title: Sequential changes in pancreatic markers in acute pancreatitis.
abstract: BACKGROUND
  Trypsinogen activation within acinar cells plays a crucial role in the pathogenesis of acute pancreatitis (AP). Our aim was to characterize temporal changes of trypsinogen-1, trypsinogen-2, complexes of trypsin-1-alpha1-antitrypsin (T1-AAT) and trypsin-2-alpha1-antitrypsin (T2-AAT), trypsinogen activation peptide (TAP) and pancreatic secretory trypsin inhibitor (PSTI) in patients with AP.
  
  
  METHODS
  The study comprised 64 consecutive patients with AP (19 with severe disease) and 32 controls. The concentrations of trypsinogen-1 and -2, PSTI, T1-AAT and T2-AAT were determined by time-resolved immunofluorometric assays (IFMA), and TAP was measured using a competitive enzyme immunoassay from serum and urine.
  
  
  RESULTS
  The concentrations of trypsinogen-1 and -2 in serum reflected similar patterns, but excretion of trypsinogen-1 into urine was markedly lower than that of trypsinogen-2, the concentration of which correlated strongly with disease severity. The concentrations of T1-AAT were no higher in severe AP than in mild AP, while T2-AAT concentrations were significantly higher in severe than in mild disease. PSTI increased over the course of several days, showing strong correlation with disease severity. The concentrations of plasma and urinary TAP decreased rapidly to undetectable levels. During the early phase of AP, TAP correlated with the disease severity in plasma and urine but there was no difference between controls and patients with mild AP.
  
  
  CONCLUSIONS
  More pronounced changes in trypsinogen-2 and its complex with AAT than in those of trypsinogen-1 were demonstrated, suggesting that trypsinogen-2 might play a more important role in the pathogenesis of AP than earlier believed. Urinary PSTI showed features warranting further investigations as a marker of disease severity.
authors.affiliation: Second Dept. of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Lempinen
authors.forename: U H
authors.initials: UH
authors.lastname: Stenman
authors.forename: P
authors.initials: P
authors.lastname: Puolakkainen
authors.forename: A
authors.initials: A
authors.lastname: Hietaranta
authors.forename: R
authors.initials: R
authors.lastname: Haapiainen
authors.forename: E
authors.initials: E
authors.lastname: Kemppainen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002352:Carrier Proteins; D005260:Female; D006133:Growth Substances / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000097:blood / Q000378:metabolism* / Q000652:urine; D010195:Pancreatitis / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D013997:Time Factors; D014357:Trypsin / Q000097:blood / Q000378:metabolism*; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; C486642:SPINK1 protein, human; D000515:alpha 1-Antitrypsin; C080396:trypsinogen activation peptide; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; D014357:Trypsin