Early Stage Of Severe Acute Pancreatitis Research Articles

Protective effects of emodin combined with danshensu on experimental severe acute pancreatitis

In the present experiment, we aimed to determine the feasibility and curative effects of emodin combined with danshensu on experimental severe acute pancreatitis (SAP) and the mutual benefit of this synergistic strategy by a prospective animal study. Eighty Wistar rats were randomly divided into four groups (n = 20). SAP was elicited by a retrograde infusion of 5.0% sodium taurocholate into the pancreatic main duct. SAP rats in each group received no further intervention, emodin alone, danshensu (DSS) alone, and emodin combined with DSS (EDSS), respectively. 48 h after SAP induction, all surviving animals were sacrificed to collect blood and tissue samples for the following measurements: serum levels of amylase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), endotoxin and D-lactate. Pancreatic levels of TNF-alpha, IL-1beta, maleic dialdehyde (MDA), myeloperoxidase (MPO) activity, nuclear factor-kappaappaB (NF-kappaB) activation as well as wet-dry weight ratio were also evaluated. Ascitic fluid was quantified and the severity of pancreatic damage was analyzed by pathological grading and scoring. Compared with the SAP group, the emodin, DSS and EDSS groups had significant differences in every index. Furthermore, EDSS obviously improved all the parameters mentioned above so as to counteract inflammatory response and oxidative stress, as well as most effectively abating pancreatic and intestinal barrier injury. EDSS exerted protective effects on SAP rats and remarkably alleviated the severity of experimental SAP. Mechanisms that might account for the beneficial effects include protecting the intestinal barrier, inhibiting over-inflammatory reaction and abating oxidative stress. The combined strategy proved to be more effective than either emodin or DSS alone and may cause synergistic effects in combination in the early stage of SAP. Broad potential for future clinical practice is foreseeable.

Effects of enteral nutrition supplemented with glutamine and arginine on gut barrier in patients with severe acute pancreatitis: a prospective randomized controlled trial

To investigate the effects of continuous early enteral nutrition (EEN) supplemented with glutamine and arginine on gut barrier function in patients with severe acute pancreatitis (SAP). Thirty two patients with a diagnosis of acute pancreatitis predicted to develop severe disease were randomized into 2 groups: EEN group (n = 18) and EEN + glutamine and arginine group (enteral immunonutrition group, n = 14). EEN was initiated when homeostasis was achieved within 72 hours after attack, and both group received isocaloric isonitrogenous nutrition. Glutamine and arginine were administered into jejunum in the enteral immunonutrition group. Serum amylase, plasma diamine oxidase (DAO), C-reactive protein (CRP), plasma endotoxin, urinary excretion of lactulose (L), and mannitol (M) were measured, and APACHE-II scores were recorded on days 1, 7, and 14. Complications, and length and cost of hospitalization were recorded as well. EEN and enteral immunonutrition were both tolerated well. There was no difference in APACHE-IIscore between the two groups (P > 0.05). The DAO, CRP, plasma endotoxin, and urinary L/M levels decreased with the course of SAP. However, the plasma endotoxin and urinary L/M on day 7 of the enteral immunonutrition group were (10.0 +/- 3.8) EU/ml and 0.29 +/- 0.15 respectively, both significantly higher than those of the EEN group [(7.9 +/- 2.8) EU/ml and 0.16 +/- 0.08 respectively, both P < 0.05]. The length of hospital stay and cost showed no differences between the two groups. EEN is safe and feasible in treatment of SAP. Enteral immunonutrition containing glutamine and arginine improves the gut barrier function by reducing the gut permeability and decreasing plasma endotoxin level in the early stage of SAP.

Improvement of Monocyte Secretion Function in a Porcine Pancreatitis Model by Continuous Dose-Dependent Veno-Venous Hemofiltration

Monocyte and its secreted cytokines play a crucial role in the process of severe acute pancreatitis (SAP). It has been known that continuous veno-venous hemofiltration (CVVH) can partially attenuate the inflammatory process by removal of cytokines, but the effect of CVVH on monocyte secretion function remains unknown. This study investigated the effect of different doses of CVVH on monocyte secretion function as well as the plasma cytokine profile in a SAP porcine model. After successful induction of SAP by pressure-controlled (100 mmHg), intraductal injection of sodium taurocholate (4%, 1 ml/kg) and trypsin (2 U/kg), 24 swine were randomly assigned to 3 groups. Swine in group I (n=8) serving as SAP controls received only standard medical therapy (SMT). Besides SMT, swine in two other groups received zero-balanced CVVH, one hour after the induction of SAP, with low volume fluid exchange (group II, n=8, ultrafiltration rate (UFR) 20 ml/kg/h, LV-CVVH) or high volume (group III, n=8, UFR 100 ml/kg/h, HV-CVVH). Using heparin as anticoagulant, the filter (AN69, Hospal, Lyon, France) was changed every 24 hours. Monocytes were isolated from porcine blood at various timepoints for detection of cytokine secretion (interleukin-6, IL-6; interleukin-10, IL-10; tumor necrosis-a, TNF-a) after LPS stimulus; plasma cytokines were measured simultaneously. CVVH showed a dose-dependent beneficial effect on the animals' survival time. In control animals, plasma pro-inflammatory cytokine levels exhibited a double-phase fluctuation after SAP induction: IL-6 and TNF-alfa rapidly increased to a peak level within 6-12 hours, then dropped to very low level in the late stage. Unlike pro-inflammatory cytokines, the plasma level of anti-inflammatory cytokine IL-10 reached a plateau within 6-12 hours but dropped little. In CVVH-treated animals, the peak-nadir patterns of 3 cytokines were all flattened, most prominently in the HV-CVVH group. Similarly to plasma cytokine patterns, the monocyte ex vivo response to LPS stimulus showed an over-production of cytokines within 6-12 hours, but low production in the late stage. Although unable to totally prevent the abnormality of the monocyte secretion function, CVVH showed a dose-dependent ameliorative effect on it. Monocytes are over-reactive to stimulus in the early stage of SAP, accompanied by a high level of plasma cytokines, and hypo-reactive to stimulus in the late stage of SAP, accompanied with a low level of plasma cytokines. CVVH treatment has a dose-dependent improvement effect on monocyte responsiveness.

Perfusion Computerized Tomography Can Predict Pancreatic Necrosis in Early Stages of Severe Acute Pancreatitis

The mortality rate associated with severe acute pancreatitis (SAP) with necrosis remains high because early prediction of pancreatic necrosis is difficult. We evaluated whether perfusion computerized tomography (CT), which is used to identify early stage ischemia in the brain, could detect ischemic changes in the pancreas in the early stages of SAP and predict development of necrosis. Thirty consecutive patients with a diagnosis of SAP according to the Atlanta criteria and whose score was greater than 6 were enrolled in this study. All patients were hospitalized within 3 days after onset of symptoms indicative of acute pancreatitis and underwent perfusion CT. Three weeks later, all patients underwent conventional contrast-enhanced CT to detect progression of their disease. Perfusion CT showed that 10 of the 30 patients had pancreatic ischemia at the time of diagnosis. Contrast-enhanced CT disclosed that pancreatic necrosis developed in 9 of these 10 patients, but not in the 20 patients who did not have pancreatic ischemia. The sensitivity and specificity of perfusion CT for predicting pancreatic necrosis was calculated to be 100% and 95.3%, respectively. Perfusion CT is a useful tool for early detection of ischemic changes in the pancreas that lead to pancreatic necrosis.

Effect of BN52021 on NFκ-Bp65 expression in pancreatic tissues of rats with severe acute pancreatitis

To investigate dynamic changes and significance of expression of NF-kappaBp65 in pancreatic tissues of rats with severe acute pancreatitis (SAP), as well as BN52021 effects. Wistar male rats were randomly divided into negative control group (NC group, n=60), SAP-model group (SAP group, n=60), and BN52021-treated group (BN group, n=60), and each of the above groups was respectively 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). By RT-PCR and Western blot, NF-kappaBp65 mRNA and its protein expression in pancreatic tissues of rats were detected respectively. The expression of NF-kappaBp65 mRNA dynamically changed in both SAP groups and BN groups. The mRNA level was higher in SAP groups than NC groups at 2 h, 3 h, 12 h, and 24 h after operation (P<0.05), higher in BN groups than NC groups at all time points (P<0.05), and higher in BN groups than SAP group at 1 h (P<0.05). The NF-kappaBp65 protein level was higher in SAP groups than NC groups at 1 h, 3 h, and 6 h (P<0.01), and 2 h, 12 h, and 24 h (P<0.05), higher in BN groups than NC groups at all time points (P<0.05), and lower in BN groups than SAP groups at 1 h, 3 h, and 6 h (P<0.05). The expression of NF-kappaBp65 in pancreatic tissues is dynamically changed and the changes play an important role in pathogenesis of SAP. BN52021 exerts therapeutic effects through reducing the expression level of NF-kappaBp65 protein in the early stage of SAP.

Effect of resveratrol on pancreatic oxygen free radicals in rats with severe acute pancreatitis

To investigate the therapeutic effects of resveratrol (RESV) as a free radical scavenger on experimental severe acute pancreatitis (SAP). Seventy-two male Sprague-Dawley rats were divided randomly into sham operation group, SAP group, and resveratrol-treated group. Pancreatitis was induced by intraductal administration of 0.1 mL/kg 4% sodium taurocholate. RESV was given intravenously at a dose of 20 mg/kg body weight. All animals were killed at 3, 6, 12 h after induction of the model. Serum amylase, pancreatic superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO) were determined. Pathologic changes of the pancreas were observed under optical microscope. The serum amylase, pancreatic MPO and the score of pathologic damage increased after the induction of pancreatitis, early (3, 6 h) SAP samples were characterized by decreased pancreatic SOD and increased pancreatic MDA. Resveratrol exhibited a protective effect against lipid peroxidation in cell membrane caused by oxygen free radicals in the early stage of SAP. This attenuation of the redox state impairment reduced cellular oxidative damage, as reflected by lower serum amylase, less severe pancreatic lesions, normal pancreatic MDA levels, as well as diminished neutrophil infiltration in pancreas. RESV may exert its therapeutic effect on SAP by lowering pancreatic oxidative free radicals and reducing pancreatic tissue infiltration of neutrophils.

Effects of granulocyte colony-stimulating factor on neutrophils and inflammatory cytokines in the early stage of severe acute pancreatitis in rats

The high mortality rate of severe acute pancreatitis (SAP) is closely associated with secondary infections of pancreatic and peripancreatic tissues. It was reported that granulocyte colony-stimulating factor (G-CSF) increased the number of leukocytes and enhanced their functions. However, an inflammatory response may be enhanced by an increased number of leukocytes. Our purpose was to study the roles of G-CSF in peritoneal-exudate neutrophils and inflammatory cytokines in the early stage of experimental SAP. SAP was induced by injecting 0.2 ml of 3% taurocholate acid into the biliopancreatic duct in male Wistar rats. G-CSF (90 microg/kg body weight) or saline was administered 1 h before the SAP induction. The number of neutrophils and their phagocytic and bactericidal activities were evaluated, and the concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta in plasma and ascitic fluid were measured 1 h and 3 h after the SAP induction. The number of peritoneal-exudate neutrophils (PENs) at 3 h was increased by G-CSF administration (81 +/- 50 x 10(5) cells/total exudate), as compared with that shown with saline administration (28 +/- 13 x 10(5) cells/total exudate; P < 0.05). The numbers of phagocytic and bactericidal neutrophils were also elevated by G-CSF administration. G-CSF administration did not increase the concentrations of TNF-alpha, IL-6, and IL-1beta in the plasma and ascitic fluid. G-CSF increases the numbers of neutrophils and enhances their functions against bacteria, but it does not enhance intraabdominal and systemic inflammatory responses in the early stage of SAP.