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Objective. Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. Materials and methods. An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-α were measured 2h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. Results. In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-α level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. Conclusion. The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy.

Pancreatite aguda é uma das principais causas de síndrome da resposta inflamatória sistêmica (SRIS). Complicações sistêmicas são os principais fatores responsáveis pela ocorrência de falência de múltiplos órgãos e sistemas e morte durante a primeira etapa da doença. Os níveis de mediadores inflamatórios possuem uma relação com a gravidade da pancreatite. O TNF-alfa tem sido descrito como o agente iniciador da resposta inflamatória da pancreatite aguda. Estudos prévios usando a pentoxifilina para bloquear a produção de TNF-alfa têm demonstrado efeitos benéficos quando usada em modelos experimentais de sepse ou choque. A infecção pancreática é a mais grave complicação da pancreatite aguda com índices de mortalidade que podem chegar a 80%. Os mecanismos que determinam a ocorrência da infecção pancreática não são bem esclarecidos. Objetivo: Determinar o efeito da inibição da produção de TNF-alfa na pancreatite aguda com a administração de pentoxifilina. Métodos: Foi utilizado um modelo experimental de pancreatite aguda grave através da injeção intraductal de taurocolato de sódio a 2,5%. Cento e vinte e quatro ratos Wistar machos foram divididos em três grupos: Controle (animais submetidos ao procedimento cirúrgico sem a administração de taurocolato de sódio), Pancreatite (animais submetidos à indução da pancreatite aguda) e Pentoxifilina (animais submetidos à indução da pancreatite aguda seguida da administração intraperitoneal de 25 mg/Kg de pentoxifilina). Foi realizada a dosagem sérica das interleucinas 6 e 10 e TNF-alfa duas horas após a indução da pancreatite. Foram analisadas a ocorrência de translocação bacteriana e a incidência de infecção pancreática, através de culturas realizadas 24 horas após a indução da pancreatite aguda e a mortalidade global. A ocorrência de infecção pancreática foi considerada como positiva quando a concentração de bactérias expressa em UFC/g foi maior que 105. Resultados: Quando comparado ao grupo Pancreatite, o grupo Pentoxifilina apresentou redução significativa da lesão histológica pancreática, dos níveis de IL-6, IL-10 e TNF-alfa e da ocorrência de infecção pancreática (p < 0,05), tais alterações se associam a redução significativa da mortalidade no grupo Pentoxifilina. Conclusão: A inibição da produção de TNF-alfa através da administração de pentoxifilina foi capaz de reduzir o processo inflamatório local e sistêmico, reduzir a translocação bacteriana e infecção pancreática e melhorar a sobrevida com redução dos índices de mortalidade desta grave doença Acute pancreatitis (AP) is considered one of the typical conditions causing systemic inflammatory response (SIRS). Systemic complications are the most important contributors to multiple organ failure and death during the first stages of severe acute pancreatitis. Levels of pro-inflammatory cytokines increase during the course of AP, and these levels appear to be correlated with the severity of pancreatic inflammation. TNF-alfa may be an initiator of inflammatory process in AP. Previous studies using pentoxifylline to block TNF-alfa production have showed beneficial effects in experimental models of sepsis and shock. The gut is a target organ of the SIRS causing gut barrier dysfunction allowing bacteria and toxin translocation. Bacterial translocation has been implicated in the development of multiple organ failure and is one of the major causes of pancreatic infection in patients with pancreatic necrosis. Aim: To determinate the effects of inhibition of TNF-? on the pancreatic and systemic inflammatory response, pancreatic infection, and mortality rate in necrotizing acute pancreatitis in rats. Methods: An experimental model of severe AP by injection of 0.5ml of 2.5% sodium taurocholate into the pancreatic duct was utilized. A hundred and twenty four male Wistar rats were divided in 3 groups: Sham (surgical procedure without AP induction), Pancreatitis (AP Induction), and Pentoxifylline (AP induction plus administration of 25 mg/kg pentoxifylline). Pancreatic inflammatory response was measured by histological studies and systemic inflammatory response was analyzed measuring the production of inflammatory cytokines (IL-6, IL-10, and TNF-alfa). Pancreatic infection was evaluated with bacterial cultures performed 24 h after the AP induction. The numbers of organisms were expressed as colony forming units (CFU) per gram. The occurrence of pancreatic infection was also analyzed and considered positive when the CFU/g was > 105. A parallel survival study was also performed. Results: Inhibition of TNF-alfa by pentoxifylline shows beneficial effects in this experimental model. The Pentoxifylline group had a statistically significant reduction of histological damage in the pancreas, inflammatory cytokines levels (IL-6, IL-10, and TNF-?), and occurrence of pancreatic infection (p < 0.05). These changes were associated with a significant reduction of mortality rate. Conclusions: Inhibition of TNF-alfa reduced local and systemic inflammatory response, reduced systemic complication as pancreatic infection, and decrease mortality rate in this model. Pentoxifylline may provide a useful therapy in the treatment of acute pancreatitis

Severe acute pancreatitis (AP) is characterized by hemodynamic alterations and a systemic inflammatory response, leading to a high mortality rate. Treatment of hemorrhagic shock with hypertonic saline solutions significantly reduces mortality through an improvement in the hemodynamic conditions and possibly by an anti-inflammatory effect. Therefore, hypertonic solutions could be effective in AP.Wistar rats were divided in 4 groups: group C, control, without AP; group NT, AP, without treatment; group NS, treatment with normal saline solution (NaCl 0.9%) 1 hour after AP; group HTS, treatment with hypertonic saline solution (NaCl 7.5%) 1 hour after AP. AP was induced by injection of 2.5% sodium taurocholate into the pancreatic duct. Mean arterial blood pressure (MAP) and heart rate were recorded at 0 and 2, 4, 24, and 48 hours after AP. After induction of AP, animals were killed at 2, 12, 24, and 48 hours for serum amylase, interleukin (IL)-6, and IL-10 analysis, pancreatic tissue culture and histologic analysis, oxidation and phosphorylation of liver mitochondria, pulmonary myeloperoxidase activity (MPO), and mortality study.In animals of groups NS and NT, a significant decrease of MAP was observed 48 hours after AP (NS: 91 +/- 3 mm Hg; NT: 89 +/- 3 mm Hg) compared with baseline (C: 105 +/- 2 mm Hg) and to HTS group (HTS: 102 +/- 2 mm Hg; P0.05). In animals of group NT, NS, and HTS, serum IL-6 and IL-10 levels were significantly higher at 2 hours after AP compared with the control group. However, IL-6 levels at 12 hours after AP and IL-10 levels at 2 and 12 hours after AP were significant lower in group HTS compared with NS and NT groups (P0.05). In group HTS, a decrease of pulmonary MPO activity and of pancreatic infection was observed 24 hours after AP compared with NT and NS groups (P0.05). A significant reduction on pancreatic acinar necrosis and mitochondrial dysfunction was observed after 48 hours of AP in animals of group HTS compared with groups NT and NS (P0.05). A significant reduction on mortality was observed in HTS (0/14) compared with NS (6/17; 35%) and NT (7/20; 35%).The administration of hypertonic saline solution in experimental AP attenuated hemodynamic alterations, decreased inflammatory cytokines, diminished systemic lesions and pancreatic acinar necrosis, prevented pancreatic infection, and reduced the mortality rate.

A 50-year-old woman presented with pancreatitis, fluctuant jaundice, weight loss, and abdominal pain. Contrast-enhanced computed tomography and abdominal ultrasound showed slight dilatation of the biliary tree and gallbladder without calculi. Endoscopy demonstrated a tumor protruding from the papilla of Vater. First endoscopically biopsy diagnosed no tumor, and a second biopsy diagnosed as papillary adenocarcinoma. The patient underwent duodenopancreatectomy. The specimen was fixed in formalin (10%). The tissue was processed routinely, and paraffin sections were stained with hematoxylin-eosin and periodic acid Schiff. Gross examination showed two tumors seen as prolapsed nodules growing isolated from the minor and major duodenal papillae measuring 1.5 and 1.0 cm, respectively, both covered by duodenal mucosa and the histologic study of both lesions demonstrated a moderately differentiated tubular adenocarcinoma, which invaded duodenal wall. After surgery, she is alive 24 months without evidence of recurrence.

OBJECTIVES: To evaluate the prevalence of cholecystopathy in chronic renal patients awaiting kidney transplants. INTRODUCTION: The prevalence and management of cholelithiasis in renal transplant patients is not well established. METHODS: A total of 342 chronic renal failure patients on the waiting list for a kidney transplant were studied. Patients were evaluated for the presence of cholelithiasis and related symptoms, previous cholecystectomies and other abdominal surgeries, time on dialysis, and general data (gender, age, number of pregnancies, and body mass index). RESULTS: Cholelithiasis was found in 41 out of 342 patients (12%). Twelve of these patients, all symptomatic, had previously undergone cholecystectomies. Five out of 29 patients who had not undergone surgery were symptomatic. Overall, 17 patients (41.5%) were symptomatic. Their mean age was 54 (range 32-74) years old; 61% were female, and their mean body mass index was 25.4. Nineteen (76%) out of 25 women had previously been pregnant, with an average of 3.6 pregnancies per woman. CONCLUSIONS: The frequency of cholelithiasis was similar to that reported in the literature for the general population. However, the high frequency of symptomatic patients points toward an indication of routine pre-transplant cholecystectomy to avoid serious post-transplant complications.

Severe acute pancreatitis is associated with high morbidity and mortality rates. At the present time, no specific therapy has been shown to be uniformly effective in reducing morbidity and mortality in this disease. The aim of this study was to determine the effects of pentoxifylline on the pancreatic and systemic inflammatory process, pancreatic infection, and mortality rate in severe acute pancreatitis in rats.One hundred and twenty male Wistar rats were divided into 3 groups: sham, pancreatitis, and pentoxifylline (acute pancreatitis induction plus administration of 25 mg/kg pentoxifylline). Inflammatory response was measured by histological studies, inflammatory cytokine production (IL-6, IL-10, and TNF-alpha), and mortality rate. Pancreatic infection was evaluated by bacterial cultures expressed in colony-forming units per gram.Pentoxifylline-treated animals had a statistically significant reduction of inflammatory cytokine levels, pancreatic histological damage, occurrence of bacterial translocation and pancreatic infection (p0.05), associated with a significant reduction in mortality rate.Pentoxifylline administration in this experimental model of acute pancreatitis reduces local and systemic inflammatory responses and decreases the pancreatic infection and the mortality rate.

The anti-invasive activity of antisense oligonucleotides (ASO) specific to the K-ras gene in hamster pancreatic cancer was investigated. HaP-T1, a cell culture derived from BHP-induced hamster pancreatic cancer, was used. After liposome-mediated transfection with mutation-matched and mutation-mismatched ASO in different concentrations, cell proliferation was studied by MTT and MTT-agarose methods. In vitro chemoinvasion assay with the reconstitution of a matrix of a basement membrane onto a filter in a Boyden chamber was performed. Mutation-matched ASO inhibited the tumor growth and invasiveness of HaP-T1 in a dose-dependent manner, while mutation-mismatched ASO were not effective in inhibiting invasion. The present study suggests that antisense oligonucleotides mutation-matched to the K-ras gene may be a new anticancer strategy for pancreatic cancer since they inhibited not only tumor growth but also invasiveness in vitro.

INTRODUÇÃO: Isquemia e reperfusão (I/R) intestinal podem ocorrer em cirurgias vasculares e abdominais, trauma, choque, grandes queimados e transplante intestinal. O órgão funciona como barreira contra agressores externos, e uma vez lesionado, sofre aumento da permeabilidade, que permite a passagem de mediadores inflamatórios e bactérias, causando sepse, inflamação sistêmica e disfunção de múltiplos órgãos, que é a maior causa de morte em unidades de terapia intensiva cirúrgica. O diazóxido tem mecanismo de ação semelhante ao pré-condicionamento isquêmico, e demonstrou proteção em I/R de diversos órgãos. De forma semelhante, em cenário de isquemia e reperfusão intestinal, supomos que ele desempenharia função protetora no intestino, através do pré-condicionamento farmacológico, e em órgãos distantes, exercendo o pré-condicionamento remoto. OBJETIVOS: Avaliar os efeitos do diazóxido em intestino, fígado e coração de ratos submetidos a uma hora de isquemia e doze horas de reperfusão intestinal. MÉTODOS: 32 ratos machos Wistar divididos em três grupos, Sham (n=6); Salina (n=13) submetido a uma hora de isquemia e doze horas de reperfusão intestinal, tendo recebido soro fisiológico; Diazóxido (n=13) submetido a I/R e diazóxido. O modelo de I/R incluiu laparotomia mediana e clampeamento da artéria mesentérica superior. No soro, estudamos citocinas, AST, ALT, troponina e IFABP. Em amostras de intestino e fígado, quantificamos a expressão gênica de citocinas e COX-2. No intestino foi estudada ainda a expressão de proteínas ligadas a barreira intestinal (tight junctions): ZO-1, ocludina e JAM-A. Realizamos preparações histológicas em hematoxiina e eosina de intestino, fígado e coração. RESULTADOS: Evidenciamos redução de expressão de IL-6 intestinal, redução de IL-10 hepática, além de menor expressão de COX-2 intestinal e de ZO-1. IL-6 tem níveis associados a dano da barreira intestinal, assim como COX-2. A menor expressão de ZO-1 indica menor esforço de reparação, proporcional ao grau de lesão em modelos não letais de dano tecidual. CONCLUSÃO: O diazóxido exerce efeito protetor sobre o intestino de ratos após uma hora de isquemia e doze horas de reperfusão, porém não foi possível demonstrar efeito protetor sobre fígado ou coração INTRODUCTION: Intestinal ischemia and reperfusion can occur in great vascular and abdominal surgeries, trauma, shock, great burns and intestinal transplantation. Since the organ works as a barrier against external threats, and once damaged, permeability increases, which permits passage of bacteria and inflammatory mediators, causing sepsis, systemic inflammation and multiple organ dysfunction, the greatest death cause in surgical intensive care units. Diazoxide has similar mechanisms to ischemic preconditioning, and proved benefit during I/R in several tissues. Similarly, in an intestinal ischemia-reperfusion situation, we suppose it can protect intestine with pharmacological preconditioning, and remote organs, with remote preconditioning. OBJECTIVE: To evaluate diazoxide effects over intestine, liver and heart of rats submitted to one-hour ischemia and twelve-hour reperfusion of intestine. METHODS: 32 male Wistar rats divided in three groups, Sham (n=6); Saline (n=13) submitted to one hour of intestinal ischemia and 12 hours of reperfusion and 0.9% saline; Diazoxide (n=13), submitted I/R and diazoxide. I/R model included median laparotomy and superior mesenteric artery clamping. In blood, we studied cytokines, TGO, TGP, troponin and IFABP. In intestine and liver, we quantified genic expression. Of cytokines and COX-2. In intestine, we also studied expression of tight junctions proteins. Also, histologic analysis in hematoxilin-eosin for intestine, liver and heart. RESULTS: We found lower expression of intestinal IL-6, hepatic IL-10, and lower levels of intestinal COX-2 and ZO-1. IL-6 high levels are associated with intestinal barrier lesion, as for COX-2. Lower levels of ZO-1 correlate with minor repair effort, proportional to lesion grade in non-letal models of damage. CONCLUSION: Diazoxide exerts protective effect over intestine of rats submitted to one hour of ischemia and twelve hours of intestinal reperfusion, but no effect was demonstrated over liver and heart