quickly and accurately treated, morbidity and costs can be significantly decreased. Several factors, such as time delay between injury and treatment, the degree of contamination, extension and depth of the wound, and the mechanism of injury, influence the treatment and prognosis and stress the importance of a patient-specific approach. Although all traumatic wounds are contaminated, antibiotic therapy is seldom required if correct wound management is installed. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic cheek ulcer caused by odontogenic cutaneous sinus tract

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Tomoya Sato

2015-06-01

Odontogenic cutaneous sinus tracts are often misdiagnosed, and they lead to facial wounds and scarring. Therefore, we must be aware of the possibility of this condition. A dental origin must be considered for chronic ulcers involving the cheek, chin and submental areas. The clinical course of this patient suggests two important clinical issues for prompt diagnosis. First, physical examination, including palpation and probing, are helpful for exploration of sinus tracts. Second, computed tomography is useful to detect the sinus tract and affected teeth. Computed tomography provides radiographic evidence of the relationship between the tooth and cutaneous region, and it may be superior to radiography.

Metalloproteinase Expression is Associated with Traumatic Wound Failure

Science.gov (United States)

2010-04-01

Traumatic amputation- no.(%) 15 Size of wound (cm3 )* Associated vascular injury- no.(%) 7 Wound closure method no.(%) Suture 29 Skin graft 9 Number...definitive closure or coverage with skin graft . Im- paired wound healing included delayed wound closure or wound dehiscence after closure or coverage...closure time period of 10 d. Dehiscence was defined as spontaneous partial or com- plete wound disruption after primary closure or > 90% skin graft loss

Primary versus secondary closure of cutaneous abscesses in the emergency department: a randomized controlled trial.

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Singer, Adam J; Taira, Breena R; Chale, Stuart; Bhat, Rahul; Kennedy, David; Schmitz, Gillian

2013-01-01

Cutaneous abscesses have traditionally been treated with incision and drainage (I&D) and left to heal by secondary closure. The objective was to compare the healing rates of cutaneous abscesses following I&D after primary or secondary closure. This was a randomized, controlled, trial, balanced by center, with blocked randomization created by a random-number generator. One urban and one suburban academic emergency department (ED) participated. Subjects were randomized to primary or secondary wound closure following I&D of the abscess. Main outcome measures were the percentage of healed wounds (wound was completely closed by visual inspection; a 40% difference in wound healing was sought) and overall failure rate (need for additional intervention including suture removal, additional drainage, antibiotics, or admission within 7 days after drainage). Fifty-six adult patients with simple localized cutaneous abscesses were included; 29 were randomized to primary closure, and 27 were randomized to secondary closure. Healing rates at 7 days were similar between the primary and secondary closure groups (69.6%, 95% confidence interval [CI] = 49.1% to 84.4% vs. 59.3%, 95% CI = 40.7% to 75.5%; difference 10.3%, 95% CI = -15.8% to 34.1%). Overall failure rates at 7 days were also similar between the primary and secondary closure groups (30.4%, 95% CI = 15.6% to 50.9% vs. 28.6%, 95% CI = 15.2% to 47.1%; difference 1.8%, 95% CI = -24.2% to 28.8%). The rates of wound healing and treatment failure following I&D of simple abscesses in the ED are similar after primary or secondary closure. The authors did not detect a difference of at least 40% in healing rates between primary and secondary closure. © 2013 by the Society for Academic Emergency Medicine.

Workload and prevalence of open wounds in the community: French Vulnus initiative.

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Meaume, S; Kerihuel, J C; Fromantin, I; Téot, L

2012-02-01

To calculate the prevalence of open cutaneous wounds presented on a routine working day in community settings in metropolitan France, and to estimate the workload associated with the care of these wounds by nurses, GPs and specialists (dermatologists, diabetologists and phlebologists). A transversal epidemiological survey was conducted on a randomly selected sample of the above practitioners between June and July 2008. The percentage of patients presenting on a routine working day with open a cutaneous lesion of any origin, location, size and duration was assessed. All local and systemic care performed on the patient during that day because of the wound was also recorded. In total, 475 GPs, 453 specialists and 238 nurses participated (n=1166) and saw a total of 29 663 patients, of whom 3037 presented with one or more cutaneous wound. The overall non-weighted prevalence of patients with a wound was 10.2% (95%CI: 9.9%;10.6%). This prevalence was similar for GPs (6.0%) and for specialists (6.9%), but was higher for nurses (22.0%). Forty-three per cent of all wounds had a duration of over 6 weeks. These chronic wounds were predominantly leg ulcers, diabetic foot ulcers or pressure ulcers, but also included wounds of all aetiologies. For 33% of all patients with wounds, the impact on their health status was serious to severe. The overwhelming majority of wounds (95%) required local care, including in 65% of cases cleansing and debridement. Despite its limitations, this initiative, the first of its type in France, strongly suggests that wound care constitutes an important part of routine care given by health professionals in the community, and for a substantial number of these patients, wounds represent a serious morbidity. The non-profit organisation 'Association Vivre avec une Plaie' financially supported this study. This association received unrestricted grants from the French Wound Healing Society (SFFPC) and a consortium of private companies (main sponsors: Conva

Delayed wound healing and postoperative surgical site infections in patients with rheumatoid arthritis treated with or without biological disease-modifying antirheumatic drugs.

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Tada, Masahiro; Inui, Kentaro; Sugioka, Yuko; Mamoto, Kenji; Okano, Tadashi; Kinoshita, Takuya; Hidaka, Noriaki; Koike, Tatsuya

2016-06-01

Biological disease-modifying antirheumatic drugs (bDMARDs) have become more popular for treating rheumatoid arthritis (RA). Whether or not bDMARDs increase the postoperative risk of surgical site infection (SSI) has remained controversial. We aimed to clarify the effects of bDMARDs on the outcomes of elective orthopedic surgery. We used multivariate logistic regression analysis to analyze risk factors for SSI and delayed wound healing among 227 patients with RA (mean age, 65.0 years; disease duration, 16.9 years) after 332 elective orthopedic surgeries. We also attempted to evaluate the effects of individual medications on infection. Rates of bDMARD and conventional synthetic DMARD (csDMARD) administration were 30.4 and 91.0 %, respectively. Risk factors for SSI were advanced age (odds ratio [OR], 1.11; P = 0.045), prolonged surgery (OR, 1.02; P = 0.03), and preoperative white blood cell count >10,000/μL (OR, 3.66; P = 0.003). Those for delayed wound healing were advanced age (OR, 1.16; P = 0.001), prolonged surgery (OR, 1.02; P = 0.007), preoperative white blood cell count >10,000/μL (OR, 4.56; P = 0.02), and foot surgery (OR, 6.60; P = 0.001). Risk factors for SSI and medications did not significantly differ. No DMARDs were risk factors for any outcome examined. Biological DMARDs were not risk factors for postoperative SSI. Foot surgery was a risk factor for delayed wound healing.

Fundamentals of pain management in wound care.

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Coulling, Sarah

Under-treated pain can result in a number of potentially serious sequelae (Australian and New Zealand College of Anaesthetists, 2006), including delayed mobilization and recovery, cardiac complications, thromboses, pulmonary complications, delayed healing, psychosocial problems and chronic pain syndromes. This article considers pain management in the context of painful wounds. An international comparative survey on wound pain (European Wound Management Association, 2002) found that practitioners in the wound care community tend to focus on healing processes rather than the patient's total pain experience involving an accurate pain assessment and selection of an appropriate pain management strategy. Procedural pain with dressing removal and cleansing caused the greatest concerns. An overview of simple, evidence-based drug and non-drug techniques is offered as potential strategies to help minimize the experience of pain.

Radiotherapy and wound healing: principles, management and prospects (review).

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Gieringer, Matthias; Gosepath, Jan; Naim, Ramin

2011-08-01

Radiation therapy is a major therapeutic modality in the management of cancer patients. Over 60% of these patients receive radiotherapy at some point during their course of treatment and over 90% will develop skin reactions after therapy. Problematic wound healing in radiation-damaged tissue constitutes a major surgical difficulty and despite all efforts, irradiated skin remains a therapeutic challenge. This review provides an overview of the fundamental principles of radiation therapy with regards to the wound healing in normal and irradiated skin. Furthermore, it presents techniques that describe how to prevent and manage skin side effects as well as prospects that may improve cutaneous wound repair in general and in irradiated skin.

Dynamic multiphoton imaging of acellular dermal matrix scaffolds seeded with mesenchymal stem cells in diabetic wound healing.

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Chu, Jing; Shi, Panpan; Deng, Xiaoyuan; Jin, Ying; Liu, Hao; Chen, Maosheng; Han, Xue; Liu, Hanping

2018-03-25

Significantly effective therapies need to be developed for chronic nonhealing diabetic wounds. In this work, the topical transplantation of mesenchymal stem cell (MSC) seeded on an acellular dermal matrix (ADM) scaffold is proposed as a novel therapeutic strategy for diabetic cutaneous wound healing. GFP-labeled MSCs were cocultured with an ADM scaffold that was decellularized from normal mouse skin. These cultures were subsequently transplanted as a whole into the full-thickness cutaneous wound site in streptozotocin-induced diabetic mice. Wounds treated with MSC-ADM demonstrated an increased percentage of wound closure. The treatment of MSC-ADM also greatly increased angiogenesis and rapidly completed the reepithelialization of newly formed skin on diabetic mice. More importantly, multiphoton microscopy was used for the intravital and dynamic monitoring of collagen type I (Col-I) fibers synthesis via second harmonic generation imaging. The synthesis of Col-I fibers during diabetic wound healing is of great significance for revealing wound repair mechanisms. In addition, the activity of GFP-labeled MSCs during wound healing was simultaneously traced via two-photon excitation fluorescence imaging. Our research offers a novel advanced nonlinear optical imaging method for monitoring the diabetic wound healing process while the ADM and MSCs interact in situ. Schematic of dynamic imaging of ADM scaffolds seeded with mesenchymal stem cells in diabetic wound healing using multiphoton microscopy. PMT, photo-multiplier tube. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds

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Kim, Ju-Won; Lee, Jong-Hwan; Lyoo, Young S; Jung, Dong-In; Park, Hee-Myung

2013-01-01

Background Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. Hypothesis Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. Animals Adult healthy beagle dogs (n = 10; 3–6 years old; 7.2–13.1 kg) were studied. Methods Full-thickness skin wounds were created on the dorsum of healthy beagles, and allogenic MSCs were injected intradermally. The rate of wound closure and the degree of collagen production were analysed histologically using haematoxylin and eosin staining and trichrome staining. The degree of cellular proliferation and angiogenesis was evaluated by immunocytochemistry using proliferating cell nuclear antigen-, vimentin- and α-smooth muscle actin-specific antibodies. Local mRNA expression levels of interleukin-2, interferon-γ, basic fibroblast growth factor and matrix metalloproteinase-2 were evaluated by RT-PCR. Results Compared with the vehicle-treated wounds, MSC-treated wounds showed more rapid wound closure and increased collagen synthesis, cellular proliferation and angiogenesis. Moreover, MSC-treated wounds showed decreased expression of pro-inflammatory cytokines (interleukin-2 and interferon-γ) and wound healing-related factors (basic fibroblast growth factor and matrix metalloproteinase-2). Conclusion and clinical importance Topical transplantation of MSCs results in paracrine effects on cellular proliferation and angiogenesis, as well as modulation of local mRNA expression of several factors related to cutaneous wound healing. Résumé Contexte Les cellules souches adultes ont été largement étudiées dans les approches de bio-ingénierie pour la thérapie de réparation tissulaire. Nous évaluons l

Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential

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M. Isakson

2015-01-01

Full Text Available Human skin is a remarkable organ that sustains insult and injury throughout life. The ability of skin to expeditiously repair wounds is paramount to survival. With an aging global population, coupled with a rise in the prevalence of conditions such as diabetes, chronic wounds represent a significant biomedical burden. Mesenchymal stem cells (MSC, a progenitor cell population of the mesoderm lineage, have been shown to be significant mediators in inflammatory environments. Preclinical studies of MSC in various animal wound healing models point towards a putative therapy. This review examines the body of evidence suggesting that MSC accelerate wound healing in both clinical and preclinical studies and also the possible mechanisms controlling its efficacy. The delivery of a cellular therapy to the masses presents many challenges from a safety, ethical, and regulatory point of view. Some of the issues surrounding the introduction of MSC as a medicinal product are also delineated in this review.

Effect of Hevea brasiliensis latex sap gel on healing of acute skin wounds induced on the back of rats

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Maria Vitória Carmo Penhavel

Full Text Available Objective : to evaluate the effect of topical delivery of latex cream-gel in acute cutaneous wounds induced on the back of rats. Methods : we subjected sixteen rats to dermo-epidermal excision of a round dorsal skin flap, with 2.5cm diameter. We divided the animals into two groups: Latex Group: application of cream-gel-based latex throughout the wound bed on postoperative days zero, three, six and nine; Control group: no treatment on the wound. Photographs of the lesions were taken on the procedure day and on the 6th and 14th postoperative days, for analyzing the area and the larger diameter of the wound. We carried out euthanasia of all animals on the 14th postoperative day, when we resected he dorsal skin and the underlying muscle layer supporting the wound for histopathological study. Results : there was no statistically significant difference in the percentage of wound closure, in the histopathological findings or in the reduction of the area and of the largest diameter of the wounds among the groups studied on the 14th postoperative day. Conclusion : according to the experimental conditions in which the study was conducted, latex cream-gel did not interfere in the healing of acute cutaneous wounds in rats.

Adenoviral Gene Delivery to Primary Human Cutaneous Cells and Burn Wounds

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Hirsch, Tobias; von Peter, Sebastian; Dubin, Grzegorz; Mittler, Dominik; Jacobsen, Frank; Lehnhardt, Markus; Eriksson, Elof; Steinau, Hans-Ulrich; Steinstraesser, Lars

2006-01-01

The adenoviral transfer of therapeutic genes into epidermal and dermal cells is an interesting approach to treat skin diseases and to promote wound healing. The aim of this study was to assess the in vitro and in vivo transfection efficacy in skin and burn wounds after adenoviral gene delivery. Primary keratinocytes (HKC), fibroblasts (HFB), and HaCaT cells were transfected using different concentrations of an adenoviral construct (eGFP). Transfection efficiency and cytotoxicity was determine...

Cryptococcosis mimicking cutaneous cellulitis in a patient suffering from rheumatoid arthritis: a case report

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Probst Corina

2010-08-01

Full Text Available Abstract Background Cryptococcus neoformans is an encapsulated yeast and the most frequent cryptococcal species found in humans. Cryptococcosis is considered an opportunistic infection as it affects mainly immunosuppressed individuals. In humans, C. neoformans causes three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and wound or cutaneous cryptococcosis. Case Presentation An 81-year-old woman developed severe necrotizing cellulitis on her left arm without any preceding injury. The patient had been treated with systemic corticosteroids over twenty years for rheumatoid arthritis (RA. Skin biopsies of the wound area were initially interpreted as cutaneous vasculitis of unknown etiology. However, periodic acid Schiff staining and smear analysis later revealed structures consistent with Cryptococcus neoformans, and the infection was subsequently confirmed by culture. After the initiation of therapy with fluconazole 400 mg per day the general condition and the skin ulcers improved rapidly and the patient was discharged to a rehabilitation facility. Subsequently surgical debridement and skin grafting were performed. Conclusions Opportunistic infections such as cryptococcosis can clinically and histologically mimic cutaneous vasculitis and have to be investigated rigorously as a differential diagnosis in immunosuppressed patients.

The Treatment of Cutaneous Abscesses: Comparison of Emergency Medicine Providers' Practice Patterns

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Schmitz, Gillian R

2013-02-01

Full Text Available AbstractObjectives: Cutaneous abscesses are commonly treated in the emergency department (ED. Although incision and drainage (I&D remains the standard treatment, there is little high quality evidence to support additional interventions such as pain control, type of incision, and use of irrigation, wound cultures, and packing. Although guidelines exist to support clinician management of abscesses, they do not clearly specify these additional interventions. This study sought to describe the ED treatments administered to adults with uncomplicated superficial cutaneous abscesses, defined as purulent lesions requiring incision and drainage, that could be managed in an ED or outpatient setting.Methods: Four hundred and seventy four surveys were distributed to 15 EDs across the United States. Participants were queried about their level of training and practice environment as well as specific questions regarding their management of cutaneous abscesses in the ED.Results: In total, 350 providers responded to the survey (74%. One hundred eighty nine respondents (54% were attending physicians, 135 (39% were residents and 26 (7% were mid-level providers. Most providers (76% used narcotics for pain management, 71% used local anesthetic over the roof of the abscess, and 60% used local anesthetic in a field block for pain control. Only 48% of responders routinely used irrigation after I&D. Eighty-five percent of responders used a linear incision to drain the abscess and 91% used packing in the wound cavity. Thirty two percent routinely sent wound cultures and 17% of providers routinely prescribed antibiotics. Most providers (73% only prescribed antibiotics if certain historical factors or physical findings were present on exam. Antibiotic treatment, if used, favored a combination of 2 or more drugs to cover both Streptococcus and methicillin-resistant Staphylococcal aureus (47%. Follow up visits were most frequently recommended at 48 hours unless wound was

[Carboxytherapy - supportive therapy in chronic wound treatment].

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Sinozić, Tamara; Kovacević, Jadranka

2013-10-01

Carboxytherapy is a supportive method in chronic wound treatment conducted by cutaneous and subcutaneous injection of medical carbon dioxide (CO2). The primary effect of the injected CO2 is the correction of tissue hypoxia due to the Bohr effect. With its effects on endothelial growth factors, it stimulates neoangiogenesis and fibroblast collagen synthesis consequently leading to better wound healing. Carboxytherapy is used in many areas from chronic wound treatment, peripheral venous and arterial diseases, dermatological diseases, to cosmetic medicine. It is minimally invasive, patients take it well, it is economically acceptable, and it can be conducted in outpatient conditions by properly trained doctors. The application of new technologic innovations in the healing processes, education and teamwork combined with developed holistic individual approach ensure good cooperation and mutual doctor-patient communication, enhance patient care and improve their quality of life.

The Immediate and Delayed Post-Debridement Effects on Tissue Bacterial Wound Counts of Hypochlorous Acid Versus Saline Irrigation in Chronic Wounds

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Hiebert, John?M.; Robson, Martin?C.

2016-01-01

Introduction: Wound debridement is considered essential in chronic wound management. Hypochlorous acid has been shown to be an effective agent in reducing wound bacterial counts in open wounds. Ultrasound-enabled wound debridement is an effective and efficient method of debridement. This study compared ultrasound irrigation with hypochlorous acid versus saline irrigation for wound debridement on pre- and postoperative wounds and determined regrowth of bacteria over 1 week period of time. Fina...

Acute Ultraviolet Radiation Perturbs Epithelialization but not the Biomechanical Strength of Full-thickness Cutaneous Wounds

DEFF Research Database (Denmark)

Danielsen, Patricia L; Lerche, Catharina M; Wulf, Hans Christian

2016-01-01

SED, 3 SED and 5 SED. Twenty-four hours after UV irradiation, inflammation was quantified by skin reflectance (erythema) and myeloperoxidase (MPO) tissue levels, and two 6 mm full-thickness excisional wounds and one 3 cm incisional wound were inflicted. Epidermal hyperplasia was assessed...... (P epithelial coverage decreased (P = 0.024) by increasing the UVR dose, whereas there was no significant difference (P = 0.765) in wound MPO levels. Neither wound width (P = 0.850) nor breaking strength (P...... = 0.320) differed among the groups. Solar-simulated UVR 24 h before wounding impaired epithelialization but was not detrimental for surgical incisional wound healing....

The Immediate and Delayed Post-Debridement Effects on Tissue Bacterial Wound Counts of Hypochlorous Acid Versus Saline Irrigation in Chronic Wounds.

Science.gov (United States)

Hiebert, John M; Robson, Martin C

2016-01-01

Introduction: Wound debridement is considered essential in chronic wound management. Hypochlorous acid has been shown to be an effective agent in reducing wound bacterial counts in open wounds. Ultrasound-enabled wound debridement is an effective and efficient method of debridement. This study compared ultrasound irrigation with hypochlorous acid versus saline irrigation for wound debridement on pre- and postoperative wounds and determined regrowth of bacteria over 1 week period of time. Finally, the outcome of definitive wound closure of the clinically clean-appearing wounds was recorded. Methods: Seventeen consenting adult patients with chronic open wounds were randomly selected for study. The patients were randomly divided into the hypochlorous acid irrigation or saline irrigation group. All patients provided pre- and postoperative tissue samples for qualitative and quantitative bacteriology. For the time (7 days) between the debridement procedure and the definitive closure procedure, the wounds were dressed with a silver-impregnated dressing and a hydroconductive dressing. Results : Both types of irrigation in the ultrasonic system initially lowered the bacterial counts by 4 to 6 logs. However, by the time of definitive closure, the saline-irrigated wounds had bacterial counts back up to 10 5 whereas the hypochlorous acid-irrigated wounds remained at 10 2 or fewer. More than 80% of patients in the saline group had postoperative closure failure compared with 25% of patients in the hypochlorous acid group. Conclusions: Hypochlorous acid irrigation with ultrasound debridement reduced bacterial growth in chronic open wounds more efficiently than saline alone. Postoperative wound closure outcomes suggest a remarkable reduction in wound complications after wound debridement using hypochlorous acid irrigation with ultrasound versus saline alone.

Saliva and wound healing.

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Brand, Henk S; Ligtenberg, Antoon J M; Veerman, Enno C I

2014-01-01

Oral wounds heal faster and with less scar formation than skin wounds. One of the key factors involved is saliva, which promotes wound healing in several ways. Saliva creates a humid environment, thus improving the survival and functioning of inflammatory cells that are crucial for wound healing. In addition, saliva contains several proteins which play a role in the different stages of wound healing. Saliva contains substantial amounts of tissue factor, which dramatically accelerates blood clotting. Subsequently, epidermal growth factor in saliva promotes the proliferation of epithelial cells. Secretory leucocyte protease inhibitor inhibits the tissue-degrading activity of enzymes like elastase and trypsin. Absence of this protease inhibitor delays oral wound healing. Salivary histatins in vitro promote wound closure by enhancing cell spreading and cell migration, but do not stimulate cell proliferation. A synthetic cyclic variant of histatin exhibits a 1,000-fold higher activity than linear histatin, which makes this cyclic variant a promising agent for the development of a new wound healing medication. Conclusively, recognition of the many roles salivary proteins play in wound healing makes saliva a promising source for the development of new drugs involved in tissue regeneration.

The reduction in inflammation and impairment in wound healing by using strontium chloride hexahydrate.

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Berksoy Hayta, Sibel; Durmuş, Kasim; Altuntaş, Emine Elif; Yildiz, Esin; Hisarciklıo, Mehmet; Akyol, Melih

2018-03-01

Numerous growth factors, cytokine, mitogen and chemotactic factors are involved in wound healing. Even though inflammation is important for the stimulation of proliferative phase, excessive inflammation also causes impairment in wound healing. Strontium salts suppress keratinocyte-induced TNF-alpha and interleukin-1 and interleukin-6 in in vitro cultures. This study was conducted to determine the effects of administration of topical strontium chloride hexahydrate on wound healing through TNF-alpha and TGF-beta in surgical wound healing model of in-vivo rat skin. Twenty-four rats were used in the study. After approximately 2 cm cutaneous-subcutaneous incision was horizontally carried out on the mid-neckline of the rats, the incision was again closed using 2.0 vicryl. The rats were assigned into three groups including eight rats in each group. Placebo emollient ointment and also the ointments, which were containing 5% and 10% strontium chloride hexahydrate and were prepared at the same base with placebo ointment, were administered to the groups by a blind executor twice a day for a week. At the end of seventh day, the rats were sacrificed and cutaneous and subcutaneous tissue of their wound site was resected for histopathological examination. Scoring of histopathological wound healing and scoring of tissue TNF-alpha and TGF-beta level with immunohistochemical staining were performed. The groups, to which both 5% and 10% strontium chloride hexahydrate was administered, had lower immunohistochemical TNF-alpha levels and histopathological wound scores compared to controls, which was statistically significant (p < 0.05). Strontium chloride hexahydrate can lead to impairment in wound healing by suppressing inflammation through TNF-alpha.

Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats.

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Lingying Liu

Full Text Available BACKGROUND: Severe burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs could on wound healing in a rat model of severe burn and its potential mechanism. METHODS: Adult male Wistar rats were randomly divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or PBS was intravenous injected into respective groups. The rate of wound closure was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo bioluminescence imaging (BLI, and human-specific DNA expression in wounds was detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and collagen types I/III in wounds were evaluated by histochemical staining. Wound blood flow was evaluated by laser Doppler blood flow meter. The levels of proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in wounds were analyzed using an ELISA. RESULTS: We found that wound healing was significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated into wound and remarkably decreased the quantity of infiltrated inflammatory cells and levels of IL-1, IL-6, TNF-α and increased levels of IL-10 and TSG-6 in wounds. Additionally, the neovascularization and levels of VEGF in wounds in the hUC-MSC therapy group were markedly higher than those in other control groups. The ratio of collagen types I and III in the hUC-MSC therapy group were markedly higher than that in the burn group at indicated time after transplantation. CONCLUSION: The study suggests that hUC-MSCs transplantation can effectively improve wound healing in severe burned rat model. Moreover, these data might provide the theoretical foundation for the further clinical application of hUC-MSC in burn areas.

Topical Application of Propolis Enhances Cutaneous Wound Healing by Promoting TGF-Beta/Smad-Mediated Collagen Production in a Streptozotocin-Induced Type I Diabetic Mouse Model

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Wael N. Hozzein

2015-09-01

Full Text Available Background/Aims: Impaired wound healing is considered to be one of the most serious complications associated with diabetes as it significantly increases the susceptibility of patients to infection. Propolis is a natural bee product used extensively in foods and beverages that has significant benefits to human health. In particular, propolis has antioxidant, anti-inflammatory and analgesic effects that could be useful for improving wound healing. In this study, we investigated the effects of topical application of propolis on the healing and closure of diabetic wounds in a streptozotocin (STZ-induced type I diabetic mouse model. Methods: Sixty male mice were distributed equally into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated daily with a topical application of propolis. Results: We found that diabetic mice exhibited delayed wound closure characterized by a significant decrease in the levels of TGF-β1 and a prolonged elevation of the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α and MMP9 in wound tissues compared with control non-diabetic mice. Moreover, the wound tissues of diabetic mice showed a marked reduction in the phosphorylation of Smad2 and Smad3 as well as a marked reduction in collagen production. Interestingly, compared with untreated diabetic mice, topical application of propolis significantly enhanced the closure of diabetic wounds and decreased the levels of IL-1β, IL-6, TNF-α and MMP9 to near normal levels. Most importantly, compared with untreated diabetic mice, the treatment of diabetic mice with propolis significantly enhanced the production of collagen via the TGF-β1/Smad2,3 signaling axis in wounded tissues. Conclusion: Our findings reveal the molecular mechanisms underlying the improved healing and closure of diabetic wounds following topical propolis application.

Cutaneous mucormycosis in a leukemic patient

International Nuclear Information System (INIS)

Salati, S.A.; Rabah, S.M.

2010-01-01

Mucormycosis is a fulminant and uncommon fungal infection of skin which mostly occurs in immunocompromised patients. Early diagnosis followed by aggressive debridement and administration of antifungal agents is the key to management. We report primary cutaneous mucormycosis in a 23 years old patient of acute leucocytic leukemia who developed this lesion over volar surface of right forearm at the site of intravenous cannulation during induction phase of chemotherapy. The condition was treated successfully by wide surgical debridement, amphotericin-B, wound care and definitive reconstruction with skin graft. (author)

Biodegradable polymer nanofiber membrane for the repair of cutaneous wounds in dogs - two case reports

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Lívia Gomes Amaral

2016-12-01

Full Text Available The study of wound healing and its treatment is extremely important in veterinary medicine due to the high frequency of wounds and the difficulty in treating wounds by second intention. Thus, the objective of this study was to evaluate the use of a nanofiber membrane made of biodegradable polymers as a method of wound treatment in dogs. This study comprised two dogs with bite wounds. Debridement and cleaning was performed followed by the application of the membrane. In one dog, the wound was in the left proximal calcaneal region with clinical signs of infection, necrotic tissue, and muscle and the gastrocnemius tendon were exposed. The wound displayed rapid formation of granulation tissue which became excessive, so it was necessary to debride several times. However, with the suspension of the use of the membrane, formation of this tissue was not observed, and the wound evolved to epithelialization and fast contraction. In the second dog, there was a deep wound on the medial aspect of the proximal right hind limb, with clinical signs of infection, with muscle exposure. Once the membrane was placed, granulation tissue formed, and the membrane was used until the level of this tissue reached the skin. The wound underwent rapid epithelialization and contraction, without developing exuberant granulation tissue. Efficient wound repair was observed and the dogs exhibited greater comfort during application and use of the membrane. More studies should be conducted in dogs focusing on the application of this membrane until the appearance of healthy granulation tissue, as continued use seems to stimulate the formation of exuberant granulation tissue.

Aloesin from Aloe vera accelerates skin wound healing by modulating MAPK/Rho and Smad signaling pathways in vitro and in vivo.

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Wahedi, Hussain Mustatab; Jeong, Minsun; Chae, Jae Kyoung; Do, Seon Gil; Yoon, Hyeokjun; Kim, Sun Yeou

2017-05-15

Cutaneous wound healing is a complex process involving various regulatory factors at the molecular level. Aloe vera is widely used for cell rejuvenation, wound healing, and skin moisturizing. This study aimed to investigate the effects of aloesin from Aloe vera on cutaneous wound healing and mechanisms involved therein. This study consisted of both in vitro and in vivo experiments involving skin cell lines and mouse model to demonstrate the wound healing effects of aloesin by taking into account several parameters ranging from cultured cell migration to wound healing in mice. The activities of Smad signaling molecules (Smad2 and Smad3), MAPKs (ERK and JNK), and migration-related proteins (Cdc42, Rac1, and α-Pak) were assessed after aloesin treatment in cultured cells (1, 5 and 10µM) and mouse skin (0.1% and 0.5%). We also monitored macrophage recruitment, secretion of cytokines and growth factors, tissue development, and angiogenesis after aloesin treatment using IHC analysis and ELISAs. Aloesin increased cell migration via phosphorylation of Cdc42 and Rac1. Aloesin positively regulated the release of cytokines and growth factors (IL-1β, IL-6, TGF-β1 and TNF-α) from macrophages (RAW264.7) and enhanced angiogenesis in endothelial cells (HUVECs). Aloesin treatment accelerated wound closure rates in hairless mice by inducing angiogenesis, collagen deposition and granulation tissue formation. More importantly, aloesin treatment resulted in the activation of Smad and MAPK signaling proteins that are key players in cell migration, angiogenesis and tissue development. Aloesin ameliorates each phase of the wound healing process including inflammation, proliferation and remodeling through MAPK/Rho and Smad signaling pathways. These findings indicate that aloesin has the therapeutic potential for treating cutaneous wounds. Copyright © 2017 Elsevier GmbH. All rights reserved.

[Delayed wound healing post molar extraction].

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Schepers, R H; De Visscher, J G A M

2009-02-01

One month post extraction of the second left maxillary molar the alveolar extraction site showed no signs of healing and was painful. The patient had been using an oral bisphosphonate during 3 years. Therefore, the lesion was diagnosed as bisphosphonate-induced maxillary osteonecrosis. Treatment was conservative. Since one month later the pain had increased and the wound healing had decreased, a biopsy was carried out. Histopathologic examination revealed a non-Hodgkin lymphoma.

Experimental closure of gunshot wounds by fibrin glue with antibiotics in pigs

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Đenić Nebojša

2015-01-01

Full Text Available Background/Aim. Gunshot wounds caused by the automatic rifle M70AB2 (AK-47 7.62 mm, after the primary surgical management, were closed with delayed primary suture during the next four to seven days. This period coincides with the fibroblastic phase of wound healing. Fibrin glue is used as a local hemostatic and as a matrix for the local dosed release of antibiotics. Antibiotics addition to fibrin glue resulted in continuous diffusion into the surrounding next 4 to 7 days. The aim of this study was to create the preconditions for gunshot wounds closing without complications by the application of fibrin glue with antibiotics 24 h after primary surgical treatment. Methods. A total of 14 pigs were wounded in the gluteofemoral region by the bullet M67, initial velocity of 720 m/s. All wounded animals were surgically treated according to the principles of the warsurgery doctrine. Seven wounds were closed with primary delayed suture four days after the primary surgical treatment (traditional approach. Fibrin glue with antibiotics was introduced in seven wounds during the primary surgical treatment and primary delayed suture was done after 24 h. The macroscopic appearance and the clinical assessment of the wound were done during the primary surgical treatment and during its revision after 24 h, as well as histopathological findings at the days 4 and 7 after wounding. Results. Gunshot wounds caused by the automatic rifle M70AB2 (AK-47 7.62 mm, and treated with fibrin glue with antibiotics after primary surgical management, were closed with primary delayed suture after 24 h. In further wound evolution there were no complications. Conclusion. Uncomplicated soft-tissue wounds caused by an automatic M70AB2 rifle may be closed primarily with delayed suture without the risk of developing complications if on revision, 24 h after primary surgery, there were no present necrotic tissues, hematoma, and any signs of infection when fibrin glue with antibiotics

Debridement and wound bed preparation.

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Falabella, Anna F

2006-01-01

Debridement can play a vital role in wound bed preparation and the removal of barriers that impair wound healing. In accordance with the TIME principles, debridement can help remove nonviable tissue, control inflammation or infection, decrease excess moisture, and stimulate a nonadvancing wound edge. There are many types of debridement, each with a set of advantages and disadvantages that must be clearly understood by the healthcare team. Failure to use the correct debridement method for a given type of wound may lead to further delays in healing, increase patient suffering, and unnecessarily increase the cost of care. This review article discusses the various methods of debridement, describes currently available debriding agents, evaluates the clinical data regarding their efficacy and safety, and describes strategies for the management of problematic nonhealing wounds.

Incisional Negative Pressure Wound Therapy in High Risk Patients Undergoing Panniculectomy: A Prospective Randomized Controlled Trial

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2018-01-16

Complications Wounds; Negative Pressure Wound Therapy; Wound Healing Delayed; Incisional; Panniculectomy; Incisional Negative Pressure Wound Therapy; Incisional Vac; Wound Vac; Obese; Renal Failure; Kidney Transplant; Complications; Wound Healing Complication

The occurrence of biofilm in an equine experimental wound model of healing by secondary intention

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Jørgensen, Elin Lisby Kastbjerg; Bay, Lene; Bjarnsholt, Thomas

2017-01-01

impaired healing. Presence of biofilm in tissue biopsies was assessed by peptide nucleic acid fluorescence in situ hybridization (PNA FISH) and confocal laser scanning microscopy (CLSM). Bandaged limb wounds developed EGT and displayed delayed healing, while shoulder and un-bandaged limb wounds healed.......009). The finding that biofilm was most prevalent in bandaged limb wounds with EGT formation suggests that biofilm may be linked to delayed wound healing in horses, as has been observed in humans. The inability to clear bacteria could be related to hypoxia and low-grade inflammation in the EGT, but the interaction......In humans, biofilm is a well-known cause of delayed healing and low-grade inflammation of chronic wounds. In horses, biofilm formation in wounds has been studied to a very limited degree. The objective of this study was thus to investigate the occurrence of biofilm in equine experimental wounds...

Skin-resident stem cells and wound healing.

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Iwata, Yohei; Akamatsu, Hirohiko; Hasebe, Yuichi; Hasegawa, Seiji; Sugiura, Kazumitsu

2017-01-01

CD271 is common stem cell marker for the epidermis and dermis. We assessed a kinetic movement of epidermal and dermal CD271 + cells in the wound healing process to elucidate the possible involvement with chronic skin ulcers. Epidermal CD271 + cells were proliferated and migrated from 3 days after wounding. Purified epidermal CD271 + cells expressed higher TGFβ2 and VEGFα transcripts than CD271 - cells. Delayed wound healing was observed in the aged mice compared with young mice. During the wound healing process, the peak of dermal CD271 + cell accumulation was delayed in aged mice compared with young mice. The expression levels of collagen-1, -3, -5, F4-80, EGF, FGF2, TGFβ1, and IL-1α were significantly increased in young mice compared with aged mice. Furthermore, purified dermal CD271 + cells expressed higher FGF2, EGF, PDGFB, and TGFβ1 gene transcripts than CD271 - cells. These results suggested that epidermal and dermal CD271 + cells were closely associated with wound healing process by producing various growth factors. Epidermal and dermal CD271 + cells in chronic skin ulcer patients were significantly reduced compared with healthy controls. Thus, both epidermal and dermal stem cells can play an important role in wound healing process.

Injury-activated glial cells promote wound healing of the adult skin in mice.

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Parfejevs, Vadims; Debbache, Julien; Shakhova, Olga; Schaefer, Simon M; Glausch, Mareen; Wegner, Michael; Suter, Ueli; Riekstina, Una; Werner, Sabine; Sommer, Lukas

2018-01-16

Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here, we report that peripheral glia are crucially involved in this process. Using a mouse model of wound healing, combined with in vivo fate mapping, we show that injury activates peripheral glia by promoting de-differentiation, cell-cycle re-entry and dissemination of the cells into the wound bed. Moreover, injury-activated glia upregulate the expression of many secreted factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling. Accordingly, depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion promotes myofibroblast formation. Thus, injury-activated glia and/or their secretome might have therapeutic potential in human wound healing disorders.

Effect of fibrin-binding synthetic oligopeptide on the healing of full-thickness skin wounds in streptozotocin-induced diabetic rats.

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Chung, Jae-Eun; Kim, Yun-Jeong; Park, Yoon-Jeong; Koo, Ki-Tae; Seol, Yang-Jo; Lee, Yong-Moo; Rhyu, In-Chul; Ku, Young

2013-01-01

The aim of this study was to investigate whether topical application of fibrin-binding oligopeptides derived from FN promotes wound healing in streptozotocin (STZ)-induced diabetic rats. Oligopeptides including fibrin-binding sequences (FF3: CFDKYTGNTYRV, FF5 : CTSRNRCNDQ) of FN repeats were synthesized. Each peptide was loaded in 15 x 15 mm fibrous alginate dressings, and the release kinetics of the peptides was evaluated using trinitrobenzene sulfonic acid for 336 hours. Two full-thickness cutaneous wounds were prepared on the dorsal skin of each 75 diabetes induced rats. Each wound was divided into FF3-loaded alginate dressing group, FF5-loaded alginate dressing group, alginate dressing group and negative control group. Animals were sacrificed at day 0,3,7 and 14. The wound closure rate, inflammation degree, expression of TGF-β1 and hydroxyproline contents were evaluated. Both FF3 and FF5 peptides were released rapidly within the first 24 hours. FF3-loaded dressing treated wounds closed significantly faster than other wounds at day 3. And at day 14, FF3- & FF5- loaded dressing treated wounds demonstrated less inflammatory cells infiltration than alginate dressing treated and negative group wounds. TGF-β1 positive cells were more abundant in FF3-, FF5-treated alginate dressing treated wound at day 3 and 14. At last, the hyrdroxyproline contents in the FF3, FF5 group were higher at day 7 and day 14. Topical application of fibrin-binding domain synthetic oligopeptides from FN resulted in acceleration of full-thickness cutaneous wound healing in diabetic rats.

Schinus terebinthifolius Raddi ( Aroeira) leaves oil attenuates inflammatory responses in cutaneous wound healing in mice 1.

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Estevão, Lígia Reis Moura; Simões, Ricardo Santos; Cassini-Vieira, Puebla; Canesso, Maria Cecilia Campos; Barcelos, Lucíola da Silva; Rachid, Milene Alvarenga; Câmara, Cláudio Augusto Gomes da; Evêncio-Neto, Joaquim

2017-09-01

To investigated the inflammatory, angiogenic and fibrogenic activities of the Schinus terebinthifolius Raddi leaves oil (STRO) on wound healing. The excisional wound healing model was used to evaluate the effects of STRO. The mice were divided into two groups: Control, subjected to vehicle solution (ointment lanolin/vaseline base), or STRO- treated group, administered topically once a day for 3, 7 and 14 days post-excision. We evaluated the macroscopic wound closure rate; the inflammation was evaluated by leukocytes accumulation and cytokine levels in the wounds. The accumulation of neutrophil and macrophages in the wounds were determined by assaying myeloperoxidase and N-acetyl-β-D-glucosaminidase activities. The levels of TNF-α, CXCL-1 and CCL-2 in wound were evaluated by ELISA assay. Angiogenesis and collagen fibers deposition were evaluated histologically. We observed that macroscopic wound closure rate was improved in wounds from STRO-group than Control-group. The wounds treated with STRO promoted a reduction in leucocyte accumulation and in pro-inflammatory cytokine. Moreover, STRO treatment increased significantly the number of blood vessels and collagen fibers deposition, as compared to control group. Topical application of STRO display anti-inflammatory and angiogenic effects, as well as improvement in collagen replacement, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, including wound healing.

Effect of topically applied Saccharomyces boulardii on the healing of acute porcine wounds: a preliminary study.

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Partlow, Jessica; Blikslager, Anthony; Matthews, Charles; Law, Mac; Daniels, Joshua; Baker, Rose; Labens, Raphael

2016-04-11

Normal wound healing progresses through a series of interdependent physiological events: inflammation, angiogenesis, re-epithelialization, granulation tissue formation and extracellular matrix remodeling. Alterations in this process as well as the bacterial type and load on a wound may alter the wound healing rate. The purpose of this study was to evaluate the effect of topical Saccharomyces boulardii on the healing of acute cutaneous wounds, using a prospective, controlled, experimental study, with six purpose bred landrace pigs. All wounds healed without apparent complications. Comparison of the mean 3D and 2D wound surface area measurements showed no significant difference between treatment groups as wounds decreased similarly in size over the duration of the study. A significant reduction in wound surface area was identified sooner using 3D assessments (by day 9) compared to 2D assessments (by day 12) (P Saccharomyces boulardii does not hasten wound healing or change the wounds' microbiome under the conditions reported in this study.

Effect of ginseng root polysaccharides on cutaneous wound repair in ...

African Journals Online (AJOL)

with WGP (15 mg or 30 mg) or mouse epidermal growth factor (mEGF, 0.1 mL, 2000 IU/mL), respectively. .... dorsal hair was clipped, and one full-thickness, round wound ..... Aloe vera induce MMP-3 and TIMP-2 gene expression during the ...

News in wound healing and management

DEFF Research Database (Denmark)

Gottrup, Finn; Jørgensen, Bo; Karlsmark, Tonny

2009-01-01

-TNFalpha) and Lactobacillus plantarum cultures have also been successfully used in hard to heal, atypical wounds. Knowledge on influencing factors as smoking and biofilm on the healing process has also been improved. Smoking results in delayed healing and increased risk of postoperative infection, whereas the role of biofilm...... is still at an exploratory level. Organizing models for optimal wound management are constantly being developed and refined. SUMMARY: Recent knowledge on the importance of new dressing materials containing active substances, new treatments for atypical wounds, influencing factors on the healing process...

Advances in the medical management of the severe cutaneous radiation syndrome

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Carsin, H.; Stephannazi, J. [Percy Hospital, Clamart (France). Burn Treatment Centre; Gourmelon, P.

2000-05-01

The cutaneous radiation syndrome is a dose dependant complex pathological syndrome which follows a brief localized exposure and characterized by erythema, swelling, moist desquamation, ulceration and necrosis (25-30 Gy). Highly penetrating gamma radiation induces severe dose dependent lesions involving skin, subcutaneous tissue, muscle, vessels, nerves and occasionally, bony structures. The classical treatment of this syndrome includes the debridement of devitalized tissues, the application of bacteriostatic agents coated in non-adherent dressings, opiate-based drugs and in some cases the use of non-steroidal anti-inflammatory drugs. For ulceration and necrosis treatment, the classical surgery is ulcerectomy, necrectomy and amputation for the distal extremity injuries. For the profound et large necrosis, the lesion should be excised and the wound bed covered with a good quality, full-thickness skin graft. Unfortunately the delayed of appearance of this syndrome results often in non specialized medical treatment. Furthermore, because of the chronic evolution (months or years) the management of the cutaneous radiation syndrome has not been considered as a priority for the medical management. Recent accident like the Georgian accident demonstrated that new techniques such as artificial skin graft could change significantly patient prognosis. This technique is routinely used for thermal burn in specialized burn units. We realized the first application of this methodology in the field of radiopathology. An important factor of this technique is that in the case of recurrence of radionecrosis. Often observed, using this technique further grafting may be employed. However the success of this procedure depends on an effective control of the infection. These has sadly been illustrated in the last accident case in Peru where it was impossible to perform the artificial skin graft due to the persistence of a non-eradicated local infection. Whether this particular approach has a

Advances in the medical management of the severe cutaneous radiation syndrome

International Nuclear Information System (INIS)

Carsin, H.; Stephannazi, J.; Gourmelon, P.

2000-01-01

The cutaneous radiation syndrome is a dose dependant complex pathological syndrome which follows a brief localized exposure and characterized by erythema, swelling, moist desquamation, ulceration and necrosis (25-30 Gy). Highly penetrating gamma radiation induces severe dose dependent lesions involving skin, subcutaneous tissue, muscle, vessels, nerves and occasionally, bony structures. The classical treatment of this syndrome includes the debridement of devitalized tissues, the application of bacteriostatic agents coated in non-adherent dressings, opiate-based drugs and in some cases the use of non-steroidal anti-inflammatory drugs. For ulceration and necrosis treatment, the classical surgery is ulcerectomy, necrectomy and amputation for the distal extremity injuries. For the profound et large necrosis, the lesion should be excised and the wound bed covered with a good quality, full-thickness skin graft. Unfortunately the delayed of appearance of this syndrome results often in non specialized medical treatment. Furthermore, because of the chronic evolution (months or years) the management of the cutaneous radiation syndrome has not been considered as a priority for the medical management. Recent accident like the Georgian accident demonstrated that new techniques such as artificial skin graft could change significantly patient prognosis. This technique is routinely used for thermal burn in specialized burn units. We realized the first application of this methodology in the field of radiopathology. An important factor of this technique is that in the case of recurrence of radionecrosis. Often observed, using this technique further grafting may be employed. However the success of this procedure depends on an effective control of the infection. These has sadly been illustrated in the last accident case in Peru where it was impossible to perform the artificial skin graft due to the persistence of a non-eradicated local infection. Whether this particular approach has a

Matching Biological Mesh and Negative Pressure Wound Therapy in Reconstructing an Open Abdomen Defect

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Fabio Caviggioli

2014-01-01

Full Text Available Reconstruction of open abdominal defects is a clinical problem which general and plastic surgeons have to address in cooperation. We report the case of a 66-year-old man who presented an abdominal dehiscence after multiple laparotomies for a sigmoid-rectal adenocarcinoma that infiltrated into the abdominal wall, subsequently complicated by peritonitis and enteric fistula. A cutaneous dehiscence and an incontinent abdominal wall resulted after the last surgery. The abdominal wall was reconstructed using a biological porcine cross-linked mesh Permacol (Covidien Inc., Norwalk, CT. Negative Pressure Wound Therapy (NPWT, instead, was used on the mesh in order to reduce wound dimensions, promote granulation tissue formation, and obtain secondary closure of cutaneous dehiscence which was finally achieved with a split-thickness skin graft. Biological mesh behaved like a scaffold for the granulation tissue that was stimulated by the negative pressure. The biological mesh was rapidly integrated in the abdominal wall restoring abdominal wall continence, while the small dehiscence, still present in the central area, was subsequently covered with a split-thickness skin graft. The combination of these different procedures led us to solve this complicated case obtaining complete wound closure after less than 2 months.

Multiple bacterial species reside in chronic wounds

DEFF Research Database (Denmark)

Gjødsbøl, Kristine; Christensen, Jens Jørgen; Karlsmark, Tonny

2006-01-01

. aeruginosa were found to be significantly larger than ulcers without the presence of P. aeruginosa (P wound is colonised by multiple bacterial species and that once they are established many of them persist in the wound. Our results suggest that the presence...... of P. aeruginosa in venous leg ulcers can induce ulcer enlargement and/or cause delayed healing....

Regularity of wound healing in rats irradiated locally with different doses of soft X-rays

International Nuclear Information System (INIS)

Liu Jianzhong; Zhou Yuanguo; Cheng Tianmin; Zhou Ping; Liu Xia; Li Ping

2002-01-01

Objective: To study the regular patter of wound healing in rats irradiated locally with different doses of soft X-rays. Methods: Rats were locally irradiated, and wounded immediately thereafter. Gross observation, histopathology and immunohistochemistry examinations, and image analysis were used to study the wound healing process. Results: The authors found that the delayed time of wound healing induced by soft X-ray irradiation of 0.50, 1.01, 1.96, 3,26, 4.00, 5.21 Gy was 1.6, 4.2, 5.4, 6.6, 8.2 and 9.4 days, respectively. Irradiation with 7.0 and 10.0 Gy caused failure of wound healing (up to 40 days). Compared to the non-irradiated wounds, the healing rates of irradiation-impaired wounds were lower during the whole healing process. From day 3 to day 9 after irradiation, the healing rates decreased along with increasing of the radiation dose, indicating the key phase of wound healing was delayed. After irradiation, the collagen synthesis was decreased, its arrangement was disordered, and the structure of granulation tissue was irregular. Conclusion: Soft X-rays irradiation may cause a delay of wound healing in a dose-dependent manner, and irradiation with 7.0 and 10.0 Gy cause failure of wound healing

Human Platelet-Rich Plasma- and Extracellular Matrix-Derived Peptides Promote Impaired Cutaneous Wound Healing In Vivo

Science.gov (United States)

Demidova-Rice, Tatiana N.; Wolf, Lindsey; Deckenback, Jeffry; Hamblin, Michael R.; Herman, Ira M.

2012-01-01

Previous work in our laboratory has described several pro-angiogenic short peptides derived from endothelial extracellular matrices degraded by bacterial collagenase. Here we tested whether these peptides could stimulate wound healing in vivo. Our experiments demonstrated that a peptide created as combination of fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal wounds created in mice treated with cyclophosphamide to impair wound healing, can improve the rate of wound closure. Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma. In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury. Results of in vivo experiments where comb1 and UN3 peptides were added together to cranial wounds in cyclophosphamide-treated mice leads to improvement of wound vascularization as shown by an increase of the number of blood vessels present in the wound beds. Application of the peptides markedly promotes cellular responses to injury and essentially restores wound healing dynamics to those of normal, acute wounds in the absence of cyclophosphamide impairment. Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects. PMID:22384158

Prolonged C1 Inhibitor Administration Improves Local Healing of Burn Wounds and Reduces Myocardial Inflammation in a Rat Burn Wound Model

NARCIS (Netherlands)

Begieneman, Mark P. V.; Kubat, Bela; Ulrich, Magda M. W.; Hahn, Nynke E.; Stumpf-Stolker, Yvette; Tempelaars, Miranda; Middelkoop, Esther; Zeerleder, Sacha; Wouters, Diana; van Ham, Marieke S.; Niessen, Hans W. M.; Krijnen, Paul A. J.

2012-01-01

In a previous study, the authors found persistent presence of acute inflammation markers such as C-reactive protein and complement factors locally in burn wounds. This persistence of acute inflammation may not only delay local burn wound healing but also have a systemic effect, for instance on the

Transcutaneous electrical nerve stimulation (TENS) accelerates cutaneous wound healing and inhibits pro-inflammatory cytokines.

Science.gov (United States)

Gürgen, Seren Gülşen; Sayın, Oya; Cetin, Ferihan; Tuç Yücel, Ayşe

2014-06-01

The purpose of this study was to evaluate transcutaneous electrical nerve stimulation (TENS) and other common treatment methods used in the process of wound healing in terms of the expression levels of pro-inflammatory cytokines. In the study, 24 female and 24 male adult Wistar-Albino rats were divided into five groups: (1) the non-wounded group having no incision wounds, (2) the control group having incision wounds, (3) the TENS (2 Hz, 15 min) group, (4) the physiological saline (PS) group and (5) the povidone iodine (PI) group. In the skin sections, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed with enzyme-linked immunosorbent assay and immunohistochemical methods. In the non-wounded group, the expression of IL-1β, IL-6, and TNF-α signaling molecules was weaker in the whole tissue; however, in the control group, significant inflammatory response occurred, and strong cytokine expression was observed in the dermis, granulation tissue, hair follicles, and sebaceous glands (P TENS group, the decrease in TNF-α, IL-1β, and IL-6 immunoreaction in the skin was significant compared to the other forms of treatment (P TENS group suggest that TENS shortened the healing process by inhibating the inflammation phase.

Topical photodynamic therapy following excisional wounding of human skin increases production of transforming growth factor-β3 and matrix metalloproteinases 1 and 9, with associated improvement in dermal matrix organization.

Science.gov (United States)

Mills, S J; Farrar, M D; Ashcroft, G S; Griffiths, C E M; Hardman, M J; Rhodes, L E

2014-07-01

Animal studies report photodynamic therapy (PDT) to improve healing of excisional wounds; the mechanism is uncertain and equivalent human studies are lacking. To explore the impact of methyl aminolaevulinate (MAL)-PDT on clinical and microscopic parameters of human cutaneous excisional wound healing, examining potential modulation through production of transforming growth factor (TGF)-β isoforms. In 27 healthy older men (60-77 years), a 4-mm punch biopsy wound was created in skin of the upper inner arm and treated with MAL-PDT three times over 5 days. An identical control wound to the contralateral arm was untreated and both wounds left to heal by secondary intention. Wounds were re-excised during the inflammatory phase (7 days, n = 10), matrix remodelling (3 weeks, n = 8) and cosmetic outcome/dermal structure (9 months, n = 9). Production of TGF-β1, TGF-β3 and matrix metalloproteinases (MMPs) was assessed by immunohistochemistry alongside microscopic measurement of wound size/area and clinical assessment of wound appearance. MAL-PDT delayed re-epithelialization at 7 days, associated with increased inflammation. However, 3 weeks postwounding, treated wounds were smaller with higher production of MMP-1 (P = 0·01), MMP-9 (P = 0·04) and TGF-β3 (P = 0·03). TGF-β1 was lower than control at 7 days and higher at 3 weeks (both P = 0·03). At 9 months, MAL-PDT-treated wounds showed greater, more ordered deposition of collagen I, collagen III and elastin (all P < 0·05). MAL-PDT increases MMP-1, MMP-9 and TGF-β3 production during matrix remodelling, ultimately producing scars with improved dermal matrix architecture. © 2014 British Association of Dermatologists.

Combing a novel device and negative pressure wound therapy for managing the wound around a colostomy in the open abdomen: A case report.

Science.gov (United States)

Sun, Xiaofang; Wu, Shaohan; Xie, Ting; Zhang, Jianping

2017-12-01

An open abdomen complicated with small-bowel fistulae becomes a complex wound for local infection, systemic sepsis and persistent soiling irritation by intestinal content. While controlling the fistulae drainage, protecting surrounding skin, healing the wound maybe a challenge. In this paper we described a 68-year-old female was admitted to emergency surgery in general surgery department with severe abdomen pain. Resection part of the injured small bowel, drainage of the intra-abdominal abscess, and fashioning of a colostomy were performed. She failed to improve and ultimately there was tenderness and lot of pus under the skin around the fistulae. The wound started as a 3-cm lesion and progressed to a 6 ×13  (78 cm) around the stoma. In our case we present a novel device for managing colostomy wound combination with negative pressure wound therapy. This tube allows for an effective drainage of small-bowel secretion and a safe build-up of granulation tissue. Also it could be a barrier between the bowel suction point and foam. Management of open abdomen wound involves initial dressing changes, antibiotic use and cutaneous closure. When compared with traditional dressing changes, the NPWT offers several advantages including increased granulation tissue formation, reduction in bacterial colonization, decreased of bowel edema and wound size, and enhanced neovascularization. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Mesotherapy and cutaneous Mycobacterium fortuitum infection.

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Difonzo, Elisa Margherita; Campanile, Grazia Lucia; Vanzi, Laura; Lotti, Lorena

2009-06-01

Cutaneous infections caused by Mycobacterium fortuitum usually are a complication of trauma or postsurgical wounds. A 41-year-old woman presented with numerous dusky red nodules, abscesses and sinuses on the right buttock and on the lateral surfaces of both thighs. The lesions developed at the injection sites of mesotherapy treatment. M. fortuitum was cultured from a biopsy specimen and purulent fluid drained from lesions. The lesions had cleared completely with ciprofloxacin 500 mg b.d. for 3 weeks, and then 250 mg b.d. for another 3 weeks. This case demonstrates the importance of suspecting mycobacterial etiology in patients with nodules and abscesses in the areas of mesotherapy treatment.

Evaluation of the effect of LED radiation in the repair of skin wounds on the dorsum of rats with iron deficiency anemia

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de Oliveira, Susana Carla Pires Sampaio; de Carvalho Monteiro, Juliana Santos; dos Santos Aciole, Gilberth Tadeu; DeCastro, Isabele Cardoso V.; Menezes, Diego Silva; de Fátima Lima Ferreira, Maria; dos Santos, Jean Nunes; Zanin, Fátima; Barbosa Pinheiro, Antônio Luiz

2010-05-01

Iron deficiency anemia causes reduction on the level of hemoglobin and of the number of RBC and affects around 35% of the human population. Laser and LED therapies have been successfully used on wound healing studies. The aim of the present study was to assess histologically the effect of LED Phototherapy on the healing of cutaneous wounds on anemic rats. Fifty one 21 days old male wistar rats weighting around 50 g were kept under iron free die (Sem ferro-AIN93-G) during 15 days in order to induce anemia. Non treated animals acted as controls. A standartized cutaneous wound was created on the dorsum of each animal whom were distributed into four groups: Group I—Anemia+LED, Group II—Non anemic+LED, Group III—Anemia+no treatment, Group IV—No anemic+no-treatment. Irradiation started immediately after surgery and repeated at 48 h intervals during 21 days. Animal death occurred after 7, 14 and 21 days after wounding. The results of the histologic analysis showed that LED Phototherapy stimulated fibroblastic proliferation. It is concluded that LED irradiation improves wound healing on iron deficient anemic animals.

Wound infiltration with local anesthetic after abdominal surgery

International Nuclear Information System (INIS)

Shah, Z.; Ahmad, R.; Haider, S.M.

2003-01-01

This study was carried out to compare the effect of analgesia with local wound infiltration with 20ml of 0.5% bupivacaine in post operative wounds with the control group having no infiltration. Patients were mobilized much earlier than in the control group while the demand of analgesics was considerably delayed in the study group. No any complications was noticed during local infiltration of wounds after abdominal surgery and is, therefore, applicable in routine surgery. (author)

Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications.

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Ojeh, Nkemcho; Pastar, Irena; Tomic-Canic, Marjana; Stojadinovic, Olivera

2015-10-23

The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular mechanisms, many of which are still poorly understood. Current chronic wound therapies are limited, so the search to develop better therapeutic strategies is ongoing. Adult stem cells are gaining recognition as potential candidates for numerous skin pathologies. In this review, we will discuss epidermal and other stem cells present in the skin, and highlight some of the therapeutic applications of epidermal stem cells and other adult stem cells as tools for cell/scaffold-based therapies for non-healing wounds and other skin disorders. We will also discuss emerging concepts and offer some perspectives on how skin tissue-engineered products can be optimized to provide efficacious therapy in cutaneous repair and regeneration.

A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair

DEFF Research Database (Denmark)

Grose, Richard; Hutter, Caroline; Bloch, Wilhelm

2002-01-01

of beta 1 integrins in keratinocytes caused a severe defect in wound healing. beta 1-null keratinocytes showed impaired migration and were more densely packed in the hyperproliferative epithelium. Surprisingly, their proliferation rate was not reduced in early wounds and even increased in late wounds....... The failure in re-epithelialisation resulted in a prolonged inflammatory response, leading to dramatic alterations in the expression of important wound-regulated genes. Ultimately, beta 1-deficient epidermis did cover the wound bed, but the epithelial architecture was abnormal. These findings demonstrate...

Transforming growth factor-β (TGF-β) activation in cutaneous wounds after topical application of aloe vera gel.

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Takzaree, Nasrin; Hadjiakhondi, Abbas; Hassanzadeh, Gholamreza; Rouini, Mohammad Reza; Manayi, Azadeh; Zolbin, Masoumeh Majidi

2016-12-01

Aloe vera is a medicinal plant used to treat various skin diseases. The effects of using aloe vera gel on the healing process were investigated by microscopic methods, cell counting, and TGF-β gene expression in the wound bed. Sixty Wistar rats weighing 200-250 g were placed under anesthesia in sterile conditions. A square 1.5 cm × 1.5 cm wound was made on the back of the neck. The rats were divided into control and 2 experimental groups. Additionally, the control and experimental groups were separated into 3 subgroups corresponding to 4, 7, and 14 days of study. In the first experimental group, aloe vera was used twice on the wound. The second experimental group received aloe vera overtreatment once on the wound. The positive control group received daily application of 1% phenytoein cream following surgical wound creation. The control group did not receive any treatment. This tissue was examined using histological staining (H&E) and Masson's Trichrome. Wound surface and wound healing were evaluated separately. TGF-β gene expression was analyzed by RT-PCR. Results showed that fibroblasts in both experimental groups were significantly increased, thereby acceleration wound healing. Application of aloe vera gel will increase TGF-β gene expression, ultimately accelerating the wound healing process.

Aged blood factors decrease cellular responses associated with delayed gingival wound repair.

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María Paz Saldías

Full Text Available Aging is a gradual biological process characterized by a decrease in cell and organism functions. Gingival wound healing is one of the impaired processes found in old rats. Here, we studied the in vivo wound healing process using a gingival repair rat model and an in vitro model using human gingival fibroblast for cellular responses associated to wound healing. To do that, we evaluated cell proliferation of both epithelial and connective tissue cells in gingival wounds and found decreased of Ki67 nuclear staining in old rats when compared to their young counterparts. We next evaluated cellular responses of primary gingival fibroblast obtained from young subjects in the presence human blood serum of individuals of different ages. Eighteen to sixty five years old masculine donors were classified into 3 groups: "young" from 18 to 22 years old, "middle-aged" from 30 to 48 years old and "aged" over 50 years old. Cell proliferation, measured through immunofluorescence for Ki67 and flow cytometry for DNA content, was decreased when middle-aged and aged serum was added to gingival fibroblast compared to young serum. Myofibroblastic differentiation, measured through alpha-smooth muscle actin (α-SMA, was stimulated with young but not middle-aged or aged serum both the protein levels and incorporation of α-SMA into actin stress fibers. High levels of PDGF, VEGF, IL-6R were detected in blood serum from young subjects when compared to middle-aged and aged donors. In addition, the pro-inflammatory cytokines MCP-1 and TNF were increased in the serum of aged donors. In old rat wound there is an increased of staining for TNF compared to young wound. Moreover, healthy gingiva (non injury shows less staining compared to a wound site, suggesting a role in wound healing. Moreover, serum from middle-aged and aged donors was able to stimulate cellular senescence in young cells as determined by the expression of senescence associated beta-galactosidase and histone H2

Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review.

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Ho, Jasmine; Walsh, Claire; Yue, Dominic; Dardik, Alan; Cheema, Umber

2017-06-01

Significance: With an aging population leading to an increase in diabetes and associated cutaneous wounds, there is a pressing clinical need to improve wound-healing therapies. Recent Advances: Tissue engineering approaches for wound healing and skin regeneration have been developed over the past few decades. A review of current literature has identified common themes and strategies that are proving successful within the field: The delivery of cells, mainly mesenchymal stem cells, within scaffolds of the native matrix is one such strategy. We overview these approaches and give insights into mechanisms that aid wound healing in different clinical scenarios. Critical Issues: We discuss the importance of the biomimetic niche, and how recapitulating elements of the native microenvironment of cells can help direct cell behavior and fate. Future Directions: It is crucial that during the continued development of tissue engineering in wound repair, there is close collaboration between tissue engineers and clinicians to maintain the translational efficacy of this approach.

ANALYSIS OF TREATMENT OF WOUNDS IN PATIENTS WITH GRADE IIIB COMPOUND FRACTURE WITH VACUUM-ASSISTED WOUND MANAGEMENT

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Ashish R. Agarwal

2017-08-01

Full Text Available BACKGROUND Delayed wound healing is a significant health problem, particularly in patients with compound fractures. It still remains a challenging task in orthopaedic surgery, which in addition to the pain and suffering, failure of the wound to heal, also imposes social and financial burdens. The aim of the study is to evaluate the results of vacuum-assisted wound therapy in patients with open musculoskeletal injuries. MATERIALS AND METHODS 30 patients of open musculoskeletal injuries underwent randomised trial of vacuum-assisted closure therapy versus standard wound therapy around the upper limb and lower limb. Mean patient age was 39 ± 18 years necrotic tissues were debrided before applying VAC therapy. Dressings were changed every 3 or 4 days. For standard wound therapy, debridement followed by daily dressings was done. Data Management and Statistical Analysis- The results obtained were subjected to statistical analysis. RESULTS Granulation tissue status and skin healing is better in patients undergoing VAC therapy. Hospital stay of patients undergoing VAC therapy was also less. CONCLUSION Vacuum-assisted wound therapy was better method of wound management.

Wound research funding from alternative sources of federal funds in 2012.

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Baquerizo Nole, Katherine L; Yim, Elizabeth; Van Driessche, Freya; Davidson, Jeffrey M; Martins-Green, Manuela; Sen, Chandan K; Tomic-Canic, Marjana; Kirsner, Robert S

2014-01-01

Chronic wounds represent a major healthcare burden, costing $25 billion annually, and are associated with high mortality. We previously reported that cutaneous wound healing represented only 0.1% ($29.8 million) of the National Institutes of Health budget. This current study focuses on quantifying the contribution by federal agencies other than the National Institutes of Health for fiscal year 2012. Federal databases including USA Spending, Veterans Affairs, Tracking Accountability in Government Grants Systems, Health Services Research Projects in Progress, and Patient-Centered Outcomes Research Institute, were searched for individual projects addressing wound healing. Twenty-seven projects were identified, totaling funding of $16,588,623 (median: $349,856). Four sponsor institutions accounted for 74% of awarded funds: Department of the Army, National Science Foundation, Department of Veterans Affairs, and Agency for Healthcare Research & Quality. Research projects and cooperative agreements comprised 44% and 37% of awarded grants. New applications and continuing projects represented 52% and 37%. Wound healing represented 0.15% of total medical research funded by the non-National Institutes of Health federal sector. Compared with potential impact on US public health, federal investment in wound research is exiguous. This analysis will draw attention to a disproportionately low investment in wound research and its perils to American public health. © 2014 by the Wound Healing Society.

Oral administration of marine collagen peptides from Chum Salmon skin enhances cutaneous wound healing and angiogenesis in rats.

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Zhang, Zhaofeng; Wang, Junbo; Ding, Ye; Dai, Xiaoqian; Li, Yong

2011-09-01

A wound is a clinical entity which often poses problems in clinical practice. The present study was aimed to investigate the wound healing potential of administering marine collagen peptides (MCP) from Chum Salmon skin by using two wound models (incision and excision) in rats. Ninety-six animals were equally divided into the two wound models and then within each model animals were randomly divided into two groups: vehicle-treated group and 2 g kg(-1) MCP-treated group. Wound closure and tensile strength were calculated. Collagen deposition was assessed by Masson staining and hydroxyproline measurement. Angiogenesis was assessed by immunohistological methods. MCP-treated rats showed faster wound closure and improved tissue regeneration at the wound site, which was supported by histopathological parameters pertaining to wound healing. MCP treatment improved angiogenesis and helped form thicker and better organised collagen fibre deposition compared to vehicle-treated group. The results show the efficacy of oral MCP treatment on wound healing in animals. Copyright © 2011 Society of Chemical Industry.

Effects of Foeniculum vulgare essential oil compounds, fenchone and limonene, on experimental wound healing.

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Keskin, I; Gunal, Y; Ayla, S; Kolbasi, B; Sakul, A; Kilic, U; Gok, O; Koroglu, K; Ozbek, H

2017-01-01

We investigated the wound healing efficacy of the Foeniculum vulgare compounds, fenchone and limonene, using an excisional cutaneous wound model in rats. An excision wound was made on the back of the rat and fenchone and limonene were applied topically to the wounds once daily, separately or together, for 10 days. Tissue sections from the wounds were evaluated for histopathology. The healing potential was assessed by comparison to an untreated control group and an olive oil treated sham group. We scored wound healing based on epidermal regeneration, granulation tissue thickness and angiogenesis. After day 6, wound contraction with limonene was significantly better than for the control group. Ten days after treatment, a significant increase was observed in wound contraction and re-epithelialization in both fenchone and limonene oil treated groups compared to the sham group. Groups treated with fenchone and with fenchone + limonene scored significantly higher than the control group, but the difference was not statistically significant compared to the olive oil treated group. Our findings support the beneficial effects of fenchone and limonene for augmenting wound healing. The anti-inflammatory and antimicrobial activities of fenchone and limonene oil increased collagen synthesis and decreased the number of inflammatory cells during wound healing and may be useful for treating skin wounds.

Experience with wound VAC and delayed primary closure of contaminated soft tissue injuries in Iraq.

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Leininger, Brian E; Rasmussen, Todd E; Smith, David L; Jenkins, Donald H; Coppola, Christopher

2006-11-01

Wartime missile injuries are frequently high-energy wounds that devitalize and contaminate tissue, with high risk for infection and wound complications. Debridement, irrigation, and closure by secondary intention are fundamental principles for the management of these injuries. However, closure by secondary intention was impractical in Iraqi patients. Therefore, wounds were closed definitively before discharge in all Iraqi patients treated for such injures at our hospital. A novel wound management protocol was developed to facilitate this practice, and patient outcomes were tracked. This article describes that protocol and discusses the outcomes in a series of 88 wounds managed with it. High-energy injuries were treated with rapid aggressive debridement and pulsatile lavage, then covered with negative pressure (vacuum-assisted closure [VAC]) dressings. Patients underwent serial operative irrigation and debridement until wounds appeared clean to gross inspection, at which time they were closed primarily. Patient treatment and outcome data were recorded in a prospectively updated database. Treatment and outcomes data from September 2004 through May 2005 were analyzed retrospectively. There were 88 high-energy soft tissue wounds identified in 77 patients. Surprisingly, for this cohort of patients the wound infection rate was 0% and the overall wound complication rate was 0%. This series of 88 cases is the first report of the use of a negative pressure dressing (wound VAC) as part of the definitive management of high-energy soft tissue wounds in a deployed wartime environment. Our experience with these patients suggests that conventional wound management doctrine may be improved with the wound VAC, resulting in earlier more reliable primary closure of wartime injuries.

Effects of low-level laser therapy on wound healing

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Fabiana do Socorro da Silva Dias Andrade

Full Text Available OBJECTIVE: To gather and clarify the actual effects of low-level laser therapy on wound healing and its most effective ways of application in human and veterinary medicine.METHODS: We searched original articles published in journals between the years 2000 and 2011, in Spanish, English, French and Portuguese languages, belonging to the following databases: Lilacs, Medline, PubMed and Bireme; Tey should contain the methodological description of the experimental design and parameters used.RESULTS: doses ranging from 3 to 6 J/cm2 appear to be more effective and doses 10 above J/cm2 are associated with deleterious effects. The wavelengths ranging from 632.8 to 1000 nm remain as those that provide more satisfactory results in the wound healing process.CONCLUSION: Low-level laser can be safely applied to accelerate the resolution of cutaneous wounds, although this fact is closely related to the election of parameters such as dose, time of exposure and wavelength.

Intralimb and Interlimb Cutaneous Reflexes during Locomotion in the Intact Cat.

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Hurteau, Marie-France; Thibaudier, Yann; Dambreville, Charline; Danner, Simon M; Rybak, Ilya A; Frigon, Alain

2018-04-25

When the foot contacts an obstacle during locomotion, cutaneous inputs activate spinal circuits to ensure dynamic balance and forward progression. In quadrupeds, this requires coordinated reflex responses between the four limbs. Here, we investigated the patterns and phasic modulation of cutaneous reflexes in forelimb and hindlimb muscles evoked by inputs from all four limbs. Five female cats were implanted to record muscle activity and to stimulate the superficial peroneal and superficial radial nerves during locomotion. Stimulating these nerves evoked short-, mid-, and longer-latency excitatory and/or inhibitory responses in all four limbs that were phase-dependent. The largest responses were generally observed during the peak activity of the muscle. Cutaneous reflexes during mid-swing were consistent with flexion of the homonymous limb and accompanied by modification of the stance phases of the other three limbs, by coactivating flexors and extensors and/or by delaying push-off. Cutaneous reflexes during mid-stance were consistent with stabilizing the homonymous limb by delaying and then facilitating its push-off and modifying the support phases of the homolateral and diagonal limbs, characterized by coactivating flexors and extensors, reinforcing extensor activity and/or delaying push-off. The shortest latencies of homolateral and diagonal responses were consistent with fast-conducting disynaptic or trisynaptic pathways. Descending homolateral and diagonal pathways from the forelimbs to the hindlimbs had a higher probability of eliciting responses compared with ascending pathways from the hindlimbs to the forelimbs. Thus, in quadrupeds, intralimb and interlimb reflexes activated by cutaneous inputs ensure dynamic coordination of the four limbs, producing a whole-body response. SIGNIFICANCE STATEMENT The skin contains receptors that, when activated, send inputs to spinal circuits, signaling a perturbation. Rapid responses, or reflexes, in muscles of the

Sucralfate prevents the delay of wound repair in intestinal epithelial cells by hydrogen peroxide through NF-kappaB pathway.

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Shindo, Kenichi; Iizuka, Masahiro; Sasaki, Kenji; Konno, Shiho; Itou, Hiroaki; Horie, Yasuo; Watanabe, Sumio

2006-05-01

Recent studies have shown that sucralfate (SF) has therapeutic effects on colonic inflammation in ulcerative colitis. The aim of this study was to clarify the function of SF for wound repair in intestinal epithelial cells (IEC). (1) Activation of signal proteins [ERK1/2 mitogen-activated protein kinase (MAPK), IkappaB-alpha] in IEC-6 cells after stimulation with 10(-4) M potassium sucrose octasulfate (SOS), which is the functional element of SF, was assessed by Western blot. (2) Induction of transforming growth factor (TGF)-beta1, TGF-alpha, EGF, and cyclooxygenase-2 (COX-2) mRNA after stimulation of IEC-6 cells with SOS was assessed by reverse transcriptase-polymerase chain reaction. (3) IEC-6 cells were wounded and cultured for 24 h with various concentrations of SOS in the absence or presence of 20 microM H(2)O(2). Epithelial migration or proliferation was assessed by counting migrating cells or bromodeoxyuridine (BrdU)-positive cells across the wound border. (1) SOS activated IkappaB-alpha, but it did not activate ERK1/2 MAPK. (2) SOS enhanced the expression of COX-2 mRNA, but it did not change the mRNA expression of other growth factors. (3) SOS did not enhance wound repair in IEC-6 cells, but it decreased the number of dead cells (maximum, 74%) (P < 0.01) in a dose-dependent manner and prevented the diminishment of epithelial migration (maximum, 61%) (P < 0.01) and proliferation (maximum, 37%) (P < 0.05) induced by H(2)O(2). These functions of SOS were suppressed by the NF-kappaB and COX-2 inhibitors. SOS prevented the delay of wound repair in IEC-6 cells induced by H(2)O(2), probably through induction of COX-2 and an anti-apoptotic mechanism. These effects of SOS might be given through the activation of the NF-kappaB pathway.

A multi-centre clinical evaluation of reactive oxygen topical wound gel in 114 wounds.

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Dryden, M; Dickinson, A; Brooks, J; Hudgell, L; Saeed, K; Cutting, K F

2016-03-01

This article reports the outcomes of the use of Surgihoney RO (SHRO), topical wound dressing in a multi-centre, international setting. The aims were to explore the clinical effects of SHRO, including a reduction in bacterial load and biofilm and improvement in healing in a variety of challenging non-healing and clinically infected wounds. This was a non-comparative evaluation, where both acute and chronic wounds with established delayed healing were treated with the dressing. Clinicians prospectively recorded wound improvement or deterioration, level of wound exudate, presence of pain, and presence of slough and necrosis. Analysis of this data provided information on clinical performance of the dressing. Semi-quantitative culture to assess bacterial bioburden was performed where possible. We recruited 104 patients, mean age 61 years old, with 114 wounds. The mean duration of wounds before treatment was 3.7 months and the mean duration of treatment was 25.7 days. During treatment 24 wounds (21%) healed and the remaining 90 (79%) wounds improved following application of the dressing. No deterioration in any wound was observed. A reduction in patient pain, level of wound exudate and in devitalised tissue were consistently reported. These positive improvements in wound progress were reflected in the wound cultures that showed a reduction in bacterial load in 39 out of the 40 swabs taken. There were two adverse events recorded: a stinging sensation following application of the dressing was experienced by 2 patients, and 2 elderly patients died of causes unrelated to the dressing or to the chronic wound. These patients' wounds and their response to SHRO have been included in the analysis. SHRO was well tolerated and shows great promise as an effective potent topical antimicrobial in the healing of challenging wounds. Matthew Dryden has become a shareholder in Matoke Holdings, the manufacturer of Surgihoney RO, since the completion of this study. Keith Cutting is a

Full-Thickness Thermal Injury Delays Wound Closure in a Murine Model

Science.gov (United States)

2015-01-01

skin replacement is achieved using autologous skin graft or skin substitute graft. While this strategy of early excision and grafting, first proposed in...several investigators have utilized the more appropriate model of burn eschar excision followed by sponta- neous wound closure or by skin graft or...without the application of a skin graft or a skin substitute graft. Furthermore, the effect of interval burn eschar excision on wound closure is also re

Effect of aging on wound healing: current concepts.

Science.gov (United States)

Pittman, Joyce

2007-01-01

The population is aging, and advanced age is commonly identified as a risk factor for delayed wound healing. Therefore, it is important for WOC nurses to be knowledgeable about how aging affects the wound healing and repair process, and strategies they can use to promote healing in the elderly population. Impaired wound healing in the aged is due partly to comorbidities common among the elderly, but evidence also suggests that inherent differences in cellular structure and function may impair tissue repair and regeneration as well. This article will address the effect of aging on wound healing, with a particular focus on processes of cellular senescence and related factors hypothesized to result in slowed or impaired wound healing in the elderly.

Methylisothiazolinone toxicity and inhibition of wound healing and regeneration in planaria.

Science.gov (United States)

Van Huizen, Alanna V; Tseng, Ai-Sun; Beane, Wendy S

2017-10-01

Methylisothiazolinone (MIT) is a common biocide used in cosmetic and industrial settings. Studies have demonstrated that MIT is a human sensitizer, to the extent that in 2013 MIT was named allergen of the year. Recently, we showed that MIT exposure in Xenopus laevis (the African clawed frog) inhibits wound healing and tail regeneration. However, it is unknown whether MIT affects these processes in other animals. Here, we investigated the effects of MIT exposure in planaria-non-parasitic freshwater flatworms able to regenerate all tissues after injury. Using a common research strain of Dugesia japonica, we determined that intact planarians exposed to 15μM MIT displayed both neuromuscular and epithelial-integrity defects. Furthermore, regenerating (head and tail) fragments exposed to 15μM MIT failed to close wounds or had significantly delayed wound healing. Planarian wounds normally close within 1h after injury. However, most MIT-exposed animals retained open wounds at 24h and subsequently died, and those few animals that were able to undergo delayed wound healing without dying exhibited abnormal regeneration. For instance, head regeneration was severely delayed or inhibited, with anterior structures such as eyes failing to form in newly produced tissues. These data suggest that MIT directly affects both wound healing and regeneration in planarians. Next, we investigated the ability of thiol-containing antioxidants to rescue planarian wound closure during MIT exposure. The data reveal both n-acetyl cysteine and glutathione were each able to fully rescue MIT inhibition of wound healing. Lastly, we established MIT toxicity levels by determining the LC 50 of 5 different planarian species: D. japonica, Schmidtea mediterranea, Girardia tigrina, Girardia dorotocephala, and Phagocata gracilis. Our LC 50 data revealed that concentrations as low as 39μM (4.5ppm) are lethal to planarians, with concentrations of just 5μM inhibiting wound healing, and suggest that phylogeny

Wound healing complications in brain tumor patients on Bevacizumab.

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Ladha, Harshad; Pawar, Tushar; Gilbert, Mark R; Mandel, Jacob; O-Brien, Barbara; Conrad, Charles; Fields, Margaret; Hanna, Teresa; Loch, Carolyn; Armstrong, Terri S

2015-09-01

Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6-559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1-16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27-345). Median time from starting BEV to developing wound complication was 47 days (range 16-173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34-346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6-559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26-69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation.

Hydroethanolic Extract of Strychnos pseudoquina Accelerates Skin Wound Healing by Modulating the Oxidative Status and Microstructural Reorganization of Scar Tissue in Experimental Type I Diabetes

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Mariáurea M. Sarandy

2017-01-01

Full Text Available The effect of topical application of ointment based on Strychnos pseudoquina hydroethanolic extract in the cutaneous wounds healing in diabetic rats was evaluated. Samples of S. pseudoquina were submitted to phytochemical prospection and in vitro antioxidant assay. Thirty Wistar rats were divided into 5 groups: Sal-wounds treated with 0.9% saline solution; VH-wounds treated with 0.6 g of lanolin cream (vehicle; SS-wounds treated with silver sulfadiazine cream (10 mg/g; ES5- and ES10-wounds treated with an ointment of S. pseudoquina extract, 5% and 10%, respectively. Fragments of wounds were removed for histological and biochemical analysis every 7 days during 21 days. ES showed equivalent levels per gram of extract of total phenols and flavonoids equal to 122.04 mg for TAE and 0.60 mg for RE. The chlorogenic acid was one of the major constituents. S. pseudoquina extract presented high antioxidant potential in vitro. ES5 and ES10 showed higher wound healing rate and higher amount of cells, blood vessels, and type III and I collagen. The oxidative stress markers were lower in the ES5 and ES10 groups, while the antioxidants enzymes levels were higher. Ointment based on S. pseudoquina extract promotes a fast and efficient cutaneous repair in diabetic rats.

Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing.

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Katsunari Makino

Full Text Available Endothelin (ET-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF-α and connective tissue growth factor (CTGF were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.

Assesment of systemic exposure form a wound contaminated by radioactive products

International Nuclear Information System (INIS)

Piechowski, Jean; Menoux, Bernadette; Chaptinel, Yves

1992-03-01

Wound contamination may occur in case of accidental exposure of workers handling radioactive products. In order to operate radio-toxicological follow-up, a fairly general model must be able to apply to the various injuries and products involved. Some principles and their applications are developed to make it possible for physicians to set up a monitoring program relevant to the assessment of the systemic burden. Only the dosimetry relative to the activity passing through the cutaneous mucous barrier into the blood flow is considered. Local doses at the wound level are not considered. For the interpretation of the measurements, both retention and excretion curves and dosimetric factors are given for the most common radionuclides. (authors) [fr

AEROBIC BACTERIAL ISOLATES FROM INFECTED WOUNDS

African Journals Online (AJOL)

boaz

most frequently reported as the cause of delay wound healing (6-9, 3). ... All isolates were resistant to Ampicillin, Amoxicillin- clavulanate and .... Ulcer bed infection. Report of a case of enlarging venous leg ulcer colonized by ... Ann. Burns Fire.

Sheng-ji Hua-yu formula promotes diabetic wound healing of re-epithelization via Activin/Follistatin regulation.

Science.gov (United States)

Kuai, Le; Zhang, Jing-Ting; Deng, Yu; Xu, Shun; Xu, Xun-Zhe; Wu, Min-Feng; Guo, Dong-Jie; Chen, Yu; Wu, Ren-Jie; Zhao, Xing-Qiang; Nian, Hua; Li, Bin; Li, Fu-Lun

2018-01-29

Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro-/anti-inflammatory factors on transforming growth factor-β(TGF-β) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula

The efficacy of moisture retentive ointment in the mangement of cutaneous wounds and ulcers: A multicenter clinical trial

Directory of Open Access Journals (Sweden)

Atiyeh B

2003-01-01

Full Text Available Local management of chronic wounds and ulcers remains one of the most costly unsolved problems in health care today. With proper clinical management, most chronic wound healing problems can be resolved and healing expected, though recurrence may be common. The recent logarithmic growth in our knowledge about wound healing and the appreciation of the importance of a moist environment in optimal wound healing has led to the introduction of new and exciting therapeutic modalities. In view of the many practical disadvantages as well as the serious complications of currently available moisture retentive dressings when applied to chronic contaminated wounds, a prospective multicenter clinical trial was conducted from December 1999 to November 2000 to evaluate the safety and efficacy of a newly introduced moisture retentive ointment (MEBO: Moist Exposed Burn Ointment (Julphar - Gulf Pharmaceutical Industries, UAE in the local wound care of problematic non-healing wounds. The active component of the ointment is β-sitosterol in a base of beeswax, sesame oil and other components. Though it was not a comparative study, the ointment was found to induce rapid reduction in ulcer size even after a prolonged stagnant state with other therapeutic modalities without complications such as skin maceration, unmanageable excessive exudation, and wound infection. As expected with such chronic wounds, the healing potential of local ointment application is limited by the mere size of the original defect and the underlying pathologies and associated diseases. however, the safety and practicality of simple ointment application was found to be a valid alternative treatment for local management of chronic wounds.

Bacterial Contribution in Chronicity of Wounds.

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Rahim, Kashif; Saleha, Shamim; Zhu, Xudong; Huo, Liang; Basit, Abdul; Franco, Octavio Luiz

2017-04-01

A wound is damage of a tissue usually caused by laceration of a membrane, generally the skin. Wound healing is accomplished in three stages in healthy individuals, including inflammatory, proliferative, and remodeling stages. Healing of wounds normally starts from the inflammatory phase and ends up in the remodeling phase, but chronic wounds remain in an inflammatory stage and do not show progression due to some specific reasons. Chronic wounds are classified in different categories, such as diabetic foot ulcer (DFU), venous leg ulcers (VLU) and pressure ulcer (PU), surgical site infection (SSI), abscess, or trauma ulcers. Globally, the incidence rate of DFU is 1-4 % and prevalence rate is 5.3-10.5 %. However, colonization of pathogenic bacteria at the wound site is associated with wound chronicity. Most chronic wounds contain more than one bacterial species and produce a synergetic effect that results in previously non-virulent bacterial species becoming virulent and causing damage to the host. While investigating bacterial diversity in chronic wounds, Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia, and Serratia were found most frequently in chronic wounds. Recently, it has been observed that bacteria in chronic wounds develop biofilms that contribute to a delay in healing. In a mature biofilm, bacteria grow slowly due to deficiency of nutrients that results in the resistance of bacteria to antibiotics. The present review reflects the reasons why acute wounds become chronic. Interesting findings include the bacterial load, which forms biofilms and shows high-level resistance toward antibiotics, which is a threat to human health in general and particularly to some patients who have acute wounds.

Emerging infectious diseases with cutaneous manifestations: Viral and bacterial infections.

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Nawas, Zeena Y; Tong, Yun; Kollipara, Ramya; Peranteau, Andrew J; Woc-Colburn, Laila; Yan, Albert C; Lupi, Omar; Tyring, Stephen K

2016-07-01

Given increased international travel, immigration, and climate change, bacterial and viral infections that were once unrecognized or uncommon are being seen more frequently in the Western Hemisphere. A delay in diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. We review the epidemiology, cutaneous manifestations, diagnosis, and management of these emerging bacterial and viral diseases. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Plant Age Affects Wound-Induced Senescense in Lactuca Sativa L

OpenAIRE

Witkowska, I.M.; Woltering, E.J.

2014-01-01

In the present study we investigated the performance of dark-stored wounded leaf discs and pieces (to some extent mimicking fresh-cut product) of Lactuca sativa L. in relation to the physiological maturity at harvest. We used two related genotypes, i.e. a green (cv. Troubadour) and a red butterhead (cv. Teodore) differing in their pigment levels. For both genotypes, senescence of the wounded (fresh-cut) tissue prepared from leaves of younger plants was significantly delayed compared to wounde...

Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011.

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Neblett Fanfair, Robyn; Benedict, Kaitlin; Bos, John; Bennett, Sarah D; Lo, Yi-Chun; Adebanjo, Tolu; Etienne, Kizee; Deak, Eszter; Derado, Gordana; Shieh, Wun-Ju; Drew, Clifton; Zaki, Sherif; Sugerman, David; Gade, Lalitha; Thompson, Elizabeth H; Sutton, Deanna A; Engelthaler, David M; Schupp, James M; Brandt, Mary E; Harris, Julie R; Lockhart, Shawn R; Turabelidze, George; Park, Benjamin J

2012-12-06

Mucormycosis is a fungal infection caused by environmentally acquired molds. We investigated a cluster of cases of cutaneous mucormycosis among persons injured during the May 22, 2011, tornado in Joplin, Missouri. We defined a case as a soft-tissue infection in a person injured during the tornado, with evidence of a mucormycete on culture or immunohistochemical testing plus DNA sequencing. We conducted a case-control study by reviewing medical records and conducting interviews with case patients and hospitalized controls. DNA sequencing and whole-genome sequencing were performed on clinical specimens to identify species and assess strain-level differences, respectively. A total of 13 case patients were identified, 5 of whom (38%) died. The patients had a median of 5 wounds (range, 1 to 7); 11 patients (85%) had at least one fracture, 9 (69%) had blunt trauma, and 5 (38%) had penetrating trauma. All case patients had been located in the zone that sustained the most severe damage during the tornado. On multivariate analysis, infection was associated with penetrating trauma (adjusted odds ratio for case patients vs. controls, 8.8; 95% confidence interval [CI], 1.1 to 69.2) and an increased number of wounds (adjusted odds ratio, 2.0 for each additional wound; 95% CI, 1.2 to 3.2). Sequencing of the D1-D2 region of the 28S ribosomal DNA yielded Apophysomyces trapeziformis in all 13 case patients. Whole-genome sequencing showed that the apophysomyces isolates were four separate strains. We report a cluster of cases of cutaneous mucormycosis among Joplin tornado survivors that were associated with substantial morbidity and mortality. Increased awareness of fungi as a cause of necrotizing soft-tissue infections after a natural disaster is warranted.

An athymic mouse model to mimic cobalt-60 cutaneous radiation injury

Energy Technology Data Exchange (ETDEWEB)

Mosca, Rodrigo Crespo; Ferreira, Danilo Cardenuto; Napolitano, Celia Marina; Santin, Stefany Plumeri; Dornelles, Leonardo Dalla Porta; Alvarenga, Eluara Ortigoso; Mathor, Monica Beatriz, E-mail: rcmosca@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2013-07-01

Propose: Cutaneous wound from irradiation is the most common complication in radiotherapy treatment, and can be lead to mortality. We describe an athymic mouse model to mimic cutaneous radiation injury by Cobalt-60. Methods: A protocol was including dosimetry with silicon diodes,10x10x5 cm arrangement made by four lead bricks and PVC pipe designed to immobilize the athymic mouse in order to irradiate one clamped back skin point that was subdivided in four parts. To get the measurements of dose rates on the arrangement in Panoramic Irradiator, it was used a silicon diode encased in an opaque protection for ambient light and connected to an electric cable, forming a dosing probe. The currents generated in diode sensitive volume as a function of time of exposure to gamma radiation coming from the radiator, with dose rate of 0,015 Gy/min in positions 1, 0,021 Gy/min in position 2, 0,55 Gy/min in position 3 and 1,45 Gy/min in position four. After the dosimetry, each athymic mouse was anesthetized using Xylazine and Ketamine dilution and entered into a PVC pipe and a small portion of skin (1 cm{sup 3}) was clamped. This tube was then fixed to arrangement and the athymic mouse was irradiate for 60 min, than it was being returned to its cage. Results: The wound was visualized in all animals and photographed after 5 days of irradiation, with the emergence of ulceration after 9 days. No systemic or lethal sequelae occurred or visualized in any animals. Late clinical signs included a wound healing after 22 days. Conclusion: While still being a baseline study, we created a new functional preclinical animal model that can be used for new therapies and may improve radiotherapy management. (author)

An athymic mouse model to mimic cobalt-60 cutaneous radiation injury

International Nuclear Information System (INIS)

Mosca, Rodrigo Crespo; Ferreira, Danilo Cardenuto; Napolitano, Celia Marina; Santin, Stefany Plumeri; Dornelles, Leonardo Dalla Porta; Alvarenga, Eluara Ortigoso; Mathor, Monica Beatriz

2013-01-01

Propose: Cutaneous wound from irradiation is the most common complication in radiotherapy treatment, and can be lead to mortality. We describe an athymic mouse model to mimic cutaneous radiation injury by Cobalt-60. Methods: A protocol was including dosimetry with silicon diodes,10x10x5 cm arrangement made by four lead bricks and PVC pipe designed to immobilize the athymic mouse in order to irradiate one clamped back skin point that was subdivided in four parts. To get the measurements of dose rates on the arrangement in Panoramic Irradiator, it was used a silicon diode encased in an opaque protection for ambient light and connected to an electric cable, forming a dosing probe. The currents generated in diode sensitive volume as a function of time of exposure to gamma radiation coming from the radiator, with dose rate of 0,015 Gy/min in positions 1, 0,021 Gy/min in position 2, 0,55 Gy/min in position 3 and 1,45 Gy/min in position four. After the dosimetry, each athymic mouse was anesthetized using Xylazine and Ketamine dilution and entered into a PVC pipe and a small portion of skin (1 cm 3 ) was clamped. This tube was then fixed to arrangement and the athymic mouse was irradiate for 60 min, than it was being returned to its cage. Results: The wound was visualized in all animals and photographed after 5 days of irradiation, with the emergence of ulceration after 9 days. No systemic or lethal sequelae occurred or visualized in any animals. Late clinical signs included a wound healing after 22 days. Conclusion: While still being a baseline study, we created a new functional preclinical animal model that can be used for new therapies and may improve radiotherapy management. (author)

Inibição da expressão de ciclooxigenase 2 em feridas cutâneas de camundongos NOD submetidos à terapia a laser de baixa intensidade Inhibition of cyclooxygenase 2 expression in NOD mice cutaneous wound by low-level laser therapy

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Carolina de Lourdes Julião Vieira Rocha

2012-09-01

cutaneous wound healing. METHODS: Thirty NOD mice were used, of which 14 were diabetic and were divided into two groups: group I (n=7 underwent a surgical procedure of skin wounds and group II (n=7 underwent a surgical procedure of skin wounds and treated with LLLT. Group II was submitted to LLLT in the following parameters: 15 mW of power, dose of 3.8 J/cm² and exposure time of 20 seconds. Seven days after surgery and after laser application, animals were euthanized with an overdose of anesthesia and tissue samples were collected for subsequent histological analysis, histomorphometry and immunohistochemistry. RESULTS: The LLLT has promoted the inhibition of COX2 expression in skin wounds in mice diabetic. Taken together the results suggest that LLLT modulate the expression of COX2 improved the control of inflammatory reaction in cutaneous wound lesions in NOD mice. CONCLUSION: Taken together, the results suggested that LLLT is able to negatively modulate the expression of COX2 enzyme contributing to the inflammatory response in cutaneous wounds in NOD mice.

MicroRNA-155 Inhibition Promoted Wound Healing in Diabetic Rats.

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Ye, Junna; Kang, Yutian; Sun, Xiaofang; Ni, Pengwen; Wu, Minjie; Lu, Shuliang

2017-06-01

Diabetes leads to amputation in approximately 15% to 20% of patients and is associated with high morbidity and mortality. Thus, improving the quality of wound healing in this condition is essential. Diabetes is associated with acute/chronic inflammation affecting all organs especially the foot, while, inhibition of microRNA-155 (miR-155) has been reported to improve or reduce inflammatory situation. However, the role of miR-155 inhibition in promoting diabetic wound healing is not clear. To further study the potential benefit of miR-155 inhibition, a study of male Sprague-Dawley rats was conducted and diabetes was induced by injection of streptozotocin. Real-time polymerase chain reaction (PCR), hematoxylin and eosin staining and immunohistochemistry were then performed. The PCR results confirmed that miR-155 expression was lower after miR-155 inhibition on days 3, 7, and 13 (all Ps healing rate between the normal glucose group (N group), diabetic PBS group (PBS group) and the topical miR-155 inhibitor group was compared. Faster healing of cutaneous wounds was observed in the miR-155 inhibitor group than in the PBS group and normal glucose group ( P healing of diabetic foot wounds.

Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing.

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Dhall, Sandeep; Alamat, Raquelle; Castro, Anthony; Sarker, Altaf H; Mao, Jian-Hua; Chan, Alex; Hang, Bo; Martins-Green, Manuela

2016-07-01

Third hand smoke (THS) is the accumulation of second hand smoke (SHS) toxins on surfaces in homes, cars, clothing and hair of smokers. It is known that 88M US nonsmokers ≥3 years old living in homes of smokers are exposed to THS toxicants and show blood cotinine levels of ≥0.05 ng/ml, indicating that the toxins are circulating in their circulatory systems. The goal of the present study is to investigate the mechanisms by which THS causes impaired wound healing. We show that mice living under conditions that mimic THS exposure in humans display delayed wound closure, impaired collagen deposition, altered inflammatory response, decreased angiogenesis, microvessels with fibrin cuffs and a highly proteolytic wound environment. Moreover, THS-exposed mouse wounds have high levels of oxidative stress and significantly lower levels of antioxidant activity leading to molecular damage, including protein nitration, lipid peroxidation and DNA damage that contribute to tissue dysfunction. Furthermore, we show that elastase is elevated, suggesting that elastin is degraded and the plasticity of the wound tissue is decreased. Taken together, our results lead us to conclude that THS toxicants delay and impair wound healing by disrupting the sequential processes that lead to normal healing. In addition, the lack of elastin results in loss of wound plasticity, which may be responsible for reopening of wounds. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Healing of excisional wound in alloxan induced diabetic sheep: A planimetric and histopathologic study

Directory of Open Access Journals (Sweden)

Farshid Sarrafzadeh-Rezaei

2013-09-01

Full Text Available Healing of skin wound is a multi-factorial and complex process. Proper treatment of diabetic wounds is still a major clinical challenge. Although diabetes mellitus can occur in ruminants, healing of wounds in diabetic ruminants has not yet been investigated. The aim of this study was to evaluate healing of ovine excisional diabetic wound model. Eight 4-month-old Iranian Makoui wethers were equally divided to diabetic and nondiabetic groups. Alloxan monohydrate (60 mg kg-1, IV was used for diabetes induction. In each wether, an excisional wound was created on the dorsum of the animal. Photographs were taken in distinct times for planimetric evaluation. Wound samples were taken on day 21 post-wounding for histopathologic evaluations of epidermal thickness, number of fibroblasts and number of new blood vessels. The planimetric study showed slightly delay in wound closure of diabetic animals, however, it was not significantly different from nondiabetic wounds (p ≥ 0.05. Furthermore, epidermal thickness, number of fibroblasts and number of blood vessels were significantly lower in diabetic group (p < 0.05. We concluded that healing of excisional diabetic wounds in sheep may be compromised, as seen in other species. However, contraction rate of these wounds may not be delayed due to metabolic features of ruminants and these animals might go under surgeries without any serious concern. However, healing quality of these wounds may be lower than normal wounds.

The efficacy of moisture retentive ointment in the mangement of cutaneous wounds and ulcers: A multicenter clinical trial

OpenAIRE

Atiyeh B; Ioannovich J; Magliacani G; Masellis M; Costagliola M; Dham R

2003-01-01

Local management of chronic wounds and ulcers remains one of the most costly unsolved problems in health care today. With proper clinical management, most chronic wound healing problems can be resolved and healing expected, though recurrence may be common. The recent logarithmic growth in our knowledge about wound healing and the appreciation of the importance of a moist environment in optimal wound healing has led to the introduction of new and exciting therapeutic modalities. In view of the...

Zosteriform cutaneous leiomyoma: a rare cutaneous neoplasm

International Nuclear Information System (INIS)

Bari, A.U.

2013-01-01

Cutaneous leiomyomas are firm, round to oval, skin-coloured to brownish papules and nodules that may present as a solitary, few discrete or multiple clustered lesions. Different uncommon patterns of multiple leiomyoma distribution have been noted as bilateral, symmetrical, linear, zosteriform, or dermatomal-like arrangement. One such rare presentation was seen in a 23-year-old patient who presented with zosteriform skin coloured, occasionally painful cutaneous lesions over left shoulder region. Histopathology confirmed the diagnosis of cutaneous leiomyoma. He was symptomatically managed with non-steroidal anti-inflammatory agents and topical capcicum cream. Case is reported here due to rare occurrence of this benign cutaneous neoplasm in an atypical pattern and on uncommon site. (author)

Managing burn wounds with SMARTPORE Technology polyurethane foam: two case reports.

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Imran, Farrah-Hani; Karim, Rahamah; Maat, Noor Hidayah

2016-05-12

Successful wound healing depends on various factors, including exudate control, prevention of microbial contaminants, and moisture balance. We report two cases of managing burn wounds with SMARTPORE Technology polyurethane foam dressing. In Case 1, a 2-year-old Asian girl presented with a delayed (11 days) wound on her right leg. She sustained a thermal injury from a hot iron that was left idle on the floor. Clinical inspection revealed an infected wound with overlying eschar that traversed her knee joint. As her parents refused surgical debridement under general anesthesia, hydrotherapy and wound dressing using SMARTPORE Technology Polyurethane foam were used. Despite the delay in presentation of this linear thermal pediatric burn injury that crossed the knee joint, the patient's response to treatment and its outcome were highly encouraging. She was cooperative and tolerated each dressing change without the need of supplemental analgesia. Her wound was healed by 24 days post-admission. In Case 2, a 25-year-old Asian man presented with a mixed thickness thermal flame burn on his left leg. On examination, the injury was a mix of deep and superficial partial thickness burn, comprising approximately 3% of his total body surface area. SMARTPORE Technology polyurethane foam was used on his wound; his response to the treatment was very encouraging as the dressing facilitated physiotherapy and mobility. The patient rated the pain during dressing change as 2 on a scale of 10 and his pain score remained the same in every subsequent change. His wound showed evidence of epithelialization by day 7 post-burn. There were no adverse events reported. Managing burn wounds with SMARTPORE Technology polyurethane foam resulted in reduced pain during dressing changes and the successful healing of partial and mixed thickness wounds. The use of SMARTPORE Technology polyurethane foam dressings showed encouraging results and requires further research as a desirable management option in

Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells.

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Boink, Mireille A; van den Broek, Lenie J; Roffel, Sanne; Nazmi, Kamran; Bolscher, Jan G M; Gefen, Amit; Veerman, Enno C I; Gibbs, Susan

2016-01-01

Oral wounds heal faster and with better scar quality than skin wounds. Deep skin wounds where adipose tissue is exposed, have a greater risk of forming hypertrophic scars. Differences in wound healing and final scar quality might be related to differences in mesenchymal stromal cells (MSC) and their ability to respond to intrinsic (autocrine) and extrinsic signals, such as human salivary histatin, epidermal growth factor, and transforming growth factor beta1. Dermis-, adipose-, and gingiva-derived MSC were compared for their regenerative potential with regards to proliferation, migration, and matrix contraction. Proliferation was assessed by cell counting and migration using a scratch wound assay. Matrix contraction and alpha smooth muscle actin was assessed in MSC populated collagen gels, and also in skin and gingival full thickness tissue engineered equivalents (reconstructed epithelium on MSC populated matrix). Compared to skin-derived MSC, gingiva MSC showed greater proliferation and migration capacity, and less matrix contraction in full thickness tissue equivalents, which may partly explain the superior oral wound healing. Epidermal keratinocytes were required for enhanced adipose MSC matrix contraction and alpha smooth muscle actin expression, and may therefore contribute to adverse scarring in deep cutaneous wounds. Histatin enhanced migration without influencing proliferation or matrix contraction in all three MSC, indicating that salivary peptides may have a beneficial effect on wound closure in general. Transforming growth factor beta1 enhanced contraction and alpha smooth muscle actin expression in all three MSC types when incorporated into collagen gels. Understanding the mechanisms responsible for the superior oral wound healing will aid us to develop advanced strategies for optimal skin regeneration, wound healing and scar formation. © 2015 by the Wound Healing Society.

Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders?

Science.gov (United States)

Artuc, M; Hermes, B; Steckelings, U M; Grützkau, A; Henz, B M

1999-02-01

Mast cells are traditionally viewed as effector cells of immediate type hypersensitivity reactions. There is, however, a growing body of evidence that the cells might play an important role in the maintenance of tissue homeostasis and repair. We here present our own data and those from the literature elucidating the possible role of mast cells during wound healing. Studies on the fate of mast cells in scars of varying ages suggest that these cells degranulate during wounding, with a marked decrease of chymase-positive cells, although the total number of cells does not decrease, based on SCF-receptor staining. Mast cells contain a plethora of preformed mediators like heparin, histamine, tryptase, chymase, VEGF and TNF-alpha which, on release during the initial stages of wound healing, affect bleeding and subsequent coagulation and acute inflammation. Various additional vasoactive and chemotactic, rapidly generated mediators (C3a, C5a, LTB4, LTC4, PAF) will contribute to these processes, whereas mast cell-derived proinflammatory and growth promoting peptide mediators (VEGF, FGF-2, PDGF, TGF-beta, NGF, IL-4, IL-8) contribute to neoangiogenesis, fibrinogenesis or re-epithelization during the repair process. The increasing number of tryptase-positive mast cells in older scars suggest that these cells continue to be exposed to specific chemotactic, growth- and differentiation-promoting factors throughout the process of tissue remodelling. All these data indicate that mast cells contribute in a major way to wound healing. their role as potential initiators of or as contributors to this process, compared to other cell types, will however have to be further elucidated.

Promotion of accelerated repair in a radiation impaired wound healing model in murine skin

International Nuclear Information System (INIS)

Walker, M.D.

2000-02-01

Surgical resection of many tumours following radiotherapy is well established as the preferred approach to eradicating the disease. However, prior irradiation compromises the healing of surgical wounds in 30-60% of cases, depending on the site of treatment. There is a need therefore, to understand the deficit in the repair process and to develop therapeutic interventions that may help address this problem. To this end, the aims of this thesis were to characterise a wound healing model in irradiated murine skin and to investigate the effects of topical- compounds and therapeutic modalities upon this wound healing model. Full-thickness dorsal skin excisions were made within a pre-irradiated area (20Gy) in male Balb/c mice and wounds were made in a corresponding area in control animals. Biopsies were removed for histological and immunohistochemical analysis, whilst wound closure experiments were used to determine effects of topical compounds and therapeutic modalities (Low Intensity Laser Therapy, Therapeutic Ultrasound and Transcutaneous Electrical Nerve Stimulation) upon the rate of repair. X-ray irradiation (20Gy) caused a significant delay in the rate of wound closure, whilst histological results indicated that prior irradiation delays the influx of inflammatory cells, delays wound reepithelialisation and reduces granulation tissue formation and collagen deposition. Macrophage and endothelial cell numbers were found to be significantly lower in the irradiated wounds when compared to unirradiated control wounds. Furthermore, apoptosis was affected by irradiation. Although results failed to support any claimed stimulatory effects of various therapeutic modalities upon wound healing, topical application of glucans were shown to have a slight beneficial effect upon the rate of repair. In conclusion, the observed cellular effects caused by irradiation may be a result of permanent damage to stem cells and their ability to replicate and reproduce. Furthermore, the

Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-β expression.

Science.gov (United States)

Hussan, F; Teoh, S Lin; Muhamad, N; Mazlan, M; Latiff, A A

2014-08-01

Transforming growth factor-β (TGF-β) plays an important role in wound healing. Delayed wound healing is a consequence of diabetes, leading to high morbidity and poor quality of life. Momordica charantia (MC) fruit possesses anti-diabetic and wound healing properties. This study aimed to explore the changes in TGF-β expression in diabetic wounds treated with topical MC fruit extract. Fifty-six male Sprague-Dawley rats were divided into a normal control group and five diabetic groups of ten rats each. Intravenous streptozotocin (50mg/kg) was given to induce diabetes in the diabetic groups. Full thickness excision wounds were created on the thoracodorsal region of the animals, and these wounds were then treated with vehicle, MC powder, MC ointment and povidone ointment or ointment base for ten days. Wound healing was determined by the rate of wound closure, total protein content and TGF-β expression in the wounds, and histological observation. Diabetic groups showed delayed wound closure rates compared to the control group. The wound closure rate in the MC ointment group was significantly faster than that of the untreated diabetic group (p<0.05). The MC ointment group also showed intense TGF-β expression and a high level of total protein content. MC ointment has a promising potential for use as an alternative topical medication for diabetic wounds. This work has shown that it accelerates wound healing in diabetic rats, and it is suggested here that this occurs by enhancing TGF-β expression. Further work is recommended to explore this effect.

Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing.

Science.gov (United States)

Kaisang, Lin; Siyu, Wang; Lijun, Fan; Daoyan, Pan; Xian, Cory J; Jie, Shen

2017-09-01

Chronic nonhealing wound is a multifactorial complication of diabetes that results specifically as a consequence of impaired angiogenesis and currently lacks in effective treatments. Although a stem cell-based therapy may provide a novel treatment to augment diabetic wound healing, inferior cell survival at the diabetic skin wound is one of the key causes that are responsible for the low efficacy of the stem cell therapy. In this work, we used an injectable, biocompatible, and thermosensitive hydrogel Pluronic F-127 to encapsulate allogeneic nondiabetic adipose-derived stem cells (ADSCs) and topically applied the cells to a full-thickness cutaneous wound in the streptozotocin-induced diabetic model in rats. The cells seeded in the hydrogel enhanced angiogenesis (CD31 marker) and promoted the cell proliferation (Ki67 marker) at the wound site and significantly accelerated wound closure, which was accompanied by facilitated regeneration of granulation tissue. Consistently, levels of the messenger RNA expression of key angiogenesis growth factor, vascular endothelial growth factor, and key wound healing growth factor, transforming growth factor beta 1, were also upregulated in the cell-treated wounds when compared with untreated wounds. The results indicated that the transplantation of allogeneic ADSCs via the hydrogel improves the efficiency of cell delivery and optimizes the performance of ADSCs for augmenting diabetic wound healing. In conclusion, this ADSC-based therapy may provide a novel therapeutic strategy for the treatment of nonhealing diabetic foot ulcers. Copyright © 2017 Elsevier Inc. All rights reserved.

Coverage of Deep Cutaneous Wounds Using Dermal Template in Combination with Negative-pressure Therapy and Subsequent Skin Graft

Science.gov (United States)

Chang, Alexandre A.; Lobato, Rodolfo C.; Nakamoto, Hugo A.; Tuma, Paulo; Ferreira, Marcus C.

2014-01-01

Background: We consider the use of dermal matrix associated with a skin graft to cover deep wounds in the extremities when tendon and bone are exposed. The objective of this article was to evaluate the efficacy of covering acute deep wounds through the use of a dermal regeneration template (Integra) associated with vacuum therapy and subsequent skin grafting. Methods: Twenty patients were evaluated prospectively. All of them had acute (up to 3 weeks) deep wounds in the limbs. We consider a deep wound to be that with exposure of bone, tendon, or joint. Results: The average area of integration of the dermal regeneration template was 86.5%. There was complete integration of the skin graft over the dermal matrix in 14 patients (70%), partial integration in 5 patients (25%), and total loss in 1 case (5%). The wound has completely closed in 95% of patients. Conclusions: The use of Integra dermal template associated with negative-pressure therapy and skin grafting showed an adequate rate of resolution of deep wounds with low morbidity. PMID:25289363

Cutaneous and systemic hypersensitivity reactions to metallic implants.

Science.gov (United States)

Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

2011-01-01

Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions remains to be fully understood. This review provides an update of the current knowledge in this field and should be valuable to health care providers who manage patients with conditions related to this field.

Leptin promotes wound healing in the skin.

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Susumu Tadokoro

Full Text Available Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties. Interestingly, skin wound healing was proven to delay in leptin-deficient ob/ob mice. However, little is known on the mechanisms of this phenomenon. In this study, we attempted to elucidate a role of leptin in wound healing of skin.Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of wound repair was histologically observed and the area of ulceration was measured over time. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated.Ob-R was expressed in epidermal cells of human and mouse skin. Topical administration of leptin significantly promoted wound healing. Histological analysis showed more blood vessels in the dermal connective tissues in the leptin-treated group. The proliferation, differentiation/function and migration of human epidermal keratinocytes were enhanced by exogenous leptin.Topically administered leptin was proven to promote wound healing in the skin by accelerating proliferation, differentiation/function and migration of epidermal keratinocytes and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the skin.

The effects of equine peripheral blood stem cells on cutaneous wound healing: a clinical evaluation in four horses.

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Spaas, J H; Broeckx, S; Van de Walle, G R; Polettini, M

2013-04-01

Stem-cell therapy represents a promising strategy for the treatment of challenging pathologies, such as large, infected wounds that are unresponsive to conventional therapies. The present study describes the clinical application of peripheral blood stem cells (PBSCs) for the treatment of four adult Warmblood horses with naturally occurring wounds, which were unresponsive to conventional therapies for at least 3 months. A visual assessment was performed, and a number of wound-healing parameters (granulation tissue, crust formation and scar formation) were evaluated. In all cases, tissue overgrowth was visible within 4 weeks after PBSC injection, followed by the formation of crusts and small scars in the centre of the wound, with hair regeneration at the edges. In conclusion, this is the first report of PBSC therapy of skin wounds in horses, and it produced a positive visual and clinical outcome. © The Author(s) CED © 2013 British Association of Dermatologists.

Recommendations for managing cutaneous disorders associated with advancing age

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Humbert P

2016-02-01

Full Text Available Philippe Humbert,1 Brigitte Dréno,2 Jean Krutmann,3 Thomas Anton Luger,4 Raoul Triller,5 Sylvie Meaume,6 Sophie Seité71Research and Studies Centre on the Integument (CERT, Clinical Investigation Centre (CIC BT506, Department of Dermatology, Besançon University Hospital, University of Franche-Comté, Besançon, France; 2Department of Dermato-Cancerology, Nantes University Hospital, Nantes, France; 3IUF-Leibniz Research Institute for Environmental Medicine, Heinrich-Heine-University, Düsseldorf, Germany; 4Department of Dermatology, University of Münster, Münster, Germany; 5International Centre of Dermatology, Hertford British Hospital, Levallois, France; 6Geriatric Service, Wounds and Healing, Rothschild Hôspital, Paris, France; 7La Roche-Posay Dermatological Laboratories, Asnières, FranceAbstract: The increasingly aged population worldwide means more people are living with chronic diseases, reduced autonomy, and taking various medications. Health professionals should take these into consideration when managing dermatological problems in elderly patients. Accordingly, current research is investigating the dermatological problems associated with the loss of cutaneous function with age. As cell renewal slows, the physical and chemical barrier function declines, cutaneous permeability increases, and the skin becomes increasingly vulnerable to external factors. In geriatric dermatology, the consequences of cutaneous aging lead to xerosis, skin folding, moisture-associated skin damage, and impaired wound healing. These problems pose significant challenges for both the elderly and their carers. Most often, nurses manage skin care in the elderly. However, until recently, little attention has been paid to developing appropriate, evidence-based, skincare protocols. The objective of this paper is to highlight common clinical problems with aging skin and provide some appropriate advice on cosmetic protocols for managing them. A review of the

Influence of dressing application time after breast augmentation on cutaneous colonization: A randomized clinical trial.

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Mendes, D A; Veiga, D F; Veiga-Filho, J; Loyola, A B A T; Paiva, L F; Novo, N F; Sabino-Neto, M; Ferreira, L M

2018-06-01

Concepts regarding the best way to treat a surgical wound vary, in literature, ranging from no dressing use to dressing maintenance for 24 to 48 hours or until suture removal. This study aimed to evaluate the influence of the length of dressing maintenance after breast augmentation with implants on cutaneous colonization and surgical site infection. This is a two-arm, parallel group, randomized clinical trial. Eighty patients who were candidates for augmentation mammoplasty with silicone implants were randomly allocated to two groups, in which the dressing was removed on postoperative day 1 (group A, n = 40) or postoperative day 6 (group B, n = 40). Cutaneous colonization was examined by culturing samples collected before and after dressing removal. The criteria defined by the Centers for Disease Control and Prevention were used to assess surgical site infection. No significant difference regarding cutaneous colonization was observed between groups before dressing application. On postoperative day 6, significantly more bacterial growth was observed in group A (p = 0.01). No surgical site infection occurred. We concluded that maintaining the dressing for 6 days led to a lower cutaneous colonization but did not influence surgical site infection rates. Copyright © 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

[PERSONALIZED APPROACH TO PATIENT WITH CHRONIC WOUND IN FAMILY MEDICINE].

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Sinožić, T; Katić, M; Kovačević, J

2016-01-01

It can be said that the occurrence and development of wounds, healing, delayed healing, and the notion of chronic wound are some of the basic characteristics of all living beings. When it comes to people, there are a number of processes that take place during wound healing, and even under ideal circumstances, they create a functionally less valuable skin tissue, along with structural and functional changes. Fibrosis in the form of hypertrophic scars and keloids, contractures and adhesions are examples of excessive healing. Microcirculation is significantly different from healthy skin circulation with consequential formation of local hypoxia and stagnation in lymph flow with edema. Poor functionality of the scar tissue, particularly in the areas exposed to stronger forces, can cause forming of wounds. Such wounds are hard to heal despite the inexistence of other possible reasons for delayed healing, precisely because of their poor functionality and placement. The presence of wound requiring long-term treatment affects all areas of patient life and leads to decline in the quality of life. Exemplified by case presentation of a patient with post-traumatic wound in the scar area, in our office we showed a model of care based on the principle of overall personalized care with the biopsychosocial approach. Diagnostic and therapeutic procedures included wound assessment, biofilm and lymphedema detection, assessment of the patient’s psychosocial status, risk factors for wound healing, vascular ultrasound diagnostics, carboxytherapy as specialized adjuvant therapy, use of modern wound dressings, and compression therapy. Supportive psychotherapy was conducted in positive communication environment during treatment. In this way, in an atmosphere of cooperation with the patient, it was possible not only to influence the process of wound healing as the primary objective, but also to improve the quality of the patient’s life, as well as to influence our professional

Effects on Glycemic Control in Impaired Wound Healing in Spontaneously Diabetic Torii (SDT) Fatty Rats.

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Katsuhiro, Miyajima; Hui Teoh, Soon; Yamashiro, Hideaki; Shinohara, Masami; Fatchiyah, Fatchiyah; Ohta, Takeshi; Yamada, Takahisa

2018-02-01

Impaired diabetic wound healing is an important issue in diabetic complications. The present study aims to evaluate the protective effect on glycemic control against impaired diabetic wound healing using a diabetic rat model. We investigated the wound healing process and effect on the impaired wound repair by glycemic control in the Spontaneously Diabetic Torii (SDT) fatty rat, which is a new animal model of obese type 2 diabetes and may be a good model for study impaired wound healing. Male SDT fatty rats at 15 weeks of age were administered orally with sodium glucose co-transporter (SGLT) 2 inhibitor for 3 weeks. Wounds were induced at 2 weeks after SGLT 2 inhibitor treatment, and the wound areas were periodically examined in morphological and histological analyses. The SDT fatty rats showed a delayed wound healing as compared with the normal rats, but a glycemic control improved the impaired wound healing. In histological analysis in the skin of SDT fatty rats showed severe infiltration of inflammatory cell, hemorrhage and many bacterial masses in the remaining and slight fibrosis of crust on skin tissue . Thought that this results skin performance to be a delay of crust formation and regeneration of epithelium; however, these findings were ameliorated in the SGLT 2 inhibitor treated group. Glycemic control is effective for treatment in diabetic wounds and the SDT fatty rat may be useful to investigate pathophysiological changes in impaired diabetic wound healing.

Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model.

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O'Loughlin, Aonghus; Kulkarni, Mangesh; Vaughan, Erin E; Creane, Michael; Liew, Aaron; Dockery, Peter; Pandit, Abhay; O'Brien, Timothy

2013-01-01

Diabetic foot ulceration is the leading cause of amputation in people with diabetes mellitus. Peripheral vascular disease is present in the majority of patients with diabetic foot ulcers. Despite standard treatments there exists a high amputation rate. Circulating angiogenic cells previously known as early endothelial progenitor cells are derived from peripheral blood and support angiogenesis and vasculogenesis, providing a potential topical treatment for non-healing diabetic foot ulcers. A scaffold fabricated from Type 1 collagen facilitates topical cell delivery to a diabetic wound. Osteopontin is a matricellular protein involved in wound healing and increases the angiogenic potential of circulating angiogenic cells. A collagen scaffold seeded with circulating angiogenic cells was developed. Subsequently the effect of autologous circulating angiogenic cells that were seeded in a collagen scaffold and topically delivered to a hyperglycemic cutaneous wound was assessed. The alloxan-induced diabetic rabbit ear ulcer model was used to determine healing in response to the following treatments: collagen seeded with autologous circulating angiogenic cells exposed to osteopontin, collagen seeded with autologous circulating angiogenic cells, collagen alone and untreated wound. Stereology was used to assess angiogenesis in wounds. The cells exposed to osteopontin and seeded on collagen increased percentage wound closure as compared to other groups. Increased angiogenesis was observed with the treatment of collagen and collagen seeded with circulating angiogenic cells. These results demonstrate that topical treatment of full thickness cutaneous ulcers with autologous circulating angiogenic cells increases wound healing. Cells exposed to the matricellular protein osteopontin result in superior wound healing. The wound healing benefit is associated with a more efficient vascular network. This topical therapy provides a potential novel therapy for the treatment of non

Giant Cutaneous Horn Overlying A Verruca at an Uncommon Site: Medical Marvel vs Superstitious Dilemma.

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Sanjeeva, Karthik Kathladka; Ali, Puttur Sainuddin Mohammed Ameer; Pinto, Malcolm; Rao, Srikar; Rai, Arvind Shivram

2015-04-01

Cutaneous horn has been a matter of discussion to mankind since time immemorial and a subject of fascination for the layman. There have been instances where certain groups saw it with angst and disgust, with a person having a large cutaneous horn on an exposed area getting a dismal look. We present a case of a 64-year-old man with a giant cutaneous horn over his left gluteal region. Cutaneous horns more commonly present in the sun-exposed areas. In our case it has presented in an uncommon site. The patient had delayed and denied medical treatment due to his superstitious beliefs, after having sought advice from faith healers leading to progression of the disease. This case has been presented for its giant size (rare variety), its location being over the gluteal region (photo-protected site) and its benign histopathology suggestive of wart in spite of the giant size.

Novel Anti-Melanogenesis Properties of Polydeoxyribonucleotide, a Popular Wound Healing Booster

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Tai Kyung Noh

2016-09-01

Full Text Available Polydeoxyribonucleotide (PDRN, a deoxyribonucleotide polymer, is popularly used for faster healing of cutaneous wounds and boosting of neocollagenesis of photoaged skin among current dermatologic practitioners. Some patients receiving PDRN injection treatment also reported improvement of photoaging-associated mottled pigmentation (PMP. To investigate the effect of PDRN on cutaneous melanogenesis, we examined the effect of PDRN and an available product (Placentex® containing PDRN on melanogenesis using human melanocytes-keratinocytes cocultures and mouse melanocytes. Melanin content, tyrosinase activity, and levels of microphthalmia-associated transcription factor (MITF, tyrosinase, and tyrosinase-related protein (TRP-1 were determined. Intracellular signaling pathways were assessed by Western blotting. PDRN and Placentex® led to decreases in melanin content, tyrosinase activity, and MITF and TRP-1 expression with concomitant increases in phosphorylated forms of extracellular signal-regulated protein kinase (ERK and AKT in mouse melanocytes. More importantly, both PDRN and Placentex® significantly suppressed the melanin content in human melanocyte–keratinocyte cocultures. Clinical evaluation of six female patients with facial hyperpigmentation after three sessions of intradermal PDRN injections using a 5-point scale revealed that PDRN led to more than noticeable improvements in hyperpigmented lesions. This is the first study to demonstrate that PDRN, which is known for its wound-healing properties, may have novel anti-melanogenesis and potential skin whitening properties.

Cutaneous polyarteritis nodosa: A rare isolated cutaneous vasculitis

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Praveen Kumar A Subbanna

2012-01-01

Full Text Available Cutaneous polyarteritis nodosa (CPAN is a rare form of cutaneous vasculitis that involves small and medium sized arteries of the dermis and subcutaneous tissue without systemic involvement. It presents with tender subcutaneous nodules, digital gangrene, livedo reticularis and subcutaneous ulcerations. The diagnosis is by skin biopsy and characteristic pathologic feature is a leukocytoclastic vasculitis in the small to medium-sized arterioles of the dermis. We report a rare case of benign cutaneous PAN in a 14-year-old girl who presented with history of fever, subcutaneous nodules with cutaneous ulcer and digital gangrene. The skin biopsy showed leukocytoclastic vasculitis with fibrinoid necrosis in the dermal vessels. She received treatment with steroids and lesions resolved completely over a period of month.

Buruli ulcer: wound care and rehabilitation

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Frimpong M

2016-06-01

Full Text Available Michael Frimpong,1 Fred Stephen Sarfo,2 Mabel Sarpong Duah,1 Mark Wansbrough-Jones,3 Richard O Phillips2 1Kumasi Centre for Collaborative Research in Tropical Medicine, 2Department of Medicine, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; 3Institute for Infection and Immunity, St George’s University of London, London, UK Abstract: Buruli ulcer caused by Mycobacterium ulcerans is a neglected tropical disease characterized by extensive ulceration involving predominantly the upper and lower limbs of patients. The disease is common in rural tropical communities in West and Central Africa, where access to proper health care is limited. Pathogenesis of the characteristic painless ulcers is linked to the elaboration by M. ulcerans of a lipid toxin called mycolactone that has potent cytopathic, immunosuppressive, and analgesic effects on a host of cells in cutaneous tissues. Mycolactone is known to profoundly inhibit secretion of a plethora of proteins that are essential for wound healing. Even though a combination antibacterial therapy of streptomycin and rifampicin for 8 weeks is effective for treatment, it relies on good and appropriate wound management to prevent secondary bacterial infections and improve healing. Evidence-based interventions for wound care in Buruli ulcer disease are often lacking and have relied on expert advice and recommendations. Surgical interventions are limited to debridement of necrotic tissue and grafting of extensive ulcers, usually after antibiotic therapy. Patients’ rehabilitation is an important component of care to reduce disabilities associated with the disease and proper integration into the community after treatment. Keywords: Buruli ulcer, Mycobacterium ulcerans disease, Mycobacterium ulcerans, wound care, rehabilitation, disability

Production of vegetable oil blends and structured lipids and their effect on wound healing

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Juliana Neves Rodrigues Ract

2015-06-01

Full Text Available Two oil blends (sunflower/canola oils 85/15 (BL1 and canola/linseed oils 70/30 (BL2, were prepared and enzymatically interesterified to be applied to surgically-induced wounds in rats. Following surgery, the animals were submitted to the Treatment with Physiological Saline (TPS (control group, Blends (TBL, and Structured Lipids (TSL. The control group (TPS received physiological saline solution for 15 days. In TBL, BL1 was administered during the inflammation phase (days 0-3 and BL2 in the tissue formation and remodeling phase (days 4-15. In TSL, Structured Lipid 1 (SL1 and Structured Lipid 2 (SL2 were used instead of BL1 and BL2, respectively. The aim of this study was to compare wound closure evolution among rats treated with the blends or structured lipids versus control rats treated with physiological saline. The wound healing process was evaluated by measuring the wound areas along the treatments and the concentrations of cytokines. An increase in the areas of wounds treated with the blends and structured lipids in the inflammatory phase was observed, followed by a steeper closure curve compared to wounds treated with physiological saline. The changes observed during the inflammatory phase suggest a potential therapeutic application in cutaneous wound healing which should be further investigated.

Integrin-linked kinase (ILK) modulates wound healing through regulation of hepatocyte growth factor (HGF)

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Serrano, Isabel; Diez-Marques, Maria L.; Rodriguez-Puyol, Manuel [Department of Physiology, University of Alcala, Alcala de Henares, Madrid (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Instituto Reina Sofia de Investigacion Nefrologica (Spain); Herrero-Fresneda, Inmaculada [Nephrology Unit, IDIBELL, Hospital de Bellvitge, Barcelona (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Garcia del Moral, Raimundo [Department of Pathology, University of Granada (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Dedhar, Shoukat [Department of Integrative Oncology, BC Cancer Research Center, Vancouver, BC (Canada); Ruiz-Torres, Maria P., E-mail: mpiedad.ruiz@uah.es [Department of Physiology, University of Alcala, Alcala de Henares, Madrid (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Instituto Reina Sofia de Investigacion Nefrologica (Spain); Rodriguez-Puyol, Diego [Nephrology Unit, Hospital Universitario Principe de Asturias, Alcala de Henares, Madrid (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Instituto Reina Sofia de Investigacion Nefrologica (Spain)

2012-11-15

Integrin-linked kinase (ILK) is an intracellular effector of cell-matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The present work analyzes the role of ILK in wound healing in adult animals using a conditional knock-out of the ILK gene generated with the tamoxifen-inducible Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded wound closure in skin. Intracellular mechanisms involved in this process were analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice and revealed that wounding promotes rapid activation of phosphatidylinositol 3-kinase (PI3K) and ILK. Knockdown of ILK resulted in a retarded wound closure due to a decrease in cellular proliferation and loss of HGF protein expression during the healing process, in vitro and in vivo. Alterations in cell proliferation and wound closure in ILK-deficient MEF or mice could be rescued by exogenous administration of human HGF. These data demonstrate, for the first time, that the activation of PI3K and ILK after skin wounding are critical for HGF-dependent tissue repair and wound healing. -- Highlights: Black-Right-Pointing-Pointer ILK deletion results in decreased HGF expression and delayed scratch wound repair. Black-Right-Pointing-Pointer PI3K/ILK/AKT pathway signals through HGF to regulate wound healing. Black-Right-Pointing-Pointer An ILK-dependent increase in HGF expression is responsible for wound healing in vivo. Black-Right-Pointing-Pointer ILK-KO mice are used to confirm the requirement for ILK function in wound healing. Black-Right-Pointing-Pointer Human HGF treatment restores delayed wound closure in vitro and in vivo.

An Analytical Study of Mammalian Bite Wounds Requiring Inpatient Management

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Young-Geun Lee

2013-11-01

Full Text Available BackgroundMammalian bite injuries create a public health problem because of their frequency, potential severity, and increasing number. Some researchers have performed fragmentary analyses of bite wounds caused by certain mammalian species. However, little practical information is available concerning serious mammalian bite wounds that require hospitalization and intensive wound management. Therefore, the purpose of this study was to perform a general review of serious mammalian bite wounds.MethodsWe performed a retrospective review of the medical charts of 68 patients who were referred to our plastic surgery department for the treatment of bite wounds between January 2003 and October 2012. The cases were analyzed according to the species, patient demographics, environmental factors, injury characteristics, and clinical course.ResultsAmong the 68 cases of mammalian bite injury, 58 (85% were caused by dogs, 8 by humans, and 2 by cats. Most of those bitten by a human and both of those bitten by cats were male. Only one-third of all the patients were children or adolescents. The most frequent site of injury was the face, with 40 cases, followed by the hand, with 16 cases. Of the 68 patients, 7 were treated with secondary intention healing. Sixty-one patients underwent delayed procedures, including delayed direct closure, skin graft, composite graft, and local flap.ConclusionsBased on overall findings from our review of the 68 cases of mammalian bites, we suggest practical guidelines for the management of mammalian bite injuries, which could be useful in the treatment of serious mammalian bite wounds.

Cutaneous Leishmaniasis Induces a Transmissible Dysbiotic Skin Microbiota that Promotes Skin Inflammation.

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Gimblet, Ciara; Meisel, Jacquelyn S; Loesche, Michael A; Cole, Stephen D; Horwinski, Joseph; Novais, Fernanda O; Misic, Ana M; Bradley, Charles W; Beiting, Daniel P; Rankin, Shelley C; Carvalho, Lucas P; Carvalho, Edgar M; Scott, Phillip; Grice, Elizabeth A

2017-07-12

Skin microbiota can impact allergic and autoimmune responses, wound healing, and anti-microbial defense. We investigated the role of skin microbiota in cutaneous leishmaniasis and found that human patients infected with Leishmania braziliensis develop dysbiotic skin microbiota, characterized by increases in the abundance of Staphylococcus and/or Streptococcus. Mice infected with L. major exhibit similar changes depending upon disease severity. Importantly, this dysbiosis is not limited to the lesion site, but is transmissible to normal skin distant from the infection site and to skin from co-housed naive mice. This observation allowed us to test whether a pre-existing dysbiotic skin microbiota influences disease, and we found that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results in exacerbated skin inflammatory responses. These findings demonstrate that a dysbiotic skin microbiota is not only a consequence of tissue stress, but also enhances inflammation, which has implications for many inflammatory cutaneous diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

A rapid and systematic review of the clinical effectiveness and cost-effectiveness of debriding agents in treating surgical wounds healing by secondary intention

NARCIS (Netherlands)

Lewis, R.; Whiting, P.; ter Riet, G.; O'Meara, S.; Glanville, J.

2001-01-01

BACKGROUND: Most surgically sutured wounds heal without any complication. However, in some cases wound healing can be delayed due to the presence of infection or wound breakdown. This can result in the wounds becoming cavity wounds and thus necessitate healing by secondary intention. Other surgical

Insight into the epidemiology of cutaneous squamous cell carcinoma with perineural spread.

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Warren, Timothy A; Whiteman, David C; Porceddu, Sandro V; Panizza, Benedict J

2016-09-01

Perineural spread (PNS) of cutaneous squamous cell carcinoma of the head and neck (SCCHN) can be associated with poor outcomes. Disease understanding and awareness is limited leading to delayed diagnosis and treatment. The purpose of this study was to identify epidemiological features of patients with PNS of cutaneous SCCHN. Tumor characteristics and demographics of patients with PNS of cutaneous SCCHN managed through a single institution were collected between 1998 and 2013. One hundred twenty patients were included in this study. The majority had a history of skin cancer (85.8%). The median time from primary tumor treatment to PNS symptom onset was 16 months (range, 1-86 months). A total of 34.2% had no perineural invasion (PNI) detected in the primary, and 22.5% had no known primary tumor. Only 5.8% of the patients had nodal involvement at presentation. Patients can present with PNS from cutaneous SCCHN with no known primary tumor or with primary tumors without PNI. The majority of patients presented without regional nodal involvement. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1416-1420, 2016. © 2016 Wiley Periodicals, Inc.

The morphological effect of electron irradiation on the healing of skin wounds and skin grafts in the rat

International Nuclear Information System (INIS)

Wang, Q.

1995-01-01

-vascularization and granulation tissue formation and remodelling. Two basic and important questions addressed by this study were whether ionizing irradiation influences individual processes in wound healing, and whether or not radiation of the graft bed is compatible with cutaneous surgery. In these two experimental models, pre-wounding radiation and radiation of the graft bed partially depressed the inflammatory reaction in response to injury, and also reduced the deposition of fibrin and presence of tissue exudate. Following this initial event, there was a delay but not a prevention of re-epithelialization and reformation of the dermo-epidermal junction (DEJ). The present study also revealed early morphological changes in the microvessels of the irradiated wound bed and in the granulation tissue, indicating an early effect on angiogenesis. This investigation also focused on the effects of radiation on granulation tissue formation and extracellular matrix (ECM) remodelling. The results demonstrated that ionizing radiation caused a decrease in the presence of fibroblasts and in the extent of granulation tissue formation and ECM remodelling. In the study of incisional wounds with pre-operative radiation treatment, granulation tissue depth and volume were decreased up to 7 days post-wounding, but were restored to around the sham-irradiated wound values by day 14. In the study of skin graft repair as affected by radiation of the graft bed, two parameters, diameter and density of collagen fibrils in the granulation tissue were examined quantitatively. The findings showed that collagen fibril diameter was significantly reduced throughout the experimental period, by comparison with that found in the grafted only group. However no differences were detected for collagen fibril density between the two groups by 2 weeks post-grafting. This work concludes that pre-wounding and wound bed radiation slows down wound healing, but does not prevent it, at single dose levels of 9.6 Gy and 10 Gy. Since

The morphological effect of electron irradiation on the healing of skin wounds and skin grafts in the rat

Energy Technology Data Exchange (ETDEWEB)

Wang, Q

1995-07-01

-vascularization and granulation tissue formation and remodelling. Two basic and important questions addressed by this study were whether ionizing irradiation influences individual processes in wound healing, and whether or not radiation of the graft bed is compatible with cutaneous surgery. In these two experimental models, pre-wounding radiation and radiation of the graft bed partially depressed the inflammatory reaction in response to injury, and also reduced the deposition of fibrin and presence of tissue exudate. Following this initial event, there was a delay but not a prevention of re-epithelialization and reformation of the dermo-epidermal junction (DEJ). The present study also revealed early morphological changes in the microvessels of the irradiated wound bed and in the granulation tissue, indicating an early effect on angiogenesis. This investigation also focused on the effects of radiation on granulation tissue formation and extracellular matrix (ECM) remodelling. The results demonstrated that ionizing radiation caused a decrease in the presence of fibroblasts and in the extent of granulation tissue formation and ECM remodelling. In the study of incisional wounds with pre-operative radiation treatment, granulation tissue depth and volume were decreased up to 7 days post-wounding, but were restored to around the sham-irradiated wound values by day 14. In the study of skin graft repair as affected by radiation of the graft bed, two parameters, diameter and density of collagen fibrils in the granulation tissue were examined quantitatively. The findings showed that collagen fibril diameter was significantly reduced throughout the experimental period, by comparison with that found in the grafted only group. However no differences were detected for collagen fibril density between the two groups by 2 weeks post-grafting. This work concludes that pre-wounding and wound bed radiation slows down wound healing, but does not prevent it, at single dose levels of 9.6 Gy and 10 Gy. Since

Topical application of Acheflan on rat skin injury accelerates wound healing: a histopathological, immunohistochemical and biochemical study.

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Perini, Jamila Alessandra; Angeli-Gamba, Thais; Alessandra-Perini, Jessica; Ferreira, Luiz Claudio; Nasciutti, Luiz Eurico; Machado, Daniel Escorsim

2015-06-30

Dermal wound healing involves a cascade of complex events including angiogenesis and extracellular matrix remodeling. Several groups have focused in the study of the skin wound healing activity of natural products. The phytomedicine Acheflan®, and its main active constituent is the oil from Cordia verbenacea which has known anti-inflammatory, analgesic and antimicrobial activities. To our knowledge, no investigation has evaluated the effect of Acheflan® in an experimental model of skin wound healing. The present study has explored the wound healing property of Acheflan® and has compared it with topical effectiveness of collagenase and fibrinolysin by using Wistar rat cutaneous excision wound model. Animals were divided into four groups: untreated animals are negative control (NC), wounds were treated topically every day with Collagenase ointment (TC), with Fibrinolysin ointment (TF) and with cream Acheflan (TAc). Skin samples were collected on zero, 8th and 15th days after wounding. The healing was assessed by hematoxylin-eosin (HE), picrosirius red, hydoxyproline content and immunohistochemical analysis of the vascular endothelial growth factor (VEGF) and matrix metalloprotease-9 (MMP-9). Statistical analysis was done by ANOVA and Student t-test (p Cordia verbenacea) and TC possess higher therapeutic properties for wound healing compared with TF. These ointments seem to accelerate wound healing, probably due to their involvement with the increase of angiogenesis and dermal remodeling.

Caveolin-1 as a novel indicator of wound-healing capacity in aged human corneal epithelium.

Science.gov (United States)

Rhim, Ji Heon; Kim, Jae Hoon; Yeo, Eui-Ju; Kim, Jae Chan; Park, Sang Chul

2010-01-01

Excess caveolin-1 has been reported to play a role in age-dependent hyporesponsiveness to growth factors in vitro. Therefore, we hypothesized that caveolin-1-dependent hyporesponsiveness to growth factors in aged corneal epithelial cells might be responsible for delayed wound healing in vivo. To test this hypothesis, we evaluated corneal wound-healing time by vital staining using fluorescein after laser epithelial keratomileusis (LASEK). We compared wound-healing times in young, middle-aged and elderly patients. We also examined caveolin-1 levels and other aging markers, such as p53 and p21, in the corneal epithelium. Elderly patients generally had higher caveolin-1 levels in the corneal epithelia than young patients. There were, however, variations among individuals with increased caveolin-1 in some young patients and decreased levels in some elderly patients. Wound-healing time after LASEK correlated well with the corneal caveolin-1 status. Therefore, we suggest that caveolin-1 status might be responsible for delayed wound healing in elderly patients after LASEK. Caveolin-1 status might be a regulator for wound-healing capacity and a novel target for in vivo adjustment.

Cutaneous and systemic hypersensitivity reactions to metallic implants

DEFF Research Database (Denmark)

Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

2011-01-01

Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous....... However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis...

Risk factors for delayed healing at the free anterolateral thigh flap donor site

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Yoshiro Abe

2018-01-01

Full Text Available Background The free anterolateral thigh (ALT flap has been widely used for various kinds of reconstructions. However, delayed healing at the donor site occasionally occurs due to wound dehiscence or the partial loss of grafted skin at the donor site. The aim of the present study was to identify reliable predictive factors for delayed healing at the donor site after the harvest of a free ALT flap. Methods This study included 52 patients who underwent reconstructive procedures using free ALT flaps. The delayed healing group included patients with wounds at the donor site that had not healed over 3 weeks after surgery, and the normal healing group included patients who showed wound healing within 3 weeks after surgery. Multivariate logistic regression models were created to identify the risk factors for delayed healing at the ALT flap donor site. Results Among the 52 patients, 24 (46.2% showed delayed healing at the donor site, and 6 patients required additional operative treatment. A high preoperative body mass index (BMI, smoking, and skin grafting were found to be significantly associated with delayed healing at the ALT donor site. Of the 37 patients who underwent skin grafting, 23 (62% experienced delayed healing at the donor site. Conclusions A high preoperative BMI, smoking, and skin grafting were risk factors for delayed healing at the free ALT donor site. Skin grafting at the ALT donor site should be avoided in patients with a high BMI or a habit of smoking.

Dendritic cells modulate burn wound healing by enhancing early proliferation.

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Vinish, Monika; Cui, Weihua; Stafford, Eboni; Bae, Leon; Hawkins, Hal; Cox, Robert; Toliver-Kinsky, Tracy

2016-01-01

Adequate wound healing is vital for burn patients to reduce the risk of infections and prolonged hospitalization. Dendritic cells (DCs) are antigen presenting cells that release cytokines and are central for the activation of innate and acquired immune responses. Studies have showed their presence in human burn wounds; however, their role in burn wound healing remains to be determined. This study investigated the role of DCs in modulating healing responses within the burn wound. A murine model of full-thickness contact burns was used to study wound healing in the absence of DCs (CD11c promoter-driven diphtheria toxin receptor transgenic mice) and in a DC-rich environment (using fms-like tyrosine kinase-3 ligand, FL- a DC growth factor). Wound closure was significantly delayed in DC-deficient mice and was associated with significant suppression of early cellular proliferation, granulation tissue formation, wound levels of TGFβ1 and formation of CD31+ vessels in healing wounds. In contrast, DC enhancement significantly accelerated early wound closure, associated with increased and accelerated cellular proliferation, granulation tissue formation, and increased TGFβ1 levels and CD31+ vessels in healing wounds. We conclude that DCs play an important role in the acceleration of early wound healing events, likely by secreting factors that trigger the proliferation of cells that mediate wound healing. Therefore, pharmacological enhancement of DCs may provide a therapeutic intervention to facilitate healing of burn wounds. © 2016 by the Wound Healing Society.

Increased cutaneous wound healing effect of biodegradable liposomes containing madecassoside: preparation optimization, in vitro dermal permeation, and in vivo bioevaluation.

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Li, Zehao; Liu, Meifeng; Wang, Huijuan; Du, Song

2016-01-01

Madecassoside (MA) is highly potent in treating skin disorders such as wounds and psoriasis. However, the topical wound healing effect of MA was hampered by its poor membrane permeability. In order to overcome this shortcoming, MA liposomes were designed and prepared by a double-emulsion method to enhance transdermal and wound healing effects. In this study, response surface methodology was adopted to yield the optimal preparation conditions of MA double-emulsion liposomes with average particle size of 151 nm and encapsulation efficiency of 70.14%. Moreover, MA double-emulsion liposomes demonstrated superior stability and homogeneous appearance in 5 months; their leakage rate was healing of MA liposomal formulations were conducted for the first time to evaluate MA delivery efficiency and wound healing effect. The transdermal property and wound cure effect of MA double-emulsion liposomes were superior to those of MA film dispersion liposomes, and both the methods were endowed with an excellent performance by polyethylene glycol modification. In conclusion, double-emulsion liposome formulation was an applicable and promising pharmaceutical preparation for enhancing MA delivery toward wound healing effect and improving wound-healing progress.

Autologous adipocyte derived stem cells favour healing in a minipig model of cutaneous radiation syndrome.

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Fabien Forcheron

Full Text Available Cutaneous radiation syndrome (CRS is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs. For experiments, Göttingen minipigs were locally gamma irradiated using a (60Co source at the dose of 50 Gy and grafted (n = 5 or not (n = 8. ASCs were cultured in MEM-alpha with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL(-1 and post irradiation were intradermally injected on days 25, 46, 67 and finally between days 95 and 115 (50 × 10(6 ASCs each time into the exposed area. All controls exhibited a clinical evolution with final necrosis (day 91. In grafted pigs an ultimate wound healing was observed in four out of five grafted animals (day 130 +/- 28. Immunohistological analysis of cytokeratin expression showed a complete epidermis recovery. Grafted ASCs accumulated at the dermis/subcutis barrier in which they attracted numerous immune cells, and even an increased vasculature in one pig. Globally this study suggests that local injection of ASCs may represent a useful strategy to mitigate CRS.

Wegener´s granulomatosis in a young patient preceded by localized cutaneous manifestations

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Jesper Smit

2011-10-01

Full Text Available Wegener´s granulomatosis (WG is a rare, systemic vasculitis involving multiple organs. The clinical presentation is highly diverse, and there is considerable risk of mortality if diagnosis and treatment are delayed. We present a case illustrating that patients with WG may initially present with localized cutaneous symptoms and signs.

Novel Stem Cell Therapies for Applications to Wound Healing and Tissue Repair.

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Grada, Ayman; Falanga, Vincent

2016-10-26

The number of individuals with chronic cutaneous wounds has been increasing worldwide due to an aging population, diabetes, obesity, and cardiovascular disease. In the United States, almost seven million Americans have chronic skin ulcers. Many therapeutic approaches have been used. However, the treatment outcomes are not always ideal because of failure to achieve complete wound closure in around 60% of cases, scarring, and high rate of recurrence. Therefore, there is a need for more effective therapies. Stem cells offer promising possibilities. Pre-clinical studies have shown that bone- or adipose tissue-derived mesenchymal stem cells (MSCs) have a competitive advantage over other types of stem cells due to their better defined multipotent differentiating potential, paracrine effects, immunomodulatory properties, and safety. However, large controlled clinical trials are needed to examine the capabilities of MSCs in humans and to assess their safety profile. In this review, we highlight emerging treatments in tissue regeneration and repair and provide some perspectives on how to translate current knowledge about stem cells-both multipotent and pluripotent-into viable clinical approaches for treating patients with difficult to heal wounds.

Pseudomonas aeruginosa infection alters the macrophage phenotype switching process during wound healing in diabetic mice.

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Chen, Sinuo; Li, Renren; Cheng, Chun; Xu, Jing-Ying; Jin, Caixia; Gao, Furong; Wang, Juan; Zhang, Jieping; Zhang, Jingfa; Wang, Hong; Lu, Lixia; Xu, Guo-Tong; Tian, Haibin

2018-03-07

Macrophages play critical roles in wound healing process. They switch from "classically activated" (M1) phenotype in the early inflammatory phase to "alternatively activated" (M2) phenotype in the later healing phase. However, the dynamic process of macrophage phenotype switching in diabetic wounds burdened with bacteria is unclear. In this report, Pseudomonas aeruginosa, frequently detected in diabetic foot ulcers, was inoculated into cutaneous wounds of db/db diabetic mice to mimic bacterium-infected diabetic wound healing. We observed that P. aeruginosa infection impaired diabetic wound healing and quickly promoted the expression of pro-inflammatory genes (M1 macrophage markers) tumor necrosis factor-α (tnf-α), interleukin-1β (il-1β) and il-6 in wounds. The expression of markers of M2 macrophages, including il-10, arginase-1, and ym1 were also upregulated. In addition, similar gene expression patterns were observed in macrophages isolated directly from wounds. Immunostaining showed that P. aeruginosa infection increased both the ratios of M1 and M2 macrophages in wounds compared with that in control groups, which was further confirmed by in vitro culturing macrophages with P. aeruginosa and skin fibroblast conditioned medium. However, the ratios of the expression levels of pro-inflammatory genes to anti-inflammatory gene il-10 was increased markedly in P. aeruginosa infected wounds and macrophages compared with that in control groups, and P. aeruginosa prolonged the presence of M1 macrophages in the wounds. These data demonstrated that P. aeruginosa in diabetic wounds activates a mixed M1/M2 macrophage phenotype with an excessive activation of M1 phenotype or relatively inadequate activation of M2 phenotype. © 2018 International Federation for Cell Biology.

Effects of aroeira (Schinus terebinthifoliu Raddi) oil on cutaneous wound healing in rats.

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Estevão, Lígia Reis Moura; Mendonça, Fábio de Souza; Baratella-Evêncio, Liriane; Simões, Ricardo Santos; Barros, Maria Edna Gomes de; Arantes, Rosa Maria Esteves; Rachid, Milene Alvarenga; Evêncio-Neto, Joaquim

2013-03-01

To evaluate the effects of aroeira (Schinus terebinthifolius) ointment on skin wound healing in rats. Adult male rats (n=20) were divided into four groups of five animals each, as follows: G4, G7, G14 and G21, which corresponds to 4th, 7th, 14th and 21th days postoperatively. Each animal were made two incisions on the skin, including the subcutaneous tissue, in the right and left sides of thoracic region, separated by a distance of two inches. The right lesion was treated with base ointment (vaseline, lanolin); the left one was treated with base ointment containing 5% of aroeira oil. At the end of each experimental period the lesions were evaluated for the contraction degree. Then held the collection of fragments that were fixed in 10% formalin and processed for paraffin embedding. In the histological sections (5μm) was evaluated the morphology and quantified the collagen and blood vessels. The data obtained were submitted to ANOVA test complemented by Tukey-Kramer test (p<0.05). The contraction of the lesions was higher in wounds treated with aroeira oil than in controls at 7th and 14th days (p<0.01), whereas in the 21st day all lesions were already completely healed. The morphology showed granulation tissue more developed, with fibroblasts more bulky and collagen fibers more arranged in the experimental group at 4th, 7th and 14th days. The morphometry showed a significant increase in the quantification of collagen fibers in the experimental group at 7th and 14th days (p<0.05). The aroeira oil accelerates the healing process of wounds as a macroscopic, morphological and morphometrical analysis.

Loss of the Desmosomal Component Perp Impairs Wound Healing In Vivo

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Veronica G. Beaudry

2010-01-01

Full Text Available Epithelial wound closure is a complex biological process that relies on the concerted action of activated keratinocytes and dermal fibroblasts to resurface and close the exposed wound. Modulation of cell-cell adhesion junctions is thought to facilitate cellular proliferation and migration of keratinocytes across the wound. In particular, desmosomes, adhesion complexes critical for maintaining epithelial integrity, are downregulated at the wound edge. It is unclear, however, how compromised desmosomal adhesion would affect wound reepithelialization, given the need for a delicate balance between downmodulating adhesive strength to permit changes in cellular morphology and maintaining adhesion to allow coordinated migration of keratinocyte sheets. Here, we explore the contribution of desmosomal adhesion to wound healing using mice deficient for the desmosomal component Perp. We find that Perp conditional knockout mice display delayed wound healing relative to controls. Furthermore, we determine that while loss of Perp compromises cell-cell adhesion, it does not impair keratinocyte proliferation and actually enhances keratinocyte migration in in vitro assays. Thus, Perp's role in promoting cell adhesion is essential for wound closure. Together, these studies suggest a role for desmosomal adhesion in efficient wound healing.

Corneal wound healing is compromised by immunoproteasome deficiency.

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Deborah A Ferrington

Full Text Available Recent studies have revealed roles for immunoproteasome in regulating cell processes essential for maintaining homeostasis and in responding to stress and injury. The current study investigates how the absence of immunoproteasome affects the corneal epithelium under normal and stressed conditions by comparing corneas from wildtype (WT mice and those deficient in two immunoproteasome catalytic subunits (lmp7(-/-/mecl-1(-/-, L7M1. Immunoproteasome expression was confirmed in WT epithelial cells and in cells of the immune system that were present in the cornea. More apoptotic cells were found in both corneal explant cultures and uninjured corneas of L7M1 compared to WT mice. Following mechanical debridement, L7M1 corneas displayed delayed wound healing, including delayed re-epithelialization and re-establishment of the epithelial barrier, as well as altered inflammatory cytokine production compared to WT mice. These results suggest that immunoproteasome plays an important role in corneal homeostasis and wound healing.

Potency of umbilical cord blood- and Wharton's jelly-derived mesenchymal stem cells for scarless wound healing.

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Doi, Hanako; Kitajima, Yuriko; Luo, Lan; Yan, Chan; Tateishi, Seiko; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Mori, Ryoichi; Masuzaki, Hideaki; Shimokawa, Isao; Hirano, Akiyoshi; Li, Tao-Sheng

2016-01-05

Postnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCB-MSCs) and Wharton's jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections. UCB-MSCs expressed lower levels of the pre-inflammatory cytokines IL1A and IL1B, but higher levels of the extracellular matrix (ECM)-degradation enzymes MMP1 and PLAU compared with WJ-MSCs, suggesting that UCB-MSCs were more likely to favor scarless wound healing. However, we failed to find significant benefits for stem cell therapy in improving wound healing and reducing collagen deposition following the direct injection of 1.0 × 10(5) UCB-MSCs and WJ-MSCs into 5 mm full-thickness skin defect sites in nude mice. Interestingly, the implantation of UCB-MSCs tended to increase the expression of MMP2 and PLAU, two proteases involved in degradation of the extracellular matrix in the wound tissues. Based on our data, UCB-MSCs are more likely to be a favorable potential stem cell source for scarless wound healing, although a better experimental model is required for confirmation.

Topical flurbiprofen or prednisolone. Effect on corneal wound healing in rabbits.

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Miller, D; Gruenberg, P; Miller, R; Bergamini, M V

1981-04-01

Flurbiprofen is a nonsteroidal anti-inflammatory (NSAI) agent currently undergoing clinical investigation. Anti-inflammatory steroids have long been known to delay the healing of corneal stromal wounds. This was designed to compare the effects of equipotent anti-inflammatory doses of flurbiprofen and of prednisolone acetate on the inflammation and the healing (as measured by the wound bursting pressure) or 4-mm through-and-through incisions treated four times a day for ten postoperative days. The results suggest that flurbiprofen and prednisolone are not different in their effect on both postoperative inflammation and postoperative wound healing. Since NSAI agents and steroids inhibit prostaglandin formation at different enzymatic steps, it is possible that prostaglandins not only are responsible for postoperative inflammation but also are required for postoperative wound healing.

Cutaneous Pseudolymphomas.

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Romero-Pérez, D; Blanes Martínez, M; Encabo-Durán, B

2016-10-01

The term cutaneous pseudolymphoma refers to benign reactive lymphoid proliferations in the skin that simulate cutaneous lymphomas. It is a purely descriptive term that encompasses various reactive conditions with a varied etiology, pathogenesis, clinical presentation, histology, and behavior. We present a review of the different types of cutaneous pseudolymphoma. To reach a correct diagnosis, it is necessary to contrast clinical, histologic, immunophenotypic, and molecular findings. Even with these data, in some cases only the clinical course will confirm the diagnosis, making follow-up essential. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Caveolin-1 as a Novel Indicator of Wound-Healing Capacity in Aged Human Corneal Epithelium

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Rhim, Ji Heon; Kim, Jae Hoon; Yeo, Eui-Ju; Kim, Jae Chan; Park, Sang Chul

2010-01-01

Excess caveolin-1 has been reported to play a role in age-dependent hyporesponsiveness to growth factors in vitro. Therefore, we hypothesized that caveolin-1–dependent hyporesponsiveness to growth factors in aged corneal epithelial cells might be responsible for delayed wound healing in vivo. To test this hypothesis, we evaluated corneal wound-healing time by vital staining using fluorescein after laser epithelial keratomileusis (LASEK). We compared wound-healing times in young, middle-aged a...

The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation.

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Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

2017-08-05

Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing.

The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation

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Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

2017-01-01

Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing. PMID:28413186

A novel hydrogel of poloxamer 407 and chitosan obtained by gamma irradiation exhibits physicochemical properties for wound management

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Leyva-Gómez, Gerardo, E-mail: gerardoleyva@hotmail.com [Laboratory of Connective Tissue, Centro Nacional de Investigación y Atención de Quemados, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City (Mexico); Santillan-Reyes, Erika, E-mail: kikita5410@gmail.com [Laboratory of Connective Tissue, Centro Nacional de Investigación y Atención de Quemados, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City (Mexico); Lima, E, E-mail: lima@iim.unam.mx [Departamento de Materiales Metálicos y Cerámicos, Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, Mexico City (Mexico); Madrid-Martínez, Abigail, E-mail: abitzy@hotmail.com [Laboratory of Connective Tissue, Centro Nacional de Investigación y Atención de Quemados, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City (Mexico); Krötzsch, E, E-mail: kroted@yahoo.com.mx [Laboratory of Connective Tissue, Centro Nacional de Investigación y Atención de Quemados, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City (Mexico); and others

2017-05-01

Application of polymers cross-linked by gamma irradiation on cutaneous wounds has resulted in the improvement of healing. Chitosan (CH) and poloxamer 407 (P407)-based hydrogels confer different advantages in wound management. To combine the properties of both compounds, a gamma-irradiated mixture of 0.75/25% (w/w) CH and P407, respectively, was obtained (CH-P), and several physical, chemical, and biological analyses were performed. Notably, gamma radiation induced changes in the mixture's thermal behavior, viscosity, and swelling, and exhibited stability at neutral pH. The thermal reversibility provided by P407 and the bacteriostatic effect of CH were maintained. Mice full-thickness wounds treated with CH-P diminished the wound area during the first days. Consequently, with this treatment, increased levels of macrophages, α-SMA, and collagen deposition in wounds were observed, indicating a more mature scar tissue. In conclusion, the new hydrogel CH-P, at physiologic pH, combined the beneficial characteristics of both polymers and produced new properties for wound management. - Highlights: • ϒ-irradiation of chitosan + poloxamer 407 produced a hydrogel (CH-P) to wound care. • ϒ-irradiation allows chitosan (CH) solubility at physiological pH (CH-P 7). • CH-P 7 copolymer exhibits antimicrobial/antifungal features. • CH-P 7 hydrogel stimulates early wound-closure rate. • CH-P 7 increases collagen deposition and macrophage/fibroblasts recruitment.

Effect of semisolid formulation of persea americana mill (avocado) oil on wound healing in rats.

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de Oliveira, Ana Paula; Franco, Eryvelton de Souza; Rodrigues Barreto, Rafaella; Cordeiro, Daniele Pires; de Melo, Rebeca Gonçalves; de Aquino, Camila Maria Ferreira; E Silva, Antonio Alfredo Rodrigues; de Medeiros, Paloma Lys; da Silva, Teresinha Gonçalves; Góes, Alexandre José da Silva; Maia, Maria Bernadete de Sousa

2013-01-01

The aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oil in natura, on incisional and excisional cutaneous wound models in Wistar rats. An additional objective was to quantify the fatty acids present in avocado oil. On the 14th day, a significant increase was observed in percentage wound contraction and reepithelialization in the groups treated with 50% SSFAO or avocado oil compared to the petroleum jelly control. Anti-inflammatory activity, increase in density of collagen, and tensile strength were observed inSSFAO 50% or avocado oil groups, when compared to control groups. The analysis of the components of avocado oil by gas chromatography detected the majority presence of oleic fatty acid (47.20%), followed by palmitic (23.66%), linoleic (13.46%) docosadienoic (8.88%), palmitoleic (3.58%), linolenic (1.60%), eicosenoic (1.29%), and myristic acids (0.33%). Our results show that avocado oil is a rich source of oleic acid and contains essential fatty acids. When used in natura or in pharmaceutical formulations for topical use, avocado oil can promote increased collagen synthesis and decreased numbers of inflammatory cells during the wound-healing process and may thus be considered a new option for treating skin wounds.

Cutaneous Serratia marcescens infections in Korea: A retrospective analysis of 13 patients.

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Seo, Jimyung; Shin, Dongyun; Oh, Sang Ho; Lee, Ju Hee; Chung, Kee Yang; Lee, Min-Geol; Kim, Dae Suk

2016-02-01

Serratia marcescens is a Gram-negative bacillus belonging to the Enterobacteriaceae family. Because of increasing reports of antimicrobial resistance, this bacterium has received considerable attention and has emerged as an important pathogen. In order to reveal clinical and microbiological characteristics of S. marcescens cutaneous infection and to suggest appropriate antibiotic treatment, we retrospectively analyzed 17 strains isolated from wound swabs of Korean patients between November 2005 and March 2014. A total of 13 patients (five men and eight women) were included in our study, with a mean age of 46.3 years (range, 21-82). Based on medical history, seven patients were classified as immunocompromised. Prior predisposing factors for infections were noted in 12 patients, including pre-existing leg ulcers or dermatitis (5/13), preceding cancer surgeries (2/13), plastic surgeries and filler injection (2/13), traumas (2/13) and medical procedures following cutaneous abscess (1/13). Cutaneous infections showed various clinical presentations, including spontaneous dermal abscess, fingernail change, painful nodules and papular erosions. We found that third- and fourth-generation cephalosporins, gentamicin, levofloxacin and meropenem appeared active against all 17 strains in vitro. Clinically, all patients treated with empirical first-generation cephalosporin showed treatment resistance, and oral quinolone monotherapy was the most preferred antibiotic regimen without treatment failure, with an average treatment duration of 25 days (range, 14-42). This study demonstrates the various clinical presentations and treatment responses for cutaneous S. marcescens infection. Moreover, we suggest that initial antibiotic coverage should be broad enough to account for multidrug resistance in this rare pathogen. © 2015 Japanese Dermatological Association.

Wound-Healing Peptides for Treatment of Chronic Diabetic Foot Ulcers and Other Infected Skin Injuries

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Ana Gomes

2017-10-01

Full Text Available As the incidence of diabetes continues to increase in the western world, the prevalence of chronic wounds related to this condition continues to be a major focus of wound care research. Additionally, over 50% of chronic wounds exhibit signs and symptoms that are consistent with localized bacterial biofilms underlying severe infections that contribute to tissue destruction, delayed wound-healing and other serious complications. Most current biomedical approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagen-based to boost reestablishment of the skin tissue. Therefore, the present review is focused on the efforts that have been made over the past years to find peptides possessing wound-healing properties, towards the development of new and effective wound care treatments for diabetic foot ulcers and other skin and soft tissue infections.

Wound-Healing Peptides for Treatment of Chronic Diabetic Foot Ulcers and Other Infected Skin Injuries.

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Gomes, Ana; Teixeira, Cátia; Ferraz, Ricardo; Prudêncio, Cristina; Gomes, Paula

2017-10-18

As the incidence of diabetes continues to increase in the western world, the prevalence of chronic wounds related to this condition continues to be a major focus of wound care research. Additionally, over 50% of chronic wounds exhibit signs and symptoms that are consistent with localized bacterial biofilms underlying severe infections that contribute to tissue destruction, delayed wound-healing and other serious complications. Most current biomedical approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagen-based) to boost reestablishment of the skin tissue. Therefore, the present review is focused on the efforts that have been made over the past years to find peptides possessing wound-healing properties, towards the development of new and effective wound care treatments for diabetic foot ulcers and other skin and soft tissue infections.

Impact of diabetes on gingival wound healing via oxidative stress.

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Daisuke Kido

Full Text Available The aim of this study is to investigate the mechanisms linking high glucose to gingival wound healing. Bilateral wounds were created in the palatal gingiva adjacent to maxillary molars of control rats and rats with streptozotocin-induced diabetes. After evaluating postsurgical wound closure by digital imaging, the maxillae including wounds were resected for histological examinations. mRNA expressions of angiogenesis, inflammation, and oxidative stress markers in the surgical sites were quantified by real-time polymerase chain reaction. Primary fibroblast culture from the gingiva of both rats was performed in high glucose and normal medium. In vitro wound healing and cell proliferation assays were performed. Oxidative stress marker mRNA expressions and reactive oxygen species production were measured. Insulin resistance was evaluated via PI3K/Akt and MAPK/Erk signaling following insulin stimulation using Western blotting. To clarify oxidative stress involvement in high glucose culture and cells of diabetic rats, cells underwent N-acetyl-L-cysteine treatment; subsequent Akt activity was measured. Wound healing in diabetic rats was significantly delayed compared with that in control rats. Nox1, Nox2, Nox4, p-47, and tumor necrosis factor-α mRNA levels were significantly higher at baseline in diabetic rats than in control rats. In vitro study showed that cell proliferation and migration significantly decreased in diabetic and high glucose culture groups compared with control groups. Nox1, Nox2, Nox4, and p47 expressions and reactive oxygen species production were significantly higher in diabetic and high glucose culture groups than in control groups. Akt phosphorylation decreased in the high glucose groups compared with the control groups. Erk1/2 phosphorylation increased in the high glucose groups, with or without insulin treatment, compared with the control groups. Impaired Akt phosphorylation partially normalized after antioxidant N

Therapy of spinal wound infections using vacuum-assisted wound closure: risk factors leading to resistance to treatment.

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Ploumis, Avraam; Mehbod, Amir A; Dressel, Thomas D; Dykes, Daryll C; Transfeldt, Ensor E; Lonstein, John E

2008-07-01

This study retrospectively reviewed spine surgical procedures complicated by wound infection and managed by a protocol including the use of vacuum-assisted wound closure (VAC). To define factors influencing the number of debridements needed before the final wound closure by applying VAC for patients with postoperative spinal wound infections. VAC has been suggested as a safe and probably effective method for the treatment of spinal wound infections. The risk factors for infection resistance and need for debridement revisions after VAC placement are unknown. Seventy-three consecutive patients with 79 wound infections after undergoing spine surgery were studied (6 of them had recurrence of infection). All patients were taken to the operating room for irrigation and debridement under general anesthesia followed by placement of the VAC with subsequent delayed closure of the wound. Linear regression and t test were used to identify if the following variables were risk factors for the resistance of infection to VAC treatment: timing of clinical appearance of infection, depth of infection (deep or superficial), presence of instrumentation, positive culture for methicillin-resistant Staphylococcus aureus (MRSA) or more than 1 microorganism, age of the patient, and presence of other comorbidities. There were 34 males and 39 females with an average age of 58.4 years (21 to 82). Once the VAC was initiated, there was an average of 1.4 procedures until and including closure of the wound. The wound was closed an average of 7 days (range 5 to 14) after the placement of the initial VAC on the wound. The average follow-up was 14 months (range 12 to 28). All of the patients but 2 achieved a clean, closed wound without removal of instrumentation at a minimum follow-up of 1 year. Sixty patients had implants (instrumentation or allograft) within the site of wound infection. Thirteen patients had a decompression with exposed dura. Sixty-four infections (81%) presented with a draining

Efficacy of a collagen-based dressing in an animal model of delayed wound healing.

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Guillemin, Y; Le Broc, D; Ségalen, C; Kurkdjian, E; Gouze, J N

2016-07-02

The aim of this study was to evaluate in vitro and in vivo the efficacy of GBT013, a collagen-based dressing, for the treatment of chronic wounds, in a db/db mouse model of diabetes. Macroscopic and histologic analyses of db/db mice wound healing with GBT013 or saline gauze were assessed. The mRNA expression and the proliferation of dermal fibroblast were investigated. Matrix metalloproteinases (MMP)-2 and MMP-9 activities were quantified. In db/db mice, GBT013 improves wound epithelialisation when compared with saline gauze. Histological analysis of scar tissue also shows an enhancement of remodelling associated with no sign of acute inflammation. In addition, GBT013 significantly decreases interleukin (IL)-6 and IL-8, significantly increases tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 fibroblast mRNA expression and significantly reduces in vitro MMP-2 and MMP-9 enzymatic activities. Moreover, GBT013 allows cell growth inside the matrix and stimulates proliferation of human dermal fibroblast. By contributing to restore MMPs/TIMPs balance, GBT013 may function in all key stages of wound healing, such as inflammation, proliferation and tissue remodelling, and ultimately may provide a favourable environment for skin repair. This work was supported by Genbiotech, the R&D subsidiary of Laboratoires Genévrier, a pharmaceutical company.

Mast Cells Regulate Wound Healing in Diabetes.

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Tellechea, Ana; Leal, Ermelindo C; Kafanas, Antonios; Auster, Michael E; Kuchibhotla, Sarada; Ostrovsky, Yana; Tecilazich, Francesco; Baltzis, Dimitrios; Zheng, Yongjun; Carvalho, Eugénia; Zabolotny, Janice M; Weng, Zuyi; Petra, Anastasia; Patel, Arti; Panagiotidou, Smaro; Pradhan-Nabzdyk, Leena; Theoharides, Theoharis C; Veves, Aristidis

2016-07-01

Diabetic foot ulceration is a severe complication of diabetes that lacks effective treatment. Mast cells (MCs) contribute to wound healing, but their role in diabetes skin complications is poorly understood. Here we show that the number of degranulated MCs is increased in unwounded forearm and foot skin of patients with diabetes and in unwounded dorsal skin of diabetic mice (P diabetic mice. Pretreatment with the MC degranulation inhibitor disodium cromoglycate rescues diabetes-associated wound-healing impairment in mice and shifts macrophages to the regenerative M2 phenotype (P diabetic mice deficient in MCs have delayed wound healing compared with their wild-type (WT) controls, implying that some MC mediator is needed for proper healing. MCs are a major source of vascular endothelial growth factor (VEGF) in mouse skin, but the level of VEGF is reduced in diabetic mouse skin, and its release from human MCs is reduced in hyperglycemic conditions. Topical treatment with the MC trigger substance P does not affect wound healing in MC-deficient mice, but improves it in WT mice. In conclusion, the presence of nondegranulated MCs in unwounded skin is required for proper wound healing, and therapies inhibiting MC degranulation could improve wound healing in diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Unusual presentation of Sturge-Weber syndrome: Progressive megalencephaly with bilateral cutaneous and cortical involvement

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Kundan Mittal

2014-01-01

Full Text Available The Sturge Weber syndrome is characterized by developmental delay, seizures in infancy, unilateral cutaneous lesions with ipsilateral leptomeningeal enhancement. We report an unusual presentation of Sturge Weber syndrome with bilateral port wine nevus on the trunk and face along with bilateral cortical involvement in a developmentally normal child with progressive megalencephaly.

Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice

DEFF Research Database (Denmark)

Lund, Leif R; Green, Kirsty A; Stoop, Allart A

2006-01-01

Simultaneous ablation of the two known activators of plasminogen (Plg), urokinase-type (uPA) and the tissue-type (tPA), results in a substantial delay in skin wound healing. However, wound closure and epidermal re-epithelialization are significantly less impaired in uPA;tPA double-deficient mice ...

Effect of UV irradiation on cutaneous cicatrices: a randomized, controlled trial with clinical, skin reflectance, histological, immunohistochemical and biochemical evaluations.

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Due, Eva; Rossen, Kristian; Sorensen, Lars Tue; Kliem, Anette; Karlsmark, Tonny; Haedersdal, Merete

2007-01-01

The aim of this study was to examine the effect of ultraviolet (UV) irradiation on human cutaneous cicatrices. In this randomized, controlled study, dermal punch biopsy wounds served as a wound healing model. Wounds healed by primary or second intention and were randomized to postoperative solar UV irradiation or to no UV exposure. Evaluations after 5 and 12 weeks included blinded clinical assessments, skin reflectance measurements, histology, immunohistochemistry, and biochemical analyses of the N-terminal propeptide from procollagen-1, hydroxyproline, hydroxylysine, and proline. Twelve weeks postoperatively, UV-irradiated cicatrices healing by second intention: (i) were significantly pointed out as the most disfiguring; (ii) obtained significantly higher scores of colour, infiltration and cicatrix area; and (iii) showed significantly higher increase in skin-reflectance measurements of skin-pigmentation vs. non-irradiated cicatrices. No histological, immunohistochemical or biochemical differences were found. In conclusion, postoperative UV exposure aggravates the clinical appearance of cicatrices in humans.

Experimental studies on the influence of irradiation (60Co) on wound healing of colonic suture

International Nuclear Information System (INIS)

Shoji, Munehiro

1980-01-01

Effects of preoperative 60 Co irradiation on wound healing of colonic suture in adult dogs of mixed breed were discussed. Wound healing 7 days after colonic suture was compared among dogs which received colonic suture immediately, or 3 days, or 7 days after the 60 Co irradiation. As a result, there was not a big difference in their wound healing among these dogs, and disorders of wound healing were not found. Bursting pressure at sutured sites was always lower in irradiated dogs than controls. Recovery of the bursting pressure was 2 days slower in irradiated dogs than non-irradiated dogs for 7 days after the suture. Bursting pressure was the lowest on the 3rd day after the suture in both groups. As to fine changes in irradiated dogs, appearance of recommunicating phenomena in blood vessels, delay of a decrease in avascular regions, delay of granulation, and hypertrophy of vascular walls seemed to be influenced by 60 Co irradiation, but there was not a big difference in these results between irradiated and non-irradiated dogs. An increase in postoperative concentration of hydroproline tended to be little lower in irradiated dogs than controls, which seemed to be influenced by the 60 Co irradiation. This result was also suggested from delay of granulation and remaining inflammations. Effects of 60 Co irradiation on wound healing of colonic suture seemed to be slight generally, because ruptured suture scarecely occurred in the irradiated dogs. When doses used in this experiment were calculated roughly by Ellis's method, irradiation of 60 Co seemed not to influence seriously wound healing if the total of 2,000 to 2,500 rad was irradiated in 8 to 10 doses to human colon. (Tsunoda, M.)

Zmpste24-/- mouse model for senescent wound healing research.

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Butala, Parag; Szpalski, Caroline; Soares, Marc; Davidson, Edward H; Knobel, Denis; Warren, Stephen M

2012-12-01

The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24(-/-)) mouse could serve as a model of senescent wound healing. Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24(-/-) mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry. Zmpste24(-/-) mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24(-/-) wounds had decreased proliferation, increased 8-hydroxy-2'-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow-derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial. The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24(-/-) progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.

Pseudomonas aeruginosa biofilm hampers murine central wound healing by suppression of vascular epithelial growth factor

DEFF Research Database (Denmark)

Trøstrup, Hannah; Lerche, Christian J; Christophersen, Lars J

2018-01-01

-wounded, infection-susceptible BALB/c mice, which display delayed wound closure compared to C3H/HeN mice. Wounds were evaluated histopathologically 4, 7 or 10 days post-infection. Photoplanimetry evaluated necrotic areas. P. aeruginosa biofilm suppressed vascular endothelial growth factor levels centrally in BALB....../c wounds but increased peripheral levels 4-7 days post-infection. Central zones of the burn wound displayed lower levels of central vascular endothelial growth factor as observed 4 and 7 days post-infection in BALB/c mice compared to their C3H/HeN counterparts. Biofilm suppressed early, centrally located S......100A8/A9 in BALB/c and centrally and peripherally later on in C3H/HeN wounds as compared to uninfected mice. Peripheral polymorphonuclear-dominated inflammation and larger necrosis were observed in BALB/c wounds. In conclusion, P. aeruginosa biofilm modulates wounds by suppressing central...

Local injection of high-molecular hyaluronan promotes wound healing in old rats by increasing angiogenesis.

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Huang, Luying; Wang, Yi; Liu, Hua; Huang, Jianhua

2018-02-02

Impaired angiogenesis contributes to delayed wound healing in aging. Hyaluronan (HA) has a close relationship with angiogenesis and wound healing. However, HA content decreases with age. In this study, we used high molecular weight HA (HMW-HA) (1650 kDa), and investigated its effects on wound healing in old rats by local injection. We found that HMW-HA significantly increases proliferation, migration and tube formation in endothelial cells, and protects endothelial cells against apoptosis. Local injection of HMW-HA promotes wound healing by increasing angiogenesis in old rats. HMW-HA increases the phosphorylation of Src, ERK and AKT, leading to increased angiogenesis, suggesting that local injection of HMW-HA promotes wound healing in elderly patients.

Temporary Relocation of the Testes in Anteromedial Thigh Pouches Facilitates Delayed Primary Scrotal Wound Closure in Fournier Gangrene With Extensive Loss of Scrotal Skin-Experience With 12 Cases.

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Okwudili, Obi Anselm

2016-03-01

To share our experience on the use of temporary testicular thigh pouches to facilitate scrotal wound closure in Fournier gangrene with extensive loss of scrotal skin. Patients seen over a 10-year period who had extensive (>50%) loss of scrotal skin precluding delayed primary closure of the residual scrotal skin over the testes were documented. Patients had serial debridement as required with scrotal wound dressing until healthy granulation tissue was achieved. The testes were placed temporarily in anteromedial thigh pouches to allow for scrotal wound closure. In the postoperative period, the testes were gradually massaged back into the residual scrotal pouch, thus acting as natural tissue expanders. Mean patient age was 38.1 ± 10.0 years. Mean duration of admission was 24.4 ± 4.7 days. Identified predisposing factors were ischiorectal fossa abscess in 2 patients and urethral stricture in 1 patient. The rest were idiopathic. Mean Fournier gangrene severity index was 6.0 ± 1.3. Mean number of debridements was 2.3 ± 0.5. There was no mortality. The residual scrotal pouches expanded sufficiently over time (3-8 months) to accommodate the testes. Normal testicular volume was maintained in all patients. Mean testicular volume was 19.0 ± 3.2 cm. Follow-up was for 14.8 ± 9.7 months. Temporarily relocating the testes in anteromedial thigh pouches facilitates scrotal wound closure in Fournier gangrene with extensive loss of scrotal skin and obviates the need for specialized reconstructive surgery.

Compromised Wound Healing in Ischemic Type 2 Diabetic Rats.

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Peilang Yang

Full Text Available Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8 weeks high fat diet (HFD feeding regimen followed by multiple injections of streptozotocin (STZ at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds.

Antimicrobial peptides secreted by equine mesenchymal stromal cells inhibit the growth of bacteria commonly found in skin wounds.

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Harman, Rebecca M; Yang, Steven; He, Megan K; Van de Walle, Gerlinde R

2017-07-04

The prevalence of chronic skin wounds in humans is high, and treatment is often complicated by the presence of pathogenic bacteria. Therefore, safe and innovative treatments to reduce the bacterial load in cutaneous wounds are needed. Mesenchymal stromal cells (MSC) are known to provide paracrine signals that act on resident skin cells to promote wound healing, but their potential antibacterial activities are not well described. The present study was designed to examine the antibacterial properties of MSC from horses, as this animal model offers a readily translatable model for MSC therapies in humans. Specifically, we aimed to (i) evaluate the in vitro effects of equine MSC on the growth of representative gram-negative and gram-positive bacterial species commonly found in skin wounds and (ii) define the mechanisms by which MSC inhibit bacterial growth. MSC were isolated from the peripheral blood of healthy horses. Gram-negative E. coli and gram-positive S. aureus were cultured in the presence of MSC and MSC conditioned medium (CM), containing all factors secreted by MSC. Bacterial growth was measured by plating bacteria and counting viable colonies or by reading the absorbance of bacterial cultures. Bacterial membrane damage was detected by incorporation of N-phenyl-1-naphthylamine (NPN). Antimicrobial peptide (AMP) gene and protein expression by equine MSC were determined by RT-PCR and Western blot analysis, respectively. Blocking of AMP activity of MSC CM was achieved using AMP-specific antibodies. We found that equine MSC and MSC CM inhibit the growth of E. coli and S. aureus, and that MSC CM depolarizes the cell membranes of these bacteria. In addition, we found that equine MSC CM contains AMPs, and blocking these AMPs with antibodies reduces the effects of MSC CM on bacteria. Our results demonstrate that equine MSC inhibit bacterial growth and secrete factors that compromise the membrane integrity of bacteria commonly found in skin wounds. We also identified

Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

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Mary Cloud B Ammons

Full Text Available Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.

Cutaneous Scar Prevention and Management; Overview of current therapies

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Sultan Al-Shaqsi

2016-02-01

Full Text Available Cutaneous scarring is common after trauma, surgery and infection and occurs when normal skin tissue is replaced by fibroblastic tissue during the healing process. The pathophysiology of scar formation is not yet fully understood, although the degree of tension across the wound edges and the speed of cell growth are believed to play central roles. Prevention of scars is essential and can be achieved by attention to surgical techniques and the use of measures to reduce cell growth. Grading and classifying scars is important to determine available treatment strategies. This article presents an overview of the current therapies available for the prevention and treatment of scars. It is intended to be a practical guide for surgeons and other health professionals involved with and interested in scar management.

Collagen sheet dressings for cutaneous lesions of toxic epidermal necrolysis

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S Bhattacharya

2011-01-01

Full Text Available Toxic epidermal necrolysis (TEN is associated with a significant mortality of 30-50% and long-term sequelae. Treatment includes early admission to a burn unit, where management with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. We have treated the cutaneous lesions of seven patients of TEN with collagen sheet dressings and have found a significant reduction in morbidity. The sheets are a one-time dressing, easy to apply and they reduce fluid loss, prevent infection, reduce pain, avoid repeated dressings and gradually peal off as the underlying lesions heal.

Experimental closure of gunshot wounds by fibrin glue with antibiotics in pigs

OpenAIRE

Đenić Nebojša; Višnjić Milan; Dragović Saša; Bojanić Vladmila; Bojanić Zoran; Đurđević Dragan; Đinđić Boris; Kostov Miloš

2015-01-01

Background/Aim. Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, after the primary surgical management, were closed with delayed primary suture during the next four to seven days. This period coincides with the fibroblastic phase of wound healing. Fibrin glue is used as a local hemostatic and as a matrix for the local dosed release of antibiotics. Antibiotics addition to fibrin glue resulted in continuous diffusion into the surrounding n...

MFG-E8 Reprogramming of Macrophages Promotes Wound Healing by Increased bFGF Production and Fibroblast Functions.

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Laplante, Patrick; Brillant-Marquis, Frédéric; Brissette, Marie-Joëlle; Joannette-Pilon, Benjamin; Cayrol, Romain; Kokta, Victor; Cailhier, Jean-François

2017-09-01

Macrophages are essential for tissue repair. They have a crucial role in cutaneous wound healing, participating actively in the inflammation phase of the process. Unregulated macrophage activation may, however, represent a source of excessive inflammation, leading to abnormal wound healing and hypertrophic scars. Our research group has shown that apoptotic endothelial and epithelial cells secrete MFG-E8, which has the ability to reprogram macrophages from an M1 (proinflammatory) to an M2 (anti-inflammatory, pro-repair) phenotype. Hence, we tested whether modulation of macrophage reprogramming would promote tissue repair. Using a mouse model of wound healing, we showed that the presence and/or addition of MFG-E8 favors wound closure associated with an increase in CD206-positive cells and basic fibroblast growth factor production in healing tissues. More importantly, adoptive transfer of ex vivo MFG-E8-treated macrophages promoted wound closure. We also observed that MFG-E8-treated macrophages produced basic fibroblast growth factor that is responsible for fibroblast migration and proliferation. Taken together, our results strongly suggest that MFG-E8 plays a key role in macrophage reprogramming in tissue healing through induction of an anti-inflammatory M2 phenotype and basic fibroblast growth factor production, leading to fibroblast migration and wound closure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Epidermal growth factor receptor inhibition by anti-CD147 therapy in cutaneous squamous cell carcinoma.

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Frederick, John W; Sweeny, Larissa; Hartman, Yolanda; Zhou, Tong; Rosenthal, Eben L

2016-02-01

Advanced cutaneous squamous cell carcinoma (SCC) is an uncommon and aggressive malignancy. As a result, there is limited understanding of its biology and pathogenesis. CD147 and epidermal growth factor receptor (EGFR) have been identified as oncologically important targets, but their relationship remains undefined in cutaneous SCC. Multiple cutaneous SCC cell lines (Colo-16, SRB-1, and SRB-12), were treated in vitro with a range of chimeric anti-CD147 monoclonal antibody (mAb) (0, 50, 100, and 200 µg/mL) or transfected with a small interfering RNA against CD147 (SiCD147). Cell proliferation, migration (scratch wound healing assay), and protein expression was then assessed. In vivo, Colo-16 flank xenografts were treated anti-CD147 mAb (150 µg i.p. triweekly). After treatment with anti-CD147 (200 µg/mL), there was a significant decrease in proliferation for all cell lines relative to controls (p CD147 (200 µg/mL) resulted in decreased cell migration for all cell lines, with an average of 43% reduction in closure compared to controls (p CD147 antibody therapy and siRNA mediated reduction in CD147 expression were both found to decrease protein expression of EGFR, which correlated with a reduction in downstream total and phosphorylated protein kinase B (pAKT). Tumor growth in vivo was reduced for both the anti-CD147 treatment group and the SiCD147 group relative to controls. Inhibition and downregulation of CD147 in cutaneous SCC resulted in suppression of the malignant phenotype in vitro and in vivo, which may be mediated in part by an alteration in EGFR expression. As a result, CD147 may serve as a potential therapeutic target for advanced cutaneous SCC. © 2014 Wiley Periodicals, Inc.

Epidermal stem cells - role in normal, wounded and pathological psoriatic and cancer skin

DEFF Research Database (Denmark)

Kamstrup, M.; Faurschou, A.; Gniadecki, R.

2008-01-01

In this review we focus on epidermal stem cells in the normal regeneration of the skin as well as in wounded and psoriatic skin. Furthermore, we discuss current data supporting the idea of cancer stem cells in the pathogenesis of skin carcinoma and malignant melanoma. Epidermal stem cells present...... or transit amplifying cells constitute a primary pathogenetic factor in the epidermal hyperproliferation seen in psoriasis. In cutaneous malignancies mounting evidence supports a stem cell origin in skin carcinoma and malignant melanoma and a possible existence of cancer stem cells Udgivelsesdato: 2008/5...

Disseminated cutaneous sporotrichosis.

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Chang, Shurong; Hersh, Andrew M; Naughton, Greg; Mullins, Kevin; Fung, Maxwell A; Sharon, Victoria R

2013-11-15

The dimorphic fungus Sporothrix schenckii commonly causes localized cutaneous disease with lymphocutaneous distribution. However, disseminated sporotrichosis occurs predominantly in immunocompromised patients. We report a case of disseminated cutaneous sporotrichosis in a patient with newly diagnosed HIV with a CD4 count of 208. The patient presented with multiple cutaneous and subcutaneous nodules as well as fever and malaise. Tissue culture and skin biopsy confirmed the diagnosis of sporotrichosis. He was started on itraconazole 200mg twice a day with rapid resolution of fever along with cessation of the development of new lesions.

Polysaccharides of Aloe vera induce MMP-3 and TIMP-2 gene expression during the skin wound repair of rat.

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Tabandeh, Mohammad Reza; Oryan, Ahmad; Mohammadalipour, Adel

2014-04-01

Polysaccharides are the main macromolecules of Aloe vera gel but no data about their effect on extracellular matrix (ECM) elements are available. Here, mannose rich Aloe vera polysaccharides (AVP) with molecular weight between 50 and 250 kDa were isolated and characterized. Open cutaneous wounds on the back of 45 rats (control and treated) were daily treated with 25mg (n=15) and 50 mg (n=15) AVP for 30 days. The levels of MMP-3 and TIMP-2 gene expression were analyzed using real time PCR. The levels of n-acetyl glucosamine (NAGA), n-acetyl galactosamine (NAGLA) and collagen contents were also measured using standard biochemical methods. Faster wound closure was observed at day 15 post wounding in AVP treated animals in comparison with untreated group. At day 10 post wounding, AVP inhibited MMP-3 gene expression, while afterwards MMP-3 gene expression was upregulated. AVP enhanced TIMP-2 gene expression, collagen, NAGLA and NAGA synthesis in relation to untreated wounds. Our results suggest that AVP has positive effects on the regulation of ECM factor synthesis, which open up new perspectives for the wound repair activity of Aloe vera polysaccharide at molecular level. Copyright © 2014 Elsevier B.V. All rights reserved.

Randomized Clinical Trial of the Innovative Bilayered Wound Dressing Made of Silk and Gelatin: Safety and Efficacy Tests Using a Split-Thickness Skin Graft Model

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Hasatsri, Sukhontha; Angspatt, Apichai

2015-01-01

We developed the novel silk fibroin-based bilayered wound dressing for the treatment of partial thickness wounds. And it showed relevant characteristics and accelerated the healing of full-thickness wounds in a rat model. This study is the clinical evaluation of the bilayered wound dressing to confirm its safety and efficacy for the treatment of split-thickness skin donor sites. The safety test was performed using a patch model and no evidence of marked and severe cutaneous reactions was found. The efficacy test of the bilayered wound dressing was conducted on 23 patients with 30 split-thickness skin graft donor sites to evaluate healing time, pain score, skin barrier function, and systemic reaction in comparison to Bactigras. We found that the healing time of donor site wounds treated with the bilayered wound dressing (11 ± 6 days) was significantly faster than those treated with Bactigras (14 ± 6 days) (p = 10−6). The wound sites treated with the bilayered wound dressing showed significantly less pain and more rapid skin functional barrier recovery than those treated with Bactigras (p = 10−5). Therefore, these results confirmed the clinical safety and efficacy of the bilayered wound dressing for the treatment of split-thickness skin graft donor sites. PMID:26221170

Effects of local and whole body irradiation on the appearance of osteoblasts during wound healing in tooth extraction sockets in rats.

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Hosokawa, Yoichiro; Sakakura, Yasunori; Irie, Kazuharu; Kudo, Kohsei; Kashiwakura, Ikuo

2010-01-01

Irradiation before tooth extraction delays wound healing in the alveolar socket. This study examined the influences of local and whole body irradiation before tooth extraction on appearance of osteoblasts in the alveolar bone of rat maxillary first molars because bone formation is observed at the initial phase of wound healing. Several osteoblasts were generated 3 days after tooth extraction, and the number of cells increased day by day. Morphological studies showed there were little differences between local irradiation and non-irradiated controls. In contrast, the extraction wound in the whole body irradiation group showed delayed healing, and there was poor granulation tissue and very few osteoblasts at the bottom of the socket. An ultrastructural study showed that the osteoblasts in the extraction socket of whole body irradiation rats were smaller, and had poorly developed organelles. Injection of bone marrow cells to whole body-irradiated animals immediately after tooth extraction partially restored the number of osteoblasts. New periosteal bone formations outside of sockets showed little delay in the whole body irradiation group. These findings suggest that bone formation in the wound healing of extraction socket requires bone marrow cells from hematopoietic organs such as the bone marrow as well as local sources around the alveolar socket, during the initial phase of wound healing.

Effects of local and whole body irradiation on the appearance of osteoblasts during wound healing in tooth extraction sockets in rats

International Nuclear Information System (INIS)

Hosokawa, Yoichiro; Kudo, Kohsei; Kashiwakura, Ikuo; Sakakura, Yasunori; Irie, Kazuharu

2010-01-01

Irradiation before tooth extraction delays wound healing in the alveolar socket. This study examined the influences of local and whole body irradiation before tooth extraction on appearance of osteoblasts in the alveolar bone of rat maxillary first molars because bone formation is observed at the initial phase of wound healing. Several osteoblasts were generated 3 days after tooth extraction, and the number of cells increased day by day. Morphological studies showed there were little differences between local irradiation and non-irradiated controls. In contrast, the extraction wound in the whole body irradiation group showed delayed healing, and there was poor granulation tissue and very few osteoblasts at the bottom of the socket. An ultrastructural study showed that the osteoblasts in the extraction socket of whole body irradiation rats were smaller, and had poorly developed organelles. Injection of bone marrow cells to whole body-irradiated animals immediately after tooth extraction partially restored the number of osteoblasts. New periosteal bone formations outside of sockets showed little delay in the whole body irradiation group. These findings suggest that bone formation in the wound healing of extraction socket requires bone marrow cells from hematopoietic organs such as the bone marrow as well as local sources around the alveolar socket, during the initial phase of wound healing. (author)

Healing Potentials of Oral Moringa Oleifera Leaves Extract and Tetracycline on Methicillin Resistant Staphylococcus Aureus Infected Wounds of Wistar rats.

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Eyarefe, Oghenemega D; Idowu, Aderayo; Afolabi, Jeremiah M

2015-12-20

The effects of oral dose of aqueous extract of Moringa oleifera and tetracycline antibiotics on cutaneous wounds infected with Staphylococcus aureus were studied in eighteen adult wistar rats (159±31.5g) randomized into three groups: Group A, n = 6, Moringa oleifera-(300 mg/kg). Group B, n = 6, tetracycline (9.4 mg/kg) and Group C, n = 6, Sterile water (control). Six millimetres diameter nape wound, created on each rat under 2% xylazine (5 mg/kg) and 5% ketamine (35 mg/kg), was contaminated with Staphylococcus aureus (108 Colony Forming Unit (CFU). Following infection, treatment was commenced with daily oral dose of test preparations and the wounds were evaluated every other day i.e., day 3, 5, 7, 9, 11, 13 and 15 for wetness (wound exudation), wound edge oedema, hyperaemia, granulation tissues and contraction (diameter). Severe wound exudation existed in all the groups between days 0-3 (p = 1.00). A significantly less wound exudation was observed at days 3-5 (p = 0.000) and 5-9 (p = 0.003) (ControlMoringa). Wound edge oedema was significantly less on days 5-9 (p = 0.000) and 9-15 (p = 0.001) (ControlMoringaMoringa Moringa> Tetracycline). Differences in wound diameter was not significant except at days 5-9 (p = 0.013) (Control> Moringa >Tetracycline). Oral doses of Moringa oleifera extract (300mg/kg) and tetracycline (9.4mg/kg) are not effective as antimicrobial or immune-boosting agents to enhance healing of wounds infected with Staphylococcus aureus and hence not recommended for rapid clearance of Staphylococcus aureus infected wounds.

Stem Cells in Wound Healing: The Future of Regenerative Medicine? A Mini-Review.

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Duscher, Dominik; Barrera, Janos; Wong, Victor W; Maan, Zeshaan N; Whittam, Alexander J; Januszyk, Michael; Gurtner, Geoffrey C

2016-01-01

The increased risk of disease and decreased capacity to respond to tissue insult in the setting of aging results from complex changes in homeostatic mechanisms, including the regulation of oxidative stress and cellular heterogeneity. In aged skin, the healing capacity is markedly diminished resulting in a high risk for chronic wounds. Stem cell-based therapies have the potential to enhance cutaneous regeneration, largely through trophic and paracrine activity. Candidate cell populations for therapeutic application include adult mesenchymal stem cells, embryonic stem cells and induced pluripotent stem cells. Autologous cell-based approaches are ideal to minimize immune rejection but may be limited by the declining cellular function associated with aging. One strategy to overcome age-related impairments in various stem cell populations is to identify and enrich with functionally superior stem cell subsets via single cell transcriptomics. Another approach is to optimize cell delivery to the harsh environment of aged wounds via scaffold-based cell applications to enhance engraftment and paracrine activity of therapeutic stem cells. In this review, we shed light on challenges and recent advances surrounding stem cell therapies for wound healing and discuss limitations for their clinical adoption. © 2015 S. Karger AG, Basel.

Surgical sutures filled with adipose-derived stem cells promote wound healing.

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Ann Katharin Reckhenrich

Full Text Available Delayed wound healing and scar formation are among the most frequent complications after surgical interventions. Although biodegradable surgical sutures present an excellent drug delivery opportunity, their primary function is tissue fixation. Mesenchymal stem cells (MSC act as trophic mediators and are successful in activating biomaterials. Here biodegradable sutures were filled with adipose-derived mesenchymal stem cells (ASC to provide a pro-regenerative environment at the injured site. Results showed that after filling, ASCs attach to the suture material, distribute equally throughout the filaments, and remain viable in the suture. Among a broad panel of cytokines, cell-filled sutures constantly release vascular endothelial growth factor to supernatants. Such conditioned media was evaluated in an in vitro wound healing assay and showed a significant decrease in the open wound area compared to controls. After suturing in an ex vivo wound model, cells remained in the suture and maintained their metabolic activity. Furthermore, cell-filled sutures can be cryopreserved without losing their viability. This study presents an innovative approach to equip surgical sutures with pro-regenerative features and allows the treatment and fixation of wounds in one step, therefore representing a promising tool to promote wound healing after injury.

PREVENTION OF CUTANEOUS SIDE EFFECTS OF TOPICAL TRETINOIN: USE OF ORAL VITAMINE E

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G FAGHIHI

2001-03-01

Full Text Available Introduction: Acne vulgaris is an inflammatory disease of pilosebaceous folicles. Tretinoin is used as one of the topical treatments for acne vulgaris. It has different cutaneous side effects such as erythema, scaling, irritation and photosensitivity. The aim of this study was to evaluate the efficacy of oral Vitamine E in preventing the cutaneous side effects of topical tretinoin in acne patients.
Methods: A clinical trial was performed in AI-Zahra Hospital in Isfahan for six months in 2000. 80 patients with mild to moderate facial acne were randomized into 2 groups. Group 1 (controls received topical solution of tretinoin 0.05 percent nightly and group 2 (cases received daily oral 100mg of Vit. E in addition. All patients were followed at 1, 4 and 6 weeks after initiation of treatment. Children under 12 years old, pregnant or lactating women were excluded.
Results: At the end of one week, no cutaneous side effects were observed in 25 percent (10 of group 1 and 15 percent (6 of group 2 (P > 0.05. At the end of 4 weeks, 25 percent (10 of group 1 and 60 percent (24 of group 2 were without any cutaneous complications, while at the end of 6 weeks, 35 percent (14 of group 1 in comparison to 75 percent (30 of group 2 were free of any cutaneous side effects (P < 0.05. The most common side effect in both groups was exfoliation.
Discussion: Daily oral 100 mg of Vit. E has been effective in preventing cutaneous complications of topical tretinoin in acne management, but there is a delay of one week in its onset of action. Meanwhile, Vitamine E is a safe modality with no undesirable effects in acne patients.

Deep sternal wound infection after coronary artery bypass surgery: management and risk factor analysis for mortality.

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Yumun, Gunduz; Erdolu, Burak; Toktas, Faruk; Eris, Cuneyt; Ay, Derih; Turk, Tamer; As, Ahmet Kagan

2014-08-01

Deep sternal wound infection is a life-threatening complication after cardiac surgery. The aim of this study was to investigate the factors leading to mortality, and to explore wound management techniques on deep sternal wound infection after coronary artery bypass surgery. Between 2008 and 2013, 58 patients with deep sternal wound infection were analyzed. Risk factors for mortality and morbidity including age, gender, body mass index, smoking status, chronic renal failure, hypertension, diabetes, and treatment choice were investigated. In this study, 19 patients (32.7%) were treated by primary surgical closure (PSC), and 39 patients (67.3%) were treated by delayed surgical closure following a vacuum-assisted closure system (VAC). Preoperative patient characteristics were similar between the groups. Fourteen patients (24.1%) died in the postoperative first month. The mortality rate and mean duration of hospitalization in the PSC group was higher than in the VAC group (P = .026, P = .034). Significant risk factors for mortality were additional operation, diabetes mellitus, and a high level of EuroSCORE. Delayed surgical closure following VAC therapy may be associated with shorter hospitalization and lower mortality in patients with deep sternal wound infection. Additional operation, diabetes mellitus, and a high level of EuroSCORE were associated with mortality.

Vacuum-assisted closure downgrades reconstructive demands in high-risk patients with severe lower extremity injuries.

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Kakagia, D; Karadimas, E; Drosos, G; Ververidis, A; Kazakos, D; Lazarides, M; Verettas, D

2009-01-01

Primary soft tissue reconstruction in complex leg injuries is mandatory in order to protect exposed tissues; however, it may be precluded by the patient's clinical status or by local wound conditions. This retrospective study aims to evaluate the use of negative pressure as an adjunct to delayed soft tissue reconstruction in patients with complex lower limb trauma. Forty-two patients with 49 complex lower limb injuries were treated with Vacuum assisted closure (VAC) 48 hours after bone fixation, vascular repair and surgical debridement. Wound swab cultures were obtained before and after every VAC application. Duration of therapy, wound flora, final reconstructive technique required, outcome and follow-up period were retrieved from medical records. Twenty-four male and eighteen female patients were recruited, with a mean age of 47 years. All were treated with VAC therapy for 15-42 days. Reconstruction was delayed due to the patients' critical condition, advanced age, medical co-morbidities, heavily exuding wounds and questionable viability of soft tissues. Patients were followed up for 90-895 days. Two wounds healed spontaneously, 6 were managed with delayed direct suture, 31 with split thickness skin grafts and 9 required local cutaneous, fasciocutaneous or muscular flaps. One patient died due to fat embolism. Wound bacterial flora progressively decreased in all but one patient. Scar formation was aesthetically acceptable by the patients while function depended on the initial injury. Negative pressure is a safe and effective adjunct to delayed soft tissue reconstruction in high-risk patients with severe lower extremity injuries, minimizing reconstructive requirements and therefore postoperative morbidity.

A Delay Line for Compression of Electromagnetic Pulses

International Nuclear Information System (INIS)

Pchelnikov, Yuriy N.; Nyce, David S.

2003-01-01

A novel method to obtain an electromagnetic signal delay is described. It is shown that the positive magnetic and electric coupling between impedance conductors produces an increase in the time delay. It is also shown that the increase in delay time is obtained without additional attenuation. This allows a reduction in electromagnetic losses, by a factor of several times, for a delay time. An approximate analysis of electromagnetic delay lines based on coupled impedance conductors with 'spiral' and 'meander' patterns allowed obtaining very simple expressions for the wave deceleration factor, wave impedance, and attenuation factor. The results of the analysis are confirmed by the results of measurements. It is shown that a delay line based on counter-wound radial spirals can be successfully used for compression of electromagnetic pulses. Although the offered delay line was designed to operate with a relatively small signal, the analysis of the 'coupling effect', taking place in this delay line, might be useful in devices for compression of high-power microwave pulses

Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

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Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

2017-05-01

Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

Impact of an angiotensin analogue in treating thermal and combined radiation injuries

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Jadhav, Sachin Suresh

Background: In recent years there has been a growing concern regarding the use of nuclear weapons by terrorists. Such incidents in the past have shown that radiation exposure is often accompanied by other forms of trauma such as burns, wounds or infection; leading to increased mortality rates among the affected individuals. This increased risk with combined radiation injury has been attributed to the delayed wound healing observed in this injury. The Renin-Angiotensin System (RAS) has emerged as a critical regulator of wound healing. Angiotensin II (A-II) and Angiotensin (1-7) [A(1-7)] have been shown to accelerate the rate of wound healing in different animal models of cutaneous injury. Nor-Leu3-Angiotensin (1-7) [Nor-Leu3-A (1-7)], an analogue of A(1-7), is more efficient than both A-II and A(1-7) in its ability to improve wound healing and is currently in phase III clinical trials for the treatment of diabetic foot ulcers. Aims: The three main goals of this study were to; 1) Develop a combined radiation and burn injury (CRBI) model and a radiation-induced cutaneous injury model to study the pathophysiological effects of these injuries on dermal wound healing; 2) To treat thermal and CRBI injuries using Nor-Leu 3-A (1-7) and decipher the mechanism of action of this peptide and 3) Develop an in-vitro model of CRBI using dermal cells in order to study the effect of CRBI on individual cell types involved in wound healing. Results: CRBI results in delayed and exacerbated apoptosis, necrosis and inflammation in injured skin as compared to thermal injury by itself. Radiation-induced cutaneous injury shows a radiation-dose dependent increase in inflammation as well as a chronic inflammatory response in the higher radiation exposure groups. Nor-Leu3-A (1-7) can mitigate thermal and CRBI injuries by reducing inflammation, oxidative stress and DNA damage while increasing the rate of proliferation of dermal stem cells and re-epithelialization of injured skin. The in

Topical application of omega-3-, omega-6-, and omega-9-rich oil emulsions for cutaneous wound healing in rats.

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Ishak, Wan Maznah Wan; Katas, Haliza; Yuen, Ng Pei; Abdullah, Maizaton Atmadini; Zulfakar, Mohd Hanif

2018-04-17

Wound healing is a physiological event that generates reconstitution and restoration of granulation tissue that ends with scar formation. As omega fatty acids are part of membrane phospholipids and participate in the inflammatory response, we investigated the effects of omega-3, omega-6, and omega-9 fatty acids in the form of oils on wound healing. Linseed (LO), evening primrose (EPO), and olive oils (OO) rich in omega-3, omega-6, and omega-9 fatty acids were formulated into emulsions and were topically applied on rats with excision wounds. All omega-3-, omega-6-, and omega-9-rich oil formulations were found to accelerate wound closure compared to untreated, with significant improvement (p < 0.05) being observed at day 14. EPO induced early deposition of collagen as evaluated by Masson trichrome staining that correlated well with the hydroxyproline content assay, with the highest level at days 3 and 7. Vascular endothelial growth factor (VEGF) showed greater amount of new microvasculature formed in the EPO-treated group, while moderate improvement occurs in the LO and OO groups. EPO increased both the expression of proinflammatory cytokines and growth factors in the early stage of healing and declined at the later stage of healing. LO modulates the proinflammatory cytokines and chemokine but did not affect the growth factors. In contrast, OO induced the expression of growth factors rather than proinflammatory cytokines. These data suggest that LO, EPO, and OO emulsions promote wound healing but they accomplish this by different mechanisms.

Effects of Pistacia atlantica (subsp. Mutica oil extracts on antioxidant activities during experimentally induced cutaneous wound healing in rats

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Ahmad Reza Hamidi

2015-01-01

Full Text Available The fruits of Pistacia atlantica (subsp. mutica have been used traditionally for the treatment of peptic ulcer, as a mouth freshener and have recently been introduced as a source of antioxidant vegetable oils. The aim of this study was to investigate the antioxidant activity of the gel forms, from P. atlantica (subsp. mutica oil extraction on enzymatic antioxidants in experimental wound created in rat. A square-shaped skin defect (2×2 cm was created aseptically by surgical excision at the first thoracic vertebrae. Then animals were randomly allocated in four groups (I, untreated controls; II, topically treated base gel; III, topically treated 5% gel; IV, topically treated 10% gel. Blood sampling was accomplished at 3, 7, 10, 14 and 21 days post-injury. Samples were collected for measuring antioxidant enzymes activities (superoxide dismutase, catalase and glutathione peroxidase activity in red cells and lipid peroxidation (plasma malondialdehyde. The data analysis generally evidenced that the activities of the main antioxidant enzymes began to decrease significantly at 7 days after the wound was created in control and base gel groups. This remarkable decline became more evident in the period between 10 to 21 days post injury but increased progressively in P. atlantica (subsp. mutica treatment groups, especially in gel 10% treatment group during wound healing. The results of this study suggest that excision of the wound leads to oxidative stress and topical administration of P. atlantica (subsp. mutica gels causes remarkable changes in antioxidant parameter during wound closure (especially gel 10% via pro-oxidative, and antioxidant activity can improve oxidative stress.

Animal models of chronic wound care: the application of biofilms in clinical research

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Trøstrup H

2016-11-01

Full Text Available Hannah Trøstrup,1 Kim Thomsen,1 Henrik Calum,2 Niels Høiby,1,3 Claus Moser1 1Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, 2Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, 3Institute for Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark Abstract: Chronic wounds are a substantial clinical problem affecting millions of people worldwide. Pathophysiologically, chronic wounds are stuck in the inflammatory state of healing. The role of bacterial biofilms in suppression and perturbation of host response could be an explanation for this observation. An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure has to be taken into consideration as underlying pathophysiological mechanisms and comorbidities display tremendous variation in humans. Confounders such as infection, smoking, chronological age, sex, medication, metabolic disturbances, and renal impairment add to the difficulty in gaining systematic and comparable studies on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s, and time of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although discrepancies between human and animal wound repair are obvious. The use of animal models should

Muscle wound healing in rainbow trout (Oncorhynchus mykiss).

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Schmidt, J G; Andersen, E W; Ersbøll, B K; Nielsen, M E

2016-01-01

We followed the progression of healing of deep excisional biopsy punch wounds over the course of 365 days in rainbow trout (Oncorhynchus mykiss) by monitoring visual wound healing and gene expression in the healing muscle at regular intervals (1, 3, 7, 14, 38 and 100 days post-wounding). In addition, we performed muscle texture analysis one year after wound infliction. The selected genes have all previously been investigated in relation to vertebrate wound healing, but only few specifically in fish. The selected genes were interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β1 and -β3, matrix metalloproteinase (MMP) -9 and -13, inducible nitric oxide synthase (iNOS), fibronectin (FN), tenascin-C (TN-C), prolyl 4-hydroxylase α1-chain (P4Hα1), lysyl oxidase (LOX), collagen type I α1-chain (ColIα1), CD41 and CD163. Wound healing progressed slowly in the presented study, which is at least partially due to the low temperature of about 8.5 °C during the first 100 days. The inflammation phase lasted more than 14 days, and the genes relating to production and remodeling of new extracellular matrix (ECM) exhibited a delayed but prolonged upregulation starting 1-2 weeks post-wounding and lasting until at least 100 days post-wounding. The gene expression patterns and histology reveal limited capacity for muscle regeneration in rainbow trout, and muscle texture analyses one year after wound infliction confirm that wounds heal with fibrosis. At 100 dpw epidermis had fully regenerated, and dermis partially regenerated. Scales had not regenerated even after one year. CD163 is a marker of "wound healing"-type M2c macrophages in mammals. M2 macrophage markers are as yet poorly described in fish. The pattern of CD163 expression in the present study is consistent with the expected timing of presence of M2c macrophages in the wound. CD163 may thus potentially prove a valuable marker of M2 macrophages - or a subset hereof - in fish. We subjected a group of fish to

Wound healing during hibernation by black bears (Ursus americanus) in the wild: elicitation of reduced scar formation.

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Iaizzo, Paul A; Laske, Timothy G; Harlow, Henry J; McClay, Carolyn B; Garshelis, David L

2012-03-01

Even mildly hypothermic body or limb temperatures can retard healing processes in mammals. Despite this, we observed that hibernating American black bears (Ursus americanus Pallas, 1780) elicit profound abilities in mounting inflammatory responses to infection and/or foreign bodies. In addition, they resolve injuries during hibernation while maintaining mildly hypothermic states (30-35 °C) and without eating, drinking, urinating or defecating. We describe experimental studies on free-ranging bears that document their abilities to completely resolve cutaneous cuts and punctures incurred during or prior to hibernation. We induced small, full-thickness cutaneous wounds (biopsies or incisions) during early denning, and re-biopsied sites 2-3 months later (near the end of denning). Routine histological methods were used to characterize these skin samples. All biopsied sites with respect to secondary intention (open circular biopsies) and primary intention (sutured sites) healed, with evidence of initial eschar (scab) formation, completeness of healed epidermis and dermal layers, dyskeratosis (inclusion cysts), and abilities to produce hair follicles. These healing abilities of hibernating black bears are a clear survival advantage to animals injured before or during denning. Bears are known to have elevated levels of hibernation induction trigger (delta-opioid receptor agonist) and ursodeoxycholic acid (major bile acid within plasma, mostly conjugated with taurine) during hibernation, which may relate to these wound-healing abilities. Further research as to the underlying mechanisms of wound healing during hibernation could have applications in human medicine. Unique approaches may be found to improve healing for malnourished, hypothermic, diabetic and elderly patients or to reduce scarring associated with burns and traumatic injuries. © 2012 ISZS, Blackwell Publishing and IOZ/CAS.

Enhanced electroscalpel incisional wound healing potential of honey in wistar rats

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David O. Eyarefe

2017-12-01

Full Text Available Electrosurgery reduces surgical bleeding, and delayed wound healing. This study evaluated comparative incisional wound healing potential of honey in wound created with electroscalpel and cold scalpel. The study used twelve (12 adult male albino rats (130 ± 20 g, randomly grouped into Electro-cautery (n = 6 and Cold scalpel (n = 6. Each rat had three full thickness (6 mm diameter skin wounds (a, b and c created on its dorsum with either Electroscalpel (ES or Cold blade scalpel (CS, and treated topically with Silver sulphadiazine (SSD, wound a, untreated (control, wound b and Bee honey (H, wound c. The wounds were evaluated for gross (exudation, edema, hyperemia, contraction, histologic (granulation, angiogenesis, fibroplasia, epithelialization and immunologic healing indices using standard techniques. Data were analyzed with Chi-square, Two-way Analysis of Variance (ANOVA and Duncan Multiple Range tests (DMRT at α = 0.05. Wound hyperemia and edge edema were prominent in the ES group from day 4 to 6 (P = .000. Percentage wound contraction was higher in the CS than ES group from days 5 to 7 (P = .006 and in the CS treated with honey than ES treated with honey from days 7 to 14 (P = .000. Granulation tissue reduced in ES group treated with SSD than in honey and control wounds. Fibroelastic tissue increased in SSD and honey treated wounds of ES group, and higher in honey treated wounds of CS group (P < .05. Fibroplasia was sustained in honey and SSD treated wounds than control. Honey can be applied to electroscalpel surgical wound to facilitate rapid healing during surgical management of tumours having vascular network. Keywords: Incisional methods, Honey, Silver sulphadiazide, Wound management

Brown seaweed Padina gymnospora is a prominent natural wound-care product

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Alegna P. Baliano

Full Text Available ABSTRACT Seaweeds are related to anti-inflammatory, anti-bacterial and anti-noceptive effects. This work aimed to verify the potential of seaweed Padina gymnospora (Kützing Sonder 1871 to improve wound healing in vitro. P. gymnospora was collected at a bethonic area in Espirito Santo. Methanolic extract of P. gymnospora was obtained by percolation. To determine cytotoxicity, colorimetric MTT tests were performed against normal fibroblasts (L929, macrophages (RAW 264.7 and human ovarian carcinoma (OVCAR-3 cell lines using concentration range of 12–110 µg ml-1. To evaluate in vitro wound healing, monolayer of fibroblasts L929 was seeded and artificial wounded. Cell proliferation was blocked by 5 µg ml-1 Mytomycin C. Nitric oxide inhibition was quantified with Raw 264.7 by Griess reaction. Minimal inhibitory concentration (MIC against Staphylococcus aureus was determined. Eletrospray ionization with Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR MS was applied to detail composition of P. gymnospora methanolic extract. No cytotoxic effect in all cell lines was detected until the maximum concentration of 110 µg ml-1. P. gymnospora promoted significantly migration at the concentration of 25 µg ml-1 (p < 0.05. A prominent inhibition of nitric oxide formation was achieved in a concentration of 20 µg ml-1 of methanolic extract of P. gymnospora (62.06 ± 1.20%. Antibacterial activity against S. aureus could be demonstrated with MIC of 500 µg ml-1. ESI-FT-ICR MS analysis indicated eleven molecules between then, linolenic, oleic and linoleic acid. P. gymnospora favored wound repair in vitro what could be related to its fatty acid composition. In addition, its antimicrobial effect, and NO inhibition activity contribute for a new approach of P. gymnospora as a promise natural product for treatment of cutaneous wound.

The genomics of oral cancer and wound healing.

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Aswini, Y B

2009-01-01

Oral cancer is the most common malignancy in India, where it is epidemiologically linked to the chewing of betel quid and other carcinogens. But various point mutations were detectable in the p53 and p15 genes. Hence, this review was conducted with the aim to find out genetic risks as well as markers for oral cancers and wound healing. Tobacco-related cancers are associated with polymorphisms of the CYP1A1 and GSTM1 genes in terms of genotype frequencies and cigarette smoking dose. Expression of E6/E7 were also found in tumors, most of which were derived from the oropharynx. Presence of homozygous arginine at codon 72 renders p53 about seven times more susceptible to E6-mediated proteolytic degradation. Erythropoietin, vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), and PDGF has been implicated as one of the principal mitogens involved in cutaneous wound healing. Activation of NF-kB is associated with enhanced cell survival. Human papilloma virus status is a significantly favorable prognostic factor in tonsilar cancer and may be used as a marker in order to optimize the treatment of patients with this type of cancer.

The genomics of oral cancer and wound healing

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Aswini Y

2009-03-01

Full Text Available Oral cancer is the most common malignancy in India, where it is epidemiologically linked to the chewing of betel quid and other carcinogens. But various point mutations were detectable in the p53 and p15 genes. Hence, this review was conducted with the aim to find out genetic risks as well as markers for oral cancers and wound healing. Tobacco-related cancers are associated with polymorphisms of the CYP1A1 and GSTM1 genes in terms of genotype frequencies and cigarette smoking dose. Expression of E6/E7 were also found in tumors, most of which were derived from the oropharynx. Presence of homozygous arginine at codon 72 renders p53 about seven times more susceptible to E6-mediated proteolytic degradation. Erythropoietin, vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF, and PDGF has been implicated as one of the principal mitogens involved in cutaneous wound healing. Activation of NF-kB is associated with enhanced cell survival. Human papilloma virus status is a significantly favorable prognostic factor in tonsilar cancer and may be used as a marker in order to optimize the treatment of patients with this type of cancer.

Candida and Porphyromonas gingivalis: the effect on wound closure in vitro

NARCIS (Netherlands)

Haverman, Thijs M.; Laheij, Alexa M. G. A.; de Soet, Johannes J.; de Lange, Jan; Rozema, Frederik R.

2017-01-01

Microorganisms play a role in oral mucositis after cancer therapy. The current study explored the hypothesis that Candida spp. alone and together with Porphyromonas gingivalis cause delayed healing of oral ulcerations due to the inhibition of wound closure. An in vitro scratch assay model was used

Temporary Rectal Stenting for Management of Severe Perineal Wounds in Two Dogs.

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Skinner, Owen T; Cuddy, Laura C; Coisman, James G; Covey, Jennifer L; Ellison, Gary W

Perineal wounds in dogs present a challenge due to limited local availability of skin for closure and constant exposure to fecal contaminants. This report describes temporary rectal stenting in two dogs following severe perineal wounds. Dog 1 presented with a 4 × 4 cm full-thickness perineal slough secondary to multiple rectal perforations. A 12 mm internal diameter endotracheal tube was placed per-rectum as a temporary stent to minimize fecal contamination. The stent was removed 18 days after placement, and the perineal wound had healed at 32 days post-stent placement, when a minor rectal stricture associated with mild, intermittent tenesmus was detected. Long-term outcome was deemed good. Dog 2 presented with multiple necrotic wounds with myiasis, circumferentially surrounding the anus and extending along the tail. A 14 mm internal diameter endotracheal tube was placed per-rectum. The perineal and tail wounds were managed with surgical debridement and wet-to-dry and honey dressings prior to caudectomy and negative pressure wound therapy (NPWT). Delayed secondary wound closure and stent removal were performed on day six without complication. Long-term outcome was deemed excellent. Temporary rectal stenting may be a useful technique for fecal diversion to facilitate resolution of complex perineal injuries, including rectal perforation.

Effect of animal products and extracts on wound healing promotion in topical applications: a review.

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Napavichayanun, Supamas; Aramwit, Pornanong

2017-06-01

Wound healing is a natural process of body reaction to repair itself after injury. Nonetheless, many internal and external factors such as aging, comorbidity, stress, smoking, alcohol drinking, infections, malnutrition, or wound environment significantly affect the quality and speed of wound healing. The unsuitable conditions may delay wound healing process and cause chronic wound or scar formation. Therefore, many researches have attempted to search for agents that can accelerate wound healing with safety and biocompatibility to human body. Widely studied wound healing agents are those derived from either natural sources including plants and animals or chemical synthesis. The natural products seem to be safer and more biocompatible to human tissue. This review paper demonstrated various kinds of the animal-derived products including chitosan, collagen, honey, anabolic steroids, silk sericin, peptides, and proteoglycan in term of mechanisms of action, advantages, and disadvantages when applied as wound healing accelerator. The benefits of these animal-derived products are wound healing promotion, anti-inflammatory, antimicrobial activity, moisturizing effect, biocompatibility, and safety. However, the drawbacks such as allergy, low stability, batch-to-batch variability, and high extraction and purification costs could not be avoided in some products.

Exercise accelerates wound healing among healthy older adults: a preliminary investigation.

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Emery, Charles F; Kiecolt-Glaser, Janice K; Glaser, Ronald; Malarkey, William B; Frid, David J

2005-11-01

Older adults are likely to experience delayed rates of wound healing, impaired neuroendocrine responsiveness, and increased daily stress. Exercise activity has been shown to have a positive effect on physiological functioning and psychological functioning among older adults. This study evaluated the effect of a 3-month exercise program on wound healing, neuroendocrine function, and perceived stress among healthy older adults. Twenty-eight healthy older adults (mean age 61.0 +/- 5.5 years) were assigned randomly to an exercise activity group (n = 13) or to a nonexercise control group (n = 15). One month following baseline randomization, after exercise participants had acclimated to the exercise routine, all participants underwent an experimental wound procedure. Wounds were measured 3 times per week until healed to calculate rate of wound healing. All participants completed assessments of exercise endurance, salivary cortisol, and self-reported stress prior to randomization and at the conclusion of the intervention. Exercise participants achieved significant improvements in cardiorespiratory fitness, as reflected by increased oxygen consumption (VO(2)max) and exercise duration. Wound healing occurred at a significantly faster rate in the exercise group [mean = 29.2 (9.0) days] than in the nonexercise group [38.9 (7.4) days; p =.012]. Exercise participants also experienced increased cortisol secretion during stress testing following the intervention. Group differences in wound healing and neuroendocrine responsiveness were found despite low levels of self-reported stress. A relatively short-term exercise intervention is associated with enhanced rates of wound healing among healthy older adults. Thus, exercise activity may be an important component of health care to promote wound healing.

Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds

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Yssel Mendoza Marí

2016-01-01

Full Text Available In addition to its cytoprotective effects, growth hormone-releasing peptide 6 (GHRP-6 proved to reduce liver fibrotic induration. CD36 as one of the GHRP-6 receptors appears abundantly represented in cutaneous wounds granulation tissue. The healing response in a scenario of CD36 agonistic stimulation had not been previously investigated. Excisional full-thickness wounds (6 mmØ were created in the dorsum of Wistar rats and topically treated twice a day for 5 days. The universal model of rabbit’s ears hypertrophic scars was implemented and the animals were treated daily for 30 days. Treatments for both species were based on a CMC jelly composition containing GHRP-6 400 μg/mL. Wounds response characterization included closure dynamic, RT-PCR transcriptional profile, histology, and histomorphometric procedures. The rats experiment indicated that GHRP-6 pharmacodynamics involves attenuation of immunoinflammatory mediators, their effector cells, and the reduction of the expression of fibrotic cytokines. Importantly, in the hypertrophic scars rabbit’s model, GHRP-6 intervention dramatically reduced the onset of exuberant scars by activating PPARγ and reducing the expression of fibrogenic cytokines. GHRP-6 showed no effect on the reversion of consolidated lesions. This evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic.

MODULATION OF THE INFLAMMATORY CYTOKINES AND CYTOPROTECTIVE ENZYME BY BILIRUBIN TREATMENT TO ENHANCE CUTANEOUS WOUND HEALING IN RATS

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Raju Prasad

2017-06-01

Full Text Available Inflammation is the main process of wound healing where expression of certain cytokines likes Interleukin-10 (IL-10 and Tumour necrosis factor ∝ (TNF ∝ plays an important role. In view of the antioxidant potential of bilirubin, the present study was aimed to evaluate time-dependent (day 3, 7, 14 wound healing effects of bilirubin ointment (0.3% in excisional wound model in rats. Thirty-six acclimatized healthy male Wistar rats (120-150g were divided into control and treated groups containing 18 rats each. Each group was further sub- divided into three sub-groups (day 3, 7 and 14 days, n= 6. The ointment base (soft paraffin 90%, lanolin 5% and hard paraffin 5% and bilirubin ointment (0.3% were applied topically once daily for 14 days in control and treated group respectively. The wound area was determined on days 3, 7, and 14. The mRNA expression of TNF ∝ gene and IL-10 gene were determined on days 3, 7 and 14 by Real Time PCR and their protein levels by ELISA method. The protein expression of cyto-protective enzyme HO-1 (Heme oxygenage-1 and growth factor VEGF (Vascular growth factor was determined by western blotting method. The mRNA expression and protein level of TNF ∝ was significantly reduced and IL-10 was significantly increased whereas the expression of HO-1 enzyme and VEGF was significantly increased in treated group on days 3, 7 and 14. It may be concluded that the bilirubin has pro-healing potential.

Epidemiological Pattern of Cutaneous Leishmaniasis in the Province of Fars, Iran (Since 2010-2014

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Ali Fattahi Bafghi

2016-10-01

Full Text Available Abstract Introduction: Cutaneous Leishmaniasis is considered as an important health problem in Iran. This disease begins as small papules and then they gradually grow and turn into wounds. Since the epidemiological study of this problem is effective in preventing and controlling it, the current research was conducted on epidemiological pattern of Cutaneous Leishmaniasis in the province of Fars, Iran (2010-2014 Materials and Methods: This cross-sectional study was conducted on the registered information (20601 patients and documents of the patients having problem in Fars province remedial and health care centers over the last 5 years. First, the registered demographic and epidemiological data of patients were extracted and then analyzed through by using SPSS software. Results: A total of 20601 patients including 10607 males (51% and 9994 females (49% participated this study. Patients were in the age range of 20-29 years old and minority of them was 5-9 years old. Most lesions were on the hand and leg of the patients. It was also found that there was a significant relationship between age groups and types of Leishmaniasis (P<0.05 as well as gender and type of Cutaneous Leishmaniasis (P<0.05. Conclusion: According to this is investigation, there was an ascending trend in disease frequency which was based on the descending process. This indicates promotion of educational- hygiene status as well as observance of personal hygiene principals.

Intraoperative boost radiation effects on early wound complications in breast cancer patients undergoing breast-conserving surgery

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Gülçelik, Mehmet Ali; Doğan, Lütfi; Karaman, Niyazi; Turan, Müjdat; Kahraman, Yavuz Selim; Akgül, Gökhan Giray; Özaslan, Cihangir

2017-08-23

Background/aim: Intraoperative radiation therapy (IORT) may pose a risk for wound complications. All technical aspects of IORT regarding early wound complications were evaluated. Materials and methods: Ninety-three consecutive patients operated on with the same surgical technique and given (study group) or not given (control group) IORT were included. Wound complications were evaluated in two groups. Results: Forty-three patients were treated with boost dose IORT and 50 patients were treated with breast-conserving surgery without IORT. When both groups were compared in terms of early postoperative complications, there were 11 (25.5%) patients with seroma in the IORT group and 3 patients (6%) in the control group (P = 0.04). While 9 (21%) patients were seen to have surgical site infection (SSI) in the IORT group, there was 1 (2%) SSI in the control group (P = 0.005). There were 15 (35%) patients with delayed wound healing in the IORT group and 4 patients (8%) in the control group (P = 0.006). Conclusion: IORT could have a negative effect on seroma formation, SSI, and delayed healing. It should be kept in mind, however, that in centers with IORT implementation, the complication rate could also increase. Necessary measures for better sterilization in the operating room should be taken, while patient wound healing should be monitored closely.

Sympathetic Denervation Accelerates Wound Contraction but Inhibits Reepithelialization and Pericyte Proliferation in Diabetic Mice

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Zhifang Zheng

2017-01-01

Full Text Available Previous studies focused on the effects of sympathetic denervation with 6-hydroxydopamine (6-OHDA on nondiabetic wounds, but the effects of 6-OHDA on diabetic wounds have not been previously reported. In this study, treated mice received intraperitoneal 6-OHDA, and control mice received intraperitoneal injections of normal saline. Full-thickness wounds were established on the backs of mice. The wounds were sectioned (four mice per group for analysis at 2, 5, 7, 10, 14, 17, and 21 days after injury. The wound areas in the control group were larger than those in the treatment group. Histological scores for epidermal and dermal regeneration were reduced in the 6-OHDA-treated group on day 21. The mast cells (MCs in each field decreased after sympathectomy on days 17 and 21. The expression levels of norepinephrine, epidermal growth factor (EGF, interleukin-1 beta, NG2 proteoglycan, and desmin in the treatment group were less than those in the control group. In conclusion, 6-OHDA delays reepithelialization during wound healing in diabetic mice by decreasing EGF, but increases wound contraction by reducing IL-1β levels and the number of MCs. Besides, 6-OHDA led to reduced pericyte proliferation in diabetic wounds, which might explain the vascular dysfunction after sympathetic nerve loss in diabetic wounds.

A Conditioned Medium of Umbilical Cord Mesenchymal Stem Cells Overexpressing Wnt7a Promotes Wound Repair and Regeneration of Hair Follicles in Mice

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Liang Dong

2017-01-01

Full Text Available Mesenchymal stem cells (MSCs can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair.

Prospective Randomized Evaluation of Intraoperative Application of Autologous Platelet-Rich Plasma on Surgical Site Infection or Delayed Wound Healing.

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SanGiovanni, Thomas P; Kiebzak, Gary M

2016-05-01

Prevention of surgical site infections and the reduction of wound-related complication rates have become increasingly emphasized by hospital task groups and government agencies given the degree of economic burden it places on the health care system. Platelet-rich plasma (PRP) contains growth factors and other biomolecules that promote endogenous microbicidal activity. We hypothesized that PRP would help prevent postoperative infection and delayed wound healing (DWH). We randomized patients having foot or ankle surgery to the treatment group receiving intraoperative PRP (applied to operative field) and platelet-poor plasma at closing (PPP, on the sutured skin) or the control group (no PRP/PPP). The incidence of deep surgical site infection and DWH (collectively called endpoints) was compared between groups (n = 250/group). PRP had a mean 5.3-fold platelet concentration compared to whole blood, with concentrated white blood cells. Mean age (±SD) of patients was 52 years (±15), 65% were women. Minor and major operative procedures were included. Patients were followed for 60 days. Seventy controls had PRP prepared for assay of growth factors. Procedure mix, ASA scores, mean operative times, and comorbidity mix were similar between groups. The primary result was no difference in number of endpoints between groups: 19 patients in the PRP group (7.6%) versus 18 controls (7.2%). Endpoints were deep surgical site infections in 2 PRP/PPP patients and 1 control, and DWH in 17 PRP/PPP patients and 17 controls. Analysis of PRP samples revealed a large variation in growth factor concentrations between patients. Intraoperative application of PRP/PPP did not reduce the incidence of postoperative infection or DWH. Growth factor profiles varied greatly between patients, suggesting that the potentially therapeutic treatment delivered was not consistent from patient-to-patient. Level I, prospective randomized trial. © The Author(s) 2015.

Cutaneous community-acquired methicillin-resistant Staphylococcus aureus infection in participants of athletic activities.

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Cohen, Philip R

2005-06-01

their initial visit. Complete resolution of the skin infection occurred after the abscesses had been drained and the athlete had been treated with systemic antimicrobial therapy for which the bacterial strain was susceptible. Cutaneous CAMRSA infection typically presents as an abscess, with or without surrounding cellulitis, in otherwise healthy participants of athletic activities who have or do not have MRSA-associated risk factors. Athletes who have MRSA skin infections include weight lifters and team members from competitive sports such as basketball, fencing, football, rugby, volleyball, and wrestling. Bacterial culture of suspected infectious skin lesions should be performed to establish the diagnosis of cutaneous MRSA infection and to determine the antibiotic susceptibility of the bacterial isolate. Treatment of cutaneous MRSA infection involves drainage of the abscess (either spontaneously or after incision) and appropriate systemic antimicrobial therapy. Direct skin-to-skin physical contact with infectious lesions or drainage, skin damage that facilitates the entry of bacteria, and sharing of infected equipment, clothing, or personal items may result in the acquisition and transmission of MRSA infection in participants of athletic activities. Earlier detection and topical treatment of the athlete's skin wounds by their coaches, avoidance of contact with other participants' cutaneous lesions and their drainage, and good personal hygiene are measures that can potentially prevent the spread of cutaneous MRSA infection in participants of athletic activities.

Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

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Cornelia Tolg

Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

Occult diaphragmatic injuries caused by stab wounds.

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Leppäniemi, Ari; Haapiainen, Reijo

2003-10-01

Missed diaphragmatic perforation caused by penetrating trauma can lead to subsequent strangulation of a hollow viscus, which has prompted the use of invasive diagnostic procedures to exclude occult diaphragmatic injuries in asymptomatic, high-risk patients. The objective of this study was to determine the incidence of occult diaphragmatic injuries caused by stab wounds of the lower chest and upper abdomen, and to examine the natural history and consequences of missed diaphragmatic injuries. On the basis of patient data from two previous randomized studies from our institution, a retrospective analysis was performed on 97 patients treated for anterior stab wounds located between the nipple line, the umbilical level, and the posterior axillary lines not having indications for immediate surgical exploration. The patients were divided into two groups on the basis of their initial randomized management (open or laparoscopic exploration vs. expectant observation). In the exploration group (n = 47), four diaphragmatic injuries (9%) were detected (three left-sided and one right-sided). Excluding patients with associated injuries requiring surgical repair, the incidence of occult diaphragmatic injuries was 3 of 43 (7%). In the observation group (n = 50), there were two patients (4%) with delayed presentation of missed left-sided diaphragmatic injury 2 and 23 months later, respectively. Both injuries resulted from stab wounds of the left flank and presented with herniation of the stomach or small bowel and colon. The overall incidence of occult diaphragmatic injuries in left-sided thoracoabdominal stab wounds was 4 of 24 (17%), and was much lower after stab wounds of left epigastrium (0%), right lower chest (0%), and right epigastrium (4%). In asymptomatic patients with anterior or flank stab wounds of the lower chest or upper abdominal area, the risk of an occult diaphragmatic injury is approximately 7% which, if undetected, is associated with a high risk of subsequent

Platelets Regulate the Migration of Keratinocytes via Podoplanin/CLEC-2 Signaling during Cutaneous Wound Healing in Mice.

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Asai, Jun; Hirakawa, Satoshi; Sakabe, Jun-ichi; Kishida, Tsunao; Wada, Makoto; Nakamura, Naomi; Takenaka, Hideya; Mazda, Osam; Urano, Tetsumei; Suzuki-Inoue, Katsue; Tokura, Yoshiki; Katoh, Norito

2016-01-01

Podoplanin is an endogenous ligand for C-type lectin-like receptor 2 (CLEC-2), which is expressed on platelets. Recent evidence indicates that this specific marker of lymphatic endothelial cells is also expressed by keratinocytes at the edge of wounds. However, whether podoplanin or platelets play a role in keratinocyte activity during wound healing remains unknown. We evaluated the effect of podoplanin expression levels on keratinocyte motility using cultured primary normal human epidermal keratinocytes (NHEKs). Down-regulation of podoplanin in NHEKs via transfection with podoplanin siRNA inhibited their migration, indicating that podoplanin plays a mandatory role in this process. In addition, down-regulation of podoplanin was correlated with up-regulation of E-cadherin, suggesting that podoplanin-mediated stimulation of keratinocyte migration is associated with a loss of E-cadherin. Both the addition of platelets and treatment with CLEC-2 inhibited the migration of NHEKs. The down-regulation of RhoA activity and the up-regulation of E-cadherin in keratinocytes were also induced by CLEC-2. In conclusion, these results suggest that podoplanin/CLEC-2 signaling regulates keratinocyte migration via modulating E-cadherin expression through RhoA signaling. Altering the regulation of keratinocyte migration by podoplanin might be a novel therapeutic approach to improve wound healing. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Hypoperfusion and Wound Healing: Another Dimension of Wound Assessment.

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Smollock, Wendy; Montenegro, Paul; Czenis, Amy; He, Yuan

2018-02-01

To examine the correlation between mean arterial pressure (MAP) and wound healing indices and describe an analytical process that can be used accurately and prospectively when evaluating all types of skin ulcerations. A correlational study in a long-term-care facility.Participants (N = 230) were adults residing in a long-term-care facility with an average age of 77.8 years (range, 35-105). Assessment through both an index of wound healing and wound surface area. Signs of wound healing included a reduction of surface area and surface necrosis and increased granulation or epithelialization. Aggregate analyses for all wound locations revealed a positive correlation between the MAP and index of wound healing (r = 0.86, n = 501, P wound healing was noted for all wound locations in this data set when MAP values were 80 mm Hg or less (r = 0.95, n = 141, P wounds and MAP of less than 80 mm Hg yielded a very strong positive correlation. The data indicated that as perfusion decreased, wounds within the sample population declined (r = 0.93, n = 102, P wound healing or worsened wounds. A predictability of wounds stalling or declining related to the MAP was observed, regardless of topical treatment or standard-of-care interventions. Therefore, the data also suggest that remediating states of low perfusion should take precedence in making treatment decisions.

Wound care centers

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Pressure ulcer - wound care center; Decubitus ulcer - wound care center; Diabetic ulcer - wound care center; Surgical wound - wound ... Common types of non-healing wounds include: Pressure sores Surgical ... flow, or swollen legs Certain wounds may not heal well due to: ...

Chitosan-aluminum monostearate composite sponge dressing containing asiaticoside for wound healing and angiogenesis promotion in chronic wound.

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Phaechamud, Thawatchai; Yodkhum, Kotchamon; Charoenteeraboon, Juree; Tabata, Yasuhiko

2015-05-01

There are many factors that delay healing in chronic wounds including lowering level of growth factors and increasing exudate level comprising high amount of tissue destructive enzymes. Asiaticoside possesses interesting wound healing and angiogenic activities that are employed to stimulate tissue regeneration in wound healing application. This study attempted to develop chitosan-aluminum monostearate (Alst) composite sponge containing asiaticoside for use as an absorbent medical dressing in chronic wound. N-methyl-2-pyrrolidone (NMP) was used to enhance homogeneity of asiaticoside in the polymer composite matrix. The sponge dressings were prepared by lyophilization and dehydrothermal treatment (DHT). Functional group interaction, crystallinity, and morphology of the prepared sponges were investigated using FT-IR, PXRD, and SEM, respectively. Physicochemical properties, porosity, hydrophilic/hydrophobic properties and mechanical property, were evaluated. Wound dressing properties, water vapor transmission rate (WVTR), fluid absorbency, oxygen permeation (OP), and bio-adhesive property, were investigated. In vitro asiaticoside release study was conducted using immersion method. Cytotoxicity was studied in normal human dermal fibroblast (NHDF) and normal human epidermal keratinocyte (NHEK). Angiogenic activity of asiaticoside was evaluated using chick-chorioallantoic membrane (CAM) assay. FT-IR and PXRD results revealed the amidation after DHT to enhance the crystallinity of the prepared sponges. The prepared sponges had high porosity comprising high Alst-loaded amount that exhibited more compact structure. Alst enhanced hydrophobicity therefore it reduced the fluid absorption and WVTR together with bio-adhesion of the prepared sponge dressings. Porosity of all sponges was more than 85% therefore resulting in their high OP. Enhancing hydrophobicity of the material by Alst and more homogeneity caused by NMP eventually retarded the asiaticoside release for 7 days. The

Pigment epithelium-derived factor as a multifunctional regulator of wound healing

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Wietecha, Mateusz S.; Król, Mateusz J.; Michalczyk, Elizabeth R.; Chen, Lin; Gettins, Peter G.

2015-01-01

During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury. PMID:26163443

Treatment of sternal wound infection with vacuum-assisted closure.

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Dezfuli, Bobby; Li, Chin-Shang; Young, J Nilas; Wong, Michael S

2013-02-01

Previous work has demonstrated the efficacy of vacuum-assisted closure (VAC) in the treatment of poststernotomy local wound infections, compared to historical treatment protocol. The negative pressure has been found to protect wounds against contamination, prevent wound fluid retention, increase blood flow, and increase rates of granulation tissue formation. For this study, a retrospective analysis compared patients receiving VAC as definitive treatment versus bridging to delayed flap closure. Sixteen patients developed sternal wound infections after cardiac surgeries at the authors' institution from 2006 to 2008. Data was gathered regarding patient comorbidities, treatment method, and outcome. Study objectives included assessment of risk factors that warranted secondary surgicalclosure and examination of long-term followup where VAC was thedefinitive treatment modality. Group A (n = 12) had VAC as the final treatment modality. Group B (n = 4) required myocutaneous flap closure. One patient in Group B passed away prior to flap surgery. Both groups had similar risk factors, except Group B had a higher risk of body mass index (BMI) > 35 that was near statistically significant (P = 0.085; odds ratio = 0.0, 95% CI = [0.0 - 1.21]). Group A required a shorter hospital stay on average. Long-term follow-up showed the majority of Group A had completely healed sternal wounds 2-3 years from initial cardiac surgery. Vacuum-assisted closure as definitive treatment modality is a successful, first line therapy for local superficial sternal wound infections. When deep infections occur, however, VAC as bridge-to-flap coverage is recommended over attempted secondary healing with VAC. .

The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia.

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Aijima, Reona; Wang, Bing; Takao, Tomoka; Mihara, Hiroshi; Kashio, Makiko; Ohsaki, Yasuyoshi; Zhang, Jing-Qi; Mizuno, Atsuko; Suzuki, Makoto; Yamashita, Yoshio; Masuko, Sadahiko; Goto, Masaaki; Tominaga, Makoto; Kido, Mizuho A

2015-01-01

The oral cavity provides an entrance to the alimentary tract to serve as a protective barrier against harmful environmental stimuli. The oral mucosa is susceptible to injury because of its location; nonetheless, it has faster wound healing than the skin and less scar formation. However, the molecular pathways regulating this wound healing are unclear. Here, we show that transient receptor potential vanilloid 3 (TRPV3), a thermosensitive Ca(2+)-permeable channel, is more highly expressed in murine oral epithelia than in the skin by quantitative RT-PCR. We found that temperatures above 33°C activated TRPV3 and promoted oral epithelial cell proliferation. The proliferation rate in the oral epithelia of TRPV3 knockout (TRPV3KO) mice was less than that of wild-type (WT) mice. We investigated the contribution of TRPV3 to wound healing using a molar tooth extraction model and found that oral wound closure was delayed in TRPV3KO mice compared with that in WT mice. TRPV3 mRNA was up-regulated in wounded tissues, suggesting that TRPV3 may contribute to oral wound repair. We identified TRPV3 as an essential receptor in heat-induced oral epithelia proliferation and wound healing. Our findings suggest that TRPV3 activation could be a potential therapeutic target for wound healing in skin and oral mucosa. © FASEB.

Comparison of the Hydroxylase Inhibitor Dimethyloxalylglycine and the Iron Chelator Deferoxamine in Diabetic and Aged Wound Healing.

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Duscher, Dominik; Januszyk, Michael; Maan, Zeshaan N; Whittam, Alexander J; Hu, Michael S; Walmsley, Graham G; Dong, Yixiao; Khong, Sacha M; Longaker, Michael T; Gurtner, Geoffrey C

2017-03-01

A hallmark of diabetes mellitus is the breakdown of almost every reparative process in the human body, leading to critical impairments of wound healing. Stabilization and activity of the transcription factor hypoxia-inducible factor (HIF)-1α is impaired in diabetes, leading to deficits in new blood vessel formation in response to injury. In this article, the authors compare the effectiveness of two promising small-molecule therapeutics, the hydroxylase inhibitor dimethyloxalylglycine and the iron chelator deferoxamine, for attenuating diabetes-associated deficits in cutaneous wound healing by enhancing HIF-1α activation. HIF-1α stabilization, phosphorylation, and transactivation were measured in murine fibroblasts cultured under normoxic or hypoxic and low-glucose or high-glucose conditions following treatment with deferoxamine or dimethyloxalylglycine. In addition, diabetic wound healing and neovascularization were evaluated in db/db mice treated with topical solutions of either deferoxamine or dimethyloxalylglycine, and the efficacy of these molecules was also compared in aged mice. The authors show that deferoxamine stabilizes HIF-1α expression and improves HIF-1α transactivity in hypoxic and hyperglycemic states in vitro, whereas the effects of dimethyloxalylglycine are significantly blunted under hyperglycemic hypoxic conditions. In vivo, both dimethyloxalylglycine and deferoxamine enhance wound healing and vascularity in aged mice, but only deferoxamine universally augmented wound healing and neovascularization in the setting of both advanced age and diabetes. This first direct comparison of deferoxamine and dimethyloxalylglycine in the treatment of impaired wound healing suggests significant therapeutic potential for topical deferoxamine treatment in ischemic and diabetic disease.

[A preliminary study of anti-aging and wound healing of recombination cytoglobin].

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Li, Zhao-Fa; Zhao, Xiao-Fang; Zhang, Ting-Ting

2012-01-01

In this paper, the preliminary study on antioxidant, enhancement of antioxidant enzymes activity, reducing the content of oxygen free radicals, delaying skin aging of the recombination cytoglobin (rCygb) purified by our lab were investigated through human keratinocyte cell line (HaCAT) H2O2 oxidative stress model, mouse skin aging model caused by continuous subcutaneous injection D-gal, rat acute liver injury model induced by CCl4 and rat skin wound healing model. The results showed that rCygb improved the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), reduced the activities of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) as well as decreased the content of malondialdehyde (MDA). Skin biopsy showed that rCygb promoted angiogenesis, increased expression of collagen and improved the anti-inflammatory ability. All results displayed that rCygb improved the oxygen free radical scavenging ability, delayed skin aging and promoted wound healing.

Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring.

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Engrav, Loren H; Tuggle, Christopher K; Kerr, Kathleen F; Zhu, Kathy Q; Numhom, Surawej; Couture, Oliver P; Beyer, Richard P; Hocking, Anne M; Carrougher, Gretchen J; Ramos, Maria Luiza C; Klein, Matthew B; Gibran, Nicole S

2011-04-20

Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1) there has been no validated animal model; 2) human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3) tissues typically have been homogenized, mixing cell populations; and 4) gene-by-gene studies are incomplete. We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc(pigmented fibroproliferative)/Yorkshire(non-pigmented non-fibroproliferative) porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model. 1) The scars are still thick at forty-six weeks post wounding further validating the model. 2) The differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3) The findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. In the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.

Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring.

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Loren H Engrav

Full Text Available BACKGROUND: Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1 there has been no validated animal model; 2 human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3 tissues typically have been homogenized, mixing cell populations; and 4 gene-by-gene studies are incomplete. METHODOLOGY/PRINCIPAL FINDINGS: We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc(pigmented fibroproliferative/Yorkshire(non-pigmented non-fibroproliferative porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model. CONCLUSIONS/SIGNIFICANCE: 1 The scars are still thick at forty-six weeks post wounding further validating the model. 2 The differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3 The findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. In the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.

Early burn wound excision and skin grafting postburn trauma restores in vivo neutrophil delivery to inflammatory lesions

International Nuclear Information System (INIS)

Tchervenkov, J.I.; Epstein, M.D.; Silberstein, E.B.; Alexander, J.W.

1988-01-01

This study assessed the effect of early vs delayed postburn wound excision and skin grafting on the in vivo neutrophil delivery to a delayed-type hypersensitivity (DTH) reaction and a bacterial skin lesion (BSL). Male Lewis rats were presensitized to keyhole-limpet hemocyanin. Group 1 comprised sham controls. Groups 2 through 4 were given a 30% 3 degrees scald burn, but the burn wounds were excised, and skin was grafted on days 1, 3, and 7, respectively, after the burn. Group 5 comprised burn controls. Twelve days after burn trauma, all rats were injected at different intervals (during a 24-hour period) with a trio of intradermal injections of keyhole-limpet hemocyanin, Staphylococcus aureus 502A, and saline at different sites. In vivo neutrophil delivery to these dermal lesions was determined by injecting indium in 111 oxyquinoline-labeled neutrophils isolated from similarly treated groups of rats. Neutrophil delivery to DTH and BSL lesions was restored to normal by excision and skin grafting of the burn wound one day after burn trauma. Waiting three days after burn trauma to excise and skin graft the wound partially, but not completely, restored the in vivo neutrophil delivery to DTH and BSL lesions. Waiting one week to excise and skin graft a burn wound resulted in no improvement in neutrophil delivery to DTH and BSL dermal lesions. It was concluded that burn wound excision and skin grafting immediately after burn trauma restored in vivo neutrophil delivery to a BSL and DTH dermal lesion. This may, in part, explain the beneficial effect of early aggressive burn wound debridement in patients with burn injuries

Bioengineering methods employed in the study of wound healing of sulphur mustard burns.

Science.gov (United States)

Graham, John S; Schomacker, Kevin T; Glatter, Robert D; Briscoe, Crystal M; Braue, Ernest H; Squibb, Katherine S

2002-02-01

Sulphur mustard (SM) is a potent incapacitating chemical warfare agent that remains a threat to war fighters and civilians worldwide. SM lesions may require weeks or months to heal, depending upon their severity. This study was undertaken to find a treatment regimen that promotes speedier healing of deep cutaneous SM burns in a weanling pig model. The principal objective of the study was to compare four treatment regimens and establish which achieved the shortest healing time. Twelve Yorkshire Cross weanling pigs were exposed to SM liquid for 2h, generating six large deep dermal/full thickness burns on the ventrum of each animal. Three additional animals served as sham-exposed controls. Surgical intervention occurred at 48 h postexposure. Treatments included: (i) full-thickness debridement of the burns with a computer controlled, raster scanned continuous wave CO2 laser followed by autologous split-thickness skin grafting; (ii) full-thickness sharp surgical tangential excision followed by skin grafting, the 'Gold Standard' used in human deep dermal/full-thickness thermal burns management; (iii) partial-thickness laser ablation with no grafting; and (iv) partial-thickness sharp surgical excision with no grafting. Several non-invasive bioengineering methods were used to monitor the progress of wound healing throughout a 36-day healing period: reflectance colourimetry, evaporimetry, laser Doppler perfusion imaging and ballistometry. Bioengineering methods indicated that laser debridement followed by autologous split-thickness skin grafting was as efficacious in improving the wound healing of deep SM burns in weanling swine as the 'Gold Standard.' Regardless of the method of debridement, barrier function, skin colour and mechanical properties returned to near-normal levels within 15 days of treatment in the grafted sites. Regardless of surgical approach, blood flux levels remained approximately 50-60% of normal tissue throughout the 36-day postsurgical observation

Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections.

Science.gov (United States)

Griffith, Gina L; Kasus-Jacobi, Anne; Pereira, H Anne

2017-06-01

Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and clearing infections. Critical Issues: An important aspect of treating ocular injuries is that treatments need to be effective and administered expeditiously. This is especially important for injuries that occur during combat and in individuals who demonstrate delayed wound healing. To overcome gaps in current treatment modalities, bioactive peptides based on naturally occurring cationic antimicrobial proteins are being investigated as new therapeutics. Future Directions: The development of new therapeutics that can treat ocular infections and promote corneal wound healing, including the healing of persistent corneal epithelial defects, would be of great clinical benefit.

Application of Three - dimensional Wound Analyzer in the Small Wound Area Measurement during the Process of Wound Healing.

Science.gov (United States)

Sheng, Jiajun; Li, Haihang; Jin, Jian; Liu, Tong; Ma, Bing; Liu, Gongcheng; Zhu, Shihui

2018-02-20

The objective of this study was to determinate the reliability of 3-dimensional wound analyzer (3-DWMD) in the wound area measurement for animal small area in the process of wound healing. Seven Sprague-Dawley rats were used to establish the skin defect model. And the wound area and time consumption were measured on days 0, 5, 10, 15 using 3-DWMD, investigators, and planimetry method. The measurement results using 3-DWMD and investigators were analyzed comparative with that using planimetry method separately. A total 46 wounds, including 32 irregular wounds and regular 14 wounds, were measured. No matter calculating the irregular wounds or the regular wounds, there was no significant difference between 3-DWMD group and planimetry group in measuring wound area (P > 0.05). However, a statistically significant difference was found in time-consuming for measuring wound area between 3-DWMD group and planimetry group (P area, and its measurement results were consistent with planimetry method. Therefore, such measuring equipment has clinical reference value for measuring precision area of the wound in the process of wound healing.

Defective Wound-healing in Aging Gingival Tissue.

Science.gov (United States)

Cáceres, M; Oyarzun, A; Smith, P C

2014-07-01

Aging may negatively affect gingival wound-healing. However, little is known about the mechanisms underlying this phenomenon. The present study examined the cellular responses associated with gingival wound-healing in aging. Primary cultures of human gingival fibroblasts were obtained from healthy young and aged donors for the analysis of cell proliferation, cell invasion, myofibroblastic differentiation, and collagen gel remodeling. Serum from young and old rats was used to stimulate cell migration. Gingival repair was evaluated in Sprague-Dawley rats of different ages. Data were analyzed by the Mann-Whitney and Kruskal-Wallis tests, with a p value of .05. Fibroblasts from aged donors showed a significant decrease in cell proliferation, migration, Rac activation, and collagen remodeling when compared with young fibroblasts. Serum from young rats induced higher cell migration when compared with serum from old rats. After TGF-beta1 stimulation, both young and old fibroblasts demonstrated increased levels of alpha-SMA. However, alpha-SMA was incorporated into actin stress fibers in young but not in old fibroblasts. After 7 days of repair, a significant delay in gingival wound-healing was observed in old rats. The present study suggests that cell migration, myofibroblastic differentiation, collagen gel remodeling, and proliferation are decreased in aged fibroblasts. In addition, altered cell migration in wound-healing may be attributable not only to cellular defects but also to changes in serum factors associated with the senescence process. © International & American Associations for Dental Research.

The molecular biology in wound healing & non-healing wound.

Science.gov (United States)

Qing, Chun

2017-08-01

The development of molecular biology and other new biotechnologies helps us to recognize the wound healing and non-healing wound of skin in the past 30 years. This review mainly focuses on the molecular biology of many cytokines (including growth factors) and other molecular factors such as extracellular matrix (ECM) on wound healing. The molecular biology in cell movement such as epidermal cells in wound healing was also discussed. Moreover many common chronic wounds such as pressure ulcers, leg ulcers, diabetic foot wounds, venous stasis ulcers, etc. usually deteriorate into non-healing wounds. Therefore the molecular biology such as advanced glycation end products (AGEs) and other molecular factors in diabetes non-healing wounds were also reviewed. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Aging influences wound healing in patients with chronic lower extremity wounds treated in a specialized Wound Care Center.

Science.gov (United States)

Wicke, Corinna; Bachinger, Andreas; Coerper, Stephan; Beckert, Stefan; Witte, Maria B; Königsrainer, Alfred

2009-01-01

With the dramatic increase in the aging population, the study and care of wounds in the elderly have become priority topics for both researchers and clinicians. The effects of aging on wound healing in humans have remained controversial. The study was a 5-year epidemiological evaluation of standardized data collected regularly during patients' visits at a specialized Wound Care Center with the aim to determine the key factors influencing the healing of chronic lower extremity wounds. In this analysis of 1,158 chronic wounds, the frequency of wound closure was statistically significantly lower in older patients compared with younger patients. The share of closed wounds decreased by nearly 25% in the elderly patients (>or=70 years). The relationship between the patient's age and the proportion of wound closure was nonlinear. The effect of aging on the frequency of wound closure of chronic wounds became clinically apparent after age 60. The chronicity of the wounds was illustrated by their recurrent nature, their long duration, the presence of multiple wounds, and the frequency of concurrent infection. Comorbidity was documented by the coprevalence of up to three underlying diseases related to impaired wound healing. The present study clearly showed that aging affects chronic wound healing negatively.

Photobiomodulation with Pulsed and Continuous Wave Near-Infrared Laser (810 nm, Al-Ga-As Augments Dermal Wound Healing in Immunosuppressed Rats.

Directory of Open Access Journals (Sweden)

Gaurav K Keshri

Full Text Available Chronic non-healing cutaneous wounds are often vulnerable in one or more repair phases that prevent normal healing and pose challenges to the use of conventional wound care modalities. In immunosuppressed subject, the sequential stages of healing get hampered, which may be the consequences of dysregulated or stagnant wound inflammation. Photobiomodulation (PBM or low-level laser (light therapy (LLLT emerges as a promising drug-free, non-invasive biophysical approach for promoting wound healing, reduction of inflammation, pain and restoration of functions. The present study was therefore undertaken to evaluate the photobiomodulatory effects of 810 nm diode laser (40 mW/cm2; 22.6 J/cm2 with pulsed (10 and 100 Hz, 50% duty cycle and continuous wave on full-thickness excision-type dermal wound healing in hydrocortisone-induced immunosuppressed rats. Results clearly delineated that 810 nm PBM at 10 Hz was more effective over continuous and 100 Hz frequency in accelerating wound healing by attenuating the pro-inflammatory markers (NF-kB, TNF-α, augmenting wound contraction (α-SM actin, enhancing cellular proliferation, ECM deposition, neovascularization (HIF-1α, VEGF, re-epithelialization along with up-regulated protein expression of FGFR-1, Fibronectin, HSP-90 and TGF-β2 as compared to the non-irradiated controls. Additionally, 810 nm laser irradiation significantly increased CCO activity and cellular ATP contents. Overall, the findings from this study might broaden the current biological mechanism that could be responsible for photobiomodulatory effect mediated through pulsed NIR 810 nm laser (10 Hz for promoting dermal wound healing in immunosuppressed subjects.

Treatment of Cutaneous Lupus Erythematosus

Science.gov (United States)

Kim, Grace K.; Del Rosso, James Q.

2013-01-01

The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice. PMID:23320123

Skin wound healing in different aged Xenopus laevis.

Science.gov (United States)

Bertolotti, Evelina; Malagoli, Davide; Franchini, Antonella

2013-08-01

Xenopus froglets can perfectly heal skin wounds without scarring. To explore whether this capacity is maintained as development proceeds, we examined the cellular responses during the repair of skin injury in 8- and 15-month-old Xenopus laevis. The morphology and sequence of healing phases (i.e., inflammation, new tissue formation, and remodeling) were independent of age, while the timing was delayed in older frogs. At the beginning of postinjury, wound re-epithelialization occurred in form of a thin epithelium followed by a multilayered epidermis containing cells with apoptotic patterns and keratinocytes stained by anti-inducible nitric oxide synthase (iNOS) antibody. The inflammatory response, early activated by recruitment of blood cells immunoreactive to anti-tumor necrosis factor (TNF)-α, iNOS, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-9, persisted over time. The dermis repaired by a granulation tissue with extensive angiogenesis, inflammatory cells, fibroblasts, and anti-α-SMA positive myofibroblasts. As the healing progressed, wounded areas displayed vascular regression, decrease in cellularity, and rearrangement of provisional matrix. The epidermis restored to a prewound morphology while granulation tissue was replaced by a fibrous tissue in a scar-like pattern. The quantitative PCR analysis demonstrated an up-regulated expression of Xenopus suppressor of cytokine signaling 3 (XSOCS-3) and Xenopus transforming growth factor-β2 (XTGF-β2) soon after wounding and peak levels were detected when granulation tissue was well developed with a large number of inflammatory cells. The findings indicate that X. laevis skin wound healing occurred by a combination of regeneration (in epidermis) and repair (in dermis) and, in contrast to froglet scarless wound healing, the growth to a more mature adult stage is associated with a decrease in regenerative capacity with scar-like tissue formation. Copyright © 2013 Wiley Periodicals, Inc.

A human model of small fiber neuropathy to study wound healing.

Directory of Open Access Journals (Sweden)

Ben M W Illigens

Full Text Available The aim of this study was to develop a human model of acute wound healing that isolated the effects of small fiber neuropathy on the healing process. Twenty-five healthy subjects had the transient receptor vanilloid 1 agonist capsaicin and placebo creams topically applied to contralateral areas on the skin of the thigh for 48 hours. Subjects had shallow (1.2 millimeter and deep (>3 millimeter punch skin biopsies from each thigh on days 1 and 14. Biopsy wound healing was monitored photographically until closure. Intra-epidermal and sweat-gland nerve fiber densities were measured for each biopsy. Shallow wounds in capsaicin-treated sites healed more slowly than in placebo treated skin with biopsies taken on day 1 (P<0.001 and day 14 (P<0.001. Deep biopsies in the capsaicin and placebo areas healed at similar rates at both time points. Nerve fiber densities were reduced only in capsaicin treated regions (P<0.01. In conclusion, topical application of capsaicin causes a small fiber neuropathy and is associated with a delay in healing of shallow, but not deep wounds. This novel human model may prove valuable in the study of wound healing in patients with neuropathy.

Assessment of the healing activity of jucá pods [Libidibia ferrea (Mart. ex Tul.) L. P. Queiroz] in cutaneous lesions of rats

OpenAIRE

Carvalho, Frascisca Gomes Carvalho; Faculdade de Saúde, Ciencias Humanas e Tecnológicas do Piauí; Sampaio, João Paulo da Silva Sampaio; Faculdade de Saúde, Ciencias Humanas e Tecnológicas do Piauí; Araújo, Maurycio Macedo dos Santos Araújo; Faculdade de Saúde, Ciencias Humanas e Tecnológicas do Piauí; Pinto, Lucielma Salmito Soares; Faculdade de Saúde, Ciencias Humanas e Tecnológicas do Piauí; Rocha, Antônio José; Universidade Federal do Ceará

2016-01-01

The study aimed to evaluate the healing activity of the powdered pod of L. ferrea in cutaneous wound healing in preclinical test in rats. Eighteen rats were divided into two groups: the positive control group (PCG) treated with Kollagenase® and the experimental group (EG) treated with an ointment prepared with the powder of Libidibia ferrea. The lesions were clinically evaluated on 0 - 21st days, when histopathological analysis was also performed. In this study, the clinical analysis showed t...

The multifunctional LigB adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans.

Directory of Open Access Journals (Sweden)

Henry A Choy

Full Text Available Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9-11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis

Three-dimensional wound measurements for monitoring wound healing

DEFF Research Database (Denmark)

Bisgaard Jørgensen, Line; Møller Jeppesen, Sune; Halekoh, Ulrich

Telemedicine is increasingly used for monitoring wound healing. Three-dimensional (3D) measurement methods enable clinicians to assess wound healing with respect to all dimensions. However, the currently available methods are inaccurate, costly or complicated to use. To address these issues, a 3D......-WAM camera was developed. This camera is able to measure wound size (2D area, 3D area, perimeter and volume) and to assess wound characteristics....

Skin appendage-derived stem cells: cell biology and potential for wound repair.

Science.gov (United States)

Xie, Jiangfan; Yao, Bin; Han, Yutong; Huang, Sha; Fu, Xiaobing

2016-01-01

Stem cells residing in the epidermis and skin appendages are imperative for skin homeostasis and regeneration. These stem cells also participate in the repair of the epidermis after injuries, inducing restoration of tissue integrity and function of damaged tissue. Unlike epidermis-derived stem cells, comprehensive knowledge about skin appendage-derived stem cells remains limited. In this review, we summarize the current knowledge of skin appendage-derived stem cells, including their fundamental characteristics, their preferentially expressed biomarkers, and their potential contribution involved in wound repair. Finally, we will also discuss current strategies, future applications, and limitations of these stem cells, attempting to provide some perspectives on optimizing the available therapy in cutaneous repair and regeneration.

Wound care clinical pathway: a conceptual model.

Science.gov (United States)

Barr, J E; Cuzzell, J

1996-08-01

A clinical pathway is a written sequence of clinical processes or events that guides a patient with a defined problem toward an expected outcome. Clinical pathways are tools to assist with the cost-effective management of clinical outcomes related to specific problems or disease processes. The primary obstacles to developing clinical pathways for wound care are the chronic natures of some wounds and the many variables that can delay healing. The pathway introduced in this article was modeled upon the three phases of tissue repair: inflammatory, proliferative, and maturation. This physiology-based model allows clinicians to identify and monitor outcomes based on observable and measurable clinical parameters. The pathway design, which also includes educational and behavioral outcomes, allows the clinician to individualize the expected timeframe for outcome achievement based on individual patient criteria and expert judgement. Integral to the pathway are the "4P's" which help standardize the clinical processes by wound type: Protocols, Policies, Procedures, and Patient education tools. Four categories into which variances are categorized based on the cause of the deviation from the norm are patient, process/system, practitioner, and planning/discharge. Additional research is warranted to support the value of this clinical pathway in the clinical arena.

Fasciocutaneous Lotus Petal Flap for Perineal Wound Reconstruction after Extralevator Abdominoperineal Excision : Application for Reconstruction of the Pelvic Floor and Creation of a Neovagina

NARCIS (Netherlands)

Hellinga, Joke; Khoe, Patrick C. K. H.; van Etten, Boudewijn; Hemmer, Patrick H. J.; Havenga, Klaas; Stenekes, Martin W.; Eltahir, Yassir

2016-01-01

The extralevator abdominoperineal excision (ELAPE) procedure creates an extensive soft tissue defect of the pelvic floor. It has been suggested that primary reconstruction reduces the risk of wound infection and delayed wound healing in this high-risk area. Use of myocutaneous flaps or omentoplasty

Aberrant Wound Healing in an Epidermal Interleukin-4 Transgenic Mouse Model of Atopic Dermatitis

Science.gov (United States)

Zhao, Yan; Bao, Lei; Chan, Lawrence S.; DiPietro, Luisa A.; Chen, Lin

2016-01-01

Wound healing in a pre-existing Th2-dominated skin milieu was assessed by using an epidermal specific interleukin-4 (IL-4) transgenic (Tg) mouse model, which develops a pruritic inflammatory skin condition resembling human atopic dermatitis. Our results demonstrated that IL-4 Tg mice had delayed wound closure and re-epithelialization even though these mice exhibited higher degrees of epithelial cell proliferation. Wounds in IL-4 Tg mice also showed a marked enhancement in expression of inflammatory cytokines/chemokines, elevated infiltration of inflammatory cells including neutrophils, macrophages, CD3+ lymphocytes, and epidermal dendritic T lymphocytes. In addition, these mice exhibited a significantly higher level of angiogenesis as compared to wild type mice. Furthermore, wounds in IL-4 Tg mice presented with larger amounts of granulation tissue, but had less expression and deposition of collagen. Taken together, an inflamed skin condition induced by IL-4 has a pronounced negative influence on the healing process. Understanding more about the pathogenesis of wound healing in a Th2- dominated environment may help investigators explore new potential therapeutic strategies. PMID:26752054

Multifunctional activities of KSLW synthetic antimicrobial decapeptide: Implications for wound healing

Science.gov (United States)

Williams, Richard Leroy

Wound healing is a complex process leading to the maintenance of skin integrity. Stress is known to increase susceptibility to bacterial infection, alter proinflammatory cytokine expression, and delay wound closure. Recently, antimicrobial peptides have generated interest due to their prokaryotic selectivity, decreased microbial resistance and multifunctional roles in wound healing, including fibroblast stimulation, keratinocyte migration and leukocyte migration. The objective of this dissertation project was to evaluate the effect of a synthetic antimicrobial decapeptide (KSLW) on bacterial clearance inflammation, and wound closure during stress-impaired healing. SKH-1 mice were randomly assigned to either control or restraint-stressed (RST) groups. Punch biopsy wounds (3.5 mm in diameter) were created bilaterally on the dorsal skin. Wounds were injected with 50 microL of empty carriers or KSLW prepared in Pluronic-F68, phospholipid micelles, or saline. Bacterial assays of harvested wounds were conducted on BHI agar. Wound closure was determined by photoplanimetry. Cytokine and growth factor mRNA expression was assessed with real-time RT-PCR. Human neutrophil migration assays and checkerboard analyses were performed using Transweli plates, and counting on hemacytometer. Oxidative burst activity was measured by spectrophotometric analysis of 2,7-dichlorofluorescein oxidation. KSLW-treatment resulted in significant reductions in bacterial load among RST mice, with no difference from control after 24h. The effect was sustained 5 days post-wounding, in RST mice treated with KSLW-F68. Temporal analysis of gene induction revealed reversals of stress-induced altered expression of growth factors, proinflammatory cytokines, and chemokines essential for favorable wound healing, at various time points. KSLW-treatment in RST mice demonstrated faster wound closure throughout the stress period. KSLW, at micromolar concentrations, demonstrated a significant effect on neutrophil

Use of a new silver barrier dressing, ALLEVYN Ag in exuding chronic wounds.

LENUS (Irish Health Repository)

Kotz, Paula

2009-06-01

Recognising and managing wounds at risk of infection is vital in wound management. ALLEVYN Ag dressings have been designed to manage exudate in chronic wounds that are at risk of infection; are displaying signs of local infection; or where a suspected increase in bacterial colonisation is delaying healing. They combine an absorbent silver sulfadiazine containing hydrocellular foam layer, with a perforated wound contact layer and highly breathable top film. The results presented are from a multi-centre clinical evaluation of 126 patients conducted to assess the performance of ALLEVYN Ag (Adhesive, Non Adhesive and Sacrum dressings) in a range of indications. Clinicians rated the dressings as acceptable for use in various wound types in 88% of patients. The majority of clinical signs of infection reduced between the initial and the final assessment. The condition of wound tissue and surrounding skin was observed to improve, and there was significant evidence of a reduction in the level of exudate from initial to final assessment (p < 0.001). Clinicians rated ALLEVYN Ag as satisfying or exceeding expectations in over 90% of patients. The evaluation showed the dressings to offer real benefits to patients and clinicians across multiple indications when used in conjunction with local protocols.

Enhanced Healing of Diabetic Wounds by Subcutaneous Administration of Human Umbilical Cord Derived Stem Cells and Their Conditioned Media

Science.gov (United States)

Shrestha, Chandrama; Zhao, Liling; Chen, Ke; He, Honghui; Mo, Zhaohui

2013-01-01

Objective. Mesenchymal stem cells (MSCs) isolated from the umbilical cord and their conditioned media (CM) can be easily obtained and refined compared with stem cells from other sources. Here, we explore the possibility of the benefits of these cells in healing diabetic wounds. Methodology and Results. Delayed wound healing animal models were established by making a standard wound on the dorsum of eighteen db/db mice, which were divided into three groups with six mice in each: groups I, II, and III received PBS, UC-MSC, and CM, respectively. UC-MSC and their CM significantly accelerated wound closure compared to PBS-treated wounds, and it was most rapid in CM-injected wounds. In day-14 wounds, significant difference in capillary densities among the three groups was noted (n = 6; P UC-MSC-injected wounds compared to the PBS-treated wounds were seen. The expression levels of PDGF-β and KGF were higher in CM-treated wounds than those in UC-MSC-treated wounds. Conclusion. Both the transplantation of UC-MSC and their CM are beneficial to diabetic wound healing, and CM has been shown to be therapeutically better than UC-MSC, at least in the context of diabetic wound healing. PMID:24089612

Effect of γ irradiation on rate of wound healing in a scored confluent monolayer of cells and the repair-promoting role of W11-a12

International Nuclear Information System (INIS)

Shu Chongxiang; Lou Shufen; Cheng Tianmin; Li Shunan; Ran Xinze

2002-01-01

Objective: To investigate the effects of ionizing radiation on healing rate of experimental wound in a scored confluent monolayer of fibroblasts and vascular endothelial cells and the repair-promoting effect of W 11 -a 12 . Methods: The healing rates of the experimental wound in a scored confluent monolayer of 3T3 cells or ECV304 cells irradiated with 6 Gy 60 Co gamma rays were assayed by measuring the width of the wound. Results: After irradiation, the closure of scored wounds both in a confluent monolayer of 3T3 cells and in that of ECV304 cells was significantly delayed. The scored wound in a confluent monolayer of 3T3 cells was completely closed in the sham irradiation group, but it was only 77% in the irradiation group at the tenth hour post wounding. The healing rate of the scored wound in a confluent monolayer of irradiated ECV304 cells was 83.6% of that in the sham irradiation group W 11 -a 12 had good promoting action on the closure of wounds in scored confluent monolayers of these two kinds of cells. Conclusion: The direct inhibitory effects of irradiation on the proliferating and migrating capacity of both fibroblasts and vascular endothelial cells might be one of the important reasons for the delay of healing in irradiation-impaired wounds and W 11 -a 12 could promote healing of irradiation-impaired wound by means of enhancing cell migration and proliferation directly

Mohs micrographic surgery of rare cutaneous tumours

NARCIS (Netherlands)

Flohil, S.C.; Lee, C.B. van; Beisenherz, J.; Mureau, M.A.M.; Overbeek, L.I.H.; Nijsten, T.; Bos, R.R.

2017-01-01

BACKGROUND: Recurrence rates after Mohs micrographic surgery (MMS) for rare cutaneous tumours are poorly defined. OBJECTIVE: To investigate the recurrence rate after MMS for rare cutaneous tumours at a university centre. METHODS & MATERIALS: Retrospective review of all rare cutaneous tumours treated

Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice

International Nuclear Information System (INIS)

El Khoury, Diala; Courty, José; Hovanessian, Ara G; Prévost-Blondel, Armelle; Destouches, Damien; Lengagne, Renée; Krust, Bernard; Hamma-Kourbali, Yamina; Garcette, Marylène; Niro, Sandra; Kato, Masashi; Briand, Jean-Paul

2010-01-01

The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity. The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse. HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice. Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or

Liposome Entrapment of Bacteriophages Improves Wound Healing in a Diabetic Mouse MRSA Infection

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Sanjay Chhibber

2018-03-01

Full Text Available Diabetic populations are more prone to developing wound infections which results in poor and delayed wound healing. Infection with drug resistant organisms further worsen the situation, driving searches for alternative treatment approaches such as phage therapy. Major drawback of phage therapy, however, is low phage persistence in situ, suggesting further refinement of the approach. In the present work we address this issue by employing liposomes as delivery vehicles. A liposome entrapped phage cocktail was evaluated for its ability to resolve a Staphylococcus aureus-induced diabetic excission wound infection. Two characterized S. aureus specific lytic phages, MR-5 and MR-10 alone, in combination (cocktail, or entrapped in liposomes (versus as free phages were assesed for their therapeutic efficacy in resolving diabetic wound infection. Mice treated with free phage cocktail showed significant reduction in wound bioburden, greater wound contraction and faster tissue healing than with free monophage therapy. However, to further enhance the availability of viable phages the encapsulation of phage cocktail in the liposomes was done. Results of in vitro stability studies and in vivo phage titer determination, suggests that liposomal entrapment of phage cocktail can lead to better phage persistence at the wound site. A 2 log increase in phage titre, however, was observed at the wound site with liposome entrapped as compared to the free phage cocktail, and this was associaed with increased rates of infection resolution and wound healing. Entrapment of phage cocktails within liposomes thus could represent an attractive approach for treatment of bacterial infections, not responding to antibiotis as increased phage persistence in vitro and in vivo at the wound site was observed.

Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation.

Science.gov (United States)

Roy, Sashwati; Driggs, Jason; Elgharably, Haytham; Biswas, Sabyasachi; Findley, Muna; Khanna, Savita; Gnyawali, Urmila; Bergdall, Valerie K; Sen, Chandan K

2011-11-01

The economic, social, and public health burden of chronic ulcers and other compromised wounds is enormous and rapidly increasing with the aging population. The growth factors derived from platelets play an important role in tissue remodeling including neovascularization. Platelet-rich plasma (PRP) has been utilized and studied for the last four decades. Platelet gel and fibrin sealant, derived from PRP mixed with thrombin and calcium chloride, have been exogenously applied to tissues to promote wound healing, bone growth, hemostasis, and tissue sealing. In this study, we first characterized recovery and viability of as well as growth factor release from platelets in a novel preparation of platelet gel and fibrin matrix, namely platelet-rich fibrin matrix (PRFM). Next, the effect of PRFM application in a delayed model of ischemic wound angiogenesis was investigated. The study, for the first time, shows the kinetics of the viability of platelet-embedded fibrin matrix. A slow and steady release of growth factors from PRFM was observed. The vascular endothelial growth factor released from PRFM was primarily responsible for endothelial mitogenic response via extracellular signal-regulated protein kinase activation pathway. Finally, this preparation of PRFM effectively induced endothelial cell proliferation and improved wound angiogenesis in chronic wounds, providing evidence of probable mechanisms of action of PRFM in healing of chronic ulcers. 2011 by the Wound Healing Society.

Radiation combined injury models to study the effects of interventions and wound biomechanics.

Science.gov (United States)

Zawaski, Janice A; Yates, Charles R; Miller, Duane D; Kaffes, Caterina C; Sabek, Omaima M; Afshar, Solmaz F; Young, Daniel A; Yang, Yunzhi; Gaber, M Waleed

2014-12-01

In the event of a nuclear detonation, a considerable number of projected casualties will suffer from combined radiation exposure and burn and/or wound injury. Countermeasure assessment in the setting of radiation exposure combined with dermal injury is hampered by a lack of animal models in which the effects of interventions have been characterized. To address this need, we used two separate models to characterize wound closure. The first was an open wound model in mice to study the effect of wound size in combination with whole-body 6 Gy irradiation on the rate of wound closure, animal weight and survival (morbidity). In this model the addition of interventions, wound closure, subcutaneous vehicle injection, topical antiseptic and topical antibiotics were studied to measure their effect on healing and survival. The second was a rat closed wound model to study the biomechanical properties of a healed wound at 10 days postirradiation (irradiated with 6 or 7.5 Gy). In addition, complete blood counts were performed and wound pathology by staining with hematoxylin and eosin, trichrome, CD68 and Ki67. In the mouse open wound model, we found that wound size and morbidity were positively correlated, while wound size and survival were negatively correlated. Regardless of the wound size, the addition of radiation exposure delayed the healing of the wound by approximately 5-6 days. The addition of interventions caused, at a minimum, a 30% increase in survival and improved mean survival by ∼9 days. In the rat closed wound model we found that radiation exposure significantly decreased all wound biomechanical measurements as well as white blood cell, platelet and red blood cell counts at 10 days post wounding. Also, pathological changes showed a loss of dermal structure, thickening of dermis, loss of collagen/epithelial hyperplasia and an increased density of macrophages. In conclusion, we have characterized the effect of a changing wound size in combination with radiation

Clinical application prospect of umbilical cord-derived mesenchymal stem cells on clearance of advanced glycation end products through autophagy on diabetic wound.

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Han, Yanfu; Sun, Tianjun; Tao, Ran; Han, Yanqing; Liu, Jing

2017-03-24

Nowadays, wound healing delay due to diabetes is considered to be closely related to the accumulation of advanced glycation end products (AGEs). Although mesenchymal stem cells (MSCs) exhibit positive effects on diabetic wound healing, related mechanisms are still not fully elucidated. It has been reported that MSCs can improve the activity of autophagy in injured tissues, thereby playing an important role in wound healing. The autophagy induced by MSCs may be beneficial to diabetic wound healing via removing AGEs, which provide new ideas for clinical treatment of diabetic wounds with the potential of broad application prospects. In this study, the current research situation and application prospect of umbilical cord-derived MSCs on the clearance of AGEs in diabetic wound were reviewed.

Chitosan–aluminum monostearate composite sponge dressing containing asiaticoside for wound healing and angiogenesis promotion in chronic wound

International Nuclear Information System (INIS)

Phaechamud, Thawatchai; Yodkhum, Kotchamon; Charoenteeraboon, Juree; Tabata, Yasuhiko

2015-01-01

There are many factors that delay healing in chronic wounds including lowering level of growth factors and increasing exudate level comprising high amount of tissue destructive enzymes. Asiaticoside possesses interesting wound healing and angiogenic activities that are employed to stimulate tissue regeneration in wound healing application. This study attempted to develop chitosan–aluminum monostearate (Alst) composite sponge containing asiaticoside for use as an absorbent medical dressing in chronic wound. N-methyl-2-pyrrolidone (NMP) was used to enhance homogeneity of asiaticoside in the polymer composite matrix. The sponge dressings were prepared by lyophilization and dehydrothermal treatment (DHT). Functional group interaction, crystallinity, and morphology of the prepared sponges were investigated using FT-IR, PXRD, and SEM, respectively. Physicochemical properties, porosity, hydrophilic/hydrophobic properties and mechanical property, were evaluated. Wound dressing properties, water vapor transmission rate (WVTR), fluid absorbency, oxygen permeation (OP), and bio-adhesive property, were investigated. In vitro asiaticoside release study was conducted using immersion method. Cytotoxicity was studied in normal human dermal fibroblast (NHDF) and normal human epidermal keratinocyte (NHEK). Angiogenic activity of asiaticoside was evaluated using chick-chorioallantoic membrane (CAM) assay. FT-IR and PXRD results revealed the amidation after DHT to enhance the crystallinity of the prepared sponges. The prepared sponges had high porosity comprising high Alst-loaded amount that exhibited more compact structure. Alst enhanced hydrophobicity therefore it reduced the fluid absorption and WVTR together with bio-adhesion of the prepared sponge dressings. Porosity of all sponges was more than 85% therefore resulting in their high OP. Enhancing hydrophobicity of the material by Alst and more homogeneity caused by NMP eventually retarded the asiaticoside release for 7 days

Chitosan–aluminum monostearate composite sponge dressing containing asiaticoside for wound healing and angiogenesis promotion in chronic wound

Energy Technology Data Exchange (ETDEWEB)

Phaechamud, Thawatchai, E-mail: thawatchaienator@gmail.com [Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom 73000 (Thailand); Yodkhum, Kotchamon, E-mail: marskotchamon@gmail.com [Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom 73000 (Thailand); Charoenteeraboon, Juree, E-mail: juree@su.ac.th [Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom 73000 (Thailand); Tabata, Yasuhiko, E-mail: yasuhiko@frontier.kyoto-u.ac.jp [Department of Biomaterials, Field of tissue engineering, Institute for Frontier Medical Science, Kyoto University, Kyoto 606-8507 (Japan)

2015-05-01

There are many factors that delay healing in chronic wounds including lowering level of growth factors and increasing exudate level comprising high amount of tissue destructive enzymes. Asiaticoside possesses interesting wound healing and angiogenic activities that are employed to stimulate tissue regeneration in wound healing application. This study attempted to develop chitosan–aluminum monostearate (Alst) composite sponge containing asiaticoside for use as an absorbent medical dressing in chronic wound. N-methyl-2-pyrrolidone (NMP) was used to enhance homogeneity of asiaticoside in the polymer composite matrix. The sponge dressings were prepared by lyophilization and dehydrothermal treatment (DHT). Functional group interaction, crystallinity, and morphology of the prepared sponges were investigated using FT-IR, PXRD, and SEM, respectively. Physicochemical properties, porosity, hydrophilic/hydrophobic properties and mechanical property, were evaluated. Wound dressing properties, water vapor transmission rate (WVTR), fluid absorbency, oxygen permeation (OP), and bio-adhesive property, were investigated. In vitro asiaticoside release study was conducted using immersion method. Cytotoxicity was studied in normal human dermal fibroblast (NHDF) and normal human epidermal keratinocyte (NHEK). Angiogenic activity of asiaticoside was evaluated using chick-chorioallantoic membrane (CAM) assay. FT-IR and PXRD results revealed the amidation after DHT to enhance the crystallinity of the prepared sponges. The prepared sponges had high porosity comprising high Alst-loaded amount that exhibited more compact structure. Alst enhanced hydrophobicity therefore it reduced the fluid absorption and WVTR together with bio-adhesion of the prepared sponge dressings. Porosity of all sponges was more than 85% therefore resulting in their high OP. Enhancing hydrophobicity of the material by Alst and more homogeneity caused by NMP eventually retarded the asiaticoside release for 7 days

Development of a wound healing index for patients with chronic wounds.

Science.gov (United States)

Horn, Susan D; Fife, Caroline E; Smout, Randall J; Barrett, Ryan S; Thomson, Brett

2013-01-01

Randomized controlled trials in wound care generalize poorly because they exclude patients with significant comorbid conditions. Research using real-world wound care patients is hindered by lack of validated methods to stratify patients according to severity of underlying illnesses. We developed a comprehensive stratification system for patients with wounds that predicts healing likelihood. Complete medical record data on 50,967 wounds from the United States Wound Registry were assigned a clear outcome (healed, amputated, etc.). Factors known to be associated with healing were evaluated using logistic regression models. Significant variables (p healing for each wound type. Some variables predicted significantly in nearly all models: wound size, wound age, number of wounds, evidence of bioburden, tissue type exposed (Wagner grade or stage), being nonambulatory, and requiring hospitalization during the course of care. Variables significant in some models included renal failure, renal transplant, malnutrition, autoimmune disease, and cardiovascular disease. All models validated well when applied to the holdout sample. The "Wound Healing Index" can validly predict likelihood of wound healing among real-world patients and can facilitate comparative effectiveness research to identify patients needing advanced therapeutics. © 2013 by the Wound Healing Society.

Photobiomodulation of surgical wound dehiscence in a diabetic individual by low-level laser therapy following median sternotomy

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Snehil Dixit

2013-01-01

Full Text Available In this single case study, we attempt to outline the possible effect of low-level laser therapy (LLLT on delayed wound healing and pain in chronic dehiscent sternotomy of a diabetic individual. The methods that were employed to evaluate changes pre and post irradiation were wound photography, wound area measurement, pressure ulcer scale of healing (PUSH, and visual analogue scale (VAS for pain. After irradiation, proliferation of healthy granulation tissue was observed with decrease in scores of PUSH for sternal dehiscence and VAS for bilateral shoulders and sternal dehiscence. We found that LLLT irradiation could be a novel method of treatment for chronic sternal dehiscence following coronary artery bypass grafting, as it augments wound healing with an early closure of the wound deficit. Hence, this might be translated into an early functional rehabilitation and decreased pain perception of an individual following surgical complication.

Wound complications and surgical events in de novo heart transplant patients treated with everolimus

DEFF Research Database (Denmark)

Rashidi, Mitra; Esmaily, Sorosh; Fiane, Arnt E

2016-01-01

OBJECTIVES: The use of mammalian target of rapamycin (mTOR) inhibitors have been limited by adverse events (AE), including delayed wound healing. We retrospectively reviewed all AE and serious AE (SAE) in The Scandinavian heart transplant (HTx) everolimus (EVE) de novo trial with early calcineurin...

[Treatment of the infected wound with exposed silver-ring vascular graft and delayed Thiersch method of skin transplant covering ].

Science.gov (United States)

Nenezić, Dragoslav; Pandaitan, Simon; Ilijevski, Nenad; Matić, Predrag; Gajin, Predag; Radak, Dorde

2005-01-01

Although the incidence of prosthetic infection is low (1%-6%), the consequences (limb loss or death) are dramatic for a patient, with high mortality rate (25%-75%) and limb loss in 40%-75% of cases. In case of Szilagyi's grade III infection, standard procedure consists of the excision of prosthesis and wound debridement. Alternative method is medical treatment. This is a case report of a patient with prosthetic infection of Silver-ring graft, used for femoropopliteal reconstruction, in whom an extreme skin necrosis developed in early postoperative period. This complication was successfully treated medically. After repeated debridement and wound-packing, the wound was covered using Thiersch skin graft.

Aloe vera for treating acute and chronic wounds.

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Dat, Anthony D; Poon, Flora; Pham, Kim B T; Doust, Jenny

2012-02-15

no difference in the proportion of patients completely healed at follow up after skin biopsies. In people with chronic wounds, one trial found no statistically significant difference in pressure ulcer healing with Aloe vera (RR 0.10, 95% CI -1.59 to 1.79) and in a trial of surgical wounds healing by secondary intention Aloe vera significantly delayed healing (mean difference 30 days, 95% CI 7.59 to 52.41). Clinical heterogeneity precluded meta-analysis. The poor quality of the included trials indicates that the trial results must be viewed with extreme caution as they have a high risk of bias. There is currently an absence of high quality clinical trial evidence to support the use of Aloe vera topical agents or Aloe vera dressings as treatments for acute and chronic wounds.

Cutaneous signs of piety.

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Ramesh, V; Al Aboud, Khalid

2014-07-01

It is important for dermatologists to be aware of cutaneous changes related to religious practices to help in their recognition and management. The anatomic location of cutaneous lesions associated with friction from praying varies based on religious practice. Allergic contact dermatitis from products and substances commonly used in worshipping also vary by religion. Some religious practices may render individuals prone to infections that manifest on the skin. Tattoos of godly figures also may adorn the body. Religious practices also have been implicated in cases of urticaria, köbnerization, and leukoderma. This article reviews the clinical presentation of some of the most common cutaneous changes that occur in individuals who practice the following religions: Christianity, Islam, Judaism, Hinduism, and Sikhism.

Emerging infectious diseases with cutaneous manifestations: Fungal, helminthic, protozoan and ectoparasitic infections.

Science.gov (United States)

Kollipara, Ramya; Peranteau, Andrew J; Nawas, Zeena Y; Tong, Yun; Woc-Colburn, Laila; Yan, Albert C; Lupi, Omar; Tyring, Stephen K

2016-07-01

Given increased international travel, immigration, changing climate conditions, and the increased incidence of iatrogenic immunosuppression, fungal, protozoan, helminthic, and ectoparasitic infections that were once uncommon are being seeing more frequently in the Western hemisphere. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. In addition, delays in the diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. We review the epidemiology, cutaneous manifestations, diagnostic modalities, and treatment options for emerging fungal, protozoan, helminthic, and ectoparasitic infections. It should be noted, however, that throughout this review we cite statistics documenting their increased incidence to back-up these infections as emerging, and although some of the diagnoses are clinical, others rely on newer laboratory tests, and the possibility exists that the increased incidence could be caused by better detection methods. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Cutaneous Manifestations of Human and Murine Leishmaniasis

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Breanna M. Scorza

2017-06-01

Full Text Available The leishmaniases are diseases caused by pathogenic protozoan parasites of the genus Leishmania. Infections are initiated when a sand fly vector inoculates Leishmania parasites into the skin of a mammalian host. Leishmania causes a spectrum of inflammatory cutaneous disease manifestations. The type of cutaneous pathology is determined in part by the infecting Leishmania species, but also by a combination of inflammatory and anti-inflammatory host immune response factors resulting in different clinical outcomes. This review discusses the distinct cutaneous syndromes described in humans, and current knowledge of the inflammatory responses associated with divergent cutaneous pathologic responses to different Leishmania species. The contribution of key hematopoietic cells in experimental cutaneous leishmaniasis in mouse models are also reviewed and compared with those observed during human infection. We hypothesize that local skin events influence the ensuing adaptive immune response to Leishmania spp. infections, and that the balance between inflammatory and regulatory factors induced by infection are critical for determining cutaneous pathology and outcome of infection.

Cell Adhesion Molecules Are Mediated by Photobiomodulation at 660 nm in Diabetic Wounded Fibroblast Cells

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Nicolette N. Houreld

2018-04-01

Full Text Available Diabetes affects extracellular matrix (ECM metabolism, contributing to delayed wound healing and lower limb amputation. Application of light (photobiomodulation, PBM has been shown to improve wound healing. This study aimed to evaluate the influence of PBM on cell adhesion molecules (CAMs in diabetic wound healing. Isolated human skin fibroblasts were grouped into a diabetic wounded model. A diode laser at 660 nm with a fluence of 5 J/cm2 was used for irradiation and cells were analysed 48 h post-irradiation. Controls consisted of sham-irradiated (0 J/cm2 cells. Real-time reverse transcription (RT quantitative polymerase chain reaction (qPCR was used to determine the expression of CAM-related genes. Ten genes were up-regulated in diabetic wounded cells, while 25 genes were down-regulated. Genes were related to transmembrane molecules, cell–cell adhesion, and cell–matrix adhesion, and also included genes related to other CAM molecules. PBM at 660 nm modulated gene expression of various CAMs contributing to the increased healing seen in clinical practice. There is a need for new therapies to improve diabetic wound healing. The application of PBM alongside other clinical therapies may be very beneficial in treatment.

Managing painful chronic wounds: the Wound Pain Management Model

DEFF Research Database (Denmark)

Price, Patricia; Fogh, Karsten; Glynn, Chris

2007-01-01

of the pain experience: location, duration, intensity, quality, onset and impact on activities of daily living. Holistic management must be based on a safe and effective mix of psychosocial approaches together with local and systemic pain management. It is no longer acceptable to ignore or inadequately...... to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions...... document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase. Udgivelsesdato: 2007-Apr...

Cutavirus in Cutaneous Malignant Melanoma

DEFF Research Database (Denmark)

Mollerup, Sarah; Fridholm, Helena; Vinner, Lasse

2017-01-01

A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains to be in...

Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

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Ayesha Bhatia

2016-01-01

Full Text Available Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5–treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs.

Science.gov (United States)

Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T; Li, Wei

2016-01-01

Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

Non-invasive in vivo characterization of skin wound healing using label-free multiphoton microscopy (Conference Presentation)

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Jones, Jake D.; Majid, Fariah; Ramser, Hallie; Quinn, Kyle P.

2017-02-01

Non-healing ulcerative wounds, such as diabetic foot ulcers, are challenging to diagnose and treat due to their numerous possible etiologies and the variable efficacy of advanced wound care products. Thus, there is a critical need to develop new quantitative biomarkers and diagnostic technologies that are sensitive to wound status in order to guide care. The objective of this study was to evaluate the utility of label-free multiphoton microscopy for characterizing wound healing dynamics in vivo and identifying potential differences in diabetic wounds. We isolated and measured an optical redox ratio of FAD/(NADH+FAD) autofluorescence to provide three-dimensional maps of local cellular metabolism. Using a mouse model of wound healing, in vivo imaging at the wound edge identified a significant decrease in the optical redox ratio of the epidermis (p≤0.0103) between Days 3 through 14 compared to Day 1. This decrease in redox ratio coincided with a decrease in NADH fluorescence lifetime and thickening of the epithelium, collectively suggesting a sensitivity to keratinocyte hyperproliferation. In contrast to normal wounds, we have found that keratinocytes from diabetic wounds remain in a proliferative state at later time points with a lower redox ratio at the wound edge. Microstructural organization and composition was also measured from second harmonic generation imaging of collagen and revealed differences between diabetic and non-diabetic wounds. Our work demonstrates label-free multiphoton microscopy offers potential to provide non-invasive structural and functional biomarkers associated with different stages of skin wound healing, which may be used to detect delayed healing and guide treatment.

Age-associated intracellular superoxide dismutase deficiency potentiates dermal fibroblast dysfunction during wound healing.

Science.gov (United States)

Fujiwara, Toshihiro; Dohi, Teruyuki; Maan, Zeshaan N; Rustad, Kristine C; Kwon, Sun Hyung; Padmanabhan, Jagannath; Whittam, Alexander J; Suga, Hirotaka; Duscher, Dominik; Rodrigues, Melanie; Gurtner, Geoffrey C

2017-07-04

Reactive oxygen species (ROS) impair wound healing through destructive oxidation of intracellular proteins, lipids and nucleic acids. Intracellular superoxide dismutase (SOD1) regulates ROS levels and plays a critical role in tissue homoeostasis. Recent evidence suggests that age-associated wound healing impairments may partially result from decreased SOD1 expression. We investigated the mechanistic basis by which increased oxidative stress links to age-associated impaired wound healing. Fibroblasts were isolated from unwounded skin of young and aged mice, and myofibroblast differentiation was assessed by measuring α-smooth muscle actin and collagen gel contraction. Excisional wounds were created on young and aged mice to study the healing rate, ROS levels and SOD1 expression. A mechanistic link between oxidative stress and fibroblast function was explored by assessing the TGF-β1 signalling pathway components in young and aged mice. Age-related wounds displayed reduced myofibroblast differentiation and delayed wound healing, consistent with a decrease in the in vitro capacity for fibroblast-myofibroblast transition following oxidative stress. Young fibroblasts with normal SOD1 expression exhibited increased phosphorylation of ERK in response to elevated ROS. In contrast, aged fibroblasts with reduced SOD1 expression displayed a reduced capacity to modulate intracellular ROS. Collectively, age-associated wound healing impairments are associated with fibroblast dysfunction that is likely the result of decreased SOD1 expression and subsequent dysregulation of intracellular ROS. Strategies targeting these mechanisms may suggest a new therapeutic approach in the treatment of chronic non-healing wounds in the aged population. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound healing by interfering with host defense and repair mechanisms.

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Athanasopoulos, Athanasios N; Economopoulou, Matina; Orlova, Valeria V; Sobke, Astrid; Schneider, Darius; Weber, Holger; Augustin, Hellmut G; Eming, Sabine A; Schubert, Uwe; Linn, Thomas; Nawroth, Peter P; Hussain, Muzaffar; Hammes, Hans-Peter; Herrmann, Mathias; Preissner, Klaus T; Chavakis, Triantafyllos

2006-04-01

Staphylococcus aureus is a major human pathogen interfering with host-cell functions. Impaired wound healing is often observed in S aureus-infected wounds, yet, the underlying mechanisms are poorly defined. Here, we identify the extracellular adherence protein (Eap) of S aureus to be responsible for impaired wound healing. In a mouse wound-healing model wound closure was inhibited in the presence of wild-type S aureus and this effect was reversible when the wounds were incubated with an isogenic Eap-deficient strain. Isolated Eap also delayed wound closure. In the presence of Eap, recruitment of inflammatory cells to the wound site as well as neovascularization of the wound were prevented. In vitro, Eap significantly reduced intercellular adhesion molecule 1 (ICAM-1)-dependent leukocyte-endothelial interactions and diminished the consequent activation of the proinflammatory transcription factor nuclear factor kappaB (NFkappaB) in leukocytes associated with a decrease in expression of tissue factor. Moreover, Eap blocked alphav-integrin-mediated endothelial-cell migration and capillary tube formation, and neovascularization in matrigels in vivo. Collectively, the potent anti-inflammatory and antiangiogenic properties of Eap provide an underlying mechanism that may explain the impaired wound healing in S aureus-infected wounds. Eap may also serve as a lead compound for new anti-inflammatory and antiangiogenic therapies in several pathologies.

Remote Cutaneous Breast Carcinoma Metastasis Mimicking Dermatitis

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Annakan V Navaratnam

2015-01-01

Full Text Available Cutaneous metastases from primary internal malignancies are an uncommon presentation. Cutaneous metastases are more frequently seen in breast cancer than in any other visceral malignancy in women. Medical practitioners should be vigilant of the possibility of unusual presentations of metastatic disease in breast cancer patients with lobular carcinoma presenting as cutaneous lesions mimicking benign dermatological conditions. Herein, we present a case of a 75-year-old woman presenting with cutaneous lobular breast carcinoma metastases on her anterior right leg, which had previously been misdiagnosed as dermatitis for 9 years.

Enhanced Healing of Diabetic Wounds by Subcutaneous Administration of Human Umbilical Cord Derived Stem Cells and Their Conditioned Media

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Chandrama Shrestha

2013-01-01

Full Text Available Objective. Mesenchymal stem cells (MSCs isolated from the umbilical cord and their conditioned media (CM can be easily obtained and refined compared with stem cells from other sources. Here, we explore the possibility of the benefits of these cells in healing diabetic wounds. Methodology and Results. Delayed wound healing animal models were established by making a standard wound on the dorsum of eighteen db/db mice, which were divided into three groups with six mice in each: groups I, II, and III received PBS, UC-MSC, and CM, respectively. UC-MSC and their CM significantly accelerated wound closure compared to PBS-treated wounds, and it was most rapid in CM-injected wounds. In day-14 wounds, significant difference in capillary densities among the three groups was noted (n=6; P<0.05, and higher levels of VEGF, PDGF, and KGF expression in the CM- and UC-MSC-injected wounds compared to the PBS-treated wounds were seen. The expression levels of PDGF-β and KGF were higher in CM-treated wounds than those in UC-MSC-treated wounds. Conclusion. Both the transplantation of UC-MSC and their CM are beneficial to diabetic wound healing, and CM has been shown to be therapeutically better than UC-MSC, at least in the context of diabetic wound healing.

Honey as a topical treatment for wounds.

Science.gov (United States)

Jull, Andrew B; Cullum, Nicky; Dumville, Jo C; Westby, Maggie J; Deshpande, Sohan; Walker, Natalie

2015-03-06

Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing. The objective of this review was to assess the effects of honey compared with alternative wound dressings and topical treatments on the of healing of acute (e.g. burns, lacerations) and/or chronic (e.g. venous ulcers) wounds. For this update of the review we searched the Cochrane Wounds Group Specialised Register (searched 15 October 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 9); Ovid MEDLINE (1946 to October Week 1 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 13 October 2014); Ovid EMBASE (1974 to 13 October 2014); and EBSCO CINAHL (1982 to 15 October 2014). Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. All data have been subsequently checked by two more authors. We identified 26 eligible trials (total of 3011 participants). Three trials evaluated the effects of honey in minor acute wounds, 11 trials evaluated honey in burns, 10 trials recruited people with different chronic wounds including two in people with venous leg ulcers, two trials in people with diabetic foot ulcers and single trials in infected post-operative wounds, pressure injuries, cutaneous Leishmaniasis and Fournier's gangrene. Two trials recruited a mixed population of people with acute and chronic wounds. The quality of the evidence varied between different comparisons and

Review on strategies for biofouling mitigation in spiral wound membrane systems

KAUST Repository

Bucs, Szilard

2018-02-01

Because of the uneven distribution of fresh water in time and space, a large number of regions are experiencing water scarcity and stress. Membrane based desalination technologies have the potential to solve the fresh water crisis in coastal areas. However, in many cases membrane performance is restricted by biofouling. The objective of this review is to provide an overview on the state of the art strategies to control biofouling in spiral wound reverse osmosis membrane systems and point to possible future research directions. A critical review on biofouling control strategies such as feed water pre-treatment, membrane surface modification, feed spacer geometry optimization and hydrodynamics in spiral wound membrane systems is presented. In conclusion, biofouling cannot be avoided in the long run, and thus biofouling control strategies should focus on delaying the biofilm formation, reducing its impact on membrane performance and enhancing biofilm removal by advanced cleaning strategies. Therefore, future studies should aim on: (i) biofilm structural characterization; (ii) understanding to what extent biofilm properties affect membrane filtration performance, and (iii) developing methods to engineer biofilm properties such that biofouling would have only a low or delayed impact on the filtration process and accumulated biomass can be easily removed.

The effects of psychological interventions on wound healing: A systematic review of randomized trials.

Science.gov (United States)

Robinson, Hayley; Norton, Sam; Jarrett, Paul; Broadbent, Elizabeth