339 results on '"Pollesello, P."'
Search Results
2. The Catechol O-Methyltransferase Inhibitor Entacapone in the Treatment of Parkinson’s Disease: Personal Reflections on a First-in-Class Drug Development Programme 40 Years On
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Pekka T. Männistö, Tapani Keränen, Kari J. Reinikainen, Anna Hanttu, and Piero Pollesello
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Catechol O-methyltransferase inhibition ,Entacapone ,Nitecapone ,Tolcapone ,Opicapone ,Levodopa ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract In the 1980s, Orion Pharma, then a mid-ranking Nordic area pharmaceutical company, established a drug development programme on the inhibition of catechol O-methyltransferase (COMT). This enzyme, which plays an important role in the inactivation of catecholamine neurotransmitters and drugs with a catechol structure, thus came under consideration as a target in the innovative translational and clinical programme we describe in this historical review. The starting point was the conjecture that a peripherally acting COMT inhibitor might improve entry of levodopa into the brain. This had potentially significant implications for the medical treatment of Parkinson’s disease (PD). The rationale was that more efficient delivery of levodopa to the brain might allow the high therapeutic doses of levodopa to be reduced and the dose interval to be extended. Elucidation of structure–activity relations paved the way for the discovery and development of entacapone, a 5-nitrocatechol that was a potent and highly specific inhibitor of COMT. Experience in phase III clinical trials established that entacapone, used as an adjunct to regular or controlled-release levodopa preparations (also including a peripherally acting dopa-decarboxylase inhibitor), increased ON-time and reduced OFF-time and improved clinical condition in patients with PD experiencing wearing-off, often with a reduced daily levodopa dose. Several of these studies also identified that entacapone improved patients’ quality of life and was cost-effective. Subsequently, entacapone has been amalgamated into a triple-combination preparation (Stalevo®) with levodopa and carbidopa to create a flexible and convenient drug therapy for patients with PD who have end-of-dose motor fluctuations not stabilised on levodopa/dopa-decarboxylase inhibitor treatment. This review offers a historical perspective on a successful programme of drug development by researchers who played central roles in the progress from exploratory hypothesis to registered pharmaceutical product.
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- 2024
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3. Integrating an artificial intelligence chatbot in scientific communication: Do’s and don’ts
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Piero Pollesello and Zoltán Papp
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Artificial intelligence ,editing ,scientific commu ,Academies and learned societies ,AS1-945 ,Bibliography. Library science. Information resources - Abstract
The art of narrative and storytelling in scientific prose is now considered as an integral part of any well-rounded scientific communication process. Hence, when the AI-driven ChatGPT facility was made available online many scientists wanted to assess this new marvel. Over the course of several months, we explored its functionalities and opportunities in the field of scientific publication and collected both positive and negative experiences.Among the latter, the most compelling example was asking ChatGPT for scientific references. In this short communication we describe dialogs in which we sought to steer the AI towards fact-based assertions while it continued to produce false citations of papers, abstracts, communication to non-existing congresses, etc.Through exchanges on the forum of the open AI platform we realized that other scientists have encountered the same problem, even when searching for patents and industrial property rights.Our recommendation is that the AI of ChatGPT would be instructed on the role and uniqueness of scientific paper citations. Moreover, relevant agencies should plan for creating and adopting policies to rule out inappropriate behaviors by AI in fields in which errors could cost (at least) loss of trust in science by the general population.
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- 2023
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4. Use of Levosimendan in Patients with Pulmonary Hypertension: What is the Current Evidence?
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Masarone, Daniele, Kittleson, Michelle, Pollesello, Piero, Tedford, Ryan J., and Pacileo, Giuseppe
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- 2023
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5. Recognizing early signs in the translational phase is essential for drug development in cardiovascular medicine
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Zoltán Papp, Piero Pollesello, and Attila Borbély
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2023
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6. Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety
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Girardis, M., Bettex, D., Bojan, M., Demponeras, C., Fruhwald, S., Gál, J., Groesdonk, H. V., Guarracino, F., Guerrero-Orriach, J. L., Heringlake, M., Herpain, A., Heunks, L., Jin, J., Kindgen-Milles, D., Mauriat, P., Michels, G., Psallida, V., Rich, S., Ricksten, S-E, Rudiger, A., Siegemund, M., Toller, W., Treskatsch, S., Župan, Ž., and Pollesello, P.
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- 2022
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7. Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety
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M. Girardis, D. Bettex, M. Bojan, C. Demponeras, S. Fruhwald, J. Gál, H. V. Groesdonk, F. Guarracino, J. L. Guerrero-Orriach, M. Heringlake, A. Herpain, L. Heunks, J. Jin, D. Kindgen-Milles, P. Mauriat, G. Michels, V. Psallida, S. Rich, S-E Ricksten, A. Rudiger, M. Siegemund, W. Toller, S. Treskatsch, Ž. Župan, and P. Pollesello
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Intensive care unit ,Emergency medicine ,Acute cardiac care ,Haemodynamic ,Inotrope ,Inodilator ,Anesthesiology ,RD78.3-87.3 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a “should be considered” recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure.
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- 2022
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8. Complex electrophysiological remodeling in postinfarction ischemic heart failure
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Hegyi, Bence, Bossuyt, Julie, Griffiths, Leigh G, Shimkunas, Rafael, Coulibaly, Zana, Jian, Zhong, Grimsrud, Kristin N, Sondergaard, Claus S, Ginsburg, Kenneth S, Chiamvimonvat, Nipavan, Belardinelli, Luiz, Varró, András, Papp, Julius G, Pollesello, Piero, Levijoki, Jouko, Izu, Leighton T, Boyd, W Douglas, Bányász, Tamás, Bers, Donald M, and Chen-Izu, Ye
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Medical Physiology ,Biomedical and Clinical Sciences ,Heart Disease ,Cardiovascular ,Heart Disease - Coronary Heart Disease ,Action Potentials ,Animals ,Arrhythmias ,Cardiac ,Calcium ,Cells ,Cultured ,Electrophysiological Phenomena ,Heart Failure ,Myocardial Infarction ,Myocytes ,Cardiac ,Swine ,ischemic heart failure ,myocardial infarction ,electrophysiology ,action potential ,ionic currents - Abstract
Heart failure (HF) following myocardial infarction (MI) is associated with high incidence of cardiac arrhythmias. Development of therapeutic strategy requires detailed understanding of electrophysiological remodeling. However, changes of ionic currents in ischemic HF remain incompletely understood, especially in translational large-animal models. Here, we systematically measure the major ionic currents in ventricular myocytes from the infarct border and remote zones in a porcine model of post-MI HF. We recorded eight ionic currents during the cell's action potential (AP) under physiologically relevant conditions using selfAP-clamp sequential dissection. Compared with healthy controls, HF-remote zone myocytes exhibited increased late Na+ current, Ca2+-activated K+ current, Ca2+-activated Cl- current, decreased rapid delayed rectifier K+ current, and altered Na+/Ca2+ exchange current profile. In HF-border zone myocytes, the above changes also occurred but with additional decrease of L-type Ca2+ current, decrease of inward rectifier K+ current, and Ca2+ release-dependent delayed after-depolarizations. Our data reveal that the changes in any individual current are relatively small, but the integrated impacts shift the balance between the inward and outward currents to shorten AP in the border zone but prolong AP in the remote zone. This differential remodeling in post-MI HF increases the inhomogeneity of AP repolarization, which may enhance the arrhythmogenic substrate. Our comprehensive findings provide a mechanistic framework for understanding why single-channel blockers may fail to suppress arrhythmias, and highlight the need to consider the rich tableau and integration of many ionic currents in designing therapeutic strategies for treating arrhythmias in HF.
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- 2018
9. Levosimendan‐induced venodilation is mediated by opening of potassium channels
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Daniel Burkhoff, Stuart Rich, Piero Pollesello, and Zoltán Papp
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Pulmonary hypertension ,Heart failure with preserved ejection fraction ,Therapy ,Venodilation ,Pharmacology ,Levosimendan ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Unique vascular responses adhere to the cardiovascular efficacy of the inodilator levosimendan. In particular, selective venodilation appears to explain its clinical benefit during pulmonary hypertension complicated by heart failure with preserved ejection fraction. Vasodilators increase vessel diameter in various parts of the vascular system to different degrees and thereby influence blood pressure, its distribution, and organ perfusion depending on their mechanisms of action. Levosimendan and its long‐lived active metabolite OR‐1896 mobilize a set of vasodilatory mechanisms, that is, the opening of the ATP‐sensitive K+ channels and other K+ channels on top of a highly selective inhibition of the phosphodiesterase III enzyme. A vessel‐specific combination of the above vasodilator mechanisms—in concert with cardiac effects and cardiovascular reflex regulations—illustrates the pharmacological profile of levosimendan in various cardiovascular disorders. While levosimendan has been known to be an inotrope, its properties as an activator of ATP‐sensitive K+ channels have gone largely ignored with respect to clinical applications. Here, we provide a summary of what is known about the ATP‐sensitive K+ channel properties in preclinical studies and now for the first time, its ATP‐sensitive K+ channel properties in a clinical trial.
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- 2021
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10. Levosimendan in Europe and China: An Appraisal of Evidence and Context
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Xiangqing Kong, Xinqun Hu, Baotong Hua, Francesco Fedele, Dimitrios Farmakis, and Piero Pollesello
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The calcium sensitiser levosimendan (SIMDAX; Orion Pharma) has been in clinical use for the management of acute heart failure and a range of related syndromes in many countries around the world for two decades. More recently, levosimendan has become available in China. The authors have examined the profile of levosimendan in clinical trials conducted inside and outside China and grouped the findings under six headings: effects on haemodynamics, effects on natriuretic peptides, effect on symptoms of heart failure, renal effects, effect on survival, and safety profile. Their conclusions are that under each of these headings there are reasonable grounds to expect that the effects and clinical benefits established in trials and with wider clinical use in Europe and elsewhere will accrue also to Chinese patients. Therefore, the authors are confident that global experience with levosimendan provides a reliable guide to its optimal use and likely therapeutic effects in patients in China.
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- 2021
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11. Haemodynamic Balance in Acute and Advanced Heart Failure: An Expert Perspective on the Role of Levosimendan
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Piergiuseppe Agostoni, Dimitrios T Farmakis, Jose M García-Pinilla, Veli-Pekka Harjola, Kristjan Karason, Dirk von Lewinski, John Parissis, Piero Pollesello, Gerhard Pölzl, Alejandro Recio-Mayoral, Alexander Reinecke, Patrik Yerly, and Endre Zima
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Acute and advanced heart failure are associated with substantial adverse short- and longer-term prognosis. Both conditions necessitate complex treatment choices to restore haemodynamic stability and organ perfusion, relieve congestion, improve symptoms and allow the patient to leave the hospital and achieve an adequate quality of life. Among the available intravenous vasoactive therapies, inotropes constitute an option when an increase in cardiac contractility is needed to reverse a low output state. Within the inotrope category, levosimendan is well suited to the needs of both sets of patients since, in contrast to conventional adrenergic inotropes, it has not been linked in clinical trials or wider clinical usage with increased mortality risk and retains its efficacy in the presence of beta-adrenergic receptor blockade; it is further believed to possess beneficial renal effects. The overall haemodynamic profile and clinical tolerability of levosimendan, combined with its extended duration of action, have encouraged its intermittent use in patients with advanced heart failure. This paper summarises the key messages derived from a series of 12 tutorials held at the Heart Failure 2019 congress organised in Athens, Greece, by the Heart Failure Association of the European Society of Cardiology.
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- 2019
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12. Levosimendan in Acute and Advanced Heart Failure: an Expert Perspective on Posology and Therapeutic Application
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Bouchez, S., Fedele, F., Giannakoulas, G., Gustafsson, F., Harjola, V.-P., Karason, K., Kivikko, M., von Lewinski, D., Oliva, F., Papp, Z., Parissis, J., Pollesello, Piero, Pölzl, G., and Tschöpe, C.
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- 2018
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13. Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use
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Zoltán Papp, Piergiuseppe Agostoni, Julian Alvarez, Dominique Bettex, Stefan Bouchez, Dulce Brito, Vladimir Černý, Josep Comin-Colet, Marisa G Crespo-Leiro, Juan F Delgado, Istvan Édes, Alexander A Eremenko, Dimitrios Farmakis, Francesco Fedele, Cândida Fonseca, Sonja Fruhwald, Massimo Girardis, Fabio Guarracino, Veli-Pekka Harjola, Matthias Heringlake, Antoine Herpain, Leo MA Heunks, Tryggve Husebye, Višnja Ivancan, Kristjan Karason, Sundeep Kaul, Matti Kivikko, Janek Kubica, Josep Masip, Simon Matskeplishvili, Alexandre Mebazaa, Markku S Nieminen, Fabrizio Oliva, Julius-Gyula Papp, John Parissis, Alexander Parkhomenko, Pentti Põder, Gerhard Pölzl, Alexander Reinecke, Sven-Erik Ricksten, Hynek Riha, Alain Rudiger, Toni Sarapohja, Robert HG Schwinger, Wolfgang Toller, Luigi Tritapepe, Carsten Tschöpe, Gerhard Wikström, Dirk von Lewinski, Bojan Vrtovec, and Piero Pollesello
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2020
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14. Novel Na+/Ca2+ Exchanger Inhibitor ORM-10962 Supports Coupled Function of Funny-Current and Na+/Ca2+ Exchanger in Pacemaking of Rabbit Sinus Node Tissue
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Zsófia Kohajda, Noémi Tóth, Jozefina Szlovák, Axel Loewe, Gergő Bitay, Péter Gazdag, János Prorok, Norbert Jost, Jouko Levijoki, Piero Pollesello, Julius Gy. Papp, András Varró, and Norbert Nagy
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Na+/Ca2+ exchanger ,funny-current ,ORM-10962 ,pacemaking ,sinus-node ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background and PurposeThe exact mechanism of spontaneous pacemaking is not fully understood. Recent results suggest tight cooperation between intracellular Ca2+ handling and sarcolemmal ion channels. An important player of this crosstalk is the Na+/Ca2+ exchanger (NCX), however, direct pharmacological evidence was unavailable so far because of the lack of a selective inhibitor. We investigated the role of the NCX current in pacemaking and analyzed the functional consequences of the If-NCX coupling by applying the novel selective NCX inhibitor ORM-10962 on the sinus node (SAN).Experimental ApproachCurrents were measured by patch-clamp, Ca2+-transients were monitored by fluorescent optical method in rabbit SAN cells. Action potentials (AP) were recorded from rabbit SAN tissue preparations. Mechanistic computational data were obtained using the Yaniv et al. SAN model.Key ResultsORM-10962 (ORM) marginally reduced the SAN pacemaking cycle length with a marked increase in the diastolic Ca2+ level as well as the transient amplitude. The bradycardic effect of NCX inhibition was augmented when the funny-current (If) was previously inhibited and vice versa, the effect of If was augmented when the Ca2+ handling was suppressed.Conclusion and ImplicationsWe confirmed the contribution of the NCX current to cardiac pacemaking using a novel NCX inhibitor. Our experimental and modeling data support a close cooperation between If and NCX providing an important functional consequence: these currents together establish a strong depolarization capacity providing important safety factor for stable pacemaking. Thus, after individual inhibition of If or NCX, excessive bradycardia or instability cannot be expected because each of these currents may compensate for the reduction of the other providing safe and rhythmic SAN pacemaking.
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- 2020
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15. Levosimendan meta-analyses: Is there a pattern in the effect on mortality?
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Pollesello, P., Parissis, J., Kivikko, M., and Harjola, V.-P.
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- 2016
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16. Calcium sensitizers: What have we learned over the last 25 years?
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Pollesello, P., Papp, Z., and Papp, J.Gy.
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- 2016
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17. Pharmaco-economics of levosimendan in cardiology: A European perspective
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Nieminen, M.S., Buerke, M., Parissis, J., Ben-Gal, T., Pollesello, P., Kivikko, M., Karavidas, A., Severino, P., Comín-Colet, J., Wikström, G., and Fedele, F.
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- 2015
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18. Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion
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Toller, W., Heringlake, M., Guarracino, F., Algotsson, L., Alvarez, J., Argyriadou, H., Ben-Gal, T., Černý, V., Cholley, B., Eremenko, A., Guerrero-Orriach, J.L., Järvelä, K., Karanovic, N., Kivikko, M., Lahtinen, P., Lomivorotov, V., Mehta, R.H., Mušič, Š., Pollesello, P., Rex, S., Riha, H., Rudiger, A., Salmenperä, M., Szudi, L., Tritapepe, L., Wyncoll, D., and Öwall, A.
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- 2015
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19. Repetitive use of levosimendan for treatment of chronic advanced heart failure: Clinical evidence, practical considerations, and perspectives: An expert panel consensus
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Nieminen, M.S., Altenberger, J., Ben-Gal, T., Böhmer, A., Comin-Colet, J., Dickstein, K., Édes, I., Fedele, F., Fonseca, C., García-González, M.J., Giannakoulas, G., Iakobishvili, Z., Jääskeläinen, P., Karavidas, A., Kettner, J., Kivikko, M., Lund, L.H., Matskeplishvili, S.T., Metra, M., Morandi, F., Oliva, F., Parkhomenko, A., Parissis, J., Pollesello, P., Pölzl, G., Schwinger, R.H.G., Segovia, J., Seidel, M., Vrtovec, B., and Wikström, G.
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- 2014
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20. The Effect of a Novel Highly Selective Inhibitor of the Sodium/Calcium Exchanger (NCX) on Cardiac Arrhythmias in In Vitro and In Vivo Experiments.
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Zsófia Kohajda, Nikolett Farkas-Morvay, Norbert Jost, Norbert Nagy, Amir Geramipour, András Horváth, Richárd S Varga, Tibor Hornyik, Claudia Corici, Károly Acsai, Balázs Horváth, János Prorok, Balázs Ördög, Szilvia Déri, Dániel Tóth, Jouko Levijoki, Piero Pollesello, Tuula Koskelainen, Leena Otsomaa, András Tóth, István Baczkó, István Leprán, Péter P Nánási, Julius Gy Papp, András Varró, and László Virág
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Medicine ,Science - Abstract
In this study the effects of a new, highly selective sodium-calcium exchanger (NCX) inhibitor, ORM-10962 were investigated on cardiac NCX current, Ca2+ transients, cell shortening and in experimental arrhythmias. The level of selectivity of the novel inhibitor on several major transmembrane ion currents (L-type Ca2+ current, major repolarizing K+ currents, late Na+ current, Na+/K+ pump current) was also determined.Ion currents in single dog ventricular cells (cardiac myocytes; CM), and action potentials in dog cardiac multicellular preparations were recorded utilizing the whole-cell patch clamp and standard microelectrode techniques, respectively. Ca2+ transients and cell shortening were measured in fluorescent dye loaded isolated dog myocytes. Antiarrhythmic effects of ORM-10962 were studied in anesthetized ouabain (10 μg/kg/min i.v.) pretreated guinea pigs and in ischemia-reperfusion models (I/R) of anesthetized coronary artery occluded rats and Langendorff perfused guinea pigs hearts.ORM-10962 significantly reduced the inward/outward NCX currents with estimated EC50 values of 55/67 nM, respectively. The compound, even at a high concentration of 1 μM, did not modify significantly the magnitude of ICaL in CMs, neither had any apparent influence on the inward rectifier, transient outward, the rapid and slow components of the delayed rectifier potassium currents, the late and peak sodium and Na+/K+ pump currents. NCX inhibition exerted moderate positive inotropic effect under normal condition, negative inotropy when reverse, and further positive inotropic effect when forward mode was facilitated. In dog Purkinje fibres 1 μM ORM-10962 decreased the amplitude of digoxin induced delayed afterdepolarizations (DADs). Pre-treatment with 0.3 mg/kg ORM-10962 (i.v.) 10 min before starting ouabain infusion significantly delayed the development and recurrence of ventricular extrasystoles (by about 50%) or ventricular tachycardia (by about 30%) in anesthetized guinea pigs. On the contrary, ORM-10962 pre-treatment had no apparent influence on the time of onset or the severity of I/R induced arrhythmias in anesthetized rats and in Langendorff perfused guinea-pig hearts.The present study provides strong evidence for a high efficacy and selectivity of the NCX-inhibitory effect of ORM-10962. Selective NCX inhibition can exert positive as well as negative inotropic effect depending on the actual operation mode of NCX. Selective NCX blockade may contribute to the prevention of DAD based arrhythmogenesis, in vivo, however, its effect on I/R induced arrhythmias is still uncertain.
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- 2016
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21. Na+/Ca2+ Exchanger (NCX) inhibition with ORM 11035 improves cardiac function and remodeling without lowering blood pressure in a model of heart failure with preserved ejection fraction: 163
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Primessnig, U, Bracic, T, Pollesello, P, Pieske, B, and Heinzel, F R
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- 2016
22. ORM-3819 promotes cardiac contractility on a dual mechanism of action: troponin-C dependent calcium sensitization is supported by selective PDE III inhibition: 19
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Nagy, L, Bodi, B, Pollesello, P, Vegh, A, Sorsa, T, Levijoki, J, Toth, A, Edes, I, Papp, J GY, and Papp, Z
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- 2016
23. Levosimendan inhibits peroxidation in hepatocytes by modulating apoptosis/autophagy interplay.
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Elena Grossini, Kevin Bellofatto, Serena Farruggio, Lorenzo Sigaudo, Patrizia Marotta, Giulia Raina, Veronica De Giuli, David Mary, Piero Pollesello, Rosalba Minisini, Mario Pirisi, and Giovanni Vacca
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Medicine ,Science - Abstract
BACKGROUND:Levosimendan protects rat liver against peroxidative injuries through mechanisms related to nitric oxide (NO) production and mitochondrial ATP-dependent K (mitoKATP) channels opening. However, whether levosimendan could modulate the cross-talk between apoptosis and autophagy in the liver is still a matter of debate. Thus, the aim of this study was to examine the role of levosimendan as a modulator of the apoptosis/autophagy interplay in liver cells subjected to peroxidation and the related involvement of NO and mitoKATP. METHODS AND FINDINGS:In primary rat hepatocytes that have been subjected to oxidative stress, Western blot was performed to examine endothelial and inducible NO synthase isoforms (eNOS, iNOS) activation, apoptosis/autophagy and survival signalling detection in response to levosimendan. In addition, NO release, cell viability, mitochondrial membrane potential and mitochondrial permeability transition pore opening (MPTP) were examined through specific dyes. Some of those evaluations were also performed in human hepatic stellate cells (HSC). Pre-treatment of hepatocytes with levosimendan dose-dependently counteracted the injuries caused by oxidative stress and reduced NO release by modulating eNOS/iNOS activation. In hepatocytes, while the autophagic inhibition reduced the effects of levosimendan, after the pan-caspases inhibition, cell survival and autophagy in response to levosimendan were increased. Finally, all protective effects were prevented by both mitoKATP channels inhibition and NOS blocking. In HSC, levosimendan was able to modulate the oxidative balance and inhibit autophagy without improving cell viability and apoptosis. CONCLUSIONS:Levosimendan protects hepatocytes against oxidative injuries by autophagic-dependent inhibition of apoptosis and the activation of survival signalling. Such effects would involve mitoKATP channels opening and the modulation of NO release by the different NOS isoforms. In HSC, levosimendan would also play a role in cell activation and possible evolution toward fibrosis. These findings highlight the potential of levosimendan as a therapeutic agent for the treatment or prevention of liver ischemia/reperfusion injuries.
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- 2015
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24. Renal Effects of Levosimendan: A Consensus Report
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Yilmaz, Mehmet B., Grossini, Elena, Silva Cardoso, José C., Édes, István, Fedele, Francesco, Pollesello, Piero, Kivikko, Matti, Harjola, Veli-Pekka, Hasslacher, Julia, Mebazaa, Alexandre, Morelli, Andrea, le Noble, Jos, Oldner, Anders, Oulego Erroz, Ignacio, Parissis, John T., Parkhomenko, Alexander, Poelzl, Gerhard, Rehberg, Sebastian, Ricksten, Sven-Erik, Rodríguez Fernández, Luís M., Salmenperä, Markku, Singer, Mervyn, Treskatsch, Sascha, Vrtovec, Bojan, and Wikström, Gerhard
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- 2013
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25. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
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Brown, P, Zhou, Y, Tan, A, El-Esawi, M, Liehr, T, Blanck, O, Gladue, D, Almeida, G, Cernava, T, Sorzano, C, Yeung, A, Engel, M, Chandrasekaran, A, Muth, T, Staege, M, Daulatabad, S, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C, Zhang, Z, Cascella, M, Flegel, W, Goodyear, C, van Raaij, M, Bukowy-Bieryllo, Z, Campana, L, Kurniawan, N, Lalaouna, D, Huttner, F, Ammerman, B, Ehret, F, Cobine, P, Tan, E, Han, H, Xia, W, Mccrum, C, Dings, R, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, V, Bengtsson-Palme, J, Bradshaw, W, Grimm, D, Kumar, N, Martis, E, Prieto, D, Sabnis, S, Amer, S, Liew, A, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, H, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, K, Boehme, K, Brenneisen, P, Brown, J, Dalrymple, B, Harvey, D, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, M, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, O, Kauppila, J, Zhang, X, Echeverria, N, Subhash, S, Sallmon, H, Tofani, M, 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A., van Meerten T., Min R., Moal I., Molari M., Molleman L., Mondal S. R., van de Mortel T., Moss W. N., Moultos O. A., Mukherjee M., Nakayama K., Narayan E., Neumann P. -A., Nie J., Nie Y., Niemeyer F., Nolan F., Nwaiwu O., Oldenmenger W. H., Olumayede E., Ou J., Pallebage-Gamarallage M., Pearce S. P., Pelkonen T., Pelleri M. C., Pereira J. L., Pheko M., Pinto K. A., Piovesan A., Pluess M., Podolsky I. M., Prescott J., Qi D., Qi X., Raikou V. D., Ranft A., Rhodes J., Rotge J. -Y., Rowe A. D., Saggar M., Schuon R. A., Shahid S., Shalchyan V., Shirvalkar P., Shiryayev O., Singh J., Smout M. J., Soares A., Song C., Srivastava K., Srivastava R. K., Sun J., Szabo A., Szymanski W., Tai C. N. P., Takeuchi H., Tanadini-Lang S., Tang F., Tao W., Theron G., Tian C. F., Tian Y. -S., Tuttle L. M., Valenti A., Verlot P., Walker M., Wang J., Welter D., Winslade M., Wu D., Wu Y. -R., Xiao H., Xu B., Xu Z., Yang D., Yang M., Yankilevich P., You Y., Yu C., Zhan J., Zhang G., Zhang K., Zhang T., Zhao G., Zhao J., Zhou X., Zhu Z., Ajani P. A., Anazodo U. C., Bagloee S. A., Bail K., Bar I., Bathelt J., Benkeser D., Bernier M. L., Blanchard A. M., Boakye D. W., Bonatsos V., Boon M. H., Bouboulis G., Bromfield E., Brown J., Bul K. C. M., Burton K. J., Butkowski E. G., Carroll G., Chao F., Charrier E. E., Chen Y. -C., Choi J. R., Christoffersen T., Comel J. C., Cosse C., Cui Y., van Dessel P., Diodato D., Duffey M., Dutt A., Egea L. G., El-Said M., Faye M., Fernandez-Fernandez B., Foley K. G., Founou L. L., Fu F., Gadelkareem R. A., Galimov E., Garip G., Gemmill A., Gouil Q., Grey J., Gridneva Z., Grothe M. J., Grebert T., Guerrero F., Guignard L., Haenssgen M. J., Hasler D., Holgate J. Y., Huang A., Hulse-Kemp A. M., Jean-Quartier C., Jeon S. -M., Jia Y., Jutzeler C., Kalatzis P., Karim M., Karsay K., Keitel A., Kempe A., Keown J. R., Khoo C. M., Khwaja N., Kievit R. A., Kosanic S., Koutoukidis D. A., Kramer P., Kumar D., Kirag N., Lanza G., Le T. D., Leem J. W., Leightley D., Leite A., Lercher L., Li Y., Lim R., Lima L. R. A., Lin L., Ling T., Liu Y., Liu Z., Lu Y., Lum F. M., Luo H., Machhi J., Macleod A., Macwan I., Madala H. R., Madani N., de Maio N., Makowiecki K., Mallinson D. J., Margelyte R., Maria C., Markonis Y., Marsili L., Mavoa S., McWilliams L., Megersa M., Souto-Maior C., Menichetti J., Mercieca-Bebber R., Miller J. J., Minde D. -P. M., Minges A., Mishra E., Mishra V. R., Moores C., Morrice N., Moskalensky A. E., Navarin N., Negera E., Nolet P., Nordberg A., Norden R., Nowicki J. P., Olova N., Olszewski P., Onzima R., Pan C. -L., Park C., Park D. I., Park S., Patil C. D., Pedro S. A., Perry S. R., Peter J., Peterson B. M., Pezzuolo A., Pozdnyakov I., Qian S., Qin L., Rafe A., Raote I., Raza A., Rebl H., Refai O., Regan T., Richa T., Richardson M. F., Robinson K. R., Rossoni L., Rouet R., Safaei S., Schneeberger P. H. H., Schwotzer D., Sebastian A., Selinski J., Seltmann S., Sha F., Shalev N., Shang J. -L., Singer J., Singh M., Smith T., Solomon-Moore E., Song L., Soraggi S., Stanley R., Steckhan N., Strobl F., Subissi L., Supriyanto I., Surve C. R., Suzuki T., Syme C., Sorelius K., Tang Y., Tantawy M., Tennakoon S., Teseo S., Toelzer C., Tomov N., Tovar M., Tran L., Tripathi S., Tuladhar A. M., Ukubuiwe A. C., Ung C. O. L., Valgepea K., Vatanparast H., Vidal A., Wang Q., Watari R., Webster R., Wei J., Wibowo D., Wingenbach T. S. H., Xavier R. M., Xiao S., Xiong P., Xu S., Yao R., Yao W., Yin Q., Zaitsu M., Zeineb Z., Zhan X. -Y., Zhang R., Zhang W., Zheng S., Zhou B., Ahmad H., Akinwumi S. A., Albery G. F., Alhowimel A., Ali J., Alshehri M., Alsuhaibani M., Anikin A., Azubuike S. O., Bach-Mortensen A., Baltiansky L., Bartas M., Belachew K. Y., Bhardwaj V., Binder K., Bland N. S., Boah M., Bullen B., Calabro G. E., Callahan T. J., Cao B., Chalmers K., Chang W., Che Z., Chen A. T. Y., Chen Z., Choi Y., Chowdhury M. A. K., Christensen M. R., Cooke R. S. C., Cottini M., Covington N. V., Cunningham C., Delarocque J., Devos L., Dhar A. R., Ding K. -F., Dong K., Dong Z., Dreyer N., Ekstrand C., Fardet T., Feleke B. E., Feurer T., Freitas A., Gao T., Giganti F., Grabowski P., Guerra-Mora J. R., Guo C., Guo X., Gupta H., He S., Heijne M., Heinemann S., Hogrebe A., Huang Z., Iskander-Rizk S., Iyer L. M., Jahan Y., James A. S., Joel E., Joffroy B., Jegousse C., Kambondo G., Karnati P., Kaya C., Ke A., Kelly D., Kickert R., Kidibule P. E., Kieselmann J. P., Kim H. J., Kitazawa T., Lamberts A., Liang H., Linn S. N., Litfin T., Liusuo W., Lygirou V., Mahato A. K., Mai Z. -M., Major R. W., Mali S., Mallis P., Mao W., Marvin-Dowle K., Mason L. D., Merideth B., Merino-Plaza M. J., Merlaen B., Messina R., Mishra A. K., Muhammad J., Musinguzi C., Nanou A., Naqash A., Nguyen J. T., Nguyen T. T. H., Ni D., Notcovich S., Ohst B., Ollivier Q. R., Osses D. F., Peng X., Plantinga A., Pulia M., Rafiq M., Raman A., Rawski R., Ray A., Razak L. A., Rudolf K., Rusch P., Sadoine M. L., Schmidt A., Schurr R., Searles S., Sharma S., Sheehan B., Shi C., Shohayeb B., Sommerlad A., Strehlow J., Sun X., Sundar R., Taherzadeh G., Tahir N. D. M., Tang J., Testa J., Tian Z., Tingting Q., Verheijen G. P., Vickstrom C., Wang T., Wang X., Wang Z., Wei P., Wilson A., Yassine A. -A., Yousefzadeh A., Zare A., Zeng Z., Zhang H., Zhou J., Zhu D., Adamo V., Adeyemo A. A., Aggelidou M., Al-Owaifeer A. M., Al-Riyami A. Z., Alzghari S. K., Andersen V., Angus K., Asaduzzaman M., Asady H., Ato D., Bai X., Baines R. L., Ballantyne M., Ban B., Beck J., Ben-Nafa W., Black E., Blancher A., Blankstein R., Bodagh N., Borges P., Brooks A., Brox-Ponce J., Brunetti A., Canham C. D., Carninci P., Carvajal R., Chang S. C., Chao J., Chatterjee P., Chen L., Chhatriwalla A. K., Chikowe I., Chuang T. -J., Collevatti R. G., Cornejo D. A. V., Cuenda A., Dao M., Dauga D., Deng Z., Devkota K., Doan L. V., Elewa Y. H. A., Fan D., Faruk M., Feifei S., Ferguson T. S., Fleres F., Foster E. J., Foster S., Furer T., Gao Y., Garcia-Rivera E. J., Gazdar A., George R. B., Ghosh S., Gianchecchi E., Gleason J. M., Hackshaw A., Hall A., Hall R., Harper P., Hogg W. E., Huang G., Hunter K. E., Ijzerman A. P., Jesus C., Jian G., Lewis J. S., Kanj S. S., Kaur H., Kheir F., Kichatova V. S., Kiyani M., Klein R., Kovesi T., Kraschnewski J. L., Kumar A. P., Labutin D., Lazo-Langner A., Leclercq G., Li M., Li Q., Li T., Liao W. -T., Liao Z. -Y., Lin J., Lizer J., Lobreglio G., Lowies C., Lu C., Majeed H., Martin A., Martinez-Sobrido L., Meresh E., Middelveen M., Mohebbi A., Mota J., Mozaheb Z., Muyaya L., Nandhakumar A., Ng S. H. X., Obeidat M., Oh D. -H., Owais M., Pace-Asciak P., Panwar A., Patterson C., Penagos-Tabaree F., Pianosi P. T., Pinzi V., Pridans C., Psaroulaki A., Pujala R. K., Pulido-Arjona L., Qi P. -F., Rahman P., Rai N. K., Rassaf T., Refardt J., Ricciardi W., Riess O., Rovas A., Sacks F. M., Saleh S., Sampson C., Schmutz A., Sepanski R., Sharma N., Spearman P., Subramaniapillai M., Swali R., Tan C. M., Tellechea J. I., Thomas L. -M., Tong X., Vavvas D. G., Veys R., Vitriol V., Wang H. -D., Waugh J., Webb S. A., Williams B. A., Workman A. D., Xiang T., Xie L. -X., Xu T., Yang C., Yoon J. G., Yuan C. M., Zaritsky A., Zhao H., Zuckerman H., Lyu R., and Pullan W.
- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science.
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- 2019
26. Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo
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Gödény, Ildikó, Pollesello, Piero, Édes, István, Papp, Zoltán, and Bagi, Zsolt
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- 2013
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27. Economic Evaluation of Levosimendan Versus Dobutamine for the Treatment of Acute Heart Failure in Italy
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Lucioni, Carlo, D’Ambrosi, Alessandra, Mazzi, Silvio, Pollesello, Piero, Apajasalo, Marjo, and Fedele, Francesco
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- 2012
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28. Differential effects of inotropes and inodilators on renal function in acute cardiac care
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Zima, E. Farmakis, D. Pollesello, P. Parissis, J.T.
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urologic and male genital diseases - Abstract
Pathological interplay between the heart and kidneys is widely encountered in heart failure (HF) and is linked to worse prognosis and quality of life. Inotropes, along with diuretics and vasodilators, are a core medical response to HF but decompensated patients who need inotropic support often present with an acute worsening of renal function. The impact of inotropes on renal function is thus potentially an important influence on the choice of therapy. There is currently relatively little objective data available to guide the selection of inotrope therapy but recent direct observations on the effects of levosimendan and milrinone on glomerular filtration favour levosimendan. Other lines of evidence indicate that in acute decompensated HF levosimendan has an immediate renoprotective effect by increasing renal blood flow through preferential vasodilation of the renal afferent arterioles and increases in glomerular filtration rate: potential for renal medullary ischaemia is avoided by an offsetting increase in renal oxygen delivery. These indications of a putative renoprotective action of levosimendan support the view that this calcium-sensitizing inodilator may be preferable to dobutamine or other adrenergic inotropes in some settings by virtue of its renal effects. Additional large studies will be required, however, to clarify the renal effects of levosimendan in this and other relevant clinical situations, such as cardiac surgery. © 2020 Oxford University Press. All rights reserved.
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- 2021
29. Selective Na+/Ca2+ exchanger inhibition prevents Ca2+ overload induced triggered arrhythmias: P3.15
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Nagy, N., Kormos, A., Kohajda, Zs., Szebeni, Á., Pollesello, P., Levijoki, J., Acsai, K., Virág, L., Nánási, P. P., Papp, J. Gy., Varró, A., and Tóth, A.
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- 2014
30. Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use
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Papp, Z. Agostoni, P. Alvarez, J. Bettex, D. Bouchez, S. Brito, D. Černý, V. Comin-Colet, J. Crespo-Leiro, M.G. Delgado, J.F. Édes, I. Eremenko, A.A. Farmakis, D. Fedele, F. Fonseca, C. Fruhwald, S. Girardis, M. Guarracino, F. Harjola, V.-P. Heringlake, M. Herpain, A. Heunks, L.M.A. Husebye, T. Ivancan, V. Karason, K. Kaul, S. Kivikko, M. Kubica, J. Masip, J. Matskeplishvili, S. Mebazaa, A. Nieminen, M.S. Oliva, F. Papp, J.G. Parissis, J. Parkhomenko, A. Põder, P. Pölzl, G. Reinecke, A. Ricksten, S.-E. Riha, H. Rudiger, A. Sarapohja, T. Schwinger, R.H.G. Toller, W. Tritapepe, L. Tschöpe, C. Wikström, G. Lewinski, D.V. Vrtovec, B. Pollesello, P.
- Abstract
Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years. © 2020 Lippincott Williams and Wilkins. All rights reserved.
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- 2020
31. The contractile apparatus as a target for drugs against heart failure: Interaction of levosimendan, a calcium sensitiser, with cardiac troponin c
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Sorsa, Tia, Pollesello, Piero, and Solaro, R. John
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- 2004
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32. ORM-10103, a novel specific inhibitor of the Na+/Ca2+ exchanger, decreases early and delayed afterdepolarizations in the canine heart
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Jost, N, Nagy, N, Corici, C, Kohajda, Z, Horváth, A, Acsai, K, Biliczki, P, Levijoki, J, Pollesello, P, Koskelainen, T, Otsomaa, L, Tóth, A, Papp, J Gy, Varró, A, and Virág, L
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- 2013
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33. CARDIOVASCULAR EFFECTS OF SIMENDANS: S8–3 Invited lecture
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Pollesello, P.
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- 2008
34. A role for the RISK pathway and KATP channels in pre- and post-conditioning induced by levosimendan in the isolated guinea pig heart
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Du Toit, E F, Genis, A, Opie, L H, Pollesello, P, and Lochner, A
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- 2008
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35. The Adenylate Cyclase Activator Forskolin Potentiates the Positive Inotropic Effect of the Phosphodiesterase Inhibitor Milrinone But Not of the Calcium Sensitizer Levosimendan nor of Its Hemodynamically Active Metabolites: An Apparent Conundrum
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Levijoki, Jouko, Pollesello, Piero, Grossini, Elena, and Papp, Zoltán
- Abstract
Supplemental Digital Content is Available in the Text.OR-1855 and OR-1896 are 2 hemodynamically active metabolites of the inodilator levosimendan, with calcium sensitizing activity, but their mechanism of action is still not fully understood. It has been previously reported that the positive inotropic effect of levosimendan is not potentiated by the adenylate cyclase activator forskolin, whereas forskolin does potentiate the effects of the phosphodiesterase (PDE) inhibitor milrinone. To ascertain whether the active metabolites follow the same pattern of levosimendan, the positive inotropic effects of OR- 1855 and OR-1896 were studied in guinea-pig-isolated papillary muscle in the presence and absence of forskolin. OR-1855 and OR-1896 were also tested as inhibitors of PDE-III and PDE-IV. Our results show that 0.1 µM forskolin did not potentiate the positive inotropic effect of OR-1855 or OR-1896, as in the case of the parent compound levosimendan. As in previous studies, the positive inotropic effect of milrinone was markedly potentiated in the presence of forskolin. From these data, we propose an explanation for the divergent behavior of the calcium sensitizing drugs and PDE inhibitors.
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- 2022
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36. Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology
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de Boer, R.A. De Keulenaer, G. Bauersachs, J. Brutsaert, D. Cleland, J.G. Diez, J. Du, X.-J. Ford, P. Heinzel, F.R. Lipson, K.E. McDonagh, T. Lopez-Andres, N. Lunde, I.G. Lyon, A.R. Pollesello, P. Prasad, S.K. Tocchetti, C.G. Mayr, M. Sluijter, J.P.G. Thum, T. Tschöpe, C. Zannad, F. Zimmermann, W.-H. Ruschitzka, F. Filippatos, G. Lindsey, M.L. Maack, C. Heymans, S.
- Abstract
Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart failure, and its treatment may be effective in preventing heart failure and its progression. A lack of pathophysiological insights and uniform definitions has hampered the research in fibrosis and heart failure. The Translational Research Committee of the Heart Failure Association discussed several aspects of fibrosis in their workshop. Early insidious perturbations such as subclinical hypertension or inflammation may trigger first fibrotic events, while more dramatic triggers such as myocardial infarction. and myocarditis give rise to full blown scar formation and ongoing fibrosis in diseased hearts. Aging itself is also associated with a cardiac phenotype that includes fibrosis. Fibrosis is an extremely heterogeneous phenomenon, as several stages of the fibrotic process exist, each with different fibrosis subtypes and a different composition of various cells and proteins — resulting in a very complex pathophysiology. As a result, detection of fibrosis, e.g. using current cardiac imaging modalities or plasma biomarkers, will detect only specific subforms of fibrosis, but cannot capture all aspects of the complex fibrotic process. Furthermore, several anti-fibrotic therapies are under investigation, but such therapies generally target aspecific aspects of the fibrotic process and suffer from a lack of precision. This review discusses the mechanisms and the caveats and proposes a roadmap for future research. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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- 2019
37. A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus
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Farmakis, D. Agostoni, P. Baholli, L. Bautin, A. Comin-Colet, J. Crespo-Leiro, M.G. Fedele, F. García-Pinilla, J.M. Giannakoulas, G. Grigioni, F. Gruchała, M. Gustafsson, F. Harjola, V.-P. Hasin, T. Herpain, A. Iliodromitis, E.K. Karason, K. Kivikko, M. Liaudet, L. Ljubas-Maček, J. Marini, M. Masip, J. Mebazaa, A. Nikolaou, M. Ostadal, P. Põder, P. Pollesello, P. Polyzogopoulou, E. Pölzl, G. Tschope, C. Varpula, M. von Lewinski, D. Vrtovec, B. Yilmaz, M.B. Zima, E. Parissis, J.
- Abstract
Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure. © 2019 The Authors
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- 2019
38. Short-term therapies for treatment of acute and advanced heart failure—why so few drugs available in clinical use, why even fewer in the pipeline?
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Pollesello, P. Gal, T.B. Bettex, D. Cerny, V. Comin-Colet, J. Eremenko, A.A. Farmakis, D. Fedele, F. Fonseca, C. Harjola, V.-P. Herpain, A. Heringlake, M. Heunks, L. Husebye, T. Ivancan, V. Karason, K. Kaul, S. Kubica, J. Mebazaa, A. Mølgaard, H. Parissis, J. Parkhomenko, A. Põder, P. Pölzl, G. Vrtovec, B. Yilmaz, M.B. Papp, Z.
- Abstract
Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio-and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g. catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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- 2019
39. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
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Brown, P. Zhou, Y. Tan, A.-C. El-Esawi, M.A. Liehr, T. Blanck, O. Gladue, D.P. Almeida, G.M.F. Cernava, T. Sorzano, C.O. Yeung, A.W.K. Engel, M.S. Chandrasekaran, A.R. Muth, T. Staege, M.S. Daulatabad, S.V. Widera, D. Zhang, J. Meule, A. Honjo, K. Pourret, O. Yin, C.-C. Zhang, Z. Cascella, M. Flegel, W.A. Goodyear, C.S. van Raaij, M.J. Bukowy-Bieryllo, Z. Campana, L.G. Kurniawan, N.A. Lalaouna, D. Hüttner, F.J. Ammerman, B.A. Ehret, F. Cobine, P.A. Tan, E.-C. Han, H. Xia, W. McCrum, C. Dings, R.P.M. Marinello, F. Nilsson, H. Nixon, B. Voskarides, K. Yang, L. Costa, V.D. Bengtsson-Palme, J. Bradshaw, W. Grimm, D.G. Kumar, N. Martis, E. Prieto, D. Sabnis, S.C. Amer, S.E.D.R. Liew, A.W.C. Perco, P. Rahimi, F. Riva, G. Zhang, C. Devkota, H.P. Ogami, K. Basharat, Z. Fierz, W. Siebers, R. Tan, K.H. Boehme, K.A. Brenneisen, P. Brown, J.A.L. Dalrymple, B.P. Harvey, D.J. Ng, G. Werten, S. Bleackley, M. Dai, Z. Dhariwal, R. Gelfer, Y. Hartmann, M.D. Miotla, P. Tamaian, R. Govender, P. Gurney-Champion, O.J. Kauppila, J.H. Zhang, X. Echeverría, N. Subhash, S. Sallmon, H. Tofani, M. Bae, T. Bosch, O. Cuív, P.O. Danchin, A. Diouf, B. Eerola, T. Evangelou, E. Filipp, F. Klump, H. Kurgan, L. Smith, S.S. Terrier, O. Tuttle, N. Ascher, D.B. Janga, S.C. Schulte, L.N. Becker, D. Browngardt, C. Bush, S.J. Gaullier, G. Ide, K. Meseko, C. Werner, G.D.A. Zaucha, J. Al-Farha, A.A. Greenwald, N.F. Popoola, S.I. Rahman, S. Xu, J. Yang, S.Y. Hiroi, N. Alper, O.M. Baker, C.I. Bitzer, M. Chacko, G. Debrabant, B. Dixon, R. Forano, E. Gilliham, M. Kelly, S. Klempnauer, K.-H. Lidbury, B.A. Lin, M.Z. Lynch, I. Ma, W. Maibach, E.W. Mather, D.E. Nandakumar, K.S. Ohgami, R.S. Parchi, P. Tressoldi, P. Xue, Y. Armitage, C. Barraud, P. Chatzitheochari, S. Coelho, L.P. Diao, J. Doxey, A.C. Gobet, A. Hu, P. Kaiser, S. Mitchell, K.M. Salama, M.F. Shabalin, I.G. Song, H. Stevanovic, D. Yadollahpour, A. Zeng, E. Zinke, K. Alimba, C.G. Beyene, T.J. Cao, Z. Chan, S.S. Gatchell, M. Kleppe, A. Piotrowski, M. Torga, G. Woldesemayat, A.A. Cosacak, M.I. Haston, S. Ross, S.A. Williams, R. Wong, A. Abramowitz, M.K. Effiong, A. Lee, S. Abid, M.B. Agarabi, C. Alaux, C. Albrecht, D.R. Atkins, G.J. Beck, C.R. Bonvin, A.M.J.J. Bourke, E. Brand, T. Braun, R.J. Bull, J.A. Cardoso, P. Carter, D. Delahay, R.M. Ducommun, B. Duijf, P.H.G. Epp, T. Eskelinen, E.-L. Fallah, M. Farber, D.B. Fernandez-Triana, J. Feyerabend, F. Florio, T. Friebe, M. Furuta, S. Gabrielsen, M. Gruber, J. Grybos, M. Han, Q. Heinrich, M. Helanterä, H. Huber, M. Jeltsch, A. Jiang, F. Josse, C. Jurman, G. Kamiya, H. de Keersmaecker, K. Kristiansson, E. de Leeuw, F.-E. Li, J. Liang, S. Lopez-Escamez, J.A. Lopez-Ruiz, F.J. Marchbank, K.J. Marschalek, R. Martín, C.S. Miele, A.E. Montagutelli, X. Morcillo, E. Nicoletti, R. Niehof, M. O'Toole, R. Ohtomo, T. Oster, H. Palma, J.-A. Paterson, R. Peifer, M. Portilla, M. Portillo, M.C. Pritchard, A.L. Pusch, S. Raghava, G.P.S. Roberts, N.J. Ross, K. Schuele, B. Sergeant, K. Shen, J. Stella, A. Sukocheva, O. Uversky, V.N. Vanneste, S. Villet, M.H. Viveiros, M. Vorholt, J.A. Weinstock, C. Yamato, M. Zabetakis, I. Zhao, X. Ziegler, A. Aizat, W.M. Atlas, L. Bridges, K.M. Chakraborty, S. Deschodt, M. Domingues, H.S. Esfahlani, S.S. Falk, S. Guisado, J.L. Kane, N.C. Kueberuwa, G. Lau, C.L. Liang, D. Liu, E. Luu, A.M. Ma, C. Ma, L. Moyer, R. Norris, A.D. Panthee, S. Parsons, J.R. Peng, Y. Pinto, I.M. Reschke, C.R. Sillanpää, E. Stewart, C.J. Uhle, F. Yang, H. Zhou, K. Zhu, S. Ashry, M. Bergsland, N. Berthold, M. Chen, C.-E. Colella, V. Cuypers, M. Eskew, E.A. Fan, X. Gajda, M. Gonzálezlez-Prendes, R. Goodin, A. Graham, E.B. Groen, E.J.N. Gutiérrez-Sacristán, A. Habes, M. Heffler, E. Higginbottom, D.B. Janzen, T. Jayaraman, J. Jibb, L.A. Jongen, S. Kinyanjui, T. Koleva-Kolarova, R.G. Li, Z. Liu, Y.-P. Lund, B.A. Lussier, A.A. Ma, L. Mier, P. Moore, M.D. Nagler, K. Orme, M.W. Pearson, J.A. Prajapati, A.S. Saito, Y. Tröder, S.E. Uchendu, F. Verloh, N. Voutchkova, D.D. Abu-Zaid, A. Bakkach, J. Baumert, P. Dono, M. Hanson, J. Herbelet, S. Hobbs, E. Kulkarni, A. Kumar, N. Liu, S. Loft, N.D. Reddan, T. Senghore, T. Vindin, H. Xu, H. Bannon, R. Chen, B. Cheung, J.T.K. Cooper, J. Esnakula, A.K. Feghali, K.A. Ghelardi, E. Gnasso, A. Horbar, J. Lai, H.M. Li, J. Ma, L. Ma, R. Pan, Z. Peres, M.A. Pranata, R. Seow, E. Sydes, M. Testoni, I. Westermair, A.L. Yang, Y. Afnan, M. Albiol, J. Albuquerque, L.G. Amir, S. Amiya, E. Amorim, R.M. An, Q. Andersen, S.U. Aplin, J.D. Argyropoulos, C. Asmann, Y.W. Assaeed, A.M. Atanasov, A.G. Atchison, D.A. Avery, S.V. Avillach, P. Baade, P.D. Backman, L. Badie, C. Baldi, A. Ball, E. Bardot, O. Barnett, A.G. Basner, M. Batra, J. Bazanova, O.M. Beale, A. Beddoe, T. Bell, M.L. Berezikov, E. Berners-Price, S. Bernhardt, P. Berry, E. Bessa, T.B. Billington, C. Birch, J. Blakely, R.D. Blaskovich, M.A.T. Blum, R. Boelaert, M. Bogdanos, D. Bosch, C. Bourgoin, T. Bouvard, D. Boykin, L.M. Bradley, G. Braun, D. Brownlie, J. Brühl, A. Burt, A. Butler, L.M. Byrareddy, S.N. Byrne, H.J. Cabantous, S. Calatayud, S. Candal, E. Carlson, K. Casillas, S. Castelvetro, V. Caswell, P.T. Cavalli, G. Cerovsky, V. Chagoyen, M. Chen, C.-S. Chen, D.F. Chen, H. Chen, H. Chen, J.-T. Chen, Y. Cheng, C. Cheng, J. Chinapaw, M. Chinopoulos, C. Cho, W.C.S. Chong, L. Chowdhury, D. Chwalibog, A. Ciresi, A. Cockcroft, S. Conesa, A. Cook, P.A. Cooper, D.N. Coqueret, O. Corea, E.M. Costa, A. Costa, E. Coupland, C. Crawford, S.Y. Cruz, A.D. Cui, H. Cui, Q. Culver, D.C. D'Angiulli, A. Dahms, T.E.S. Daigle, F. Dalgleish, R. Danielsen, H.E. Darras, S. Davidson, S.M. Day, D.A. Degirmenci, V. Demaison, L. Devriendt, K. Ding, J. Dogan, Y. Dong, X.C. Donner, C.F. Dressick, W. Drevon, C.A. Duan, H. Ducho, C. Dumaz, N. Dwarakanath, B.S. Ebell, M.H. Eisenhardt, S. Elkum, N. Engel, N. Erickson, T.B. Fairhead, M. Faville, M.J. Fejzo, M.S. Festa, F. Feteira, A. Flood-Page, P. Forsayeth, J. Fox, S.A. Franks, S.J. Frentiu, F.D. Frilander, M.J. Fu, X. Fujita, S. Galea, I. Galluzzi, L. Gani, F. Ganpule, A.P. García-Alix, A. Gedye, K. Giordano, M. Giunta, C. Gleeson, P.A. Goarant, C. Gong, H. Gora, D. Gough, M.J. Goyal, R. Graham, K.E. Grande-Pérez, A. Graves, P.M. Greidanus, H. Grice, D. Grunau, C. Gumulya, Y. Guo, Y. Gurevich, V.V. Gusev, O. Hacker, E. Hage, S.R. Hagen, G. Hahn, S. Haller, D.M. Hammerschmidt, S. Han, J. Han, R. Handfield, M. Hapuarachchi, H.C. Harder, T. Hardingham, J.E. Heck, M. Heers, M. Hew, K.F. Higuchi, Y. Hilaire, C.St. Hilton, R. Hodzic, E. Hone, A. Hongoh, Y. Hu, G. Huber, H.P. Hueso, L.E. Huirne, J. Hurt, L. Idborg, H. Ikeo, K. Ingley, E. Jakeman, P.M. Jensen, A. Jia, H. Jia, H. Jia, S. Jiang, J. Jiang, X. Jin, Y. Jo, D. Johnson, A.M. Johnston, M. Jonscher, K.R. Jorens, P.G. Jorgensen, J.O.L. Joubert, J.W. Jung, S.-H. Junior, A.M. Kahan, T. Kamboj, S.K. Kang, Y.-K. Karamanos, Y. Karp, N.A. Kelly, R. Kenna, R. Kennedy, J. Kersten, B. Khalaf, R.A. Khalid, J.M. Khatlani, T. Khider, T. Kijanka, G.S. King, S.R.B. Kluz, T. Knox, P. Kobayashi, T. Koch, K.-W. Kohonen-Corish, M.R.J. Kong, X. Konkle-Parker, D. Korpela, K.M. Kostrikis, L.G. Kraiczy, P. Kratz, H. Krause, G. Krebsbach, P.H. Kristensen, S.R. Kumari, P. Kunimatsu, A. Kurdak, H. Kwon, Y.D. Lachat, C. Lagisz, M. Laky, B. Lammerding, J. Lange, M. Larrosa, M. Laslett, A.L. Laverman, G.D. Leclair, E.E. Lee, K.-W. Lee, M.-Y. Lee, M.-S. Li, G. Li, J. Lieb, K. Lim, Y.Y. Lindsey, M.L. Line, P.-D. Liu, D. Liu, F. Liu, H. Liu, H. Lloyd, V.K. Lo, T.-W. Locci, E. Loidl, J. Lorenzen, J. Lorkowski, S. Lovell, N.H. Lu, H. Lu, W. Lu, Z. Luengo, G.S. Lundh, L.-G. Lysy, P.A. Mabb, A. Mack, H.G. Mackey, D.A. Mahdavi, S.R. Maher, P. Maher, T. Maity, S.N. Malgrange, B. Mamoulakis, C. Mangoni, A.A. Manke, T. Manstead, A.S.R. Mantalaris, A. Marsal, J. Marschall, H.-U. Martin, F.L. Martinez-Raga, J. Martinez-Salas, E. Mathieu, D. Matsui, Y. Maza, E. McCutcheon, J.E. McKay, G.J. McMillan, B. McMillan, N. Meads, C. Medina, L. Merrick, B.A. Metzger, D.W. Meunier, F.A. Michaelis, M. Micheau, O. Mihara, H. Mintz, E.M. Mizukami, T. Moalic, Y. Mohapatra, D.P. Monteiro, A. Montes, M. Moran, J.V. Morozov, S.Y. Mort, M. Murai, N. Murphy, D.J. Murphy, S.K. Murray, S.A. Naganawa, S. Nammi, S. Nasios, G. Natoli, R.M. Nguyen, F. Nicol, C. van Nieuwerburgh, F. Nilsen, E.B. Nobile, C.J. O'Mahony, M. Ohlsson, S. Olatunbosun, O. Olofsson, P. Ortiz, A. Ostrikov, K. Otto, S. Outeiro, T.F. Ouyang, S. Paganoni, S. Page, A. Palm, C. Paradies, Y. Parsons, M.H. Parsons, N. Pascal, P. Paul, E. Peckham, M. Pedemonte, N. Pellizzon, M.A. Petrelli, M. Pichugin, A. Pinto, C.J.C. Plevris, J.N. Pollesello, P. Polz, M. Ponti, G. Porcelli, P. Prince, M. Quinn, G.P. Quinn, T.J. Ramula, S. Rappsilber, J. Rehfeldt, F. Reiling, J.H. Remacle, C. Rezaei, M. Riddick, E.W. Ritter, U. Roach, N.W. Roberts, D.D. Robles, G. Rodrigues, T. Rodriguez, C. Roislien, J. Roobol, M.J. Rowe, A. Ruepp, A. van Ruitenbeek, J. Rust, P. Saad, S. Sack, G.H. Santos, M. Saudemont, A. Sava, G. Schrading, S. Schramm, A. Schreiber, M. Schuler, S. Schymkowitz, J. Sczyrba, A. Seib, K.L. Shi, H.-P. Shimada, T. Shin, J.-S. Shortt, C. Silveyra, P. Skinner, D. Small, I. Smeets, P.A.M. So, P.-W. Solano, F. Sonenshine, D.E. Song, J. Southall, T. Speakman, J.R. Srinivasan, M.V. Stabile, L.P. Stasiak, A. Steadman, K.J. Stein, N. Stephens, A.W. Stewart, D.I. Stine, K. Storlazzi, C. Stoynova, N.V. Strzalka, W. Suarez, O.M. Sultana, T. Sumant, A.V. Summers, M.J. Sun, G. Tacon, P. Tanaka, K. Tang, H. Tanino, Y. Targett-Adams, P. Tayebi, M. Tayyem, R. Tebbe, C.C. Telfer, E.E. Tempel, W. Teodorczyk-Injeyan, J.A. Thijs, G. Thorne, S. Thrift, A.G. Tiffon, C. Tinnefeld, P. Tjahjono, D.H. Tolle, F. Toth, E. Del Tredici, A.L. Tsapas, A. Tsirigotis, K. Turak, A. Tzotzos, G. Udo, E.E. Utsumi, T. Vaidyanathan, S. Vaillant, M. Valsesia, A. Vandenbroucke, R.E. Veiga, F.H. Vendrell, M. Vesk, P.A. Vickers, P. Victor, V.M. Villemur, R. Vohl, M.-C. Voolstra, C.R. Vuillemin, A. Wakelin, S. Waldron, L. Walsh, L.J. Wang, A.Y. Wang, F. Wang, Y. Watanabe, Y. Weigert, A. Wen, J.-C. Wham, C. White, E.P. Wiener, J. Wilharm, G. Wilkinson, S. Willmann, R. Wilson, C. Wirth, B. Wojan, T.R. Wolff, M. Wong, B.M. Wu, T.-W. Wuerbel, H. Xiao, X. Xu, D. Xu, J.W. Xu, J. Xue, B. Yalcin, S. Yan, H. Yang, E.-C. Yang, S. Yang, W. Ye, Y. Ye, Z.-Q. Yli-Kauhaluoma, J. Yoneyama, H. Yu, Y. Yuan, G.-C. Yuh, C.-H. Zaccolo, M. Zeng, C. Zevnik, B. Zhang, C. Zhang, L. Zhang, Y. Zhang, Y. Zhang, Z. Zhang, Z.-Y. Zhao, Y. Zhou, M. Zuberbier, T. Aanei, C.M. Ahmad, R. Al-Lawama, M. Alanio, A. Allardyce, J. Alonso-Caneiro, D. Atack, J.M. Baier, D. Bansal, A. Benezeth, Y. Berbesque, C. Berrevoet, F. Biedermann, P.H.W. Bijleveld, E. Bittner, F. Blombach, F. van den Bos, W. Boudreau, S.A. Bramoweth, A.D. Braubach, O. Cai, Y. Campbell, M. Cao, Z. Catry, T. Chen, X. Cheng, S. Chung, H.-J. Chávez-Fumagalli, M.A. Conway, A. Costa, B.M. Cyr, N. Dean, L.T. Denzel, M.S. Dlamini, S.V. Dudley, K.J. Dufies, M. Ecke, T. Eckweiler, D. Eixarch, E. El-Adawy, H. Emmrich, J.V. Eustace, A.J. Falter-Wagner, C.M. Farhoudi, R. Fuss, J. Gao, J. Gill, M.R. Gloyn, L. Goggs, R. Govinden, U. Greene, G. Greiff, V. Grundle, D.S. Grüneberg, P. Gumede, N. Haore, G. Harrison, P. Hoenner, X. Hojsgaard, D. Hori, H. Ikonomopoulou, M.P. Jeurissen, P. Johnson, D.M. Kabra, D. Kamagata, K. Karmakar, C. Kasian, O. Kaye, L.K. Khan, M.M. Kim, Y.-M. Kish, J.K. Kobold, S. Kohanbash, G. Kohls, G. Kugler, J.-M. Kumar, G. Lacy-Colson, J. Latif, A. Lauschke, V.M. Li, B. Lim, C.J. Liu, F. Liu, X. Lu, J.-J. Lu, Q. Mahavadi, P. Marzocchi, U. McGarrigle, C.A. van Meerten, T. Min, R. Moal, I. Molari, M. Molleman, L. Mondal, S.R. van de Mortel, T. Moss, W.N. Moultos, O.A. Mukherjee, M. Nakayama, K. Narayan, E. Navaratnarajah Neumann, P.-A. Nie, J. Nie, Y. Niemeyer, F. Nolan, F. Nwaiwu, O. Oldenmenger, W.H. Olumayede, E. Ou, J. Pallebage-Gamarallage, M. Pearce, S.P. Pelkonen, T. Pelleri, M.C. Pereira, J.L. Pheko, M. Pinto, K.A. Piovesan, A. Pluess, M. Podolsky, I.M. Prescott, J. Qi, D. Qi, X. Raikou, V.D. Ranft, A. Rhodes, J. Rotge, J.-Y. Rowe, A.D. Saggar, M. Schuon, R.A. Shahid, S. Shalchyan, V. Shirvalkar, P. Shiryayev, O. Singh, J. Smout, M.J. Soares, A. Song, C. Srivastava, K. Srivastava, R.K. Sun, J. Szabo, A. Szymanski, W. Tai, C.N.P. Takeuchi, H. Tanadini-Lang, S. Tang, F. Tao, W. Theron, G. Tian, C.F. Tian, Y.-S. Tuttle, L.M. Valenti, A. Verlot, P. Walker, M. Wang, J. Welter, D. Winslade, M. Wu, D. Wu, Y.-R. Xiao, H. Xu, B. Xu, J. Xu, Z. Yang, D. Yang, M. Yankilevich, P. You, Y. Yu, C. Zhan, J. Zhang, G. Zhang, K. Zhang, T. Zhang, Y. Zhao, G. Zhao, J. Zhou, X. Zhu, Z. Ajani, P.A. Anazodo, U.C. Bagloee, S.A. Bail, K. Bar, I. Bathelt, J. Benkeser, D. Bernier, M.L. Blanchard, A.M. Boakye, D.W. Bonatsos, V. Boon, M.H. Bouboulis, G. Bromfield, E. Brown, J. Bul, K.C.M. Burton, K.J. Butkowski, E.G. Carroll, G. Chao, F. Charrier, E.E. Chen, X. Chen, Y.-C. Chenguang Choi, J.R. Christoffersen, T. Comel, J.C. Cosse, C. Cui, Y. van Dessel, P. Dhaval Diodato, D. Duffey, M. Dutt, A. Egea, L.G. El-Said, M. Faye, M. Fernandez-Fernandez, B. Foley, K.G. Founou, L.L. Fu, F. Gadelkareem, R.A. Galimov, E. Garip, G. Gemmill, A. Gouil, Q. Grey, J. Gridneva, Z. Grothe, M.J. Grébert, T. Guerrero, F. Guignard, L. Haenssgen, M.J. Hasler, D. Holgate, J.Y. Huang, A. Hulse-Kemp, A.M. Jean-Quartier, C. Jeon, S.-M. Jia, Y. Jutzeler, C. Kalatzis, P. Karim, M. Karsay, K. Keitel, A. Kempe, A. Keown, J.R. Khoo, C.M. Khwaja, N. Kievit, R.A. Kosanic, S. Koutoukidis, D.A. Kramer, P. Kumar, D. Kiraǧ, N. Lanza, G. Le, T.D. Leem, J.W. Leightley, D. Leite, A. Lercher, L. Li, Y. Lim, R. Lima, L.R.A. Lin, L. Ling, T. Liu, Y. Liu, Z. Lu, Y. Lum, F.M. Luo, H. Machhi, J. Macleod, A. Macwan, I. Madala, H.R. Madani, N. de Maio, N. Makowiecki, K. Mallinson, D.J. Margelyte, R. Maria, C. Markonis, Y. Marsili, L. Mavoa, S. McWilliams, L. Megersa, M. Souto-Maior, C. Menichetti, J. Mercieca-Bebber, R. Miller, J.J. Minde, D.-P.M. Minges, A. Mishra, E. Mishra, V.R. Moores, C. Morrice, N. Moskalensky, A.E. Navarin, N. Negera, E. Nolet, P. Nordberg, A. Nordén, R. Nowicki, J.P. Olova, N. Olszewski, P. Onzima, R. Pan, C.-L. Park, C. Park, D.I. Park, S. Patil, C.D. Pedro, S.A. Perry, S.R. Peter, J. Peterson, B.M. Pezzuolo, A. Pozdnyakov, I. Qian, S. Qin, L. Rafe, A. Raote, I. Raza, A. Rebl, H. Refai, O. Regan, T. Richa, T. Richardson, M.F. Robinson, K.R. Rossoni, L. Rouet, R. Safaei, S. Schneeberger, P.H.H. Schwotzer, D. Sebastian, A. Selinski, J. Seltmann, S. Sha, F. Shalev, N. Shang, J.-L. Singer, J. Singh, M. Smith, T. Solomon-Moore, E. Song, L. Soraggi, S. Stanley, R. Steckhan, N. Strobl, F. Subissi, L. Supriyanto, I. Surve, C.R. Suzuki, T. Syme, C. Sörelius, K. Tang, Y. Tantawy, M. Tennakoon, S. Teseo, S. Toelzer, C. Tomov, N. Tovar, M. Tran, L. Tripathi, S. Tuladhar, A.M. Ukubuiwe, A.C. Ung, C.O.L. Valgepea, K. Vatanparast, H. Vidal, A. Wang, F. Wang, Q. Watari, R. Webster, R. Webster, R. Wei, J. Wibowo, D. Wingenbach, T.S.H. Xavier, R.M. Xiao, S. Xiong, P. Xu, S. Xu, S. Yao, R. Yao, W. Yin, Q. Yu, Y. Zaitsu, M. Zeineb, Z. Zhan, X.-Y. Zhang, J. Zhang, R. Zhang, W. Zhang, X. Zheng, S. Zhou, B. Zhou, X. Ahmad, H. Akinwumi, S.A. Albery, G.F. Alhowimel, A. Ali, J. Alshehri, M. Alsuhaibani, M. Anikin, A. Azubuike, S.O. Bach-Mortensen, A. Baltiansky, L. Bartas, M. Belachew, K.Y. Bhardwaj, V. Binder, K. Bland, N.S. Boah, M. Bullen, B. Calabrò, G.E. Callahan, T.J. Cao, B. Chalmers, K. Chang, W. Che, Z. Chen, A.T.Y. Chen, H. Chen, H. Chen, Y. Chen, Z. Choi, Y. Chowdhury, M.A.K. Christensen, M.R. Cooke, R.S.C. Cottini, M. Covington, N.V. Cunningham, C. Delarocque, J. Devos, L. Dhar, A.R. Ding, K.-F. Dong, K. Dong, Z. Dreyer, N. Ekstrand, C. Fardet, T. Feleke, B.E. Feurer, T. Freitas, A. Gao, T. Gebremedhin Giganti, F. Grabowski, P. Guerra-Mora, J.R. Guo, C. Guo, X. Gupta, H. He, S. Heijne, M. Heinemann, S. Hogrebe, A. Huang, Z. Iskander-Rizk, S. Iyer, L.M. Jahan, Y. 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Zaritsky, A. Zhang, Y. Zhao, H. Zuckerman, H. Lyu, R. Pullan, W. RELISH Consortium
- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press.
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40. Long‐term effects of Na+/Ca2+ exchanger inhibition with ORM‐11035 improves cardiac function and remodelling without lowering blood pressure in a model of heart failure with preserved ejection fraction
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Primessnig, U., Bracic, T., Levijoki, J., Otsomaa, L., Pollesello, P., Falcke, M., Pieske, B., and Heinzel, F.R.
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Na+/Ca2+ exchanger ,Heart failure with preserved ejection fraction ,ORM-11035 ,Cardiovascular and Metabolic Diseases ,Calcium ,Cardiomyocyte ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit - Abstract
AIMS: Heart failure with preserved ejection fraction (HFpEF) is increasingly common but there is currently no established pharmacological therapy. We hypothesized that ORM-11035, a novel specific Na(+)/Ca(2+) exchanger (NCX) inhibitor, improves cardiac function and remodelling independent of effects on arterial blood pressure in a model of cardiorenal HFpEF. METHODS AND RESULTS: Rats were subjected to subtotal nephrectomy (NXT) or sham operation. Eight weeks after intervention, treatment for 16 weeks with ORM-11035 (1 mg/kg body weight) or vehicle was initiated. At 24 weeks, blood pressure measurements, echocardiography and pressure-volume loops were performed. Contractile function, Ca(2+) transients and NCX-mediated Ca(2+) extrusion were measured in isolated ventricular cardiomyocytes. NXT rats (untreated) showed a HFpEF phenotype with left ventricular (LV) hypertrophy, LV end-diastolic pressure (LVEDP) elevation, increased brain natriuretic peptide (BNP) levels, preserved ejection fraction and pulmonary congestion. In cardiomyocytes from untreated NXT rats, early relaxation was prolonged and NCX-mediated Ca(2+) extrusion was decreased. Chronic treatment with ORM-11035 significantly reduced LV hypertrophy and cardiac remodelling without lowering systolic blood pressure. LVEDP [14 ± 3 vs. 9 ± 2 mmHg; NXT (n = 12) vs. NXT + ORM (n = 12); P = 0.0002] and BNP levels [71 ± 12 vs. 49 ± 11 pg/mL; NXT (n = 12) vs. NXT + ORM (n = 12); P
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41. Analysis of Mixtures of Phospholipids in Dimethylformamide : Use of ID pulsed-field-gradient decoupled 1 H-31 P HMBC NMR experiments
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Pollesello, P., Culeddu, N., Bosco, M., Toffanin, R., Carmona, P., editor, Navarro, R., editor, and Hernanz, A., editor
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- 1997
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42. Effects of levosimendan on cardiac remodeling and cardiomyocyte apoptosis in hypertensive Dahl/Rapp rats
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Louhelainen, M, Vahtola, E, Kaheinen, P, Leskinen, H, Merasto, S, Kytö, V, Finckenberg, P, Colucci, W S, Levijoki, J, Pollesello, P, Haikala, H, and Mervaala, E M A
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- 2007
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43. Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper
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Herpain, A, Bouchez, S, Girardis, M, Guarracino, F, Knotzer, J, Levy, B, Liebregts, T, Pollesello, P, Ricksten, S-E, Riha, H, Rudiger, A, Sangalli, F, Herpain, A, Bouchez, S, Girardis, M, Guarracino, F, Knotzer, J, Levy, B, Liebregts, T, Pollesello, P, Ricksten, S-E, Riha, H, Rudiger, A, and Sangalli, F
- Abstract
Levosimendan is an inodilator that promotes cardiac contractility primarily via calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate-sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects via a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland) examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is affirmative and encouraging, which is not the case with other cardio- and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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- 2019
44. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
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M., Tellechea, J. I., Thomas, L. -M., Tong, X., Vavvas, D. G., Veys, R., Vitriol, V., Wang, H. -D., Waugh, J., Webb, S. A., Williams, B. A., Workman, A. D., Xiang, T., Xie, L. -X., Xu, T., Yang, C., Yoon, J. G., Yuan, C. M., Zaritsky, A., Zhao, H., Zuckerman, H., Lyu, R., Pullan, W., Calabro G. E. (ORCID:0000-0003-0259-3797), and Ricciardi W. (ORCID:0000-0002-5655-688X)
- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science.
- Published
- 2019
45. Lipid extracts from different algal species:1H and13C-NMR spectroscopic studies as a new tool to screen differences in the composition of fatty acids, sterols and carotenoids
- Author
-
Pollesello, Piero, Toffanin, Renato, Murano, Erminio, Paoletti, Sergio, Rizzo, Roberto, and Kvam, Bjarne J.
- Published
- 1992
- Full Text
- View/download PDF
46. 1H- and13C-NMR spectroscopic studies of lipid extracts of the red algaGracilaria longa
- Author
-
Pollesello, Piero, Toffanin, Renato, Murano, Erminio, Rizzo, Roberto, Paoletti, Sergio, and Kvam, Bjarne J.
- Published
- 1992
- Full Text
- View/download PDF
47. Interaction of levosimendan with cardiac troponin C in the presence of cardiac troponin I peptides
- Author
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Sorsa, T, Pollesello, P, Permi, P, Drakenberg, T, and Kilpeläinen, I
- Published
- 2003
- Full Text
- View/download PDF
48. The Future for Inotropes in Heart Failure. Do Not Throw the Baby Out With the Bathwater!
- Author
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Pollesello, Piero and Papp, Zoltán
- Published
- 2023
- Full Text
- View/download PDF
49. Heart failure and diabetes: Metabolic alterations and therapeutic interventions: A state-of-The-Art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology
- Author
-
Maack, C. Lehrke, M. Backs, J. Heinzel, F.R. Hulot, J.-S. Marx, N. Paulus, W.J. Rossignol, P. Taegtmeyer, H. Bauersachs, J. Bayes-Genis, A. Brutsaert, D. Bugger, H. Clarke, K. Cosentino, F. De Keulenaer, G. Cas, A.D. González, A. Huelsmann, M. Iaccarino, G. Lunde, I.G. Lyon, A.R. Pollesello, P. Rena, G. Riksen, N.P. Rosano, G. Staels, B. Van Laake, L.W. Wanner, C. Farmakis, D. Filippatos, G. Ruschitzka, F. Seferovic, P. De Boer, R.A. Heymans, S.
- Published
- 2018
50. Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology
- Author
-
Maack, C., Lehrke, M., Backs, J., Heinzel, F.R., Hulot, J.S., Marx, N., Paulus, W.J., Rossignol, P., Taegtmeyer, H., Bauersachs, J., Bayes-Genis, A., Brutsaert, D., Bugger, H., Clarke, K., Cosentino, F., Keulenaer, G. De, Cas, A. Dei, Gonzalez, A., Huelsmann, M., Iaccarino, G., Lunde, I.G., Lyon, A.R., Pollesello, P., Rena, G., Riksen, N.P., Rosano, G., Staels, B., Laake, L.W. van, Wanner, C., Farmakis, D., Filippatos, G., Ruschitzka, F., Seferovic, P., Boer, R.A. de, Heymans, S., Maack, C., Lehrke, M., Backs, J., Heinzel, F.R., Hulot, J.S., Marx, N., Paulus, W.J., Rossignol, P., Taegtmeyer, H., Bauersachs, J., Bayes-Genis, A., Brutsaert, D., Bugger, H., Clarke, K., Cosentino, F., Keulenaer, G. De, Cas, A. Dei, Gonzalez, A., Huelsmann, M., Iaccarino, G., Lunde, I.G., Lyon, A.R., Pollesello, P., Rena, G., Riksen, N.P., Rosano, G., Staels, B., Laake, L.W. van, Wanner, C., Farmakis, D., Filippatos, G., Ruschitzka, F., Seferovic, P., Boer, R.A. de, and Heymans, S.
- Abstract
Contains fulltext : 200148.pdf (Publisher’s version ) (Open Access)
- Published
- 2018
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