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 intestin...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.展开更多
AIM:To investigate the effects of bombesin (BBS) and neurotensin (NTS) on apoptosis and colitis in an ulcerative colitis model. METHODS:In this study, a total of 50 rats were divided equally into 5 groups. In the cont...AIM:To investigate the effects of bombesin (BBS) and neurotensin (NTS) on apoptosis and colitis in an ulcerative colitis model. METHODS:In this study, a total of 50 rats were divided equally into 5 groups. In the control group, no colitis induction or drug administration was performed. Colitis was induced in all other groups. Following the induction of colitis, BBS, NTS or both were applied to three groups of rats. The remaining group (colitis group) received no treatment. On the 11th d after induction of colitis and drug treatment, blood samples were collected for TNF-α and IL-6 level studies. Malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO) and caspase-3 activities, as well as histopathological findings, evaluated in colonic tissues. RESULTS:According to the macroscopic and microscopic findings, the study groups treated with BBS, NTS and BBS + NTS showed significantly lower damage and inflammation compared with the colitis group (macroscopic score, 2.1 ± 0.87, 3.7 ± 0.94 and 2.1 ± 0.87 vs 7.3 ± 0.94;microscopic score, 2.0 ± 0.66, 3.3 ± 0.82 and 1.8 ± 0.63 vs 5.2 ± 0.78, P < 0.01). TNF-α and IL-6 levels were increased significantly in all groups compared with the control group. These increases were significantly smaller in the BBS, NTS and BBS + NTS groups compared with the colitis group (TNF-α levels, 169.69 ± 53.56, 245.86 ± 64.85 and 175.54 ± 42.19 vs 556.44 ± 49.82;IL-6 levels, 443.30 ± 53.99, 612.80 ± 70.39 and 396.80 ± 78.43 vs 1505.90 ± 222.23, P < 0.05). The colonic MPO and MDA levels were significantly lower in control, BBS, NTS and BBS + NTS groups than in the colitis group (MPO levels, 24.36 ± 8.10, 40.51 ± 8.67 and 25.83 ± 6.43 vs 161.47 ± 38.24;MDA levels, 4.70 ± 1.41, 6.55 ± 1.12 and 4.51 ± 0.54 vs 15.60 ± 1.88, P < 0.05). Carbonyl content and caspase-3 levels were higher in the colitis and NTS groups than in control, BBS and BBS + NTS groups (carbonyl levels, 553.99 ± 59.58 and 336.26 ± 35.72 vs 209.76 ± 30.92, 219.76 ± 25.77 and 220.34 ± 36.95;caspase-3 levels, 451.70 ± 68.27 and 216.20 ± 28.17 vs 28.60 ± 6.46, 170.50 ± 32.37 and 166.50 ± 30.95, P < 0.05). CONCLUSION:The results of this study suggest BBS and NTS, through their anti-inflammatory actions, support the maintenance of colonic integrity and merit consideration as potential agents for ameliorating colonic inflammation.展开更多
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 i...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 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, antiapoptotic, mitogenic, and antioxidant effect on the intestinal epithelium. This observation might be of potential value in patients undergoing liver resection.展开更多
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, nutrie...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.展开更多
AIM： To investigate the mechanism of bombesin-induced circular smooth muscle cell contraction in cat esophagus. METHODS： Specific G protein or phospholipase C involved in cat esophagus contraction was identified, mu...AIM： To investigate the mechanism of bombesin-induced circular smooth muscle cell contraction in cat esophagus. METHODS： Specific G protein or phospholipase C involved in cat esophagus contraction was identified, muscle cells were permeabilized with saponin. After per- meabilization of muscle cells, the Gi3 antibody inhibited bombesin-induced smooth muscle cell contraction. RESULTS： Incubation of permeabilized circular muscle cells with PLC-β3 antibody could inhibit bombesin-induced contraction. H-7, chelerythrine （PKC inhibitor） and genistein （protein tyrosine kinase inhibitor） inhibited bombesin-induced contraction, but DAG kinase inhibitor, R59949, could not inhibit it. To examine which mitogen-activated protein kinase （MAPK） was involved in bombesin-induced contTaction, the specific MAPK inhibitors （MEK inhibitor, PD98059 and p38 MAPK inhibitor, SB202190） were used. Preincubation of PD98059 blocked the contraction induced by bombesin in a concentration-dependent manner. However, SB202190 had no effects on contraction. CONCLUSION： Bombesin-induced circular muscle cell contraction in cat esophagus is mediated via a PKC or a PTK-dependent pathway or p44/p42 HAPK pathway.展开更多
This Bombesin (BBN), a tetradecapeptide analog of human gastrin-releasing peptide (GRP) with a high binding affinity for GRP receptors (GRPR), is over- expressed in early stages of androgen-dependent prostate carcinom...This Bombesin (BBN), a tetradecapeptide analog of human gastrin-releasing peptide (GRP) with a high binding affinity for GRP receptors (GRPR), is over- expressed in early stages of androgen-dependent prostate carcinomas, but not in advanced stages. Therefore, there is a need to develop effective tracers for the accurate and specific detection of this disease. The objective of this study was to evaluate Lys<sup>1</sup>, Lys<sup>3</sup>-DOTA-BBN (1,14) analog with the radiolabeled positron emitter [<sup>68</sup>Ga]-Ga-BBN for receptor imaging with PET, and to determine its biodistribution and radiation dosimetry using whole-body (WB) PET scans in healthy volunteers. The highest uptake was in the pancreas, followed by urinary bladder. The critical organ was pancreas with a mean absorbed dose of 206 ± 0.7, 210 ± 0.7, 120 ± 0.9, 390.23 ± 0.6 μGy/MBq and the effective doses were estimated as 73.2 ± 0.6, 49.8 ± 0.3 μGy/MBq (women and men, respectively).展开更多
文摘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.
基金Grant (SBAG-105S338) from the Scientific and Technical Research Council of Turkey (TUBITAK)
文摘AIM:To investigate the effects of bombesin (BBS) and neurotensin (NTS) on apoptosis and colitis in an ulcerative colitis model. METHODS:In this study, a total of 50 rats were divided equally into 5 groups. In the control group, no colitis induction or drug administration was performed. Colitis was induced in all other groups. Following the induction of colitis, BBS, NTS or both were applied to three groups of rats. The remaining group (colitis group) received no treatment. On the 11th d after induction of colitis and drug treatment, blood samples were collected for TNF-α and IL-6 level studies. Malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO) and caspase-3 activities, as well as histopathological findings, evaluated in colonic tissues. RESULTS:According to the macroscopic and microscopic findings, the study groups treated with BBS, NTS and BBS + NTS showed significantly lower damage and inflammation compared with the colitis group (macroscopic score, 2.1 ± 0.87, 3.7 ± 0.94 and 2.1 ± 0.87 vs 7.3 ± 0.94;microscopic score, 2.0 ± 0.66, 3.3 ± 0.82 and 1.8 ± 0.63 vs 5.2 ± 0.78, P < 0.01). TNF-α and IL-6 levels were increased significantly in all groups compared with the control group. These increases were significantly smaller in the BBS, NTS and BBS + NTS groups compared with the colitis group (TNF-α levels, 169.69 ± 53.56, 245.86 ± 64.85 and 175.54 ± 42.19 vs 556.44 ± 49.82;IL-6 levels, 443.30 ± 53.99, 612.80 ± 70.39 and 396.80 ± 78.43 vs 1505.90 ± 222.23, P < 0.05). The colonic MPO and MDA levels were significantly lower in control, BBS, NTS and BBS + NTS groups than in the colitis group (MPO levels, 24.36 ± 8.10, 40.51 ± 8.67 and 25.83 ± 6.43 vs 161.47 ± 38.24;MDA levels, 4.70 ± 1.41, 6.55 ± 1.12 and 4.51 ± 0.54 vs 15.60 ± 1.88, P < 0.05). Carbonyl content and caspase-3 levels were higher in the colitis and NTS groups than in control, BBS and BBS + NTS groups (carbonyl levels, 553.99 ± 59.58 and 336.26 ± 35.72 vs 209.76 ± 30.92, 219.76 ± 25.77 and 220.34 ± 36.95;caspase-3 levels, 451.70 ± 68.27 and 216.20 ± 28.17 vs 28.60 ± 6.46, 170.50 ± 32.37 and 166.50 ± 30.95, P < 0.05). CONCLUSION:The results of this study suggest BBS and NTS, through their anti-inflammatory actions, support the maintenance of colonic integrity and merit consideration as potential agents for ameliorating colonic inflammation.
文摘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 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, antiapoptotic, mitogenic, and antioxidant effect on the intestinal epithelium. This observation might be of potential value in patients undergoing liver resection.
文摘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.
文摘AIM： To investigate the mechanism of bombesin-induced circular smooth muscle cell contraction in cat esophagus. METHODS： Specific G protein or phospholipase C involved in cat esophagus contraction was identified, muscle cells were permeabilized with saponin. After per- meabilization of muscle cells, the Gi3 antibody inhibited bombesin-induced smooth muscle cell contraction. RESULTS： Incubation of permeabilized circular muscle cells with PLC-β3 antibody could inhibit bombesin-induced contraction. H-7, chelerythrine （PKC inhibitor） and genistein （protein tyrosine kinase inhibitor） inhibited bombesin-induced contraction, but DAG kinase inhibitor, R59949, could not inhibit it. To examine which mitogen-activated protein kinase （MAPK） was involved in bombesin-induced contTaction, the specific MAPK inhibitors （MEK inhibitor, PD98059 and p38 MAPK inhibitor, SB202190） were used. Preincubation of PD98059 blocked the contraction induced by bombesin in a concentration-dependent manner. However, SB202190 had no effects on contraction. CONCLUSION： Bombesin-induced circular muscle cell contraction in cat esophagus is mediated via a PKC or a PTK-dependent pathway or p44/p42 HAPK pathway.
文摘This Bombesin (BBN), a tetradecapeptide analog of human gastrin-releasing peptide (GRP) with a high binding affinity for GRP receptors (GRPR), is over- expressed in early stages of androgen-dependent prostate carcinomas, but not in advanced stages. Therefore, there is a need to develop effective tracers for the accurate and specific detection of this disease. The objective of this study was to evaluate Lys<sup>1</sup>, Lys<sup>3</sup>-DOTA-BBN (1,14) analog with the radiolabeled positron emitter [<sup>68</sup>Ga]-Ga-BBN for receptor imaging with PET, and to determine its biodistribution and radiation dosimetry using whole-body (WB) PET scans in healthy volunteers. The highest uptake was in the pancreas, followed by urinary bladder. The critical organ was pancreas with a mean absorbed dose of 206 ± 0.7, 210 ± 0.7, 120 ± 0.9, 390.23 ± 0.6 μGy/MBq and the effective doses were estimated as 73.2 ± 0.6, 49.8 ± 0.3 μGy/MBq (women and men, respectively).
