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Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine

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World Journal of Gastroenterology 2018年第47期24卷 5366-5378页

作者： Fedor Amic Domagoj Drmic zdenko bilic Ivan Krezic Helena Zizek Marina Peklic Robert Klicek Alen Pajtak Enio Amic Tinka Vidovic Mislav Rakic Marija Milkovic Perisa Katarina Horvat Pavlov Antonio Kokot Ante Tvrdeic Alenka Boban Blagaic Mario Zovak Sven Seiwerth Predrag Sikiric Department of Pharmacology Medical Faculty University of Zagreb Department of Pathology Medical Faculty University of Zagreb

AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system *** Male Wistar rats underwent superior anterior pancreaticoduodenal vein(SAPDV)-ligation and were treated with a bath at the ligated SAPDV site(BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 m L bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation(filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein(IAPDV) and superior mesenteric vein(SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO-and oxidative stress [malondialdehyde(MDA)]-levels in *** Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal *** BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and

关键词： Major venous occlusion Duodenal lesions BPC 157 L-NAME Bypassing L-arginine Reduction of free radical formation Rats

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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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On Ductile Damage Modelling of Heterogeneous Material Using Second-Order Homogenization Approach

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Computer Modeling in Engineering & Sciences 2021年第3期126卷 915-934页

作者： Jurica Soric Tomislav Lesicar zdenko Tonkovic Faculty of Mechanical Engineering and Naval Architecture University of ZagrebZagreb10000Croatia

The paper deals with the numerical modelling of ductile damage responses in heterogeneous materials using the classical second-order homogenization *** scale transition methodology in the multiscale framework is *** structure at the macrolevel is discretized by the triangular C^(1) finite elements obeying nonlocal continuum theory,while the discretization of microstructural volume element at the microscale is conducted by means of the mixed type quadrilateral finite element with the nonlocal equivalent plastic strain as an additional nodal *** ductile damage evolution at the microlevel is modelled by using the gradient enhanced *** macrolevel softening is governed by two criterions expressed by the increase in homogenized damage variable and the threshold of the local equivalent *** softening at each material point at the macrolevel is detected by the critical value of the homogenized damage,where homogenization of the damage variable is performed onlywithin softening *** to the nonlocal continuumtheory applied,a realistic softening behaviour is demonstrated after the damage initiation,compared to the widely used first-order homogenization *** algorithms derived have been embedded into the finite element code ABAQUS by means of the user subroutines and verified on the standard benchmark *** damage evolution at both microlevel and macrolevel has been demonstrated.

关键词： Ductile damage second-order homogenization multiscale approach C1 finite element

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Pathophysiology profile-an outcome of international survey:General pathophysiology and integrative clinical reasoning

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中国病理生理杂志 2009年第11期25卷 2243-2244页

作者： zdenko Kovac Department of Pathophysiology Medical School University of Zagreb

Short international survey has been done among the members of International Society for Pathophysiology. 42 to 46 valid answers,which came from 22 countries,were accumulated and analyzed. The average of teaching hours of pathophysiology course in various curricula is 146 out of 5 788 total teaching hours of medical curricula (lecture 58,seminars 44,practical 52). Average teaching materials consist of 863 pages of obligatory texts and 1 225 pages of recommended materials. An estimated students' 'study time' for successful mastering of the exam is 164 hours (along with 146 contact teaching/learning hours). A survey concerning an educational profile of the pathophysiologist (A),contents of teaching (B),a selective advantage of pathophysiology teaching (C) and personal advise of pathophysiologists with respect of educational curricula (D) have been quantified by number 1 through 10; one being the weakest and ten being the strongest. Each of the survey features (A through D) was described in advance by 8 different statements,among which participants gave their 'intensity of support' using numerical values 1-10. The outcome indicates that the best profile of pathophysiologists' education scheme is that with 'MD + PhD + postdoctoral training + any residency' (score 8.57) and weakest profile 'PhD in the field of molecular biology' (4.93). The strongest 'power and relevance of pathophysiology' has been given to type of the subject which '…represents an integrative frame of reference describing common principles of disease' (8.59),whereas the weakest to the 'It leads to the evidence based practice and reduces medical costs' (7.65). With reference to the teaching contents the highest rank was given to 'Symptoms/signs/dysfunctions correlations with molecular nature of etiopathogenetic processes' (8.67),whereas the weakest points were given to 'quantitative aspects of etiopathogenetic processes' (6.60). When pathophysiologists were asked to give 'an educated

关键词：病理生理学国际调查配置文件推理临床教学时数学习时间课程

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A Multiscale Method for Damage Analysis of Quasi-Brittle Heterogeneous Materials

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Computer Modeling in Engineering & Sciences 2019年第7期120卷 123-156页

作者： Filip Putar Jurica Soric Tomislav Lesicar zdenko Tonkovic Faculty of Mechanical Engineering and Naval Architecture University of ZagrebIvana Lucica 5Zagreb 10000Croatia

A novel multiscale algorithm based on the higher-order continuum at both micro-and macrostructural level is proposed for the consideration of the quasi-brittle damage response of heterogeneous ***,the microlevel damage is modelled by the degradation of the homogenized stress and tangent stiffness tensors,which are then upscaled to govern the localization at the *** C^1 continuity finite element employing a modified case of Mindlin’s form II strain energy density is derived for the softening *** the authors’knowledge,the finite element discretization based on the strain gradient theory is applied for the modeling of damage evolution at the microstructural level for heterogeneous materials for the first *** advantage of the novel C1 finite element formulation in comparison with the standard finite element discretization in terms of the regularization efficiency as well as the objectivity has been *** isotropic damage law is used for the reduction of the constitutive and nonlocal material behaviour,which is necessary for the physically correct description of the localization formation in quasi-brittle *** capabilities of the derived finite element to capture the fully developed localization zones are tested on a random representative volume element(RVE)for several different loading *** employing the conventional second-order computational homogenization,the microstructural material constitutive response is averaged over the whole RVE *** order to model the loss of structural integrity when sharp localization is formed across RVE,the specific conditions which detect a completely formed localization zone are developed.A new failure criterion at the microstructural level has been *** derived finite element formulation,as well as the multiscale damage algorithm,are implemented into the finite element program *** capabilities of the presented multiscale scheme to capture the effects of the deformat

关键词： Multiscale analysis second-order computational homogenization damage,C^(1) continuity finite element quasi-brittle material

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How far along are we in revealing the connection between metformin and colorectal cancer?

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World Journal of Gastroenterology 2021年第14期27卷 1362-1368页

作者： Maja Cigrovski Berkovic Danko Mikulic Ines bilic-Curcic Anna Mrzljak Department of Kinesiological Anthropology and Methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia Clinical Hospital Dubrava Zagreb 10000Croatia Department of Surgery Merkur University HospitalZagreb 10000Croatia Department of Pharmacology Faculty of MedicineUniversity of J.J.Strossmayer OsijekOsijek 31000Croatia Clinical Hospital Center Osijek Osijek 31000Croatia Department of Medicine Merkur University HospitalSchool of MedicineZagreb 10000Croatia

Colorectal cancer(CRC)is among the most prevalent cancers worldwide,and its prevention and reduction of incidence is *** presence of diabetes has been associated with a 30%increased risk of CRC,likely through the mechanism of hyperinsulinemia,which promotes tumorigenesis via the insulin receptor in the epithelium or by insulin-like growth factor pathways,inflammation,or adipokines,inducing cancer cell proliferation and cancer ***,the first-line agent in treating type 2 diabetes,has a chemopreventive role in CRC ***,preclinical studies suggest synergistic effects of metformin with oxaliplatin in inhibiting in vitro models of colon *** preclinical studies on the post diagnostic use of metformin were promising and suggested its synergistic effects with chemotherapy,the data on the possible effects of metformin after surgery and other CRC treatment in the clinical setting are less conclusive,and randomized controlled trials are still lacking.

关键词： Metformin Type 2 diabetes mellitus Colorectal cancer Chemoprevention Recurrence-free survival Surgery

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Biobased Aromatic-Aliphatic Polyols from Cardanol by Thermal Thiol-Ene Reaction

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Journal of Renewable Materials 2018年第1期6卷 87-101页

作者： Maha LShrestha Mihail Ionescu Xianmei Wan Nikola bilic′ Zoran SPetrovic′ Tom Upshaw Pittsburg State University Kansas Polymer Research Center1701 South BroadwayPittsburgKansas66762USA Chevron Phillips Chemical Company LP Bartlesville Technology CenterBartlesvilleOklahoma74003-6670USA

Cardanol is a natural phenol which is obtained from high vacuum distillation of cashew nut shell *** contains a hydrocarbon chain of 15 carbon atoms in the meta position,either with one,two or three nonconjugated double *** article describes thermal thiol-ene reaction to synthesize new cardanol-based polyols for polyurethanes with aromatic-aliphatic *** hydroxyl group was blocked by alkoxylation and 2-mercaptoethanol was added to the double bonds of propoxylated *** resultant product is a mixture of polyols that may contain one,two,three or four hydroxyl groups,as a function of the number of double bonds reacted with *** polyols,but with much higher functionality,were also synthesized from condensation of cardanol-based novolacs with *** cardanolbased polyols were further utilized to prepare rigid polyurethane foams(PUs)with excellent physical and mechanical properties,useful for various applications in chemical and food industries.

关键词： Thiol-ene mercaptans cashew nut shell liquid polyurethanes

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Important parameters in plasma jets for the production of RONS in liquids for plasma medicine: A brief review

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Frontiers of Chemical Science and Engineering 2019年第2期13卷 238-252页

作者： Anna Khlyustova Cédric Labay zdenko Machala Maria-Pau Ginebra Cristina Canal Biomaterials Biomechanics and Tissue Engineering GroupDepartment of Materials Science and MetallurgyUniversitat Politecnica de CatalunyaBarcelona 08019Spain Research centre in Multiscale Science and Engineering Universitat Politecnica de CatalunyaBarcelona 08019Spain Faculty of Mathematics Physics and InformaticsComenius UniversityBratislava 84248Slovakia

Reactive oxygen and nitrogen species (RONS) are among the key factors in plasma medicine. They are generated by atmospheric plasmas in biological fluids, living tissues and in a variety of liquids. This ability of plasmas to create a delicate mix of RONS in liquids has been used to design remote or indirect treatments for oncological therapy by treating biological fluids by plasmas and putting them in contact with the tumour;Documented effects include selective cancer cell toxicity, even though the exact mechanisms involved are still under investigation. However, the "right" dose for suitable therapeutical activity is crucial and still under debate. The wide variety of plasma sources hampers comparisons. This review focuses on atmospheric pressure plasma jets as the most studied plasma devices in plasma medicine and compiles the conditions employed to generate RONS in relevant liquids and the concentration ranges obtained. The concentrations of H2O2, NO2^-, NO3^- and short-lived oxygen species are compared critically to provide a useful overview for the reader.

关键词： atmospheric plasma jets liquids ROS RNS plasma-dose

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Semaglutide might be a key for breaking the vicious cycle of metabolically associated fatty liver disease spectrum?

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World Journal of Clinical Cases 2022年第20期10卷 6759-6768页

作者： Maja Cigrovski Berkovic Tanja Rezic Ines bilic-Curcic Anna Mrzljak Department of Endocrinology DiabetesMetabolism and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Endocrinology and Diabetes Clinical Hospital DubravaZagreb 10000Croatia Department of Endocrinology and Diabetes University Hospital Centre OsijekOsijek 31000Croatia Department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia

Metabolically associated fatty liver disease(MAFLD)is a liver manifestation of metabolic syndrome potentially related to unfavorable hepatic and extrahepatic outcomes and progression to *** to date,there are no approved pharmacotherapies for the treatment of MAFLD,so management focused on lifestyle interventions to encourage weight loss,and treatment of coexisting conditions is the only available ***,the aforementioned is often not potent enough to offer reversal or slow down hepatic inflammation and ***-like peptide-1 receptor agonists have a favorable effect on glycemic management and weight loss of patients with type 2 diabetes mellitus and recently published data suggest their potential in MAFLD *** addition,some of the agents have proven cardiovascular and renal benefits in dedicated cardiovascular outcome trials,making them an interesting therapeutic *** this opinion review,we discuss the role of semaglutide in MAFLD.

关键词： Semaglutide Non-alcoholic fatty liver disease Glucagon-like peptide-1 receptor agonists Metabolically associated fatty liver disease

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What is the gut feeling telling us about physical activity in colorectal carcinogenesis?

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World Journal of Clinical Cases 2020年第23期8卷 5844-5851页

作者： Maja Cigrovski Berkovic Vjekoslav Cigrovski Ines bilic-Curcic Anna Mrzljak Department for Endocrinology Diabetes and MetabolismClinical Hospital DubravaZagreb 10000Croatia Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Pharmacology Faculty of MedicineJ J Strossmayer University OsijekOsijek 31000Croatia Department of Medicine Merkur University HospitalZagreb 10000Croatia Department of Medicine School of MedicineUniversity of ZagrebZagreb 10000Croatia

In the last decades,more efforts are focused on the prevention and treatment of malignant diseases,given the increase in all cancers incidence A lifestyle change,including healthy eating habits and regular physical activity,has significantly impacted colorectal cancer *** effect of dose-dependent physical activity on mortality and recurrence rates of colorectal carcinoma has been unequivocally demonstrated in observational ***,clear recommendations are not available on the frequency,duration,and intensity of exercise in patients with colorectal cancer due to the lack of evidence in randomized clinical *** pathophysiological mechanisms,the most plausible explanation appears to be the influence of physical activity on reducing chronic inflammation and insulin resistance with a consequent positive effect on insulin growth factor 1 signaling pathways.

关键词： Physical activity Colorectal cancer Insulin signaling pathway Inflammation Gut microbiota

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