Proteinase Inhibitors of Microbial Origin in the Treatment of Experimental Acute Haemorrhagic Pancreatitis
It is generally accepted that the basic pathogenetic principle responsible for damage of pancreatic tissue in acute pancreatitis is autodigestion (3). The inappropriate release of activated exocrine enzymes into the surrounding tissues, peritoneal cavity and circulation results in metastatic proteolysis and its pathophysiological consequences (12, 5, 4, 2). Active proteinases in the blood stream become complexed with macromolecular inhibitors, predominantly alpha 2 macroglobulin (11). Although constrained, the alpha 2 macroglobulin bound proteinase retains enzymic activity which is likely to contribute substantially to the metabolic defects in severe acute pancreatitis (10). For example, alpha 2 macroglobulin-trypsin rapidly abolished the bioactivity of endogenous parathormone in human plasma (6) Inhibition of this reaction was completed by low concentrations of leupeptin, a proteinase inhibitor of microbial origin, but not by Trasylol (6).
KeywordsAcute Pancreatitis Severe Acute Pancreatitis Sodium Taurocholate Microbial Origin Inappropriate Release
Unable to display preview. Download preview PDF.
- 1.Aoyagi T, Takenchi T, Matsuzaki A, Kawamura K, Kondo S, Hamade M, Maeda K, Umezawa H (1969) Leupeptins, new protease inhibitors from actinomycetes. J Antibiot (Tokyo) 22: 283–286Google Scholar
- 3.Durr GHK (1979) In: Howat, Sarles (eds) The exocrine pancreas. Saunders, London, pp 352–401Google Scholar
- 7.Jones PA (to be published) Automated estimation of time of death in unrestrained rats. Lab AnimGoogle Scholar
- 8.Jones PA, Hermon-Taylor J, Grant DAW (to be published) Single agent antiproteinase chemotherapy of acute experimental pancreatitis using the low molecular weight oligopeptide aldehyde leupeptin. GutGoogle Scholar
- 9.Jones PA, Hynd J (1981) Long term continuous intravenous infusion in unrestrained rats — a novel method. Lab Anim 15.29–33Google Scholar
- 11.Starky PM, Barrett AJ (1977) In: Barrett AJ (ed) Proteinases in mammalian cells and tissues. North-Holland, Amsterdam, pp 663–696Google Scholar