C-reactive protein accurately predicts severity of acute pancreatitis in children (original) (raw)
Related papers
Apigenin inhibits pancreatic stellate cell activity in pancreatitis
Journal of Surgical Research, 2015
Pancreatic stellate cells Parathyroid hormoneerelated protein a b s t r a c t Background: Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation, necrosis, and fibrosis. There are currently no drugs limiting pancreatic fibrosis associated with CP, and there is a definite need to fill this void in patient care.
Apigenin Decreases Acinar Cell Damage in Pancreatitis
Pancreas
Objective: Chronic pancreatitis is the consequence of multiple episodes of recurrent acute pancreatitis (RAP). We hypothesized that apigenin can minimize the sequelae of RAP by limiting acinar cells' pro-inflammatory signaling pathways. Methods: AR42J acinar cells were treated in vitro with transforming growth factor beta (TGF-β), apigenin, and other inhibitors. Dual luciferase reporter assay measured parathyroid hormone related protein (PTHrP) promoter activity. MAPK/ERK pathway activity was assessed by immunoblotting and in vivo by immunohistochemistry with a cerulein-induced RAP mouse model. Nuclear factor kappa B (NF-κB) nuclear localization was analyzed in vitro in cells stimulated with tumor necrosis factor alpha (TNF-α). Primary acini were isolated and treated with cerulein; interleukin 6 (IL-6) mRNA were measured comparing PTHrP wild-type and knockout mice. Results: Apigenin and PD98059 each downregulated TGF-β stimulation of PTHrP P3 promoter activity. In a RAP mouse model, apigenin reduced pERK nuclear localization in acinar cells and preserved acinar cell architecture. Apigenin suppressed TNF-α mediated signaling by decreasing NF-κB nuclear localization and decreased IL-6 mRNA levels via a PTHrP-dependent mechanism. Conclusions: Apigenin reduced inflammatory responses in experimental models of RAP. The mechanisms mediating the actions of apigenin, in part, are due to attenuation of PTHrP and TGF-β pro-inflammatory signaling.
In Vivo
Background/Aim: This study investigated the anti-inflammatory effect of apigenin in an experimental model of acute pancreatitis. Inflammatory response was reflected by tissue expression of the cytokine TNF-α coupled with histological examination. Materials and Methods: Wistar rats were divided into three groups: Sham-group animals underwent laparotomy only, without any other interventions. Control-group animals underwent laparotomy and bilio-pancreatic duct ligation to induce pancreatitis without apigenin administration. Apigenin group animals were further treated with apigenin. Euthanasia was performed at 6, 12, 24, 48 and 72 h post-operatively. Results: Over-expression of TNF-α in relation to postoperative time was observed in the control group (p<0.001). In the apigenin group, under-expression of TNF-α in relation to postoperative time was observed (p<0.013). At 72 h, apigenin reduced pancreatic TNF-α expression and prevented pancreatic necrosis. Conclusion: Apigenin slows progression and reduces severity of acute pancreatitis. Apigenin may serve as an adjunct to a more successful therapeutic strategy in acute pancreatitis.
Disordered Pancreatic Inflammatory Responses and Inhibition of Fibrosis in CD39-Null Mice
Gastroenterology, 2008
Background & Aims-Extracellular nucleotides are released from injured cells and bind to purinergic-type 2 receptors (P2-R) that modulate inflammatory responses. Ectonucleotidases, such as CD39/NTPDase1, hydrolyze extracellular nucleotides to integrate purinergic signaling responses. As the role of extracellular nucleotides and CD39 in mediating inflammation and fibrosis are poorly understood, we studied the impact of CD39 gene deletion in a model of pancreatic disease.
British Journal of Surgery, 2006
Background: It remains unclear whether interleukin (IL) 6 plays a role in initiating either the inflammatory or antiapoptotic responses in severe acute pancreatitis. This study examined the effect of neutralizing antibody against IL-6 on the induction of pancreatic acinar cell apoptosis and attenuation of the severity of severe acute pancreatitis. Methods: Experiments were conducted on laboratory mice with severe acute pancreatitis induced by lipopolysaccharide injection following six injections of caerulein at intervals of 6 h. Neutralizing monoclonal anti-IL-6 antibody was administered either 5 min or 2 h after the first caerulein injection. Apoptosis in pancreatic sections was determined by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labelling method.
PLoS ONE, 2013
Pancreatic fibrosis, a prominent histopathological feature of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma, is essentially a dynamic process that leads to irreversible scarring of parenchymal tissues of the pancreas. Though the exact mechanisms of its initiation and development are poorly understood, recent studies suggested that the activation of pancreatic stellate cells (PSCs) plays a critical role in eliciting such active course of fibrogenesis. Anthraquinone compounds possess anti-inflammatory bioactivities whereas its natural derivative rhein has been shown to effectively reduce tissue edema and free-radical production in rat models of inflammatory conditions. Apart from its anti-inflammatory properties, rhein actually exerts strong anti-fibrotic effects in our current in-vivo and in-vitro experiments. In the mouse model of cerulein-induced CP, prolonged administration of rhein at 50 mg/kg/day significantly decreased immunoreactivities of the principal fibrotic activators alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β) on pancreatic sections implicating the activation of PSCs, which is the central tread to fibrogenesis, was attenuated. Consequently, the overwhelmed deposition of extracellular matrix proteins fibronectin 1 (FN1) and type I collagen (COL I-α1) in exocrine parenchyma was found accordingly reduced. In addition, the expression levels of sonic hedgehog (SHH), which plays important roles in molecular modulation of various fibrotic processes, and its immediate effector GLI1 in pancreatic tissues were positively correlated to the degree of cerulein-induced fibrosis. Such up-regulation of SHH signaling was restrained in rhein-treated CP mice. In cultured PSCs, we demonstrated that the expression levels of TGF-β-stimulated fibrogenic markers including α-SMA, FN1 and COL I-α1 as well as SHH were all notably suppressed by the application of rhein at 10 μM. The present study firstly reported that rhein attenuates PSC activation and suppresses SHH/GLI1 signaling in pancreatic fibrosis. With strong anti-fibrotic effects provided, rhein can be a potential remedy for fibrotic and/or PSC-related pathologies in the pancreas. .hk PLOS ONE | www.plosone.org 1 December 2013 | Volume 8 | Issue 12 | e82201 experimental groups were subjected to standard H&E staining. Abnormal architecture, glandular atrophy and inflammatory cell infiltrates were evaluated from the H&E sections. Magnification 200 ×. (B) By means of Western blotting analyses, the expression levels of α-SMA and FN1 in pancreatic homogenates were examined. (C) Integrated densities of the immunobands of α-SMA and FN1 were measured, normalized to the loading reference β-ACTIN and calculated as fold changes over the Control group. Readings were taken from 4 individual blots. (D) Synthesis of collagen I-α1 mRNA and protein was determined by means of qPCR and Sirius Red staining respectively. Collagen proteins were stained with Sirius Red whereas non-collagenous proteins were stained with Fast Green. Color was eluted from the tissue sections and measured at 540 nm and 640 nm. * p< 0.05 when comparing to the Control group whereas Φp< 0.05 when comparing to the Cerulein group. (E) In paraffin-embedded pancreatic tissues, the activated PSCs were stained green (FITC) with α-SMA-antibody whereas nuclei were stained blue with DAPI. Magnification 200 ×. (F) Images enlarged from (E) using the SPOT Advanced program for a more detailed view of the activated PSCs. (G) mRNA expression levels of Acta2 and Tgf-β in pancreatic tissues were determined by means of qPCR using SYBR Green reagent, normalized to the internal reference Gapdh and expressed as fold changes over the Control group. * p< 0.05 when comparing to the Control group whereas Φ p< 0.05 when comparing to the Cerulein group.
The role of apigenin in an experimental model of acute pancreatitis
Journal of Surgical Research, 2013
Bilio-pancreatic duct ligation a b s t r a c t Aim: The aim of the present study is to evaluate pathologic changes in the pancreatic parenchyma in an experimental model of acute pancreatitis (AP) following bilio-pancreatic duct ligation. An effort was made to clarify the role of apigenin, a substance that is wellknown for its antioxidant and anti-inflammatory role and its likely beneficial activity to the pancreatic parenchyma following AP in rats.
Acute pancreatitis induces FasL gene expression and apoptosis in the liver1,2
Journal of Surgical Research, 2004
Background. Liver injury is an important prognostic indicator in acute pancreatitis. We previously demonstrated that Kupffer cell-derived cytokines mediate liver injury. In this work, we sought to characterize the role of Fas Ligand (FasL) in liver injury during acute pancreatitis. Methods. Acute pancreatitis was induced in mice using cerulein; serum FasL, AST, ALT, liver FasL, p38-MAPK, and caspase-3 were measured. FasL mRNA and protein and its receptor (Fas) were determined in rat Kupffer cells treated with elastase (1 U/ml) to mimic acute pancreatitis. Apoptosis was measured by flow cytometry. Results. Cerulein-induced pancreatitis increased serum AST, ALT, and FasL and up-regulated liver FasL (1315 ؎ 111 versus 310 ؎ 164 pg/ml, P ؍ 0.002 versus sham), while inducing p38-MAPK phosphorylation (P < 0.01 versus sham) and cleavage of caspase-3 (P < 0.04 versus sham); all were attenuated by pretreatment with the Kupffer cell inhibitor, gadolinium (all P < 0.003). In vitro, elastase induced a time-dependent increase in Kupffer cell FasL protein (FasL ؍ 404 ؎ 94 versus 170 ؎ 40, P ؍ 0.02, versus control), a 100-fold increase in FasL mRNA, and up-regulated Fas (FasL receptor). Gadolinium significantly attenuated the elastase-induced increase in FasL and FasL mRNA (FasL ؍ 230 ؎ 20 versus 404 ؎ 94, P ؍ 0.01, versus elastase) but had little effect on Fas. Additionally, elastase-primed Kupffer cell media induced apoptosis in hepatocytes (29 ؎ 1 versus 16% ؎ 1%; versus control, P < 0.001). Conclusions. Acute pancreatitis induces liver injury and hepatocyte death while up-regulating FasL, p38-MAPK, and caspase-3. Fas is up-regulated within Kupffer cells, suggesting that FasL may autoregulate its production by inducing its originator-cell death. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.
Use of activated protein C has no avail in the early phase of acute pancreatitis
HPB, 2008
Objectives. Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Subjects and method. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancratitis induction. Animals in group one (n 020) had a sham operation while animals in group two (n 020) received saline and animals in group three (n020) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activites were collected, and blood for serum amylase, urea, creatinine, and inleukin-6 measurements was withdrawn. Results. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,4359432 U/L vs. 27,4269 118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (9709323 pg/mL vs. 3309368 pg/mL, respectively). Conclusion. In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions.