Homocysteine? A Stealth Mediator of Impaired Wound Healing: A Preliminary Study
Abstract: The objective of this study was to clinically evaluate the amino acid homocysteine (Hcy) as a risk factor for impaired wound healing in 12 patients receiving topical human fibroblast-derived dermal substitute treatment for nonhealing lower-extremity wounds. Homocysteine is a significant risk factor for atherosclerotic vascular disease and is an inhibitor of nitric oxide (NO) bioactivity. The data from this preliminary study documented a correlation between elevated serum Hcy, significantly (P < 0.05) decreased wound NO bioactivity by measurement of wound fluid nitrate and nitrite (NOx, the stable oxidation products of NO), and impaired wound healing. In a single case report, successful treatment of elevated Hcy was documented to restore normal wound healing. In the authors? wound center, untreated, elevated Hcy was observed in 50% of patients with chronic, nonhealing wounds, 63% of patients with diabetic, neuropathic ulcers, and 47% of patients without diabetes with chronic, venous stasis ulcerations (n = 138). Elevated Hcy may inhibit wound NO bioactivity and impair wound healing by multiple pathways and may also alter wound granulation tissue formation by occupying the fibronectin domain of fibrin during provisional wound matrix formation. The authors suggest 1) that elevated Hcy may be a frequently encountered risk factor for impaired wound healing that may promote chronic wound development by significantly decreasing wound NO bioactivity and, perhaps, by modification of provisional wound matrix formation and 2) that the preferred treatment of elevated Hcy is with daily administration of L-methylfolate, pyridoxal 5?-phosphate, and methylcobalamin.
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Effect of Low-Energy Gallium Arsenide (GaAs, 904 nm) Laser Irradiation on Wound Healing in Rat Skin
The effect of laser on wound healing is controversial. This study examines the effects of low-level gallium arsenide (904 nm) laser irradiation on the wound healing process in a rat model. Twenty-four rats were used. Paired wounds were made on the shaved dorsal skin on either side of the midline. The rats were randomly divided into 3 groups (n = 8 in each group). Using a gallium arsenide laser, Group 1, Group 2, and Group 3 were irradiated with 0.31 J/cm2, 2.48 J/cm2, and 19 J/cm2, respectively. The wound on the right side of each animal received laser irradiation for 7 consecutive days, and the left side wound served as a control. On Day 21, bilateral wounds were excised and processed for light microscopy examination. Impaired collagen synthesis, large defect areas, degeneration of skin appendages, and presence of dermal granulation tissue were observed in laser-treated groups, while normal wound healing was found in control wounds. High-dose gallium arsenide laser irradiation appears to impair wound healing on Day 21 in a rat model.
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Compression Therapy for Foot Wounds: Overview and Case Reports
Abstract: Interstitial edema can impair wound healing. Compression is a well-documented, effective method to reduce interstitial edema associated with venous leg ulcers. However, there are few reports of its effectiveness in the management of foot wounds. The author presents 2 cases where multilayer compression bandages were instrumental in the treatment of foot wounds.
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PART II: Modulation of Radiation-Induced Delay in the Wound Healing by Ascorbic Acid in Mice Exposed to Different Doses of Hemi-Body Gamma Radiation
Abstract: Hemi-body irradiation in multiple fractionated doses is frequently used alone or in combination with surgery for the treatment of cancer. It produces both acute and late effects on the skin that have profound effects on surgical wounds. Because of the crucial practical importance of radiation exposure associated with skin wounds, it is imperative to investigate the efficacy of cost-effective nutritional factors in the reconstruction of irradiated wounds. Therefore, the effect of ascorbic acid treatment was studied on the healing of excision wounds in mice exposed to 2, 4, 6, or 8 Gy hemi-body gamma radiation. A full-thickness skin wound was created on the dorsum of 8- to 10-week-old Swiss albino mice after hemi-body exposure to 2, 4, 6, or 8 Gy. The progression of wound contraction was monitored periodically by capturing video images of wounds. Collagen, hexosamine, deoxyribonucleic acid (DNA), nitric oxide (NO), and histological profiles of excision wounds were also evaluated and either treated or not treated with ascorbic acid before exposure to 0 or 6 Gy. Irradiation caused a dose-dependent delay in wound contraction and wound healing time, while ascorbic acid pretreatment resulted in a significant elevation in the rate of wound contraction and a decrease in mean wound healing time. Treatment with ascorbic acid before irradiation enhanced the synthesis of collagen, hexosamine, DNA, and NO, while histological assessment revealed an improved collagen deposition and an increase in fibroblast and vascular densities. The present study demonstrates that ascorbic acid pretreatment has a beneficial effect on irradiated wounds and could be part of a strategy to ameliorate radiation-induced delay in wound repair.
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Vacuum-assisted Closure Therapy Attenuates the Inflammatory Response in a Porcine Acute Wound Healing Model
Porcine full-thickness wounds were treated with V.A.C.® Therapy (KCI, San Antonio, Tex) or moist wound dressing without negative pressure. V.A.C. Therapy related systemic effects included post-wound reduction in the number of peripheral blood monocytes and neutrophils during the inflammatory phase of wound healing, as well as reduced serum levels of the pro-inflammatory cytokines IFN-g and IL-6. Local effects included reduced concentrations of IL-8, TGF-b1, and TNF-a in wound fluid following V.A.C. Therapy. Collectively, these responses suggest that V.A.C. Therapy may attenuate the pro-inflammatory response following cutaneous wounding.
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Editorial Message
Rader and Barry (Football dressing for neuropathic forefoot ulcerations) describe an easy-to-use dressing technique that is repeatable, inexpensive, and effective for offloading the neuropathic plantar forefoot ulcer. Following the 2004 tsunami, many victims developed severe wound infections. Boykin and Baylis (Homocysteine—A stealth mediator of impaired wound ...
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A Topical Wound Disinfectant (Ethacridine Lactate) Differentially Affects the Production of Immunoregulatory Cytokines in Human Whole-Blood Cultures
Abstract: In order to ensure normal wound repair, the widespread use of topical antiseptics to control bacterial infections requires these chemicals to exhibit minimal interference with the physiological process of wound healing. Therefore, the influence of a topical antiseptic, ethacridine lactate, on the immune system was investigated in a whole-blood culture model. The effects of ethacridine lactate on the co-stimulated synthesis of a wide pattern of products and mediators (prostaglandin E2, transforming growth factor beta 1, interleukin-6, interleukin-10, interleukin-12, interferon-gamma, interleukin-5, and monocyte chemoattractant protein-1) were examined. Additionally, an immunosuppressive environment to simulate a condition that slows wound healing was generated by adding hydrocortisone to the cultures. The results revealed highly differentiated modifications of the leukocyte response caused by ethacridine lactate. The synthesis of some of the cytokines was strongly stimulated (interleukin-12, interferon-gamma), whereas that of others (interleukin-5, interleukin-10, or interleukin-6) was inhibited dose-dependently and with inter-individual variations. In conclusion, this is the first report to show that the topical antiseptic ethacridine lactate preferentially modulates Th1-type lymphocytes, suggesting an enhancement of antibacterial activities of the immune system.
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Matrix-Immobilized Growth Factor Gene Therapy Enhances Tissue Repair
Abstract: Multiple growth factor proteins have been evaluated as therapeutic agents for the treatment of chronic wounds. All have failed with the exception of one to produce clinically significant results. This is in part due to the labile nature of proteins, inadequate delivery methods, and poor retention within the wound. The authors have developed a matrix-immobilized gene therapy approach to overcome the limitations of protein therapy. This gene-activated matrix (GAM) approach consists of a biocompatible matrix that holds the gene therapy vector, increasing its availability to cells invading the wound site and serves as a scaffold to promote cellular in-growth. The wound healing activity of bovine Type I collagen formulated with a replication-incompetent adenoviral vector encoding platelet-derived growth factor-B is reviewed in three animal models. Increased granulation tissue formation and vascularization was seen in all three models compared to collagen alone-treated animals. These promising results have enabled the clinical evaluation of gene-activated matrices for the treatment of diabetic ulcers of the lower extremities.
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PART I: Modulation of Radiation-Induced Delay in the Wound Healing by Ascorbic Acid in Mice Exposed to Different Doses of Hemi-Body Gamma Radiation
Abstract: Hemi-body irradiation in multiple fractionated doses is frequently used alone or in combination with surgery for the treatment of cancer. It produces both acute and late effects on the skin that have profound effects on surgical wounds. Because of the crucial practical importance of radiation exposure associated with skin wounds, it is imperative to investigate the efficacy of cost-effective nutritional factors in the reconstruction of irradiated wounds. Therefore, the effect of ascorbic acid treatment was studied on the healing of excision wounds in mice exposed to 2, 4, 6, or 8 Gy hemi-body gamma radiation. A full-thickness skin wound was created on the dorsum of 8- to 10-week-old Swiss albino mice after hemi-body exposure to 2, 4, 6, or 8 Gy. The progression of wound contraction was monitored periodically by capturing video images of wounds. Collagen, hexosamine, deoxyribonucleic acid (DNA), nitric oxide (NO), and histological profiles of excision wounds were also evaluated and either treated or not treated with ascorbic acid before exposure to 0 or 6 Gy. Irradiation caused a dose-dependent delay in wound contraction and wound healing time, while ascorbic acid pretreatment resulted in a significant elevation in the rate of wound contraction and a decrease in mean wound healing time. Treatment with ascorbic acid before irradiation enhanced the synthesis of collagen, hexosamine, DNA, and NO, while histological assessment revealed an improved collagen deposition and an increase in fibroblast and vascular densities. The present study demonstrates that ascorbic acid pretreatment has a beneficial effect on irradiated wounds and could be part of a strategy to ameliorate radiation-induced delay in wound repair.
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Emerging Treatments in Diabetic Wound Care
Abstract: This paper reviews the physiology of wound healing and properties of the ?ideal? dressing and also reviews advanced wound therapeutics and dressings, such as growth factors and biological skin substitutes.
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