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Multimodal management - of value in fulminant acute pancreatitis?

Haraldsen, P ; Sun, Z W ; Börjesson, Anna LU ; Olanders, Knut LU ; Lasson, Åke LU and Andersson, Roland LU (2003) In Pancreatology 3(1). p.14-25
Abstract
Abstract in Undetermined
Background: The multiple organ dysfunction syndrome (MODS) is the major cause of morbidity and mortality associated with acute pancreatitis. Presently, therapy is merely organ supportive as no effective therapy against underlying causative pathophysiologicla mechanisms exists. Aims: To evaluate the effect of treatmetn with a platelet-activating factor inhibitor (PAFI), a monoclonal antibody against platelet endothelial cell adhesion molecule (PECAM-1-MAb) and an oxygen free radical scavenger (N-acetylcystein; NAC), alone or in combination, on systemic organ dysfunction in experimental acute pancreatitis. Methods: Severe acute pancreatitis induced in rats by the intraductal administration of tauro-deoxycholate.... (More)
Abstract in Undetermined
Background: The multiple organ dysfunction syndrome (MODS) is the major cause of morbidity and mortality associated with acute pancreatitis. Presently, therapy is merely organ supportive as no effective therapy against underlying causative pathophysiologicla mechanisms exists. Aims: To evaluate the effect of treatmetn with a platelet-activating factor inhibitor (PAFI), a monoclonal antibody against platelet endothelial cell adhesion molecule (PECAM-1-MAb) and an oxygen free radical scavenger (N-acetylcystein; NAC), alone or in combination, on systemic organ dysfunction in experimental acute pancreatitis. Methods: Severe acute pancreatitis induced in rats by the intraductal administration of tauro-deoxycholate. Treatment was given after 1 or 3 h, and evaluations were performed 6 h after induction. Organ dysfunction was evaluated by means of endothelial integrity impairment expressed as endothelial barrier leakage index. Results: Severe acute pancreatitis caused a significant impairment in endothelial integrity in all organs studied and decreased levels of protease inhibitors compared to controls. The endothelial barrier impairment was significantly ameliorated by all treatment modalities, either given early or later. Combinations of NAC and the PECAM-1-MAb or the PECAM-1-MAb and the PAFI were the only schedules to restore endothelial barrier integrity to normal levels in most of the organs studied. Conclusion: Combination therapy with NAC and PECAM-1-MAb and/or PAFI may offer effective, causative-directed supplements to organ-supportive therapy of MODS in severe acute pancreatitis. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
monoclonal antibodies, endothelial barrier permeability, organ dysfunction, oxygen free radicals, protease inhibitors, platelet-activating factor antagonist, rat, scavenger, acute pancreatitis
in
Pancreatology
volume
3
issue
1
pages
14 - 25
publisher
Karger
external identifiers
  • wos:000182246400004
  • pmid:12649560
  • scopus:0037229995
ISSN
1424-3903
DOI
10.1159/000069148
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Surgery Research Unit (013242220), Anaesthesiology and Intensive Care (013230022), Surgery (Lund) (013009000), Emergency medicine/Medicine/Surgery (013240200)
id
5e4e5e5a-c114-4d15-b361-41be0485af19 (old id 112597)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12649560&dopt=Abstract
date added to LUP
2016-04-01 12:17:20
date last changed
2022-04-13 08:55:03
@article{5e4e5e5a-c114-4d15-b361-41be0485af19,
  abstract     = {{Abstract in Undetermined<br/>Background: The multiple organ dysfunction syndrome (MODS) is the major cause of morbidity and mortality associated with acute pancreatitis. Presently, therapy is merely organ supportive as no effective therapy against underlying causative pathophysiologicla mechanisms exists. Aims: To evaluate the effect of treatmetn with a platelet-activating factor inhibitor (PAFI), a monoclonal antibody against platelet endothelial cell adhesion molecule (PECAM-1-MAb) and an oxygen free radical scavenger (N-acetylcystein; NAC), alone or in combination, on systemic organ dysfunction in experimental acute pancreatitis. Methods: Severe acute pancreatitis induced in rats by the intraductal administration of tauro-deoxycholate. Treatment was given after 1 or 3 h, and evaluations were performed 6 h after induction. Organ dysfunction was evaluated by means of endothelial integrity impairment expressed as endothelial barrier leakage index. Results: Severe acute pancreatitis caused a significant impairment in endothelial integrity in all organs studied and decreased levels of protease inhibitors compared to controls. The endothelial barrier impairment was significantly ameliorated by all treatment modalities, either given early or later. Combinations of NAC and the PECAM-1-MAb or the PECAM-1-MAb and the PAFI were the only schedules to restore endothelial barrier integrity to normal levels in most of the organs studied. Conclusion: Combination therapy with NAC and PECAM-1-MAb and/or PAFI may offer effective, causative-directed supplements to organ-supportive therapy of MODS in severe acute pancreatitis.}},
  author       = {{Haraldsen, P and Sun, Z W and Börjesson, Anna and Olanders, Knut and Lasson, Åke and Andersson, Roland}},
  issn         = {{1424-3903}},
  keywords     = {{monoclonal antibodies; endothelial barrier permeability; organ dysfunction; oxygen free radicals; protease inhibitors; platelet-activating factor antagonist; rat; scavenger; acute pancreatitis}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{14--25}},
  publisher    = {{Karger}},
  series       = {{Pancreatology}},
  title        = {{Multimodal management - of value in fulminant acute pancreatitis?}},
  url          = {{http://dx.doi.org/10.1159/000069148}},
  doi          = {{10.1159/000069148}},
  volume       = {{3}},
  year         = {{2003}},
}