TY - JOUR AU - Czikora, Ágnes AU - Rutkai, Ibolya AU - Pásztorné, Tóth Enikő AU - Szalai, Andrea AU - Pórszász, Róbert AU - Boczán, Judit AU - Édes, István AU - Papp, Zoltán AU - Tóth, Attila TI - Different desensitization patterns for sensory and vascular TRPV1 populations in the rat: Expression, localization and functional consequences JF - PLOS ONE J2 - PLOS ONE VL - 8 PY - 2013 IS - 11 PG - 8 SN - 1932-6203 DO - 10.1371/journal.pone.0078184 UR - https://m2.mtmt.hu/api/publication/3065667 ID - 3065667 N1 - Funding Agency and Grant Number: TAMOP [4.2.2.A-11/1/KONV-2012-0045]; European Social Fund; Hungarian Academy of Sciences OTKA [K84300]; Bolyai Janos Research Fellowship; Baross Gabor EletMent; National Office for Research and Technology, Hungary Funding text: The work is supported by the TAMOP 4.2.2.A-11/1/KONV-2012-0045 project (to IE, ZP and AT, National Development Agency, http://www.nfu.hu/?lang=en). This project is implemented through the New Hungary Development Plan, co-financed by the European Social Fund. In addition, the study was supported by the Hungarian Academy of Sciences OTKA (K84300 to AT, RP, http://www.otka.hu/en) and Bolyai Janos Research Fellowship (to AT, http://mta.hu/english/) and by Baross Gabor EletMent grant by the National Office for Research and Technology, Hungary (http://www.nih.gov.hu/english). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. LA - English DB - MTMT ER - TY - JOUR AU - Pető, Katalin AU - Szentmiklósi, József András AU - Schmidt, E AU - Kovács, J AU - Furka, István AU - Mikó, Irén TI - A veseműtétek során alkalmazott érleszorítás hatása a veseartéria funkcionális aktivitására – az érkárosodás farmakológiai prevenciója JF - MAGYAR UROLÓGIA J2 - MAGYAR UROLÓGIA VL - 15 PY - 2013 IS - 4 SP - 175 EP - 180 PG - 6 SN - 0864-8921 UR - https://m2.mtmt.hu/api/publication/2504650 ID - 2504650 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Hegedűs, Csaba AU - Kovacs, D AU - Drimba, László Péter AU - Sari, R AU - Varga, Angelika AU - Nemeth, J AU - Szilvássy, Zoltán AU - Peitl, Barna TI - Investigation of the metabolic effects of chronic clozapine treatment on CCK-1 receptor deficient Otsuka Long Evans Tokushima Fatty (OLETF) rats. JF - EUROPEAN JOURNAL OF PHARMACOLOGY J2 - EUR J PHARMACOL VL - 718 PY - 2013 IS - 1-3 SP - 188 EP - 196 PG - 9 SN - 0014-2999 DO - 10.1016/j.ejphar.2013.08.034 UR - https://m2.mtmt.hu/api/publication/2442826 ID - 2442826 N1 - Export Date: 27 January 2024; CODEN: EJPHA AB - Clozapine increases meal size and meal duration, effects similar to the pharmacological blockade or congenital deficiency of CCK-1 receptor. We aimed to investigate the role of CCK-1 receptor in clozapine-induced weight gain and insulin sensitivity in CCK-1 receptor deficient, male Otsuka Long Evans Tokushima Fatty rats (OLETF). Long Evans Tokushima Otsuka (LETO) rats served as healthy control. Animals were orally treated with either clozapine (10mg/kg) or its vehicle over 25 days. Daily metabolic parameters were measured by metabolic cages. The insulin sensitivity was determined by hyperinsulinaemic euglycaemic glucose clamping (HEGC). Adiposity was determined by measuring the perirenal, intraabdominal and epididymal white adipose tissue fat pads. Hypothalamic mRNA expression of CCK-1 and CCK-2 receptor was measured by real-time PCR, plasma insulin by radioimmunoassay. Clozapine failed to increase weight gain or daily food intake, but it increased adiposity, 1st meal size and duration and decreased insulin sensitivity both in OLETF or LETO rats. The glucose infusion rate during the steady state of the HEGC was unaltered, but the metabolic clearance rate of insulin was reduced by the clozapine treatment. Hypothalamic mRNA of CCK-1 and CCK-2 receptor was elevated in LETO rats, but the mRNA of CCK-2 receptor was reduced by clozapine in OLETF rats. Our results suggest that the CCK-1 receptor has no direct role in the clozapine-induced adiposity and insulin resistance. We also demonstrated that atypical antipsychotic treatment can induce insulin resistance in the absence of manifest obesity in male rats. LA - English DB - MTMT ER - TY - JOUR AU - Kovacs, D AU - Simon, Zoltán AU - Hari, P AU - Málnási Csizmadia, András AU - Hegedűs, Csaba AU - Drimba, László Péter AU - Nemeth, J AU - Sari, R AU - Szilvássy, Zoltán AU - Peitl, Barna TI - Identification of PPARgamma ligands with One-dimensional Drug Profile Matching. JF - DRUG DESIGN DEVELOPMENT AND THERAPY J2 - DRUG DES DEV THER VL - 7 PY - 2013 SP - 917 EP - 928 PG - 12 SN - 1177-8881 DO - 10.2147/DDDT.S47173 UR - https://m2.mtmt.hu/api/publication/2442825 ID - 2442825 N1 - Department of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary Drugmotif, Ltd, Veresegyház, Hungary Printnet, Ltd, Budapest, Hungary Department of Biochemistry, Institute of Biology, Eötvös Loránd University, Budapest, Hungary Molecular Biophysics Research Group, Hungarian Academy of Sciences - Eötvös Loránd University, Budapest, Hungary Cera-Med Ltd, Debrecen-Józsa, Hungary Cited By :7 Export Date: 23 April 2024 Correspondence Address: Peitl, B.; Department of Pharmacology and Pharmacotherapy, H-4032, Nagyerdei Boulevard 98, Debrecen, Hungary; email: barna.peitl@gmail.com AB - INTRODUCTION: Computational molecular database screening helps to decrease the time and resources needed for drug development. Reintroduction of generic drugs by second medical use patents also contributes to cheaper and faster drug development processes. We screened, in silico, the Food and Drug Administration-approved generic drug database by means of the One-dimensional Drug Profile Matching (oDPM) method in order to find potential peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. The PPARgamma action of the selected generics was also investigated by in vitro and in vivo experiments. MATERIALS AND METHODS: The in silico oDPM method was used to determine the binding potency of 1,255 generics to 149 proteins collected. In vitro PPARgamma activation was determined by measuring fatty acid-binding protein 4/adipocyte protein gene expression in a Mono Mac 6 cell line. The in vivo insulin sensitizing effect of the selected compound (nitazoxanide; 50-200 mg/kg/day over 8 days; n = 8) was established in type 2 diabetic rats by hyperinsulinemic euglycemic glucose clamping. RESULTS: After examining the closest neighbors of each of the reference set's members and counting their most abundant neighbors, ten generic drugs were selected with oDPM. Among them, four enhanced fatty acid-binding protein/adipocyte protein gene expression in the Mono Mac 6 cell line, but only bromfenac and nitazoxanide showed dose-dependent actions. Induction by nitazoxanide was higher than by bromfenac. Nitazoxanide lowered fasting blood glucose levels and improved insulin sensitivity in type 2 diabetic rats. CONCLUSION: We demonstrated that the oDPM method can predict previously unknown therapeutic effects of generic drugs. Nitazoxanide can be the prototype chemical structure of the new generation of insulin sensitizers. LA - English DB - MTMT ER - TY - JOUR AU - Drimba, László Péter AU - Nemeth, J. AU - Sári, R. AU - Di, Y. AU - Kovács, A. AU - Szénási, Gábor AU - Szilvássy, Zoltán AU - Peitl, Barna TI - In Vivo Preclinical Evaluation of a Promising Antiarrhythmic Agent, EGIS‐7229 JF - DRUG DEVELOPMENT RESEARCH J2 - DRUG DEVELOP RES VL - 74 PY - 2013 IS - 3 SP - 173 EP - 185 PG - 13 SN - 0272-4391 DO - 10.1002/ddr.21058 UR - https://m2.mtmt.hu/api/publication/2392796 ID - 2392796 AB - The basic hemodynamic, electrophysiological, and pharmacological effects of EGIS-7229 (E-7229) were evaluated and compared with those of a pure “Class III“ antiarrhythmic drug (GLG-V-13) in conscious rabbits. Both compounds decreased heart rate dose-dependently. Mean arterial blood pressure was not influenced by E-7229; however, GLG-V-13 produced a significant elevation on this parameter. Left ventricular end-diastolic pressure was gradually increased by E-7229, while GLG-V-13 induced more considerable elevation on that at intermediate doses. QT and QTcb were lengthened by both compounds; however, higher doses of E-7229 resulted in shortening of the prolonged QT and QTcb. Ventricular effective refractory period (VERP) was significantly prolonged by either drug studied. Threshold doses to produce QT50%, QTmax, VERP50%, and VERPmax were significantly higher for E-7229 compared with GLG-V-13. Significantly higher doses were required for E-7229 to induce arrhythmias. The safety ratio was comparable for both of the compounds. E-7229 can exert multiple actions on cardiac ion channels with minimal influence on hemodynamic parameters and reduced proarrhytmic profile in our preclinical model. LA - English DB - MTMT ER - TY - JOUR AU - Vos, M AU - Tőkési, Károly AU - Benkő, Ilona TI - The potential of materials analysis by electron rutherford backscattering as illustrated by a case study of mouse bones and related compounds JF - MICROSCOPY AND MICROANALYSIS J2 - MICROSC MICROANAL VL - 19 PY - 2013 IS - 3 SP - 576 EP - 586 PG - 11 SN - 1431-9276 DO - 10.1017/S143192761300041X UR - https://m2.mtmt.hu/api/publication/2389065 ID - 2389065 N1 - Megjegyzés-23460255 FN: Thomson Reuters Web of Knowledge AB - Electron Rutherford backscattering (ERBS) is a new technique that could be developed into a tool for materials analysis. Here we try to establish a methodology for the use of ERBS for materials analysis of more complex samples using bone minerals as a test case. For this purpose, we also studied several reference samples containing Ca: calcium carbonate (CaCO3) and hydroxyapatite and mouse bone powder. A very good understanding of the spectra of CaCO3 and hydroxyapatite was obtained. Quantitative interpretation of the bone spectrum is more challenging. A good fit of these spectra is only obtained with the same peak widths as used for the hydroxyapatite sample, if one allows for the presence of impurity atoms with a mass close to that of Na and Mg. Our conclusion is that a meaningful interpretation of spectra of more complex samples in terms of composition is indeed possible, but only if widths of the peaks contributing to the spectra are known. Knowledge of the peak widths can either be developed by the study of reference samples (as was done here) or potentially be derived from theory. Copyright © Microscopy Society of America 2013 Â. LA - English DB - MTMT ER - TY - JOUR AU - Drimba, László Péter AU - Dobronte, R AU - Hegedűs, Csaba AU - Sari, R AU - Di, Y AU - Nemeth, J AU - Szilvássy, Zoltán AU - Peitl, Barna TI - The role of acute hyperinsulinemia in the development of cardiac arrhythmias. JF - NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY J2 - N-S ARCH PHARMACOL VL - 386 PY - 2013 IS - 5 SP - 435 EP - 444 PG - 10 SN - 0028-1298 DO - 10.1007/s00210-013-0845-4 UR - https://m2.mtmt.hu/api/publication/2387075 ID - 2387075 N1 - Export Date: 27 January 2024; CODEN: NSAPC AB - Patients with perturbed metabolic control are more prone to develop cardiac rhythm disturbances. The main purpose of the present preclinical study was to investigate the possible role of euglycemic hyperinsulinemia in development of cardiac arrhythmias. Euglycemic hyperinsulinemia was induced in conscious rabbits equipped with a right ventricular pacemaker electrode catheter by hyperinsulinemic euglycemic glucose clamp (HEGC) applying two different rates of insulin infusion (5 and 10 mIU/kg/min) and variable rate of glucose infusion to maintain euglycemia (5.5 +/- 0.5 mmol/l). The effect of hyperinsulinemia on cardiac electrophysiological parameters was continuously monitored by means of 12-lead surface ECG recording. Arrhythmia incidence was determined by means of programmed electrical stimulation (PES). The possible role of adrenergic activation was investigated by determination of plasma catecholamine levels and intravenous administration of a beta adrenergic blocking agent, metoprolol. All of the measurements were performed during the steady-state period of HEGC and subsequent to metoprolol administration. Both 5 and 10 mIU/kg/min insulin infusion prolonged significantly QTend, QTc, and Tpeak-Tend intervals. The incidence of ventricular arrhythmias generated by PES was increased significantly by euglycemic hyperinsulinemia and exhibited linear relationship to plasma levels of insulin. No alteration on plasma catecholamine levels could be observed; however, metoprolol treatment restored the prolonged QTend, QTc, and Tpeak-Tend intervals and significantly reduced the hyperinsulinemia-induced increase of arrhythmia incidence. Euglycemic hyperinsulinemia can exert proarrhythmic effect presumably due to the enhancement of transmural dispersion of repolarization. Metoprolol treatment may be of benefit in hyperinsulinemia associated with increased incidence of cardiac arrhythmias. LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Zsuzsanna Mária AU - Pák, Krisztián AU - Zsuga, Judit AU - Juhász, Béla AU - Varga, Balázs AU - Szentmiklósi, József András AU - Haines, David AU - Tósaki, Árpád AU - Gesztelyi, Rudolf TI - The guinea pig atrial A1 adenosine receptor reserve for the direct negative inotropic effect of adenosine JF - GENERAL PHYSIOLOGY AND BIOPHYSICS J2 - GEN PHYSIOL BIOPHYS VL - 32 PY - 2013 IS - 3 SP - 325 EP - 335 PG - 11 SN - 0231-5882 DO - 10.4149/gpb_2013041 UR - https://m2.mtmt.hu/api/publication/2360355 ID - 2360355 LA - English DB - MTMT ER - TY - JOUR AU - Literáti-Nagy, Zsuzsanna AU - Tory, K AU - Literáti-Nagy, Botond AU - Bajza, A AU - Vígh, László Jr. AU - Vigh, László AU - Mandl, József AU - Szilvássy, Zoltán TI - Synergetic Insulin Sensitizing Effect of Rimonabant and BGP-15 in Zucker-Obes Rats JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 19 PY - 2013 IS - 3 SP - 571 EP - 575 PG - 5 SN - 1219-4956 DO - 10.1007/s12253-013-9620-6 UR - https://m2.mtmt.hu/api/publication/2286566 ID - 2286566 AB - Abdominal obesity is referred for as a common pathogenic root of multiple risk factors, which include insulin resistance, dyslipidemia, hypertension, and a pro-atherogenic and pro- inflammatory state. Irrespective of its psychiatric side effects, rimonabant through blocking cannabinoid-1 receptor (CB1R) induces an increase in whole body insulin sensitivity. The aim of this work was to study the effect of selected doses of another insulin sensitizer compound BGP-15, and rimonabant on insulin resistance in Zucker obese rats with a promise of inducing insulin sensitization together at lower doses than would have been expected by rimonabant alone. We found that BGP- 15 potentiates the insulin sensitizing effect of rimonabant. The combination at doses, which do not induce insulin sensitization by themselves, improved insulin signaling. Furthermore our results suggest that capsaicin-induced signal may play a role in insulin sensitizing effect of both molecules. Our data might indicate that a lower dose of rimonabant in the treatment of insulin resistance and type 2 diabetes is sufficient to administer, thus a lower incidence of the unfavorable psychiatric side effects of rimonabant are to be expected. LA - English DB - MTMT ER - TY - JOUR AU - Crul, Tim AU - Crul-Tóth, Noémi AU - Piotto, S AU - Literáti-Nagy, Péter AU - Tory, K AU - Haldimann, P AU - Kalmar, B AU - Greensmith, L AU - Török, Zsolt AU - Balogh, Gábor AU - Gombos, Imre AU - Campana, F AU - Concilio, S AU - Gallyas, Ferenc AU - Nagy, G AU - Berente, Zoltán AU - Güngör, Burcin AU - Péter, Mária AU - Glatz, Attila AU - Hunya, Ákos AU - Literáti-Nagy, Zsuzsanna AU - Vígh, László Jr. AU - Hoogstra-Berends, F AU - Heeres, A AU - Kuipers, I AU - Loen, L AU - Seerden, JP AU - Zhang, D AU - Meijering, RA AU - Henning, RH AU - Brundel, BJ AU - Kampinga, HH AU - Korányi, László AU - Szilvássy, Zoltán AU - Mandl, József AU - Sümegi, Balázs AU - Febbraio, MA AU - Horváth, Ibolya AU - Hooper, PL AU - Vigh, László TI - Hydroximic Acid Derivatives: Pleiotropic Hsp Co-Inducers Restoring Homeostasis and Robustness JF - CURRENT PHARMACEUTICAL DESIGN J2 - CURR PHARM DESIGN VL - 19 PY - 2013 IS - 3 SP - 309 EP - 346 PG - 38 SN - 1381-6128 DO - 10.2174/1381612811306030309 UR - https://m2.mtmt.hu/api/publication/2096112 ID - 2096112 AB - According to the "membrane sensor" hypothesis, the membranes physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy. LA - English DB - MTMT ER -