TY - JOUR AU - Grandits, Thomas AU - Augustin, Christoph M AU - Haase, Gundolf AU - Jost, Norbert László AU - Mirams, Gary R AU - Niederer, Steven A AU - Plank, Gernot AU - Varró, András AU - Virág, László AU - Jung, Alexander TI - Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies JF - ELIFE J2 - ELIFE VL - 12 PY - 2024 SN - 2050-084X DO - 10.7554/eLife.91911 UR - https://m2.mtmt.hu/api/publication/34786266 ID - 34786266 N1 - Funding Agency and Grant Number: Austrian Science Fund; Austrian Science Fund (FWF); German Research Foundation (DFG); National Institutes of Health; National Research, Development and Innovation Office (NRDI); Hungarian Research Network (HUN-REN); Wellcome Trust Funding text: This research was funded by the Austrian Science Fund (FWF), the German Research Foundation (DFG), the National Institutes of Health, the National Research, Development and Innovation Office (NRDI), the Hungarian Research Network (HUN-REN), and the Wellcome Trust. For the purpose of open access, the authors have applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission. AB - Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimental data can become a significant computational burden. To mitigate the computational burden, the present study introduces a neural network (NN) that emulates the AP for given maximum conductances of selected ion channels, pumps, and exchangers. Its applicability in pharmacological studies was tested on synthetic and experimental data. The NN emulator potentially enables massive speed-ups compared to regular simulations and the forward problem (find drugged AP for pharmacological parameters defined as scaling factors of control maximum conductances) on synthetic data could be solved with average root-mean-square errors (RMSE) of 0.47 mV in normal APs and of 14.5 mV in abnormal APs exhibiting early afterdepolarizations (72.5% of the emulated APs were alining with the abnormality, and the substantial majority of the remaining APs demonstrated pronounced proximity). This demonstrates not only very fast and mostly very accurate AP emulations but also the capability of accounting for discontinuities, a major advantage over existing emulation strategies. Furthermore, the inverse problem (find pharmacological parameters for control and drugged APs through optimization) on synthetic data could be solved with high accuracy shown by a maximum RMSE of 0.22 in the estimated pharmacological parameters. However, notable mismatches were observed between pharmacological parameters estimated from experimental data and distributions obtained from the Comprehensive in vitro Proarrhythmia Assay initiative. This reveals larger inaccuracies which can be attributed particularly to the fact that small tissue preparations were studied while the emulator was trained on single cardiomyocyte data. Overall, our study highlights the potential of NN emulators as powerful tool for an increased efficiency in future quantitative systems pharmacology studies. LA - English DB - MTMT ER - TY - JOUR AU - Nemes, Attila AU - Kormányos, Árpád AU - Orosz, Andrea AU - Ambrus, Nóra AU - Várkonyi, Tamás AU - Lengyel, Csaba Attila TI - Autonomic function and specific right atrial functions - Is there a relationship? Correlations from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study JF - JOURNAL OF CLINICAL ULTRASOUND J2 - J CLIN ULTRASOUND PY - 2024 PG - 8 SN - 0091-2751 DO - 10.1002/jcu.23672 UR - https://m2.mtmt.hu/api/publication/34778284 ID - 34778284 N1 - Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Export Date: 23 April 2024 CODEN: JCULD Correspondence Address: Nemes, A.; Department of Medicine, H-6725 Szeged, emmelweis street 8, P.O. Box 427, Hungary; email: nemes.attila@med.u-szeged.hu AB - Similarly to the ventricles, the atria are under sympathetic/parasympathetic neural regulation. Accordingly, correlations were investigated between Ewing's standard cardiovascular reflex tests (SCRTs) and three-dimensional speckle-tracking echocardiography (3DSTE)-derived right atrial (RA) volumes and strains in healthy subjects.The study comprised 45 healthy adults, but 5 subjects were excluded due to inferior image quality for 3DSTE-derived RA assessments. The remaining 40 individuals being in sinus rhythm had a mean age of 35.1 ± 3.5 years (20 men). Two-dimensional, Doppler, 3DSTE and SCRTs were performed in all cases.RA maximum volume and total and passive RA stroke volumes correlated with the Valsalva ratio. Active RA stroke volume and emptying fraction showed correlations with 30/15 ratio. Peak global and mean segmental RA circumferential (CS) and longitudinal strains (LS) showed correlation with the Valsalva ratio. At atrial contraction, global RA-LS and mean segmental RA-CS showed correlations with the Valsalva ratio. Moreover, mean segmental RA-CS correlated with 30/15 ratio and mean segmental RA radial strain showed correlations with systolic blood pressure in response to standing. Autonomic neuropathy score correlated with peak global RA-LS.Autonomic function parameters have significant associations with specific RA functions in healthy adults, making the latter possible indicators of autonomic dysregulation. LA - English DB - MTMT ER - TY - JOUR AU - Mohammed, Aiman AU - Mohácsi, Gábor AU - Naveed, Muhammad AU - Prorok, János AU - Jost, Norbert László AU - Virág, László AU - Baczkó, István AU - Topal, Leila AU - Varró, András TI - Cellular electrophysiological effects of the citrus flavonoid hesperetin in dog and rabbit cardiac ventricular preparations JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 14 PY - 2024 IS - 1 PG - 10 SN - 2045-2322 DO - 10.1038/s41598-024-57828-y UR - https://m2.mtmt.hu/api/publication/34763568 ID - 34763568 N1 - Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi School of Medicine, University of Szeged, Szeged, Hungary HUN-REN-SZTE Research Group for Cardiovascular Pharmacology, Hungarian Research Network, Szeged, Hungary Export Date: 17 April 2024 Correspondence Address: Baczkó, I.; Department of Pharmacology and Pharmacotherapy, Hungary; email: baczko.istvan@med.u-szeged.hu Correspondence Address: Varró, A.; Department of Pharmacology and Pharmacotherapy, Hungary; email: varro.andras@med.u-szeged.hu AB - Recent experimental data shows that hesperetin, a citrus flavonoid, affects potassium channels and can prolong the QT c interval in humans. Therefore, in the present study we investigated the effects of hesperetin on various transmembrane ionic currents and on ventricular action potentials. Transmembrane current measurements and action potential recordings were performed by patch-clamp and the conventional microelectrode techniques in dog and rabbit ventricular preparations. At 10 µM concentration hesperetin did not, however, at 30 µM significantly decreased the amplitude of the I K1 , I to , I Kr potassium currents. Hesperetin at 3–30 µM significantly and in a concentration-dependent manner reduced the amplitude of the I Ks current. The drug significantly decreased the amplitudes of the I NaL and I CaL currents at 30 µM. Hesperetin (10 and 30 µM) did not change the action potential duration in normal preparations, however, in preparations where the repolarization reserve had been previously attenuated by 100 nM dofetilide and 1 µg/ml veratrine, caused a moderate but significant prolongation of repolarization. These results suggest that hesperetin at close to relevant concentrations inhibits the I Ks outward potassium current and thereby reduces repolarization reserve. This effect in certain specific situations may prolong the QT interval and consequently may enhance proarrhythmic risk. LA - English DB - MTMT ER - TY - JOUR AU - Ébert, Attila AU - Gál, Eleonóra AU - Tóth, Emese AU - Szögi, Titanilla AU - Hegyi, Péter AU - Venglovecz, Viktória TI - Role of CFTR in diabetes‐induced pancreatic ductal fluid and HCO 3 − secretion JF - JOURNAL OF PHYSIOLOGY-LONDON J2 - J PHYSIOL-LONDON VL - 602 PY - 2024 IS - 6 SP - 1065 EP - 1083 PG - 19 SN - 0022-3751 DO - 10.1113/JP285702 UR - https://m2.mtmt.hu/api/publication/34677129 ID - 34677129 N1 - Funding Agency and Grant Number: CF-Trust CFRD-SRC [SRC 007]; National Research, Development and Innovation Office [SNN134497]; New National Excellence Program Of The Ministry Of Human Capacities [UNKP-18-4] Funding text: We are grateful for support for this study provided by the CF-Trust CFRD-SRC Grant (No.: SRC 007) and the National Research, Development and Innovation Office (SNN134497) and New National Excellence Program Of The Ministry Of Human Capacities (UNKP-18-4 to VV). LA - English DB - MTMT ER - TY - JOUR AU - Saif-alnasr H, Mohammed AU - Mirdamadi, Seyedmohsen AU - Szűcs, Kálmán Ferenc AU - Gáspár, Róbert TI - Non-genomic actions of steroid hormones on the contractility of non-vascular smooth muscles JF - BIOCHEMICAL PHARMACOLOGY J2 - BIOCHEMIC PHARMACOL VL - 222 PY - 2024 PG - 10 SN - 0006-2952 DO - 10.1016/j.bcp.2024.116063 UR - https://m2.mtmt.hu/api/publication/34656993 ID - 34656993 N1 - Export Date: 22 March 2024 CODEN: BCPCA Correspondence Address: Gaspar, R.; Department of Pharmacology and Pharmacotherapy, Hungary; email: gaspar.robert@med.u-szeged.hu Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: Project No. TKP2021-EGA-32 was implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development, and Innovation Fund , financed under the TKP2021-EGA funding scheme. This work was also supported by the Stipendium Hungaricum Scholarship. AB - Steroid hormones play an important role in physiological processes. The classical pathway of steroid actions is mediated by nuclear receptors, which regulate genes to modify biological processes. Non-genomic pathways of steroid actions are also known, mediated by cell membrane-located seven transmembrane domain receptors. Sex steroids and glucocorticoids have several membrane receptors already identified to mediate their rapid actions. However, mineralocorticoids have no identified membrane receptors, although their rapid actions are also measurable. In non-vascular smooth muscles (bronchial, uterine, gastrointestinal, and urinary), the rapid actions of steroids are mediated through the modification of the intracellular Ca2+ level by various Ca-channels and the cAMP and IP3 system. The non-genomic action can be converted into a genomic one, suggesting that these distinct pathways may interconnect, resulting in convergence between them. Sex steroids mostly relax all the non-vascular smooth muscles, except androgens and progesterone, which contract colonic and urinary bladder smooth muscles, respectively. Corticosteroids also induce relaxation in bronchial and uterine tissues, but their actions on gastrointestinal and urinary bladder smooth muscles have not been investigated yet. Bile acids also contribute to the smooth muscle contractility. Although the therapeutic application of the rapid effects of steroid hormones and their analogues for smooth muscle contractility disorders seems remote, the actions and mechanism discovered so far are promising. Further research is needed to expand our knowledge in this field by using existing experience. One of the greatest challenges is to separate genomic and non-genomic effects, but model molecules are available to start this line of research. LA - English DB - MTMT ER - TY - JOUR AU - Nemes, Attila AU - Kormányos, Árpád AU - Orosz, Andrea AU - Ambrus, Nóra AU - Várkonyi, Tamás AU - Lengyel, Csaba Attila TI - Correlations between vegetative autonomic function and specific left atrial functions in healthy adults: Insights from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study JF - JOURNAL OF CLINICAL ULTRASOUND J2 - J CLIN ULTRASOUND VL - 52 PY - 2024 IS - 2 SP - 178 EP - 185 PG - 8 SN - 0091-2751 DO - 10.1002/jcu.23603 UR - https://m2.mtmt.hu/api/publication/34400260 ID - 34400260 N1 - Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Cited By :2 Export Date: 23 April 2024 CODEN: JCULD Correspondence Address: Nemes, A.; Department of Medicine, Semmelweis Street 8, P.O. Box 427, Hungary; email: nemes.attila@med.u-szeged.hu AB - The functioning of the left atrium (LA) is partly controlled by the neural system. It was purposed to evaluate correlations between the result of Ewing's 5 standard cardiovascular reflex tests (SCRTs) characterizing autonomic function and LA volumetric and functional features as assessed by three-dimensional speckle-tracking echocardiography (3DSTE) in healthy individuals.The current study comprised 18 healthy volunteers being in sinus rhythm (mean age: 35 ± 12 years, 10 men). Measurement of blood pressure, ECG, 5 SCRTs, two-dimensional Doppler echocardiography and 3DSTE were performed. These parameters were in normal ranges in all cases.From LA volumetric parameters, only systolic total atrial emptying fraction (r = 0.559, p = 0.037) and early diastolic passive atrial emptying fraction (r = 0.539, p = 0.047) correlated with systolic blood pressure response to standing representing sympathetic autonomic function. From LA strains, peak mean segmental LA radial strain (RS) (r = -0.532, p = 0.050), global and mean segmental LA circumferential strain (CS) (r = 0.662, p = 0.010 and r = 0.635, p = 0.015, respectively) representing systolic LA function correlated with Valsalva ratio representing parasympathetic autonomic function. Global LA-RS (r = -0.713, p = 0.040) and LA-CS (r = 0.657, p = 0.011) and mean segmental LA-CS (r = 0.723, p = 0.003) at atrial contraction representing end-diastolic atrial contraction showed correlations with Valsalva ratio, as well. Peak global and mean segmental LA-CS (r = 0.532, p = 0.050 and r = 0.530, p = 0.050) and the same strains at atrial contraction (r = 0.704, p = 0.005 and r = 0.690, p = 0.006) representing systolic function and end-diastolic atrial contraction correlated with systolic blood pressure response to standing representing both parasympathetic and sympathetic autonomic functions.Significant correlations between features of vegetative autonomic function represented by Ewing's 5 SCRTs and specific LA functions represented by 3DSTE-derived LA volume-based functional properties and strains could be demonstrated in healthy adults. LA - English DB - MTMT ER - TY - JOUR AU - Fodor, Eszter AU - Nagy, Regina Norma AU - Nógrádi, András AU - Toovey, Stephen AU - Kamal, Mohamed A. AU - Vadász, Péter AU - Bencsik, Péter AU - Görbe, Anikó AU - Ferdinandy, Péter TI - An Observational Study on the Pharmacokinetics of Oseltamivir in Lactating Influenza Patients JF - CLINICAL PHARMACOLOGY & THERAPEUTICS J2 - CLIN PHARMACOL THER VL - 115 PY - 2024 IS - 2 SP - 318 EP - 323 PG - 6 SN - 0009-9236 DO - 10.1002/cpt.3107 UR - https://m2.mtmt.hu/api/publication/34368153 ID - 34368153 AB - Influenza infection may lead to serious complications in the postpartum period, therefore, oseltamivir treatment in these patients and their breastfed infants is of great importance. However, the pharmacokinetics of oseltamivir in postpartum lactating women with acute influenza infection, and the consequent infant exposure to oseltamivir are still unknown, and these data would help in assessing risk and the need for dose adjustment in breastfed infants. LA - English DB - MTMT ER - TY - JOUR AU - Vágvölgyi, Anna AU - Nyiraty, Szabolcs AU - Máthéné, Köteless É AU - Korom, A AU - Ábrahám, Erzsébet Judit AU - Barnai, Mária AU - Szűcs, Mónika AU - Orosz, Andrea AU - Nemes, Attila AU - Baczkó, István AU - Kempler, Péter AU - Várkonyi, Tamás AU - Kósa, István AU - Lengyel, Csaba Attila TI - Három hónapos edzésprogram javítja a kardiovaszkuláris autonóm funkciót a metabolikus szindrómás páciensekben JF - MAGYAR BELORVOSI ARCHIVUM J2 - MBA VL - 76 PY - 2023 IS - 5-6 SP - 338 EP - 339 PG - 2 SN - 0133-5464 UR - https://m2.mtmt.hu/api/publication/34519512 ID - 34519512 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Baczkó, István AU - Papp, Zoltán TI - Merre tart a hazai experimentális kardiológia? JF - CARDIOLOGIA HUNGARICA J2 - CARDIOL HUNG VL - 53 PY - 2023 IS - 5 SP - 414 SN - 0133-5596 UR - https://m2.mtmt.hu/api/publication/34486449 ID - 34486449 LA - Hungarian DB - MTMT ER - TY - CHAP AU - Köteles, Dávid AU - Baccouri, Wissem AU - Tóth, Violetta AU - Gáspár, Róbert AU - Csaba, Utasi AU - Mikó, Edit ED - Denis, Kučević TI - Comparison of different thermometric instruments and their potential applications in stress and noncontact production by testing parameters of intensive breeding pigs T2 - The International Symposium on Animal Science PB - University of Novi Sad, Faculty of Agriculture CY - Novi Sad SN - 9788675205937 PY - 2023 SP - 41 UR - https://m2.mtmt.hu/api/publication/34434798 ID - 34434798 LA - English DB - MTMT ER -