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Knorr C.,Justus Liebig University | Marks D.,Justus Liebig University | Gerstberger R.,Justus Liebig University | Muhlradt P.F.,Wound Healing Research Group | And 2 more authors.
Neuroscience Letters | Year: 2010

We investigated whether an inflammation-dependent activation of the brain occurs in response to systemic intraperitoneal (i.p.) or local injections of macrophage-activating lipopeptide-2 (MALP-2) into a subcutaneous (s.c.) air pouch, and whether local (peripheral) or central cyclooxygenase (COX)-2-dependent formations of prostaglandin E2 (PGE2) are involved in MALP-2-induced illness responses. Body temperature, activity, food and water intake were measured telemetrically. Local (s.c.) and circulating levels of PGE2 were measured by an ELISA. Inflammatory activation of the brain in response to MALP-2 was determined by immunohistochemical detection of the transcription factors NFκB and STAT3 in cell nuclei as well as the appearance of COX-2 at the same sites. S.c. treatment with the preferential COX-2 inhibitor meloxicam attenuated, but not abolished fever induced by local injections of MALP-2 into the pouch. Local MALP-2-induced formation of PGE2 was blunted by treatment with meloxicam. In the brain, i.p. stimulation with MALP-2-induced nuclear STAT3- and NFκB-translocation in the vasculature and the sensory circumventricular organs, which was accompanied by an increase in COX-2 immunoreactivity (IR) in endothelial cells. Local MALP-2-treatment induced a moderate STAT3 activation and a small but significant increase in COX-2 IR while no NFκB-activation could be observed in the brains of these animals. We demonstrated that the activation of the brain STAT3 (NFκB)-COX-2 singling cascade seems to be involved in the manifestation of brain-controlled illness symptoms induced by systemic and local inflammatory stimulation with MALP-2. The present data further suggest a contribution of peripherally produced PGE2 to MALP-2-induced activation of brain sites implicated in fever. © 2010 Elsevier Ireland Ltd. Source


Zuo K.J.,Wound Healing Research Group | Tredget E.E.,University of Alberta
Burns | Year: 2014

Marjolin's ulcer is an aggressive ulcerating cutaneous malignancy that may arise in chronically inflamed or traumatized skin. Frequently overlooked, this rare condition is classically associated with burn scars, with the process of malignant degeneration typically occurring over two to three decades. The most common histopathological pattern is squamous cell carcinoma; however, compared to typical squamous cell carcinomas, Marjolin's ulcers have an increased rate of metastasis. The correlation between radiotherapy for benign hypertrophic scarring and carcinogenesis is controversial, with few reports in the literature. We present a unique case of a 61 year old Caucasian male who was burned by scald at age 4, received radiotherapy for his post-burn hypertrophic scars, and later developed multiple Marjolin's ulcers on his left arm, chest, and right temporal scalp. Source


Medina A.,Wound Healing Research Group | Tredget E.E.,Wound Healing Research Group | Tredget E.E.,University of Alberta
Journal of Burn Care and Research | Year: 2013

Total nasal reconstruction requires the management of skin, cartilage, and nasal mucosa. This three-dimensional surgical approach is especially restricted in patients with severe deformities after deep panfacial burns. In this regard, the development of tissue fibrosis reduces the quality and reliability of surrounded donor sites, limiting the surgical options and flap survival outcomes. This report discusses the benefit of tissue protection procedures, such as flap delay and leech therapy, in the total nasal reconstruction of a patient with split-thickness skin grafts on donor sites for forehead and nasolabial flaps. © 2013 by the American Burn Association. Source


Zhu Z.,Wound Healing Research Group | Zhu Z.,Shantou University | Ding J.,Wound Healing Research Group | Ma Z.,Wound Healing Research Group | And 3 more authors.
Wound Repair and Regeneration | Year: 2016

Hypertrophic scars are caused by trauma or burn injuries to the deep dermis and can cause cosmetic disfigurement and psychological issues. Studies suggest that M2-like macrophages are pro-fibrotic and contribute to hypertrophic scar formation. A previous study from our lab showed that M2 macrophages were present in developing hypertrophic scar tissues in vivo at 3–4 weeks after wounding. In this study, the effect of systemic macrophage depletion on scar formation was explored at subacute phase of wound healing. Thirty-six athymic nude mice that received human skin transplants were randomly divided into macrophage depletion group and control group. The former received intraperitoneal injections of clodronate liposomes while the controls received sterile saline injections on day 7, 10, and 13 postgrafting. Wound area, scar thickness, collagen abundance and collagen bundle structure, mast cell infiltration, myofibroblast formation, M1, and M2 macrophages together with gene expression of M1 and M2 related factors in the grafted skin were investigated at 2, 4, and 8 weeks postgrafting. The transplanted human skin from the control group developed contracted, elevated, and thickened scars while the grafted skin from the depletion group healed with significant less contraction and elevation. Significant reductions in myofibroblast number, collagen synthesis, and hypertrophic fiber morphology as well as mast cell infiltration were observed in the depletion group compared to the control group. Macrophage depletion significantly reduced M1 and M2 macrophage number in the depletion group 2 weeks postgrafting as compared to the control group. These findings suggest that systemic macrophage depletion in subacute phase of wound healing reduces scar formation, which provides evidence for the pro-fibrotic role of macrophages in fibrosis of human skin as well as insight into the potential benefits of specifically depleting M2 macrophages in vivo. © 2016 by the Wound Healing Society Source


Ding J.,Wound Healing Research Group | Ma Z.,Wound Healing Research Group | Shankowsky H.A.,Wound Healing Research Group | Medina A.,Wound Healing Research Group | And 2 more authors.
Wound Repair and Regeneration | Year: 2013

Hypertrophic scars are a significant fibroproliferative disorder complicating deep injuries to the skin. We hypothesize that activated deep dermal fibroblasts are subject to regulation by bone marrow-derived mesenchymal stem cells (BM-MSCs), which leads to the development of excessive fibrosis following deep dermal injury. We found that the expression of fibrotic factors was higher in deep burn wounds compared with superficial burn wounds collected from burn patients with varying depth of skin injury. We characterized deep and superficial dermal fibroblasts, which were cultured from the deep and superficial dermal layers of normal uninjured skin obtained from abdominoplasty patients, and examined the paracrine effects of BM-MSCs on the fibrotic activities of the cells. In vitro, deep dermal fibroblasts were found higher in the messenger RNA (mRNA) levels of type 1 collagen, alpha smooth muscle actin, transforming growth factor beta, stromal cell-derived factor 1, and tissue inhibitor of metalloproteinase 1, an inhibitor of collagenase (matrix metalloproteinase 1). As well, deep dermal fibroblasts had low matrix metalloproteinase 1 mRNA, produced more collagen, and contracted collagen lattices significantly greater than superficial fibroblasts. By co-culturing layered fibroblasts with BM-MSCs in a transwell insert system, BM-MSCs enhanced the fibrotic behavior of deep dermal fibroblasts, which suggests a possible involvement of BM-MSCs in the pathogenesis of hypertrophic scarring. © 2013 by the Wound Healing Society. Source

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