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  • 2000-2004  (3)
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  • 1
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The new era of pharmacogenetics has identified a potential for individuals to receive customized treatments for a variety of disease states. For such individualized treatments to fulfil their potential, it will be essential for clinicians to be able to monitor disease activity, ideally in a rapid, noninvasive fashion. The accessibility of the skin offers much potential to develop noninvasive tests of metabolic and disease activity for clinical use. Impaired human wound healing in the skin is a chronic inflammatory disorder in which the development of such tests has considerable potential, aiding clinical decision making and monitoring responses to treatment. This review article discusses how studies in other human diseases have highlighted potential biochemical markers (biomarkers) of disease activity in secreted biofluids, as aids to determining disease and metabolic activity within tissues. Using, as examples, lessons learned in the study of disease activity and prognosis of other chronic inflammatory conditions, such as osteoarthritis and periodontal disease, this review highlights the potential of dermal extracellular matrix (ECM) components (collagens, proteoglycans, hyaluronan and glycoproteins) for such uses. The limitations of currently utilized techniques and the concept that analysis of ECM components in wound fluid may represent useful biomarkers of disease activity are also discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Background Anaerobic cocci are estimated to be present in the deep tissues of over 50% of chronic skin wounds. While the part they play in the chronicity of these wounds is uninvestigated, anaerobic cocci have previously been shown to be involved in other chronic inflammatory human conditions. Methods In this study the anaerobic microflora of the deep tissues of 18 patients with refractory chronic venous leg ulcers (mean age 80·3 years; mean duration 〉 24 months) was characterized using strict anaerobic culture conditions. The effect of the anaerobic organisms isolated from these tissues on extracellular matrix (ECM) proteolysis and cellular wound healing responses was studied using in vitro models. Results Anaerobic organisms were present in the deep tissues of 14 of 18 wounds and were principally Peptostreptococcus spp. The effects of three Peptostreptococcus spp. isolated from these wounds (P. magnus, P. vaginalis and P. asaccharolyticus) on cellular wound healing responses were compared with those of two pathogenic organisms also isolated from these wounds (Pseudomonas aeruginosa and Citrobacter diversus). While the direct ECM proteolytic activity exhibited by the Peptostreptococcus spp. was limited, they did significantly inhibit both fibroblast and keratinocyte proliferation, but only at high concentrations. However, at lower concentrations peptostreptococcal supernatants profoundly inhibited keratinocyte wound repopulation and endothelial tubule formation. The magnitude of these effects varied between strains and they were distinct from those demonstrated by Pseudomonas aeruginosa and Citrobacter diversus. Conclusions These studies confirm the importance of anaerobic organisms in chronic wounds and demonstrate an indirect, strain-specific mechanism by which these microorganisms may play a part in mediating the chronicity of these wounds.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Oral mucosal wounds are characterized by rapid re-epithelialization and remodelling. In vitro, oral mucosal fibroblasts exhibit a fetal phenotype with increased extracellular matrix reorganizational ability, migration and experimental wound repopulation when compared with skin fibroblasts. Objectives To investigate whether phenotypic differences in the expression and production of matrix metalloproteinase (MMP) -2 and tissue inhibitors of metalloproteinases (TIMPs) could play an important part in mediating these in vitro differences. Methods Skin and oral mucosal fibroblast MMP-2, TIMP-1 and TIMP-2 mRNA expression and protein production were studied in three-dimensional collagen lattices using quantitative competitive reverse transcriptase–polymerase chain reaction (QCRT–PCR), enzyme-linked immunosorbent assay (ELISA), zymography and reverse zymography. Results Oral mucosal fibroblasts exhibited increased levels of the 62-kDa active form of MMP-2 and lattice contraction when compared with skin fibroblasts. Oral mucosal and skin fibroblast MMP-2 gene expression and synthesis of the 72-kDa pro-MMP-2 was similar as assessed by QCRT–PCR, zymography and ELISA. Differential MMP-2 activation was, however, related to phenotypic differences in TIMP activity between the skin and oral mucosal fibroblasts, as assessed by reverse zymography. Conclusions These studies propose a mechanism by which fibroblast phenotype may contribute directly to the observed preferential remodelling of oral wounds.
    Type of Medium: Electronic Resource
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