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Ardeshir Bayat - One of the best experts on this subject based on the ideXlab platform.
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Optical coherence tomography: a reliable alternative to invasive histological assessment of Acute Wound healing in human skin?
The British journal of dermatology, 2014Co-Authors: Nicholas S. Greaves, Brian Benatar, Sigrid Whiteside, Teresa A Alonso-rasgado, Mohamed Baguneid, Ardeshir BayatAbstract:BACKGROUND: Gold-standard assessment of Acute Wound healing has traditionally been through histological analysis of biopsied tissue. However, this process is invasive with recognized side-effects. Optical coherence tomography (OCT) is a noninvasive technique generating high-resolution real-time images of cutaneous architecture. OBJECTIVES: To compare OCT with histological assessment of in vivo Acute Wound healing and ascertain the level of agreement between modalities for measurement of defined cutaneous structures. METHODS: Punch biopsies (5�mm) were harvested from 50 healthy volunteers. Wounds healed by secondary intention until they were re-excised 7, 14, 21 or 28�days later depending on random group allocation. Wounds were assessed weekly for 6�weeks using OCT and compared with histological findings derived from time-matched biopsies. Dimensions of four cutaneous structures were measured using both modalities and the level of agreement was established by Bland-Altman analysis. The mean greyscale value (MGV) of the upper reticular dermis was derived from OCT images at all time points. RESULTS: Both techniques showed anatomical congruity in normal and Wounded skin with correlating architectural changes associated with inflammatory, proliferative and remodelling Wound healing phases. MGV was significantly increased 6�weeks after Wounding (P�=�0�001) and may represent a novel measure of Wound fibrosis. Despite good association of histomorphometric values with low but consistent bias (range -4�181 to 0�431�?m), Bland-Altman plots demonstrated poor agreement between OCT and histology. CONCLUSIONS: Optical coherence tomography enabled accurate assessment of healing tissue comparable with histological analysis of biopsy specimens. This noninvasive tool is highly suited to Wound assessment and may represent a diagnostic alternative to punch biopsies.
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current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during Acute Wound healing
Journal of Dermatological Science, 2013Co-Authors: Nicholas S. Greaves, Mohamed Baguneid, Kevin J Ashcroft, Ardeshir BayatAbstract:Cutaneous Wound healing ultimately functions to facilitate barrier restoration following injury-induced loss of skin integrity. It is an evolutionarily conserved, multi-cellular, multi-molecular process involving co-ordinated inter-play between complex signalling networks. Cellular proliferation is recognised as the third stage of this sequence. Within this phase, fibroplasia and angiogenesis are co-dependent processes which must be successfully completed in order to form an evolving extracellular matrix and granulation tissue. The resultant structures guide cellular infiltration, differentiation and secretory profile within the Wound environment and consequently have major influence on the success or failure of Wound healing. This review integrates in vitro, animal and human in vivo studies, to provide up to date descriptions of molecular and cellular interactions involved in fibroplasia and angiogenesis. Significant molecular networks include adhesion molecules, proteinases, cytokines and chemokines as well as a plethora of growth factors. These signals are produced by, and affect behaviour of, cells including fibroblasts, fibrocytes, keratinocytes, endothelial cells and inflammatory cells resulting in significant cellular phenotypic and functional plasticity, as well as controlling composition and remodelling of structural proteins including collagen and fibronectin. The interdependent relationship between angiogenesis and fibroplasia relies on dynamic reciprocity between cellular components, matrix proteins and bioactive molecules. Unbalanced regulation of any one component can have significant consequences resulting in delayed healing, chronic Wounds or abnormal scar formation. Greater understanding of angiogenic and fibroplastic mechanisms underlying chronic Wound pathogenesis has identified novel therapeutic targets and enabled development of improved treatment strategies including topical growth factors and skin substitutes.
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Identification of biomarkers in sequential biopsies of patients with chronic Wounds receiving simultaneous Acute Wounds: A genetic, histological, and noninvasive imaging study
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2012Co-Authors: Barbara Shih, Muhammad J. Sultan, Iskander H. Chaudhry, Kian T. Tan, Kavan S. Johal, Arshiya Marstan, Melody Tsai, Mohammed Baguneid, Ardeshir BayatAbstract:Chronic Wounds are common and lead to significant patient morbidity. A better understanding of their pathogenesis and relevant biomarkers are required. We compared Acute and chronic Wounds in the same individual using noninvasive imaging including spectrophotometric intracutaneous analysis (SIAscopy) and full-field laser perfusion imaging. Gene expression analysis was also performed on sequential biopsies. Whole genome gene expression microarray analysis (44k), quantitative polymerase chain reaction, and immunohistochemistry were carried out to determine gene expression levels in tissue biopsies. Fifteen Caucasian patients with chronic venous ulcers had biopsies of the Wound edges and simultaneously had an Acute Wound created on their upper arm on days 0, 7, and 14. SIAscopy revealed increased levels of melanin (p
Nicholas S. Greaves - One of the best experts on this subject based on the ideXlab platform.
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Optical coherence tomography: a reliable alternative to invasive histological assessment of Acute Wound healing in human skin?
The British journal of dermatology, 2014Co-Authors: Nicholas S. Greaves, Brian Benatar, Sigrid Whiteside, Teresa A Alonso-rasgado, Mohamed Baguneid, Ardeshir BayatAbstract:BACKGROUND: Gold-standard assessment of Acute Wound healing has traditionally been through histological analysis of biopsied tissue. However, this process is invasive with recognized side-effects. Optical coherence tomography (OCT) is a noninvasive technique generating high-resolution real-time images of cutaneous architecture. OBJECTIVES: To compare OCT with histological assessment of in vivo Acute Wound healing and ascertain the level of agreement between modalities for measurement of defined cutaneous structures. METHODS: Punch biopsies (5�mm) were harvested from 50 healthy volunteers. Wounds healed by secondary intention until they were re-excised 7, 14, 21 or 28�days later depending on random group allocation. Wounds were assessed weekly for 6�weeks using OCT and compared with histological findings derived from time-matched biopsies. Dimensions of four cutaneous structures were measured using both modalities and the level of agreement was established by Bland-Altman analysis. The mean greyscale value (MGV) of the upper reticular dermis was derived from OCT images at all time points. RESULTS: Both techniques showed anatomical congruity in normal and Wounded skin with correlating architectural changes associated with inflammatory, proliferative and remodelling Wound healing phases. MGV was significantly increased 6�weeks after Wounding (P�=�0�001) and may represent a novel measure of Wound fibrosis. Despite good association of histomorphometric values with low but consistent bias (range -4�181 to 0�431�?m), Bland-Altman plots demonstrated poor agreement between OCT and histology. CONCLUSIONS: Optical coherence tomography enabled accurate assessment of healing tissue comparable with histological analysis of biopsy specimens. This noninvasive tool is highly suited to Wound assessment and may represent a diagnostic alternative to punch biopsies.
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current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during Acute Wound healing
Journal of Dermatological Science, 2013Co-Authors: Nicholas S. Greaves, Mohamed Baguneid, Kevin J Ashcroft, Ardeshir BayatAbstract:Cutaneous Wound healing ultimately functions to facilitate barrier restoration following injury-induced loss of skin integrity. It is an evolutionarily conserved, multi-cellular, multi-molecular process involving co-ordinated inter-play between complex signalling networks. Cellular proliferation is recognised as the third stage of this sequence. Within this phase, fibroplasia and angiogenesis are co-dependent processes which must be successfully completed in order to form an evolving extracellular matrix and granulation tissue. The resultant structures guide cellular infiltration, differentiation and secretory profile within the Wound environment and consequently have major influence on the success or failure of Wound healing. This review integrates in vitro, animal and human in vivo studies, to provide up to date descriptions of molecular and cellular interactions involved in fibroplasia and angiogenesis. Significant molecular networks include adhesion molecules, proteinases, cytokines and chemokines as well as a plethora of growth factors. These signals are produced by, and affect behaviour of, cells including fibroblasts, fibrocytes, keratinocytes, endothelial cells and inflammatory cells resulting in significant cellular phenotypic and functional plasticity, as well as controlling composition and remodelling of structural proteins including collagen and fibronectin. The interdependent relationship between angiogenesis and fibroplasia relies on dynamic reciprocity between cellular components, matrix proteins and bioactive molecules. Unbalanced regulation of any one component can have significant consequences resulting in delayed healing, chronic Wounds or abnormal scar formation. Greater understanding of angiogenic and fibroplastic mechanisms underlying chronic Wound pathogenesis has identified novel therapeutic targets and enabled development of improved treatment strategies including topical growth factors and skin substitutes.
Esther Middelkoop - One of the best experts on this subject based on the ideXlab platform.
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Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus Acute Wounds
The Journal of investigative dermatology, 1998Co-Authors: Miriam A.m. Loots, Evert N. Lamme, Jimmy Zeegelaar, Jan R. Mekkes, Jan D. Bos, Esther MiddelkoopAbstract:In diabetic patients, Wound healing is impaired. We studied the pathogenesis behind this clinical observation by characterizing the pattern of deposition of extracellular matrix (ECM) molecules and the cellular infiltrate in chronic (>8 wk) diabetic Wounds, compared with chronic venous ulcers and an Acute Wound healing model. Punch biopsies were obtained from the chronic ulcer margins and control samples were collected from upper leg skin 5, 19, 28 d and 12 and 18 mo postWounding (p.w.). T cells, B cells, plasma cells, granulocytes and macrophages, and the ECM molecules fibronectin (FN), chondroitin sulfate (CS), and tenascin (TN) were visualized using immunohistochemical techniques. Expression of FN, CS, and TN was detected in dermal tissue early in normal Wound healing (5–19 d p.w.). Abundant staining was seen 3 mo p.w., returning to preWounding levels after 12–18 mo p.w. In the dermis of chronic diabetic and venous ulcers with a duration of 12 mo or more, a prolonged presence of these ECM molecules was noted. Compared with normal Wound healing: (i) the CD4/CD8 ratio in chronic Wounds was significantly lower (p + T cells; (ii) a significantly higher number of macrophages was present in the edge of both type of chronic ulcers (p versus day 29 p.w.); and (iii) more B cells and plasma cells were detected in both type of chronic Wounds compared with any day in the Acute Wound healing model (p + and p + cells). These data indicate that important differences exist in the cellular infiltrate and ECM expression patterns of Acute, healing versus chronic Wounds, which may be related to the nonhealing status of chronic Wounds.
Vincent Falanga - One of the best experts on this subject based on the ideXlab platform.
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Human Wound fluid from Acute Wounds stimulates fibroblast and endothelial cell growth
Journal of the American Academy of Dermatology, 1991Co-Authors: Matthew H. Katz, William H. Eaglstein, Alfred F. Alvarez, Robert S. Kirsner, Vincent FalangaAbstract:One proposed mechanism for the beneficial effect of occlusive dressings on healing is the maintenance of contact between the Wound bed and accumulated Wound fluid, which is thought to contain growth stimulatory substances. We have examined the effect of human Wound fluid on the in vitro growth of human dermal fibroblasts and umbilical vein endothelial cells. Acute Wound fluid was collected from six patients undergoing split-thickness skin grafting. The Acute Wound fluid was sterilely collected daily from underneath a vapor-permeable membrane applied to the donor site and changed every 24 hours for 3 days postoperatively. After seeding in optimal growth media (control) on day 0, cultures of human dermal fibroblasts and umbilical vein endothelial cells were supplemented with or without Acute Wound fluid on the next day (day 1) and on day 3. As determined by cell counts, 2% Acute Wound fluid stimulated the growth of human dermal fibroblasts (p
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Human Wound fluid from Acute Wounds stimulates fibroblast and endothelial cell growth.
Journal of the American Academy of Dermatology, 1991Co-Authors: Matthew H. Katz, William H. Eaglstein, Alfred F. Alvarez, Robert S. Kirsner, Vincent FalangaAbstract:One proposed mechanism for the beneficial effect of occlusive dressings on healing is the maintenance of contact between the Wound bed and accumulated Wound fluid, which is thought to contain growth stimulatory substances. We have examined the effect of human Wound fluid on the in vitro growth of human dermal fibroblasts and umbilical vein endothelial cells. Acute Wound fluid was collected from six patients undergoing split-thickness skin grafting. The Acute Wound fluid was sterilely collected daily from underneath a vapor-permeable membrane applied to the donor site and changed every 24 hours for 3 days postoperatively. After seeding in optimal growth media (control) on day 0, cultures of human dermal fibroblasts and umbilical vein endothelial cells were supplemented with or without Acute Wound fluid on the next day (day 1) and on day 3. As determined by cell counts, 2% Acute Wound fluid stimulated the growth of human dermal fibroblasts (p less than 0.05) and umbilical vein endothelial cells (p less than 0.01) when these cells were cultured in 2% fetal bovine serum and endothelial growth medium, respectively. Wound fluid from postoperative days 1 or 3 caused the same level of stimulation. The addition of an anti-platelet-derived growth factor antibody to Wound fluid resulted in a 45% mean reduction in its stimulatory effect on fibroblast growth (p less than 0.02), suggesting that platelet-derived growth factor contributes to the observed effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Michael Stacey - One of the best experts on this subject based on the ideXlab platform.
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Induction of MMP-1, MMP-3 and TIMP-1 in normal dermal fibroblasts by chronic venous leg ulcer Wound fluid*.
International wound journal, 2008Co-Authors: Kavitha Subramaniam, Michael Stacey, Cheryl M. Pech, Hilary J. WallaceAbstract:In the Wound bed of chronic venous leg ulcers, an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may cause excessive proteolysis and impair Wound granulation. Soluble mediators in the Wound environment may be responsible for this imbalance. The in vitro effect of Wound fluid from venous leg ulcers on dermal fibroblast production of MMP-1, MMP-3 and TIMP-1 was compared with the effect of Acute Wound fluid from two different sources: fluid from post-mastectomy axillary drains and fluid from skin graft donor sites. Significantly higher MMP-1 and MMP-3 levels were induced by chronic venous leg ulcer Wound fluid compared with both types of Acute Wound fluid (P < 0.005). Chronic venous ulcer Wound fluid reduced TIMP-1 protein levels significantly more than Acute graft fluid (P < 0.05). Venous ulcer Wound fluid significantly increased MMP-1 and MMP-3 production in dermal fibroblasts and reduced TIMP-1 production, confirming that mediators in the leg ulcer microenvironment can potentially induce excessive proteolysis in the ulcer dermis by altering the balance between MMPs and TIMPs. Inflammatory mediators including interleukin-1beta and tumour necrosis factor-alpha can induce these MMPs. Further work is required to confirm the factors responsible for the induction of a high MMP and low TIMP profile in fibroblasts by venous ulcer Wound fluid.
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iron and 8 isoprostane levels in Acute and chronic Wounds
Journal of Investigative Dermatology, 2003Co-Authors: Sim Yeohellerton, Michael StaceyAbstract:The purpose of this study was to determine differences in iron and iron protein (ferritin and transferrin) levels in chronic venous ulcers and Acute Wounds. The deleterious effect of iron in free-radical-induced tissue damage was indirectly examined by assessing 8-isoprostane levels and antioxidant status in Wound fluid samples. Wound fluid samples from chronic leg ulcers in nonhealing and healing phases and Wound fluid from mastectomy Wounds were assayed for ferritin, transferrin, total iron, 8-isoprostane, and total antioxidant status. Immunohistochemistry and Perls' staining were performed on paired biopsies from chronic leg ulcers and on normal skin biopsies. Chronic Wound fluid had significantly greater levels of ferritin (p < 0.05) and lower levels of transferrin (p < 0.001) than Acute Wound fluid and there was a significant reduction in the level of ferritin in healing compared to nonhealing chronic leg ulcers (p < 0.05). No significant differences were observed in the levels of total iron present in the Wound fluids. Histologic staining showed consistently more ferritin and ferric iron in chronic Wound tissue than in normal skin. Elevated levels of 8-isoprostane and antioxidants were observed for chronic Wound fluid compared to Acute Wound fluid (p < 0.001). These results suggest the existence of an environment of oxidative stress in chronic Wounds and the likely contribution of iron to exacerbating tissue damage and delaying healing in these Wounds.