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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Wound repair and regeneration 13 (2005), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Nitric oxide (NO) is a critical mediator of normal tissue repair and is inhibited by homocysteine (Hcy). Following 8 weeks of lower extremity ulcer (LEU) treatment with human fibroblast-derived dermal substitute (Dermagraft®) for 12 (n = 12) patients, a correlation was observed between patients with a poor wound healing response to Dermagraft and elevated serum homocysteine (Hcy). The responders group (R) to Dermagraft treatment (n = 6) was observed with robust granulation tissue, epidermal migration and a 67% rate of healed ulcerations. All R-group patients (6/6) had normal serum Hcy. The nonresponders (NR) group (n = 6) exhibited poor granulation tissue formation and epidermal migration and a complete absence of healed wounds. Five of the NR patients (5/6) were observed with elevated serum Hcy. There was no significant (p 〈 0.05) difference between the wound areas (cm2 ± SE) of each group [35.43(±28.99)-R vs. 19.90(±7.55)-NR]. After 2 weeks of treatment, the R-group demonstrated significantly greater %Δwound area than the NR-group [62.17 (±7.96)-R group vs. 23.17(±8.82)-NR group; p 〈 0.05]. Wound fluid nitrate (WFNOx), a surrogate measurement (μM ± SE) for local NO bioactivity, was significantly lower for the NR-group than the R-group [3.17(±1.46)μM-NR group vs. 12.98(±1.73)μM-R group; p 〈 0.05]. In a large group of LEU patients (n = 138) we observed a 50% incidence of elevated Hcy; 69% for diabetic neuropathic LEU patients and 47% for nondiabetic LEU patients. Hcy inhibits NO production by multiple pathways and may also inhibit wound repair by occupying the fibronectin domain of fibrin during provisional matrix formation. Our study suggests that elevated serum Hcy is a common finding in chronic LEU patients. The high Hcy may contribute to impaired wound healing by decreasing wound NO production and, perhaps, by inhibition of fibronectin-fibrin-mediated wound matrix development.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Wound repair and regeneration 13 (2005), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been speculated that a prolonged and elevated neutrophilic response has an important role in the pathogenesis of chronic wounds. This has raised the possibility that one or more of these proteases might be useful as a diagnostic or prognostic biomarker for chronic wounds. The purpose of this study was to examine several primarily neutrophil-derived proteases present in pressure ulcer tissues and to determine whether protease activity could be correlated with neutrophil levels. Biopsies of pressure ulcers were taken from consented subjects (n = 13) and again after 3 months standard care. Mean wound volume decreased 2.4 cm3 per month; however, volumes of six wounds were increased at the end of the study. Levels of extractable myeloperoxidase (MPO), elastase, collagenase-2 (MMP-8), and gelatinase (MMP-9) activities were determined. Mean levels of MPO (n = 11) at study initiation and after 3 months were nearly identical (2945 and 2845 milliunits per mg extract, respectively). Interestingly, these levels were similar to that previously found in healing open dermal wounds at 4 days postwounding. MPO levels increased in the extracts obtained from three subjects and declined in five subjects. Elastase (corr. 0.265 p = 0.233) and MMP-8 (corr. −0.05 p = 0.835) activities correlated poorly with MPO. This is likely a reflection of differences in the access of protease inhibitors (e.g., alpha1-antitrypsin, TIMP, and alpha2–macroglobulin) to these wounds. As expected, a greater correlation level was observed between the proteases (MMP-8 vs. elastase corr. 0.362 p = 0.097; MMP-8 vs. MMP-9 corr. 0.55 p = 0.009). The results from this study highlight the high degree of variability that can be observed in the pressure ulcer environment. This further suggests that a combination of biomarkers will be required for making accurate diagnostic assessments of chronic wounds.This work was supported by NIH GM 58530.
    Type of Medium: Electronic Resource
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