Leflunomide: is a new oral agent in treatment of acute pancreatitis?

OBJECTIVES: Nuclear factor-kappaB (NF-kappaB) is a potent mediator in several steps of acute pancreatitis. Leflunomide is a novel immunomodulating drug that is also a potent inhibitor of NF-kappaB activation. The aim of this study was to investigate the effects of leflunomide pretreatment in severe necrotizing pancreatitis in rats. METHODS: Fifty rats were randomly divided into 5 groups. Severe necrotizing pancreatitis was induced by retrograde injection of 3% sodium taurocholate into the common biliopancreatic duct. Leflunomide (10 mg/kg) was given intragastrically for 2 doses before the experiment. Serum amylase activity, pancreatic histopathologic condition, malondialdehyde level, myeloperoxidase enzyme activity, nitric oxide level, and pulmonary changes were assessed. RESULTS: Leflunomide pretreatment significantly ameliorated pancreatic hemorrhage, edema, and neutrophil infiltration and decreased histopathological score compared with the untreated severe necrotizing pancreatitis group (pathological score [mean +/- SEM]: 6.70 +/- 1.19 vs 12.36 +/- 1.08 in the leflunomide treated and untreated groups, respectively, P < 0.01). Pulmonary changes was decreased in the leflunomide treated group (3.90 +/- 0.45 vs 4.75 +/- 0.25, respectively). Change in pulmonary alveolar distention was significant. Although serum amylase levels also decreased, the difference was not significant (5922 +/- 3290 vs 15547 +/- 5090 U/mL). CONCLUSIONS: Leflunomide is a beneficial agent in the severe form of acute pancreatitis in rats and should be considered as a potential agent for treatment of acute pancreatitis.

Effects of etanercept on sodium taurocholate-induced acute pancreatitis in rats.

In this study, we examined the effects of etanercept (ETA) on experimentally induced pancreatitis. Acute pancreatitis was induced with Na taurocholate. ETA was simultaneously administered to treatment groups. Serum amylase and lipase activity, pancreatic histopathology, apoptosis, malondialdehyde (MDA), and myeloperoxidase enzyme activity (MPO) were assessed. Although rats in the groups 1, 2, and 3 were sacrificed 24h later, groups 4, 5, and 6 were sacrificed 5 days later. ETA treatment significantly decreased serum amylase activity (nontreated, 2636.16+/-191.94; treated, 1898.71+/-262.53; control, 506.28+/-17.31 U/L, P<0.001), lipase activity (nontreated, 3049.67+/-972.65; treated, 2538.85+/-660.45; control, 88.57+/-7.54 U/L, P<0.001), histopathologic score (nontreated, 5.43+/-0.43; treated, 2.57+/-0.20; control, 0.71+/-0.18, P<0.001), MDA (nontreated, 105.77+/-13.29; treated, 92.89+/-10.39; control, 41.26+/-2.54 nmol/g, P<0.001), and MPO (nontreated, 0.64+/-1.15; treated, 0.59+/-0.13; control, 0.17+/-0.02 units/g/wet weight, P<0.001) activity in 24-h groups. In 5-day groups, ETA treatment decreased amylase activity (nontreated, 738.67+/-48.60; treated, 497.14+/-47.25; control, 389.00+/-9.17 U/L, P<0.001), lipase activity (nontreated, 101.33+/-39.32; treated, 34.57+/-7.29; control, 23.42+/-2.12 U/L, P<0.001), histopathologic score (nontreated, 5.43+/-0.43; treated, 3.71+/-0.68; control, 0.00+/-0.00, P<0.001), MDA (nontreated, 67.91+/-4.28; treated, 60.91+/-3.57; control, 14.85+/-1.16 nmol/g, P<0.001), and MPO (nontreated, 0.36+/-0.04; treated, 0.27+/-0.02; control, 0.14+/-0.02 units/g/wet weight, P<0.001) activity. Caspase-positive cells numbers around the necrosis significantly decreased by ETA treatment in both 24-h groups (nontreated, 74.28+/-3.26; treated, 67.00+/-1.15; control, 3.85+/-0.63, P<0.001) and 5-day groups (nontreated, 79.85+/-3.01; treated, 47.85+/-5.76; control, 2.22+/-0.63, P<0.001). These results showed that ETA has an ameliorating effect on sodium taurocholate-induced acute necrotic pancreatitis.

The incidence of Mirizzi syndrome in patients undergoing endoscopic retrograde cholangiopancreatography.

BACKGROUND: Mirizzi syndrome is a rare complication of cholelithiasis, characterized by the narrowing of the common hepatic duct as a result of mechanical compression and/or inflammation due to biliary calculus impacted in the infundibula of the gallbladder or in the cystic duct. In this study, we aimed to describe the clinical presentations, investigations, operative details, and complications of seven patients who underwent endoscopic retrograde cholangiopancreatography and were finally diagnosed with Mirizzi syndrome in our center. METHOD: We performed a retrospective analysis of the records of 7 patients with Mirizzi syndrome who underwent endoscopic retrograde cholangiopancreatography. RESULTS: The incidence of Mirizzi syndrome was 1.07% of 656 patients given endoscopic retrograde cholangiopancreatography. Ultrasonography was able to diagnose one case. Endoscopic retrograde cholangiopancreatography suggested the diagnosis in five cases and helped further in the management of these patients. Four patients had cholecystectomy and T-tube placement, and two had cholecystectomy and choledochoduodenostomy. One patient with type I Mirizzi syndrome according to the Csendes classification successfully underwent laparoscopic cholecystectomy. CONCLUSIONS: In the study, the incidence of Mirizzi syndrome was 1.07% of patients who underwent endoscopic retrograde cholangiopancreatography. Preoperative diagnosis of Mirizzi syndrome by endoscopic retrograde cholangiopancreatography is important to prevent complications.

H pylori iceA alleles are disease-specific virulence factors.

AIM: To characterize and compare genotype profiles of H pylori strains isolated from patients with chronic gastritis and duodenal ulcer in western part of Turkey. METHODS: A total of 46 patients [30 chronic gastritis (CG) and 16 duodenal ulcer (DU)] who had undergone endoscopy because of dyspeptic complaints were studied. The antral biopsy specimens were evaluated for the presence of H pylori by rapid urease test and culture, and the genotype profiles were determined by real-time PCR. RESULTS: The cagA gene was observed in 43 (93.5%) isolates. The vacA s1m2 genotype was the predominant subtype, found in 63.3% and 68.7% of isolates in patients with CG and DU, respectively. Twenty (66.6%) isolates from patients with CG were iceA2 positive while the iceA1 was predominant in those with DU (68.8%). In terms of the association of the iceA alleles to other genes, both alleles were significantly associated with the cagA vacA s1m2 genotype. CONCLUSION: The prevalent circulating genotypes in CG and DU were cagA vacA s1m2 iceA2 and cagA vacA s1m2 iceA1 genotype, respectively. It was found that cagA vacA s1m2 genotype seems to be common virulence factors in both CG and DU while iceA alleles show specificity for gastroduodenal pathologies in this study.

Endoscopic injection therapy of bleeding Dieulafoy lesion of the stomach.

BACKGROUND/AIMS: Dieulafoy's lesion is a rare cause of upper gastrointestinal bleeding and is potentially life threatening. The aim of this study is to determine the clinical features of these lesions and the efficacy of the endoscopic injection sclerotherapy in patients with Dieulafoy's lesion. METHODOLOGY: Between January 1994 and December 2001, twenty-eight patients with upper gastrointestinal bleeding due to Dieulafoy's lesion were treated by endoscopic injection sclerotherapy. Efficacy of endoscopic therapy and clinical findings of these cases were analyzed. RESULTS: The study group consisted of 22 male (78.5%) and 6 female (21.5%) patients with a mean age of 57 years (range 22-82 years). Significant comorbidity was present in 22 (78.5%) patients. Hemoglobin values of the patients ranged from 5.4-10.3 g/dL at hospitalization. The median transfusion requirement was 5 (range 0-12) units. Dieulafoy's lesion was observed in the proximal half of stomach in 25 cases (89.3%), in the antrum in 2 cases (7.1%) and in the angulus in 1 case (3.5%). Endoscopic injection sclerotherapy was successful in stopping the bleeding in 26 out of 28 patients (92.8%). CONCLUSIONS: Dieulafoy's lesions mostly affect the proximal stomach and cause serious upper gastrointestinal bleeding. Endoscopic injection sclerotherapy is an effective and a safe therapeutic method for Dieulafoy's lesion.

Is procalcitonin a reliable marker for the diagnosis of infected pancreatic necrosis?

BACKGROUND: Infected necrosis in acute pancreatitis is the main factor in determining the prognosis of the disease. Early and accurate diagnosis of infected pancreatic necrosis might decrease mortality. The aim of the present study is to identify a reliable marker for the onset infection in three different experimentally induced pancreatitis models. METHODS: Ninety female Wistar albino rats were randomly divided into nine groups. In three different experimental models, including cerulein induced acute oedematous pancreatitis (AEP), sterile pancreatic necrosis due to taurocholate-induced acute pancreatitis (SPN) and infected pancreatic necrosis taurocholate-induced acute pancreatitis (IPN). Serum levels of procalcitonin (PCT), C-reactive protein (CRP), tumour necrosis factor a (TNF-alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8), amylase were measured. The degree of pancreatic damage also evaluated pathologically. RESULTS: Procalcitonin levels were increased significantly in AEP, SPN and IPN compared to control groups (P < 0.05). PCT and IL-6 level were the highest in the IPN group (P < 0.05). Serum amylase, CRP, TNF-alpha, IL-2, and IL-8 levels were similar between IPN and SPN groups (P > 0.05), but higher than in other groups. The results of histological evaluation also correlated with the advent of the disease. CONCLUSION: Procalcitonin and IL-6 acts as reliable acute phase reactant in an experimental model of AEP, SPN and IPN in the rat. PCT and IL-6 combination might be surrogate marker of infected pancreatic necrosis and should be preferred to other markers assay especially in severe pancreatitis.

Effects of pentoxifylline on alcohol-induced gastric injury and acid secretion in rats.

We aimed to evaluate the protective effects of pentoxifylline on alcohol-induced gastric injury, its relation with nitric oxide and prostaglandin synthesis, as well as gastric acidity in rats. Acute gastric mucosal injury was induced by intragastric infusion of 2 ml 98% alcohol. Pentoxifylline was given at 100 mg/kg intraperitoneally. Indomethacin and N(G)-nitro-L arginine were used to inhibit prostaglandin and nitric oxide synthesis, respectively. Macroscopic and microscopic gastric injuries were evaluated. Gastric pH, tissue malondialdehyde levels, oxidized and reduced glutathion (GSSG/GSH) levels, and effects of pentoxifylline on gastric acid output were measured. Pentoxifylline pretreatment significantly reduced macroscopic and microscopic gastric injury. Malondialdehyde level was lower in pentoxifylline treated rats (351.1 +/- 94.1 nmol/g vs 624.3 +/- 234.2 nmol/g). Pentoxifylline has a protective role on alcohol-induced gastric mucosal injury in rats. This effect is not related to synthesis of prostaglandins and changes in gastric acidity but does seem to be related to nitric oxide-mediated pathways. In contrast, pentoxifylline increases gastric acid output significantly.

Effects of methimazole pretreatment on cerulein induced acute pancreatitis in rats.

BACKGROUND: Many interrelationships exist between the thyroid gland and the gastrointestinal tract. Several past and recent studies have shown that the thyroid gland profoundly influences the structure and function of the exocrine pancreas in the rat. In the present study we investigated the effect of methimazole (METZ), an antithyroid drug, on cerulein induced acute pancreatitis (AP) in rats. METHODS: Rats were divided into 3 groups (10-12 weeks age, 200-250 g weight, n: 10). Group B was made hypothyroid with methimazole 5 mg/kg daily for 10 days and the others were untreated euthyroid groups. After 10 days, acute pancreatitis was induced with four doses of 20 microg/kg body weight of cerulein administered s.c at hourly intervals in group A and B while the control group C was given 4 doses of I ml saline. Pancreas wet weight (mg), plasma amylase activity (IU/l) and pancreatic histology were used as endpoints to quantify the severity of the AP. RESULTS: Plasma tri-iodothyronine (T3) (ng/dl) and thyroxine (T4) (microg/dl) levels were significantly reduced after METZ treatment for 10 days (p < 0.01). METZ pretreatment reduced significantly the cerulein induced increase in pancreatic weight (1,205 +/- 12 mg in METZ treated AP group versus 1,617 +/- 14 mg in AP group, p < 0.05) and the rise in amylase activity (7,078 +/- 816 IU/l in METZ treated AP group versus 8,611 +/- 830 IU/l in AP group p < 0.05). CONCLUSION: METZ reduces the severity of cerulein induced AP in rats. This effect might be through its antithyroid property.

Effects of Mast-Cell Stabilization in Cerulein-Induced Acute Pancreatitis in Rats.

Acute pancreatitis is characterized by inflammationof the pancreas that ranges from mild inflammationto severe necrotizing pancreatitis (1-3).Several factors can initiate a cascade of pathologic events that results in AP (4). A key feature in thispathogenesis is inflammatory reaction. However,causes of exaggerated inflammatory reaction are notwell understood (4,5). Since the pathogenesis of pancreatitisis still unclear, most of the treatment modalitiesare largely supportive and independent of thepathogenesis (1,2).