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The healing of chronic venous leg ulcers
Başlık:
The healing of chronic venous leg ulcers
Yazar:
Herrick, Sarah Elizabeth, author.
ISBN:
9780438043947
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (296 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
In the chronic wound, the normal repair process is arrested either initially or at some stage during it's formation. Chronic wounds such as venous leg ulcers therefore heal slowly, if at all, and have a high recurrence rate so causing major medical and social problems. Chronic leg ulcer healing has not been studied in as much detail as acute wound healing due to a lack of suitable animal models limiting the investigation to biopsies taken from venous ulcer patients. Sequential biopsies were obtained from the margins of chronic venous leg ulcers to include surrounding skin, ulcer edge and ulcer base. The first aim of the study was to document the initial appearance and subsequent changes in tissue architecture during the healing process using histological and immunocytological techniques. A clear sequence of events was observed during the healing of venous ulcers. Pericapillary cuffs consisted of extracellular matrix molecules, growth factors and endothelial cell adhesion molecules and not just fibrin as thought previously. The complex organisation of these cuffs may inhibit angiogenesis but offer protection against increased venous pressure. The numbers of pericapillary cuffs decreased during ulcer healing. In addition, fibronectin initially absent from the ulcer base appeared during ulcer healing. Biochemical analysis of ulcer tissue using immunoblotting, immunoprecipitation and gelatin sepharose affinity, showed that ulcer base tissue derived from initial biopsies was deficient in fibronectin. By performing a hydroxyproline assay, ulcer tissue (surrounding skin, ulcer edge and base) was shown to have a reduced collagen content compared to normal leg skin from age- matched subjects. The second aim was to establish venous ulcer fibroblasts in culture from initial biopsy explants. Using metabolically labelled media and performing a collagenase digestion assay, the ability of ulcer-derived fibroblasts (passage number 7-12) to synthesise collagen in vitro was found to be impaired compared to normal dermal fibroblasts. However, the ability to synthesise fibronectin was the same for both normal and ulcer-derived fibroblasts. As oxygen is an essential substrate for collagen synthesis, hypoxia has been suggested as a contributing factor which could result in decreased extracellular matrix synthesis in the ulcer base. Ulcer fibroblasts and normal dermal fibroblasts subjected to hypoxia synthesised less protein and collagen, but the same amounts of fibronectin as in normoxia. The low amount of collagen found in the ulcer tissue in vivo may therefore be partly attributed to exposure of ulcer fibroblasts to a chronically hypoxic wound environment. However, the low fibronectin levels may be the consequence of other hostile factors such as proteases produced in venous ulcers by a repetitive ischaemia and reperfusion injury. Using microchemotaxis chambers, it was shown that ulcer-derived fibroblasts were not as motile as normal dermal fibroblasts, but could respond to the stimulatory effects of serum, and growth factors (TGF-beta1 and PDGF) known to be present in acute wound fluid. Impaired migration of matrix synthesising fibroblasts in vivo could also explain the low amounts of collagen and fibronectin in the ulcer base and the delay in ulcer healing. In summary, these findings suggest that the wound bed of chronic venous leg ulcers is deficient in essential extracellular matrix molecules needed for healthy granulation tissue formation, subsequent re-epithelialisation and ulcer healing.
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(684331.1) | 684331-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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