ceruletide and Bacterial-Infections

Bacterial infection of the pancreas aggravates the course of acute pancreatitis. Since bacterial translocation from the gut is likely to be an early event, in an animal model of pancreatitis, we investigated the effect of early bacterial supra-infection of the pancreas on the course of the disease.. Six hours after the induction of acute pancreatitis in male Wistar rats (n = 180) by supramaximal stimulation with cerulein (or placebo in a control group), the animals were operated and a suspension of Helicobacter pylori, Escherichia coli or saline were introduced either in the pancreatic duct or interstitium (12 groups of 15 rats each); after 24 h, animals were killed and the following parameters analysed: macroscopic and histologic appearance of the pancreas (score), wet-to-dry weight ratio, pancreas trypsinogen activation peptide level, serum amylase, interleukin-6 and phospholipase A2 activity.. All parameters were increased in rats with cerulein-induced pancreatitis in comparison to placebo. Interstitial and intraductal application of bacteria increased the pancreatic damage. This effect was more evident with the application of E. coli in both cerulein and placebo groups. Application of E. coli but not of H. pylori determined pancreatic activation of trypsinogen, increased mortality and induced the production of interleukin-6.. Bacterial invasion of the pancreas worsens the histologic and clinical picture of disease and induces a systemic inflammatory response.

Topics: Acute Disease; Amylases; Animals; Bacterial Infections; Ceruletide; Disease Models, Animal; Interleukin-6; Male; Organ Size; Pancreas; Pancreatitis; Pancreatitis, Acute Necrotizing; Phospholipases A; Phospholipases A2; Rats; Rats, Wistar; Systemic Inflammatory Response Syndrome

Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for prophylaxis are unknown and difficult to study in humans.. The time course of bacterial infection of the pancreas in a rodent model of acute necrotizing pancreatitis was characterized. The authors ascertained if there is a correlation with the degree of necrosis.. Acute pancreatitis (AP) of graded severity was induced under sterile conditions by an intravenous infusion of cerulein (5 micrograms/kg/hr) for 6 hours (mild AP), or a combination of intravenous cerulein with an intraductal infusion of 10-mM glycodeoxycholic acid (0.2 mL for 2 min for moderate AP, 0.5 mL for 10 min for severe AP). Sham-operated animals (intravenous and intraductal NaCl 0.9%) served as controls. Ninety-six hours after induction, animals were killed for quantitative bacterial examination and histologic scoring of necrosis. In addition, groups of animals with severe AP were investigated at 12, 24, 48, 96, and 144 hours.. No significant pancreatic necrosis was found in control animals (0.3 +/- 0.1) or animals with mild AP (0.6 +/- 0.1) killed at 96 hours. Necrosis scores were 1.1 +/- 0.2 for animals with moderate AP and 1.9 +/- 0.2 for animals with severe AP. Control animals did not develop significant bacterial infection of the pancreas (> or = 10(3) CFU/g). At 96 hours, the prevalence of infection was 37.5% in animals with mild AP and 50% in animals with moderate AP. In animals with severe AP, infection of the pancreas increased from 33% in the first 24 hours to 75% between 48 and 96 hours (p < 0.05). The bacterial counts and the number of different species increased with time and was maximal (> 10(11) CFU/g) at 96 hours.. Bacterial infection of the pancreas in rodent AP increases during the first several days, and its likelihood correlates with the severity of the disease. This model, which closely mimics the features of human acute pancreatitis, provides a unique opportunity to study the pathogenesis of infected necrosis and test therapeutic strategies.

Topics: Acute Disease; Animals; Bacterial Infections; Ceruletide; Colony Count, Microbial; Disease Models, Animal; Edema; Enterococcus; Escherichia coli Infections; Glycodeoxycholic Acid; Gram-Positive Bacterial Infections; Leukocytes; Male; Necrosis; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley; Staphylococcal Infections; Survival Rate; Time Factors