Acute Pancreatitis. Studies on smoking and protease activation.

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 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
• supervisor: Anders Borgström
• opponent: Professor Haglund, Caj, Helsinki University Hospital
• organization: Surgery (research group)
• publishing date: 2005
• type: Thesis
• publication status: published
• subject: Surgery
• 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
• defense location: Kirurgiska klinikens föreläsningssal, Universitetssjukhuset MAS, ingång 42.
• defense date: 2005-12-15 09:15:00
• ISSN: 1652-8220
• ISBN: 91-85481-25-4
• language: English
• LU publication?: yes
• additional info: Björn Lindkvist, Ignacio Fajardo, Gunnar Pejler and Anders Borgström. . Cathepsin B activates human trypsinogen 1 but not proelastase 2 or procarboxypeptidase B. Pancreatology, (inpress); Björn Lindkvist, Stefan Appelros, Jonas Manjer and Anders Borgström. 2004. Trends in incidence of acute pancreatitis in a Swedish population: is there really an increase? Clinical Gastroenterology and Hepatology, vol 2 pp 831-837.; Björn Lindkvist, Stefan Appelros, Göran Berglund, Jonas Manjer and Anders Borgström. . Smoking is associated with acute pancreatitis -Report from a population-based prospective cohort study. (submitted); Björn Lindkvist, Nils Wierup, Frank Sundler and Anders Borgström. . Long term nicotine exposure causes increased concentration of trypsinogens and amylase in pancreatic extracts in the rat. (submitted)
• id: 03437769-3f43-47b9-adb0-7d2ae3409389 (old id 545926)
• date added to LUP: 2016-04-01 16:41:42
• date last changed: 2019-05-21 14:09:34