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The role of collagenase in the healing of colonic anastomoses - A reappraisal

Chowcat, Naomi Loretta; (1991) The role of collagenase in the healing of colonic anastomoses - A reappraisal. Masters thesis (M.S), UCL (University College London). Green open access

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Collagenase, the initiating enzyme in collagen degradation, has been implicated as a contributory factor in colonic anastomotic dehiscence. Mammalian collagenase is synthesised on demand in a latent form and its activity is normally tightly controlled. Contemporary methods of investigation were developed and adapted to reassess this specific enzyme in colonic healing in rabbits. Hydroxyproline and protein measurements confirmed that collagen concentration in the colon wall proximal to an anastomosis decreases three days after operation. Collagenase activity, assessed by culture of colonic explants and radiochemical assay of the medium, showed a corresponding increase after three days on both sides of the anastomosis and more marked distally. Immunohistochemical localisation of collagenase and its inhibitor, tissue inhibitor of metalloproteinases (TIMP) , demonstrated extracellular enzyme and secreting cells in the edges of bowel wall twelve hours after both everted and 'end-on' anastomoses. Collagenase was accompanied by TIMP within twenty-four hours and secretion was decreasing by the third day. At seven ABSTRACT days I only small aggregates of cells secreting enzyme and inhibitor were found within the maturing scar. The distribution of collagenase was always extremely localised and confined to the immediate vicinity of the suture line. TIMP secreting cells appeared in a protective serosal layer on the third day; TIMP distribution indicated close control of collagenase activity in the healing tissue. No collagenase or TIMP was localised in colon after sham laparotomy. The histochemical and biochemical findings cannot be correlated but critical evaluation of the techniques indicates that immunolocalisation is more likely to represent the true 'in vivo' situation. Collagenase appears to initiate the degradation of tissue which will be removed during healing and which does not contribute to the integrity of the anastomosis. The enzyme remains tightly controlled by TIMP and there is no evidence for excessive collagenase activity in uncomplicated colonic healing.

Type: Thesis (Masters)
Qualification: M.S
Title: The role of collagenase in the healing of colonic anastomoses - A reappraisal
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10120792
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