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4. Language production impairments in patients with a first episode of psychosis

Author

Gargano, G, Caletti, E, Perlini, C, Turtulici, N, Bellani, M, Bonivento, C, Garzitto, M, Siri, F, Longo, C, Bonetto, C, Cristofalo, D, Scocco, P, Semrov, E, Preti, A, Lazzarotto, L, Gardellin, F, Lasalvia, A, Ruggeri, M, Marini, A, Brambilla, P, Bertani, M, Bissoli, S, De Santi, K, Lunardi, S, Negretto, V, Poli, S, Tosato, S, Zamboni, M, Ballarin, M, De Girolamo, G, Fioritti, A, Neri, G, Pileggi, F, Rucci, P, Chiavetto, L, Scasselatti, C, Zanardini, R, Bertoldo, A, Marinelli, V, Rambaldelli, G, Bardella, S, Lamonaca, D, Lunardon, M, Magnabosco, R, Martucci, M, Nicolau, S, Nifosi, F, Pavanati, M, Rossi, M, Piazza, C, Piccione, G, Sala, A, Sale, A, Stefani, B, Zotos, S, Balbo, M, Boggian, I, Ceccato, E, Dall'Agnola, R, Girotto, B, Goss, C, Leoni, R, Mai, A, Pasqualini, A, Roccato, S, Rossi, A, Strizzolo, S, Urbani, A, Aldi, F, Bianchi, B, Cappellari, P, Conti, R, De Battisti, L, Lazzarin, E, Merlin, S, Migliorini, G, Pozzan, T, Sarto, L, Visona, S, Brazzoli, A, Campi, A, Carmagnani, R, Giambelli, S, Gianella, A, Lunardi, L, Madaghiele, D, Maestrelli, P, Paiola, L, Posteri, E, Viola, L, Zamberlan, V, Zenari, M, Zanoni, M, Bonadonna, G, Bonomo, M, Santonastaso, P, Cremonese, C, Veronese, A, Anderle, P, Angelozzi, A, Baron, I, Candeago, E, Castelli, F, Chieco, M, Di Costanzo, E, Derossi, M, Doriguzzi, M, Galvano, O, Lattanzi, M, Lezzi, R, Marcato, M, Marcolin, A, Marini, F, Matranga, M, Scalabrin, D, Zucchetto, M, Zadro, F, Austoni, G, Bianco, M, Bordino, F, Dario, F, De Risio, A, Gatto, A, Grana, S, Favero, E, Franceschini, A, Friederici, S, Marangon, V, Pascolo, M, Ramon, L, Zambolin, S, Riolo, R, Buffon, A, Di Bortolo, E, Fortin, S, Matarrese, F, Mogni, S, Codemo, N, Russi, A, Silvestro, A, Turella, E, Viel, P, Dominoni, A, Andreose, L, Boemio, M, Bressan, L, Cabbia, A, Canesso, E, Cian, R, Dal Piccol, C, Pasqua, M, Di Prisco, A, Mantellato, L, Luison, M, Morgante, S, Santi, M, Sacillotto, M, Scabbio, M, Sponga, P, Sguotto, M, Stach, F, Vettorato, M, Martinello, G, Dassie, F, Marino, S, Cibiniel, L, Masetto, I, Cabianca, O, Valente, A, Caberlotto, L, Passoni, A, Flumian, P, Daniel, L, Gion, M, Stanziale, S, Alborino, F, Bortolozzo, V, Bacelle, L, Bicciato, L, Basso, D, Navaglia, F, Manoni, F, Ercolin, M, Giubilini, F, Imbesi, M, Leuci, E, Mazzi, F, Anelli, S, Amore, M, Bigi, L, Britta, W, Anna, G, Bonatti, U, Borziani, M, Crosato, S, Fabris, I, Galluccio, R, Galeotti, M, Gozzi, M, Greco, V, Guagnini, E, Pagani, S, Maccherozzi, S, Malvasi, R, Marchi, F, Melato, E, Mazzucchi, E, Marzullo, F, Pellegrini, P, Petrolini, N, Volta, P, Bonara, F, Brusamonti, E, Croci, R, Flamia, I, Fontana, F, Losi, R, Marchioro, R, Raffaini, L, Ruju, L, Saginario, A, Tondelli, M, Marrama, D, Bernardelli, L, Bonacini, F, Florindo, A, Merli, M, Nappo, P, Sola, L, Tondelli, O, Tonna, M, Torre, M, Tosatti, M, Venturelli, G, Zampolla, D, Bernardi, A, Cavalli, C, Cigala, L, Ciraudo, C, Di Bari, A, Ferri, L, Gombi, F, Leurini, S, Mandatelli, E, Maccaferri, S, Oroboncoide, M, Pisa, B, Ricci, C, Poggi, E, Zurlini, C, Malpeli, M, Colla, R, Teodori, E, Vecchia, L, D'Andrea, R, Trenti, T, Paolini, P, Carpeggiani, P, Ghigi, D, Gagliostro, M, Pratelli, M, Antonelli, A, Battistini, L, Bellini, F, Bonini, E, Capelli, C, Didomizio, C, Drei, C, Fucci, G, Gualandi, A, Grazia, M, Losi, A, Mazzoni, F, Marangoni, D, Monna, G, Morselli, M, Oggioni, A, Oprandi, S, Paganelli, W, Passerini, M, Piscitelli, M, Reggiani, G, Rossi, G, Salvatori, F, Trasforini, S, Uslenghi, C, Veggetti, S, Bartolucci, G, Baruffa, R, Bertelli, R, Borghi, L, Ciavarella, P, Paltrinieri, E, Rizzardi, F, Serra, P, Suzzi, D, Arienti, P, Aureli, F, Avanzi, R, Callegari, V, Corsino, A, Host, P, Michetti, R, Rizzo, F, Simoncelli, P, Soldati, E, Succi, E, Bertozzi, M, Canetti, E, Cavicchioli, L, Ceccarelli, E, Cenni, S, Marzola, G, Gallina, V, Leoni, C, Olivieri, A, Piccolo, E, Ravagli, S, Russo, R, Tedeschini, D, Verenini, M, Abram, W, Granata, V, Curcio, A, Guerra, G, Granini, S, Natali, L, Montanari, E, Pasi, F, Ventura, U, Valenti, S, Francesca, M, Farneti, R, Ravagli, P, Floris, R, Maroncelli, O, Volpones, G, Casali, D, Miceli, M, Bencini, A, Cellini, M, De Biase, L, Barbara, L, Charles, L, Pratesi, C, Tanini, A, Loparrino, R, Ulivelli, C, Cussoto, C, Dei, N, Fumanti, E, Pantani, M, Zeloni, G, Bellini, R, Cellesi, R, Dorigo, N, Gulli, P, Ialeggio, L, Pisanu, M, Rinaldi, G, Konze, A, Cocchi, A, Meneghelli, A, Frova, M, Monzani, E, Zanobio, A, Malagoli, M, Pagani, R, Barbera, S, Morganti, C, Amade, E, Brambilla, V, Montanari, A, Caterina, G, Lopez, C, Marocchi, A, Moletta, A, Sberna, M, Cascio, M, Scarone, S, Gargano G., Caletti E., Perlini C., Turtulici N., Bellani M., Bonivento C., Garzitto M., Siri F. M., Longo C., Bonetto C., Cristofalo D., Scocco P., Semrov E., Preti A., Lazzarotto L., Gardellin F., Lasalvia A., Ruggeri M., Marini A., Brambilla P., Bertani M. E., Bissoli S., De Santi K., Lunardi S., Negretto V., Poli S., Tosato S., Zamboni M. G., Ballarin M., De Girolamo G., Fioritti A., Neri G., Pileggi F., Rucci P., Chiavetto L. B., Scasselatti C., Zanardini R., Bertoldo A., Marinelli V., Rambaldelli G., Bardella S., Lamonaca D., Lunardon M., Magnabosco R., Martucci M., Nicolau S., Nifosi F., Pavanati M., Rossi M., Piazza C., Piccione G., Sala A., Sale A., Stefani B., Zotos S., Balbo M., Boggian I., Ceccato E., Dall'Agnola R., Girotto B., Goss C., Leoni R., Mai A., Pasqualini A., Roccato S., Rossi A., Strizzolo S., Urbani A., Aldi F., Bianchi B., Cappellari P., Conti R., De Battisti L., Lazzarin E., Merlin S., Migliorini G., Pozzan T., Sarto L., Visona S., Brazzoli A., Campi A., Carmagnani R., Giambelli S., Gianella A., Lunardi L., Madaghiele D., Maestrelli P., Paiola L., Posteri E., Viola L., Zamberlan V., Zenari M., Zanoni M., Bonadonna G., Bonomo M., Santonastaso P., Cremonese C., Veronese A., Anderle P., Angelozzi A., Baron I. A. G., Candeago E. B. F., Castelli F., Chieco M., Di Costanzo E., Derossi M., Doriguzzi M., Galvano O., Lattanzi M., Lezzi R., Marcato M., Marcolin A., Marini F., Matranga M., Scalabrin D., Zucchetto M., Zadro F., Austoni G., Bianco M., Bordino F., Dario F., De Risio A., Gatto A., Grana S., Favero E., Franceschini A., Friederici S., Marangon V., Pascolo M., Ramon L., Zambolin S., Riolo R., Buffon A., Di Bortolo E., Fortin S., Matarrese F., Mogni S., Codemo N., Russi A., Silvestro A., Turella E., Viel P., Dominoni A., Andreose L., Boemio M., Bressan L., Cabbia A., Canesso E., Cian R., Dal Piccol C., Pasqua M. M. D., Di Prisco A., Mantellato L., Luison M., Morgante S., Santi M., Sacillotto M., Scabbio M., Sponga P., Sguotto M., Stach F., Vettorato M., Martinello G., Dassie F., Marino S., Cibiniel L., Masetto I., Cabianca O., Valente A., Caberlotto L., Passoni A., Flumian P., Daniel L., Gion M., Stanziale S., Alborino F., Bortolozzo V., Bacelle L., Bicciato L., Basso D., Navaglia F., Manoni F., Ercolin M., Giubilini F., Imbesi M., Leuci E., Mazzi F., Anelli S., Amore M., Bigi L., Britta W., Anna G. B., Bonatti U., Borziani M., Crosato S., Fabris I., Galluccio R., Galeotti M., Gozzi M., Greco V., Guagnini E., Pagani S., Maccherozzi S., Malvasi R., Marchi F., Melato E., Mazzucchi E., Marzullo F., Pellegrini P., Petrolini N., Volta P., Bonara F., Brusamonti E., Croci R., Flamia I., Fontana F., Losi R., Marchioro R., Raffaini L., Ruju L., Saginario A., Tondelli M., Marrama D., Bernardelli L., Bonacini F., Florindo A., Merli M., Nappo P., Sola L., Tondelli O., Tonna M., Torre M., Tosatti M., Venturelli G., Zampolla D., Bernardi A., Cavalli C., Cigala L., Ciraudo C., Di Bari A., Ferri L., Gombi F., Leurini S., Mandatelli E., Maccaferri S., Oroboncoide M., Pisa B., Ricci C., Poggi E., Zurlini C., Malpeli M., Colla R., Teodori E., Vecchia L., D'Andrea R., Trenti T., Paolini P., Carpeggiani P., Ghigi D., Gagliostro M., Pratelli M., Antonelli A., Battistini L., Bellini F., Bonini E., Capelli C. B. R., DiDomizio C., Drei C., Fucci G., Gualandi A., Grazia M. R., Losi A. M., Mazzoni F. M. P., Marangoni D., Monna G., Morselli M., Oggioni A., Oprandi S., Paganelli W., Passerini M., Piscitelli M., Reggiani G., Rossi G., Salvatori F., Trasforini S., Uslenghi C., Veggetti S., Bartolucci G., Baruffa R., Bertelli R., Borghi L., Ciavarella P., Paltrinieri E., Rizzardi F., Serra P., Suzzi D., Arienti P., Aureli F., Avanzi R., Callegari V., Corsino A., Host P., Michetti R., Rizzo F., Simoncelli P., Soldati E., Succi E., Bertozzi M., Canetti E., Cavicchioli L., Ceccarelli E., Cenni S., Marzola G., Gallina V., Leoni C., Olivieri A., Piccolo E., Ravagli S., Russo R., Tedeschini D., Verenini M., Abram W., Granata V., Curcio A., Guerra G., Granini S., Natali L., Montanari E., Pasi F., Ventura U., Valenti S., Francesca M., Farneti R., Ravagli P., Floris R., Maroncelli O., Volpones G., Casali D., Miceli M., Bencini A., Cellini M., De Biase L., Barbara L., Charles L., Pratesi C., Tanini A., Loparrino R., Ulivelli C., Cussoto C., Dei N., Fumanti E., Pantani M., Zeloni G., Bellini R., Cellesi R., Dorigo N., Gulli P., Ialeggio L., Pisanu M., Rinaldi G., Konze A., Cocchi A., Meneghelli A., Frova M., Monzani E., Zanobio A., Malagoli M., Pagani R., Barbera S., Morganti C., Amade E. S., Brambilla V., Montanari A., Caterina G., Lopez C., Marocchi A., Moletta A., Sberna M., Cascio M. T., Scarone S., Gargano, G, Caletti, E, Perlini, C, Turtulici, N, Bellani, M, Bonivento, C, Garzitto, M, Siri, F, Longo, C, Bonetto, C, Cristofalo, D, Scocco, P, Semrov, E, Preti, A, Lazzarotto, L, Gardellin, F, Lasalvia, A, Ruggeri, M, Marini, A, Brambilla, P, Bertani, M, Bissoli, S, De Santi, K, Lunardi, S, Negretto, V, Poli, S, Tosato, S, Zamboni, M, Ballarin, M, De Girolamo, G, Fioritti, A, Neri, G, Pileggi, F, Rucci, P, Chiavetto, L, Scasselatti, C, Zanardini, R, Bertoldo, A, Marinelli, V, Rambaldelli, G, Bardella, S, Lamonaca, D, Lunardon, M, Magnabosco, R, Martucci, M, Nicolau, S, Nifosi, F, Pavanati, M, Rossi, M, Piazza, C, Piccione, G, Sala, A, Sale, A, Stefani, B, Zotos, S, Balbo, M, Boggian, I, Ceccato, E, Dall'Agnola, R, Girotto, B, Goss, C, Leoni, R, Mai, A, Pasqualini, A, Roccato, S, Rossi, A, Strizzolo, S, Urbani, A, Aldi, F, Bianchi, B, Cappellari, P, Conti, R, De Battisti, L, Lazzarin, E, Merlin, S, Migliorini, G, Pozzan, T, Sarto, L, Visona, S, Brazzoli, A, Campi, A, Carmagnani, R, Giambelli, S, Gianella, A, Lunardi, L, Madaghiele, D, Maestrelli, P, Paiola, L, Posteri, E, Viola, L, Zamberlan, V, Zenari, M, Zanoni, M, Bonadonna, G, Bonomo, M, Santonastaso, P, Cremonese, C, Veronese, A, Anderle, P, Angelozzi, A, Baron, I, Candeago, E, Castelli, F, Chieco, M, Di Costanzo, E, Derossi, M, Doriguzzi, M, Galvano, O, Lattanzi, M, Lezzi, R, Marcato, M, Marcolin, A, Marini, F, Matranga, M, Scalabrin, D, Zucchetto, M, Zadro, F, Austoni, G, Bianco, M, Bordino, F, Dario, F, De Risio, A, Gatto, A, Grana, S, Favero, E, Franceschini, A, Friederici, S, Marangon, V, Pascolo, M, Ramon, L, Zambolin, S, Riolo, R, Buffon, A, Di Bortolo, E, Fortin, S, Matarrese, F, Mogni, S, Codemo, N, Russi, A, Silvestro, A, Turella, E, Viel, P, Dominoni, A, Andreose, L, Boemio, M, Bressan, L, Cabbia, A, Canesso, E, Cian, R, Dal Piccol, C, Pasqua, M, Di Prisco, A, Mantellato, L, Luison, M, Morgante, S, Santi, M, Sacillotto, M, Scabbio, M, Sponga, P, Sguotto, M, Stach, F, Vettorato, M, Martinello, G, Dassie, F, Marino, S, Cibiniel, L, Masetto, I, Cabianca, O, Valente, A, Caberlotto, L, Passoni, A, Flumian, P, Daniel, L, Gion, M, Stanziale, S, Alborino, F, Bortolozzo, V, Bacelle, L, Bicciato, L, Basso, D, Navaglia, F, Manoni, F, Ercolin, M, Giubilini, F, Imbesi, M, Leuci, E, Mazzi, F, Anelli, S, Amore, M, Bigi, L, Britta, W, Anna, G, Bonatti, U, Borziani, M, Crosato, S, Fabris, I, Galluccio, R, Galeotti, M, Gozzi, M, Greco, V, Guagnini, E, Pagani, S, Maccherozzi, S, Malvasi, R, Marchi, F, Melato, E, Mazzucchi, E, Marzullo, F, Pellegrini, P, Petrolini, N, Volta, P, Bonara, F, Brusamonti, E, Croci, R, Flamia, I, Fontana, F, Losi, R, Marchioro, R, Raffaini, L, Ruju, L, Saginario, A, Tondelli, M, Marrama, D, Bernardelli, L, Bonacini, F, Florindo, A, Merli, M, Nappo, P, Sola, L, Tondelli, O, Tonna, M, Torre, M, Tosatti, M, Venturelli, G, Zampolla, D, Bernardi, A, Cavalli, C, Cigala, L, Ciraudo, C, Di Bari, A, Ferri, L, Gombi, F, Leurini, S, Mandatelli, E, Maccaferri, S, Oroboncoide, M, Pisa, B, Ricci, C, Poggi, E, Zurlini, C, Malpeli, M, Colla, R, Teodori, E, Vecchia, L, D'Andrea, R, Trenti, T, Paolini, P, Carpeggiani, P, Ghigi, D, Gagliostro, M, Pratelli, M, Antonelli, A, Battistini, L, Bellini, F, Bonini, E, Capelli, C, Didomizio, C, Drei, C, Fucci, G, Gualandi, A, Grazia, M, Losi, A, Mazzoni, F, Marangoni, D, Monna, G, Morselli, M, Oggioni, A, Oprandi, S, Paganelli, W, Passerini, M, Piscitelli, M, Reggiani, G, Rossi, G, Salvatori, F, Trasforini, S, Uslenghi, C, Veggetti, S, Bartolucci, G, Baruffa, R, Bertelli, R, Borghi, L, Ciavarella, P, Paltrinieri, E, Rizzardi, F, Serra, P, Suzzi, D, Arienti, P, Aureli, F, Avanzi, R, Callegari, V, Corsino, A, Host, P, Michetti, R, Rizzo, F, Simoncelli, P, Soldati, E, Succi, E, Bertozzi, M, Canetti, E, Cavicchioli, L, Ceccarelli, E, Cenni, S, Marzola, G, Gallina, V, Leoni, C, Olivieri, A, Piccolo, E, Ravagli, S, Russo, R, Tedeschini, D, Verenini, M, Abram, W, Granata, V, Curcio, A, Guerra, G, Granini, S, Natali, L, Montanari, E, Pasi, F, Ventura, U, Valenti, S, Francesca, M, Farneti, R, Ravagli, P, Floris, R, Maroncelli, O, Volpones, G, Casali, D, Miceli, M, Bencini, A, Cellini, M, De Biase, L, Barbara, L, Charles, L, Pratesi, C, Tanini, A, Loparrino, R, Ulivelli, C, Cussoto, C, Dei, N, Fumanti, E, Pantani, M, Zeloni, G, Bellini, R, Cellesi, R, Dorigo, N, Gulli, P, Ialeggio, L, Pisanu, M, Rinaldi, G, Konze, A, Cocchi, A, Meneghelli, A, Frova, M, Monzani, E, Zanobio, A, Malagoli, M, Pagani, R, Barbera, S, Morganti, C, Amade, E, Brambilla, V, Montanari, A, Caterina, G, Lopez, C, Marocchi, A, Moletta, A, Sberna, M, Cascio, M, Scarone, S, Gargano G., Caletti E., Perlini C., Turtulici N., Bellani M., Bonivento C., Garzitto M., Siri F. M., Longo C., Bonetto C., Cristofalo D., Scocco P., Semrov E., Preti A., Lazzarotto L., Gardellin F., Lasalvia A., Ruggeri M., Marini A., Brambilla P., Bertani M. E., Bissoli S., De Santi K., Lunardi S., Negretto V., Poli S., Tosato S., Zamboni M. G., Ballarin M., De Girolamo G., Fioritti A., Neri G., Pileggi F., Rucci P., Chiavetto L. B., Scasselatti C., Zanardini R., Bertoldo A., Marinelli V., Rambaldelli G., Bardella S., Lamonaca D., Lunardon M., Magnabosco R., Martucci M., Nicolau S., Nifosi F., Pavanati M., Rossi M., Piazza C., Piccione G., Sala A., Sale A., Stefani B., Zotos S., Balbo M., Boggian I., Ceccato E., Dall'Agnola R., Girotto B., Goss C., Leoni R., Mai A., Pasqualini A., Roccato S., Rossi A., Strizzolo S., Urbani A., Aldi F., Bianchi B., Cappellari P., Conti R., De Battisti L., Lazzarin E., Merlin S., Migliorini G., Pozzan T., Sarto L., Visona S., Brazzoli A., Campi A., Carmagnani R., Giambelli S., Gianella A., Lunardi L., Madaghiele D., Maestrelli P., Paiola L., Posteri E., Viola L., Zamberlan V., Zenari M., Zanoni M., Bonadonna G., Bonomo M., Santonastaso P., Cremonese C., Veronese A., Anderle P., Angelozzi A., Baron I. A. G., Candeago E. B. F., Castelli F., Chieco M., Di Costanzo E., Derossi M., Doriguzzi M., Galvano O., Lattanzi M., Lezzi R., Marcato M., Marcolin A., Marini F., Matranga M., Scalabrin D., Zucchetto M., Zadro F., Austoni G., Bianco M., Bordino F., Dario F., De Risio A., Gatto A., Grana S., Favero E., Franceschini A., Friederici S., Marangon V., Pascolo M., Ramon L., Zambolin S., Riolo R., Buffon A., Di Bortolo E., Fortin S., Matarrese F., Mogni S., Codemo N., Russi A., Silvestro A., Turella E., Viel P., Dominoni A., Andreose L., Boemio M., Bressan L., Cabbia A., Canesso E., Cian R., Dal Piccol C., Pasqua M. M. D., Di Prisco A., Mantellato L., Luison M., Morgante S., Santi M., Sacillotto M., Scabbio M., Sponga P., Sguotto M., Stach F., Vettorato M., Martinello G., Dassie F., Marino S., Cibiniel L., Masetto I., Cabianca O., Valente A., Caberlotto L., Passoni A., Flumian P., Daniel L., Gion M., Stanziale S., Alborino F., Bortolozzo V., Bacelle L., Bicciato L., Basso D., Navaglia F., Manoni F., Ercolin M., Giubilini F., Imbesi M., Leuci E., Mazzi F., Anelli S., Amore M., Bigi L., Britta W., Anna G. B., Bonatti U., Borziani M., Crosato S., Fabris I., Galluccio R., Galeotti M., Gozzi M., Greco V., Guagnini E., Pagani S., Maccherozzi S., Malvasi R., Marchi F., Melato E., Mazzucchi E., Marzullo F., Pellegrini P., Petrolini N., Volta P., Bonara F., Brusamonti E., Croci R., Flamia I., Fontana F., Losi R., Marchioro R., Raffaini L., Ruju L., Saginario A., Tondelli M., Marrama D., Bernardelli L., Bonacini F., Florindo A., Merli M., Nappo P., Sola L., Tondelli O., Tonna M., Torre M., Tosatti M., Venturelli G., Zampolla D., Bernardi A., Cavalli C., Cigala L., Ciraudo C., Di Bari A., Ferri L., Gombi F., Leurini S., Mandatelli E., Maccaferri S., Oroboncoide M., Pisa B., Ricci C., Poggi E., Zurlini C., Malpeli M., Colla R., Teodori E., Vecchia L., D'Andrea R., Trenti T., Paolini P., Carpeggiani P., Ghigi D., Gagliostro M., Pratelli M., Antonelli A., Battistini L., Bellini F., Bonini E., Capelli C. B. R., DiDomizio C., Drei C., Fucci G., Gualandi A., Grazia M. R., Losi A. M., Mazzoni F. M. P., Marangoni D., Monna G., Morselli M., Oggioni A., Oprandi S., Paganelli W., Passerini M., Piscitelli M., Reggiani G., Rossi G., Salvatori F., Trasforini S., Uslenghi C., Veggetti S., Bartolucci G., Baruffa R., Bertelli R., Borghi L., Ciavarella P., Paltrinieri E., Rizzardi F., Serra P., Suzzi D., Arienti P., Aureli F., Avanzi R., Callegari V., Corsino A., Host P., Michetti R., Rizzo F., Simoncelli P., Soldati E., Succi E., Bertozzi M., Canetti E., Cavicchioli L., Ceccarelli E., Cenni S., Marzola G., Gallina V., Leoni C., Olivieri A., Piccolo E., Ravagli S., Russo R., Tedeschini D., Verenini M., Abram W., Granata V., Curcio A., Guerra G., Granini S., Natali L., Montanari E., Pasi F., Ventura U., Valenti S., Francesca M., Farneti R., Ravagli P., Floris R., Maroncelli O., Volpones G., Casali D., Miceli M., Bencini A., Cellini M., De Biase L., Barbara L., Charles L., Pratesi C., Tanini A., Loparrino R., Ulivelli C., Cussoto C., Dei N., Fumanti E., Pantani M., Zeloni G., Bellini R., Cellesi R., Dorigo N., Gulli P., Ialeggio L., Pisanu M., Rinaldi G., Konze A., Cocchi A., Meneghelli A., Frova M., Monzani E., Zanobio A., Malagoli M., Pagani R., Barbera S., Morganti C., Amade E. S., Brambilla V., Montanari A., Caterina G., Lopez C., Marocchi A., Moletta A., Sberna M., Cascio M. T., and Scarone S.

Abstract

Language production has often been described as impaired in psychiatric diseases such as in psychosis. Nevertheless, little is known about the characteristics of linguistic difficulties and their relation with other cognitive domains in patients with a first episode of psychosis (FEP), either affective or non-affective. To deepen our comprehension of linguistic profile in FEP, 133 patients with FEP (95 non-affective, FEP-NA; 38 affective, FEP-A) and 133 healthy controls (HC) were assessed with a narrative discourse task. Speech samples were systematically analyzed with a well-established multilevel procedure investigating both micro- (lexicon, morphology, syntax) and macro-linguistic (discourse coherence, pragmatics) levels of linguistic processing. Executive functioning and IQ were also evaluated. Both linguistic and neuropsychological measures were secondarily implemented with a machine learning approach in order to explore their predictive accuracy in classifying participants as FEP or HC. Compared to HC, FEP patients showed language production difficulty at both micro- and macro-linguistic levels. As for the former, FEP produced shorter and simpler sentences and fewer words per minute, along with a reduced number of lexical fillers, compared to HC. At the macro-linguistic level, FEP performance was impaired in local coherence, which was paired with a higher percentage of utterances with semantic errors. Linguistic measures were not correlated with any neuropsychological variables. No significant differences emerged between FEP-NA and FEP-A (p≥0.02, after Bonferroni correction). Machine learning analysis showed an accuracy of group prediction of 76.36% using language features only, with semantic variables being the most impactful. Such a percentage was enhanced when paired with clinical and neuropsychological variables. Results confirm the presence of language production deficits already at the first episode of the illness, being such impairment not related to ot

Published
2022

6. Language production impairments in patients with a first episode of psychosis

Author

Gargano G., Caletti E., Perlini C., Turtulici N., Bellani M., Bonivento C., Garzitto M., Siri F. M., Longo C., Bonetto C., Cristofalo D., Scocco P., Semrov E., Preti A., Lazzarotto L., Gardellin F., Lasalvia A., Ruggeri M., Marini A., Brambilla P., Bertani M. E., Bissoli S., De Santi K., Lunardi S., Negretto V., Poli S., Tosato S., Zamboni M. G., Ballarin M., De Girolamo G., Fioritti A., Neri G., Pileggi F., Rucci P., Chiavetto L. B., Scasselatti C., Zanardini R., Bertoldo A., Marinelli V., Rambaldelli G., Bardella S., Lamonaca D., Lunardon M., Magnabosco R., Martucci M., Nicolau S., Nifosi F., Pavanati M., Rossi M., Piazza C., Piccione G., Sala A., Sale A., Stefani B., Zotos S., Balbo M., Boggian I., Ceccato E., Dall'Agnola R., Girotto B., Goss C., Leoni R., Mai A., Pasqualini A., Roccato S., Rossi A., Strizzolo S., Urbani A., Aldi F., Bianchi B., Cappellari P., Conti R., De Battisti L., Lazzarin E., Merlin S., Migliorini G., Pozzan T., Sarto L., Visona S., Brazzoli A., Campi A., Carmagnani R., Giambelli S., Gianella A., Lunardi L., Madaghiele D., Maestrelli P., Paiola L., Posteri E., Viola L., Zamberlan V., Zenari M., Zanoni M., Bonadonna G., Bonomo M., Santonastaso P., Cremonese C., Veronese A., Anderle P., Angelozzi A., Baron I. A. G., Candeago E. B. F., Castelli F., Chieco M., Di Costanzo E., Derossi M., Doriguzzi M., Galvano O., Lattanzi M., Lezzi R., Marcato M., Marcolin A., Marini F., Matranga M., Scalabrin D., Zucchetto M., Zadro F., Austoni G., Bianco M., Bordino F., Dario F., De Risio A., Gatto A., Grana S., Favero E., Franceschini A., Friederici S., Marangon V., Pascolo M., Ramon L., Zambolin S., Riolo R., Buffon A., Di Bortolo E., Fortin S., Matarrese F., Mogni S., Codemo N., Russi A., Silvestro A., Turella E., Viel P., Dominoni A., Andreose L., Boemio M., Bressan L., Cabbia A., Canesso E., Cian R., Dal Piccol C., Pasqua M. M. D., Di Prisco A., Mantellato L., Luison M., Morgante S., Santi M., Sacillotto M., Scabbio M., Sponga P., Sguotto M., Stach F., Vettorato M., Martinello G., Dassie F., Marino S., Cibiniel L., Masetto I., Cabianca O., Valente A., Caberlotto L., Passoni A., Flumian P., Daniel L., Gion M., Stanziale S., Alborino F., Bortolozzo V., Bacelle L., Bicciato L., Basso D., Navaglia F., Manoni F., Ercolin M., Giubilini F., Imbesi M., Leuci E., Mazzi F., Anelli S., Amore M., Bigi L., Britta W., Anna G. B., Bonatti U., Borziani M., Crosato S., Fabris I., Galluccio R., Galeotti M., Gozzi M., Greco V., Guagnini E., Pagani S., Maccherozzi S., Malvasi R., Marchi F., Melato E., Mazzucchi E., Marzullo F., Pellegrini P., Petrolini N., Volta P., Bonara F., Brusamonti E., Croci R., Flamia I., Fontana F., Losi R., Marchioro R., Raffaini L., Ruju L., Saginario A., Tondelli M., Marrama D., Bernardelli L., Bonacini F., Florindo A., Merli M., Nappo P., Sola L., Tondelli O., Tonna M., Torre M., Tosatti M., Venturelli G., Zampolla D., Bernardi A., Cavalli C., Cigala L., Ciraudo C., Di Bari A., Ferri L., Gombi F., Leurini S., Mandatelli E., Maccaferri S., Oroboncoide M., Pisa B., Ricci C., Poggi E., Zurlini C., Malpeli M., Colla R., Teodori E., Vecchia L., D'Andrea R., Trenti T., Paolini P., Carpeggiani P., Ghigi D., Gagliostro M., Pratelli M., Antonelli A., Battistini L., Bellini F., Bonini E., Capelli C. B. R., DiDomizio C., Drei C., Fucci G., Gualandi A., Grazia M. R., Losi A. M., Mazzoni F. M. P., Marangoni D., Monna G., Morselli M., Oggioni A., Oprandi S., Paganelli W., Passerini M., Piscitelli M., Reggiani G., Rossi G., Salvatori F., Trasforini S., Uslenghi C., Veggetti S., Bartolucci G., Baruffa R., Bertelli R., Borghi L., Ciavarella P., Paltrinieri E., Rizzardi F., Serra P., Suzzi D., Arienti P., Aureli F., Avanzi R., Callegari V., Corsino A., Host P., Michetti R., Rizzo F., Simoncelli P., Soldati E., Succi E., Bertozzi M., Canetti E., Cavicchioli L., Ceccarelli E., Cenni S., Marzola G., Gallina V., Leoni C., Olivieri A., Piccolo E., Ravagli S., Russo R., Tedeschini D., Verenini M., Abram W., Granata V., Curcio A., Guerra G., Granini S., Natali L., Montanari E., Pasi F., Ventura U., Valenti S., Francesca M., Farneti R., Ravagli P., Floris R., Maroncelli O., Volpones G., Casali D., Miceli M., Bencini A., Cellini M., De Biase L., Barbara L., Charles L., Pratesi C., Tanini A., Loparrino R., Ulivelli C., Cussoto C., Dei N., Fumanti E., Pantani M., Zeloni G., Bellini R., Cellesi R., Dorigo N., Gulli P., Ialeggio L., Pisanu M., Rinaldi G., Konze A., Cocchi A., Meneghelli A., Frova M., Monzani E., Zanobio A., Malagoli M., Pagani R., Barbera S., Morganti C., Amade E. S., Brambilla V., Montanari A., Caterina G., Lopez C., Marocchi A., Moletta A., Sberna M., Cascio M. T., Scarone S., Gargano, G, Caletti, E, Perlini, C, Turtulici, N, Bellani, M, Bonivento, C, Garzitto, M, Siri, F, Longo, C, Bonetto, C, Cristofalo, D, Scocco, P, Semrov, E, Preti, A, Lazzarotto, L, Gardellin, F, Lasalvia, A, Ruggeri, M, Marini, A, Brambilla, P, Bertani, M, Bissoli, S, De Santi, K, Lunardi, S, Negretto, V, Poli, S, Tosato, S, Zamboni, M, Ballarin, M, De Girolamo, G, Fioritti, A, Neri, G, Pileggi, F, Rucci, P, Chiavetto, L, Scasselatti, C, Zanardini, R, Bertoldo, A, Marinelli, V, Rambaldelli, G, Bardella, S, Lamonaca, D, Lunardon, M, Magnabosco, R, Martucci, M, Nicolau, S, Nifosi, F, Pavanati, M, Rossi, M, Piazza, C, Piccione, G, Sala, A, Sale, A, Stefani, B, Zotos, S, Balbo, M, Boggian, I, Ceccato, E, Dall'Agnola, R, Girotto, B, Goss, C, Leoni, R, Mai, A, Pasqualini, A, Roccato, S, Rossi, A, Strizzolo, S, Urbani, A, Aldi, F, Bianchi, B, Cappellari, P, Conti, R, De Battisti, L, Lazzarin, E, Merlin, S, Migliorini, G, Pozzan, T, Sarto, L, Visona, S, Brazzoli, A, Campi, A, Carmagnani, R, Giambelli, S, Gianella, A, Lunardi, L, Madaghiele, D, Maestrelli, P, Paiola, L, Posteri, E, Viola, L, Zamberlan, V, Zenari, M, Zanoni, M, Bonadonna, G, Bonomo, M, Santonastaso, P, Cremonese, C, Veronese, A, Anderle, P, Angelozzi, A, Baron, I, Candeago, E, Castelli, F, Chieco, M, Di Costanzo, E, Derossi, M, Doriguzzi, M, Galvano, O, Lattanzi, M, Lezzi, R, Marcato, M, Marcolin, A, Marini, F, Matranga, M, Scalabrin, D, Zucchetto, M, Zadro, F, Austoni, G, Bianco, M, Bordino, F, Dario, F, De Risio, A, Gatto, A, Grana, S, Favero, E, Franceschini, A, Friederici, S, Marangon, V, Pascolo, M, Ramon, L, Zambolin, S, Riolo, R, Buffon, A, Di Bortolo, E, Fortin, S, Matarrese, F, Mogni, S, Codemo, N, Russi, A, Silvestro, A, Turella, E, Viel, P, Dominoni, A, Andreose, L, Boemio, M, Bressan, L, Cabbia, A, Canesso, E, Cian, R, Dal Piccol, C, Pasqua, M, Di Prisco, A, Mantellato, L, Luison, M, Morgante, S, Santi, M, Sacillotto, M, Scabbio, M, Sponga, P, Sguotto, M, Stach, F, Vettorato, M, Martinello, G, Dassie, F, Marino, S, Cibiniel, L, Masetto, I, Cabianca, O, Valente, A, Caberlotto, L, Passoni, A, Flumian, P, Daniel, L, Gion, M, Stanziale, S, Alborino, F, Bortolozzo, V, Bacelle, L, Bicciato, L, Basso, D, Navaglia, F, Manoni, F, Ercolin, M, Giubilini, F, Imbesi, M, Leuci, E, Mazzi, F, Anelli, S, Amore, M, Bigi, L, Britta, W, Anna, G, Bonatti, U, Borziani, M, Crosato, S, Fabris, I, Galluccio, R, Galeotti, M, Gozzi, M, Greco, V, Guagnini, E, Pagani, S, Maccherozzi, S, Malvasi, R, Marchi, F, Melato, E, Mazzucchi, E, Marzullo, F, Pellegrini, P, Petrolini, N, Volta, P, Bonara, F, Brusamonti, E, Croci, R, Flamia, I, Fontana, F, Losi, R, Marchioro, R, Raffaini, L, Ruju, L, Saginario, A, Tondelli, M, Marrama, D, Bernardelli, L, Bonacini, F, Florindo, A, Merli, M, Nappo, P, Sola, L, Tondelli, O, Tonna, M, Torre, M, Tosatti, M, Venturelli, G, Zampolla, D, Bernardi, A, Cavalli, C, Cigala, L, Ciraudo, C, Di Bari, A, Ferri, L, Gombi, F, Leurini, S, Mandatelli, E, Maccaferri, S, Oroboncoide, M, Pisa, B, Ricci, C, Poggi, E, Zurlini, C, Malpeli, M, Colla, R, Teodori, E, Vecchia, L, D'Andrea, R, Trenti, T, Paolini, P, Carpeggiani, P, Ghigi, D, Gagliostro, M, Pratelli, M, Antonelli, A, Battistini, L, Bellini, F, Bonini, E, Capelli, C, Didomizio, C, Drei, C, Fucci, G, Gualandi, A, Grazia, M, Losi, A, Mazzoni, F, Marangoni, D, Monna, G, Morselli, M, Oggioni, A, Oprandi, S, Paganelli, W, Passerini, M, Piscitelli, M, Reggiani, G, Rossi, G, Salvatori, F, Trasforini, S, Uslenghi, C, Veggetti, S, Bartolucci, G, Baruffa, R, Bertelli, R, Borghi, L, Ciavarella, P, Paltrinieri, E, Rizzardi, F, Serra, P, Suzzi, D, Arienti, P, Aureli, F, Avanzi, R, Callegari, V, Corsino, A, Host, P, Michetti, R, Rizzo, F, Simoncelli, P, Soldati, E, Succi, E, Bertozzi, M, Canetti, E, Cavicchioli, L, Ceccarelli, E, Cenni, S, Marzola, G, Gallina, V, Leoni, C, Olivieri, A, Piccolo, E, Ravagli, S, Russo, R, Tedeschini, D, Verenini, M, Abram, W, Granata, V, Curcio, A, Guerra, G, Granini, S, Natali, L, Montanari, E, Pasi, F, Ventura, U, Valenti, S, Francesca, M, Farneti, R, Ravagli, P, Floris, R, Maroncelli, O, Volpones, G, Casali, D, Miceli, M, Bencini, A, Cellini, M, De Biase, L, Barbara, L, Charles, L, Pratesi, C, Tanini, A, Loparrino, R, Ulivelli, C, Cussoto, C, Dei, N, Fumanti, E, Pantani, M, Zeloni, G, Bellini, R, Cellesi, R, Dorigo, N, Gulli, P, Ialeggio, L, Pisanu, M, Rinaldi, G, Konze, A, Cocchi, A, Meneghelli, A, Frova, M, Monzani, E, Zanobio, A, Malagoli, M, Pagani, R, Barbera, S, Morganti, C, Amade, E, Brambilla, V, Montanari, A, Caterina, G, Lopez, C, Marocchi, A, Moletta, A, Sberna, M, Cascio, M, and Scarone, S

Subjects
Language Disorders, Multidisciplinary, Comprehension, Humans, Language, Neuropsychological Tests, Psychotic Disorders, Psychosis, Language Disorder, Psychosis, Language, Cognition, Neuropsychology, Cognition, Neuropsychology, Neuropsychological Test, Settore MED/25 - Psichiatria, Human
Abstract

Language production has often been described as impaired in psychiatric diseases such as in psychosis. Nevertheless, little is known about the characteristics of linguistic difficulties and their relation with other cognitive domains in patients with a first episode of psychosis (FEP), either affective or non-affective. To deepen our comprehension of linguistic profile in FEP, 133 patients with FEP (95 non-affective, FEP-NA; 38 affective, FEP-A) and 133 healthy controls (HC) were assessed with a narrative discourse task. Speech samples were systematically analyzed with a well-established multilevel procedure investigating both micro- (lexicon, morphology, syntax) and macro-linguistic (discourse coherence, pragmatics) levels of linguistic processing. Executive functioning and IQ were also evaluated. Both linguistic and neuropsychological measures were secondarily implemented with a machine learning approach in order to explore their predictive accuracy in classifying participants as FEP or HC. Compared to HC, FEP patients showed language production difficulty at both micro- and macro-linguistic levels. As for the former, FEP produced shorter and simpler sentences and fewer words per minute, along with a reduced number of lexical fillers, compared to HC. At the macro-linguistic level, FEP performance was impaired in local coherence, which was paired with a higher percentage of utterances with semantic errors. Linguistic measures were not correlated with any neuropsychological variables. No significant differences emerged between FEP-NA and FEP-A (p≥0.02, after Bonferroni correction). Machine learning analysis showed an accuracy of group prediction of 76.36% using language features only, with semantic variables being the most impactful. Such a percentage was enhanced when paired with clinical and neuropsychological variables. Results confirm the presence of language production deficits already at the first episode of the illness, being such impairment not related to other cognitive domains. The high accuracy obtained by the linguistic set of features in classifying groups support the use of machine learning methods in neuroscience investigations.

Published
2022

10. Dual HDAC–BRD4 inhibitors endowed with antitumor and antihyperalgesic activity

Author

Maach, S., Chiaramonte, N., Borgonetti, V., Sarno, F., Pierucci, F., Dei, S., Teodori, E., Altucci, L., Meacci, E., Galeotti, N., and Romanelli, M. N.

Subjects
Antihyperalgesic activity, Antiproliferative activity, BRD4 inhibitors, Dual inhibitors, HDAC inhibitors, Spared Nerve Injury model
Published
2022

16. Presynaptic Cholinergic Modulators as Potent Cognition Enhancers and Analgesic Drugs. 2. 2-Phenoxy-, 2-(Phenylthio)-, and 2-(Phenylamino)alkanoic Acid Esters

Author

Gualtieri, F., Bottalico, C., Calandrella, A., Dei, S., Giovannoni, M. P., Mealli, S., Romanelli, M. N., Scapecchi, S., Teodori, E., Nicoletta Galeotti, Ghelardini, C., Giotti, A., and Bartolini, A.

Subjects
Stereochemistry, Analgesic, Acetates, Nootropic, Mice, Structure-Activity Relationship, Cognition, Drug Discovery, Muscarinic acetylcholine receptor, medicine, Animals, Analgesics, Molecular Structure, Chemistry, Stereoisomerism, Biological activity, Acetylcholine, Mechanism of action, Synapses, Morphine, Molecular Medicine, Cholinergic, Analgesia, Propionates, medicine.symptom, Enantiomer, Tropanes, medicine.drug
Abstract

Further modifications of the leads ((R)-(+)-hyoscyamine and (p-chlorophenyl)propionic acid alpha-tropanyl ester), which show analgesic and nootropic activities as a consequence of increased central presynaptic ACh release, are reported. 2-Phenoxy- and 2-(phenylthio)alkanoic acid esters showed the best results. Several members of these classes possess analgesic properties which are comparable to that of morphine and at the same time are able to reverse dicyclomine-induced amnesia. Confirmation was found that the mechanism of action is due to an increase in ACh release at central muscarinic synapses and that both auto- and heteroreceptors controlling ACh release are very likely involved. According to the results obtained with (R)-(+)-hyoscyamine, analgesic activity is stereochemistry dependent, since the R-(+)-enantiomers are always more efficacious than the corresponding S-(-)-ones. On the basis of their potency and acute toxicity, compounds (+/-)-28 (SM21) and (+/-)-42 (SM32) were selected for further study.

Published
1994

18. A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Author

Ruggeri, Mirella, Bonetto, Chiara, Lasalvia, Antonio, Girolamo, De, G, Fioritti, A, Rucci, P, Santonastaso, P, Neri, G, Pileggi, F, Ghigi, D, Miceli, M, Scarone, S, Cocchi, A, Torresani, S, Faravelli, C, Zimmermann, Christa, Meneghelli, A, Cremonese, C, Scocco, P, Leuci, E, Mazzi, F, Gennarelli, M, Brambilla, P, Bissoli, S, Bertani, Me, Tosato, Sarah, DE SANTI, Katia, Poli, Sara, Cristofalo, Doriana, Tansella, Michele, Get, Up, Group, Ruggeri, M, Mirella, Me, Bonetto, C, Cristofalo, D, De Santi, K, Lasalvia, A, Lunardi, S, Negretto, V, Poli, S, Tosato, S, Zamboni, Mg, Ballarin, M, Bocchio, Chiavetto, L, Scasselatti, C, Zanardini, R, Bellani, Marcella, Bertoldo, A, Marinelli, Veronica, Perlini, Cinzia, Rambaldelli, Gianluca, Bertani, M, Lazzarotto, L, Bardella, S, Gardellin, F, Lamonaca, D, Lunardon, M, Magnabosco, R, Martucci, M, Nicolau, S, Nifosì, F, Pavanati, M, Rossi, M, Piazza, C, Piccione, G, Sala, A, Sale, A, Stefan, B, Zotos, S, Balbo, M, Boggian, I, Ceccato, E, Dall'Agnola, R, Girotto, B, Goss, Claudia, Leoni, R, Mai, A, Pasqualini, A, Roccato, S, Rossi, A, Strizzolo, S, Urbani, A, Ald, F, Bianchi, B, Cappellari, P, Conti, R, Battisti, De, Lazzarin, E, Merlin, S, Migliorini, G, Pozzan, T, Sarto, L, Visonà, S, Brazzoli, A, Campi, A, Carmagnani, R, Giambelli, S, Gianella, A, Lunardi, L, Madaghiele, D, Maestrelli, P, Paiola, L, Posteri, E, Viola, L, Zamberlan, V, Zenari, M, Zanoni, M, Bonadonna, G, Bonomo, M, Veronese, A, Anderle, P, Angelozz, A, Amalric, I, Baron, G, Candeago, Eb, Castelli, F, Chieco, M, Costanzo, Di, E, Derossi, M, Doriguzzi, M, Galvano, O, Lattanz, M, Lezzi, R, Marcato, M, Marcolin, A, Marini, F, Matranga, M, Scalabrin, D, Zucchetto, M, Zadro, F, Austoni, G, Bianco, M, Bordino, F, Dario, F, Risio, De, A, Gatto, A, Granà, S, Favero, E, Franceschin, A, Friederici, S, Marangon, V, Pascolo, M, Ramon, L, Zambolin, S, Riolo, R, Buffon, A, Bortolo, Di, Fortin, S, Matarrese, F, Mogni, S, Codemo, N, Russi, A, Silvestro, A, Turella, E, Viel, P, Dominoni, A, Andreose, L, Boemio, M, Bressan, L, Cabbia, A, Canesso, E, Cian, R, Dal, Piccol, Dalla, C, Pasqua, Mm, Prisco, Di, Mantellato, L, Luison, M, Morgante, S, Santi, M, Sacillotto, M, Scabbio, M, Sponga, P, Sguotto, Ml, Stach, F, Vettorato, Mg, Martinello, G, Dassiè, F, Marino, S, Cibiniel, L, Masetto, I, Cabianca, O, Valente, A, Caberlotto, L, Passoni, A, Flumian, P, Daniel, L, Gion, M, Stanziale, S, Alborino, F, Bortolozzo, V, Bacelle, L, Bicciato, L, Basso, D, Navaglia, F, Manoni, F, Ercolin, M, Giubilini, F, Imbesi, M, Semrov, E, Giovanni, Cs, Taro, E, Ceno, V, Ovest, P, Anelli, S, Amore, M, Bigi, L, Britta, W, Anna, Gb, Bonatti, U, Borziani, M, Crosato, I, Galluccio, R, Galeotti, M, Gozzi, M, Greco, V, Guagnini, E, Pagani, S, Maccherozzi, M, Marchi, F, Melato, E, Mazzucchi, E, Marzullo, F, Pellegrini, P, Petrolini, N, Volta, P, Bonara, F, Brusamonti, E, Croci, R, Flamia, I, Fontana, F, Losi, R, Marchioro, R, Raffaini, L, Ruju, L, Saginario, A, Tondelli, Mg, Marrama, D, Bernardelli, L, Bonacini, F, Florindo, A, Merli, M, Nappo, P, Sola, L, Tondelli, O, Tonna, M, Torre, Mt, Tosatti, M, Venturelli, G, Zampolla, D, Bernardi, A, Cavalli, C, Cigala, L, Ciraudo, C, Bari, Di, Ferri, L, Gombi, F, Leurini, S, Mandatelli, E, Maccaferri, S, Oroboncoide, M, Pisa, B, Ricci, C, Poggi, E, Zurlini, C, Malpeli, M, Colla, R, Teodori, E, Vecchia, L, D'Andrea, R, Trenti, T, Paolini, P, Carpeggiani, P, Gagliostro, M, Pratelli, M, Lazzaro, S, Antonelli, A, Battistini, L, Bellini, F, Bonini, E, Capelli, Cb, Didomizio, C, Drei, C, Fucci, G, Gualandi, A, Grazia, Mr, Losi, Am, Mazzoni, Fm, Marangoni, D, Monna, G, Morselli, M, Oggioni, A, Oprandi, S, Paganelli, W, Passerini, M, Piscitelli, M, Reggiani, G, Rossi, G, Salvatori, F, Trasforini, S, Uslenghi, C, Veggetti, S, Bartolucci, G, Baruffa, R, Bertelli, R, Borghi, L, Ciavarella, P, Paltrinieri, E, Rizzardi, F, Serra, P, Suzzi, D, Carlo, U, Arienti, P, Aureli, F, Avanzi, R, Callegari, V, Corsino, A, Host, P, Michetti, R, Rizzo, F, Simoncelli, P, Soldati, E, Succi, E, Bertozzi, M, Canetti, E, Cavicchioli, L, Ceccarelli, E, Cenni, S, Marzola, G, Gallina, V, Leoni, C, Olivieri, A, Piccolo, E, Ravagli, S, Russo, R, Tedeschini, D, Verenini, M, Abram, W, Granata, V, Curcio, A, Guerra, G, Granini, S, Natali, L, Montanari, E, Pasi, F, Ventura, U, Valenti, S, Francesca, M, Farneti, R, Ravagli, P, Floris, R, Maroncelli, O, Volpones, G, Casali, D, Bencini, A, Cellini, M, Biase, De, Barbara, L, Charles, L, Pratesi, C, Tanini, A, Loparrino, R, Ulivelli, C, Cussoto, C, Dei, N, Fumanti, E, Pantani, M, Zeloni, G, Bellini, R, Cellesi, R, Dorigo, N, Gullì, P, Ialeggio, L, Pisanu, M, Rinaldi, G, Konze, A, Modignani, L, Frova, M, Monzani, E, Zanobio, A, Malagoli, M, Pagani, R, Barbera, S, Morganti, C, Amadè, Es, Brambilla, V, Montanari, A, Caterina, G, Lopez, C, Marocchi, A, Moletta, A, Sberna, M, Cascio, Mt, Manzone, Ml, Barbara, B, Mari, L, Razzini, E, Bianchi, Y, Pellizzer, Mr, Verdecchia, A, Sferrazza, Mg, Pismataro, R, D'Eril, Gv, Barassi, A, Pacciolla, R, Faraci, G, Rosmini, B, Carpi, F, Soelva, M, Anderlan, M, Francesco, De, M, Duregger, E, Vettori, C, Doimo, S, Kompatscher, E, Forer, M, Kerschbaumer, H, Gampe, A, Nicoletti, M, Acerbi, C, Aquilino, D, Azzali, S, Bensi, L, Cappellari, D, Casana, E, Campagnola, N, Dal, Corso, Di, E, Micco, E, Gobbi, E, Mairaghi, L, Malak, S, Mesiano, L, Paterlini, F, Perini, M, Puliti, Em, Rispoli, R, Rizzo, E, Sergenti, C, Soave, M, Alpi, A, Bislenghi, L, Bolis, T, Colnaghi, F, Fascendini, S, Grignani, S, Patelli, G, Casale, S, Zimmermann, C, Deledda, G, Goss, C, Mazzi, Maria Angela, Rimondini, Michela, Scassellati, C, Bonvicini, C, Longo, S, Ventriglia, M, Squitti, R, Frisoni, G, Pievani, M, Balestrieri, M, Perlini, C, Marinelli, V, Bellani, M, Rambaldelli, G, Atzori, M, Beltramello, A, Alessandrini, F, Pizzini, Francesca, Zoccatelli, G, Politi, P, Emanuele, E, Brondino, N, Martino, G, Bergami, A, Zarbo, R, Riva, Ma, Fumagalli, F, Molteni, R, Calabrese, F, Guidotti, G, Luoni, A, Macchi, F, Artioli, S, Baldetti, M, Bizzocchi, M, Bolzon, D, Bonello, E, Cacciari, G, Carraresi, C, Caselli, G, Furlato, K, Garlassi, S, Gavarini, A, Macchetti, F, Marteddu, V, Plebiscita, G, Totaro, S, Bebbington, P, Birchwood, M, Dazzan, P, Kuipers, E, Thornicroft, G, Pariante, C, Lawrie, S, Soares, J. C., Ruggeri, M., Bonetto, C., Lasalvia, A., De Girolamo, G., Bertani, M., Rucci, P., Santonastaso, P., Neri, G., Pileggi, F., Ghigi, D., Miceli, M., Scarone, S., Cocchi, A., Torresani, S., Faravelli, C., Zimmermann, C., Meneghelli, A., Cremonese, C., Scocco, P., Leuci, E., Mazzi, F., Gennarelli, Massimo, Brambilla, P., Bissoli, S., Lazzarotto, L., Bardella, S., Gardellin, F., Lamonaca, D., Lunardon, M., Magnabosco, R., Martucci, M., Nicolau, S., Nifosì, F., Bertani, M. E., Tosato, S., De Santi, K., Poli, S., Cristofalo, D., Tansella, Michele, Lunardi, S., Negretto, V., Zamboni, M. G., Ballarin, M., Chiavetto, Luisella Bocchio, Scasselatti, C., Zanardini, R., Bellani, M., Bertoldo, A., Marinelli, Valentina, Perlini, C., Rambaldelli, G., Pasqualini, A., Pavanati, M., Rossi, M., Piazza, C., Piccione, G., Sala, A., Roccato, S., Rossi-, A., Sale, A., Stefan, B., Strizzolo, S., Zotos, S., Balbo, M., Boggian, I., Ceccato, E., Dall’Agnola, R., Girotto, B., Leoni, R., Mai, A., Urbani, Alessandro, Ald, F., Bianchi, Benedetta, Cappellari, P., Conti, R., De Battisti, L., Lazzarin, E., Merlin, S., Migliorini, G., Pozzan, T., Sarto, L., Visonà, S., Brazzoli, A., Campi, A., Carmagnani, R., Giambelli, S., Gianella, A., Lunardi-, L., Madaghiele, D., Maestrelli, P., Paiola, L., Posteri, E., Viola, L., Zamberlan, V., Zenari, M., Zanoni, M., Bonadonna, G., Bonomo, M., Veronese, A., Anderle, P., Angelozz, A., Amalric, I., Baron, G., Candeago, E. B., Castelli, F., Chieco, M., Di Costanzo, E., Derossi, M., Doriguzzi, M., Galvano, O., Lattanz, M., Lezzi, R., Marcato, M., Marcolin, A., Marini, F., Matranga, M., Scalabrin, D., Zucchetto, M., Zadro, F., Austoni, G., Bianco, M., Bordino, F., Dario, F., DE RISIO, Alfredo, Gatto, A., Granà, S., Favero, E., Franceschin, A., Friederici, S., Marangon, V., Pascolo, M., Ramon, L., Zambolin, S., Riolo, R., Buffon, A., Di Bortolo, E., Fortin, S., Matarrese, F., Mogni, S., Codemo, N., Russi, A., Silvestro, Antonina, Turella, E., Viel, P., Dominoni, A., Andreose, L., Boemio, M., Bressan, L., Cabbia, A., Canesso, E., Cian, R., Dal Piccol, C., Dalla Pasqua, M. M., Di Prisco, A., Mantellato, L., Luison, M., Morgante, S., Santi, M., Sacillotto, M., Scabbio, M., Sponga, P., Sguotto, M. L., Stach, F., Vettorato, M. G., Martinello, G., Dassiè, F., DI MARINO, Simone, Cibiniel, L., Masetto, I., Cabianca, O., Valente, MADDALENA AGNESE, Caberlotto, L., Passoni, A., Flumian, P., Daniel, L., Gion, M., Stanziale, S., Alborino, F., Bortolozzo, V., Bacelle, L., Bicciato, L., Basso, D., Navaglia, F., Manoni, F., Ercolin, M., Giubilini, F., Imbesi, M., Semrov, E., Giovanni, C. S., Taro e Ceno, V., Ovest, P., Anelli, S., Amore, M., Bigi, L., Britta, W., Anna, G. B., Bonatti, U., Borziani, M., Crosato, I., Galluccio, R., Galeotti, M., Gozzi, M., Greco, V., Guagnini, E., Pagani, S., Maccherozzi, M., Marchi, F., Melato, E., Mazzucchi, E., Marzullo, F., Pellegrini, Pietro Carlo, Petrolini, N., Volta, P., Bonara, F., Brusamonti, E., Croci, R., Flamia, I., Fontana, F., Losi, R., Marchioro, R., Raffaini, L., Ruju, L., Saginario, A., Tondelli, M. G., Marrama, D., Bernardelli, L., Bonacini, F., Florindo, A., Merli, M., Nappo, P., Sola, L., Tondelli-, O., Tonna, M., Torre, M. T., Tosatti, M., Venturelli, G., Zampolla, D., Bernardi, A., Cavalli, Chiara, Cigala, L., Ciraudo, C., Di Bari, A., Ferri, L., Gombi, F., Leurini, S., Mandatelli, E., Maccaferri, S., Oroboncoide, M., Pisa, B., Ricci, Carmine, Poggi, E., Zurlini, C., Malpeli, M., Colla, R., Teodori, E., Vecchia, L., D’Andrea, R., Trenti, T., Paolini, P., Carpeggiani, P., Gagliostro, M., Pratelli, M., Lazzaro, S., Antonelli, A., Battistini, Luca, Bellini, Fiorella, Bonini, E., Capelli, C. B., Didomizio, C., Drei, C., Fucci, G., Gualandi, A., Grazia, M. R., Losi-, A. M., Mazzoni, F. M., Marangoni, D., Monna, G., Morselli, M., Oggioni, A., Oprandi, S., Paganelli, W., Passerini, M., Piscitelli, M., Reggiani, G., Rossi-, G., Salvatori, Franco, Trasforini, S., Uslenghi, C., Veggetti, S., Bartolucci, Giuliana, Baruffa, R., Bertelli, R., Borghi, L., Ciavarella, P., Paltrinieri, E., Rizzardi, F., Serra, P., Suzzi, D., Carlo, U., Arienti, P., Aureli, F., Avanzi, R., Callegari, V., Corsino, A., Host, P., Michetti, R., Rizzo, F., Simoncelli, P., Soldati, E., Succi, E., Bertozzi, M., Canetti, E., Cavicchioli, L., Ceccarelli, E., Cenni, S., Marzola, G., Gallina, V., Leoni, C., Olivieri, A., Piccolo, Elisa, Ravagli, S., Russo, R., Tedeschini, D., Verenini, M., Abram, W., Granata, V., Curcio, A., Guerra, G., Granini, S., Natali, L., Montanari, Eleonora, Pasi, F., Ventura, U., Valenti, S., Francesca, M., Farneti, R., Ravagli-, P., Floris, R., Maroncelli, O., Volpones, G., Casali, D., Bencini, A., Cellini, M., De Biase, L., Barbara, L., Charles, L., Pratesi, C., Tanini, A., Loparrino, R., Ulivelli, C., Cussoto, C., Dei, N., Fumanti, E., Pantani, M., Zeloni, G., Bellini-, R., Cellesi, R., Dorigo, N., Gullì, P., Ialeggio, L., Pisanu, M., Rinaldi, G., Konze, A., Modignani, L., Frova, M., Monzani, E., Amadè, E. S., Zanobio, A., Malagoli, M., Pagani-, R., Barbera, S., Morganti, C., Brambilla-, V., Montanari-, A., Caterina, G., LOPEZ CORTES, Carlo, Marocchi, A., Moletta, A., Sberna, M., Cascio, M. T., Manzone, M. L., Barbara-, B., Mari, L., Razzini, E., Bianchi-, Y., Pellizzer, M. R., Verdecchia, A., Sferrazza, M. G., Pismataro, R., D’Eril, G. V., Barassi, A., Pacciolla, R., Faraci, G., Rosmini, B., Carpi, F., Soelva, M., Anderlan, M., De Francesco, M., Duregger, E., Vettori, C., Doimo, S., Kompatscher, E., Forer, M., Kerschbaumer, H., Gampe, A., Nicoletti, M., Acerbi, C., Aquilino, D., Azzali, S., Bensi, L., Cappellari-, D., Casana, E., Campagnola, N., Dal Corso, E., Di Micco, E., Gobbi, E., Mairaghi, L., Malak, S., Mesiano, L., Paterlini, F., Perini, Matteo, Puliti, E. M., Rispoli, R., Rizzo-, E., Sergenti, C., Soave, M., Alpi, A., Bislenghi, L., Bolis, T., Colnaghi, F., Fascendini, S., Grignani, S., Patelli, G., Casale, S., Deledda, G., Goss, C., Mazzi-, M., Rimondini, M., Scassellati, C., Bonvicini, C., Longo, Salvatore, Bocchio Chiavetto, L., Ventriglia, M., Squitti, R., Frisoni, G., Pievani, M., Balestrieri, M., Atzori, M., Beltramello, A., Alessandrini, F., Pizzini, F., Zoccatelli, G., Politi, P., Emanuele, E., Brondino, N., Martino, G., Bergami, A., Zarbo, R., Riva, M. A., Fumagalli, F., Molteni, R., Calabrese, F., Guidotti, Giovanni, Luoni, Alessia, Macchi, F., Artioli, S., Baldetti, M., Bizzocchi, M., Bolzon, D., Bonello, E., Cacciari, G., Carraresi, C., Caselli, G., Furlato, K., Garlassi, S., Gavarini, A., Macchetti, F., Marteddu, V., Plebiscita, G., Totaro, S., Bebbington, P., Birchwood, M., Dazzan, P., Kuipers, E., Thornicroft, G., Pariante, C., Lawrie, S., Soares, J. C., Mirella Ruggeri, Chiara Bonetto, Antonio Lasalvia, Giovanni De Girolamo, Angelo Fioritti, Paola Rucci, Paolo Santonastaso, Giovanni Neri, Francesca Pileggi, Daniela Ghigi, Maurizio Miceli, Silvio Scarone, Angelo Cocchi, Stefano Torresani, Carlo Faravelli, Christa Zimmermann, Anna Meneghelli, Carla Cremonese, Paolo Scocco, Emanuela Leuci, Fausto Mazzi, Massimo Gennarelli, Paolo Brambilla, Sarah Bissoli, Maria Elena Bertani, Sarah Tosato, Katia De Santi, Sara Poli, Doriana Cristofalo, Michele Tansella, and and THE GET UP GROUP

Subjects
Research design, Time Factors, early psychosis, psychosocial interventions, cluster randomized triales, medicine.medical_treatment, Psychological intervention, Medicine (miscellaneous), Assertive community treatment, Severity of Illness Index, law.invention, Study Protocol, Randomized controlled trial, law, Recurrence, Early psychosi, Cluster Analysis, Pharmacology (medical), lcsh:R5-920, Family Relation, Community Mental Health Service, First-episode psychosis, Community Mental Health Center, Community Mental Health Services, Cognitive behavioral therapy, Treatment Outcome, Cognitive Therapy, Italy, Research Design, First-episode psychosisEarly psychosisCognitive behavioral therapyPsychosocial interventionAssertive community treatment, Family Relations, lcsh:Medicine (General), Psychosocial, Human, pragmatic trial, Early psychosis, Family intervention, Psychosocial intervention, Community Mental Health Centers, Humans, Patient Selection, Psychotic Disorders, Sample Size, Case Management, Cognitive Behavioral Therapy, medicine.medical_specialty, psychosocial interventions, Time Factor, cluster randomized triales, Psychotic Disorder, First-episode psychosi, medicine, Psychiatry, Cluster Analysi, business.industry, Mental health, Cognitive therapy, business
Abstract

Background Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in ‘real-world’ services. Methods/Design The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design. The randomized units (clusters) are the CMHCs, and the units of observation are the centers’ patients and their family members. Patients in the experimental group will receive TAU plus: 1) cognitive behavioral therapy sessions, 2) psycho-educational sessions for family members, and 3) case management. Patient enrolment will take place over a 1-year period. Several psychopathological, psychological, functioning, and service use variables will be assessed at baseline and follow-up. The primary outcomes are: 1) change from baseline to follow-up in positive and negative symptoms’ severity and subjective appraisal; 2) relapse occurrences between baseline and follow-up, that is, episodes resulting in admission and/or any case-note records of re-emergence of positive psychotic symptoms. The expected number of recruited patients is about 400, and that of relatives about 300. Owing to the implementation of the intervention at the CMHC level, the blinding of patients, clinicians, and raters is not possible, but every effort will be made to preserve the independency of the raters. We expect that this study will generate evidence on the best treatments for FEP, and will identify barriers that may hinder its feasibility in ‘real-world’ clinical settings, patient/family conditions that may render this intervention ineffective or inappropriate, and clinical, psychological, environmental, and service organization predictors of treatment effectiveness, compliance, and service satisfaction. Trial registration ClinicalTrials.gov Identifier NCT01436331

Published
2012

19. Evaluation of pool boiling heat transfer over micro-structured surfaces by combining high-speed visualization and PIV measurements

Author

Teodori, E. (author), Moita, A.S. (author), Moreira, A.L.N. (author), Teodori, E. (author), Moita, A.S. (author), and Moreira, A.L.N. (author)

Abstract

The present work introduces an alternative approach which combines heat transfer measurements, high speed visualization and PIV to infer on the effect of surface micro-structuring in the various heat transfer parcels. The PIV provides particularly interesting information on the bubbles vertical velocity, allowing to infer how the microstructures affect the bulk induced flow. The micro-patterns are composed by arrays of cavities with fixed shape and depth, only varying the distance between cavities, S. The results confirm the importance of enhancing the pool boiling performance, by promoting the increase of the bubble frequency and active nucleation sites density with micro-patterned surfaces. The role of the patterns is different, depending on the properties of the fluids. Hence, for liquids with very high latent heat of evaporation and surface tension, the parcel of heat transfer related to the phase change is very important. Based on the force balance on the departing bubbles, it is evident that in this case the micro-patterns will mainly affect the bubble coalescence, which may lead to steep deterioration of the heat transfer coefficient. On the other hand, for liquids with lower thermal properties (and lower surface tension) the micro-patterns play an important role in increasing and stabilizing the vertical velocity of the bubbles, thus favoring a very efficient boiling performance, with high boiling frequencies and large active nucleation sites density. This role of the micro-patterned surfaces is well captured by the representation proposed here, which relates the heat transfer coefficient with the distance between micro-patterns S, made dimensionless by the characteristic dimension (Lc=(?lv/(?l-?v))1/2). This representation actually shows the best performance of the HFE7000 in comparison to that of ethanol, when the micro-patterned surfaces are used, despite the lower thermal properties of HFE7000. This trend was confirmed experimentally in our measurements.

Published
2013

23. In vitro and in silico analysis of the vascular effects of asymmetrical N, N-bis(alkanol)amine aryl esters, novel multidrug resistance-reverting agents.

Author

Fusi, F., Durante, M., Spiga, O., Trezza, A., Frosini, M., Floriddia, E., Teodori, E., Dei, S., and Saponara, S.

Abstract

Asymmetrical N, N-bis(alkanol)amine aryl esters (FRA77, GDE6, and GDE19) are potent multidrug resistance (MDR) reversers. Their structures loosely remind that of the Ca antagonist verapamil. Therefore, the aim of this study was to investigate their vascular activity in vitro. Their effects on the mechanical activity of fresh and cultured rat aorta rings on Ca1.2 channel current ( I ) of A7r5 cells and their cytotoxicity on A7r5 and EA.hy926 cells were analyzed. Docking at the rat α subunit of the Ca1.2 channel was simulated in silico. Compounds tested were cytotoxic at concentrations >1 μM (FRA77, GDE6, GDE19) and >10 μM (verapamil) in EA.hy926 cells, or >10 μM (FRA77, GDE6, GDE19) and at 100 μM (verapamil) in A7r5 cells. In fresh rings, the three compounds partly antagonized phenylephrine and 60 mM K (K60)-induced contraction at concentrations ≥1 and ≥3 μM, respectively. On the contrary, verapamil fully relaxed rings pre-contracted with both agents. In cultured rings, 10 μM GDE6, GDE19, FRA77, and verapamil significantly reduced the contractile response to both phenylephrine and K60. Similarly to verapamil, the three compounds docked at the α subunit, interacting with the same amino acids residues. FRA77, GDE6, and GDE19 inhibited I with IC values 1 order of magnitude higher than that of verapamil. FRA77-, GDE6-, and GDE19-induced vascular effects occurred at concentrations that are at least 1 order of magnitude higher than those effectively reverting MDR. Though an unambiguous divergence between MDR reverting and vascular activity is of overwhelming importance, these findings consistently contribute to the design and synthesis of novel and potent chemosensitizers. [ABSTRACT FROM AUTHOR]

Published
2016
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43. The medicinal chemistry of multidrug resistance (MDR) reversing drugs.

Author

Teodori, E., Dei, S., Scapecchi, S., and Gualtieri, F.

Subjects
*MULTIDRUG resistance, *PHARMACEUTICAL chemistry
Abstract

Multidrug resistance (MDR) is a kind of resistance of cancer cells to multiple classes of chemotherapic drugs that can be structurally and mechanistically unrelated. Classical MDR regards altered membrane transport that results in lower cell concentrations of cytotoxic drug and is related to the over expression of a variety of proteins that act as ATP-dependent extrusion pumps. P-glycoprotein (Pgp) and multidrug resistance protein (MRP1) are the most important and widely studied members of the family that belongs to the ABC superfamily of transporters. It is apparent that, besides their role in cancer cell resistance, these proteins have multiple physiological functions as well, since they are expressed also in many important non-tumoural tissues and are largely present in prokaryotic organisms. A number of drugs have been identified which are able to reverse the effects of Pgp, MRP1 and sister proteins, on multidrug resistance. The first MDR modulators discovered and studied in clinical trials were endowed with definite pharmacological actions so that the doses required to overcome MDR were associated with unacceptably high side effects. As a consequence, much attention has been focused on developing more potent and selective modulators with proper potency, selectivity and pharmacokinetics that can be used at lower doses. Several novel MDR reversing agents (also known as chemosensitisers) are currently undergoing clinical evaluation for the treatment of resistant tumours. This review is concerned with the medicinal chemistry of MDR reversers, with particular attention to the drugs that are presently in development. [Copyright &y& Elsevier]

Published
2002
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45. N,N-bis(Cyclohexanol)amine Aryl Esters: The Discovery of a New Class of Highly Potent Inhibitors of ransporter-Dependent Multidrug Resistance (MDR)

Author

Teodori, E., Dei, S., Martelli, C., and Scapecchi, S.

Abstract

Multidrug resistance (MDR) is a kind of acquired resistance of microorganisms and cancer cells to chemotherapeutic drugs that are characterized by different chemical structure and different mechanism of action. Classic MDR is due to a lower intracellular concentration of cytotoxic drugs that is associated with accelerated efflux of the chemotherapeutic drugs and is the consequence of the over expression of transporter proteins that act as extrusion pumps. Pglycoprotein (P-gp/ABCB1) is the most important and studied member of such proteins belonging to the ATP Binding Cassette (ABC) superfamily of transporters that use ATP as energy source. Inhibition of the functions of P-gp and other ABC proteins could represent a way to circumvent appearance of MDR in cancer cells and the most classical pharmacological strategy is the administration of agents able to modulate the P-gp function. On the basis of the known characteristics of the recognition site of P-gp, we have designed a new class of P-gp-mediated MDR reverters. These compounds are flexible molecules carrying a basic nitrogen atom flanked, at properly modulated distance, by two aromatic moieties; most of them possess MDR inhibitory activity on anthracycline-resistant erytroleukemia K562 cells. By applying the frozen analog approach to that series of very flexible MDR reverters, we identified a new series of N,N-bis(cyclohexanol)amine aryl esters that show very interesting MDR-reversing properties. Among them, compound 15d, that consistently shows low nanomolar potency and high efficacy in all the tests used, appears as a new pharmacological tool for P-gp studies and a promising lead for the development of potent, efficient and safe MDR reverters.

Published
2010

46. Exploratory Chemistry toward the Identification of a New Class of Multidrug Resistance Reverters Inspired by Pervilleine and Verapamil Models

Author

Teodori, E., Dei, S., Garnier-Suillerot, A., Gualtieri, F., Manetti, D., Martelli, C., Romanelli, M. N., Scapecchi, S., Sudwan, P., and Salerno, M.

Abstract

On the basis of the present knowledge of the substrate recognition site of ABC transporter proteins and inspired by the structures of verapamil and pervilleine A, a new class of Pgp-mediated multidrug resistance (MDR) reverters has been designed and synthesized. The new compounds are flexible molecules carrying one or two basic nitrogen atoms flanked, at properly modulated distance, by two aromatic moieties. Most of the molecules studied possess MDR inhibitory activity on anthracycline-resistant erythroleukemia K 562 cells, showing a potency that is higher than that of the reference compound verapamil and, in a few cases (7, 12, 13, 17, 20, 22, 28), is in the high nanomolar range. These compounds may be useful leads to develop new MDR reverting agents. In fact, the chemical structure of the class is fairly simple and can be implemented in a variety of ways that will allow the synthesis of new compounds that might be useful leads for the development of drugs to control Pgp-dependent MDR.

Published
2005

47. Design, Synthesis, and Preliminary Pharmacological Evaluation of a Set of Small Molecules That Directly Activate Gi Proteins

Author

Manetti, D., Mannelli, L. Di Cesare, Dei, S., Galeotti, N., Ghelardini, C., Romanelli, M. N., Scapecchi, S., Teodori, E., Pacini, A., Bartolini, A., and Gualtieri, F.

Abstract

Heterotrimeric G proteins play a pivotal role in the communication of cells with the environment. G proteins are stimulated by cell surface receptors (GPCR) that catalyze the exchange of GDP, bound to Gα subunit, with GTP and can per se be the target of drugs. Based on the structure of two nonpeptidic modulators of Gi proteins, a series of new molecules characterized by a long hydrophobic chain and at least two nitrogen atoms protonated at physiological pH was designed. The compounds were tested for their ability to stimulate binding of GTPγS to recombinant Gi proteins. Gi activation properties were also evaluated by inhibition of adenylyl cyclase activity in intact lymphocytes. Most compounds were able to stimulate GTPγS binding and to inhibit cAMP production at micromolar doses. Among the active compounds, 34 showed good efficacy and was the most potent compound studied, particularly on αo subtype; its regioisomer, 36, was the most efficacious one. Compound 7 showed also an interesting profile as it showed selectivity toward the αo subtype, in both efficacy and potency. Some of the compounds synthesized and found to be active may be useful leads to develop more potent and selective Gi protein modulators.

Published
2005

48. Design, Synthesis, and Preliminary Pharmacological Evaluation of 4-Aminopiperidine Derivatives as N-Type Calcium Channel Blockers Active on Pain and Neuropathic Pain

Author

Teodori, E., Baldi, E., Dei, S., Gualtieri, F., Romanelli, M. N., Scapecchi, S., Bellucci, C., Ghelardini, C., and Matucci, R.

Abstract

Several compounds with a 4-aminopiperidine scaffold decorated on both nitrogen atoms by alkyl or acyl moieties containing the structural motifs of verapamil and of flunarizine, as well as those that are more frequent in known N-type calcium channel antagonists, have been synthesized. Antinociceptive activity on the mouse hot-plate test was used to select molecules to be submitted to further studies. Active compounds were tested in vitro on a PC12 rat pheochromocytoma clonal cell line, to evaluate their action on N-type calcium channels, and on a rat model of neuropathic pain. Two compounds that show N-type calcium channel antagonism and are endowed with potent action on pain and neuropathic pain (3 and 18) have been selected for further studies.

Published
2004

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