Indoleamine-2,3-dioxygenase-related anti-inflammatory effects of 3-aminobenzamide and infliximab in experimental colitis.

OBJECTIVE: This study aimed to investigate the presence of indoleamine-2,3-dioxygenase and bacterial translocation after the administration of 3-aminobenzamide and infliximab in the TNBS model of rat colitis. METHODS: The study group was divided into five categories as follows: group 1: (control), group 2: colitis+saline, group 3: colitis+3-aminobenzamide, group 4: colitis+infliximab, and group 5: colitis+3-aminobenzamide+infliximab. Intestinal mesenteric cultures were incubated on specific agar media plates under aerobic and anaerobic conditions, bacterial translocation was evaluated and assessed as colony-forming units per gram of tissue. Colonic tissue samples were evaluated by Western blotting method to detect the presence of indoleamine-2,3-dioxygenase. RESULTS: The results obtained were as follows: group 1: normal gut flora; group 2: eight of nine samples had bacterial translocation, of which six of them had positive indoleamine-2,3-dioxygenase protein; group 3: five of nine samples had bacterial translocation, of which seven of them had positive indoleamine-2,3-dioxygenase; group 4: three of nine samples had bacterial translocation, of which seven of them had positive indoleamine-2,3-dioxygenase; and group 5: only one sample had exact indoleamine-2,3-dioxygenase protein. CONCLUSION: Altered expression of indoleamine-2,3-dioxygenase results in a lower bacterial translocation via infliximab compared with 3-aminobenzamide treatment. Combined treatments emphasized different approaches for the new molecules related to indoleamine-2,3-dioxygenase.

Indoleamine-2,3-dioxygenase-related anti-inflammatory effects of 3-aminobenzamide and infliximab in experimental colitis

SUMMARY OBJECTIVE: This study aimed to investigate the presence of indoleamine-2,3-dioxygenase and bacterial translocation after the administration of 3-aminobenzamide and infliximab in the TNBS model of rat colitis. METHODS: The study group was divided into five categories as follows: group 1: (control), group 2: colitis+saline, group 3: colitis+3-aminobenzamide, group 4: colitis+infliximab, and group 5: colitis+3-aminobenzamide+infliximab. Intestinal mesenteric cultures were incubated on specific agar media plates under aerobic and anaerobic conditions, bacterial translocation was evaluated and assessed as colony-forming units per gram of tissue. Colonic tissue samples were evaluated by Western blotting method to detect the presence of indoleamine-2,3-dioxygenase. RESULTS: The results obtained were as follows: group 1: normal gut flora; group 2: eight of nine samples had bacterial translocation, of which six of them had positive indoleamine-2,3-dioxygenase protein; group 3: five of nine samples had bacterial translocation, of which seven of them had positive indoleamine-2,3-dioxygenase; group 4: three of nine samples had bacterial translocation, of which seven of them had positive indoleamine-2,3-dioxygenase; and group 5: only one sample had exact indoleamine-2,3-dioxygenase protein. CONCLUSION: Altered expression of indoleamine-2,3-dioxygenase results in a lower bacterial translocation via infliximab compared with 3-aminobenzamide treatment. Combined treatments emphasized different approaches for the new molecules related to indoleamine-2,3-dioxygenase.

Elevated serum S100B levels in medication naïve children and adolescents with obsessive-compulsive disorder.

PURPOSE: Obsessive-compulsive disorder (OCD) is a condition characterized by obsessions and/or compulsions. S100B protein is shown to be involved in microglial activation besides intracellular signaling, intercellular communication and cell growth. The relation between S100B protein and various psychiatric disorders except OCD has been studied so far. This study aimed to analyze serum S100B levels for the first time in medication naive OCD diagnosed children and adolescents and to compare them with the control group. MATERIALS AND METHODS: Peripheral blood S100B levels of 27 children and adolescents with OCD were compared to 27 control group subjects to assess any possible association between OCD and S100B levels. All the children and adolescents completed the child version of the Obsessive-Compulsive Inventory (OCI - CV). RESULTS: Compared to control group, higher serum S100B levels were found in OCD group (z = -2.258, p = 0.024). We also found that obsessing and washing subscales' scores and total score of OCI - CV were statistically significantly correlated with S100B levels (respectively, r = .292, p = 0.032; r = .306, p = 0.025; r = .296, p = 0.030). CONCLUSIONS: The present study's findings are in accord with previous studies demonstrating the significance of S100B protein in other psychiatric disorders and suggesting a relation in children and adolescents with OCD for the first time. The role of S100B protein in OCD etiology and pathogenesis should be evaluated further.

Altered microRNA 5692b and microRNA let-7d expression levels in children and adolescents with attention deficit hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Its etiology is not clearly understood yet, but neurobiological, genetic and environmental factors are shown to play a role. The relationship between ADHD and miRNAs has been studied quite recently, and few studies have been conducted up to now. In this study, peripheral blood expression levels of miR-5692b, miR-let-7d, miR-124-3p, miR-4447 and miR-107 of 30 children and adolescents with combined type ADHD were compared to 30 healthy controls to understand the roles of these miRNAs in the ADHD etiopathogenesis. Compared to controls, levels of miR-5692b (p = 0.006) were found higher and levels of miR-let-7d (p = 0.017) were found lower in the ADHD group. There was no significant difference in terms of miR-124-3p, miR-4447, and miR-107 levels between the groups. In conclusion, our findings support other studies suggesting the importance of miRNAs in the pathogenesis of ADHD. Regarding the regulatory role of miRNAs in gene regulation, their contribution to etiopathogenesis and heterogeneity of ADHD should be investigated further.

Effect of 3-aminobenzamide on perforation an experimental colitis model.

BACKGROUND/AIMS: The anti-inflammatory activity of 3-aminobenzamide (3-AB) has been shown via histopathology and immunohistochemistry in various colitis models. We aimed to study the effects of 3-AB on tissue mechanical endurance and, associatively, preventing perforation in colitis. MATERIALS AND METHODS: Thirty male Wistar albino rats were randomly divided into three groups. Rectal saline was administered to Group 1 (sham+saline). Rectal trinitrobenzensulphonic acid was applied to induce colitis in Group 2 (colitis+saline) and Group 3 (colitis+3-AB). Groups 1 and 2 were treated intraperitoneally with saline (1 ml every 12 hours) and Group 3 was treated with 3-AB (10 mg/kg every 12 hours). After seven days, rats were sacrificed and colon lipid peroxidation levels, the serum tumor necrosis factor alpha (TNF-α) level, bowel bursting pressures, and bowel wall tensions were measured. RESULTS: Bowel bursting pressure in Group 2 was significantly lower than in Groups 1 and 3 (p<0.001 for both groups). Bowel wall tension in Group 2 was significantly lower than in Groups 1 and 3 (p<0.001 for both groups). There were no significant differences between groups for serum TNF-α levels. For lipid peroxidation, malondialdehyde (MDA) levels were increased in Groups 2 and 3 compared to Group 1. CONCLUSION: 3-AB may aid prevention of perforations that develop in inflammatory bowel disease, requiring surgical treatment.

Invagination of the appendix due to endometriosis presenting as acute appendicitis.

Appendicitis and endometriosis are commonly encountered surgical problems. Endometrial involvement of the appendix is rare and very few cases have been reported in the literature. True diagnosis of appendix invagination is highly difficult due to variable symptoms. Noting the findings which are in favour of invagination in patients diagnosed with acute appendicitis is of great significance in order to be prepared for changing surgical attempts. This case describes a 34 year old female patient diagnosed with infertility who was operated on for acute appendicitis. In the pathological assessment, endometrial involvement of the appendix was seen. The classification, symptoms, radiological appearance and treatment of appendix invagination described in the literature are discussed.

Effects of infliximab on bacterial translocation in experimental acute necrotizing pancreatitis.

BACKGROUND & OBJECTIVES: Translocation of bacteria from the gut is an important factor in the development of septic complications and mortality in acute pancreatitis (AP). The present study was designed to assess the effects of infliximab treatment on bacterial translocation (BT) in experimental acute necrotizing pancreatitis. METHODS: Male Sprague-Dawley rats (n=45) were allocated into three groups. AP was induced in group II (positive control, n=15) and group III (Infliximab; n=15) by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (Sham; n=15) received normal saline infusion into the common biliopancreatic duct as placebo. Groups I and II were treated by normal saline and group III was treated with infliximab intraperitoneally on 6, 30 and 54 h after induction of pancreatitis. All surviving animals were killed 60 h after the induction of pancreatitis, and specimens were collected for amylase measurement as well as histopathologic and microbiologic examinations. RESULTS: Oedema, acinar cell necrosis, inflammatory infiltration, haemorrhage, fat necrosis and perivascular inflammation in group III rats were decreased with infliximab treatment when compared with group II (P<0.001). BT to mesentery lymph node in groups I, II and III were 20, 100 and 46 per cent, respectively. BT to peritoneum and pancreas in group III was lower than group II (P<0.05). INTERPRETATION & CONCLUSIONS: Infliximab administration resulted in beneficial effects on BT and histopathologic changes in the experimental necrotizing pancreatitis. Whether anti-TNF therapy has a role in prevention of complications of ANP needs to be established.

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.

Tracheal diverticulum: a rare cause of dysphagia.

Tracheal diverticulum is a rarely encountered entity which is frequently an incidental finding in the postmortem examination, reported in 1% of patients in an autopsy series. Most cases are asymptomatic, but when symptoms are present they usually have airway symptoms with cough or recurrent respiratory infection. We herein report a case of a tracheal diverticulum, which had cervical dysphagia and sensation of friction.

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.

The role of allopurinol in experimental acute necrotizing pancreatitis.

BACKGROUND & OBJECTIVES: Acute pancreatitis (AP) in its severe form can lead to severe complications and death. Translocation of bacteria from the gut is one of the most important factors in the development of septic complications and mortality in acute pancreatitis. Oxygen-derived free radicals have been suggested to play a major role in the pathogenesis of AP. Xanthine oxidase enzyme is an important source of reactive oxygen metabolites. We undertook this study to evaluate the effect of allopurinol on bacterial translocation, oxidative stress and the course of AP in a rat model. METHODS: Male Sprague-Dawley rats (n=48) were randomly allocated into three equal groups. Acute pancreatitis (AP) was induced in group II (AP+Saline), and group III (AP+allopurinol) by retrograde infusion of taurocholate into the common biliopancreatic duct. Group I rats (Sham) received normal saline infusion into the common biliopancreatic duct for mimicking pressure effect. Group III rats were treated with allopurinol intraperitoneally for 48 h after induction of pancreatitis. Blood samples were drawn from all animals for biochemical analyses and pancreatic tissues were examined for bacterial translocation. RESULTS: Acute pancreatitis was developed in all groups, but not in group I (Sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Pathologic score of the pancreatitis in the allopurinol group (14.0 +/- 0.5) was lower when compared with group II (19.2 +/- 0.6) (P<0.001). Bacterial translocation to pancreas in group treated with allopurinol was significantly lower when compared with control group (p<0.02). Plasma glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels were higher and malondialdehyde (MDA) levels were lower in allopurinol group when compared with those in control groups. INTERPRETATION & CONCLUSION: Our findings suggested that addition of allopurinol to the treatment protocol in the acute pancreatitis might improve the pathologic score, bacterial translocation and oxidative stress parameters. However, more studies need to be done to confirm these findings.

The effect of activated protein C on experimental acute necrotizing pancreatitis.

INTRODUCTION: Acute 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 METHOD: Forty-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-alpha, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured. RESULTS: Acute 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-alpha, and IL-6 levels were also significantly decreased in comparison with positive controls (P < 0.001, P < 0.04 and P < 0.001, respectively). CONCLUSION: APC improved the severity of pancreatic tissue histology, superinfection rates and serum markers of inflammation during the course of acute necrotizing pancreatitis.