Experimental Acute Pancreatitis In Rats Research Articles

Examination of protective and therapeutic effects of ruscogenin on cerulein-induced experimental acute pancreatitis in rats.

PurposeTo determine the potential protective and therapeutic effects and action mechanism of ruscogenin on cerulein-induced acute pancreatitis (AP) model in rats.MethodsOverall, 32 rats were attenuated to the sham (2-mL/kg/day isotonic solution for 4 weeks), control (20-µg/kg cerulein-induced AP for 12 hours), prophylaxis groups (cerulein-induced AP following 3-mL/kg/day ruscogenin for 4 weeks) and treatment (3-mL/kg/day ruscogenin following cerulein-induced AP for 12 hours). Blood samples were collected for biochemical analysis of nitric oxide synthase 1 (NOS1/neuronal NOS), malondialdehyde (MDA) and intercellular adhesion molecule 1 (ICAM-1). After sacrification, pancreas tissues were collected and prepared for light microscopic (hematoxylin and eosin), immunohistochemical (nuclear factor kappa B) and biochemical analysis (tumor necrosis factor-alpha [TNF-α], interleukin-6 and 1β [IL-6 and IL-1β], CRP, high-sensitivity CRP [hs-CRP] amylase, lipase, and ICAM-1). Ultrastructural analysis was performed by transmission electron microscopy.ResultsThe protective and therapeutic actions of ruscogenin were accomplished by improvements in histopathology, by decreasing blood cytokine levels of CRP, hs-CRP levels, TNF-α, IL-6, IL-1β, ICAM-1, by reducing the pancreatic enzymes amylase and lipase in blood, and by suppressing the expression of nuclear factor kappa B, ICAM-1, and NOS-1, but not MDA in pancreatic tissues. Ruscogenin also improved cerulein-induced ultrastructural degenerations in endocrine and exocrine cells, especially in treatment group.ConclusionThe present findings have demonstrated the beneficial protective and therapeutical effects of ruscogenin, nominating it as a highly promising supplementary agent to be considered in the treatment of AP, and even as a protective agent against the damages induced by disease.

Fentanyl impairs the severity of L-ornithine-induced experimental acute pancreatitis in rats

Pancreatic incidentalomas (PI) are nowadays common but the benefit-risk balance of surgery remains difficult to determine.Monocentric retrospective study of 881 pancreatectomies comparing resected PI with symptomatic lesion. Univariate and multivariate (MV) analyses were done to identify risk factors of malignancy in PI undergoing surgery.Overall, 32% of pancreatectomies were performed for PI. Median size of PI was 30 mm (vs 28 mm; p = 0.15) and 49% were cystic (vs 42%; p = 0.197). Resected PI were mostly located in distal pancreas (61% vs 34%; p < 0.001), less frequently malignant (49% vs 59%; p = 0.004). PNETs were more frequent in PI (50% vs 21%; p < 0.001). Distal pancreatectomy (36% vs 23%; p < 0.001) or parenchyma-sparing surgery (34% vs 13%; p < 0.001) were more frequently performed for PI. Overall mortality (1.1% vs 1.2%) and morbidity (70% vs 68%) were not significantly different between both groups. Severe morbidity was lower for PI (15% vs 22%; p = 0.007). In multivariate analysis, age>55 years (HR 6.14; p < 0.001), size >20 mm (HR:26.7; p < 0.001) and biliary dilatation (HR 29.9; p = 0.027) were independent risk factors of malignancy and, when associated, the likelihood of malignancy was above 90%.PI represent about 30% of indications for pancreatectomy and when resected after careful selection are malignant in 50% of cases.

Astragaloside IV ameliorates acute pancreatitis in rats by inhibiting the activation of nuclear factor-κB

This study aimed to investigate the effects of astragaloside IV (AS-IV; 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosylcycloastragenol), which has been reported to have comprehensive pharmacological functions, on sodium taurocholate (NaTc)/L-arginine (L-Arg)-induced acute pancreatitis (AP) in rats in vivo and in rat pancreatic acinar cells in vitro. NaTc-induced experimental AP was induced in rats by injecting 4% NaTc (0.1 ml/100 g) in the retrograde direction of the biliopancreatic duct. L-Arg-induced experimental AP was induced in rats by 2 intraperitoneal injections of 20% L-arg (3 g/kg), with an interval of 1 h between the injections. The rats were pre-treated AS-IV (50 mg/kg) or the vehicle (DMSO) 2 h prior to the induction of AP. Enzyme-linked immunosorbent assay, H&E staining, myeloperoxidase (MPO) activity, reverse transcription-quantitative PCR, western blot analysis and immunohistochemistry were used to evaluate the effects of AS-IV on AP. The results revealed that treatment with AS-IV significantly reduced serum amylase and lipase levels, pancreatic pathological alterations, the secretion of pro-inflammatory cytokines, MPO activity, and the protein expression of nuclear factor-κB (NF-κB) in vivo. Moreover, pre-treatment with AS-IV significantly increased the expression levels of manganese superoxide dismutase and cuprum/zinc superoxide dismutase. In the in vitro experiment, treatment of the cells with AS-IV aslo reduced rat pancreatic acinar cell necrosis and nuclear NF-κB activity, and enhanced the protein expression of superoxide dismutase. In conclusion, this study indicates that the protective effects of AS-IV on experimental AP in rats may be closely related to the inhibition of NF-κB. In addition, our results indicate that AS-IV may exert potential antioxidant effects on AP. Therefore, AS-IV may be an effective therapeutic agent for AP.

Tissue Pharmacology of Da-Cheng-Qi Decoction in Experimental Acute Pancreatitis in Rats.

Objectives. The Chinese herbal medicine Da-Cheng-Qi Decoction (DCQD) can ameliorate the severity of acute pancreatitis (AP). However, the potential pharmacological mechanism remains unclear. This study explored the potential effective components and the pharmacokinetic characteristics of DCQD in target tissue in experimental acute pancreatitis in rats. Methods. Acute pancreatitis-like symptoms were first induced in rats and then they were given different doses of DCQD (6 g/kg, 12 g/kg, and 24 g/kg body weight) orally. Tissue drug concentration, tissue pathological score, and inflammatory mediators in pancreas, intestine, and lung tissues of rats were examined after 24 hours, respectively. Results. Major components of DCQD could be found in target tissues and their concentrations increased in conjunction with the intake dose of DCQD. The high-dose compounds showed maximal effect on altering levels of anti-inflammatory (interleukin-4 and interleukin-10) and proinflammatory markers (tumor necrosis factor α and interleukin-6) and ameliorating the pathological damage in target tissues (P < 0.05). Conclusions. DCQD could alleviate pancreatic, intestinal, and lung injury by altering levels of inflammatory cytokines in AP rats with tissue distribution of its components.

Effectiveness of interleukin-1 receptor antagonist (Anakinra) on cerulein-induced experimental acute pancreatitis in rats

Aim. Acute pancreatitis (AP) is defined as an inflammatory disease of the pancreas. The purpose of this study was to examine the effectiveness of Anakinra on cerulein-induced experimental pancreatitis rat model by using the results of biochemical and histopathological findings. Materials and methods. Cerulein was administered to induce AP in rats. Group 1 was the sham group. Subcutancerulein was injected to the rats in group 2 for experimental pancreatitis group. In groups 3 and 4, 100 and 50 mg/kg intraperitoneal Anakinra were injected after the induction of experimental pancreatitis by subcutaneous cerulein in rats, respectively. Lastly, in group 5, rats were injected with intraperitoneal saline and subcutan cerulean for placebo group. The following parameters were evaluated: histopathological score of pancreatitis, apoptotic index, amylase, lipase, TNF-α levels, IL-1β and the leukocyte count. Results. When the results of serum amylase, lipase, TNF-α and IL-1β levels, the leukocyte count, histopathologic scores and apoptotic indices of control group compared to the results of other groups, the differences exhibited statistical significance (all p < 0.05). On the other hand, when the results of fourth group compared with the results of third group, the data demonstrated statistical insignificance (p > 0.05). However, no any significant differences were found between the results of fourth and fifth groups (p > 0.05). Conclusion. In the light of these results, cerulein is an appropriate agent for experimental AP rat model and Anakinra has a favorable therapeutic effect on acute experimental pancreatitis model. Moreover, Anakinra significantly decreases cerulein-related pancreatic tissue injury and pancreatic apoptosis.

Treatment with an Nrf2 Activator Ameliorates Acute Pancreatitis in Experimental Animals

Nrf2 is the master regulator of genes encoding anti-oxidant, phase II detoxifying and cytoprotective molecules and as such plays a key role in protection against oxidative stress and inflammation. Dimethyl Fumarate (DMF) is a Nrf2 activator that exerts its cytoprotective effects through attenuation of oxidative stress, inhibition of NF-κB, and moderation of the T Helper 1 response. The purpose of this study is to test the hypothesis that treatment with DMF may ameliorate experimental acute pancreatitis in rats.

Effect of a new compounds of substituted 5R1, 6H2–1,3,4‐thiadiazine‐2‐amines on the histological pictures in ligation models of experimental acute myocardial infarction and experimental acute pancreatitis in rats.

Models of experimental acute myocardial infarction (EAMI) and experimental acute pancreatitis (EAP) have been developed to solve this problem. The animals got injection of the compound from the group of substituted 5R1, 6H2–1,3,4‐thiadiazine‐2‐amines, dozed 40 mg/kg. Histological study has been carried out at the 1st, 5st and 7th days. All animal experimental procedures were performed in accordance with the APS's Guiding Principles and in accordance with the Laboratory Practice Regulations of RF.Already during the 1st day of the EAMI no leucopenia was observed and the signs of proliferative inflammation were detected. Later, at the 5th day, the necrosis area got surrounded by demarcation bank, and further on (7th day) had been entirely replaced by granulation tissue. Withal, the application of compound in EAP results in occurrence of proliferative inflammation, prevents lympho‐ and monocytopenia development and cuts down the lethality rate two‐fold.Conduction research enabled to state repeatability of the mechanism of the compounds impact on ischemia‐induced inflammation process, both in case of EAMI and EAP. The compounds modulated the transition of destructive inflammation into proliferative one, thereby preventing spreading of the inflammation process to tissues surrounding the necrotic zone and promoting reparative processes as well.Research Grant 12‐Ì‐34–2064 of Ural Branch of RAS.

Does tobacco stimulate proliferation and migration of pancreatic stellate cells (PSC)?

Introduction: Although microcirculatory disturbances play pivotal role in the pathomechanism of acute pancreatitis (AP), very few papers can be found in which any of hemorheological parameters had been tested. The aim of our study was to analyze the hemorheological changes in cerulein-induced experimental acute pancreatitis in rat in two doses (5 and 10 mg/kg, s.c.), aiming to analyze the possible gender difference in hemorheological response, too. Methods: Male and female rats were subjected to Control group, or AP with 5 or 10 mg/kg cerulein groups. Blood samplings (lateral caudal vein) were completed before cerulein administration, and 1, 2 and 24 hours later. Hematological parameters, amylase activity, erythrocyte deformability (ektacytometry) and aggregation (light-transmission method) were tested.

Micro-rheological changes during experimental acute pancreatitis in the rat

Although microcirculatory disturbances play pivotal role in the pathomechanism of acute pancreatitis (AP), very few papers can be found which had been tested any of hemorheological parameters. The aim of our study was to analyze the hemorheological changes in cerulein-induced experimental acute pancreatitis in rat in two doses (5 and 10 μg/kg, s.c.). Male and female rats were subjected to Control group, or AP with 5 or 10 μg/kg cerulein groups. Blood samplings (lateral caudal vein) were completed before cerulein administration, and 1, 2 and 24 hours later. Hematological parameters, amylase activity, erythrocyte deformability (ektacytometry) and aggregation (light-transmission method) were tested. The presence of AP could be confirmed by amylase testing and histological examination. The earliest impairment of the red blood cell deformability could be observed 1 hour after cerulein administration in 10 μg/kg dosage. Female animals had the worst rheological results with high mortality. In conclusion, subcutaneously administrated cerulein in dosage of 5 and 10 μg/kg resulted in AP in rats, with significant changes in red blood cell deformability and alterations in erythrocyte aggregation. This model seems to be suitable for further comparative studies.

Sesamol attenuates oxidative stress–mediated experimental acute pancreatitis in rats

Acute pancreatitis is a potentially fatal disease with no known cure. The initial events in acute pancreatitis may occur within the acinar cells. We examined the effect of sesamol on (i) a cerulein-induced pancreatic acinar cancer cell line, AR42J, and (ii) cerulein-induced experimental acute pancreatitis in rats. Sesamol inhibited amylase activity and increased cell survival. It also inhibited medium lipid peroxidation and 8-hydroxydeoxyguanosine in AR42J cells compared with the cerulein-alone groups. In addition, in cerulein-treated rats, sesamol inhibited serum amylase and lipase levels, pancreatic edema, and lipid peroxidation, but it increased pancreatic glutathione and nitric oxide levels. Thus, we hypothesize that sesamol attenuates cerulein-induced experimental acute pancreatitis by inhibiting the pancreatic acinar cell death associated with oxidative stress in rats.

Protective Effects of Lycopene on Cerulein-Induced Experimental Acute Pancreatitis in Rats

The purpose of our study was to evaluate the protective effect of the strong antioxidant and anti-inflammatory agent, lycopene, on oxidative stress in a rat model of cerulein-induced acute edematous pancreatitis. Sprague-Dawley rats were pretreated with lycopene (50 mg/kg, i.p.) or saline 15 min before cerulein was given 20 μg/kg (i.p.) at 1-h intervals within 4 h. Twelve hours after cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and proinflammatory cytokines (TNF-α and IL-1ß). Pancreatic tissues were taken for the determination of tissue glutathione (GSH) and malondialdehyde (MDA) levels, Na(+)/K(+)-ATPase, and myeloperoxidase (MPO) activities. Tissue samples were also examined histologically. Acute pancreatitis caused significant decrease in tissue GSH levels and Na(+)/K(+)-ATPase activity, while pancreatic MDA levels and MPO activity were increased. Furthermore, TNF-α, IL-1ß, and amylase lipase levels were also significantly increased. On the other hand, lycopene pretreatment reserved all these biochemical indices as well as histopathologic alterations that were induced by cerulein. According to the results, lycopene protects the pancreatic tissues from oxidative damage induced by cerulein, and this effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation. These results suggest that high dietary intake of tomatoes may have protective effects against acute pancreatitis.

Beneficial effects of alpha lipoic acid on cerulein-induced experimental acute pancreatitis in rats

The present study aimed to determine the effects of alpha lipoic acid (ALA) on blood and tissue biochemical parameters, as well as tissue histopathology, in an experimental rat model of cerulein-induced acute pancreatitis (AP). Three groups consisting of eight rats each were used, as follows: Group 1, controls; Group 2, cerulein-induced pancreatitis group treated with saline; and Group 3, cerulein-induced pancreatitis group treated with ALA. AP was induced by intraperitoneal administration of cerulein (20 µg/kg) 4 times at 1-hour intervals. The animals were decapitated 12 hours after the last dose of cerulein. Blood amylase, lipase, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α levels, pancreas tissue glutathione (GSH) and malondialdehyde (MDA) levels, as well as myeloperoxidase (MPO) and Na+-K+-ATPase activity were measured. Pancreatic tissue samples were also evaluated histopathologically under a light microscope. While plasma amylase, lipase, IL-1ß, and TNF-α levels, and tissue MDA and MPO levels significantly increased in rats with cerulean-induced AP, tissue GSH and Na+-K+-ATPase activity significantly reduced. These changes were reversed and improved with ALA treatment. Our findings suggest that ALA may significantly reduce morbidity and mortality by preventing organ dysfunction induced by free radicals in the pancreas.

Effect of Procainhydrochloride on Phospholipase A2 Catalytic Activity in Sodium Taurocholate-Induced Acute Experimental Pancreatitis in Rats

Background: In human acute pancreatitis (AP) the local anaesthetic procainhydrochloride (procain-HCl) is given intravenously for pain treatment. Procain has been shown to inhibit catalytic activity of pancreatic (group I) phospholipase A2 (PLA2) and non-pancreatic (group II) PLA2. Both enzymes are important mediators for the local and systemic inflammatory process in AP. To determine the effect of procain, we examined serum and tissue levels of both types of PLA2 activity in the experimental rodent taurocholate model of AP. Methods: In 60 rats, severe pancreatitis was induced by taurocholate. Forty rats were treated with procain-HCl intravenously at a dosage of 2 mg/kg body weight/h either at or 1 h after induction of pancreatitis. Twenty rats served as controls. We measured catalytic activities of group I and group II PLA2 in serum and tissue samples of lung and pancreas. Results: Serum group II PLA2 catalytic activity was significantly reduced 3 and 6 h after AP induction in rats treated with procain-HCl (p < 0.001) in both treatment groups. In pancreatic and lung tissue, group II PLA2 catalytic activity was significantly reduced compared with normal values (p < 0.001). Conclusion: Procain-HCl given intravenously either at or 1 h after induction of necrotizing pancreatitis significantly inhibits group II PLA2 catalytic activity in serum and tissues.

Dachengqi Decoction induces pancreatic acinar cell apoptosis in experimental acute pancreatitis in rats

To explore the effects of Dachengqi Decoction (DCQD), a compound traditional Chinese herbal medicine, on pancreatic acinar cell apoptosis in a rat model of experimental acute pancreatitis. A total of 36 Sprague-Dawley rats were randomly divided into sham-operated group, untreated group and DCQD-treated group (12 rats in each group). Acute pancreatitis was induced in 24 rats by retrograde injection of 3.5% sodium taurocholate into pancreatic bile duct. The other 12 rats were allocated as sham-operated group. After the operation, the spray-dried DCQD (2 g/mL of crude drugs) or normal saline at 10 mL/kg body weight of rats were orally administered. The rats were sacrificed by decapitation 12 h and 24 h after the administration, and samples were collected. Amylase activity in serum, nitric oxide (NO) content and inducible NO synthetase (iNOS) activity in pancreatic tissue were measured respectively. Pancreatic acinar cell apoptosis was identified by terminal deoxy-nucleotidyl transferase mediated dUTP nick end-labeling, and pathological scores of pancreatic tissues were determined under a light microscope. At the two time points after treatment, the activities of serum amylase in the treated group were significantly lower than those in the untreated group (P<0.05), while the contents of pancreatic NO and activities of iNOS were higher than those in the untreated group (P<0.05), respectively. The pancreatic acinar cell apoptosis rates in the treatment group at 12 h and 24 h were higher than those in the untreated group, and the mean pancreatic pathomorphologic scores decreased correspondingly (P<0.05). DCQD can induce pancreatic acinar cell apoptosis by increasing NO content and iNOS activity in the pancreas of experimental acute pancreatitis, which helps attenuate the pancreatic pathomorphology.

Inhibition of renin-angiotensin system in experimental acute pancreatitis in rats: A new therapeutic target?

Objective Pancreatic renin-angiotensin system has been implied to play a role in the regulation of pancreatic functions and could be a new therapeutic target in acute pancreatitis. The aim of this study was to evaluate the therapeutic potential of angiotensin-converting-enzyme inhibition by captopril and angiotensin II type1 receptor inhibition by L-158809 and losartan experimentally in acute pancreatitis. Design Rats were randomly divided into 15 groups. Acute edematous pancreatitis was induced by injection of cerulein 20 μg/kg SC four times at hourly intervals. Severe necrotizing pancreatitis was induced by retrograde injection of 3% taurocholate into the biliary-pancreatic duct. Interventions Captopril, L-158809 and losartan were given intraperitoneally. Main outcome features: pancreatic pathology, pancreatic myeloperoxidase activity and serum amylase activity were assessed. Results Captopril decreased serum amylase (10,809±1867 vs. 4085±1028 U/L, p<0.01), myeloperoxidase activity (3.5±0.5 vs. 1.5±0.1, p<0.05) and histopathological score (5.0±0.4 vs. 1.1±0.5, p<0.01) in acute edematous pancreatitis. In taurocholate induced severe necrotizing pancreatitis captopril ameliorated histopathological score (10.1±1.2 vs. 3.4±0.5, p<0.01), pancreatic parenchymal necrosis (4.5±0.6 vs. 0.0±0.0, p<0.001), fatty necrosis (2.8±0.9 vs. 0.1±0.1, p<0.01) and edema (2.1±0.3 vs. 1.4±0.3, p<0.05). However, L-158809 did not have similar beneficial effects on acute pancreatitis in rats while losartan decreased pancreatic parenchymal necrosis and neutrophil infiltration. Conclusions This study not only demonstrated the differential effects of captopril, losartan and L-158809 in acute pancreatitis but also showed that there is still much to investigate about pancreatic renin-angiotensin system. Inhibition of angiotensin-converting enzyme should be evaluated carefully as a potential new therapeutic target in acute pancreatitis.

Effect of early antibiotic prophylaxis with ertapenem and meropenem in experimental acute pancreatitis in rats

The clinical course in acute necrotizing pancreatitis is mainly influenced by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic treatments for early prophylaxis was studied in the taurocholate model of necrotizing pancreatitis in the rat. Sixty male Sprague-Dawley rats were divided into three pancreatitis groups (15 animals each) and a sham-operated group (15 animals, control group). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals were placed on one of two different antibiotic regimens (15 mg/kg ertapenem or 20 mg/kg meropenem, one shot) after the induction of pancreatitis or received no antibiotics (control). All animals were sacrificed after 24 h to study pancreatic and extrapancreatic infection. Early antibiotic prophylaxis with either erapenam or meropenem significantly decreased pancreatic infection from 12/15 (control group) to 4/15 (ertapenem antibiotic group) and 3/15 (meropenem antibiotic group) (P < 0.05). In our animal model of necrotizing pancreatitis, early antibiotic prophylaxis with ertapenem and meropenem reduced bacterial infection of the pancreas. The efficacy of early antibiotic prophylaxis with ertapenem in the clinical setting should be subject to further research.

Acinar Cell Membrane Disruption Is an Early Event in Experimental Acute Pancreatitis in Rats

To test the hypothesis that disruption of acinar cell membranes is the earliest event that takes place after the onset of acute pancreatitis. Cerulein and taurocholate pancreatitis were induced in rats. Furthermore, stimulation with different doses of bombesin, pilocarpine, and cerulein was performed. Five to 180 minutes after initiation of treatment, animals were killed. Disruption of cell membranes was detected by the penetration of the experimental animal's own albumin or immunoglobulin G (IgG) into acinar cells by immunocytological localization. Tissue was further analyzed by electron microscopy and electron microscopic immunostaining. Animals with pancreatitis displayed significantly greater antialbumin and anti-IgG immunostaining in the cytoplasm of acinar cells and in vacuoles in comparison with controls, confirming membrane disruption. This was not detectable after stimulation with bombesin, pilocarpine, and nonsupramaximal doses of cerulein. The first changes were seen after 5 minutes of induction of pancreatitis. Results were verified by electron microscopy and electron microscopic immunohistochemistry. The penetration of albumin and IgG into acinar cells indicates that wounding of their plasma membrane occurs at the onset of acute pancreatitis. Disruption of the membranes could be expected to allow the influx of calcium ions, causing massive intracellular alterations, and exit of molecules, such as enzymes from acinar cells.

Acute Experimental Pancreatitis in Rats Is Ameliorated by Treatment with Pramlintide, a Synthetic Analogue of the β-Cell Hormone Amylin

Purpose: Acute pancreatitis is a common and major complication of endoscopic retrograde cholangiopancreatography (ERCP) and limits the use of this otherwise safe procedure. Antisecretory drugs such as somatostatin (SST) and its long-acting analogue octreotide, or protease inhibitors such as gabexate mesilate, have been tested as therapies for pharmacological prevention of post-ERCP pancreatitis, but uncertainty still exists over their clinical benefit. At physiologically relevant doses in animal models, the β-cell hormone amylin slows gastric emptying, inhibits gastric acid secretion and exocrine pancreatic secretion, and protects the gastric mucosa. The present study examined the effect of pramlintide (pram), a synthetic human amylin analogue, on prevention of caerulein-induced acute pancreatitis in anesthetized Sprague Dawley®TM (SD) rats. Methods: Saline, pram (300 μg/kg/h), SST (10 μg/kg bolus) or pram+SST in combination (N = 16, 5, 5, 6, respectively) was infused intravenously from 30 min before until 240 min after caerulein IP injection (10 μg/kg) into fasted, male, anesthetized SD rats (320–360 g). As an index of acute pancreatitis, plasma lipase and amylase were measured for up to 240 minutes after caerulein injection. Results: Following caerulein injection, plasma amylase increased 2.23-fold at 240 min in saline-treated controls compared to 1.40-, 1.61- and 1.51-fold in rats receiving pram, SST or the combination (P < 0.01, P < 0.04 and P < 0.01, respectively). Plasma lipase increased by 20.3-fold in the control saline group compared to 8.1-, 6.1- and 5.0-fold in pram, SST or combination groups (P < 0.02, P < 0.01 and P < 0.01, respectively). Although each was different from controls, there were no significant differences between SST, pram or pram+SST treatments in attenuating caerulein-induced increases in plasma amylase and lipase in this animal model of pancreatitis. Conclusion: Pramlintide ameliorated increases in pancreatic enzyme activity in this rat model of acute pancreatitis. Future studies are warranted to explore the potential use of pramlintide in the prevention of pancreatitis, which may occur during ERCP procedures. This research was funded in part by Amylin Pharmaceuticals, Inc., San Diego, CA.

Effect of early and late antibiotic treatment in experimental acute pancreatitis in rats

The clinical course in acute necrotizing pancreatitis is mainly determined by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic regimens for early and late treatment was investigated in the taurocholate model of necrotizing pancreatitis in the rat. Seventy male Wistar rats were divided into five pancreatitis groups (12 animals each) and a sham-operated group (10 animals). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals received two different antibiotic regimes (20 mg/kg imipenem or 20 mg/kg ciprofloxacin plus 20 mg/kg metronidazole) early at 2, 12, 20, and 28 h after induction of pancreatitis or late at 16 and 24 h after induction of pancreatitis or no antibiotics (control). Animals were examined after 30 h for pancreatic and extrapancreatic infection. Early and late antibiotic treatment with both regimes could significantly reduce pancreatic infection from 58 to 8-25%. However, extrapancreatic infection was only reduced by early antibiotic therapy. While quinolones also reduced bacterial counts in small and large bowel, imipenem did not. In our animal model of necrotizing pancreatitis, early and late treatment with ciprofloxacin/metronidazole and imipenem reduce bacterial infection of the pancreas. Extrapancreatic infection, however, is reduced significantly only by early antibiotic treatment. The effectivity of early antibiotic treatment in the clinical setting should be subject to further investigation with improved study design and sufficient patient numbers.

Does the Septic Shock Interfere Experimental Acute Pancreatitis in Rats?

Acute pancreatitis is a disease involving pro-inflammatory mediators. Two complex and multifactorial pathogenetic ways lead to edematous or necrotizing pancreatitis. The course of the disease is thought to be the consequence of an acute inflammatory response. The authors examined the impact of Escherichia coli LPS on the acute cerulein pancreatitis in rats. The study was performed on rats using the ceruleine pancreatitis model. The activation status of polymorphonuclear cells, blood IL-6 concentration, oxidative stress parameters, pancreatic enzymes concentration and microscopic alterations were determined at 5th and 9th h observations. In acute pancreatitis and acute pancreatitis with LPS groups, the peripheral polymorphonuclear cells activity was lower than in control one. Authors noticed the same neutrophil activation in acute pancreatitis after lipopolysaccharide administration although the peripheral blood polymorphonuclear cells count was significantly higher at the 9th h observation. LPS neither changed the oxidative stress within pancreatic gland, nor amylase or serum lipase activity. LPS given to acute pancreatitis animals resulted in significant increase of serum IL-6 concentration at 5th observation turning normal after 9th h. Collected data supports thesis of early polymorphonuclear cells involvement in acute pancreatitis and oxidative stress evidence in pancreatic parenchyma. However, results did not reveal that administration of LPS amplified inflammatory response during the course of acute pancreatitis.