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Pleiotropic effects of bombesin and neurotensin on intestinal mucosa: Not just trefoil peptides

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World Journal of Gastroenterology 2008年第22期14卷 3602-3603页

作者： Stelios F Assimakopoulos chrisoula d scopa Vassiliki N Nikolopoulou Constantine E Vagianos department of Internal Medicine School of Medicine University of Patras Patras 26110 Greece department of Pathology School of Medicine University of Patras Patras 26110 Greece division of Gastroenterology Department of Internal Medicine School of Medicine University of Patras Patras 26110 Greece First Surgical department "Saint Panteleimon" General Hospital of Nikaia Piraeus 18454 Greece

Bombesin and neurotensin are neuropeptides which exert a wide spectrum of biological actions on gastrointestinal tissues influencing intestinal growth and adaptation, intestinal motility, blood flow, secretion, nutrient absorption and immune response. Based mainly on their well-established potent enterotrophic effect, numerous experimental studies investigated their potential positive effect on the atrophic or injured intestinal mucosa. These peptides proved to be effective mucosa-healing factors, but the potential molecular and cellular mechanisms for this action remained unresolved. In a recently published study (World J Gastroenterol 2008; 14(8): 1222-1230), it was shown that their protective effect on the intestine in experimentally induced inflammatory bowel disease was related to anti-inflammatory, antioxidant and antiapoptotic actions. These results are in close agreement with our previous studies on jaundiced and hepatectomized rats that showed a regulatory effect of bombesin and neurotensin on critical cellular processes such as enterocyte' proliferation and death, oxidative stress and redox equilibrium, tight junctions' formation and function, and inflammatory response. The pleiotropic effects of bombesin and neurotensin on diverse types of intestinal injury may justify their consideration for clinical trials.

关键词： Bombesin Neurotensin Pleiotropic Neuropeptides Regulatory peptides

Effect of bombesin and neurotensin on gut barrier function in partially hepatectomized rats

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World Journal of Gastroenterology 2005年第43期11卷 6757-6764页

作者： Stelios F Assimakopoulos Ilias H Alexandris chrisoula d scopa Panagiotis G Mylonas Konstantinos C Thomopoulos Christos d Georgiou Vassiliki N Nikolopoulou Constantine E Vagianos department of Internal Medicine department of Surgery department of Pathology department of Internal edicine department of Biology

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 = 10）： controls, Ⅱ （n = 20）： sham operated, Ⅲ （n = 20）： partial hepatectomy 70% （PHx）, Ⅳ （n = 20）： PHx＋BBS （30 μg/kg/d）, Ⅴ （n = 20）： PHx＋NT （300 μg/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 pep

关键词： Hepatectomy Rats Bombesin Neurotensin Intestinal barrier Apoptosis Oxidative stress

Intestinal failure in obstructive jaundice

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World Journal of Gastroenterology 2005年第24期11卷 3806-3807页

作者： Stelios F.Assimakopoulos Constantine E.Vagianos Aristides Charonis Vassiliki N.Nikolopoulou chrisoula d.scopa department of Internal Medicine department of Surgery Laboratory of Cell Biology department of Pathology

TO THE EdITORWe read with great interest the article by ding LA and LiJS, which aimed to review the current knowledge on the physiology of normal intestinal barrier function and highlight the role of intestinal failure after various injurious insults in the development of septic complications or multiple organ failure with subsequent rapid clinical deterioration or even death.

关键词： Intestinal failure Obstructive jaundice

Experimental obstructive jaundice alters claudin-4 expression in intestinal mucosa: Effect of bombesin and neurotensin

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World Journal of Gastroenterology 2006年第21期12卷 3410-3415页

作者： Stelios F Assimakopoulos Constantine E Vagianos Aristides S Charonis Ilias H Alexandris Iris Spiliopoulou Konstantinos C Thomopoulos Vassiliki N Nikolopoulou chrisoula d scopa department of Internal Medicine School of Medicine University of PatrasPatrasGreece department of Surgery School of Medicine University of PatrasPatrasGreece Section of Histology Center for Basic Research Foundation of Biomedical Research of the Academy of AthensAthensGreece department of Microbiology School of Medicine University of PatrasPatrasGreece department of Internal Medicine division of Gastroenterology School of MedicineUniversity of PatrasPatrasGreece department of Pathology School of Medicine University of PatrasPatrasGreece

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 （30μg/kg per d）, V = BdL＋NT （300μg/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.

关键词： Obstructive jaundice Tight junctions Claudin-4 Intestinal permeability Intestinal barrier Regulatory peptides Bombesin Neurotensin

Stimulation of oval cell and hepatocyte proliferation by exogenous bombesin and neurotensin in partially hepatectomized rats

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World Journal of Gastrointestinal Pathophysiology 2011年第6期2卷 146-154页

作者： Stelios F Assimakopoulos Athanassios C Tsamandas Ilias H Alexandris Christos Georgiou Constantine E Vagianos chrisoula d scopa department of Internal Medicine University Hospital of PatrasPatras 26504Greece department of Pathology University Hospital of PatrasPatras 26504Greece department of Surgery General Hospital of AmfissaAmfissa 33100Greece department of Biology Section of GeneticsCell Biology and DevelopmentUniversity of PatrasPatras 26100Greece 1st department of Surgical "Saint Panteleimon"General Hospital of NikaiaPiraeus 18454Greece

AIM:To investigate the effect of the neuropeptides bombesin(BBS)and neurotensin(NT)on oval cell proliferation in partially hepatectomized rats not pretreated with a known hepatocyte ***:Seventy male Wistar rats were randomly divided into five groups:Ⅰ=controls,Ⅱ=sham operated,Ⅲ=partial hepatectomy 70%(PHx),Ⅳ=PHx+ BBS(30μg/kg per day),Ⅴ=PHx+NT(300μg/kg per day).Forty eight hours after liver resection,portal en-dotoxin levels and hepatic glutathione redox state were determined.α-fetoprotein(AFP)mRNA(in situ hybridisation),cytokeratin-19 and Ki67 antigen expression (immunohistochemistry)and apoptosis(TUNEL)were evaluated on liver tissue *** with morphological features of oval cells that were cytokeratin-19 (+)and AFP mRNA(+)were scored in morphometric analysis and their proliferation was *** addition,the proliferation and apoptotic rates of hepatocytes were ***:In the control and sham operated groups,oval cells were significantly less compared to groups Ⅲ,ⅣandⅤ(Pdes BBS and NT significantly increased the proliferation of oval cells compared to groupⅢ(Pddition,BBS and NT induced a significant increase of hepatocyte proliferation(Pdecreased their apoptotic activity(Pd to groupⅢ.BBS and NT significantly decreased portal endotoxemia (Pd increased the hepatic GSH:GSSG ratio (Pd Pd to groupⅢ.CONCLUSION:BBS and NT stimulated oval cell proliferation in a model of liver regeneration,without use of concomitant suppression of hepatocyte proliferation as oval cell activation stimuli,and improved the hepatocyte regenerative *** peptides-induced combined stimulation of oval cell and hepatocyte proliferation might serve as a possible treatment modality for several liver diseases.

关键词： Liver regeneration Partial hepatectomy Hepatic progenitor cells Oval cells Apoptosis Proliferation Oxidative stress

Ultrasonography in differentiation between chronic viral hepatitis and compensated early stage cirrhosis

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World Journal of Gastroenterology 2008年第13期14卷 2072-2079页

作者： Panagiotis Iliopoulos Marianna Vlychou chrisoula Karatza Spyros d Yarmenitis Maria Repanti Ioannis Tsamis Kostantinos Tepetes department of Radiology "Agios Andreas" General Hospital Patras Greece department of Radiology University of Thessaly Greece department of Hepatology-Gastroenterology University of Patras Greece department of Radiology University of Crete Greece department of Pathology "Agios Andreas" General Hospital Patras Greece department of Surgery University of Thessaly Greece

AIM: To assess the value of gray scale (GS) and colour doppler ultrasonography (CdU) in differentiating the progression of chronic viral hepatitis (CVH) and compensated liver cirrhosis (CIR). METHOdS: Seventy-two patients and 32 normal individuals who were used as controls were studied. Forty-four patients suffered from CVH and 28 from CIR. All patients were underwent to liver biopsy. Multiple qualitative and quantitative variables were studied in liver, portal vein (PV), hepatic artery (HA) and spleen with GS and CdU. On the basis of the obtained CdU data, several known indexes were calculated. In addition, alternative indices [PV diameter (d)/time average mean velocity (VTAM), HA/PV VTAM ratio] were calculated and studied. RESULTS: ROC analysis showed that PV congestion index, PV d/VTAM and HA/PV VTAM indices had the best sensitivity and specificity in discriminating CVH from CIR. Stepwise discriminant analysis showed that 88.9% of the originally grouped cases could be correctly classified by the three qualitative and four quantitative variables selected as statistically significant predictors. Among the CVH patients who underwent to biopsy, statistically significant changes were found in those at fibrosis stage 5 compared to fibrosis stages 1-4. CONCLUSION: Simple GS and CdU parameters discri-minate CVH from CIR. The alternative doppler indexes can accurately differentiate chronic virus hepatitis from cirrhosis. These indexes can be used in monitoring chronic virus hepatitis and avoiding unnecessary biopsies.

关键词： Liver cirrhosis Virus hepatitis Portal hypertension doppler ultrasonography