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Acute Pancreatitis. Studies on smoking and protease activation.

Lindkvist, Björn LU (2005) In Faculty of Medicine Dissertation Series 2005:124.
Abstract
Background and aims: Activation of pancreatic proteases is considered to be a crucial event in the early phase of acute pancreatitis but the cause of this activation is not known. Most cases of acute pancreatitis can be attributed to either gallstone disease or alcohol abuse. However, little is known about other risk factors. The aim of this thesis is to investigate the mechanisms involved in the initiation of acute pancreatitis, trends in the incidence, and risk factors for the disease. The potential role of smoking as a risk factor was given special attention and the effect of nicotine on exocrine pancreas was studied in a rat model.



Results and conclusions: Cathepsin B activated trypsinogen but not proelastase or... (More)
Background and aims: Activation of pancreatic proteases is considered to be a crucial event in the early phase of acute pancreatitis but the cause of this activation is not known. Most cases of acute pancreatitis can be attributed to either gallstone disease or alcohol abuse. However, little is known about other risk factors. The aim of this thesis is to investigate the mechanisms involved in the initiation of acute pancreatitis, trends in the incidence, and risk factors for the disease. The potential role of smoking as a risk factor was given special attention and the effect of nicotine on exocrine pancreas was studied in a rat model.



Results and conclusions: Cathepsin B activated trypsinogen but not proelastase or procarboxypeptidase B. Hence, if cathepsin B is to play a role in the activation of digestive enzymes in acute pancreatitis, this probably occurs through activation of trypsinogen. The incidence of gallstone-related acute pancreatitis increased by 7.6% per year (95% confidence interval (CI), 4.0 to 11.4) in Malmö 1985?1999. The incidence of alcohol-related acute pancreatitis decreased by ?5.1% per year (95 % CI, ?7.4 to ?2.8). The risk for acute pancreatitis was increased in smokers (relative risk 2.14, (95% CI, 1.48 to 3.09)), after adjustment for age, sex, body mass index and alcohol consumption. There was a weak association between body mass index and the risk for acute pancreatitis (p=0.02). Nicotine induced increased concentrations of pancreatic proenzymes in pancreatic extract but had no impact on the production of the same enzymes. These findings suggest that nicotine impairs acinar cell secretion. We propose that this might be a contributory mechanism behind the association between smoking and pancreatic disease. (Less)
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author
supervisor
opponent
  • Professor Haglund, Caj, Helsinki University Hospital
organization
publishing date
type
Thesis
publication status
published
subject
keywords
trypsinogen, Acute pancreatitis, trypsinogen activation peptide cathepsin B, incidence, smoking, nicotine, traumatologi, ortopedi, Kirurgi, traumatology, Surgery, orthopaedics, Gastroenterologi, Public health, epidemiology, Folkhälsa, epidemiologi, Gastro-enterology
in
Faculty of Medicine Dissertation Series
volume
2005:124
publisher
Lund University Department of Clinical Sciences Malmö University Hospital
defense location
Kirurgiska klinikens föreläsningssal, Universitetssjukhuset MAS, ingång 42.
defense date
2005-12-15 09:15
ISSN
1652-8220
ISBN
91-85481-25-4
language
English
LU publication?
yes
id
03437769-3f43-47b9-adb0-7d2ae3409389 (old id 545926)
date added to LUP
2007-09-20 15:48:22
date last changed
2016-09-19 08:44:57
@phdthesis{03437769-3f43-47b9-adb0-7d2ae3409389,
  abstract     = {Background and aims: Activation of pancreatic proteases is considered to be a crucial event in the early phase of acute pancreatitis but the cause of this activation is not known. Most cases of acute pancreatitis can be attributed to either gallstone disease or alcohol abuse. However, little is known about other risk factors. The aim of this thesis is to investigate the mechanisms involved in the initiation of acute pancreatitis, trends in the incidence, and risk factors for the disease. The potential role of smoking as a risk factor was given special attention and the effect of nicotine on exocrine pancreas was studied in a rat model.<br/><br>
<br/><br>
Results and conclusions: Cathepsin B activated trypsinogen but not proelastase or procarboxypeptidase B. Hence, if cathepsin B is to play a role in the activation of digestive enzymes in acute pancreatitis, this probably occurs through activation of trypsinogen. The incidence of gallstone-related acute pancreatitis increased by 7.6% per year (95% confidence interval (CI), 4.0 to 11.4) in Malmö 1985?1999. The incidence of alcohol-related acute pancreatitis decreased by ?5.1% per year (95 % CI, ?7.4 to ?2.8). The risk for acute pancreatitis was increased in smokers (relative risk 2.14, (95% CI, 1.48 to 3.09)), after adjustment for age, sex, body mass index and alcohol consumption. There was a weak association between body mass index and the risk for acute pancreatitis (p=0.02). Nicotine induced increased concentrations of pancreatic proenzymes in pancreatic extract but had no impact on the production of the same enzymes. These findings suggest that nicotine impairs acinar cell secretion. We propose that this might be a contributory mechanism behind the association between smoking and pancreatic disease.},
  author       = {Lindkvist, Björn},
  isbn         = {91-85481-25-4},
  issn         = {1652-8220},
  keyword      = {trypsinogen,Acute pancreatitis,trypsinogen activation peptide cathepsin B,incidence,smoking,nicotine,traumatologi,ortopedi,Kirurgi,traumatology,Surgery,orthopaedics,Gastroenterologi,Public health,epidemiology,Folkhälsa,epidemiologi,Gastro-enterology},
  language     = {eng},
  publisher    = {Lund University Department of Clinical Sciences Malmö University Hospital},
  school       = {Lund University},
  series       = {Faculty of Medicine Dissertation Series},
  title        = {Acute Pancreatitis. Studies on smoking and protease activation.},
  volume       = {2005:124},
  year         = {2005},
}