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Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage:A prospective case control study

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World Journal of Clinical Cases 2022年第17期10卷 5551-5565页

作者： Tajana Pavic Stipe Pelajic Nina Blazevic dominik kralj Milan Milosevic Ivana Mikolasevic Ivan Lerotic Davor Hrabar Department of Gastroenterology and Hepatology University Hospital Center Sestre MilosrdniceZagreb 10000Croatia Andrija Stampar School of Public Health WHO Collaborative Centre for Occupational Health University of ZagrebSchool of MedicineZagreb 10000Croatia Department of Gastroenterology University Hospital Center RijekaRijeka 51000Croatia

BACKGROUND Biliary obstruction is a relatively common condition that affects approximately 5 in 1000 people *** is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality,it is important to identify factors and mechanisms involved in its *** To determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive *** This was a prospective case control study performed in a tertiary center in Zagreb,*** with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were *** excluding patients who developed procedure related complications or were lost in the follow-up,out of initial 73 patients,55 patients were included in the analysis,including 34 with benign and 21 with malignant ***,40 non-jaundiced controls were also ***,nutritional status,and serum ghrelin,cholecystokinin(CCK),interleukin 6(IL-6),and tumor necrosis factorα(TNF-α)were determined at admission,48 h and 28 d after internal biliary *** square test was used for categorical *** variables were analysed for normality by Kolmogorov-Smirnov test and relevant non-parametric(Mann-Whitney,Kruskal-Wallis,and Friedman)or parametric(t-test and analysis of variance)tests were *** Patients with obstructive jaundice were significantly malnourished compared to controls,regardless of disease *** ghrelin and CCK levels were significantly higher in patients with obstructive *** bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α,but had no correlation with CCK *** internal biliary drainage,a significant improvement of nutritional status was observed although serum concentrations of ghrelin,IL-6,and TNF-α remained significantly elevated even 28 d after the *** level

关键词： Ghrelin Cholecystokinin Biliary obstruction Malnutrition

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Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia

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World Journal of Gastrointestinal Surgery 2021年第12期13卷 1708-1720页

作者： Sanja Stojsavljevic-Shapeski Lucija Virovic-Jukic Davor Tomas Marko Duvnjak Vedran Tomasic Davor Hrabar dominik kralj Ivan Budimir Neven Barsic Neven Ljubicic Division of Gastroenterology Department of Internal Medicine«Sestre Milosrdnice»University Hospital CenterZagreb 10000Croatia Department of Internal Medicine School of MedicineUniversity of ZagrebZagreb 10000Croatia Ljudevit Jurak Department of Pathology «Sestre Milosrdnice»University Hospital CenterZagreb 10000Croatia Department of Pathology School of MedicineUniversity of ZagrebZagreb 10000Croatia

BACKGROUNDGhrelin is an adipokine that plays an important role in energy balance. Expressionof ghrelin and ghrelin receptor has been investigated in different tissues andtumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectaltumors are scarce and no data on expression of ghrelin and its receptor incolorectal adenomas has been published. Ghrelin and ghrelin receptor werehighly expressed in colon carcinoma cells while expression was decreased in lessdifferentiated tumors, presuming that ghrelin might be important in early phasesof *** investigate the expression of ghrelin and ghrelin receptor in human colorectaladenomas and adjacent colorectal *** this prospective study (conducted from June 2015 until May 2019) we included92 patients (64 male and 28 female) who underwent polypectomy for colorectaladenomas in the Department of Gastroenterology and Hepatology, “Sestre milosrdnice” Clinical Hospital Center in Zagreb, Croatia. After endoscopicremoval of colorectal adenoma, an additional sample of colon mucosa in theproximity of the adenoma was collected for pathohistological analysis. Adenomaswere graded according to the stage of dysplasia, and ghrelin and ghrelin receptorexpression were determined immunohistochemically in both adenoma andadjacent colon tissue using the polyclonal antibody for ghrelin (ab150514,ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAMInc, Cambridge, United States). Categorical and nominal variables were describedthrough frequencies and proportions and the difference between specific groupswere analyzed with Fisher’s and Fisher-Freeman-Halton’s method ***'s rank correlation coefficient was determined for correlation ofexpression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissuewith the grade of adenoma *** 92 patients with colorectal adenoma 43 had adenomas with high-gradedysplasia (46.7%). High expression of ghre

关键词： Ghrelin Ghrelin receptor Adipokines Colorectal adenoma Colorectal adenoma dysplasia Large intestine

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Hepatitis C Virus, Insulin Resistance, and Steatosis

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Journal of Clinical and Translational Hepatology 2016年第1期4卷 66-75页

作者： dominik kralj Lucija Virovi(c) Juki(c) Sanja Stojsavljevi(c) Marko Duvnjak Martina Smoli(c) Ines Bili(c) (C)ur(c)i(c) Department of Gastroenterology and Hepatology Sisters of Charity University Hospital Center Zagreb Croatia Department of Pharmacology Faculty of Medicine University of Osijek Osijek Croatia Department of Pharmacology Faculty of MedicineUniversity of Osijek Department of Endocrinology and metabolism disorders University Hospital Center Osijek Osijek Croatia

Hepatitis C virus (HCV) is one of the main causes of liver disease *** steatosis is a common finding in many hepatic and extrahepatic disorders,the most common being metabolic syndrome (MS).Overtime,it has been shown that the frequent coexistence of these two conditions is not coincidental,since many epidemiological,clinical,and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic ***,we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this *** has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple *** research has suggested that HCV interferes with insulin signaling both directly and indirectly,inducing the production of several proinflammatory *** replication,assembly,and release from hepatocytes require close interactions with lipid droplets and host *** modulation of lipid metabolism in host cells can induce hepatic steatosis,which is more pronounced in patients with HCV genotype *** risk of steatosis depends on several viral factors (including genotype,viral load,and gene mutations) and host features (visceral obesity,type 2 diabetes mellitus,genetic predisposition,medication use,and alcohol consumption).HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life,due to their association with resistance to antiviral therapy,progression of hepatic fibrosis,and development of hepatocellular ***,HCV-induced IR,oxidative stress,and changes in lipid and iron metabolism lead to glucose intolerance,arterial hypertension,hyperuricemia,and atherosclerosis,resulting in increased cardiovascular mortality.

关键词： Hepatitis C virus Metabolic syndrome Insulin resistance Steatosis

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Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights

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World Journal of Gastroenterology 2017年第48期23卷 8465-8488页

作者： Antonija Duzel Josipa Vlainic Marko Antunovic dominik Malekinusic Borna Vrdoljak Mariam Samara Slaven Gojkovic Ivan Krezic Tinka Vidovic Zdenko Bilic Mario Knezevic Marko Sever Nermin Lojo Antonio Kokot Marijan Kolovrat Domagoj Drmic Jaksa Vukojevic Tamara kralj Katarina Kasnik Marko Siroglavic Sven Seiwerth Predrag Sikiric Departments of Pharmacology and Pathology Medical Faculty University of Zagreb Medical Faculty J.J.Strossmayer University of Osijek OsijekCroatia Rudjer Boskovic Institute Department of Molecular Medicine

AIM To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. METHODS Medication [BPC 157,L-NAME,L-arginine(alone/combined),saline] was bath at the blood deprived colon segment. During reperfusion,medication was BPC 157 or saline. We recorded(USB microscope camera) vessel presentation through next 15 min of ischemic colitis(ICrats) or reperfusion(removed ligations)(IC + RL-rats);oxidative stress as MDA(increased(IC-and IC + RLrats)) and NO levels(decreased(IC-rats);increased(IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction(OB)] for 3 d(IC + OBrats),then received BPC 157 bath. RESULTS Commonly,in colon segment(25 mm,2 ligations on left colic artery and vein,3 arcade vessels within ligated segment),in IC-,IC + RL-,IC + OB-rats,BPC 157(10 μg/kg) bath(1 m L/rat) increased vessel presentation,inside/outside arcade interconnections quickly reappeared,mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME(5 mg) and L-arginine(100 mg). MDA-and NO-levels were normal in BPC 157 treated IC-rats and IC + RLrats. In addition,on day 10,BPC 157-treated IC + OBrats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects;the treated colon segment was of normal diameter,and only small adhesions were *** BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system.

关键词： Ischemic colitis Blood flow rescue Collaterals BPC 157 L-NAME L-arginine Oxidative stress NO Rats

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Pentadecapeptide BPC 157 resolves Pringle maneuver in rats,both ischemia and reperfusion

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World Journal of Hepatology 2020年第5期12卷 184-206页

作者： Marijan Kolovrat Slaven Gojkovic Ivan Krezic dominik Malekinusic Borna Vrdoljak Katarina Kasnik Kovac Tamara kralj Domagoj Drmic Ivan Barisic Katarina Horvat Pavlov Andreja Petrovic Antonija Duzel Mario Knezevic Ivan Mirkovic Antonio Kokot Alenka Boban Blagaic Sven Seiwerth Predrag Sikiric Departments of Pharmacology and Pathology School of MedicineUniversity of ZagrebZagreb 10000Croatia

BACKGROUND The Pringle maneuver[portal triad obstruction(PTO)]provides huge disturbances during ischemia and even more thereafter in ***,a possible solution may be stable gastric pentadecapeptide BPC 157,with already documented beneficial effects in ischemia/reperfusion ***,BPC 157,as a cytoprotective agent,successfully resolved vessel occlusions in rats(ischemic colitis;deep vein thrombosis,superior anterior pancreaticoduodenal vein;bile duct cirrhosis)through rapid collateral vessel recruitment to circumvent vessel ***,medication BPC 157 regimens were administered as a single challenge before and during ischemia or,alternatively,at various time points during *** To introduce BPC 157 therapy against pringle *** In deeply anesthetised rats,the portal triad was clamped up for 30 *** then underwent reperfusion for either 15 min or 24 ***[(10μg,10 ng/kg)regimens,administered as a single challenge]picked(a)ischemia,PTO period[at 5 min before(ip)or at 5 or 30 min of ligation time(as a bath to PTO)]or(b)reperfusion,post-PTO period[at 1 or 15 min(bath during surgery)or 24 h(ip)reperfusion-time].We provided gross,microscopy,malondialdehyde,serum enzymes,electrocardiogram,portal,caval,and aortal pressure,thrombosis and venography *** BPC 157 counteracts electrocardiogram disturbances(increased P wave amplitude,S1Q3T3 QRS pattern and tachycardia).Rapidly presented vascular pathway(portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein)as the adequate shunting immediately affected disturbed *** hypertension and severe aortal hypotension during PTO,as well as portal and caval hypertension and mild aortal hypotension in reperfusion and refractory ascites formation were markedly attenuated(during PTO)or completely abrogated(reperfusion);thrombosis in portal vein tributaries and inferior caval vein o

关键词： BPC 157 Pringle maneuver Rats Portal hypertension Caval hypertension Ischemia

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