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Protease Activation and Inflammation in Acute Pancreatitis

Regnér, Sara LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:20.
Abstract
Approximately 10—20 % of patients with acute pancreatitis (AP) develop a severe disease with high mortality and morbidity. Activation of pancreatic proteases, the inflammatory response and impaired pancreatic circulation are pathophysiological events that are important in order for the disease to develop. There is no specific treatment for severe AP, and no useful marker for predicting the severity of the disease upon admission to the hospital.

In this thesis, markers of early pathophysiological events in AP are investigated, with emphasis on protease activation and inflammation.

ProCarboxypeptidase B (proCAP) is a pancreatic proenzyme which, particularly in severe AP, is activated by trypsin thereby forming... (More)
Approximately 10—20 % of patients with acute pancreatitis (AP) develop a severe disease with high mortality and morbidity. Activation of pancreatic proteases, the inflammatory response and impaired pancreatic circulation are pathophysiological events that are important in order for the disease to develop. There is no specific treatment for severe AP, and no useful marker for predicting the severity of the disease upon admission to the hospital.

In this thesis, markers of early pathophysiological events in AP are investigated, with emphasis on protease activation and inflammation.

ProCarboxypeptidase B (proCAP) is a pancreatic proenzyme which, particularly in severe AP, is activated by trypsin thereby forming Carboxypeptidase B (aCAP ) and the activation peptide of proCarboxypeptidase B (CAPAP).

An ELISA method for measurement of serum aCAP in patients with AP was developed, and aCAP was shown to inhibit fibrinolysis in vitro. This may contribute to formation of necrosis in AP. The prediction of severity and pathophysiology was studied in patients with mild (n=124) and severe (n=16) AP. Markers of protease activation (aCAP, CAPAP) and inflammation (Monocyte Chemoattractant protein-1 (MCP-1) and CRP) were found to be elevated within 24 hours in patients with severe AP. Protease activation decreased after 48 hours, yet inflammation persisted for a longer period of time. Markers of pancreatic leakage (proCAP) decreased with time without differences in patients with mild and severe AP. MCP-1 exhibited a good capacity at predicting severe AP upon hospital admission. CAPAP and aCAP may also be useful in predicting the degree of severity. (Less)
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author
supervisor
opponent
  • Prof Permert, Johan, Inst for Clinical Sciences, Intervention and Technique (CLINTEC), Karolinska Institutet, Dept of Surgery, Karolinska Universitetssjukhuset, Stockholm
organization
publishing date
type
Thesis
publication status
published
subject
keywords
prediction of severity, CAPAP, proCAP, aCAP, Acute pancreatitis, MCP-1, Carboxypeptidase B, fibrinolysis
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:20
pages
104 pages
publisher
Department of Surgery, Clinical Sciences Lund, Lund University
defense location
Main Hall, CRC, Malmö University Hospital
defense date
2008-03-14 09:15
ISSN
1652-8220
ISBN
978-91-85897-73-5
language
English
LU publication?
yes
id
e43dcbe0-318f-4e44-8f48-3af5c6660632 (old id 1037175)
date added to LUP
2008-02-26 11:17:31
date last changed
2016-09-19 08:44:48
@phdthesis{e43dcbe0-318f-4e44-8f48-3af5c6660632,
  abstract     = {Approximately 10—20 % of patients with acute pancreatitis (AP) develop a severe disease with high mortality and morbidity. Activation of pancreatic proteases, the inflammatory response and impaired pancreatic circulation are pathophysiological events that are important in order for the disease to develop. There is no specific treatment for severe AP, and no useful marker for predicting the severity of the disease upon admission to the hospital.<br/><br>
	In this thesis, markers of early pathophysiological events in AP are investigated, with emphasis on protease activation and inflammation.<br/><br>
ProCarboxypeptidase B (proCAP) is a pancreatic proenzyme which, particularly in severe AP, is activated by trypsin thereby forming Carboxypeptidase B (aCAP ) and the activation peptide of proCarboxypeptidase B (CAPAP). <br/><br>
An ELISA method for measurement of serum aCAP in patients with AP was developed, and aCAP was shown to inhibit fibrinolysis in vitro. This may contribute to formation of necrosis in AP. The prediction of severity and pathophysiology was studied in patients with mild (n=124) and severe (n=16) AP. Markers of protease activation (aCAP, CAPAP) and inflammation (Monocyte Chemoattractant protein-1 (MCP-1) and CRP) were found to be elevated within 24 hours in patients with severe AP. Protease activation decreased after 48 hours, yet inflammation persisted for a longer period of time. Markers of pancreatic leakage (proCAP) decreased with time without differences in patients with mild and severe AP. MCP-1 exhibited a good capacity at predicting severe AP upon hospital admission. CAPAP and aCAP may also be useful in predicting the degree of severity.},
  author       = {Regnér, Sara},
  isbn         = {978-91-85897-73-5},
  issn         = {1652-8220},
  keyword      = {prediction of severity,CAPAP,proCAP,aCAP,Acute pancreatitis,MCP-1,Carboxypeptidase B,fibrinolysis},
  language     = {eng},
  pages        = {104},
  publisher    = {Department of Surgery, Clinical Sciences Lund, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Protease Activation and Inflammation in Acute Pancreatitis},
  volume       = {2008:20},
  year         = {2008},
}