Nuket Mas

The effect of activated protein C on experimental acute necrotizing pancreatitis

IntroductionAcute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30–40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis.Materials and methodForty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-α, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured.ResultsAcute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid.Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 ± 0.47 versus 14.00 ± 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis factor--α, and IL-6 levels were also significantly decreased in comparison with positive controls (P < 0.001, P < 0.04 and P < 0.001, respectively).ConclusionAPC improved the severity of pancreatic tissue histology, superinfection rates and serum markers of inflammation during the course of acute necrotizing pancreatitis.

The effect of antibiotic and probiotic combination therapy on secondary pancreatic infections and oxidative stress parameters in experimental acute necrotizing pancreatitis.

Introduction Ciprofloxacin and meropenem have effects on intestinal bacteria that are responsible for pancreatic infection, and on the basis of recent data it has been argued that probiotics, especially those used in the food industry, could improve efforts to prevent and treat secondary pancreatic infections by inhibiting bacterial translocation. Aims To evaluate the effects of probiotic treatment alone or in combination with early administration of two different antibiotics on serum amylase, pancreatic histopathology, bacterial translocation, and oxidative markers. Methodology Acute pancreatitis was induced in rats with 3% sodium taurocholate (1 mL/kg intraductally), except in group VI (sham group). After the stabilization period, the rats were divided into seven groups (n = 20) randomly. At hour 6 after injection, group I rats received probiotic Saccharomyces boulardii (25 mg/d orally q.d.), group II received meropenem (60 mg/kg intraperitoneally b.i.d.), group III received ciprofloxacin (40 mg/kg intraperitoneally b.i.d.), group IV received the same dose of probiotic plus meropenem, and group V received probiotic plus ciprofloxacin. Treatment was not given to group VI (sham group) and group VII (pancreatitis group). At hour 48 after induction, specimens were collected. Results and Conclusion Although histopathologic scores in treatment groups were found to be lower than in group VII, the difference was statistically significant only in group V (p < 0.001). In evaluation of oxidative stress, we found that MDA levels decreased and SOD levels increased in treatment groups in comparison with levels in group VII. Probiotic treatment alone reduced bacterial translocation. Probiotic–antibiotic combination therapy was shown to improve histopathologic scores and oxidative parameters.

Rat liver fibrosis regresses better with pegylated interferon alpha2b and ursodeoxycholic acid treatments than spontaneous recovery.

Abstract: Background/aims: Fibrosis and cirrhosis are common complications of chronic liver diseases. An imbalance between fibrogenesis and fibrolysis results in scarring of the liver parenchyma. We aimed to investigate the possible antifibrotic effectiveness of a newly modified interferon molecule peginterferon α2b (PEG‐IFNα2b) which has better antiviral activity, and ursodeoxycholic acid (UDCA).

Allopurinol in rat chronic pancreatitis: effects on pancreatic stellate cell activation.

Objectives: Activation of pancreatic stellate cells (PSCs) is a key event in pancreatic fibrosis. Xanthine oxidase-derived free radicals are involved in the mechanism of chronic pancreatitis (CP). We here searched the in vivo effects of allopurinol on PSC activation and its relation to tissue oxidative stress and histological findings in rat CP. Methods: Rat CP was induced with intraductal trinitrobenzene sulfonic acid in groups 1 (n = 16) and 2 (n = 10). Group 3 (n = 10) received intraductal saline. Four weeks after induction, group 1 received allopurinol (200 mg/kg, SC), and groups 2 and 3 received saline. After 4 weeks, oxidative stress parameters, histological evaluation, and immunostaining for α-smooth muscle actin (+) PSCs were performed in the pancreata. Results: Oxidative stress parameters improved significantly in group 1 compared with groups 2 and 3. Collagen deposition and lobular/sublobular atrophy were significantly lower in group 1 than in group 2. α-smooth muscle actin (+) PSCs counts in group 1 were significantly lower than in group 2, and were in correlation with the degree of fibrosis and atrophy. Conclusions: Allopurinol inhibits PSC activation in vivo. Pancreatic fibrosis can be prevented, at least in part, by antioxidant treatment through xanthine oxidase metabolism. Long-term use of allopurinol and its analogs may be considered in clinical trials with CP.

Unusual Relation of the Median Nerve with the Accessory Head of the Biceps Brachii Muscle: An Original Case Report

Durante una diseccion de rutina de la region anterior del brazo, se observo una relacion anormal del nervio mediano con una cabeza accesoria del musculo biceps braquial, en un miembro superior derecho de un cadaver masculino. Mientras que las cabezas larga y corta tuvieron un origen normal, una tercera cabeza se origino de la superficie anteromedial de la parte superior del cuerpo humeral. Algunas fibras de esta cabeza accesorias, se originaron del lado medial de la fascia profunda que rodea al musculo braquial. Las fibras cruzaban al nervio mediano superficialmente, antes de unirse a la tercera cabeza, la cual se inserto a traves de un tendon comun con las cabezas larga y corta. El conocimiento de tales variaciones es de importancia tanto para anatomistas o clinicos, asi como esencialmente para cirujanos plasticos en las cirugias, que se usan colgajos

The effect of combination therapy of hyperbaric oxygen, meropenem, and selective nitric oxide synthase inhibitor in experimental acute pancreatitis.

Despite the new diagnostic and therapeutic advancements, acute pancreatitis has still high rate of morbidity and mortality. We aimed to evaluate the effects of hyperbaric oxygen (HBO) therapy alone or combined with S-methylisothiourea (SMT), and meropenem (MER) therapy in an experimental rat model of acute necrotizing pancreatitis. Rats were randomly divided into 8 groups, and acute pancreatitis was induced in all groups except group 1. Treatment protocols were saline for group 2, SMT for group 3, SMT + MER for group 4, SMT + HBO for group 5, HBO for group 6, HBO + MER for group 7, and MER for group 8. All surviving animals were killed 48 hours after the induction of pancreatitis, and specimens were collected. Oxidative stress parameters, histopathologic scores and amylase levels were better in treatment groups than in the positive control group (group 2). The most favorable results were obtained in HBO treatment groups, especially in HBO + MER group (group 7). Our results indicate that adding HBO therapy to the antibiotic therapy will decrease oxidative stress parameters, serum amylase levels, and histopathological score. We suggest that adding the HBO therapy as an adjunctive to the treatment protocol of acute necrotizing pancreatitis may yield improvement in the morbidity and mortality of the disease.

Antioxidant treatment with taurine ameliorates chronic pancreatitis in an experimental rat model.

Objectives: Based on the results of recent studies that reported depleted antioxidant capacity in patients with chronic pancreatitis (CP), prevention of free radical production has gained importance in antifibrotic treatment strategies in CP. The aim of this study was to investigate the effects of taurine on oxidative capacity and fibrosis in experimental chronic rat pancreatic fibrosis. Methods: CP was induced in male Sprague-Dawley rats by intraductal trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol. Taurine was given intraperitoneally at a concentration of 1000 mg/kg. The treatment groups were as follows: group 1, TNBS plus normal saline (NS); group 2, TNBS plus taurine; group 3, ethanol plus NS; and group 4, NS plus NS. Each group contained 15 animals. Treatment was started after established CP. After 4 weeks of treatment, markers of oxidative stress and the degree of pancreatic fibrosis were determined. Results: The amount of weight loss was significantly lower in the taurine-treated group with CP (P < 0.002). Tissue malondialdehyde levels increased and superoxide dismutase and glutathione peroxidase activities decreased significantly after treatment as well (P < 0.001). Histopathologic scores were also lower in taurine-treated animals with CP (P < 0.005). Conclusions: Taurine treatment improved the degree of oxidative stress and fibrosis in rat CP. Antioxidant treatment might be considered a novel option to alleviate the fibrotic process in CP.

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.

Quantitative Analysis of Myelinated Axons of Commissural Fibers in the Rat Brain

In this study, the myelinated axons of the rostrum, genu, truncus and splenium parts of the corpus callosum and of the anterior, posterior and habenular commissures were counted in the rat brain by using a camera lucida. The numerical densities of these axons were compared with each other by means of quantitative analytical statistical methods. In parts of the corpus callosum, a statistically significant difference was found between the rostrum and genu, rostrum and truncus, rostrum and the splenium, genu and truncus, and the genu and splenium. However, no statistically significant difference was found between the truncus and splenium. When comparing the number of myelinated axons of the anterior, posterior and habenular commissures, statistically significant differences were found between the anterior and posterior commissures, and between the anterior and habenular commissures. No statistically significant difference was found between the posterior and habenular commissures. Small sized myelinated axons were present in all parts of the corpus callosum and in the anterior commissure. However, a heterogeneous distribution of myelinated axons was present in the posterior and habenular commissures.

Hyperbaric oxygen-induced changes in bacterial translocation and acinar ultrastructure in rat acute necrotizing pancreatitis

BackgroundWe aimed to investigate the effects of hyperbaric oxygen therapy on bacterial translocation and acinar cell ultrastructure in a rat model of acute necrotizing pancreatitis.MethodsForty-eight male Sprague-Dawley rats were randomly divided into three groups. Acute pancreatitis was induced in groups II and III. Groups I and II did not receive any treatment, and group III was treated with hyperbaric oxygen. All surviving animals were killed 48 h after the induction of pancreatitis. Bacterial translocation and histological and ultrastructural changes were determined.ResultsThe incidence of bacterial translocation in group III was significantly lower in comparison with group II (P < 0.001). Histopathological and ultrastructural injury scores were also significantly lower in group III (P < 0.001 and P < 0.04, respectively).ConclusionsHyperbaric oxygen therapy displayed beneficial effects on pancreatic superinfection and or histopathological and ultrastructural changes in experimental necrotizing pancreatitis.