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Effective peritoneal therapy of acute pancreatitis in the rat with glutaryl-trialanin-ethylamide: a novel inhibitor of pancreatic elastase.

Abstract
The six hour peritoneal lavage with glutaryl-trialanin-ethylamide, a low molecular competitive inhibitor of pancreatic elastase (IC50-8 mumol/l), effectively suppresses the evolution of taurocholate induced acute pancreatitis in the rat. The lavage alone is followed by a marked decrease of fat necrosis and amylase and lipase activity in serum. The area of pancreatic haemorrhage was significantly reduced only after the lavage solution was supplemented with Glt-Ala3-NHEt. The effect was not enhanced by a bolus injection of the inhibitor before starting the lavage. The combination of Glt-Ala3-NHEt with aprotinin or nafamstate mesilate produced only marginal greater benefit. The effect of Glt-Ala3-NHEt on pancreatic haemorrhage is time and dose related even with delayed onset of the lavage. Animals treated with peritoneal lavage without Get-Ala3-NHEt lived longer than controls (p less than 0.05), but by 60 hours the survival rate of both groups was almost the same (76 v 74%). All animals lavaged with Glt-Ala3-NHEt survived 120 hours and the difference in the survival rate between this and both remaining groups was significant (100% v 76% v 74% - p less than 0.05). The results were considered favourable and preliminary clinical trials of Glt-Ala3-NHEt in subjects with acute pancreatitis justified.
AuthorsP Fric, J Slabý, E Kasafírek, P Kocna, J Marek
JournalGut (Gut) Vol. 33 Issue 5 Pg. 701-6 (May 1992) ISSN: 0017-5749 [Print] England
PMID1377154 (Publication Type: Journal Article)
Chemical References
  • Oligopeptides
  • Taurocholic Acid
  • glutaryl-alanyl-alanyl-alanyl-ethylamide
  • Lipase
  • Amylases
  • Pancreatic Elastase
Topics
  • Amylases (blood)
  • Animals
  • Dose-Response Relationship, Drug
  • Fat Necrosis (prevention & control)
  • Lipase (blood)
  • Male
  • Oligopeptides (therapeutic use)
  • Pancreatic Elastase (antagonists & inhibitors)
  • Pancreatitis (chemically induced, drug therapy, enzymology)
  • Peritoneal Lavage
  • Rats
  • Rats, Inbred Strains
  • Taurocholic Acid
  • Time Factors

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