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2005 Abstracts: Trypsin Activation Is Followed By Pancreatic Polyamine Depletion in Severe Sublethal Acute Pancreatitis Model
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Trypsin Activation Is Followed By Pancreatic Polyamine Depletion in Severe Sublethal Acute Pancreatitis Model
Haitao Jin, Teemu Lämsä, Juhani Sand, Sari Räty, Gastroenterol and Alimentary Tract Surg, Tampere Univ Hosp, FINLAND, Tampere, Europe, Finland; Karl-Heinz Herzig, A.I. VIrtanen Institute for Molecular Sciences, Kuopio, Europe, Finland; Leena Alhonen, A.I.Virtanen Institute for Molecular Sciences, Kuopio, Europe, Finland; Isto Nordback, Gastroenterol and Alimentary Tract Surg, Tampere Univ Hosp, FINLAND, Tampere, Europe, Finland

Background: Previous findings have demonstrated that activation of polyamine catabolism in transgenic rats (over-expressing spermidine/spermine N'-acetyltransferase, SSAT) results in acute pancreatic inflammation, suggesting that depletion of polyamines (spermine and spermidine) may be one step in the evolution of acute pancreatitis. The purpose of this study was to explore this hypothesis in another model, and to study the timing of the changes in the polyamine metabolism in relation to trypsin activation.

Methods: 36 rats (300g~350g) were divided into 2 groups (pancreatitis group and sham group). In pancreatitis group 0.2 ml of 2.0% sodium taurodeoxycholate was infused into the pancreatic duct. In sham group the animals underwent laparotomy only. All animals were sacrificed and sampled under anesthesia at 3h, 24h and 48h. 6 rats served as 0 hour controls without operation. Serum amylase and pancreatic SSAT activities were measured. Pancreatic histology, water content and concentrations of spermine, spermidine and trypsin activation peptide (TAP) were analysed. Results: In the pancreatitis group with hyperamylasemia, pancreatic edema, and pancreatitis histology SSAT was induced early, in association with trypsin, resulting in substantial decrease of both spermine and spermidine (Table). Pancreatic SSAT activity and TAP content correlated with each other (correlation coefficient 0.782, P<0.05).
Group Parameters 0 h (controls) 3 hours 24 hours 48 hours
pancreatitis group Amylase (U/I) 1915±138 8013±935* 11292±2097 3867±925
SSAT (pmol/mg protein/10min) 4,2±0,2 56,4±13,8 13,8±5,3 4,7±0,9
TAP (pmol/mg protein) 7,2±1,2 71,6±11* 25,3±4,7 9±4,3
Spermidine (pmol/mg protein) 1646±27 1023±188 660±155* 1478±195
Spermine (pmol/mg protein) 189±6 170±15 132±7* 205±28
sham group Amylase (U/I) 1915±138 2685±202 6436±1240 2836±399
SSAT(pmol/mg protein/10min) 4,2±0,2 8,4±2,1 7,5±0,7 7,0±1,9
TAP(pmol/mg protein) 7,2±1,2 9,6±3,4 10,1±2,2 4,4±0,7
Spermidine(pmol/mg protein) 1646±27 1489±22 1259±86 1310±234
Spermine(pmol/mg protein) 189±6 194±7 183±14 209±8
Conclusions: Another pancreatitis model (sodium taurocholate pancreatitis) is associated with the depletion of polyamines after induction of SSAT that occurs in association with the trypsin activation. Because polyamine depletion occurs between 3 and 24 h after induction of pancreatitis, it may serve as a target for therapy in pancreatitis.


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