A new combination therapy in severe acute pancreatitis--hyperbaric oxygen plus 3-aminobenzamide: an experimental study.

OBJECTIVES: This study was designed to evaluate effects of hyperbaric oxygen (HBO) plus 3-aminobenzamide (3-AB) cotreatment on tissue oxidative stress parameters (TOSp), tissue histopathology scores (THSc), and bacterial translocations (Bact-Trans) in an experimental model of severe acute pancreatitis (AP). METHODS: Seventy-five Sprague-Dawley rats were randomized into 5 groups. Group 1 received sham. Severe AP was induced by intraductal taurocholate infusion and then group 2 received saline, group 3 received 3-AB, group 4 received 3-AB plus HBO, and group 5 received HBO. 3-Aminobenzamide (10 mg/kg per day, once daily, intraperitoneal) and saline (1 mL/kg) were started right after the induction, whereas HBO (2,8 atm pressure, BID, 90 minutes each) was started at the sixth hour. The rats were euthanized at the 54th hour, and TOSp, THSc, and Bact-Trans were studied. RESULTS: In treatment groups 3 and 5, Bact-Trans (P < 0.05, P < 0.05), TOSp (P < 0.05, P < 0.05), and THSc (P < 0.001, P < 0.001) were significantly lower than controls. In addition to these findings, group 4 (cotreatment) showed the most significant effect on Bact-Trans and THSc (P < 0.001, P < 0.001) and also better in TOSp (P < 0.02). CONCLUSIONS: Poly(ADP-ribose) polymerase inhibition by 3-AB and HBO treatment alone was effective in the course of severe AP, and favorable with cotreatment because of the improved cascades of inflammatory process by different aspects.

Does the 3-aminobenzamide effect on bacterial translocation affect experimental acute necrotizing pancreatitis?

BACKGROUND/AIMS: One of the most important complications of acute pancreatitis is the secondary bacterial infections of the pancreas and gut. Translocation of bacteria from the gut is accepted as being responsible for the development of septic complications in acute pancreatitis. In this study, our aim was to investigate the effect of PARP inhibition via 3-aminobenzamide on the bacterial translocation in acute pancreatitis. METHODS: 45 male Sprague-Dawley rats were randomly allocated into three groups. Group I (Sham+saline) received normal saline infusion into the common biliopancreatic duct. Acute pancreatitis was induced in Group II (acute pancreatitis+saline) and Group III (acute pancreatitis+ 3-aminobenzamide) by the retrograde injection of taurocholate into the common biliopancreatic duct. Six hours after induction of pancreatitis, the rats in Group I and II were treated with saline (1 ml, every 12 hours), while the rats in Group III were treated with 3-aminobenzamide (10 mg/kg/day every 12 hours), intraperitoneally. In the 54th hour of the study, blood and tissue samples were taken for biochemical, microbiological and histopathological analysis. RESULTS: Acute pancreatitis developed in Groups II and III. Pathologic score [median (25-75% percentiles)] of the pancreatitis in Group III [8 (7-9)] was significantly lower than in Group II [19 (18-21)] (p<0.001). Bacterial translocation to mesenteric lymph node (53.3%), peritoneum (60%) and pancreas (46.7%) in Group III was significantly lower than in Group II (100% for all) (p<0.02, p<0.03, p<0.005, respectively). Pancreatic tissue glutathione peroxidase, superoxide dismutase, and malondialdehyde levels were better in Group III compared to Group II (p<0.001 for all). Comparison of Groups II and III demonstrated reduced severity of inflammation of the gut in Group III (p>0.05). Improvement in bacterial translocation was correlated with reducing oxidative stress. CONCLUSIONS: We demonstrated that 3-aminobenzamide therapy improved histopathologic score and oxidative stress in experimental pancreatitis. In addition, it was demonstrated microbiologically and histopathologically that 3-aminobenzamide therapy improves bacterial translocation. Further survival studies demonstrating the efficacy of 3-aminobenzamide therapy and explaining the potential mechanisms of bacterial translocation prevention in acute necrotizing pancreatitis will be beneficial.

Combination of allopurinol and hyperbaric oxygen therapy: a new treatment in experimental acute necrotizing pancreatitis?

AIM: To investigate the individual and combined effects of allopurinol and hyperbaric oxygen (HBO) therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation (BT) in the experimental rat acute pancreatitis (AP). METHODS: Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls (sham, Group I). AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group II received saline, Group III allopurinol, Group IV allopurinol plus HBO and Group V HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS: Serum amylase levels were lower in Groups III, IV and V compared to Group II (974 +/- 110, 384 +/- 40, 851 +/- 56, and 1664 +/- 234 U/L, respectively, P < 0.05, for all). Combining the two treatment options revealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations (13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P < 0.01). Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups III, IV and V compared to Group II (54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P < 0.05 for all). CONCLUSION: The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.

Is late antibiotic prophylaxis effective in the prevention of secondary pancreatic infection?

BACKGROUND: Secondary infection of the inflamed pancreas is the principal cause of death after severe acute pancreatitis (AP). Although patients are not always managed early in the course of AP in clinical practice, prophylactic antibiotics that were used in experimental studies in rats were always initiated early after induction of pancreatitis. The effectiveness of antibiotics initiated later is unknown. AIM: The aim of this study was to compare the effectiveness of ciprofloxacin and meropenem initiated early versus later in the course of acute necrotizing pancreatitis (ANP) in rats. METHODS: 100 Sprague-Dawley rats were studied. ANP was induced in rats by intraductal injection of 3% taurocholate. Rats were divided randomly into five groups: group I rats received normal saline as a placebo, group II and IV rats received three times daily meropenem 60 mg/kg i.p. at 2 and 24 h, respectively and group III and V rats received twice daily ciprofloxacin 50 mg/kg i.p. at 2 and 24 h, respectively, after induction. At 96 h, all rats were killed for quantitative bacteriologic study. A point-scoring system of histological features was used to evaluate the severity of pancreatitis. RESULTS: Meropenem and ciprofloxacin initiated 2 h after induction of pancreatitis significantly reduced the prevalence of pancreatic infection (p < 0.001 and p < 0.04, respectively) as compared to controls. Neither of the antibiotics initiated later during the course of AP caused a significant decrease in pancreatic infection in rats (p > 0.05). Although the rats treated early infected less frequently than the rats treated later, the comparison reached statistical significance only in the meropenem group (p < 0.02). CONCLUSION: Early antibiotic treatment reduces pancreatic infection more efficiently than late antibiotic treatment in ANP in rats.

Symptomatic intestinal amoebiasis and climatic parameters.

Symptomatic intestinal amoebiasis is an important problem, especially in the developing world. The relationships between climatic parameters and amoebic dysentery cases were evaluated in this study. Climatic data were obtained from the local meteorological department and the diagnosis of amoebic dysentery was established by clinical and laboratory investigation. Monthly mean temperature (r = 0.755, p = 0.005), monthly mean maximum temperature (r = 0.711, p = 0.01), monthly mean temperature at 100 cm underground (r = 0.818, p = 0.001) and monthly mean humidity values (r = -0.656, p = 0.02) correlated significantly with symptomatic disease. Although inverse relationships were found for humidity and atmospheric pressure, the monthly mean atmospheric pressure (r = -0.084) did not seem to have a significant effect on intestinal amoebiasis (p = 0.80). Thus, when the weather warmed up, the frequency of symptomatic intestinal amoebiasis increased significantly. To improve the ability to predict disease trends, it seems logical to assess the independent and interactive effects of climatic parameters on disease impact.