Na Shi

Rectal indomethacin for the prevention of post-ERCP pancreatitis: A meta-analysis of randomized controlled trials.

BACKGROUND/AIMS This meta-analysis was undertaken to evaluate the effect of rectal indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. MATERIALS AND METHODS Major databases including Embase, Medline, Science Citation Index Expanded, Pubmed and the Cochrane Central Register of Controlled Trials, were searched to identify all relevant studies from January 1960 to July 2013. Randomized controlled trials (RCTs) comparing prophylactic use of rectal indomethacin versus placebo were included. Risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed- or random-effect models. RESULTS Three studies met the inclusion criteria and were included in the final analyses. The overall incidence of post-ERCP pancreatitis (PEP) was significantly decreased by prophylactic rectal indomethacin compared with the placebo (RR=0.51; 95% CI=0.37-0.70). The pooled incidence of moderate to severe pancreatitis was also decreased by rectal indomethacin prophylaxis (RR=0.43; 95% CI=0.23-0.80). CONCLUSION Rectal indomethacin can reduce the overall incidence and the severity of PEP.

Circulating microRNA 216 as a Marker for the Early Identification of Severe Acute Pancreatitis

Background: To study the value of circulating microRNA 216 (miR‐216) as a marker for the severity of acute pancreatitis (AP) in both murine models and patients. Materials and Methods: Mice with AP were induced by intraperitoneal injection of 50 &mgr;g/kg/hour cerulean either 7 times, sacrificed at 8, 9, 10, 11 or 12 hours after the first injection, or 12 times, sacrificed at 24 hours after the first injection. Plasma samples and data from patients with AP were obtained from a prospective cohort. Quantitative reverse transcription polymerase chain reaction was used to determine the miR‐216a and miR‐216b level. Results: The upregulation of miR‐216a and miR‐216b in the serum of mice was induced by cerulean injection in both the 7‐ and 12‐injection groups (P < 0.05). The downregulation of miR‐216a in pancreatic tissues of mice with AP was detected (P < 0.05), but no difference was observed in pancreatic miR‐216b levels among any of the groups (all P > 0.05). The serum miR‐216a level was positively correlated with pancreatic histopathology severity scores, and was negatively correlated with pancreatic miR‐216a (r = −0.483, P = 0.009). The plasma miR‐216a level was significantly upregulated in patients with severe AP (SAP) compared with patients with mild AP (MAP) or moderate severe AP (MSAP) (SAP versus MAP, P = 0.04; SAP versus MSAP, P = 0.00), but no difference was seen between patients with MAP and those with MSAP (P = 0.73). Conclusions: Circulating miR‐216a might be a potential biomarker for the early identification of SAP.

Underexpression of Receptor for Activated C Kinase 1 (RACK1) in Leukocytes from Patients with Severe Acute Pancreatitis

Receptor for activated C kinase 1 (RACK1) plays an important role in regulating the immune response and cytokine expression. However, little is known about its role in acute pancreatitis (AP). We therefore investigated the role of RACK1 in AP and explored its relationship with interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), both of which are related to AP severity. Two rat models of chemically induced AP with different severities were used: acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP). The expression levels of IL-6 and TNF-α mRNAs and proteins were significantly increased in leukocytes from AEP and ANP rats, compared with the levels in the control animals, while the expression levels of RACK1 mRNA and protein were significantly decreased in leukocytes from these AP rats. Moreover, the RACK1 levels in leukocytes were significantly lower in ANP rats than those in AEP rats. Consequently, AP patients and healthy volunteers (HVs) were enrolled in this study. Compared with the HVs (n = 5), the expression levels of IL-6 and TNF-α mRNAs and proteins were significantly higher in leukocytes from 15 AP patients, including patients with mild AP (n = 5). By contrast, the expression levels of RACK1 mRNA and protein in leukocytes were significantly lower among patients with severe AP (n = 5) and with moderately severe AP (n = 5), compared with the HVs. The expression levels of RACK1 mRNA were negatively correlated with the IL-6 and TNF-α mRNA levels. Thus, RACK1 may alleviate the severity of AP.

Protective effects of flavonoids from Coreopsis tinctoria Nutt. on experimental acute pancreatitis via Nrf-2/ARE-mediated antioxidant pathways

ETHNOPHARMACOLOGICAL RELEVANCE Oxidative stress is a prominent feature of clinical acute pancreatitis (AP). Coreopsis tinctoria has been used traditionally to treat pancreas disorders like diabetes mellitus in China and Portugal and its flavonoid-rich fraction contain the main phytochemicals that have antioxidant and anti-inflammatory activities. AIM OF THE STUDY To investigate the effects of flavonoids isolated from C. tinctoria on experimental AP and explore the potential mechanism. MATERIALS AND METHODS LC-MS based online technique was used to analyse and isolate targeted flavonoids from C. tinctoria. Freshly isolated mouse pancreatic acinar cells were treated with taurocholic acid sodium salt hydrate (NaT, 5 mM) with or without flavonoids. Fluorescence microscopy and a plate reader were used to determine necrotic cell death pathway activation (propidium iodide), reactive oxygen species (ROS) production (H2-DCFDA) and ATP depletion (luminescence) where appropriate. AP was induced by 7 repeated intraperitoneal caerulein injections (50 μg/kg) at hourly interval in mice or retrograde infusion of taurolithocholic acid 3-sulfate disodium salt (TLCS; 5 mM, 50 μL) into the pancreatic duct in mice or infusion of NaT (3.5%, 1 mL/kg) in rats. A flavonoid was intraperitoneally administered at 0, 4, and 8 h after the first caerulein injection or post-operation. Disease severity, oxidative stress and antioxidant markers were determined. RESULTS Total flavonoids extract and flavonoids 1-6 (C1-C6) exhibited different capacities in reducing necrotic cell death pathway activation with 0.5 mM C1, (2 R,3 R)-taxifolin 7-O-β-D-glucopyranoside, having the best effect. C1 also significantly reduced NaT-induced ROS production and ATP depletion. C1 at 12.5 mg/kg and 8.7 mg/kg (equivalent to 12.5 mg/kg for mice) significantly reduced histopathological, biochemical and immunological parameters in the caerulein-, TLCS- and NaT-induced AP models, respectively. C1 administration increased pancreatic nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-medicated haeme oxygenase-1 expression and elevated pancreatic antioxidant enzymes superoxide dismutase and glutathione peroxidase levels. CONCLUSIONS Flavonoid C1 from C. tinctoria was protective in experimental AP and this effect may at least in part be attributed to its antioxidant effects by activation of Nrf2-mediated pathways. These results suggest the potential utilisation of C. tinctoria to treat AP.

Plasma cytokines can help to identify the development of severe acute pancreatitis on admission

Abstract Severe acute pancreatitis (AP) is associated with high morbidity and mortality. Early severity stratification remains a challenging issue to overcome to improve outcomes. We aim to find novel plasma cytokines for the early identification of severe AP according to the revised Atlanta criteria. In this prospective observational study, 30 cytokines, screened semiquantitatively with a human multicytokine array, were submitted to quantitative determination using either microparticle-based multiplex immunoassays analyzed on a Luminex 100 platform or enzyme-linked immunosorbent assay kits. The cytokine profiles of patients and the discriminative value of cytokines for severe AP were analyzed. Plasma samples of 70 patients with AP (20 mild, 30 moderately severe, and 20 severe) were selected in this study if they were admitted within 48 hours of the onset of symptoms. Plasma from healthy volunteers was collected as the healthy control. Growth differentiation factor-15 (GDF-15) and pentraxin 3 (PTX3) on admission were independent prognostic markers for the development of severe AP and had higher discriminative powers than conventional markers (GDF-15 vs hematocrit, P = .003; GDF-15 vs C-reactive protein, P = .037; GDF-15 vs creatinine, P = .048; GDF-15 vs Acute Physiology and Chronic Health Evaluation II, P = .007; PTX3 vs hematocrit, P = .006; PTX3 vs C-reactive protein, P = .047; PTX3 vs Acute Physiology and Chronic Health Evaluation II, P = .011; PTX3 vs Bedside Index for Severity in Acute Pancreatitis, P = .048). Plasma GDF-15 and PTX3 can help to identify the development of severe AP on admission. Future work should validate their accuracy in a larger, multicenter patient cohort.

Chai-Qin-Cheng-Qi Decoction and Carbachol Improve Intestinal Motility by Regulating Protein Kinase C-Mediated Ca2

Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 μg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-β1) mRNA and PLC protein (both P < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P < 0.05). Neither treatment significantly altered L-arginine-induced PKC-β1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC.

Is MicroRNA-127 a Novel Biomarker for Acute Pancreatitis with Lung Injury?

Background and Aims The aim of this study was to determine the expression of microRNA-127 (miR-127) in both rat models and patients of acute pancreatitis (AP) with lung injury (LI). Methods Rats were administrated with retrograde cholangiopancreatography injection of 0.5% or 3.5% sodium taurocholate to induce AP with mild or severe LI and were sacrificed at 6, 12, and 24 h. Rats from the control group received a laparotomy only. Plasma from a prospective cohort of AP patients was collected. The levels of miR-127 in the tissues and plasma were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results The upregulation of miR-127 in the lungs of rats was detected in the groups of AP with severe LI at 6 h and 24 h, whereas it was scarcely detectable in plasma. In the pilot study that included 18 AP patients and 5 healthy volunteers, the plasma miR-127 level was significantly downregulated in AP patients with respiratory failure compared with the healthy volunteers (P = 0.014) and those without respiratory failure (P = 0.043). Conclusion miR-127 might serve as a potential marker for the identification of AP with LI.