Unilateral leg edema in a cirrhotic patient with tense ascites.
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Ascites↗
Biomedical subjects
Constantine E Vagianos
Publications and source records attributed to Constantine E Vagianos.
Experimental obstructive jaundice alters claudin-4 expression in intestinal mucosa: effect of bombesin and neurotensin.
AIM: To investigate the influence of experimental obstructive jaundice and exogenous bombesin (BBS) and neurotensin (NT) administration on the expression of the tight junction (TJ)-protein claudin-4 in intestinal epithelium of rats. METHODS: Forty male Wistar rats were randomly divided into five groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL+BBS (30 microg/kg per d), V = BDL+NT (300 microg/kg per d). At the end of the experiment on d 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and immunohistochemically for evaluation of claudin-4 expression in intestinal epithelium. RESULTS: Obstructive jaundice led to intestinal barrier failure demonstrated by significant portal and aortic endotoxemia. Claudin-4 expression was significantly increased in the upper third of the villi in jaundiced rats and an upregulation of its lateral distribution was noted. Administration of BBS or NT restored claudin-4 expression to the control state and significantly reduced portal and aortic endotoxemia. CONCLUSION: Experimental obstructive jaundice increases claudin-4 expression in intestinal epithelium, which may be a key factor contributing to the disruption of the mucosal barrier. Gut regulatory peptides BBS and NT can prevent this alteration and reduce portal and systemic endotoxemia.
Animals↗
Effect of bombesin and neurotensin on gut barrier function in partially hepatectomized rats.
AIM: To investigate the effect of regulatory peptides bombesin (BBS) and neurotensin (NT) on intestinal barrier function in partially hepatectomized rats. METHODS: Ninety male Wistar rats were randomly divided into five groups: I (n=0): controls, II (n= 20): sham operated, III (n=20): partial hepatectomy 70% (PHx), IV (n=20): PHx+BBS (30 microg/kg/d), V (n=20): PHx+NT (300 microg/kg/d). Groups IV and V were treated for 8 days before PHx and 48 h post surgery. At the end of the experiment, on day 10, intestinal barrier function was assessed by measuring endotoxin concentrations in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content and microbiological analysis was performed in cecal contents. To estimate intestinal oxidative stress, lipid peroxidation was determined on tissue homogenates from terminal ileum. RESULTS: BBS or NT administration significantly reduced portal and systemic endotoxemia observed 48 h after partial hepatectomy. In hepatectomized rats (group III), a trend towards induction of mucosal atrophy was observed, demonstrated by the reduction of villus density, mucosal thickness, protein content and significant reduction of DNA, while these alterations were reversed by regulatory peptides administration. This trophic effect of BBS and NT was accompanied by induction of mitoses above control levels and a significant reduction of apoptosis in intestinal crypts. Intestinal lipid peroxidation was found significantly lower in PHx group and regulatory peptides exerted an antioxidant action, further decreasing this parameter of oxidative stress. The bacterial population of E. coli and aerobic Gram (+) cocci was increased in cecal content of hepatectomized rats, while this parameter was not affected by the administration of BBS or NT. CONCLUSION: Gut regulatory peptides BBS and NT improve intestinal barrier function and reduce endotoxemia in experimental partial hepatectomy. This effect is, at least in part, mediated by their trophic, anti-apoptotic, mitogenic, and antioxidant effect on the intestinal epithelium. This observation might be of potential value in patients undergoing liver resection.
Animals↗
Intestinal failure in obstructive jaundice.
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Animals↗
Beneficial effects of glutamine on intestinal barrier function in obstructive jaundice.
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Animals↗
Effect of oral glutamine administration on bacterial tanslocation, endotoxemia, liver and ileal morphology, and apoptosis in rats with obstructive jaundice.
Postoperative complications in patients with obstructive jaundice remain increased when associated with endotoxemia and the inflammatory response due to gut barrier failure. Administration of glutamine has been proposed to maintain the integrity of the gut mucosa and thus reduce bacterial translocation (BT), but the effects of this pretreatment on apoptosis and histologic morphology of various organs affected by BT in obstructive jaundice have not been studied. We therefore studied the effects of oral glutamine supplementation on endotoxemia, BT, liver and terminal ileal morphology, and apoptosis in an experimental model of obstructive jaundice. A total of 60 male Wistar rats were randomly divided into four groups of 15 each: I, controls; II, sham-operated; III, bile duct ligation (BDL); IV, BDL + glutamine (4.5 g/kg/day in drinking water). Ileal samples for histology, DNA and protein content, liver biopsies, mesenteric lymph nodes (MLNs) for culture, and portal and systemic blood samples for endotoxin measurements were obtained 10 days later. Compared to the controls, a significant increase in contaminated MLN and liver samples and increased endotoxemia were noted in group III (p < 0.01) but were significantly reduced in group IV (p < 0.05). Group IV also had a significantly higher number of mitoses per crypt (M/c) (p < 0.05), less apoptotic body counts (ABCs) (p < 0.05), and a higher DNA content than did group III (p < 0.05). Liver biopsies from group III displayed typical changes of large duct obstruction that significantly improved after glutamine treatment, with decreased ductular proliferation. We concluded that supplementation of oral glutamine in the presence of obstructive jaundice ameliorates BT, endotoxemia, and apoptosis and improves the ileal and liver histology.
Administration, Oral↗
Bombesin and neurotensin reduce endotoxemia, intestinal oxidative stress, and apoptosis in experimental obstructive jaundice.
OBJECTIVE: To evaluate the effect of bombesin (BBS) and neurotensin (NT) on intestinal histopathology, intestinal oxidative stress, and endotoxemia in experimental obstructive jaundice. SUMMARY BACKGROUND DATA: Obstructive jaundice compromises gut barrier function, resulting in endotoxemia. BBS and NT, exerting various biologic actions on gastrointestinal tissues, preserve gut mucosal integrity in cases of injury or atrophy. METHODS: Seventy male Wistar rats were randomly divided into 5 groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL + BBS (30 microg/kg/d), V = BDL + NT (300 microg/kg/d). By the end of the experiment, on day 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically, and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content. To estimate intestinal oxidant/antioxidant equilibrium, lipid peroxidation, protein oxidation, and thiol redox state (reduced glutathione [GSH], oxidized glutathione [GSSG], total nonprotein mixed disulfides [NPSSR], protein thiols [PSH], and protein disulfides [PSSP]) were determined on tissue homogenates from the terminal ileum. RESULTS: BBS or NT administration significantly reduced portal and systemic endotoxemia observed in obstructive jaundice. Both factors reversed obstructive jaundice-induced morphologic features of intestinal atrophy, increasing villus density and mucosal thickness. This effect was accompanied by induction of mitoses and reduction of apoptosis in intestinal crypts. Mucosal DNA and protein content were reduced, although not to significant levels, in BDL animals and restored to control levels after BBS or NT treatment. Moreover, BBS or NT administration protected the intestine in jaundiced rats against oxidative stress, as demonstrated by reduction of intestinal lipid peroxidation, increase of the antioxidant GSH, and decrease of the oxidized forms GSSG and NPSSR, while BBS additionally reduced protein oxidation as well. CONCLUSIONS: Administration of BBS or NT in bile duct-ligated rats exerts beneficial effects on intestinal oxidative stress, cell proliferation, apoptosis, and endotoxemia. This observation might be of potential value in patients with extrahepatic cholestasis.
Animals↗
Gut regulatory peptides bombesin and neurotensin reduce hepatic oxidative stress and histological alterations in bile duct ligated rats.
Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL + BBS (10 microg/kg, s.c. x3), BDL + NT (300 microg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.
Alanine Transaminase↗
Oxidative state in intestine and liver after partial hepatectomy in rats. Effect of bombesin and neurotensin.
OBJECTIVES: Extended liver resection is a situation with major implication of the gut-liver axis. In the present study, we aimed to investigate intestinal and liver oxidative stress after partial hepatectomy and explore the influence of exogenous administration of gut regulatory peptides bombesin (BBS) and neurotensin (NT). DESIGN AND METHODS: Ninety male Wistar rats were randomly divided into five groups: control, sham operated, partially hepatectomized (70%), and partially hepatectomized treated with either BBS or NT. Forty-eight hours after surgery, lipid peroxidation, protein oxidation, reduced and oxidized glutathione were measured on intestinal and liver homogenates. Endotoxin levels were determined in portal and aortic blood. RESULTS: In hepatectomized rats, all parameters of oxidative stress in remnant liver were decreased. In the intestine, oxidative protein damage was increased, while lipid peroxidation and glutathione oxidation were reduced. BBS and NT reduced protein and glutathione oxidation in both tissues and prevented lipid peroxidation in the intestine. Furthermore, portal and aortic endotoxemia were decreased in peptides-treated rats. CONCLUSIONS: After partial hepatectomy, liver regeneration takes place under low oxidative stress, while increased oxidative damage to proteins occurs in the intestine. Gut regulatory peptides BBS and NT exert an antioxidant effect in both organs and prevent endotoxemia.
Animals↗
Experimental obstructive jaundice disrupts intestinal mucosal barrier by altering occludin expression: beneficial effect of bombesin and neurotensin.
BACKGROUND: Little is known of the molecular events leading to increased intestinal permeability in obstructive jaundice. This study was undertaken to investigate the influence of experimental obstructive jaundice on the expression of the tight junction-associated protein occludin in the intestinal epithelium. STUDY DESIGN: Seventy male Wistar rats were randomly divided into five groups: I, controls; II, sham-operated; III, bile duct ligation (BDL); IV, BDL+Bombesin (BBS) (30 microg/kg/d); and V, BDL+Neurotensin (NT) (300 microg/kg/d). At the end of the experiment, on day 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and immunohistochemically for evaluation of occludin expression in the intestinal epithelium. Lipid peroxidation and protein oxidation were determined on tissue homogenates from terminal ileum and microbiologic analysis was performed in cecal contents. RESULTS: Obstructive jaundice resulted in portal and aortic endotoxemia, which was significantly reduced after BBS or NT administration. In the BDL group, there was total loss of occludin expression in numerous enterocytes mainly at the upper third of the villi, while a gradient of positivity existed from crypt to tip. Occludin expression was restored to control state after treatment with BBS or NT. In addition, both peptides reduced intestinal lipid peroxidation, while BBS reduced protein oxidation as well. CONCLUSIONS: Experimental obstructive jaundice induces regional loss of occludin expression in the intestinal epithelium, which may be a key factor contributing to the disruption of the mucosal barrier. Gut regulatory peptides BBS and NT prevent this alteration, leading to lower portal and systemic endotoxemia.
Animals↗
Bacterial translocation, endotoxaemia and apoptosis following Pringle manoeuvre in rats.
BACKGROUND: Intraoperative occlusion of the hepatoduodenal ligament (Pringle manoeuvre (Pm)) is often employed for the reduction of blood loss during liver surgery. No data exist to date on the effects of Pm on mucosal barrier dysfunction, systemic bacterial translocation (BT), endotoxaemia and apoptosis. MATERIALS AND METHODS: Sixty-five male Wistar rats in three groups: I (n=25) controls, II (n=20) sham operation, III (n=20) occlusion of the hepatoduodenal ligament (Pm). Tissue samples from mesenteric lymph nodes (MLNs), liver, lungs and spleen were analysed after 30 min and at 24 h. Endotoxin was measured in portal and aortic blood and routine haematological and biochemical parameters were measured before and after Pm. RESULTS: No differences were found in the blood parameters before and after Pm, but a significant increase in contaminated MLNs and liver was noted. All cultured bacteria were enteric in origin. Portal and aortic endotoxin were significantly increased. Overall the ileal architecture remained intact in all specimens studied and no significant pathology was observed. The ABC increased after Pm significantly (P<0.01). CONCLUSION: Normothermic Pm of 30 min duration results in immediate and delayed gut barrier failure by significantly increasing BT and endotoxaemia which might be attributed to portal stasis leading to intestinal congestion as well as temporary liver ischaemia. Apoptosis increased significantly 30 min after performing the Pm.
Animals↗
Changes in aetiology and clinical outcome of acute upper gastrointestinal bleeding during the last 15 years.
OBJECTIVES: The diagnostic and therapeutic approaches to patients with acute upper gastrointestinal bleeding have been improved during the last decades. The aim of this study was to compare the aetiology and clinical outcome of acute upper gastrointestinal bleeding (AUGIB) between two distinct periods during the last 15 years. METHODS: The causes of AUGIB and clinical outcome of 668 patients hospitalised with the problem in 1986-1987 were compared to 636 patients with AUGIB in 2000-2001. Patients were admitted to our hospital or they bled while they were inpatients for other reasons. No patient was excluded because of age or concurrent diseases. Endoscopic haemostasis with adrenaline injection for bleeding peptic ulcers was performed in the second period while no endoscopic method of haemostasis was performed in the first period. RESULTS: We observed an increase in the age of patients (56.5 +/- 16.9 vs 62.9 +/- 17.5 years, P < 0.0001) and the percentage of patients who received non-steroidal anti-inflammatory drugs (NSAIDs) before bleeding (from 44% to 63.5%, P < 0.0001). An increase in the diagnosis rate of gastric ulcer (12% vs 19.2%, P = 0.005) and varices (13.2% vs 3.3%, P < 0.001) with a simultaneous decrease in that of erosive gastroduodenitis (18.4% vs 7.2%, P < 0.0001) and duodenal ulcer (48.7% vs 33.3%, P < 0.0001) as a cause of bleeding was also observed. In peptic ulcer bleeding, emergency surgical haemostasis was reduced from 14% to 5.3%, P < 0.001. Overall mortality was also reduced from 5.2% to 3.1% and in peptic ulcer bleeding patients from 3.3% to 2.4%, respectively, but the differences are not statistically significant. CONCLUSION: The aetiology of AUGIB has changed during the last 15 years probably due to the better therapeutic approach to chronic duodenal ulcers and increasing use of NSAIDs in the elderly. Emergency surgical haemostasis has been reduced but the reduction of mortality was not significant.
Acute Disease↗