Treatment with Lexipafant Ameliorates the Severity of Pancreatic Microvascular Endothelial Barrier Dysfunction in Rats with Acute Hemorrhagic Pancreatitis

Wang, Xiangdong; Sun, Zhengwu; Börjesson, Anna; Haraldsen, Pernille; Aldman, Malin Hagstrand; Deng, Xiaoming; Leveau, Per; Andersson, Roland

doi:10.1385/ijgc:25:1:45

Cited by 24 publications

(12 citation statements)

References 12 publications

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“…Several animal models of pancreatitis have shown that hemoconcentration is associated with the microcirculatory compromise that contributes to the tissue damage seen in acute pancreatitis (35)(36)(37). A number of therapeutic interventions aimed at correcting hemoconcentration have been studied in this critical period (9,35,(38)(39)(40)(41)(42). Our study, however, did not show any difference in those patients whose hemoconcentration was corrected versus those in whom it was not, and volume of fluid given in the first 24 hr was not associated with prognosis.…”

Section: Discussionmentioning

confidence: 99%

Admission Hematocrit: A Simple, Useful and Early Predictor of Severe Pancreatitis

Gan

Romagnuolo

2004

Dig Dis Sci

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Existing predictor systems of severe pancreatitis are cumbersome and can require up to 48 hr to complete. This study aimed to determine whether useful likelihood ratios exist for the prediction of severe pancreatitis, corresponding to various ranges of admission hematocrit. A retrospective cohort of 200 patients admitted with acute pancreatitis was identified. Likelihood ratios were calculated for a priori defined hematocrit ranges. Using multivariate logistic regression, initial hematocrit was evaluated as a predictor of severe pancreatitis as defined a priori by local and/or systemic complications (Atlanta criteria, 1992). Planned subgroup analysis was performed on those with a hematocrit >50%, stratified by 24-hr hematocrit. Fourteen patients (7%) developed severe pancreatitis. Likelihood ratios were 0.45, 0.70, and 7.5 for hematocrit ranges of < or =45, 45.1-49.9, and > or =50%, respectively. Hematocrit (as increases by 5%) was a significant predictor of severe pancreatitis (odds ratio [OR] = 2.8; P = 0.001), length of stay (P < 0.0001), necrosis (OR = 3.9; P = 0.001), and need for intensive care (OR 4.5; P = 0.002). The negative predictive value of the lowest range and positive predictive value of the highest range were 97% (95% CI: 92-99%) and 37% (16-62%), respectively. Lack of normalization of hematocrit by 24 hr did not predict severe pancreatitis. Initial hematocrit appears to be an early, simple, and useful predictor of severe pancreatitis. A normal 24-hr hematocrit does not appear to alter the prediction made by the initial hematocrit.

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Section: Discussionmentioning

confidence: 99%

Admission Hematocrit: A Simple, Useful and Early Predictor of Severe Pancreatitis

Gan

Romagnuolo

2004

Dig Dis Sci

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“…Furthermore, PAF seems to be partly involved in the activation of the protease-antiprotease system [21]. Numerous studies support the belief that PAF antagonists help preserve mucosal barrier function in both physiological and pathophysiological conditions, possibly by triggering endothelial and epithelial barrier permeability [8,9,21,22], or inhibiting tissue leukocyte recruitment in the small intestine and colon [22,23]. In the present study, we investigated the effect of PAF receptor antagonists on BT in acute edematous pancreatitis.…”

Section: Discussionmentioning

confidence: 93%

“…PAF seems to be involved in the release of cytokines, such as IL-1 and IL-6. Wang et al [8] have shown that intestinal epithelial damage occurs in AP and PAF antagonists decrease this damage as well as serum IL-1 levels. Liu et al [32] have shown that the PAF antagonist, BB-882, decreases BT but not TNF-· in acute necrotizing pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

“…In a cerulein rat model of pancreatitis, pretreatment with a PAF receptor antagonist reduced inflammatory injury in the pancreas [6,7]. PAF antagonists also exert beneficial effects on intestinal epithelial dysfunction in AP [8,9]. The present study was designed to discover whether PAF antagonists would reduce BT in acute edematous pancreatitis.…”

Section: Introductionmentioning

confidence: 99%

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Beneficial Effects of Recombinant Platelet-Activating Factor Acetylhydrolase and BN 52021 on Bacterial Translocation in Cerulein-Induced Pancreatitis

Bedirli

Gökahmetoğlu²,

Şakrak³

et al. 2004

Eur Surg Res

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Background: Bacterial translocation (BT) has been suggested to be responsible for the high incidence of infections occurring after acute pancreatitis (AP). The aim of this study was to investigate the effects of the platelet-activating factor (PAF) inactivator, recombinant PAF-acetylhydrolase (rPAF-AH), and the PAF receptor antagonist, BN 52021, in AP. Methods: Forty-eight male Wistar rats were divided into 4 groups: the sham group received saline intraperitoneally every hour for 6 h; the control group received cerulein 50 g/kg i.p. every hour for 6 h; the rPAF-AH group received AP plus rPAF-AH (5 mg/kg i.v. bolus), and the BN52021 group received AP plus BN 52021 (5 mg/kg i.v. bolus). The animals were sacrificed 12 h after the first cerulein injection. Results: Supramaximal cerulein stimulation induced an increase in serum pancreatic enzymes, interleukin (IL)-6, pancreatic edema, and produced histologic evidence of AP. Compared with the control group, the addition of PAF receptor antagonists had a significant effect on serum pancreatic enzymes, pancreatic edema, and the histologic score of the pancreatitis. AP caused significant increases in BT in mesenteric lymph nodes (MLNs), pancreas, liver, spleen and blood. Compared with the control group, both rPAF-AH and BN 52021 decreased BT in the pancreas and blood. In addition, rPAF-AH decreased BT in the MLNs. We also found that PAF receptor antagonists suppressed the elevation in IL-6 levels. Conclusion: PAF antagonists attenuated the severity of experimental AP and reduced pancreatitis-induced BT to distant sites.

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“…), arachidonic acids metabolites, as well as other activated fluid and cellular substances (free oxygen radicals, lysozyme, cytokines, etc.). Current studies have shown that PAF may transmit signals and exert its biological effects through the signal transduction system consisting of PAF-R, G-protein, and membrane effector enzyme [14] . PAF-R was found in the ligand-binding experiment of [15] .…”

Section: Xia Sh Et Al Effect Of Bn52021 On Paf-r In Pancreatitismentioning

confidence: 99%

Significance of platelet activating factor receptor expression in pancreatic tissues of rats with severe acute pancreatitis and effects of BN52021

Xia¹

2007

WJG

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± 0.04 vs 0.43 ± 0.09, P < 0.05), whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h, when compared with those in the NC group (0.90 ± 0.02 or 0.80 ± 0.05 vs 0.48 ± 0.02, 1.69 ± 0.06 or 1.58 ± 0.02 vs 0.48 ± 0.03, 1.12 ± 0.10 or 0.98 ± 0.03 vs 0.49 ± 0.09, 1.04 ± 0.14 or 0.87 ± 0.02 vs 0.52 ± 0.08, 0.97 ± 0.16 or 0.90 ± 0.05 vs 0.49 ± 0.10, P < 0.05), whereas there was no significant difference between the BN group and the SAP group.CONCLUSION: PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues. INTRODUCTIONSevere acute pancreatitis (SAP) is a serious condition which has an acute onset and a high death rate. So far, as pathogenesis of SAP has not been clarified, there is no clinically effective therapeutic strategy for it. Therefore, research on its pathogenesis and treatment is quite important. In recent years, people are concerned with the significance of the signal transduction pathway of platelet activating factor (PAF) in the pathogenesis. PAF is an endogenous active substance produced by multiple cells,which has extensively biological effects. Through binding with platelet activating factor receptor (PAF-R), PAF may, through G-protein transduction, activate RAPID COMMUNICATIONSignificance of platelet activating factor receptor expression in pancreatic tissues of rats with severe acute pancreatitis and effects of BN52021 Abstract AIM: To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B). METHODS:Wistar male rats were randomly assigned to the negative control group (NC group), SAP model group (SAP group), and BN52051-remedy group (BN group), and each of the groups was divided into 6 subgroups at different time points after operation (1 h, 2 h, 3 h, 6 h, 12 h, and 24 h) (n = 10 in each). PT-PCR and Western blot methods were used to detect PAFRmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected. RESULTS: Serum amylase and pathological resultsshowed the that SAP model was successfully prepared, BN52021 was able to decrease serum amylase, and the pathological ratings in BN group at 3 h, 6 h, and 12 h significantly decreased compared with those in the SAP group (8.85 ± 0.39 vs 5.95 ± 0.19, 9.15 ± 0.55 vs 5.55 ± 0.36, 10.10 ± 0.65 vs 6.72 ± 0.30, P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups, which increased gradually in early stage, reached a peak a...

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Treatment with Lexipafant Ameliorates the Severity of Pancreatic Microvascular Endothelial Barrier Dysfunction in Rats with Acute Hemorrhagic Pancreatitis

Cited by 24 publications

References 12 publications

Admission Hematocrit: A Simple, Useful and Early Predictor of Severe Pancreatitis

Admission Hematocrit: A Simple, Useful and Early Predictor of Severe Pancreatitis

Beneficial Effects of Recombinant Platelet-Activating Factor Acetylhydrolase and BN 52021 on Bacterial Translocation in Cerulein-Induced Pancreatitis

Significance of platelet activating factor receptor expression in pancreatic tissues of rats with severe acute pancreatitis and effects of BN52021

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