TY - JOUR AU - Ovari, Ignac AU - Viczjan, Gabor AU - Erdei, Tamas AU - Takacs, Barbara AU - Tarjanyi, Vera AU - Zsuga, Judit AU - Szucs, Miklos AU - Szilvássy, Zoltán AU - Juhasz, Bela AU - Gesztelyi, Rudolf TI - The influence of the way of regression on the results obtained by the receptorial responsiveness method (RRM), a procedure to estimate a change in the concentration of a pharmacological agonist near the receptor JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 15 PY - 2024 SN - 1663-9812 DO - 10.3389/fphar.2024.1375955 UR - https://m2.mtmt.hu/api/publication/34834656 ID - 34834656 AB - The receptorial responsiveness method (RRM) enables the estimation of a change in concentration of an (even degradable) agonist, near its receptor, via curve fitting to (at least) two concentration-effect (E/c) curves of a stable agonist. One curve should be generated before this change, and the other afterwards, in the same system. It follows that RRM yields a surrogate parameter (“c x ”) as the concentration of the stable agonist being equieffective with the change in concentration of the other agonist. However, regression can be conducted several ways, which can affect the accuracy, precision and ease-of-use. This study utilized data of previous ex vivo investigations. Known concentrations of stable agonists were estimated with RRM by performing individual (local) or global fitting, this latter with one or two model(s), using a logarithmic (logc x ) or a nonlogarithmic (c x ) parameter (the latter in a complex or in a simplified equation), with ordinary least-squares or robust regression, and with an “all-at-once” or “pairwise” fitting manner. We found that the simplified model containing logc x was superior to all alternative models. The most complicated individual regression was the most accurate, followed closely by the moderately complicated two-model global regression and then by the easy-to-perform one-model global regression. The two-model global fitting was the most precise, followed by the individual fitting (closely) and by the one-model global fitting (from afar). Pairwise fitting (two E/c curves at once) improved the estimation. Thus, the two-model global fitting, performed pairwise, and the individual fitting are recommended for RRM, using the simplified model containing logc x . LA - English DB - MTMT ER - TY - JOUR AU - Takács, Barbara AU - Szilágyi, Anna AU - Priksz, Dániel AU - Bombicz, Mariann AU - Szabó, Adrienn Mónika AU - Pelles-Taskó, Beáta AU - Rusznyák, Ágnes AU - Haimhoffer, Ádám AU - Gesztelyi, Rudolf AU - Szilvássy, Zoltán AU - Juhász, Béla AU - Varga, Balázs TI - Electroretinographical Analysis of the Effect of BGP-15 in Eyedrops for Compensating Global Ischemia–Reperfusion in the Eyes of Sprague Dawley Rats JF - BIOMEDICINES J2 - BIOMEDICINES VL - 12 PY - 2024 IS - 3 SP - 637 SN - 2227-9059 DO - 10.3390/biomedicines12030637 UR - https://m2.mtmt.hu/api/publication/34768269 ID - 34768269 AB - Retinal vascular diseases and consequential metabolic disturbances in the eye are major concerns for healthcare systems all around the world. BGP-15, a drug candidate small-molecule [O-(3-piperidino-2-hydroxy-1-propyl) nicotinic amidoxime dihydrochloride], has been formerly demonstrated by our workgroup to be retinoprotective both in the short and long term. Based on these results, the present study was performed to investigate the efficacy of BGP in an eyedrop formulation containing sulfobutylether-β-cyclodextrin (SBECD), which is a solubility enhancer as well. Electroretinographical evaluations were carried out and BGP was demonstrated to improve both scotopic and photopic retinal a- and b-waves, shorten their implicit times and restore oscillatory potentials after ischemia–reperfusion. It was also observed to counteract retinal thinning after ischemia–reperfusion in the eyes of Sprague Dawley rats. This small-molecule drug candidate is able to compensate for experimental global eye ischemia–reperfusion injury elicited by ligation of blood vessels in rats. We successfully demonstrated that BGP is able to exert its protective effects on the retina even if administered in the form of eyedrops. LA - English DB - MTMT ER - TY - JOUR AU - Tarjányi, Vera AU - Ménes, Ákos AU - Hamid, Leila AU - Kurucz, Andrea AU - Priksz, Dániel AU - Varga, Balázs AU - Gesztelyi, Rudolf AU - Kiss, Rita AU - Horváth, Ádám István AU - Szentes, Nikolett AU - Helyes, Zsuzsanna AU - Szilvássy, Zoltán AU - Bombicz, Mariann TI - Assessing the Impact of Influenza Vaccination Timing on Experimental Arthritis : Effects on Disease Progression and Inflammatory Biomarkers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 6 PG - 16 SN - 1661-6596 DO - 10.3390/ijms25063292 UR - https://m2.mtmt.hu/api/publication/34763932 ID - 34763932 N1 - Funding Agency and Grant Number: European Union; State of Hungary; University of Debrecen [GINOP-2.3.4-15-2016-00002]; Hungarian Research Network (Chronic Pain Research Group); National Research, Development and Innovation Office (PharmaLab) [RRF-2.3.1-21-2022-00015, TKP2021-EGA-13, OTKA-K 134214]; National Research, Development and Innovation Fund of Hungary [TKP2021-EGA-13, TKP2021-EGA-16]; European Union and the European Regional Development Fund; National Research, Development and Innovation Fund of Hungary under the TKP2021-EGA funding scheme [TKP2021-EGA-18] Funding text: The present research was supported by the European Union, the State of Hungary, and the University of Debrecen under grant number GINOP-2.3.4-15-2016-00002 (V.T., D.P., R.G., Z.H., B.V., A.K., R.K., Z.S., M.B.), the Hungarian Research Network (Chronic Pain Research Group; Z.H.), National Research, Development and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015; Z.H.), TKP2021-EGA-13 (Z.H.), and OTKA-K 134214 (Z.H.). Projects no. TKP2021-EGA-13 and TKP2021-EGA-16 have been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the EGA 13 and EGA 16 funding schemes. The project is co-financed by the European Union and the European Regional Development Fund. Project no. TKP2021-EGA-18 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme. AB - Numerous studies have indicated a link between vaccines and the exacerbation of autoimmune diseases including rheumatoid arthritis (RA). However, there is no consensus in clinical practice regarding the optimal timing of immunization. Therefore, this study aimed to investigate the impact of the 3Fluart influenza vaccine on the complete Freund's adjuvant (CFA)-induced chronic arthritis rat model and to identify new biomarkers with clinical utility. CFA was injected into the plantar surface of one hind paw and the root of the tail on day 0, and the tail root injection was repeated on day 1. Flu vaccination was performed on day 1 or 7. Paw volume was measured by plethysmometry, mechanonociceptive threshold by dynamic plantar aesthesiometry, neutrophil myeloperoxidase (MPO) activity, and vascular leakage using in vivo optical imaging throughout the 21-day experiment. Inflammatory markers were determined by Western blot and histopathology. CFA-induced swelling, an increase in MPO activity, plasma extravasation in the tibiotarsal joint. Mechanical hyperalgesia of the hind paw was observed 3 days after the injection, which gradually decreased. Co-administration of the flu vaccine on day 7 but not on day 1 resulted in significantly increased heme oxygenase 1 (HO-1) expression. The influenza vaccination appears to have a limited impact on the progression and severity of the inflammatory response and associated pain. Nevertheless, delayed vaccination could alter the disease activity, as indicated by the findings from assessments of edema and inflammatory biomarkers. HO-1 may serve as a potential marker for the severity of inflammation, particularly in the case of delayed vaccination. However, further investigation is needed to fully understand the regulation and role of HO-1, a task that falls outside the scope of the current study. LA - English DB - MTMT ER - 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 - 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 - CHAP AU - Szabó, Renáta AU - Börzsei, Denise AU - Nagyné Hoffmann, Alexandra AU - Gesztelyi, Rudolf AU - Imre, Gálóczi AU - Patrícia, Pálszabó AU - Varga, Csaba AU - Pósa, Anikó ED - Dela, F. ED - Piacentini, M.F. ED - Helge, J.W. ED - Calvo Lluch, Á. ED - Sáez, E. ED - Pareja Blanco, F. ED - Tsolakidis, E. TI - The cardiac effects of nutrition and voluntary physical exercise on the raas and oxidative/inflammatory parameters in spontaneously hypertensive stroke prone rats T2 - 27th Annual Congress of the EUROPEAN COLLEGE OF SPORT SCIENCE PB - European College of Sport Science CY - Köln SN - 9783981841459 PY - 2022 UR - https://m2.mtmt.hu/api/publication/33569018 ID - 33569018 LA - English DB - MTMT ER - TY - JOUR AU - Viczján, Gábor AU - Szilagyi, Anna AU - Takács, Barbara AU - Ovari, Ignac AU - Szekeres, Réka Mária AU - Tarjányi, Vera AU - Erdei, Tamas AU - Teleki, Vanda AU - Zsuga, Judit AU - Szilvássy, Zoltán AU - Juhász, Béla AU - Varga, Balázs AU - Gesztelyi, Rudolf TI - The effect of a long-term treatment with cannabidiol-rich hemp extract oil on the adenosinergic system of the zucker diabetic fatty (ZDF) rat atrium JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 13 PY - 2022 SN - 1663-9812 DO - 10.3389/fphar.2022.1043275 UR - https://m2.mtmt.hu/api/publication/33538911 ID - 33538911 AB - Cannabidiol (CBD), the most extensively studied non-intoxicating phytocannabinoid, has been attracting a lot of interest worldwide owing to its numerous beneficial effects. The aim of this study was to explore the effect that CBD exerts on the adenosinergic system of paced left atria isolated from obese type Zucker Diabetic Fatty (ZDF) rats, maintained on diabetogenic rat chow, received 60 mg/kg/day CBD or vehicle via gavage for 4 weeks. We found that N6-cyclopentyladenosine (CPA), a relatively stable and poorly transported A1 adenosine receptor agonist, elicited a significantly weaker response in the CBD-treated group than in the vehicle-treated one. In contrast, adenosine, a quickly metabolized and transported adenosine receptor agonist, evoked a significantly stronger response in the CBD-treated group than in the vehicle-treated counterpart (excepting its highest concentrations). These results can be explained only with the adenosine transport inhibitory property of CBD (and not with its adenosine receptor agonist activity). If all the effects of CBD are attributed to the interstitial adenosine accumulation caused by CBD in the myocardium, then a significantly increased adenosinergic activation can be assumed during the long-term oral CBD treatment, suggesting a considerably enhanced adenosinergic protection in the heart. Considering that our results may have been influenced by A1 adenosine receptor downregulation due to the chronic interstitial adenosine accumulation, an adenosinergic activation smaller than it seemed cannot be excluded, but it was above the CBD-naïve level in every case. Additionally, this is the first study offering functional evidence about the adenosine transport inhibitory action of CBD in the myocardium. LA - English DB - MTMT ER - TY - JOUR AU - Óvári, Ignác AU - Szilágyi, Viktória AU - Viczján, Gábor AU - Lampé, Nóra AU - Bege, Miklós AU - Borbás, Anikó AU - Herczeg, Pál AU - Juhász, Béla AU - Gesztelyi, Rudolf AU - Erdei, Tamás Dániel TI - Egy újonnan szintetizált adenozin analóg, a hipoxantin-triciklánó hatása izolált patkány bal és jobb pitvaron JF - EGÉSZSÉGÜGYI INNOVÁCIÓS SZEMLE J2 - EÜ INNOV SZLE VL - 1 PY - 2022 IS - 1 SP - 9 EP - 16 PG - 8 SN - 2939-6026 DO - 10.56626/egis.v1i1.7059 UR - https://m2.mtmt.hu/api/publication/33037647 ID - 33037647 AB - A hipoxantin-triciklánó egy a DE GYTK Gyógyszerészi Kémia Tanszéken szintetizált adenozin analóg, melyben az adenint hipoxantin, a ribózt pedig egy kondenzált triciklikus molekularész helyettesíti. Munkánk során a hipoxantin-triciklánó hatását vizsgáltuk a pitvari myocardium A1 adenozinerg rendszerére, melynek (pozitív agonista általi) aktivációja számos protektív folyamatért, köztük negatív trop hatásokért felelős. A vizsgálatokat hím Wistar patkányokból izolált bal pitvari fülcsén és teljes jobb pitvaron végeztük. A preparátumokat 95% O2 és 5% CO2 gázeleggyel szellőztetett, 36°C-os Krebs oldatot tartalmazó szervkádakban függesztettük fel 10 mN alapfeszülés mellett. A bal pitvarokat állandó frekvencián ingereltük (3 Hz; 1 ms; 1-1,5 V), míg a jobb pitvarok spontán húzódtak össze. A preparátumokon az adenozin és a hipoxantin-triciklánó inotrop és chronotrop hatását vizsgáltuk külön-külön és együtt, továbbá CPX (8-cyclopentyl-1,3-dipropylxanthine; reverzibilis A1 adenozin receptor antagonista) hiányában és jelenlétében. Eredményeink alapján az adenozin mind a bal, mind a jobb pitvarokon hasonló mértékű, erőteljes negatív inotrop hatást fejtett ki. A hipoxantin-triciklánó ezzel szemben mérsékelt pozitív inotrop hatást váltott ki, ami hasonló mértékű volt a jobb és a bal pitvarokon. Az inotropia alakulásával összhangban, az adenozin markánsan negatív, míg a hipoxantin-triciklánó kismértékben pozitív chronotrop hatásúnak bizonyult a jobb pitvarokon. A CPX erősen (és szignifikánsan) gátolta az adenozin hatásait, de csak kisebb mértékű (és nem szignifikáns) gátlást hozott létre a hipoxantin-triciklánó hatásaival szemben. A hipoxantin-triciklánó hatásai teljes mértékben áttörhetőek voltak adenozinnal. Mindezek hátterében felvethető, hogy az adenozin könnyen le tudja szorítani a hipoxantin-triciklánót az A1 adenozin receptorról, de (ehelyett vagy emellett) elképzelhető, hogy a hipoxantin-triciklánó az A1 adenozin receptortól független útvonalon is hat. A hipoxantin-triciklánó tehát feltehetően a myocardialis A1 adenozin receptor reverzibilis, ortosztérikus, inverz agonistája, melynek ugyanakkor más támadáspontja is lehet a myocardiumban. The hypoxanthine-tricyclano is a new adenosine analogue, in which adenine and ribose are replaced by hypoxanthine and a fused tricyclic moiety, respectively, synthetized in the Department of Pharma-ceutical Chemistry (Faculty of Pharmacy, University of Debrecen). In the current study, we investigated the effect of hypoxanthine-tricyclano on the A1 adenosinergic system of the rat atrial myocardium, ac-tivation of which (by a positive agonist) is responsible for several protective actions, including negative tropic effects.The left atrial auricle and the whole right atrium were isolated from male Wistar rats and mounted at 10 mN resting tension in 10 mL vertical organ chambers containing Krebs solution (36 °C) oxygenated with 95% O2 and 5% CO2. Left atria were paced (3 Hz, 1 ms, 1-2 V), while right atria worked spontaneous-ly. The inotropic and chronotropic effects of adenosine and hypoxanthine-tricyclano were investigated (separately and in combination), in the absence and presence of CPX (8-cyclopenty l-1,3-dipropylxan-thine), a reversible A1 adenosine receptor antagonist.Adenosine elicited a strong negative inotropic effect on both the left and right atria (to a similar extent). In contrast, hypoxanthine-tricyclano produced a moderate positive inotropic effect in the left and right atria (also to a similar extent). In consistent with the inotropic effects, adenosine exerted a substantial negative chronotropic effect, and hypoxanthine-tricyclano elicited a slight positive chronotropic effect in the right atria. CPX strongly (and statistically significantly) blunted the effects of adenosine but it pro-duced only a minor (and not significant) inhibition against actions of hypoxanthine-tricyclano. In addi-tion, the effects of hypoxanthine-tricyclano were completely surmountable with adenosine. This can be explained by supposing that adenosine can easily displace hypoxanthine-tricyclano from their receptor, and, alternatively or in addition, that hypoxanthine-tricyclano may also act in a pathway independent from the A1 adenosine receptor. Thus, hypoxanthine-tricyclano is probably a reversible, orthosteric, inverse agonist of the myocardial A1 adenosine receptor that might also have another target in the myocardium. LA - Hungarian 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 - Szabó, Renáta AU - Szabó, Zsuzsanna AU - Börzsei, Denise AU - Nagyné Hoffmann, Alexandra AU - Lesi, Zelma Nadin AU - Pálszabó, Patrícia AU - Pálszabó, Andrea AU - Dvorácskó, Szabolcs AU - Gesztelyi, Rudolf AU - Kupai, Krisztina AU - Priksz, Dániel AU - Juhász, Béla AU - Altmayer, Anita AU - Varga, Csaba AU - Pósa, Anikó TI - Potential Implications of Rimonabant on Age-Related Oxidative Stress and Inflammation JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 11 PY - 2022 IS - 1 PG - 14 SN - 2076-3921 DO - 10.3390/antiox11010162 UR - https://m2.mtmt.hu/api/publication/32607973 ID - 32607973 LA - English DB - MTMT ER -