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| 1 | Pathophysiology of increased intestinal permeability in obstructive jaundice显示文摘Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome. | Stelios F Assimakopoulos Chrisoula D Scopa Constantine E Vagianos | 2007 | World Journal of Gastroenterology2007，13，48： | 48 |
| 2 | Experimental obstructive jaundice alters claudin-4 expression in intestinal mucosa: Effect of bombesin and neurotensin显示文摘瞄准:调查试验性的妨碍的黄疸和外长的 bombesin 和 neurotensin (NT )(BBS ) 的影响紧密的连接(TJ ) 的表示上的管理在老鼠的肠上皮的蛋白质 claudin-4。方法:四十只男 Wistar 老鼠随机被划分成五个组:我 = 控制, II = 假冒操作, III = 胆汁管结扎(BDL ) , IV = BDL+BBS (30 microg/kg 每 d ) , V = BDL+NT (300 microg/kg 每 d ) 。在 d 的实验的结束 10,内毒素在门和大动脉的血被测量。终端回肠的织物节组织学地被检验并且免疫组织化学地为在肠上皮的 claudin-4 表示的评估。结果:妨碍的黄疸导致了重要的门和大动脉的 endotoxemia 表明的肠的障碍失败。Claudin-4 表示显著地被增加在上面在 jaundiced 老鼠的第三根绒毛并且一起来它的侧面的分发的规定被注意。BBS 或 NT 的管理恢复了 claudin-4 表示到控制状态并且显著地减少了门和大动脉的 endotoxemia。结论:在肠上皮的试验性的妨碍的黄疸增加 claudin-4 表示,它可以是贡献粘膜障碍的混乱的一个关键因素。毁坏规章的肽 BBS, NT 能阻止这扇改变和还原剂门和全身的 endotoxemia。 | Stelios F Assimakopoulos Constantine E Vagianos Aristides S Charonis Ilias H Alexandris Iris Spiliopoulou Konstantinos C Thomopoulos Vassiliki N Nikolopoulou Chrisoula D Scopa | 2006 | World Journal of Gastroenterology2006，12，21： | 21 |
| 3 | Effect of bombesin and neurotensin on gut barrier function in partially hepatectomized rats显示文摘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. | Stelios F Assimakopoulos Ilias H Alexandris Chrisoula D Scopa Panagiotis G Mylonas Konstantinos C Thomopoulos Christos D Georgiou Vassiliki N Nikolopoulou Constantine E Vagianos | 2005 | World Journal of Gastroenterology2005，11，43： | 8 |
| 4 | Transradial versus transfemoral access for anterior circulation mechanical thrombectomy: analysis of 375 consecutive cases显示文摘Objective To compare transradial artery access(TRA)to the gold standard of transfemoral artery access(TFA)in mechanical thrombectomy(MT)for stroke caused by anterior circulation large vessel occlusion.Methods The clinical outcomes,procedural speed,angiographic efficacy and safety of both techniques were analysed in 375 consecutive cases over an 18-month period in a high volume statewide neurointerventional service.Results There was no significant difference in patient characteristics,stroke parameters,imaging techniques or intracranial techniques.The median time elapsed between CT scanning and reperfusion was 96.5 min(IQR 68-123)in the TFA group and 95 min(IQR 68-123)in the TRA group(p=0.456).Of 336 patients who were independent at presentation 58%(124/214)of the TFA group and 67%(82/122)of the TRA group had a modified Rankin score of 0-2 at 90-day follow-up(p=0.093).Cross-over from radial to femoral was 4.6%(4/130)compared with 1.6%cross-over from femoral to radial(4/245),but did not meet the predetermined level of statistical significance(OR2.92,95% CI 0.81 to 10.52,p=0.088) and did not impact median procedural speed.Adequate angiographic reperfusion,first pass reperfusion,embolisation to new territory and symptomatic intracranial haemorrhage were similar in both groups.There was a significant difference in major access site complications requiring an additional procedure.None of the TRA cases had a major access site complication but 6.5%(16/245)of the TFA cases did(p=0.003).Conclusion This study suggests that using TRA for anterior circulation MT is fast,efficacious,safe and not inferior to the gold standard of TFA. | Timothy John Phillips Matthew Thomas Crockett Gregory D Selkirk Ruchi Kabra Albert Ho Yuen Chiu Tejinder Singh Constantine Phatouros William McAuliffe | 2021 | Stroke & Vascular Neurology2021，6，2： | 7 |
| 5 | Pleiotropic effects of bombesin and neurotensin on intestinal mucosa: Not just trefoil peptides显示文摘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. | Stelios F Assimakopoulos Chrisoula D Scopa Vassiliki N Nikolopoulou Constantine E Vagianos | 2008 | World Journal of Gastroenterology2008，14，22： | 4 |
| 6 | Stimulation of oval cell and hepatocyte proliferation by exogenous bombesin and neurotensin in partially hepatectomized rats显示文摘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 inhibitor.METHODS: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 samples.Cells with morphological features of oval cells that were cytokeratin-19 (+)and AFP mRNA(+)were scored in morphometric analysis and their proliferation was recorded.In addition,the proliferation and apoptotic rates of hepatocytes were determined.RESULTS:In the control and sham operated groups,oval cells were significantly less compared to groups Ⅲ,ⅣandⅤ(P<0.001).The neuropeptides BBS and NT significantly increased the proliferation of oval cells compared to groupⅢ(P<0.001).In addition,BBS and NT induced a significant increase of hepatocyte proliferation(P<0.001),whereas it decreased their apoptotic activity(P<0.001)compared to groupⅢ.BBS and NT significantly decreased portal endotoxemia (P<0.001)and increased the hepatic GSH:GSSG ratio (P<0.05 and P<0.001,respectively)compared 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 response.This peptides-induced combined stimulation of oval cell and hepatocyte proliferation might serve as a possible treatment modality for several liver diseases. | Stelios F Assimakopoulos Athanassios C Tsamandas Ilias H Alexandris Christos Georgiou Constantine E Vagianos Chrisoula D Scopa | 2011 | World Journal of Gastrointestinal Pathophysiology2011，2，6： | 2 |
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