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Your search keyword '"Del Lungo, M."' showing total 21 results
Start Over Author "Del Lungo, M." Publication Year Range Last 50 years
21 results on '"Del Lungo, M."'

1. Analysis of fatal adverse drug events recorded in several Italian emergency departments (the MEREAFaPS study)

Author

Pagani, S., Lombardi, N., Crescioli, G., Vighi, G. V., Spada, G., Romoli, I., Andreetta, P., Capuano, A., Marrazzo, E., Marra, A., Leoni, O., Vannacci, A., Venegoni, M., Vighi, G. D., Bettoni, D., Blandizzi, C., Bonaiuti, R., Borsi, V., Cecchi, E., Convertino, I., Del Lungo, M., Di Mauro, C., Farina, G., Ferraro, S., Fucile, A., Galfrascoli, E., Geninatti, E., Giovannetti, L., Leonardi, L., Liccardo, R., Monina, G., Mugelli, A., Parrilli, M., Rafaniello, C., Rossi, F., Rostan, S., Ruocco, M., Sironi, M., Sportiello, L., Tuccori, M., Pagani, S., Lombardi, N., Crescioli, G., Vighi, G. V., Spada, G., Romoli, I., Andreetta, P., Capuano, A., Marrazzo, E., Marra, A., Leoni, O., Vannacci, A., Venegoni, M., Vighi, G. D., Bettoni, D., Blandizzi, C., Bonaiuti, R., Borsi, V., Cecchi, E., Convertino, I., Del Lungo, M., Di Mauro, C., Farina, G., Ferraro, S., Fucile, A., Galfrascoli, E., Geninatti, E., Giovannetti, L., Leonardi, L., Liccardo, R., Monina, G., Mugelli, A., Parrilli, M., Rafaniello, C., Rossi, F., Rostan, S., Ruocco, M., Sironi, M., Sportiello, L., and Tuccori, M.

Subjects
Drug, Male, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, media_common.quotation_subject, Adverse drug reaction, 030204 cardiovascular system & hematology, 03 medical and health sciences, Appropriateness of drug use, Pharmacovigilance, 0302 clinical medicine, Older patients, Internal Medicine, Medicine, Humans, 030212 general & internal medicine, Adverse effect, Drug safety, media_common, Aged, Medication error, business.industry, Public health, Anticoagulants, Mean age, medicine.disease, Italy, Concomitant, Emergency medicine, Emergency Medicine, Female, business, Emergency Service, Hospital, Algorithms, Platelet Aggregation Inhibitors
Abstract

Fatal Adverse Events (FADEs) are a major public health problem, and some FADEs could be preventable. The aim of the present study is to describe the frequency, the drugs involved and the preventability in the FADEs collected through the MEREAFaPS Study between 2012 and 2018. All cases including the outcome “death” have been examined. We excluded cases with vaccine-related ADEs, overdose or suicide, and ADEs occurred during the hospitalisation. Two trained assessors evaluated all cases fulfilling the inclusion criteria. ADEs’ preventability was evaluated applying the Schumock and Thornton algorithm. During the study period, we observed 429 cases of death, 92 of which were excluded. The remaining 337 cases involved 187 women and 150 men, with a mean age of 79 and of 77years, respectively. For each report, the suspected drugs and concomitant ones were 1.26 and 4.20, respectively. Anticoagulants and antiplatelet agents account for more than 40% of FADE cases and the most frequent reactions are haemorrhages (37.5%). The 25% of the FADEs were preventable. This study confirms that FADEs are still a relevant clinical occurrence, and are often caused by widely used old drugs associated with adverse events. The death of one in four patients was preventable. Further efforts should be done to improve the appropriateness of the therapy, especially in older patients who are treated with anticoagulants.

Published
2021

6. Poster session 2

Author

Perez-Pomares, J. M., primary, Ruiz-Villalba, A., additional, Ziogas, A., additional, Segovia, J. C., additional, Ehrbar, M., additional, Munoz-Chapuli, R., additional, De La Rosa, A., additional, Dominguez, J. N., additional, Hove-Madsen, L., additional, Sankova, B., additional, Sedmera, D., additional, Franco, D., additional, Aranega Jimenez, A., additional, Babaeva, G., additional, Chizh, N., additional, Galchenko, S., additional, Sandomirsky, B., additional, Schwarzl, M., additional, Seiler, S., additional, Steendijk, P., additional, Huber, S., additional, Maechler, H., additional, Truschnig-Wilders, M., additional, Pieske, B., additional, Post, H., additional, Simrick, S., additional, Kreutzer, R., additional, Rao, C., additional, Terracciano, C. M., additional, Kirchhof, P., additional, Fabritz, L., additional, Brand, T., additional, Theveniau-Ruissy, M., additional, Parisot, P., additional, Francou, A., additional, Saint-Michel, E., additional, Mesbah, K., additional, Kelly, R. G., additional, Wu, H.-T., additional, Sie, S.-S., additional, Chen, C.-Y., additional, Kuan, T.-C., additional, Lin, C. S., additional, Ismailoglu, Z., additional, Guven, M., additional, Yakici, A., additional, Ata, Y., additional, Ozcan, S., additional, Yildirim, E., additional, Ongen, Z., additional, Miroshnikova, V., additional, Demina, E., additional, Rodygina, T., additional, Kurjanov, P., additional, Denisenko, A., additional, Schwarzman, A., additional, Rubanenko, A., additional, Shchukin, Y., additional, Germanov, A., additional, Goldbergova, M., additional, Parenica, J., additional, Lipkova, J., additional, Pavek, N., additional, Kala, P., additional, Poloczek, M., additional, Vasku, A., additional, Parenicova, I., additional, Spinar, J., additional, Gambacciani, C., additional, Chiavacci, E., additional, Evangelista, M., additional, Vesentini, N., additional, Kusmic, C., additional, Pitto, L., additional, Chernova, A., additional, Nikulina, S. U. Y., additional, Arvanitis, D. A., additional, Mourouzis, I., additional, Pantos, C., additional, Kranias, E. G., additional, Cokkinos, D. V., additional, Sanoudou, D., additional, Vladimirskaya, T. E., additional, Shved, I. A., additional, Kryvorot, S. G., additional, Schirmer, I. M., additional, Appukuttan, A., additional, Pott, L., additional, Jaquet, K., additional, Ladilov, Y., additional, Archer, C. R., additional, Bootman, M. D., additional, Roderick, H. L., additional, Fusco, A., additional, Sorriento, D., additional, Santulli, G., additional, Trimarco, B., additional, Iaccarino, G., additional, Hagenmueller, M., additional, Riffel, J., additional, Bernhold, E., additional, Katus, H. A., additional, Hardt, S. E., additional, Maqsood, A., additional, Zi, M., additional, Prehar, S., additional, Neyses, L., additional, Ray, S., additional, Oceandy, D., additional, Khatami, N., additional, Wadowski, P., additional, Wagh, V., additional, Hescheler, J., additional, Sachinidis, A., additional, Mohl, W., additional, Chaudhry, B., additional, Burns, D., additional, Henderson, D. J., additional, Bax, N. A. M., additional, Van Marion, M. H., additional, Shah, B., additional, Goumans, M. J., additional, Bouten, C. V. C., additional, Van Der Schaft, D. W. J., additional, Van Oorschot, A. A. M., additional, Maas, S., additional, Braun, J., additional, Van Tuyn, J., additional, De Vries, A. A. F., additional, Gittenberger-De Groot, A. C., additional, Bageghni, S., additional, Drinkhill, M. J., additional, Batten, T. F. C., additional, Ainscough, J. F. X., additional, Onate, B., additional, Vilahur, G., additional, Ferrer-Lorente, R., additional, Ybarra, J., additional, Diez-Caballero, A., additional, Ballesta-Lopez, C., additional, Moscatiello, F., additional, Herrero, J., additional, Badimon, L., additional, Martin-Rendon, E., additional, Clifford, D. M., additional, Fisher, S. A., additional, Brusnkill, S. J., additional, Doree, C., additional, Mathur, A., additional, Clarke, M., additional, Watt, S. M., additional, Hernandez-Vera, R., additional, Kavanagh, D., additional, Yemm, A. I., additional, Frampton, J., additional, Kalia, N., additional, Terajima, Y., additional, Shimizu, T., additional, Tsuruyama, S., additional, Ishii, H., additional, Sekine, H., additional, Hagiwara, N., additional, Okano, T., additional, Vrijsen, K. R., additional, Chamuleau, S. A. J., additional, Sluijter, J. P. G., additional, Doevendans, P. F. 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A., additional, Burton, F. L., additional, Smith, G. L., additional, Del Lungo, M., additional, Sartiani, L., additional, Spinelli, V., additional, Baruscotti, M., additional, Difrancesco, D., additional, Mugelli, A., additional, Cerbai, E., additional, Thomas, A. M., additional, Aziz, Q., additional, Khambra, T., additional, Addlestone, J. M. A., additional, Cartwright, E. J., additional, Wilkinson, R., additional, Song, W., additional, Marston, S., additional, Jacquet, A., additional, Mougenot, N. M., additional, Lipskaia, A. J., additional, Paalberends, E. R., additional, Stam, K., additional, Van Dijk, S. J., additional, Van Slegtenhorst, M., additional, Dos Remedios, C., additional, Ten Cate, F. J., additional, Michels, M., additional, Niessen, H. W. M., additional, Stienen, G. J. M., additional, Van Der Velden, J., additional, Read, M. I., additional, Andreianova, A. A., additional, Harrison, J. C., additional, Goulton, C. S., additional, Kerr, D. S., additional, Sammut, I. A., additional, Wallner, M., additional, Von Lewinski, D., additional, Kindsvater, D., additional, Saes, M., additional, Morano, I., additional, Muegge, A., additional, Buyandelger, B., additional, Kostin, S., additional, Gunkel, S., additional, Vouffo, J., additional, Ng, K., additional, Chen, J., additional, Eilers, M., additional, Isaacson, R., additional, Milting, H., additional, Knoell, R., additional, Cattin, M.-E., additional, Crocini, C., additional, Schlossarek, S., additional, Maron, S., additional, Hansen, A., additional, Eschenhagen, T., additional, Carrier, L., additional, Bonne, G., additional, Coppini, R., additional, Ferrantini, C., additional, Olivotto, I., additional, Belardinelli, L., additional, Poggesi, C., additional, Leung, M. C., additional, Messer, A. E., additional, Copeland, O., additional, Marston, S. B., additional, Mills, A. M., additional, Collins, T., additional, O'gara, P., additional, Thum, T., additional, Regalla, K., additional, Macleod, K. T., additional, Prodromakis, T., additional, Chaudhry, U., additional, Darzi, A., additional, Yacoub, M. H., additional, Athanasiou, T., additional, Bogdanova, A., additional, Makhro, A., additional, Hoydal, M., additional, Stolen, T. O., additional, Johnssen, A. B., additional, Alves, M., additional, Catalucci, D., additional, Condorelli, G., additional, Koch, L. G., additional, Britton, S. L., additional, Wisloff, U., additional, Bito, V., additional, Claus, P., additional, Vermeulen, K., additional, Huysmans, C., additional, Ventura-Clapier, R., additional, Sipido, K. R., additional, Seliuk, M. N., additional, Burlaka, A. P., additional, Sidorik, E. P., additional, Khaitovych, N. V., additional, Kozachok, M. M., additional, Potaskalova, V. S., additional, Driesen, R. B., additional, Galan, D. T., additional, De Paulis, D., additional, Arnoux, T., additional, Schaller, S., additional, Pruss, R. M., additional, Poitz, D. M., additional, Augstein, A., additional, Braun-Dullaeus, R. 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G., additional, Hermenegildo, C., additional, Lazaro-Franco, M., additional, Sobrino, A., additional, Bueno-Beti, C., additional, Martinez-Gil, N., additional, Walther, T., additional, Peiro, C., additional, Sanchez-Ferrer, C. F., additional, Novella, S., additional, Ciccarelli, M., additional, Franco, A., additional, Dorn, G. W., additional, Cseplo, P., additional, Torok, O., additional, Springo, Z. S., additional, Vamos, Z., additional, Kosa, D., additional, Hamar, J., additional, Koller, A., additional, Bubb, K. J., additional, Ahluwalia, A., additional, Stepien, E. L., additional, Gruca, A., additional, Grzybowska, J., additional, Goralska, J., additional, Dembinska-Kiec, A., additional, Stolinski, J., additional, Partyka, L., additional, Zhang, H., additional, Sweeney, D., additional, Thomas, G. N., additional, Fish, P. V., additional, Taggart, D. 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J., additional, Mangold, A., additional, Puthenkalam, S., additional, Distelmaier, K., additional, Adlbrecht, C., additional, Lang, I. M., additional, Koizumi, T., additional, Inoue, I., additional, Komiyama, N., additional, Nishimura, S., additional, Korneeva, O. N., additional, Drapkina, O. M., additional, Fornai, L., additional, Angelini, A., additional, Kiss, A., additional, Giskes, F., additional, Eijkel, G., additional, Fedrigo, M., additional, Valente, M. L., additional, Thiene, G., additional, Heeren, R. M. A., additional, Padro, T., additional, Casani, L., additional, Suades, R., additional, Bertoni, B., additional, Carminati, R., additional, Carlini, V., additional, Pettinari, L., additional, Martinelli, C., additional, Gagliano, N., additional, Noppe, G., additional, Buchlin, P., additional, Marquet, N., additional, Baeyens, N., additional, Morel, N., additional, Baysa, A., additional, Sagave, J., additional, Dahl, C. P., additional, Gullestad, L., additional, Carpi, A., additional, Di Lisa, F., additional, Giorgio, M., additional, Vaage, J., additional, Valen, G., additional, Vafiadaki, E., additional, Papalouka, V., additional, Terzis, G., additional, Spengos, K., additional, Manta, P., additional, Gales, C., additional, Genet, G., additional, Dague, E., additional, Cazorla, O., additional, Payre, B., additional, Mias, C., additional, Ouille, A., additional, Lacampagne, A., additional, Pathak, A., additional, Senard, J. M., additional, Abonnenc, M., additional, Da Costa Martins, P., additional, Srivastava, S., additional, Gautel, M., additional, De Windt, L., additional, Comelli, L., additional, Lande, C., additional, Ucciferri, N., additional, Ikonen, L., additional, Vuorenpaa, H., additional, Kujala, K., additional, Sarkanen, J.-R., additional, Heinonen, T., additional, Ylikomi, T., additional, Aalto-Setala, K., additional, Capros, H., additional, Sprincean, N., additional, Usurelu, N., additional, Egorov, V., additional, Stratu, N., additional, Matchkov, V., additional, Bouzinova, E., additional, Moeller-Nielsen, N., additional, Wiborg, O., additional, Gutierrez, P. S., additional, Aparecida-Silva, R., additional, Borges, L. F., additional, Moreira, L. F. P., additional, Dias, R. R., additional, Kalil, J., additional, Stolf, N. A. G., additional, Zhou, W., additional, Suntharalingam, K., additional, Brand, N., additional, Vilar Compte, R., additional, Ying, L., additional, Bicknell, K., additional, Dannoura, A., additional, Dash, P., additional, Brooks, G., additional, Tsimafeyeu, I., additional, Tishova, Y., additional, Wynn, N., additional, Oyeyipo, I. P., additional, Olatunji, L. A., additional, Maegdefessel, L., additional, Azuma, J., additional, Toh, R., additional, Raaz, U., additional, Merk, D. R., additional, Deng, A., additional, Spin, J. M., additional, Tsao, P. S., additional, Tedeschi, L., additional, Taranta, M., additional, Naldi, I., additional, Grimaldi, S., additional, Cinti, C., additional, Bousquenaud, M., additional, Maskali, F., additional, Poussier, S., additional, Marie, P. Y., additional, Boutley, H., additional, Karcher, G., additional, Wagner, D. R., additional, Devaux, Y., additional, Torre, I., additional, Psilodimitrakopoulos, S., additional, Iruretagoiena, I., additional, Gonzalez-Tendero, A., additional, Artigas, D., additional, Loza-Alvarez, P., additional, Gratacos, E., additional, Amat-Roldan, I., additional, Murray, L., additional, Carberry, D. M., additional, Dunton, P., additional, Miles, M. J., additional, Suleiman, M.-S., additional, Kanesalingam, K., additional, Taylor, R., additional, Mc Collum, C. N., additional, Parniczky, A., additional, Solymar, M., additional, Porpaczy, A., additional, Miseta, A., additional, Lenkey, Z. S., additional, Szabados, S., additional, Cziraki, A., additional, Garai, J., additional, Myloslavska, I., additional, Menazza, S. M., additional, Canton, M. C., additional, Di Lisa, F. D. L., additional, Oliveira, S. H. V., additional, Morais, C. A. S., additional, Miranda, M. R., additional, Oliveira, T. T., additional, Lamego, M. R. A., additional, Lima, L. M., additional, Goncharova, N. S., additional, Naymushin, A. V., additional, Kazimli, A. V., additional, Moiseeva, O. M., additional, Carvalho, M. G., additional, Sabino, A. P., additional, Mota, A. P. L., additional, Sousa, M. O., additional, Niessner, A., additional, Richter, B., additional, Hohensinner, P. J., additional, Rychli, K., additional, Zorn, G., additional, Berger, R., additional, Moertl, D., additional, Pacher, R., additional, Wojta, J., additional, Huelsmann, M., additional, Kukharchik, G., additional, Nesterova, N., additional, Pavlova, A., additional, Gaykovaya, L., additional, Krapivka, N., additional, Konstantinova, I., additional, Sichinava, L., additional, Prapa, S., additional, Mccarthy, K. P., additional, Kilner, P. J., additional, Xu, X. Y., additional, Johnson, M. R., additional, Ho, S. Y., additional, Gatzoulis, M. A., additional, Stoupel, E. G., additional, Garcia, R., additional, Merino, D., additional, Montalvo, C., additional, Hurle, M. A., additional, Nistal, J. F., additional, Villar, A. V., additional, Perez-Moreno, A., additional, Gilabert, R., additional, and Ros, E., additional

Published
2012
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7. Abstracts: Pharmacology (Basic Science)

Author

Viero, C., primary, Carney, J., additional, Mason, S., additional, Davies, M., additional, Bannister, M., additional, Williams, A., additional, Sartiani, L., additional, Del Lungo, M., additional, Melchiorre, M., additional, Biel, M., additional, Varro, A., additional, Mugelli, A., additional, Romanelli, M. N., additional, Cerbai, E., additional, Sciarra, L., additional, Marras, E., additional, Zuccaro, L., additional, Allocca, G., additional, De Ruvo, E., additional, Lioy, E., additional, Delise, P., additional, Calo', L., additional, Van Ryn, J., additional, Kink-Eiband, M., additional, Priepke, H., additional, Wienen, W., additional, Gay-Jordi, G., additional, Benito, B., additional, Guasch, E., additional, Serrano-Mollar, A., additional, Sirenko, V., additional, Brugada, J., additional, and Mont, L., additional

Published
2009
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10. Italian Emergency Department Visits and Hospitalizations for Outpatients’ Adverse Drug Events: 12-Year Active Pharmacovigilance Surveillance (The MEREAFaPS Study)

Author

Niccolò Lombardi, Giada Crescioli, Alessandra Bettiol, Marco Tuccori, Annalisa Capuano, Roberto Bonaiuti, Alessandro Mugelli, Mauro Venegoni, Giuseppe Danilo Vighi, Alfredo Vannacci, the MEREAFaPS Study group, Maria Luisa Aiezza, Daria Bettoni, Corrado Blandizzi, Valentina Borsi, Errica Cecchi, Irma Convertino, Martina Del Lungo, Cristina Di Mauro, Gabriella Farina, Sara Ferraro, Annamaria Fucile, Elena Galfrascoli, Elisabetta Geninatti, Linda Giovannetti, Luca Leonardi, Rosa Liccardo, Anna Marra, Eleonora Marrazzo, Giovanna Monina, Silvia Pagani, Maria Parrilli, Concetta Rafaniello, Francesco Rossi, Marco Rossi, Stefania Rostan, Marco Ruocco, Marita Sironi, Giulia Spada, Liberata Sportiello, Giuditta Violetta Vighi, Lombardi, N., Crescioli, G., Bettiol, A., Tuccori, M., Capuano, A., Bonaiuti, R., Mugelli, A., Venegoni, M., Vighi, G. D., Vannacci, A., Aiezza, M. L., Bettoni, D., Blandizzi, C., Borsi, V., Cecchi, E., Convertino, I., Del Lungo, M., Di Mauro, C., Farina, G., Ferraro, S., Fucile, A., Galfrascoli, E., Geninatti, E., Giovannetti, L., Leonardi, L., Liccardo, R., Marra, A., Marrazzo, E., Monina, G., Pagani, S., Parrilli, M., Rafaniello, C., Rossi, F., Rossi, M., Rostan, S., Ruocco, M., Sironi, M., Spada, G., and Sportiello, L.

Subjects
0301 basic medicine, medicine.medical_specialty, drug safety, emergency department, Population, Context (language use), 03 medical and health sciences, seriousness, 0302 clinical medicine, preventability, Pharmacovigilance, Medicine, Pharmacology (medical), education, adverse drug event, Original Research, Pharmacology, education.field_of_study, business.industry, lcsh:RM1-950, Retrospective cohort study, Odds ratio, Emergency department, Confidence interval, 030104 developmental biology, lcsh:Therapeutics. Pharmacology, adverse drug events, hospitalization, pharmacovigilance, 030220 oncology & carcinogenesis, Emergency medicine, Observational study, business
Abstract

Background Adverse drug event (ADEs) are a significant cause of emergency department (ED) visits and consequent hospitalization. Preventing ADEs and their related ED visits in outpatients remains a public health safety challenge. In this context, the aims of the present study were to describe the frequency, seriousness and preventability of outpatients' ADE-related ED visits and hospitalizations in the Italian general population, and to identify the presence of potential predictors of ADE-related hospitalization. Methods We performed a nationwide, multicentre, observational, retrospective study based on reports of suspected ADEs collected between January 1, 2007 and December 31, 2018 in 94 EDs involved in the MEREAFaPS project. Patients' demographic characteristics, their clinical status, suspected and concomitant drugs, ADE description, and its degree of seriousness, were collected. Causality and preventability were assessed using validated algorithms, and logistic regression analyses were used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of ADE-related hospitalization, considering the following covariates: age, sex, ethnicity, number of implicated medications, parenteral administration, presence of interaction, therapeutic error, and/or complementary and alternative medicines (CAM). Results Within 12 years, 61,855 reports of suspected ADE were collected, of which 18,918 (30.6%) resulted in hospitalization (ADE defined as serious). Patients were mostly female (56.6%) and Caucasians (87.7%), with a mean age of 57.5 ± 25.0 years. 58% of patients were treated with more than two drugs, and 47% of ADEs leading to hospitalization were preventable. Anticoagulants, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently implicated agents for ED visits and/or hospitalization, which included clinically significant ADEs, such as haemorrhage for anticoagulants, moderate to severe allergic reactions for antibiotics, and dermatologic reactions and gastrointestinal disturbances for NSAIDs. Older age (1.54 [1.48-1.60]), higher number of concomitantly taken drugs (2.22 [2.14-2.31]), the presence of drug-drug interactions (1.52 [1.28-1.81]), and therapeutic error (1.54 [1.34-1.78]), were significantly associated with an increased risk of hospitalization. Conclusion Our long-term active pharmacovigilance study in ED provided a valid estimation of ADE-related hospitalization in a representative sample of the Italian general population and can suggest further focus on medication safety in outpatients, in order to early recognise and prevent ADEs.

Published
2020

11. Adverse events following cannabis for medical use in Tuscany: An analysis of the Italian Phytovigilance database.

Author

Crescioli G, Lombardi N, Bettiol A, Menniti-Ippolito F, Da Cas R, Parrilli M, Del Lungo M, Gallo E, Mugelli A, Maggini V, Firenzuoli F, and Vannacci A

Subjects
Adverse Drug Reaction Reporting Systems, Databases, Factual, Female, Humans, Italy epidemiology, Middle Aged, Cannabis adverse effects, Drug-Related Side Effects and Adverse Reactions
Abstract

Aims: Despite a significant increase in using cannabis for medical purposes, current evidence on its safety in real-world clinical practice is still poorly characterised. By a case-by-case analysis of spontaneous reports of suspected adverse events (AEs) collected in Tuscany within the Italian Phytovigilance database, the aim of the present study was to describe AEs occurred in patients exposed to medical cannabis., Methods: We evaluated all reports of cannabis-related suspected AEs collected within the Phytovigilance database up to December 2018. Information regarding cannabis therapy, patient's demographic and clinical characteristics, concomitant medications, AE description according to the Medical Dictionary for Regulatory Activities (MedDRA) classification, AE seriousness and AE outcome, were collected. The causality assessment was performed following World Health Organisation-Uppsala Monitoring Centre criteria., Results: Fifty-three cannabis-related AE reports were analysed. The majority of patients were females (77.3%), with a mean age of 61.9 years. Thirty-nine (73.6%) cases were defined as nonserious and the majority of them (86.9%) showed a complete resolution or improvement. Forty-six (86.8%) cases were judged as probably related to cannabis consumption. The most frequently reported system organ class was psychiatric and nervous system disorders, and a potential drug-drug interaction was present in 16 cases., Conclusion: Cannabis was generally well tolerated and the majority of AEs were mild and transient. Our analysis highlighted important safety issues for clinical practice, in particular the need for an accurate prescription monitoring during the titration phase, particularly in the presence of concomitant medications., (© 2019 The British Pharmacological Society.)

Published
2020
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12. EC18 as a Tool To Understand the Role of HCN4 Channels in Mediating Hyperpolarization-Activated Current in Tissues.

Author

Romanelli MN, Del Lungo M, Guandalini L, Zobeiri M, Gyökeres A, Árpádffy-Lovas T, Koncz I, Sartiani L, Bartolucci G, Dei S, Manetti D, Teodori E, Budde T, and Cerbai E

Abstract

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are membrane proteins encoded by four genes (HCN1-4) and widely distributed in the central and peripheral nervous system and in the heart. HCN channels are involved in several physiological functions, including the generation of rhythmic activity, and are considered important drug targets if compounds with isoform selectivity are developed. At present, however, few compounds are known, which are able to discriminate among HCN channel isoforms. The inclusion of the three-methylene chain of zatebradine into a cyclohexane ring gave a compound ( 3a ) showing a 5-fold preference for HCN4 channels, and ability to selectively modulate I h in different tissues. Compound 3a has been tested for its ability to reduce I h and to interact with other ion channels in the heart and the central nervous system. Its preference for HCN4 channels makes this compound useful to elucidate the contribution of this isoform in the physiological and pathological processes involving hyperpolarization-activated current., Competing Interests: The authors declare no competing financial interest.

Published
2019
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13. Selective Blockade of HCN1/HCN2 Channels as a Potential Pharmacological Strategy Against Pain.

Author

Dini L, Del Lungo M, Resta F, Melchiorre M, Spinelli V, Di Cesare Mannelli L, Ghelardini C, Laurino A, Sartiani L, Coppini R, Mannaioni G, Cerbai E, and Romanelli MN

Abstract

A prominent role of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels has been suggested based on their expression and (dys)function in dorsal root ganglion (DRG) neurons, being likely involved in peripheral nociception. Using HCN blockers as antinociceptive drugs is prevented by the widespread distribution of these channels. However, tissue-specific expression of HCN isoforms varies significantly, HCN1 and HCN2 being considered as major players in DRG excitability. We characterized the pharmacological effect of a novel compound, MEL55A, able to block selectively HCN1/HCN2 isoforms, on DRG neuron excitability in-vitro and for its antiallodynic properties in-vivo . HEK293 cells expressing HCN1, HCN2, or HCN4 isoforms were used to verify drug selectivity. The pharmacological profile of MEL55A was tested on mouse DRG neurons by patch-clamp recordings, and in-vivo in oxaliplatin-induced neuropathy by means of thermal hypersensitivity. Results were compared to the non-isoform-selective drug, ivabradine. MEL55A showed a marked preference toward HCN1 and HCN2 isoforms expressed in HEK293, with respect to HCN4. In cultured DRG, MEL55A reduced I h amplitude, both in basic conditions and after stimulation by forskolin, and cell excitability, its effect being quantitatively similar to that observed with ivabradine. MEL55A was able to relieve chemotherapy-induced neuropathic pain. In conclusion, selective blockade of HCN1/HCN2 channels, over HCN4 isoform, was able to modulate electrophysiological properties of DRG neurons similarly to that reported for classical I h blockers, ivabradine, resulting in a pain-relieving activity. The availability of small molecules with selectivity toward HCN channel isoforms involved in nociception might represent a safe and effective strategy against chronic pain.

Published
2018
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14. Perturbations of heart development and function in cardiomyocytes from human embryonic stem cells with trisomy 21.

Author

Bosman A, Letourneau A, Sartiani L, Del Lungo M, Ronzoni F, Kuziakiv R, Tohonen V, Zucchelli M, Santoni F, Guipponi M, Dumevska B, Hovatta O, Antonarakis SE, and Jaconi ME

Subjects
Action Potentials, Cell Differentiation, Cell Line, Chromosomes, Human, Pair 21 genetics, Down Syndrome genetics, Gene Expression Regulation, Developmental, Genetic Association Studies, Heart Defects, Congenital genetics, Humans, Models, Biological, Myocytes, Cardiac metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Sequence Analysis, RNA, Transcriptome genetics, Down Syndrome pathology, Down Syndrome physiopathology, Heart embryology, Heart physiopathology, Human Embryonic Stem Cells metabolism, Myocytes, Cardiac pathology
Abstract

Congenital heart defects (CHD) occur in approximately 50% of patients with Down syndrome (DS); the mechanisms for this occurrence however remain unknown. In order to understand how these defects evolve in early development in DS, we focused on the earliest stages of cardiogenesis to ascertain perturbations in development leading to CHD. Using a trisomy 21 (T21) sibling human embryonic stem cell (hESC) model of DS, we show that T21-hESC display many significant differences in expression of genes and cell populations associated with mesodermal, and more notably, secondary heart field (SHF) development, in particular a reduced number of ISL1(+) progenitor cells. Furthermore, we provide evidence for two candidate genes located on chromosome 21, ETS2 and ERG, whose overexpression during cardiac commitment likely account for the disruption of SHF development, as revealed by downregulation or overexpression experiments. Additionally, we uncover an abnormal electrophysiological phenotype in functional T21 cardiomyocytes, a result further supported by mRNA expression data acquired using RNA-Seq. These data, in combination, revealed a cardiomyocyte-specific phenotype in T21 cardiomyocytes, likely due to the overexpression of genes such as RYR2, NCX, and L-type Ca(2+) channel. These results contribute to the understanding of the mechanisms involved in the development of CHD. Stem Cells 2015;33:1434-1446., (© 2015 AlphaMed Press.)

Published
2015
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15. Chronic atrial fibrillation alters the functional properties of If in the human atrium.

Author

Stillitano F, Lonardo G, Giunti G, Del Lungo M, Coppini R, Spinelli V, Sartiani L, Poggesi C, Mugelli A, and Cerbai E

Subjects
Action Potentials, Adrenergic beta-Agonists pharmacology, Adult, Aged, Aged, 80 and over, Atrial Fibrillation genetics, Atrial Natriuretic Factor pharmacology, Chronic Disease, Female, Heart Atria metabolism, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels genetics, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels metabolism, Male, MicroRNAs metabolism, Middle Aged, Muscle Proteins genetics, Muscle Proteins metabolism, Potassium Channels drug effects, Potassium Channels genetics, RNA Processing, Post-Transcriptional, RNA, Messenger metabolism, Serotonin 5-HT4 Receptor Agonists pharmacology, Transcription, Genetic, Atrial Fibrillation metabolism, Potassium Channels metabolism
Abstract

Introduction: Despite the evidence that the hyperpolarization-activated current (If) is highly modulated in human cardiomyopathies, no definite data exist in chronic atrial fibrillation (cAF). We investigated the expression, function, and modulation of If in human cAF., Methods and Results: Right atrial samples were obtained from sinus rhythm (SR, n = 49) or cAF (duration >1 year, n = 31) patients undergoing corrective cardiac surgery. Among f-channel isoforms expressed in the human atrium (HCN1, 2 and 4), HCN4 mRNA levels measured by RT-PCR were significantly reduced. However, protein expression was preserved in cAF compared to SR (+85% for HCN4); concurrently, miR-1 expression was significantly reduced. In patch-clamped atrial myocytes, current-specific conductance (gf) was significantly increased in cAF at voltages around the threshold for If activation (-60 to -80 mV); accordingly, a 10-mV rightward shift of the activation curve occurred (P < 0.01). β-Adrenergic and 5-HT4 receptor stimulation exerted similar effects on If in cAF and SR cells, while the ANP-mediated effect was significantly reduced (P < 0.02), suggesting downregulation of natriuretic peptide signaling., Conclusions: In human cAF modifications in transcriptional and posttranscriptional mechanisms of HCN channels occur, associated with a slight yet significant gain-of-function of If , which may contribute to enhanced atrial ectopy., (© 2013 Wiley Periodicals, Inc.)

Published
2013
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16. Response to letter regarding article, "Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy".

Author

Coppini R, Ferrantini C, Del Lungo M, Stillitano F, Sartiani L, Tosi B, Suffredini S, Tesi C, Poggesi C, Cerbai E, Mugelli A, Yao L, Fan P, Belardinelli L, Yacoub M, and Olivotto I

Subjects
Female, Humans, Male, Acetanilides pharmacology, Action Potentials drug effects, Cardiomyopathy, Hypertrophic physiopathology, Myocytes, Cardiac drug effects, Piperazines pharmacology, Sodium Channel Blockers pharmacology
Published
2013
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17. Molecular and functional evidence of HCN4 and caveolin-3 interaction during cardiomyocyte differentiation from human embryonic stem cells.

Author

Bosman A, Sartiani L, Spinelli V, Del Lungo M, Stillitano F, Nosi D, Mugelli A, Cerbai E, and Jaconi M

Subjects
Caveolae metabolism, Cell Differentiation, Cells, Cultured, Cyclic Nucleotide-Gated Cation Channels metabolism, Electrophysiological Phenomena, Humans, Patch-Clamp Techniques, Sarcolemma, Caveolin 3 metabolism, Embryonic Stem Cells physiology, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels metabolism, Muscle Proteins metabolism, Myocytes, Cardiac cytology, Myocytes, Cardiac metabolism, Potassium Channels metabolism
Abstract

Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) is accompanied by changes in ion channel expression, with relevant electrophysiological consequences. In rodent CM, the properties of hyperpolarization-activated cyclic nucleotide-gated channel (HCN)4, a major f-channel isoform, depends on the association with caveolin-3 (Cav3). To date, no information exists on changes in Cav3 expression and its associative relationship with HCN4 upon hESC-CM maturation. We hypothesize that Cav3 expression and its compartmentalization with HCN4 channels during hESC-CM maturation accounts for the progression of f-current properties toward adult phenotypes. To address this, hESC were differentiated into spontaneously beating CM and examined at ∼30, ∼60, and ∼110 days of differentiation. Human adult and fetal CM served as references. HCN4 and Cav3 expression and localization were analyzed by real time PCR and immunocyto/histochemistry. F-current was measured in patch-clamped single cells. HCN4 and Cav3 colocalize in adult human atrial and ventricular CM, but not in fetal CM. Proteins and mRNA for Cav3 were not detected in undifferentiated hESC, but expression increased during hESC-CM maturation. At 110 days, HCN4 appeared to be colocalized with Cav3. Voltage-dependent activation of the f-current was significantly more positive in fetal CM and 60-day hESC-CM (midpoint activation, V1/2, ∼ -82 mV) than in 110-day hESC-CM or adult CM (V1/2∼-100 mV). In the latter cells, caveolae disruption reversed voltage dependence toward a more positive or an immature phenotype, with V1/2 at -75 mV, while in fetal CM voltage dependence was not affected. Our data show, for the first time, a developmental change in HCN4-Cav3 association in hESC-CM. Cav3 expression and its association with ionic channels likely represent a crucial step of cardiac maturation.

Published
2013
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18. Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes.

Author

Paci M, Sartiani L, Del Lungo M, Jaconi M, Mugelli A, Cerbai E, and Severi S

Subjects
Calcium metabolism, Electric Conductivity, Fibroblasts cytology, Humans, Intracellular Space drug effects, Intracellular Space metabolism, Myocytes, Cardiac drug effects, Myocytes, Cardiac metabolism, Potassium Channel Blockers pharmacology, Time Factors, Action Potentials drug effects, Cell Differentiation drug effects, Embryonic Stem Cells cytology, Models, Biological, Myocytes, Cardiac cytology
Abstract

Background: Human embryonic stem cell derived cardiomyocytes (hESC-CMs) hold high potential for basic and applied cardiovascular research. The development of a reliable simulation platform able to mimic the functional properties of hESC-CMs would be of considerable value to perform preliminary test complementing in vitro experimentations., Methods: We developed the first computational model of hESC-CM action potential by integrating our original electrophysiological recordings of transient-outward, funny, and sodium-calcium exchanger currents and data derived from literature on sodium, calcium and potassium currents in hESC-CMs., Results: The model is able to reproduce basal electrophysiological properties of hESC-CMs at 15 40 days of differentiation (Early stage). Moreover, the model reproduces the modifications occurring through the transition from Early to Late developmental stage (50-110, days of differentiation). After simulated blockade of ionic channels and pumps of the sarcoplasmic reticulum, Ca2+ transient amplitude was decreased by 12% and 33% in Early and Late stage, respectively, suggesting a growing contribution of a functional reticulum during maturation. Finally, as a proof of concept, we tested the effects induced by prototypical channel blockers, namely E4031 and nickel, and their qualitative reproduction by the model., Conclusions: This study provides a novel modelling tool that may serve useful to investigate physiological properties of hESC-CMs.

Published
2012
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19. Novel blockers of hyperpolarization-activated current with isoform selectivity in recombinant cells and native tissue.

Author

Del Lungo M, Melchiorre M, Guandalini L, Sartiani L, Mugelli A, Koncz I, Szel T, Varro A, Romanelli MN, and Cerbai E

Subjects
Animals, Dogs, Female, Ganglia, Spinal cytology, Guinea Pigs, HEK293 Cells, Humans, In Vitro Techniques, Male, Mice, Muscle Cells drug effects, Muscle Cells physiology, Neurons drug effects, Neurons physiology, Patch-Clamp Techniques, Protein Isoforms antagonists & inhibitors, Purkinje Fibers drug effects, Sinoatrial Node cytology, Benzazepines pharmacology, Cyclic Nucleotide-Gated Cation Channels antagonists & inhibitors, Cyclohexanes pharmacology
Abstract

BACKGROUND AND PURPOSE Selective hyperpolarization activated, cyclic nucleotide-gated channel (HCN) blockers represent an important therapeutic goal due to the wide distribution and multiple functions of these proteins, representing the molecular correlate of f- and h-current (I(f) or I(h) ). Recently, new compounds able to block differentially the homomeric HCN isoforms expressed in HEK293 have been synthesized. In the present work, the electrophysiological and pharmacological properties of these new HCN blockers were characterized and their activities evaluated on native channels. EXPERIMENTAL APPROACH HEK293 cells expressing mHCN1, mHCN2 and hHCN4 isoforms were used to verify channel blockade. Selected compounds were tested on native guinea pig sinoatrial node cells and neurons from mouse dorsal root ganglion (DRG) by patch-clamp recordings and on dog Purkinje fibres by intracellular recordings. KEY RESULTS In HEK293 cells, EC18 was found to be significantly selective for HCN4 and MEL57A for HCN1 at physiological membrane potential. When tested on guinea pig sinoatrial node cells, EC18 (10 µM) maintained its activity, reducing I(f) by 67% at -120 mV, while MEL57A (3 µM) reduced I(f) by 18%. In contrast, in mouse DRG neurons, only MEL57A (30 and 100 µM) significantly reduced I(h) by 60% at -80 mV. In dog cardiac Purkinje fibres, EC18, but not MEL57A, reduced the amplitude and slowed the slope of the spontaneous diastolic depolarization. CONCLUSIONS Our results have identified novel and highly selective HCN isoform blockers, EC18 and MEL57A; the selectivity found in recombinant system was maintained in various tissues expressing different HCN isoforms., (© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.)

Published
2012
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20. Design, synthesis, and preliminary biological evaluation of new isoform-selective f-current blockers.

Author

Melchiorre M, Del Lungo M, Guandalini L, Martini E, Dei S, Manetti D, Scapecchi S, Teodori E, Sartiani L, Mugelli A, Cerbai E, and Romanelli MN

Subjects
Animals, Benzazepines chemistry, Benzazepines pharmacology, Cell Line, Guinea Pigs, Heart Rate drug effects, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, In Vitro Techniques, Mice, Patch-Clamp Techniques, Potassium Channels, Propylamines chemistry, Propylamines pharmacology, Protein Isoforms antagonists & inhibitors, Stereoisomerism, Stimulation, Chemical, Benzazepines chemical synthesis, Cyclic Nucleotide-Gated Cation Channels antagonists & inhibitors, Ion Channels antagonists & inhibitors, Muscle Proteins antagonists & inhibitors, Propylamines chemical synthesis
Abstract

New I(f) blockers have been designed and tested on HEK293 cells stably expressing the HCN1, HCN2, and HCN4 channels to find compounds able to discriminate among the channel isoforms. Among the synthesized compounds, the cis-butene derivative (R)-5 shows some preference for HCN2 while the pseudodimeric product (R)-6 shows selectivity for HCN1. These compounds can be important pharmacological tools to study the channels in native tissues and may be useful to design safe drugs.

Published
2010
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21. [Not Available].

Author

Del Lungo M

Subjects
History, Early Modern 1451-1600, History, Modern 1601-, Italy, Public Health history, Sexually Transmitted Diseases history
Published
1983

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