Acute Pancreatitis. Studies on smoking and protease activation.

Björn Lindkvist

Research output: ThesisDoctoral Thesis (compilation)

51 Downloads (Pure)

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.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Surgery
Supervisors/Advisors
  • Borgström, Anders, Supervisor
Award date2005 Dec 15
Publisher
ISBN (Print)91-85481-25-4
Publication statusPublished - 2005

Bibliographical note

Defence details

Date: 2005-12-15
Time: 09:15
Place: Kirurgiska klinikens föreläsningssal, Universitetssjukhuset MAS, ingång 42.

External reviewer(s)

Name: Haglund, Caj
Title: Professor
Affiliation: Helsinki University Hospital

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<div class="article_info">Björn Lindkvist, Ignacio Fajardo, Gunnar Pejler and Anders Borgström. <span class="article_issue_date"></span>. <span class="article_title">Cathepsin B activates human trypsinogen 1 but not proelastase 2 or procarboxypeptidase B.</span> <span class="journal_series_title">Pancreatology</span>, (inpress)</div>
<div class="article_info">Björn Lindkvist, Stefan Appelros, Jonas Manjer and Anders Borgström. <span class="article_issue_date">2004</span>. <span class="article_title">Trends in incidence of acute pancreatitis in a Swedish population: is there really an increase?</span> <span class="journal_series_title">Clinical Gastroenterology and Hepatology</span>, <span class="journal_volume">vol 2</span> <span class="journal_pages">pp 831-837</span>.</div>
<div class="article_info">Björn Lindkvist, Stefan Appelros, Göran Berglund, Jonas Manjer and Anders Borgström. <span class="article_issue_date"></span>. <span class="article_title">Smoking is associated with acute pancreatitis -Report from a population-based prospective cohort study.</span> (submitted)</div>
<div class="article_info">Björn Lindkvist, Nils Wierup, Frank Sundler and Anders Borgström. <span class="article_issue_date"></span>. <span class="article_title">Long term nicotine exposure causes increased concentration of trypsinogens and amylase in pancreatic extracts in the rat.</span> (submitted)</div>

Subject classification (UKÄ)

  • 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

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