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 - Ráduly, Arnold Péter AU - Sárkány, Fruzsina AU - Kovács, Máté Balázs AU - Juhász, Béla AU - Horváth, Balázs AU - Szentandrássy, Norbert AU - Nánási, Péter Pál AU - Édes, István AU - Csanádi, Zoltán AU - Tóth, Attila AU - Papp, Zoltán AU - Priksz, Dániel AU - Borbély, Attila TI - A kardiális miozinaktivátorok klinikai alkalmazhatósága a preklinikai vizsgálatok tükrében [= Clinical applications of cardiac myosin activators in the light of preclinical studies] JF - CARDIOLOGIA HUNGARICA J2 - CARDIOL HUNG VL - 53 PY - 2023 IS - 5 SP - 476 EP - 483 PG - 8 SN - 0133-5596 DO - 10.26430/CHUNGARICA.2023.53.5.476 UR - https://m2.mtmt.hu/api/publication/34400338 ID - 34400338 AB - A csökkent ejekciós frakciójú szívelégtelenség (HFrEF) gyógyszeres kezelésében az utóbbi évtizedben jelentős fejlődés következett be. A kórkép patomechanizmusának középpontjában álló kontraktilis diszfunkciót direkten javító, úgynevezett pozitív inotróp szerek azonban továbbra sem hoztak átütő sikert. Az ideális pozitív inotróp szer nem fokozza a myocardium energiaigényét és oxigénfelhasználását. Az eddig használt gyógyszerek sajnos maradéktalanul nem tudtak megfelelni ezeknek az elvárásoknak. Az aktin-miozin-interakció direkt modulálása miozinaktivátorokkal egy új terápiás célpont a kontrakciós erő fokozására, a korábbi szerekre jellemző káros mellékhatások nélkül. Klinikai vizsgálatokban az első ilyen gyógyszer, az omecamtiv-mecarbil (OM) – a III. fázis vizsgálatok kezdeti pozitív eredményei ellenére – megfelelő hatékonyság hiánya miatt mégsem került bevezetésre a klinikai gyakorlatba. Ezen vegyület alkalmazhatóságát korlátozó tényezőket számos preklinikai tanulmány vizsgálta. Az OM sikertelensége ugyanakkor egy új típusú miozinaktivátor, a danicamtiv kifejlesztését is potencírozta. A danicamtivval kapcsolatos preklinikai és klinikai vizsgálatok jelenleg még korlátozott számban érhetőek el. Az eddigi eredmények biztatóbbak a danicamtivval kapcsolatban, azonban ennek megerősítésére még számos vizsgálatra van szükség. Feltételezhetően mindkét gyógyszerjelölt jövőbeli alkalmazhatóságát diasztolés diszfunkciót okozó hatásuk korlátozhatja. Summary: There have been significant advances in the management of heart failure with reduced ejection fraction (HFrEF) over the last decade. However, the so-called positive inotropic agents, which directly correct the contractile dysfunction at the heart of the pathomechanism of the disease, have still not been a resounding success. The ideal positive inotropic agent does not increase myocardial energy demand and oxygen consumption. Unfortunately, the drugs used so far have not fully met these requirements. Direct modulation of the actin-myosin interaction by myosin activators is a new therapeutic target to enhance contractile force without the adverse side effects typical of previous agents. In clinical trials, the first such drug, omecamtiv mecarbil (OM), has not been introduced into clinical practice due to lack of adequate efficacy, despite initial positive results in phase III trials. Several preclinical studies have investigated the limiting factors for the applicability of this compound. However, the failure of OM has also stimulated the development of a new type of myosin activator, danicamtiv. Preclinical and clinical studies on danicamtiv are currently limited. The results to date are more encouraging for danicamtiv, but many more studies are needed to confirm this. Presumably, the future applicability of both candidates may be limited by their adverse effects on diastolic function. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Al-Smadi, Mohammad AU - Fazekas, László Ádám AU - Aslan, Siran AU - Bernát, Brigitta Renáta AU - Beqain, Anas AU - Al-Khafaji, Mustafa Qais Muhsin AU - Priksz, Dániel AU - Orlik, Brigitta AU - Németh, Norbert TI - A Microsurgical Arteriovenous Malformation Model on Saphenous Vessels in the Rat JF - BIOMEDICINES J2 - BIOMEDICINES VL - 11 PY - 2023 IS - 11 SP - 2970 SN - 2227-9059 DO - 10.3390/biomedicines11112970 UR - https://m2.mtmt.hu/api/publication/34394226 ID - 34394226 AB - Arteriovenous malformation (AVM) is an anomaly of blood vessel formation. Numerous models have been established to understand the nature of AVM. These models have limitations in terms of the diameter of the vessels used and the impact on the circulatory system. Our goal was to establish an AVM model that does not cause prompt and significant hemodynamic and cardiac alterations but is feasible for follow-up of the AVM’s progression. Sixteen female rats were randomly divided into sham-operated and AVM groups. In the AVM group, the saphenous vein and artery were interconnected using microsurgical techniques. The animals were followed up for 12 weeks. Anastomosis patency and the structural and hemodynamic changes of the heart were monitored. The hearts and vessels were histologically analyzed. During the follow-up period, shunts remained unobstructed. Systolic, diastolic, mean arterial pressure, and heart rate values slightly and non-significantly decreased in the AVM group. Echocardiogram results indicated minor systolic function impact, with slight and insignificant changes in aortic pressure and blood velocity, and minimal left ventricular wall enlargement. The small-caliber saphenous AVM model does not cause acute hemodynamic changes. Moderate but progressive alterations and venous dilatation confirmed AVM-like features. The model seems to be suitable for studying further the progression, enlargement, or destabilization of AVM. 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 - Matusovits, Danica AU - Murlasits, Zsolt AU - Kupai, Krisztina AU - Baráth, Zoltán Lajos AU - Hsu, Linkang AU - Osváth, Péter AU - Szűcs, Miklós AU - Priksz, Dániel AU - Juhász, Béla AU - Radák, Zsolt AU - Várkonyi, Tamás AU - Pávó, Imre AU - Pósa, Anikó TI - Paclitaxel Protects against Isoproterenol-Induced Damage in Rat Myocardium: Its Heme-Oxygenase Mediated Role in Cardiovascular Research JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 12 PY - 2023 IS - 5 PG - 13 SN - 2076-3921 DO - 10.3390/antiox12051129 UR - https://m2.mtmt.hu/api/publication/33856409 ID - 33856409 N1 - Megosztott első szerzőség AB - (1) Background: In cardiovascular applications, paclitaxel inhibits smooth muscle cell proliferation and migration and significantly reduces the occurrence of restenosis and target lesion revascularization. However, the cellular effects of paclitaxel in the myocardium are not well understood; (2) Methods: Wistar rats were divided into four groups: control (CTRL), isoproterenol (ISO) treated (1 mg/kg) and two groups treated with paclitaxel (PAC), which was administrated (10 mg/kg/day) for 5 days by gavage/per os alone or in combination (ISO + PAC) 3 weeks after ISO treatment. Ventricular tissue was harvested 24 h later for measurements of heme oxygenase (HO-1), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), NF-κB, TNF-α and myeloperoxidase (MPO); (3) Results: HO-1 protein concentration, HO-1 activity, SOD protein concentration and total glutathione significantly decreased in response to ISO treatment. When PAC was administered in conjunction with ISO, HO-1, SOD concentration and total glutathione were not different from control levels. MPO activity, NF-κB concentration and TNF-α protein concentration were significantly increased in the ISO-only group, while the levels of these molecules were restored when PAC was co-administered; (4) Conclusions: Oral administration of PAC can maintain the expression of important antioxidants, anti-inflammatory molecules, HO-1, SOD and GSH, and suppress the production of TNF-α, MPO and NF-κB, which are involved in myocardial damage. The principal component of this cellular defense seems to be the expression of HO-1. 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 - Ráduly, Arnold AU - Sárkány, Fruzsina AU - Kovács, Máté Balázs AU - Bernát, Brigitta Renáta AU - Juhász, Béla AU - Szilvássy, Zoltán AU - Pórszász, Róbert AU - Horváth, Balázs AU - Szentandrássy, Norbert AU - Nánási, Péter Pál AU - Csanádi, Zoltán AU - Édes, István AU - Tóth, Attila AU - Papp, Zoltán AU - Priksz, Dániel AU - Borbély, Attila TI - The Novel Cardiac Myosin Activator Danicamtiv Improves Cardiac Systolic Function at the Expense of Diastolic Dysfunction In Vitro and In Vivo. Implications for Clinical Applications TS - Implications for Clinical Applications JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 1 PG - 17 SN - 1661-6596 DO - 10.3390/ijms24010446 UR - https://m2.mtmt.hu/api/publication/33547730 ID - 33547730 AB - Recent cardiotropic drug developments have focused on cardiac myofilaments. Danicamtiv, the second direct myosin activator, has achieved encouraging results in preclinical and clinical studies, thus implicating its potential applicability in the treatment of heart failure with reduced ejection fraction (HFrEF). Here, we analyzed the inotropic effects of danicamtiv in detail. To this end, changes in sarcomere length and intracellular Ca2+ levels were monitored in parallel, in enzymatically isolated canine cardiomyocytes, and detailed echocardiographic examinations were performed in anesthetized rats in the absence or presence of danicamtiv. The systolic and diastolic sarcomere lengths decreased; contraction and relaxation kinetics slowed down with increasing danicamtiv concentrations without changes in intracellular Ca2+ transients in vitro. Danicamtiv evoked remarkable increases in left ventricular ejection fraction and fractional shortening, also reflected by changes in systolic strain. Nevertheless, the systolic ejection time was significantly prolonged, the ratio of diastolic to systolic duration was reduced, and signs of diastolic dysfunction were also observed upon danicamtiv treatment in vivo. Taken together, danicamtiv improves cardiac systolic function, but it can also limit diastolic performance, especially at high drug concentrations. 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 -