The pathogenic mutations of APOA5 in Chinese patients with hyperlipidemic acute pancreatitis.

BACKGROUND AND AIMS: To study the role of gene mutations in the development of severe hypertriglyceridemia (HTG) in patients with hyperlipidemic acute pancreatitis (HLAP), especially different apolipoprotein A5 (APOA5) mutations. METHODS: Whole-exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The pathogenicity of mutations was then assessed by combining clinical information, predictions of bioinformatics programs, information from multiple gene databases, and residue location and conservation. The pathogenic mutations of APOA5 were visualized using the software. RESULTS: 1. Compared with BAP patients, pathogenic mutations of APOA5 were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common. 2. All six pathogenic mutations of APOA5 identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, and p.H182fs) were positively correlated with severe HTG; they were all in the important domains of apolipoprotein A-V (apoA-V). Residue 223 is strictly conserved in multiple mammals and is located in the lipoprotein lipase (LPL)-binding domain (Pro215-Phe261). When Arg 223 is mutated to Cys 223, the positive charge of this residue is reduced, which is potentially destructive to the binding function of apoA-V to LPL. 3. Four new APOA5 mutations were identified, namely c.563A > T, c.667C > T, c.788G > A, and c.544_545 insGGTGC. CONCLUSIONS: The pathogenic mutations of APOA5 were specific to the patients with HLAP and severe HTG in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment.

New technique for the endoscopic removal of long foreign bodies

Removing long foreign bodies (LFBs) is a challenge due to the risk of perforation is high, especially in anatomically narrow or acute angulations areas. Here we report a new technique for removing LFBs under endoscope. (AU)

Comparison of different intensive triglyceride-lowering therapies in patients with hyperlipidemic acute pancreatitis.

OBJECTIVES: The goal of this study was to investigate the clinical value of emergent triglyceride (TG)-lowering therapies for hyperlipidemic acute pancreatitis (HLAP). METHODS: 126 HLAP patients were assigned randomly to receive either conventional treatment (CT), normal saline (NS) alone, or continuous veno-venous hemofiltration (CVVH) as an intensive TG-lowering therapy. TG levels, clinical outcomes, and inflammatory biomarkers were compared among the three groups. RESULTS: Baseline characteristics did not differ significantly among the groups. CVVH removed TG from the plasma and achieved its target TG (<500 mg/dL) in approximately 25 h, compared to 40 h in the NS alone group and no targeted effect within 48 h in the CT group (P < 0.05). Although the majority of clinical outcomes did not differ significantly, an unexpectedly higher incidence of organ failure occurred in the CVVH group compared to the others. Hospital costs, severe AP patients and length of stay were significantly higher in the CVVH group compared to the other groups (P < 0.005). CONCLUSIONS: Early CVVH lowers TG levels more efficiently than NS alone or CT therapy, but is not superior in terms of clinical outcomes and costs. NS also lowers TG levels and is significantly less costly than the other two treatments. Further multicenter studies are needed to determine the feasibility of NS alone treatment for HLAP patients.

New technique for endoscopic removal of long foreign bodies.

Removing long foreign bodies (LFBs) is a challenge due to the risk of perforation is high, especially in anatomically narrow or acute angulations areas. Here we report a new technique for removing LFBs under endoscope.

The clinical significance of serum HbA1c to diagnose diabetes mellitus during acute pancreatitis.

AIMS: To investigate the prevalence of diabetes mellitus (DM) in acute pancreatitis (AP) patients and to explore the extent to which inflammatory stress affects plasma glucose (PG) levels in AP patients. METHODS: A retrospective analysis of 2163 AP patients was performed. The PG differences among AP patients under differing pancreatic necrosis conditions and inflammation severity were compared. Receiver operating characteristic curves were used to assess whether fasting PG in the inflammatory stage of AP might be used for DM screening. RESULTS: The overall DM prevalence was 19.97% in AP patients, 32.41% of whom had newly diagnosed DM (based on HbA1c levels in patients who self-reported no DM). The DM prevalence was 46.93% in hyperlipidemic AP patients, 44.14% of whom had newly diagnosed DM. In patients with and without pancreatic necrosis, the optimal PG thresholds for the screening of newly diagnosed DM were 10.40 mmol/L and 8.21 mmol/L, respectively, with an AUC of 0.959 ± 0.034 (P < 0.001) and 0.972 ± 0.006 (P < 0.001), respectively. CONCLUSIONS: For hospitalized AP patients and fasting PG levels exceeding 10 mmol/L (with necrosis) or 8 mmol/L (without necrosis) (P < 0.001), HbA1c testing is recommended to investigate the presence of comorbid undiagnosed DM.

Percutaneous transhepatic cholangiography and drainage and endoscopic retrograde cholangiopancreatograph for hilar cholangiocarcinoma: which one is preferred?

INTRODUCTION: both percutaneous transhepatic cholangiography and drainage (PTCD) and endoscopic retrograde cholangiopancreatography (ERCP) with SEMS implantation have been used for unresectable hilar cholangiocarcinoma (HC) in the clinic for many years. However, which one is preferred is still unknown. OBJECTIVE: to study the effects of biliary drainage of self-expanding metal stents (SEMS) implantation under PTCD or ERCP to treat HC. METHODS: the clinical data of 82 patients with HC from January 2006 to January 2015 were recorded retrospectively. Patients were treated with biliary implantation of self-expanding metal stents (SEMS) under PTCD (PTCD group, 40 patients) or ERCP (ERCP group, 42 patients). Clinical data, including total bilirubin concentrations, complications and survival time were analyzed. RESULTS: the remission of jaundice was similar in both groups (p > 0.05). The median survival time of the ERCP group and PTCD group were 237 d and 252 d respectively, with no significant differences (p > 0.05). The biliary infection rates under ERCP and PTCD procedure were 52.4 % and 20.0 % respectively, with a significant statistical difference (p < 0.05). For those HC patients of Bismuth III/IV, the infection rates under ERCP and PTCD procedure were 58.3 % and 14.3 %, respectively (p < 0.05). CONCLUSIONS: both PTCD and ERCP with SEMS implantation were effective to prolong the survival time of HC patients. The biliary infection rates were higher in the ERCP group, especially for Bismuth III/IV HC patients

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Percutaneous transhepatic cholangiography and drainage and endoscopic retrograde cholangiopancreatograph for hilar cholangiocarcinoma: which one is preferred?

INTRODUCTION: both percutaneous transhepatic cholangiography and drainage (PTCD) and endoscopic retrograde cholangiopancreatography (ERCP) with SEMS implantation have been used for unresectable hilar cholangiocarcinoma (HC) in the clinic for many years. However, which one is preferred is still unknown. OBJECTIVE: to study the effects of biliary drainage of self-expanding metal stents (SEMS) implantation under PTCD or ERCP to treat HC. METHODS: the clinical data of 82 patients with HC from January 2006 to January 2015 were recorded retrospectively. Patients were treated with biliary implantation of self-expanding metal stents (SEMS) under PTCD (PTCD group, 40 patients) or ERCP (ERCP group, 42 patients). Clinical data, including total bilirubin concentrations, complications and survival time were analyzed. RESULTS: the remission of jaundice was similar in both groups (p > 0.05). The median survival time of the ERCP group and PTCD group were 237 d and 252 d respectively, with no significant differences (p > 0.05). The biliary infection rates under ERCP and PTCD procedure were 52.4 % and 20.0 % respectively, with a significant statistical difference (p < 0.05). For those HC patients of Bismuth III/IV, the infection rates under ERCP and PTCD procedure were 58.3 % and 14.3 %, respectively (p < 0.05). CONCLUSIONS: both PTCD and ERCP with SEMS implantation were effective to prolong the survival time of HC patients. The biliary infection rates were higher in the ERCP group, especially for Bismuth III/IV HC patients.

EndoClot®SIS Polysaccharide Injection as a Submucosal Fluid Cushion for Endoscopic Mucosal Therapies: Results of Ex Vivo and In Vivo Studies.

BACKGROUND: There are many studies on submucosal injection materials, but their clinical use is restricted for various reasons. The objective of this study was to compare the feasibility and safety of injected EndoClot®SIS polysaccharide as a submucosal injection material (SFC) in ESD in the pig stomach to that of injected sigMAVisc™ or Eleview™. METHODS: Four pig stomachs were used for the ex vivo study. Eighteen pigs were used for the in vivo study. In the ex vivo study, four injections were made in the gastric submucosa to induce submucosal uplift and extend its duration. Tissue change was observed. The in vivo study was performed in 2 steps. First, 3 injections were made in the esophageal mucosa to induce submucosal uplift and extend its duration. Histological change was observed. Second, ESD was performed in the stomach by injecting EndoClot®SIS polysaccharide, sigMAVisc™, or Eleview™ (each, n = 6) as an SFC. The effects of these agents on wound healing were examined. We evaluated the efficacy and safety of endoscopic surgery after EndoClot®SIS polysaccharide injection. RESULTS: EndoClot®SIS polysaccharide produced a longer-lasting elevation with clearer margins than was achieved by sigMAVisc™, Eleview™, or 0.9% NaCl and thereby enabled precise ESD without complications, such as bleeding and perforation. No obvious histopathological damage was observed at the injection site on endoscopy and histology. CONCLUSION: Submucosally injected EndoClot®SIS polysaccharide increased the effective separation of the mucosa and submucosa and reduced surgical complications. Hence, EndoClot®SIS polysaccharide injection is a safe and effective submucosal injection material.

Analyses of predictive factors for pathological complete remission in neoadjuvant therapy for locally advanced rectal cancer.

PURPOSE: To analyze relevant factors for pathological complete remission (pCR) after neoadjuvant therapy for locally advanced rectal cancer. METHODS: The clinical data of 531 patients with the American Joint Committee on Cancer (AJCC) stage II or III rectal cancer from January 2014 to December 2017 were retrospectively analyzed. Among these patients, 100 (18.83%) patients achieved pCR. Univariate and multivariate logistic regression analyses were applied to analyze the predictive factors for pCR after neoadjuvant therapy. RESULTS: According to univariate analysis, carcinoembryonic antigen (CEA) before chemo-radiotherapy (CRT) (p=0.021), tumor (T) stage before CRT (p=0.002), interval between the end of CRT and surgery (p<0.001) and maximum depth of tumor invasion before CRT (p=0.039) influenced significantly pCR. Multivariate analysis manifested that the CEA level before CRT [p=0.037, odds ratio (OR) =0.435] and the interval between the end of CRT and surgery (p=0.004, OR=2.864) were significant predictive factors for pCR. Stratified analysis showed that low-level CEA before CRT (p=0.029) affected pCR only in non-smoking group. CONCLUSIONS: pCR can be observed in some patients with locally advanced rectal cancer after neoadjuvant therapy. Low-level CEA before CRT and long interval between CRT and surgery are predictive factors for pCR of preoperative neoadjuvant therapy for locally advanced rectal cancer, but low-level CEA is effective in predicting pCR in non-smokers only.

Luteolin Ameliorates Experimental Chronic Pancreatitis Induced by Trinitrobenzenesulfonic Acid in Rats.

OBJECTIVES: The purpose of this study is to assess the effect and possible mechanism of luteolin on chronic pancreatitis (CP). METHODS: Trinitrobenzenesulfonic acid-induced CP was used as CP models in vivo. After the intervention of luteolin for 28 days, chronic pancreatic injury was assessed by serum hydroxyproline and pancreatic histology. α-Smooth muscle actin (α-SMA) expression was performed to detect the activation of pancreatic stellate cells (PSCs). Pancreatic stellate cells were also isolated and cultured in vitro, and the effect of luteolin on PSCs was evaluated. Transforming growth factor ß (TGF-ß1) signaling and its regulated mRNA expression was tested by Western blot and quantitative real-time polymerase chain reaction, respectively. RESULTS: The protective role of luteolin on CP was confirmed by increased pancreas/body weight ratio, decreased pancreas hydroxyproline level, and reduced fibrosis. α-SMA expressions in PSCs were significantly decreased both in vitro and in vivo after the management of luteolin. Pancreas TGF-ß1 expression was significantly decreased by luteolin. Luteolin inhibited the proliferation and activation of PSCs in a dose-dependent manner. CONCLUSIONS: Luteolin played a protective role in CP in many aspects, partly by regulating release of inflammatory cytokines through TGF-ß1 signaling pathway.

Enhancement of Proliferation and Invasion of Gastric Cancer Cell by KDM5C Via Decrease in p53 Expression.

Gastric cancer is a malignancy with high incidence and the second leading cause of cancer death worldwide. Development of efficient therapies against gastric cancer is urgent. Until now, the mechanisms of gastric cancer genesis remain elusive. The KDM5C is a histone demethylase that promotes cancer cell growth and is enriched in drug-resistant cancer cells. But the pathogenic breadth and mechanistic aspects of this effect relative to gastric cancer have not been defined. In present study, we found that KDM5C was overexpressed in gastric cancer cell lines and gastric cancer tissues but not in normal gastric tissues. The proliferation and invasive potential of gastric cancer cells was significantly increased by ectopic expression of KDM5C. Contrarily, RNA interference targeting KDM5C in gastric cancer cells significantly decreased the proliferation and invasive potential of cells. Moreover, we also found that the expression of p53 was modulated by KDM5C. Cells with overexpression of KDM5C exhibited greatly decreased p53 expression, whereas silencing of KDM5C expression dramatically increased p53 expression at both the messenger RNA and protein levels. Inhibition of p53 by small-interfering RNA reversed the shKDM5C-induced proliferation and invasion. Our results collectively suggested that KDM5C played a role in gastric cancer cells proliferation and invasion, which may be partly associated with the p53 expression.

Role of Microvesicles From Bone Marrow Mesenchymal Stem Cells in Acute Pancreatitis.

OBJECTIVES: Mesenchymal stem cells (MSCs) have shown an obvious protective effect on acute pancreatitis (AP). The purpose of the present study was to analyze the effect of bone marrow MSC-derived microvesicles (bmMSC-MVs) on AP and explore the underlying mechanisms. METHODS: Bone marrow MSCs and bmMSC-MVs were isolated from Sprague-Dawley rats. Cerulein-induced mild AP (MAP) and sodium taurocholate-induced severe AP (SAP) were used as AP models in vivo and in vitro. Pancreatic injury was evaluated by measuring serum levels of amylase, lipase, chemokines, and interleukins, and by pancreatic histology, reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. The effects of bmMSC-MVs on the survival rates of pancreatic acinar cells in vitro were also assessed. RESULTS: Bone marrow MSC-MVs attenuated acute pancreatic injury in MAP and SAP by regulating IL-1α, IL-6, and TNF-α, and dramatically attenuated the nuclear translocation of NF-κB p65 in MAP and SAP. Bone marrow MSC-MVs improved the survival rates of pancreatic acinar cells in MAP and SAP models in vitro. CONCLUSIONS: Bone marrow MSC-MVs played a protective role in AP by reducing the levels of proinflammatory cytokines and regulating the nuclear translocation of NF-κB p65. Bone marrow MSC-MVs could be developed as a strategy for the clinical treatment of SAP.

Halitosis and helicobacter pylori infection: A meta-analysis.

BACKGROUND: Halitosis is used to describe any disagreeable odor of expired air regardless of its origin. Numerous trials published have investigated the relation between Helicobacter pylori (H pylori) infection and halitosis, and even some regimes of H pylori eradication have been prescribed to those patients with halitosis in the clinic. We conducted a meta-analysis to define the correlation between H pylori infection and halitosis. OBJECTIVES: To evaluate whether there is a real correlation between H pylori infection and halitosis, and whether H pylori eradication therapy will help relieve halitosis. METHODS: We searched several electronic databases (The Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, and Wanfangdata) up to December 2015. Studies published in English and Chinese were considered in this review. After a final set of studies was identified, the list of references reported in the included reports was reviewed to identify additional studies. Screening of titles and abstracts, data extraction and quality assessment was undertaken independently and in duplicate. All analyses were done using Review Manager 5.2 software. RESULTS: A total of 115 articles were identified, 21 of which met the inclusion criteria and presented data that could be used in the analysis. The results showed that the OR of H pylori infection in the stomach between halitosis-positive patients and halitosis-negative patients was 4.03 (95% CI: 1.41-11.50; P = 0.009). The OR of halitosis between H pylori-positive patients and H pylori-negative patients was 2.85 (95% CI: 1.40-5.83; P = 0.004); The RR of halitosis after successful H pylori eradication in those H pylori-infected halitosis-positive patients was 0.17 (95% CI: 0.08-0.39; P <0.0001), compared with those patients without successful H pylori eradication. And the RR of halitosis before successful H pylori eradication therapy was 4.78 (95% CI: 1.45-15.80; P = 0.01), compared with after successful H pylori eradication therapy. CONCLUSIONS: There is clear evidence that H pylori infection correlates with halitosis. H pylori infection might be important in the pathophysiological mechanism of halitosis, and H pylori eradication therapy may be helpful in those patients with refractory halitosis.

Simple risk factors to predict urgent endoscopy in nonvariceal upper gastrointestinal bleeding pre-endoscopically.

The goal of this study is to evaluate how to predict high-risk nonvariceal upper gastrointestinal bleeding (NVUGIB) pre-endoscopically. A total of 569 NVUGIB patients between Match 2011 and January 2015 were retrospectively studied. The clinical characteristics and laboratory data were statistically analyzed. The severity of NVUGIB was based on high-risk NVUGIB (Forrest I-IIb), and low-risk NVUGIB (Forrest IIc and III). By logistic regression and receiver-operating characteristic curve, simple risk score systems were derived which predicted patients' risks of potentially needing endoscopic intervention to control bleeding. Risk score systems combined of patients' serum hemoglobin (Hb) ≤75 g/L, red hematemesis, red stool, shock, and blood urine nitrogen ≥8.5 mmol/L within 24 hours after admission were derived. As for each one of these clinical signs, the relatively high specificity was 97.9% for shock, 96.4% for red stool, 85.5% for red hematemesis, 76.7% for Hb ≤75 g/L, and the sensitivity was 50.8% for red hematemesis, 47.5% for Hb ≤75 g/L, 14.2% for red stool, and 10.9% for shock. When these 5 clinical signs were presented as a risk score system, the highest area of receiver-operating characteristic curve was 0.746, with sensitivity 0.675 and specificity 0.733, which discriminated well with high-risk NVUGIB. These simple risk factors identified patients with high-risk NVUGIB of needing treatment to manage their bleeding pre-endoscopically. Further validation in the clinic was required.

Retinoic Acid Ameliorates Pancreatic Fibrosis and Inhibits the Activation of Pancreatic Stellate Cells in Mice with Experimental Chronic Pancreatitis via Suppressing the Wnt/ß-Catenin Signaling Pathway.

Pancreatic fibrosis, a prominent feature of chronic pancreatitis (CP), induces persistent and permanent damage in the pancreas. Pancreatic stellate cells (PSCs) provide a major source of extracellular matrix (ECM) deposition during pancreatic injury, and persistent activation of PSCs plays a vital role in the progression of pancreatic fibrosis. Retinoic acid (RA), a retinoid, has a broad range of biological functions, including regulation of cell differentiation and proliferation, attenuating progressive fibrosis of multiple organs. In the present study, we investigated the effects of RA on fibrosis in experimental CP and cultured PSCs. CP was induced in mice by repetitive cerulein injection in vivo, and mouse PSCs were isolated and activated in vitro. Suppression of pancreatic fibrosis upon administration of RA was confirmed based on reduction of histological damage, α-smooth muscle actin (α-SMA) expression and mRNA levels of ß-catenin, platelet-derived growth factor (PDGF)-Rß transforming growth factor (TGF)-ßRII and collagen 1α1 in vivo. Wnt 2 and ß-catenin protein levels were markedly down-regulated, while Axin 2 expression level was up-regulated in the presence of RA, both in vivo and in vitro. Nuclear translation of ß-catenin was significantly decreased following RA treatment, compared with cerulein-induced CP in mice and activated PSCs. Furthermore, RA induced significant PSC apoptosis, inhibited proliferation, suppressed TCF/LEF-dependent transcriptional activity and ECM production of PSC via down-regulation of TGFßRII, PDGFRß and collagen 1α1 in vitro. These results indicate a critical role of the Wnt/ß-catenin signaling pathway in RA-induced effects on CP and PSC regulation and support the potential of RA as a suppressor of pancreatic fibrosis in mice.

Rosmarinic Acid Attenuates Sodium Taurocholate-Induced Acute Pancreatitis in Rats by Inhibiting Nuclear Factor-κB Activation.

Rosmarinic Acid (RA), a caffeic acid ester, has been shown to exert anti-inflammation, anti-oxidant and antiallergic effects. Our study aimed to investigate the effect of RA in sodium taurocholate ( NaTC )-induced acute pancreatitis, both in vivo and in vitro. In vivo, RA (50 mg/kg) was administered intraperitoneally 2 h before sodium taurocholate injection. Rats were sacrificed 12 h, 24 h or 48 h after sodium taurocholate injection. Pretreatment with RA significantly ameliorated pancreas histopathological changes, decreased amylase and lipase activities in serum, lowered myeloperoxidase activity in the pancreas, reduced systematic and pancreatic interleukin-1 ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) levels, and inhibited NF-κB translocation in pancreas. In vitro, pretreating the fresh rat pancreatic acinar cells with 80 µ mol/L RA 2 h before 3750 nmol/L sodium taurocholate or 10 ng/L TNF-α administration significantly attenuated the reduction of isolated pancreatic acinar cell viability and inhibited the nuclear activation and translocation of NF-κB. Based on our findings, RA appears to attenuate damage in sodium taurocholate-induced acute pancreatitis and reduce the release of inflammatory cytokines by inhibiting the activation of NF-κB. These findings might provide a basis for investigating the therapeutic role of RA in managing acute pancreatits.

Different Clinical Presentations of Hyperlipidemic Acute Pancreatitis: A Retrospective Study.

OBJECTIVES: The goal of this study was to summarize the clinical features of hyperlipidemic acute pancreatitis (HLAP), and help clinicians understand the characteristic presentations of HLAP. METHODS: From July 2009 to June 2013, 1073 cases of acute pancreatitis were retrospectively assessed. The clinical characteristics of HLAP and non-HLAP were statistically analyzed. RESULTS: The etiologic ratio of HLAP in acute pancreatitis rose from 13% in 2009 to 25.6% in 2013. Diabetes mellitus, fatty liver, and acute pancreatitis recurrence were positively correlated with HLAP, and female sex, age (>60 years), and alkaline phosphatase level were negatively correlated with HLAP. The diagnostic accuracy of amylase in HLAP was only 40.38%, compared with lipase (91.83%). Different cutoff points of serum triglyceride on day 1 (5.33 mmol/L), day 2 (2.77 mmol/L), and day 3 (2.18 mmol/L) could be used to obtain an accurate diagnosis of HLAP. Higher incidences of acute peripancreatic fluid collection, renal failure, and severe acute pancreatitis were also observed in patients with HLAP. CONCLUSIONS: Different clinical presentations of HLAP should be applied to be distinguished from non-HLAP in the clinic.

Role of bone marrow mesenchymal stem cells in L-arg-induced acute pancreatitis: effects and possible mechanisms.

OBJECTIVES: Mesenchymal stem cells (MSCs) have shown an obvious protective effect on systemic inflammation. The purpose of this study is to assess the effect and possible mechanism of bone marrow MSCs (bmMSCs) on acute pancreatitis (AP). METHODS: BmMSCs of SD rats were isolated and cultured in vitro. L-Arginine-induced acute pancreatitis was used as AP model in vivo. Pancreatic injury was assessed by serum amylase, lipase, cytokines and pancreatic histology. RT-PCR was applied to investigate mRNA expression of pancreas tissue. Western-blot and immunohistochemistry (IHC) were applied to test the role of NF-κB p65 signaling pathway. Tracking and Positioning of CM-Dil labeled bmMSCs in vivo was further studied. RESULTS: Treatment with bmMSCs attenuated acute pancreatic injury and AP-associated lung injury obviously, with decreased serum IL-1ß, IL-6, TNF-α, down-regulated expressions of IL-1α, IL-6, TNFα in pancreas tissue and reduced nuclear translocation of NF-κB p65 in AP. Localization of bmMSCs in vivo was due to being passively trapped in related organs, but not actively homing to inflammatory sites of pancreas during the early phase of AP. CONCLUSIONS: Taken together, the results showed that bmMSCs played a protective role in AP in many aspects, which might protect against experimental pancreatitis partly by regulating release of inflammatory cytokines by an exocrine secretion.