TY - JOUR AU - Rumbus, Zoltán AU - Fekete, Kata AU - Kelava, Leonardo AU - Gardos, Bibor AU - Klonfar, Krisztian AU - Kéringer, Patrik AU - Pintér, Erika AU - Pákai, Eszter AU - Garami, András TI - Ammonium chloride-induced hypothermia is attenuated by transient receptor potential channel vanilloid-1, but augmented by ankyrin-1 in rodents JF - LIFE SCIENCES J2 - LIFE SCI VL - 346 PY - 2024 PG - 12 SN - 0024-3205 DO - 10.1016/j.lfs.2024.122633 UR - https://m2.mtmt.hu/api/publication/34804165 ID - 34804165 N1 - Export Date: 22 April 2024; CODEN: LIFSA AB - Systemic administration of ammonium chloride (NH4Cl), an acidifying agent used in human patients and experimental conditions, causes hypothermia in mice, however, the mechanisms of the thermoregulatory response to NH4Cl and whether it develops in other species remained unknown.We studied body temperature (Tb) changes in rats and mice induced by intraperitoneal administration of NH4Cl after blockade of transient receptor potential vanilloid-1 (TRPV1) or ankyrin-1 (TRPA1) channels.In rats, NH4Cl decreased Tb by 0.4-0.8°C (p < 0.05). The NH4Cl-induced hypothermia also developed in Trpv1 knockout (Trpv1-/-) and wild-type (Trpv1+/+) mice, however, the Tb drop was exaggerated in Trpv1-/- mice compared to Trpv1+/+ controls with maximal decreases of 4.0 vs. 2.1°C, respectively (p < 0.05). Pharmacological blockade of TRPV1 channels with AMG 517 augmented the hypothermic response to NH4Cl in genetically unmodified mice and rats (p < 0.05 for both). In contrast, when NH4Cl was infused to mice genetically lacking the TRPA1 channel, the hypothermic response was significantly attenuated compared to wild-type controls with maximal mean Tb difference of 1.0°C between the genotypes (p = 0.008). Pretreatment of rats with a TRPA1 antagonist (A967079) also attenuated the NH4Cl-induced Tb drop with a maximal difference of 0.7°C between the pretreatment groups (p = 0.003).TRPV1 channels limit, whereas TRPA1 channels exaggerate the development of NH4Cl-induced hypothermia in rats and mice, but other mechanisms are also involved. Our results warrant for regular Tb control and careful consideration of NH4Cl treatment in patients with TRPA1 and TRPV1 channel dysfunctions. LA - English DB - MTMT ER - TY - JOUR AU - Garai, János AU - Radnai, Balázs AU - Vámos, Eszter AU - Kovács, Dominika AU - Bagóné Vántus, Viola AU - Rumbus, Zoltán AU - Pákai, Eszter AU - Garami, András AU - Gulyás, Gergely AU - Agócs, Attila AU - Krekó, Marcell AU - Zaman, K. AU - Prókai, L. AU - Őrfi, László AU - Jakus, Péter AU - Lóránd, Tamás TI - Synthesis and evaluation of a new class of MIF-inhibitors in activated macrophage cells and in experimental septic shock in mice JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY J2 - EUR J MED CHEM VL - 247 PY - 2023 PG - 11 SN - 0223-5234 DO - 10.1016/j.ejmech.2022.115050 UR - https://m2.mtmt.hu/api/publication/33546311 ID - 33546311 LA - English DB - MTMT ER - TY - JOUR AU - Bálint, Alexandra AU - Hanák, Lilla AU - Hegyi, Péter AU - Szakács, Zsolt AU - Eitmann, Szimonetta AU - Garami, András AU - Varjú-Solymár, Margit AU - Márta, Katalin AU - Rumbus, Zoltán AU - Komócsi, András TI - Increased risk of adverse events in patients with low-on clopidogrel platelet reactivity after percutaneous coronary intervention : A systematic review and meta-analysis JF - CARDIOLOGY JOURNAL J2 - CARDIOL J VL - 30 PY - 2023 IS - 3 SP - 391 EP - 400 PG - 10 SN - 1897-5593 DO - 10.5603/CJ.a2021.0084 UR - https://m2.mtmt.hu/api/publication/32127261 ID - 32127261 N1 - Heart Institute, Medical School, University of Pécs, Hungary Institute for Translational Medicine, Medical School, University of Pécs, Hungary Szentágothai Research Center, University of Pécs, Hungary Department of Thermophysiology, Institute for Translational Medicine, Medical School, University of Pecs, Hungary Export Date: 12 October 2023 Correspondence Address: Bálint, A.; Heart Institute, Ifjúság útja 13, Hungary; email: balint.alexandra@pte.hu Chemicals/CAS: acetylsalicylic acid, 493-53-8, 50-78-2, 53663-74-4, 53664-49-6, 63781-77-1; clopidogrel, 113665-84-2, 120202-66-6, 90055-48-4, 94188-84-8, 120202-65-5, 120202-67-7, 894353-16-3, 744256-69-7; ticagrelor, 274693-27-5; Clopidogrel; Platelet Aggregation Inhibitors Manufacturers: R Foundation AB - Clinical evidence has been controversial regarding the influence of low platelet reactivity (LPR), ischemic and bleeding outcomes among patients receiving coronary stent implantation. Hence, the present study performed a meta-analysis to systematically evaluate the significance of LPR on adverse cardiovascular events.MEDLINE, EMBASE and CENTRAL databases were searched up to November 2020 for relevant studies including patients with acute coronary syndrome undergoing percutaneous coronary intervention. LPR was the exposed arm while the non-LPR group represented the control. The primary outcome of interest was bleeding risk including major and minor bleeding events. Secondary outcomes included all-cause mortality, repeated revascularization, nonfatal myocardial infarction, and stent thrombosis. Study-level outcomes were evaluated in random-effect models.A total of 20 studies with 19,064 patients were included. Pooled analysis showed that LPR was associated with an increased bleeding risk (relative risk [RR] 2.80, 95% confidence interval [CI] 1.95-4.02, p < 0.01). Patients with LPR had a lower risk of non-fatal myocardial infarction (RR 0.59, 95% CI 0.38-0.91, p < 0.05) and of serious vascular events (RR 0.50, 95% CI 0.30-0.84, p < 0.01).LPR is associated with an increased bleeding risk of patients who underwent coronary stent implantation. The results suggest possible benefits of this marker in risk stratification, with potential improvement in risk prediction. There are potential advantages using combinations with other factors in prediction models, however, they require further study. PROSPERO registration number: CRD42019136393). LA - English DB - MTMT ER - TY - JOUR AU - Jávor, Péter János AU - Hanák, Lilla AU - Hegyi, Péter AU - Csonka, Endre AU - Butt, Edina AU - Horváth, Tamara AU - Góg, István AU - Lukács, Anita AU - Soós, Alexandra AU - Rumbus, Zoltán AU - Pákai, Eszter AU - Toldi, János AU - Hartmann, Petra TI - Predictive value of tachycardia for mortality in trauma-related haemorrhagic shock: a systematic review and meta-regression JF - BMJ OPEN J2 - BMJ OPEN VL - 12 PY - 2022 IS - 10 PG - 8 SN - 2044-6055 DO - 10.1136/bmjopen-2021-059271 UR - https://m2.mtmt.hu/api/publication/33192543 ID - 33192543 AB - Objectives Heart rate (HR) is one of the physiological variables in the early assessment of trauma-related haemorrhagic shock, according to Advanced Trauma Life Support (ATLS). However, its efficiency as predictor of mortality is contradicted by several studies. Furthermore, the linear association between HR and the severity of shock and blood loss presented by ATLS is doubtful. This systematic review aims to update current knowledge on the role of HR in the initial haemodynamic assessment of patients who had a trauma. Design This study is a systematic review and meta-regression that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Data sources EMBASE, MEDLINE, CENTRAL and Web of Science databases were systematically searched through on 1 September 2020. Eligibility criteria Papers providing early HR and mortality data on bleeding patients who had a trauma were included. Patient cohorts were considered haemorrhagic if the inclusion criteria of the studies contained transfusion and/or positive focused assessment with sonography for trauma and/or postinjury haemodynamical instability and/or abdominal gunshot injury. Studies on burns, traumatic spinal or brain injuries were excluded. Papers published before January 2010 were not considered. Data extraction and synthesis Data extraction and risk of bias were assessed by two independent investigators. The association between HR and mortality of patients who had a trauma was assessed using meta-regression analysis. As subgroup analysis, meta-regression was performed on patients who received blood products. Results From a total of 2017 papers, 19 studies met our eligibility criteria. Our primary meta-regression did not find a significant relation (p=0.847) between HR and mortality in patients who had a trauma with haemorrhage. Our subgroup analysis included 10 studies, and it could not reveal a linear association between HR and mortality rate. Conclusions In accordance with the literature demonstrating the multiphasic response of HR to bleeding, our study presents the lack of linear association between postinjury HR and mortality. Modifying the pattern of HR derangements in the ATLS shock classification may result in a more precise teaching tool for young clinicians. LA - English DB - MTMT ER - TY - JOUR AU - Lőrincz, Aba Tamás AU - Váradi, Alex AU - Hegyi, Péter AU - Rumbus, Zoltán AU - Tuba, Máté AU - Lamberti, Anna Gabriella AU - Varjú-Solymár, Margit AU - Párniczky, Andrea AU - Erőss, Bálint Mihály AU - Garami, András AU - Józsa, Gergő TI - Paediatric Partial-Thickness Burn Therapy: A Meta-Analysis and Systematic Review of Randomised Controlled Trials JF - LIFE-BASEL J2 - LIFE-BASEL VL - 12 PY - 2022 IS - 5 PG - 24 SN - 2075-1729 DO - 10.3390/life12050619 UR - https://m2.mtmt.hu/api/publication/32823871 ID - 32823871 LA - English DB - MTMT ER - TY - JOUR AU - Ruzsics, István AU - Mátrai, Péter AU - Hegyi, Péter AU - Németh, Dávid AU - Tenk, Judit AU - Csenkey, Alexandra AU - Erőss, Bálint Mihály AU - Varga, Gábor AU - Balaskó, Márta AU - Pétervári, Erika AU - Veres, Gábor AU - Sepp, Róbert AU - Rakonczay, Zoltán AU - Vincze, Áron AU - Garami, András AU - Rumbus, Zoltán TI - Noninvasive ventilation improves the outcome in patients with pneumonia-associated respiratory failure: Systematic review and meta-analysis JF - JOURNAL OF INFECTION AND PUBLIC HEALTH J2 - J INFECT PUBLIC HEALTH VL - 15 PY - 2022 IS - 3 SP - 349 EP - 359 PG - 11 SN - 1876-0341 DO - 10.1016/j.jiph.2022.02.004 UR - https://m2.mtmt.hu/api/publication/32692193 ID - 32692193 AB - Background Noninvasive ventilation (NIV) is beneficial in exacerbations of chronic obstructive pulmonary disease (COPD), but its effectiveness in pneumonia-associated respiratory failure is still controversial. In the current meta-analysis, we aimed to investigate whether the use of NIV before intubation in pneumonia improves the mortality and intubation rates of respiratory failure as compared to no use of NIV in adults. Methods We searched three databases from inception to December 2019. We included studies, in which pneumonia patients were randomized initially into either NIV-treated or non-NIV-treated groups. Five full-text publications, including 121 patients, reported eligible data for statistical analysis. Results With NIV the overall hospital mortality rate seemed lower in patients with pneumonia-associated respiratory failure, but this was not significant [odds ratio (OR) = 0.39; 95% confidence interval (CI): 0.13–1.14; P = 0.085]. In the intensive care unit, the mortality was significantly lower when NIV was applied compared to no NIV treatment (OR = 0.22; 95% CI: 0.07–0.75; P = 0.015). NIV also decreased mortality compared to no NIV in patient groups, which did not exclude patients with COPD (OR = 0.25; 95% CI: 0.08–0.74; P = 0.013). The need for intubation was significantly reduced in NIV-treated patients (OR = 0.22; 95% CI: 0.09–0.53; P = 0.001), which effect was more prominent in pneumonia patient groups not excluding patients with pre-existing COPD (OR = 0.13; 95% CI: 0.03–0.46; P = 0.002). Conclusion NIV markedly decreases the death rate in the intensive care unit and reduces the need for intubation in patients with pneumonia-associated respiratory failure. The beneficial effects of NIV seem more pronounced in populations that include patients with COPD. Our findings suggest that NIV should be considered in the therapeutic guidelines of pneumonia, given that future clinical trials confirm the results of our meta-analysis. Availability of data and materials All data and materials generated during the current study are available from the corresponding author on reasonable request. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Dóra Krisztina AU - Gede, Noémi AU - Szabó, László AU - Hegyi, Péter AU - Szakács, Zsolt AU - Faludi, Béla AU - Sebők, Ágnes AU - Garami, András AU - Varjú-Solymár, Margit AU - Kósa, Dániel AU - Hanák, Lilla AU - Rumbus, Zoltán AU - Balaskó, Márta TI - Weight reduction added to CPAP decreases blood pressure and triglyceride level in OSA : systematic review and meta-analysis JF - CTS-CLINICAL AND TRANSLATIONAL SCIENCE J2 - CTS-CLIN TRANSL SCI VL - 15 PY - 2022 IS - 5 SP - 1238 EP - 1248 PG - 11 SN - 1752-8054 DO - 10.1111/cts.13241 UR - https://m2.mtmt.hu/api/publication/32654314 ID - 32654314 AB - Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension and high cardiovascular risk. Continuous positive airway pressure (CPAP) fails to reduce cardiovascular risks consistently. Obesity and OSA show reciprocal association and they synergistically increase hypertension via different pathways. Our meta-analysis aimed to assess the cardiovascular benefits of combining weight reduction (WL) with CPAP (versus WL or CPAP alone) in OSA. Outcomes included systolic and diastolic blood pressure (BP) and blood lipid parameters. We explored Medline, Embase, Cochrane and Scopus. Eight randomized controlled studies (2627 patients) were included. The combined therapy decreased systolic BP more than CPAP alone. Weighted mean difference (WMD) for CPAP+WL vs. CPAP was -8.89 mmHg, 95%confidence interval (95%CI)[-13.67; -4.10], p<0.001 for systolic BP. For diastolic BP this decrease was not significant. In case of blood lipids, the combined treatment decreased triglyceride levels more than CPAP alone (WMD= -0.31, 95%CI [-0.58; -0.04] p =0.027). On the other hand, addition of CPAP to WL failed to suppress BP further. The certainty of evidence according to GRADE was very low to moderate. In conclusion, our results showed that the addition of WL to CPAP significantly improved BP and blood lipid values in OSA. On the other hand, the addition of CPAP to WL could not significantly improve BP or blood lipid values. Review protocol: PROSPERO CRD42019138998. LA - English DB - MTMT ER - TY - JOUR AU - Kéringer, Patrik AU - Füredi, Nóra AU - Gaszner, Balázs AU - Mikó, Alexandra AU - Pákai, Eszter AU - Fekete, Kata AU - Pótóné Oláh, Emőke AU - Kelava, Leonardo AU - Romanovsky, Andrej A AU - Rumbus, Zoltán AU - Garami, András TI - The hyperthermic effect of central cholecystokinin is mediated by the cyclooxygenase-2 pathway JF - AMERICAN JOURNAL OF PHYSIOLOGY: ENDOCRINOLOGY AND METABOLISM J2 - AM J PHYSIOL ENDOC M VL - 322 PY - 2022 IS - 1 SP - E10 EP - E23 PG - 14 SN - 0193-1849 DO - 10.1152/ajpendo.00223.2021 UR - https://m2.mtmt.hu/api/publication/32501308 ID - 32501308 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office [FK 138722]; Medical School, University of Pecs [KA-2019-27]; New National Excellence Program of the Hungarian Ministry for Innovation and Technology [UNKP-20-4-II-PTE-547, UNKP-21-3-IIPTE-1317]; Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary [20765-3/2018/FEKUTSTRAT]; European Union; European Social Fund [EFOP-3.6.1-16-2016-00004]; National Research, Development and Innovation Fund of Hungary [2020-4.1.1-TKP2020, TKP2020-IKA-08, NAP 2017-1.2.1-NKP-2017-00002, GINOP-2.3.2-15-2016-00050, MTA-TKI14016, EFOP-3.6.3-VEKOP-16-2017-00009, EFOP3.6.2-16-2017-00008] Funding text: This work was supported by the National Research, Development and Innovation Office Grant FK 138722 (to A.G.), the Medical School, University of Pecs Grant KA-2019-27 (to A.G.), the New National Excellence Program of the Hungarian Ministry for Innovation and Technology Grants UNKP-20-4-II-PTE-547 (to N.F.) and UNKP-21-3-IIPTE-1317 (to Z.R.), the Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary Grant 20765-3/2018/FEKUTSTRAT (to A.G.), and the European Union, cofinanced by the European Social Fund EFOP-3.6.1-16-2016-00004 (to B.G. and A.G.). B.G. was funded by the National Research, Development and Innovation Fund of Hungary, financed under the 2020-4.1.1-TKP2020 funding scheme (Project No: TKP2020-IKA-08); NAP 2017-1.2.1-NKP-2017-00002; GINOP-2.3.2-15-2016-00050; MTA-TKI14016; EFOP-3.6.3-VEKOP-16-2017-00009; and EFOP3.6.2-16-2017-00008. LA - English DB - MTMT ER - TY - JOUR AU - Kelava, Leonardo AU - Németh, Dávid AU - Hegyi, Péter AU - Kéringer, Patrik AU - Kovács, Dóra Krisztina AU - Balaskó, Márta AU - Varjú-Solymár, Margit AU - Pákai, Eszter AU - Rumbus, Zoltán AU - Garami, András TI - Dietary supplementation of transient receptor potential vanilloid-1 channel agonists reduces serum total cholesterol level : a meta-analysis of controlled human trials JF - CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION J2 - CRIT REV FOOD SCI VL - 62 PY - 2022 IS - 25 SP - 7025 EP - 7035 PG - 11 SN - 1040-8398 DO - 10.1080/10408398.2021.1910138 UR - https://m2.mtmt.hu/api/publication/31963955 ID - 31963955 AB - Abnormal cholesterol level is a major risk factor in the development of atherosclerosis, which is a fundamental derangement in cardiovascular diseases. Any efforts should be undertaken to lower blood cholesterol levels. Among dietary interventions, capsaicinoid supplementation is also considered as a novel cholesterol-lowering approach, but human studies concluded contradictory results about its effectiveness. The present meta-analysis aimed at determining the effects of capsaicinoids on serum lipid profile in humans. We searched the PubMed, EMBASE, and CENTRAL databases from inception to February 2021. We included 10 controlled studies, which involved 398 participants. We found that dietary capsaicinoid supplementation alone or in combination with other substances significantly (p = 0.004 and 0.001, respectively) reduced serum total cholesterol level compared to controls with an overall standardized mean difference of -0.52 (95% confidence interval: -0.83, -0.21). Capsaicinoids also decreased low-density lipoprotein level significantly (p = 0.035), whereas no effect was observed on serum levels of high-density lipoprotein and triglycerides. Our findings provide novel quantitative evidence for the efficacy of dietary capsaicin supplementation in lowering serum total cholesterol and low-density lipoprotein levels in humans. To validate our conclusion, further randomized controlled trials in a diverse population of adult humans receiving dietary capsaicinoid supplementation are warranted. LA - English DB - MTMT ER - TY - JOUR AU - Pótóné Oláh, Emőke AU - Rumbus, Zoltán AU - Kormos, Viktória AU - Tékus, Valéria AU - Pákai, Eszter AU - Wilson, Hannah V. AU - Fekete, Kata AU - Varjú-Solymár, Margit AU - Kelava, Leonardo AU - Kéringer, Patrik AU - Gaszner, Balázs AU - Whiteman, Matthew AU - Keeble, Julie AU - Pintér, Erika AU - Garami, András TI - The Hypothermic Effect of Hydrogen Sulfide Is Mediated by the Transient Receptor Potential Ankyrin-1 Channel in Mice JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 14 PY - 2021 IS - 10 PG - 20 SN - 1424-8247 DO - 10.3390/ph14100992 UR - https://m2.mtmt.hu/api/publication/32266649 ID - 32266649 N1 - * Megosztott szerzőség AB - Hydrogen sulfide (H2S) has been shown in previous studies to cause hypothermia and hypometabolism in mice, and its thermoregulatory effects were subsequently investigated. However, the molecular target through which H2S triggers its effects on deep body temperature has remained unknown. We investigated the thermoregulatory response to fast-(Na2S) and slow-releasing (GYY4137) H2S donors in C57BL/6 mice, and then tested whether their effects depend on the transient receptor potential ankyrin-1 (TRPA1) channel in Trpa1 knockout (Trpa1−/−) and wild-type (Trpa1+/+) mice. Intracerebroventricular administration of Na2S (0.5–1 mg/kg) caused hypothermia in C57BL/6 mice, which was mediated by cutaneous vasodilation and decreased thermogenesis. In contrast, intraperitoneal administration of Na2S (5 mg/kg) did not cause any thermoregulatory effect. Central administration of GYY4137 (3 mg/kg) also caused hypothermia and hypometabolism. The hypothermic response to both H2S donors was significantly (p < 0.001) attenuated in Trpa1−/− mice compared to their Trpa1+/+ littermates. Trpa1 mRNA transcripts could be detected with RNAscope in hypothalamic and other brain neurons within the autonomic thermoeffector pathways. In conclusion, slow- and fast-releasing H2S donors induce hypothermia through hypometabolism and cutaneous vasodilation in mice that is mediated by TRPA1 channels located in the brain, presumably in hypothalamic neurons within the autonomic thermoeffector pathways. LA - English DB - MTMT ER -