TY - JOUR AU - Szekeres, Réka Mária AU - Priksz, Dániel AU - Kiss, Rita AU - Romanescu, Dana Diana AU - Bombicz, Mariann AU - Varga, Balázs AU - Gesztelyi, Rudolf AU - Szilágyi, Anna AU - Takács, Barbara AU - Tarjányi, Vera AU - Pelles-Tasko, Beata AU - Forgács, Ildikó Noémi AU - Gálné Remenyik, Judit AU - Szilvássy, Zoltán AU - Juhász, Béla TI - Therapeutic Aspects of Prunus cerasus Extract in a Rabbit Model of Atherosclerosis-Associated Diastolic Dysfunction JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 17 PG - 19 SN - 1661-6596 DO - 10.3390/ijms241713253 UR - https://m2.mtmt.hu/api/publication/34126717 ID - 34126717 AB - This study evaluates the potential therapeutic effects of anthocyanin-rich Prunus cerasus (sour cherry) extract (PCE) on atherosclerosis-associated cardiac dysfunction, described by the impairment of the NO-PKG (nitric oxide–protein kinase G) pathway and the antioxidant capacity. Initially, a rabbit model of atherosclerotic cardiovascular disease was established by administering a cholesterol-rich diet, enabling the examination of the impact of 9 g/kg PCE on the pre-existing compromised cardiovascular condition. After that, the animals were divided into four groups for 12 weeks: the (1) untreated control group; (2) PCE-administered healthy rabbits; (3) hypercholesterolemic (HC) group kept on an atherogenic diet; and (4) PCE-treated HC group. Dyslipidemia, impaired endothelial function, and signs of diastolic dysfunction were evident in hypercholesterolemic rabbits, accompanied by a reduced cardiac expression of eNOS (endothelial nitric oxide synthase), PKG, and SERCA2a (sarco/endoplasmic reticulum calcium ATPase 2a). Subsequent PCE treatment improved the lipid profile and the cardiac function. Additionally, PCE administration was associated with elevated myocardial levels of eNOS, PKG, and SERCA2a, while no significant changes in the vascular status were observed. Western blot analysis further revealed hypercholesterolemia-induced increase and PCE-associated reduction in heme oxygenase-1 expression. The observed effects of anthocyanins indicate their potential as a valuable addition to the treatment regimen for atherosclerosis-associated cardiac dysfunction. LA - English DB - MTMT ER - TY - JOUR AU - Bernát, Brigitta Renáta AU - Erdelyi, Rita AU - Fazekas, László Ádám AU - Garami, Greta AU - Szekeres, Réka Mária AU - Takács, Barbara AU - Bombicz, Mariann AU - Varga, Balázs AU - Sárkány, Fruzsina AU - Ráduly, Arnold AU - Romanescu, Dana Diana AU - Papp, Zoltán AU - Tóth, Attila AU - Szilvássy, Zoltán AU - Juhász, Béla AU - Priksz, Dániel TI - Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 16 PY - 2023 IS - 3 PG - 22 SN - 1424-8247 DO - 10.3390/ph16030359 UR - https://m2.mtmt.hu/api/publication/33703433 ID - 33703433 N1 - Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Department of Dentoalveolar Surgery, Faculty of Dentistry, University of Debrecen, Debrecen, H-4032, Hungary Department of Operative Techniques and Surgical Research, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Department of Diabetology, Pelican Clinical Hospital, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, 410087, Romania Export Date: 5 October 2023 Correspondence Address: Priksz, D.; Department of Pharmacology and Pharmacotherapy, Hungary; email: priksz.daniel@pharm.unideb.hu Chemicals/CAS: cefuroxime, 55268-75-2, 56238-63-2; dipyrone, 50567-35-6, 5907-38-0, 68-89-3; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; o (2 hydroxy 3 piperidinopropyl)nicotinic amidoxime, 66611-37-8 Tradenames: bgp 15, Sigma Aldrich, Germany; bgp 15, Merck, Germany Manufacturers: Merck, Germany; Sigma Aldrich, Germany Funding details: ÚNKP-21-2-I-DE-392 Funding details: European Commission, EC Funding details: Debreceni Egyetem, DE, GINOP-2.3.4-15-2020-00008, TKP2020-NKA-04 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, 2020-4.1.1-TKP2020 Funding details: Innovációs és Technológiai Minisztérium Funding text 1: This research was supported by the European Union, the State of Hungary, and the University of Debrecen under grant number GINOP-2.3.4-15-2020-00008 (D.P., R.M.S., B.T., B.V., M.B., B.B., B.J., Z.S.). Project no. TKP2020-NKA-04 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the 2020-4.1.1-TKP2020 funding scheme. The research was financed by the Thematic Excellence Programme of the Ministry for Innovation and Technology in Hungary (TKP2020-NKA-04), within the framework of the Space Sciences thematic program of the University of Debrecen. The publication was supported by the ÚNKP-21-2-I-DE-392 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. (B.B., D.P.) AB - Multi-target drug candidate BGP-15 has shown cardioprotective and antiarrhythmic actions in diseased models. Here, we investigated the effects of BGP-15 on ECG and echocardiographic parameters, heart rate variability (HRV), and arrhythmia incidence in telemetry-implanted rats, under beta-adrenergic stimulation by isoproterenol (ISO). In total, 40 rats were implanted with radiotelemetry transmitters. First, dose escalation studies (40–160 mg/kg BGP-15), ECG parameters, and 24 h HRV parameters were assessed. After, rats were divided into Control, Control+BGP-15, ISO, and ISO+BGP-15 subgroups for 2 weeks. ECG recordings were obtained from conscious rats, arrhythmias and HRV parameters were assessed, and echocardiography was carried out. ISO-BGP-15 interaction was also evaluated on an isolated canine cardiomyocyte model. BGP-15 had no observable effects on the ECG waveforms; however, it decreased heart rate. HRV monitoring showed that BGP-15 increased RMSSD, SD1, and HF% parameters. BGP-15 failed to counteract 1 mg/kg ISO-induced tachycardia, but diminished the ECG of ischemia and suppressed ventricular arrhythmia incidence. Under echocardiography, after low-dose ISO injection, BGP-15 administration lowered HR and atrial velocities, and increased end-diastolic volume and ventricle relaxation, but did not counteract the positive inotropic effects of ISO. Two weeks of BGP-15 treatment also improved diastolic function in ISO-treated rats. In isolated cardiomyocytes, BGP-15 prevented 100 nM ISO-induced aftercontractions. Here, we show that BGP-15 increases vagally mediated HRV, reduces arrhythmogenesis, enhances left ventricle relaxation, and suppresses the aftercontractions of cardiomyocytes. As the drug is well tolerated, it may have a clinical value in preventing fatal arrhythmias. LA - English DB - MTMT ER - TY - JOUR AU - Blaga, Zsanett AU - Czine, Péter AU - Takács, Barbara AU - Szilagyi, Anna AU - Szekeres, Réka Mária AU - Juhászné Wachal, Zita Eszter AU - Hegedus, Csaba AU - Buchholcz, Gyula AU - Varga, Balázs AU - Priksz, Dániel AU - Bombicz, Mariann AU - Vargáné Szabó, Adrienn Mónika AU - Kiss, Rita AU - Gesztelyi, Rudolf AU - Romanescu, Dana Diana AU - Szabó, Zoltán AU - Szűcs, Miklós AU - Balogh, Péter AU - Szilvássy, Zoltán AU - Juhász, Béla TI - Examination of Preferences for COVID-19 Vaccines in Hungary Based on Their Properties—Examining the Impact of Pandemic Awareness with a Hybrid Choice Approach JF - INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH J2 - INT J ENV RES PUB HE VL - 20 PY - 2023 IS - 2 PG - 16 SN - 1661-7827 DO - 10.3390/ijerph20021270 UR - https://m2.mtmt.hu/api/publication/33560204 ID - 33560204 AB - The COVID-19 pandemic has posed a huge challenge to the world in recent years. The development of vaccines that are as effective as possible and accessible to society offers a promising alternative for addressing the problems caused by this situation as soon as possible and to restore the pre-epidemic system. The present study investigated the preferences of residents in Hungary’s second-largest city (Debrecen) for the COVID-19 vaccine. To achieve this aim, a discrete choice experiment was conducted with 1011 participants, and the vaccine characteristics included in the design of the experiment were determined by qualitative methods and a pilot survey: (1) country of origin; (2) efficiency; (3) side effect; and (4) duration of protection. During the data collection at three vaccination sites, respondents were asked to choose between three vaccine alternatives and one “no choice” option in eight decision situations. Discrete choice model estimations were performed using a random parameter logit (RPL) specification with the final model extended to include a latent variable measuring pandemic awareness. The results showed that the vaccine with a Chinese country of origin is the least preferred among the respondents, while the Hungarian and the European vaccines are the most preferred. Furthermore, the increase in the vaccine efficiency level increased the respondents’ sense of utility for the vaccine; the short-term side effect was preferred to the long-term one; and the increase in the duration of protection provided by the vaccine increased the respondents’ sense of utility for the vaccine. Based on the parameter estimated for the latent variable, it can be concluded that as the level of pandemic awareness (which is more positive among people with chronic diseases and less important among health workers) increases, the choice of a vaccine option becomes more preferred among respondents compared to the “no choice“. The results of our investigation could contribute towards increasing compliance in the case of the vaccination-rejecting population, not only for COVID-19, but for any kind of vaccination procedure. LA - English DB - MTMT ER - TY - JOUR AU - Juhászné Wachal, Zita Eszter AU - Szilágyi, Anna AU - Takács, Barbara AU - Vargáné Szabó, Adrienn Mónika AU - Priksz, Dániel AU - Bombicz, Mariann AU - Szilvássy, Judit AU - Juhász, Béla AU - Szilvássy, Zoltán AU - Varga, Balázs TI - Corrigendum: Improved survival and retinal function of aging ZDF rats in long-term, uncontrolled diabetes by BGP-15 treatment, (Front. Pharmacol, (2021), 12, (650207), 10.3389/fphar.2021.650207) JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 13 PY - 2022 SN - 1663-9812 DO - 10.3389/fphar.2022.1034389 UR - https://m2.mtmt.hu/api/publication/33571706 ID - 33571706 AB - In the published article, there was an error in affiliation 1. Instead of “Department of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary”, it should be “Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary”. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. © 2022 Wachal, Szilágyi, Takács, Szabó, Priksz, Bombicz, Szilvássy, Juhász, Szilvássy and Varga. LA - English DB - MTMT ER - TY - JOUR AU - Szilágyi, Anna AU - Takács, Barbara AU - Szekeres, Réka Mária AU - Tarjányi, Vera AU - Bombicz, Mariann AU - Priksz, Dániel AU - Kovács, Attila AU - Juhász, Béla AU - Frecska, Ede AU - Szilvássy, Zoltán AU - Varga, Balázs TI - Therapeutic Properties of Ayahuasca Components in Ischemia/Reperfusion Injury of the Eye JF - BIOMEDICINES J2 - BIOMEDICINES VL - 10 PY - 2022 IS - 5 PG - 19 SN - 2227-9059 DO - 10.3390/biomedicines10050997 UR - https://m2.mtmt.hu/api/publication/32850670 ID - 32850670 AB - Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective effects of N'N-dimethyltryptamine (DMT) were investigated. To inhibit its rapid breakdown by monoamine-oxidase A (MAO-A) enzyme, DMT was co-administered with harmaline, a β-carboline in the Amazonian Ayahuasca brew. Using ligation, 60 min of ischemia was provoked in eyes of rats, followed by 7 days of reperfusion whilst animals received harmaline alone, DMT + harmaline, or vehicle treatment. After 1 week of reperfusion, electroretinographical (ERG) measurements, histological analysis, and Western blot were performed. Harmaline alone exhibited retinoprotection in ischemia-reperfusion (I/R) which was, surprisingly, counterbalanced by DMT in case of co-administration. As both MAO-A inhibition and DMT increase serotoninergic tone synergistically, communicated to be anti-ischemic, thus, involvement of other pathways was investigated. Based on our experiments, DMT and harmaline exert opposite effects on important ocular proteins such as PARP1, NFκB, MMP9, or HSP70, each having a critical role in a different mechanism of eye-ischemia-related pathologies, e.g., cell death, inflammation, tissue destruction, and oxidative stress. Since DMT is proclaimed to be a promising drug candidate, its potentially undesirable effect on eye-ischemia should be further investigated. Meanwhile, this experiment revealed the potential therapeutic effect of MAO-A inhibitor harmaline in I/R-related eye diseases. LA - English DB - MTMT ER - TY - JOUR AU - Kozma, Mate AU - Bombicz, Mariann AU - Varga, Balázs AU - Priksz, Dániel AU - Gesztelyi, Rudolf AU - Tarjányi, Vera AU - Kiss, Rita AU - Szekeres, Réka Mária AU - Takács, Barbara AU - Menes, Akos AU - Balla, József AU - Balla, György AU - Szilvássy, Judit AU - Szilvássy, Zoltán AU - Juhász, Béla TI - Cardioprotective Role of BGP-15 in Ageing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 14 PY - 2022 IS - 2 PG - 16 SN - 1999-4923 DO - 10.3390/pharmaceutics14020226 UR - https://m2.mtmt.hu/api/publication/32607988 ID - 32607988 LA - English DB - MTMT ER - TY - JOUR AU - Priksz, Dániel AU - Lampé, Nóra AU - Kovács, Árpád AU - Herwig, Melissa AU - Bombicz, Mariann AU - Varga, Balázs AU - Wilisicz, Tician AU - Szilvássy, Judit AU - Pósa, Anikó AU - Kiss, Rita AU - Gesztelyi, Rudolf AU - Ráduly, Arnold AU - Szekeres, Réka Mária AU - Sieme, Marcel AU - Papp, Zoltán AU - Tóth, Attila AU - Hamdani, Nazha AU - Szilvássy, Zoltán AU - Juhász, Béla TI - Nicotinic-acid derivative BGP-15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy JF - BRITISH JOURNAL OF PHARMACOLOGY J2 - BR J PHARMACOL VL - 179 PY - 2022 IS - 10 SP - 2240 EP - 2258 PG - 19 SN - 0007-1188 DO - 10.1111/bph.15749 UR - https://m2.mtmt.hu/api/publication/32555207 ID - 32555207 N1 - 326335 AB - Background and purpose: Small molecule BGP-15 has been reported to alleviate signs of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP-15 in a rabbit model of atherosclerotic cardiomyopathy. Experimental approach: Rabbits were maintained on standard chow (Control) or atherogenic diet (HC) for 16 weeks. BGP-15 was administered intravenously (once) or orally (for 16 weeks), to assess acute and chronic effects. Cardiac function was evaluated by echocardiography, endothelium-dependent vasorelaxation was assessed, and key molecules of the protein kinase G (PKG) axis were examined by ELISA and Western blot. Passive force generation was investigated in skinned cardiomyocytes. Key results: Both acute and chronic BGP-15 treatment improved the diastolic performance of the diseased heart, however, vasorelaxation and serum lipid markers were unaffected. Myocardial cGMP levels were elevated in the BGP-15-treated group, along with preserved PKG activity and increased phospholamban Ser16-phosphorylation. PDE5 expression decreased in the BGP-15-treated group, and the substance inhibited PDE1 enzyme. Cardiomyocyte passive tension reduced in BGP-15-treated rabbits, the ratio of titin N2BA/N2B isoforms increased, and PKG-dependent N2B-titin phosphorylation elevated in the BGP-15-treated group. Conclusions and implications: Here we report that BGP-15-treatment improves diastolic function, reduces cardiomyocyte stiffness, and restores titin compliance in a rabbit model of atherosclerotic cardiomyopathy by increasing the activity of the cGMP-PKG axis. As BGP-15 is proven to be safe, it may have clinical value in the treatment of diastolic dysfunction. LA - English DB - MTMT ER - TY - JOUR AU - Kozma, Bence AU - Damjanovich, Péter Gábor AU - Pákozdy, Krisztina Lili AU - Sipos, Attila Gergely AU - Bombicz, Mariann AU - Takács, Péter TI - Vaginal elasticity is significantly decreased in vaginal atrophy: a strain elastography study JF - INTERNATIONAL UROGYNECOLOGY JOURNAL J2 - INT UROGYNECOL J VL - 31 PY - 2021 IS - Suppl1 SP - S33 EP - S34 SN - 0937-3462 DO - 10.1007/s00192-020-04555-3 UR - https://m2.mtmt.hu/api/publication/32870919 ID - 32870919 N1 - 310735 LA - English DB - MTMT ER - TY - JOUR AU - Viczján, Gábor AU - Erdei, Tamás Dániel AU - Óvári, Ignác AU - Lampé, Nóra AU - Szekeres, Réka Mária AU - Bombicz, Mariann AU - Takács, Barbara AU - Szilágyi, Anna AU - Zsuga, Judit AU - Szilvássy, Zoltán AU - Juhász, Béla AU - Gesztelyi, Rudolf TI - A Body of Circumstantial Evidence for the Irreversible Ectonucleotidase Inhibitory Action of FSCPX, an Agent Known as a Selective Irreversible A1 Adenosine Receptor Antagonist So Far JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 18 PG - 21 SN - 1661-6596 DO - 10.3390/ijms22189831 UR - https://m2.mtmt.hu/api/publication/32193722 ID - 32193722 AB - In previous studies using isolated, paced guinea pig left atria, we observed that FSCPX, known as a selective A(1) adenosine receptor antagonist, paradoxically increased the direct negative inotropic response to A(1) adenosine receptor agonists (determined using concentration/effect (E/c) curves) if NBTI, a nucleoside transport inhibitor, was present. Based on mathematical modeling, we hypothesized that FSCPX blunted the cardiac interstitial adenosine accumulation in response to nucleoside transport blockade, probably by inhibiting CD39 and/or CD73, which are the two main enzymes of the interstitial adenosine production in the heart. The goal of the present study was to test this hypothesis. In vitro CD39 and CD73 inhibitor assays were carried out; furthermore, E/c curves were constructed in isolated, paced rat and guinea pig left atria using adenosine, CHA and CPA (two A(1) adenosine receptor agonists), FSCPX, NBTI and NBMPR (two nucleoside transport inhibitors), and PSB-12379 (a CD73 inhibitor), measuring the contractile force. We found that FSCPX did not show any inhibitory effect during the in vitro enzyme assays. However, we successfully reproduced the paradox effect of FSCPX in the rat model, mimicked the "paradox" effect of FSCPX with PSB-12379, and demonstrated the lipophilia of FSCPX, which could explain the negative outcome of inhibitor assays with CD39 and CD73 dissolved in a water-based solution. Taken together, these three pieces of indirect evidence are strong enough to indicate that FSCPX possesses an additional action besides the A(1) adenosine receptor antagonism, which action may be the inhibition of an ectonucleotidase. Incidentally, we found that POM-1 inhibited CD73, in addition to CD39. LA - English DB - MTMT ER - TY - JOUR AU - Tánczos, Bence AU - Somogyi, Viktória AU - Bombicz, Mariann AU - Juhász, Béla AU - Németh, Norbert AU - Deák, Ádám TI - Changes of Hematological and Hemorheological Parameters in Rabbits with Hypercholesterolemia JF - METABOLITES J2 - METABOLITES VL - 11 PY - 2021 IS - 4 PG - 12 SN - 2218-1989 DO - 10.3390/metabo11040249 UR - https://m2.mtmt.hu/api/publication/32033226 ID - 32033226 N1 - The work was supported by The National Research, Development and Innovation Fund, Hungary NKFIH-1150-6/2019 and TKP-2019, ED_18-1-2019-0028 and co-financed by the European Union and the European Regional Development Fund GINOP-2.3.4-15-2016-00002 project, and by the Bridging Fund of the Faculty of Medicine, University of Debrecen. LA - English DB - MTMT ER -