Showing papers on "Chronic wound published in 1998"

Animal models for wound repair

Abstract: Progress in wound pharmacology is dependent on the availability of suitable animal wound models. All animal models try to reflect human wound healing problems. In acute models it is easier to achieve approximations to the clinical situation than in models for the chronic wound.

Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers

Abstract: Controlled proteolysis is needed for cell migration, angiogenesis, and matrix remodeling during normal wound repair. Our objective has been to investigate how chronic leg ulcers differ from normally healing wounds (pinch graft donor sites) with respect to their metalloproteinase expression patterns. Using in situ hybridization and immunohistochemistry, we found that collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) were expressed in keratinocytes bordering both acute and chronic wounds. Unlike MMP-1, signal for collagenase-3 (MMP-13) was not detected in keratinocytes but exclusively in fibroblasts deep in the ulcer bed of chronic wounds, suggesting that while MMP-1 production is important for migration, MMP-13 plays a role in matrix remodeling. Tissue inhibitor of metalloproteinase (TIMP)-1 was not detected in the epidermis of any chronic wound sample while it was expressed in keratinocytes bordering normally healing wounds. TIMP-3 was abundantly expressed in stromal fibroblast- and macrophage-like cells surrounding vessels and sweat glands in both types of wounds. Our results suggest that there are no qualitative differences in the expression of MMPs-1, -3 and -10 in the epidermis of chronic vs normally healing wounds. However, the number of stromal cells expressing MMP-1 and MMP-3 was greater in chronic vs acute wounds, whereas MMP-10 was never detected in the dermis. TIMP-1 expression near the basement membrane in acute, but not in chronic, wounds suggests that the balance between MMPs and their inhibitors may be altered in poorly healing wounds. Analogous to chronic cutaneous wounds, MMP-1 and -3 are abundantly expressed in chronic small and large bowel ulcers, while the migrating surface epithelium is negative for TIMP-1 expression.

Interleukin-1alpha and collagenase activity are elevated in chronic wounds

Abstract: Interleukin-1-alpha (IL-1alpha) is a member of a family of proinflammatory polypeptide mediators that has been shown in vitro to stimulate collagenase production. Collagenase is a proteolytic enzyme classified as one of the matrix metalloproteinases (MMP-1) that specifically recognizes and cleaves collagen. Therefore, the objective of this study was to compare the levels of these two proteins in chronic wounds as possible factors in the pathogenesis of chronic wounds. Fluids from 10 chronic wounds were collected before and after a 1-week treatment with a hydroactive dressing (Cutinova cavity). In addition, fluids were collected from 20 acute wounds for comparison. IL-1alpha and MMP-1 levels were quantified using sandwich ELISA. Collagenase activity was measured using a radiolabeled collagen as substrate. Clinically, the chronic wounds showed decreased area (-21.0 cm2) and reduced volume (-134.5 cm3) by 4 weeks after treatment with the hydroactive dressing. There were no significant differences in the protein concentrations between acute wound fluids (21.0 +/- 3.0 mg/ml) and chronic wound fluids before and after treatment with the hydroactive dressing (18.3 +/- 5.5 and 25.2 +/- 7.6 mg/ml, respectively). Levels of IL-1alpha in the acute wound fluids were low (0.019 pg/mg), whereas in the chronic wound fluid before treatment they had been significantly elevated (44.9 + 21.8 pg/mg). Following treatment with the hydroactive dressing, the IL-1alpha levels dropped to 10.3 + 3.3 pg/mg (p < 0.05). Collagenase activity was not detectable in acute wound fluid, elevated in pretreatment chronic wounds (12.9 + 3.4 units), and decreased in chronic wounds after treatment (11.4 + 3.3 units). This study correlated clinical healing of chronic wounds with biochemical changes in the ulcer microenvironment. As the chronic wounds began to heal, there was a significant decrease in the IL-1alpha levels and collagenase activity, thus suggesting that these two proteins may contribute to the lack of healing characteristic of chronic wounds.

Effect of chronic wound fluid on fibroblasts.

Abstract: This study examines how the microenvironment created by fluid in chronic wounds influences the growth of dermal fibroblasts. Newborn fibroblasts, which are known to grow rapidly, were used as a model system to explore how chronic wound fluid affects the growth of regenerative fibroblasts. Wound fluid was collected from patients with chronic venous leg ulcers (duration longer than two months). The biological properties of this fluid were then further characterised to elucidate its molecular effects on cell growth. Results indicate that chronic wound fluid dramatically inhibited the growth of newborn dermal fibroblasts. This growth inhibitory effect was variable among donors, reversible and heat-sensitive. The inhibitory effect was due not to cytotoxicity or impaired plating efficiency of these cells, but to specific interference with the cell cycle. Chronic wound fluid arrested newborn fibroblast growth by preventing entry into the S-phase, or DNA synthesis-phase, of the cell cycle. In contrast to its effe...

The basic principles of wound care.

Abstract: A chronic wound should prompt a search for the underlying causes. Knowledge of the physiology of the normal wound healing trajectory through the stages of hemostasis, inflammation, granulation, and maturation provides a framework for understanding the advantages of moist interactive wound healing. Good chronic wound care is patient-centered, holistic, interdisciplinary, and evidence-based.

Role of Cytokines in Healing Chronic Skin Wounds

Abstract: In the chronic wound, the normal cascade of inflammation, granulation and reconstruction phases of healing is interrupted. Cytokines are now known to orchestrate different biochemical mediators resulting in the restoration of the healing phases. Growth factors may play a significant role in stimulating wound repair by stimulating growth and proliferation. Since growth factors stimulate a variety of functions depending on cell type and wound stage and since wound-healing defects may occur at any phase of healing, a mixed combination of growth factors would be predicted to be more effective than a single factor. Factors that may modulate the action of growth factors include electrical stimulation, weight bearing, debriding and ischemia.

Effects of chronic wound fluid on the structure and biological activity of becaplermin (rhPDGF–BB) and becaplermin gel

Abstract: In this study, the effects of chronic wound fluid on the structure and biological activity of becaplermin (recombinant human platelet-derived growth factor-BB [rhPDGF-BB]) were evaluated. Wound fluid was collected from 12 subjects with diabetic ulcers or pressure ulcers. Wound fluid +/- becaplermin was added to cell cultures before- and after incubation for 12 hours at 37 degrees C or after 12 hours' topical treatment. Biological activity, concentration, and immunogenicity were determined by [3H]thymidine incorporation into quiescent human foreskin fibroblasts, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis, respectively. No PDGF-BB or mitogenic activity was detected in chronic wound fluid alone. Mitogenic activity was present in post-treatment samples from becaplermin-treated subjects but not placebo-treated subjects. Exposure to chronic wound fluid for 12 hours did not alter the amount, banding pattern, or mitogenic activity of becaplermin. Biologically active becaplermin remains in wound fluid 12 hours after topical application of becaplermin gel.

Transition theory and its relevance to patients with chronic wounds.

Abstract: A wound, in the broadest sense, is a disruption of normal anatomic structure and function. Acute wounds progress through a timely and orderly sequence of repair that leads to the restoration of functional integrity. In chronic wounds, this timely and orderly sequence goes awry. As a result, people with chronic wounds often face not only physiological difficulties but emotional ones as well. The study of body image and its damage as a result of a chronic wound fits well with Selder's transition theory. This article describes interviews with seven patients with chronic wounds. The themes that emerged from those interviews were compared with Selder's theory to describe patients' experience with chronic wounds as a transition process that can be identified and better understood by healthcare providers.

Tissue viability supplement

Abstract: A person’s nutritional requirements increase following trauma or surgery, and in the presence of a chronic wound. If the increased demand for nutrients is not met, this can have a significant impact on wound healing, but it is nevertheless a factor that is often overlooked by health professionals in their patient assessments. Metabolic demand rises in the presence of a wound because the cell activity in the region is greatly increased. The process of wound healing requires cell division and migration of macrophages, fibroblasts and endothelial cells bringing in new blood vessels and epithelial cells from the surrounding tissues. Cellular processes during wound healing During wound healing, the cells, particularly fibro-blasts, synthesise and secrete proteins to form scar tissue, while macrophages secrete the growth factors which direct the activity of surrounding cells and, thus, the sequence of wound healing. All of these activities place extra nutritional demands on the patient, and wounds; fistulae and burns also cause an increased loss of protein from the body through exudate. At times, especially when burns are extensive, this loss can be severe and even lifethreatening. This article reviews the criteria for nutritional assessment of patients with wounds, explains the specific nutritional requirements for the healing wound and examines particular conditions where nutritional risk may be increased.

Chronic wound model

Abstract: A novel wound healing model and method for studying the pathophysiology of chronic wounds is disclosed. Diabetes is induced in a pig via injection of streptozotocin. Levels of collagenase and elastase are increased in the diabetic pig wounds versus non-diabetic pigs thereby simulating conditions in a chronic wound.