title: Treatment with lexipafant ameliorates the severity of pancreatic microvascular endothelial barrier dysfunction in rats with acute hemorrhagic pancreatitis.
abstract: CONCLUSIONS
  Treatment with lexipafant reduced the severity of pancreatitis-associated endothelial barrier compromise, also associated with a decrease in systemic concentrations of interleukin (IL) 1. Thus, the present findings imply that platelet-activating factor (PAF) may play an important role in the pathogenesis of pancreatic endothelial dysfunction by signaling and triggering the production and release of certain cytokines.
  
  
  BACKGROUND
  Pancreatic capillary endothelial barrier dysfunction is an initial and characteristic feature of acute pancreatic injury and pancreatitis. PAF, a proinflammatory mediator and an intercellular signaling substance, has been considered to be involved in the inflammatory reaction and the systemic endothelial dysfunction of acute pancreatitis.
  
  
  METHODS
  The development of pancreatic capillary endothelial barrier dysfunction was monitored by tissue edema and exudation of plasma albumin into the interstitium, 3 and 12 h after induction of acute pancreatitis by intraductal infusion of 5% sodium taurodeoxycholate in rats. Pancreatic leukocyte recruitment was reflected by measuring myeloperoxidase activity. Serum levels of IL-1 beta and IL-6 were determined by an enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Pretreatment with lexipafant, a potent PAF receptor antagonist, significantly reduced the pancreatitis-induced increase in pancreatic endothelial barrier dysfunction, pancreatic leukocyte recruitment and serum levels of IL-1 beta, although a difference persisted between animals with sham operation and pancreatitis.
authors.affiliation: Department of Surgery, Lund University Hospital, Sweden.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.forename: A
authors.initials: A
authors.lastname: Börjesson
authors.forename: P
authors.initials: P
authors.lastname: Haraldsen
authors.forename: M
authors.initials: M
authors.lastname: Aldman
authors.forename: X
authors.initials: X
authors.lastname: Deng
authors.forename: P
authors.initials: P
authors.lastname: Leveau
authors.forename: R
authors.initials: R
authors.lastname: Andersson
mesh_terms: D000208:Acute Disease; D000818:Animals; D001834:Body Water / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors
chemical_list: D007093:Imidazoles; D007375:Interleukin-1; D015850:Interleukin-6; D010972:Platelet Activating Factor; D012709:Serum Albumin; D007930:Leucine; C103289:lexipafant