Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-10-20
pubmed:abstractText
Platelet-activating factor (PAF) may play a critical and primary role in the pathogenesis of acute pancreatitis and pancreatitis-associated distant organ injury. The present study evaluated the effect of a PAF antagonist, lexipafant (an (S)-4-methyl-2[methyl-imidazo[4,5-c]pyridin-1-ylmethyl)-benzene sulphonyl]-amino]pentanoic acid ethyl ester, BB-882; British Biotech Ltd.), on the potential prevention of gut barrier dysfunction, by measuring gut origin sepsis, bidirectional permeability of the intestinal barrier, and pancreatic capillary endothelial barrier integrity, in acute pancreatitis induced by intraductal infusion of 5% sodium taurodeoxycholate. Pancreatic endothelial permeability significantly increased in animals with acute pancreatitis, whereas pretreatment with lexipafant had a preventive effect (p < 0.05 vs. pancreatitis with saline). Similarly, alterations noted in hematocrit and plasma levels of lipase and calcium were counteracted by the PAF antagonist. It also prevented the increase in albumin leakage from blood to the mucosal interstitium and from blood to the intestinal lumen in acute pancreatitis. Albumin passage from the gut lumen to blood in animals with pancreatitis pretreated with saline increased from 3 h and on, and lexipafant prevented alterations in mucosal epithelial permeability. Bacterial translocation was commonly seen in pancreatitis, whereas only a few positive cultures were observed in pancreatitis animals given lexipafant. Microthrombosis in intestinal villi seemed less frequent after lexipafant pretreatment. We conclude that (a) PAF may play a role in the pathogenesis of pancreatitis-associated intestinal dysfunction, (b) PAF may be involved in the development of distant organ dysfunction by triggering endothelial barrier dysfunction, and (c) PAF antagonists may provide potential agents for preventing pancreatitis-associated gut barrier dysfunction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0885-3177
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
107-19
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9700940-Acute Disease, pubmed-meshheading:9700940-Animals, pubmed-meshheading:9700940-Bacterial Translocation, pubmed-meshheading:9700940-Calcium, pubmed-meshheading:9700940-Capillary Permeability, pubmed-meshheading:9700940-Endothelium, Vascular, pubmed-meshheading:9700940-Enterobacteriaceae, pubmed-meshheading:9700940-Hematocrit, pubmed-meshheading:9700940-Imidazoles, pubmed-meshheading:9700940-Intestinal Mucosa, pubmed-meshheading:9700940-Leucine, pubmed-meshheading:9700940-Lipase, pubmed-meshheading:9700940-Male, pubmed-meshheading:9700940-Pancreas, pubmed-meshheading:9700940-Pancreatitis, pubmed-meshheading:9700940-Platelet Activating Factor, pubmed-meshheading:9700940-Rats, pubmed-meshheading:9700940-Rats, Sprague-Dawley, pubmed-meshheading:9700940-Taurodeoxycholic Acid
pubmed:year
1998
pubmed:articleTitle
Effect of a platelet-activating factor antagonist on pancreatitis-associated gut barrier dysfunction in rats.
pubmed:affiliation
Department of Surgery, Lund University Hospital, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't