Unilateral leg edema in a cirrhotic patient with tense ascites.
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Ascites↗
Biomedical subjects
Stelios F Assimakopoulos
Publications and source records attributed to Stelios F Assimakopoulos.
Effect of N-acetylcysteine, allopurinol and vitamin E on jaundice-induced brain oxidative stress in rats.
We examined the possible protective effect of certain antioxidants (N-acetylcysteine, allopurinol and vitamin E) against the oxidative stress of brain tissue induced by experimental obstructive jaundice in rats. Thirty-six male Wistar rats were randomly divided into six groups; group I control, group II sham operated, group III bile duct ligated and groups IV, V, and VI in which the rats, after bile duct ligation, were given every day an intraperitoneal injection with N-acetylcysteine, allopurinol and Vit-E respectively. All rats were sacrificed on the tenth day by exsanguination and the oxidative state in samples from cortex, midbrain and cerebellum was assessed by measuring the thiol redox state and lipid peroxidation quantified by MDA measurements. The main finding was that all three antioxidants decrease lipid peroxidation in the three brain areas. Cysteine levels increased and protein thiol levels were reserved only in the group treated with N-acetylcysteine, whereas oxidized glutathione increased dramatically in the group treated with allopurinol, suggesting that each antioxidant agent had a certain influence profile on the different antioxidant defense systems. The observed effects of the antioxidants in this experimental model could also provide insight into some aspects of jaundice-induced hepatic encephalopathy in humans.
Acetylcysteine↗
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↗
A case of chondrosarcoma developing in a recurrent retroperitoneal mass after chemotherapy for testicular germ cell tumor.
Teratomas with malignant transformation occur in a small proportion of patients with metastatic germ cell tumors treated with platinum-based chemotherapy. Chondrosarcoma has rarely been reported as a component of the second non-germ cell malignancy. We report the case of a 37-year-old man who developed a chondrosarcoma in a recurrent retroperitoneal mass after chemotherapy for testicular germ cell tumor. Malignant transformation of the retroperitoneal teratomatous mass occurred in the absence of any symptoms or clinical signs, elevation in serum tumor markers, or the presence of atypical elements in previously resected specimens, suggesting the need for close radiographic follow-up of these patients.
Adult↗
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↗
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↗
Dose related effects of ifosfamide on enterocyte apoptosis in different sites of the rabbit intestine.
OBJECTIVE: We investigated the potential dose related apoptotic effect of subchronic administration of the alkylating chemotherapeutic agent ifosfamide in different sites of the small and large rabbit intestine. MATERIALS AND METHODS: Twenty New Zealand White rabbits received intravenously every week, for 10 weeks, 0 (group S, controls, n = 5), 30 (group A, n = 5), 45 (group B, n = 5) or 60 mg/kg ifosfamide (group C, n = 5). One day after the end of the treatment period, segments of jejunum, ileum, cecum, proximal and distal colon were excised. Intestinal mucosa apoptosis was detected by agarose gel electrophoresis and quantified by DNA fragmentation and standard terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick-end labelling (TUNEL) assays by which the percentage of fragmented DNA and the ratio of apoptotic cells per crypt (apoptotic index) were determined, respectively. RESULTS: At low dose (group A), ifosfamide had minor apoptotic effect on enterocytes, which was enhanced mainly in the small intestine when the dose was increased (group B); at the highest dose tested (group C), this effect was extended to the large intestine. In all groups of animals, the observed crypt cell apoptosis was maximal in the ileum, while minimal in the proximal colon. CONCLUSIONS: Our results show a dose and intestinal site-dependent induction of enterocyte apoptosis after subchronic ifosfamide administration in the rabbit.
Animals↗
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↗
Mesna ameliorates intestinal mucosa damage after ifosfamide administration in the rabbit at a dose-related manner.
BACKGROUND: Cancer chemotherapy may lead to mucositis, a serious dose-limiting side effect. The alkylating agent ifosfamide is used in the treatment of various forms of cancer in combination with the uroprotective thiol mesna (2-mercaptoethane-sulfonate). The aims of this study were to assess the dose response intestinal mucosa damage of ifosfamide and to investigate the potential protective effect of mesna on rabbit intestinal epithelium. MATERIALS AND METHODS: Fifty New Zealand White rabbits were randomly assigned to 10 groups of five animals each and received intravenously every week for 10 weeks either normal saline, ifosfamide, mesna, or ifosfamide plus mesna at three escalating dose levels (ifosfamide: 30, 45, or 60 mg/kg; mesna: 12, 18, or 24 mg/kg divided into two equal doses administered 4 h apart). Intestinal mucosa damage was assessed on the basis of crypt cell apoptosis and proliferation as well as intestinal morphometry. Apoptosis was detected by agarose gel electrophoresis and quantified by the DNA fragmentation assay and a standard terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) method by which the percentage of fragmented DNA and the apoptotic index were determined, respectively. The mitotic index and the crypt-villus (c/v) unit height were also measured in histological sections. RESULTS: Ifosfamide caused a dose-related increase of crypt cell apoptosis and shortening of c/v unit, while it had a steady antimitotic effect. Mesna as a sole agent had no apoptotic or trophic effect on intestinal mucosa and hence no effect on intestinal morphometry. However, mesna, when administered concurrently with ifosfamide, ameliorated apoptosis, hypoproliferation, and mucosal atrophy at a dose-related manner. CONCLUSIONS: Ifosfamide causes intestinal mucosa damage, which may be ameliorated in a dose-related manner by coadministration of mesna.
Animals↗