ceruletide and Ascites

To investigate the effects of hyperlipidemia on acute pancreatitis (AP) and the possible mechanisms.. Rat models of hyperlipidemia and AP were established by Triton WR1339 and cerulein respectively. Human albumin was used to treat AP complicated by hyperlipidemia. In each group, we compared the histological score, volume of ascites, ratio of pancreatic wet/dry weight, serum amylase (AMY) and pancreatic acinar cell apoptosis. The level of protein kinase C (PKC) membrane translocation in pancreatic tissue was detected by Western blot.. In the hyperlipidemia model established by Triton WR1339, triglyceride (TG) increased remarkably and reached its peak 6 h after injection, and most rats developed mild acute pancreatitis. Histological score, volume of ascites, ratio of wet/dry weight and serum AMY in AP animals with hyperlipidemia were obviously higher than those in AP animals (P < 0.05) and decreased after albumin therapy but not significantly (P > 0.05). Apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) increased in AP animals with hyperlipidemia and did not change distinctly after albumin therapy. PKC membrane translocation level increased in AP animals with hyperlipidemia and decreased remarkably after albumin therapy (P < 0.05).. Hyperlipidemia may induce AP or intensify pancreatic injury. Albumin therapy can not alleviate pancreatic lesion effectively. PKC activation may be one mechanism by which AP is intensified by hyperlipidemia.

Topics: Acute Disease; Amylases; Animals; Apoptosis; Ascites; Ceruletide; Enzyme Activation; Hyperlipidemias; In Situ Nick-End Labeling; Lipids; Male; Organ Size; Pancreas; Pancreatitis; Polyethylene Glycols; Protein Kinase C; Rats; Rats, Sprague-Dawley

The molecular mechanisms that lead from acute pancreatitis (AP) to multiple organ failure remain to be clarified. We previously reported that ascitic fluids from a rat model of severe acute pancreatitis (pancreatitis-associated ascitic fluids, PAAF) transcriptionally activated endothelial cells and leukocytes in vitro. To clarify the role of ascitic fluids on the development of multiple organ failure in AP, we examined the effects of PAAF on the prognosis and immunohistologic findings in cerulein pancreatitis, an experimental model of mild pancreatitis in vivo. Intraperitoneal injection of PAAF decreased the survival rates in a dose-dependent manner. Histologically, destruction of vessels, alveolar septal thickening, interstitial hypertrophy, and infiltration of inflammatory cells were prominent in the lung of PAAF-injected rats. Transcription factor, nuclear factor KB (NF-kappaB) was activated and the mRNA levels of tumor necrosis factor-alpha and interleukin-1beta were increased in the lung of the PAAF-injected rats. The permeability index assessed by Evans blue assay and the lung myeloperoxidase activity levels were significantly higher in the PAAF-injected rats than in controls. Inhibition of NF-kappaB ameliorated the histologic findings and improved the survival rates. Our results suggest that PAAF play a role in the pathogenesis of lung injury in severe AP, at least in part through the activation of NF-kappaB.

Topics: Acute Disease; Animals; Ascites; Ascitic Fluid; Ceruletide; Disease Models, Animal; Evans Blue; Immunohistochemistry; Interleukin-1; Lung; Lung Diseases; Male; NF-kappa B; Pancreatitis; Peroxidase; Prognosis; Rats; Rats, Wistar; RNA, Messenger; Survival Rate; Tumor Necrosis Factor-alpha

Bacterial infectious complications are the most common cause of morbidity and mortality associated with acute pancreatitis. Most pathogens are common gastrointestinal flora, indicating that the gut is the source of pancreatitis-related infections. However, the route whereby the microorganisms reach distant organs remains speculative. We tested the hypothesis that spread of bacteria occurs via a transperitoneal pathway. Acute interstitial pancreatitis (AIP) was induced in antibiotic (gentamicin, bacithracin, neomycin)-decontaminated rats by intravenous infusion of cerulein. Effects of pancreatic necrosis (PN) were studied in rats that received additional injections into the peritoneal cavity of pancreatic tissue obtained from donor rats. The rats were inoculated with Escherichia coli (O2:KN:H18) resistant to the antibiotics used for decontamination either orally (10(12) microorganisms; experiment I) or intraperitoneally (10(8) microorganisms; experiment II). Moreover, the rat peritoneal cavity wash was inoculated with 10(8) E. coli in vitro (experiment III). In rats with AIP and PN, recovery of the bacteria from liver, spleen, pancreas, lung, and blood following oral inoculation demonstrated that acute pancreatitis promotes bacterial translocation from the gut. The absence of E. coli in these organs following intraperitoneal inoculation showed that the bacteria do not spread from the peritoneal cavity. Rats with PN cleared E. coli from the peritoneal cavity in a shorter period than rats with AIP and controls (5 vs. 7 and 8 days; p < 0.05). The multiplication rate of E. coli in peritoneal cavity wash was lower in rats with PN than in rats with AIP and controls (p < 0.01). We conclude that (1) translocation of E. coli from the gut during cerulein-induced acute pancreatitis occurs via nonperitoneal pathways, (2) the peritoneal cavity acts as a trap for the bacteria rather than a source of bacterial seeding, and (3) PN impairs survival of E. coli in the peritoneal cavity via inhibition of the bacterial multiplication in this model.

Topics: Acute Disease; Animals; Ascites; Bacterial Translocation; Ceruletide; Escherichia coli; Male; Pancreatitis; Peritoneal Cavity; Rats; Rats, Sprague-Dawley

Contrast-enhanced computed tomography (CECT) is used to show areas of decreased pancreatic perfusion in severe acute pancreatitis (AP). To evaluate possible adverse effects of the contrast medium (CM) on the course of AP, the impact of intravenous CM in AP of graded severity in the rat was studied.. Pancreatitis of three levels of severity was induced in Sprague-Dawley rats with intravenous cerulein hyperstimulation plus time- and pressure-controlled intraductal infusion of saline or glycodeoxycholic acid. At 7 hours, control and pancreatitis animals received intravenous ionic CM, nonionic CM, or saline. The principal outcome measures were 24-hour survival, trypsinogen activation peptides (TAP) in ascites, and histological acinar necrosis score.. There was no measurable effect of CM on the index features in control animals or animals with mild or moderate AP. In severe AP, CM caused a significant increase in mortality, ascites TAP, and necrosis score.. Intravenous CM increases pancreatic injury when administered early in the course of severe experimental AP. Because CM may convert borderline ischemia to irreversible necrosis, CECT performed early in pancreatitis to show poor perfusion and predict areas of necrosis may depict a self-fulfilling prophecy. Early CECT should be reconsidered and perhaps avoided.

Topics: Acute Disease; Animals; Ascites; Ceruletide; Contrast Media; Glycodeoxycholic Acid; Injections; Injections, Intravenous; Male; Necrosis; Pancreatic Ducts; Pancreatitis; Peptides; Rats; Rats, Sprague-Dawley; Sodium Chloride; Survival Analysis; Time Factors; Trypsinogen

As a result of pancreas stimulation with secretin-ceruletid we were able to measure the release of phospholipase A in ascites, serum, lymph, and urine in acute experimental pancreatitis in the dog. After induction of acute pancreatitis we found no increase over the normal range in serum, lymph, and urine phospholipase A activities. In addition, the stimulation of the exocrine pancreas did not show a significant change in phospholipase A activity. The excessively high phospholipase A activity in ascites following induction of acute pancreatitis fell significantly after pancreas stimulation with secretin-ceruletid.

Topics: Acute Disease; Animals; Ascites; Ceruletide; Dogs; Lymph; Male; Pancreatic Function Tests; Pancreatitis; Phospholipases; Phospholipases A; Secretin