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1. 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

2. 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

5. New scenarios for experiments in Psychology: The online modality

Author

Scerrati E., Marzola G., Villani C., Lugli L., D'Ascenzo E. S., Scerrati E., Marzola G., Villani C., Lugli L., and D'Ascenzo E.S.

Subjects
Behavioral research, online platform, Covid-19, gorilla experiment Builder
Abstract

An increasing number of behavioral studies are conducted online with the aim of including a wider and more heterogeneous sample of participants. this practice was encouraged by the outbreak of the Covid-19 pandemic, which implied social distancing, hence preventing access to laboratories as a measure to contain the infection. in the present work some online platforms will be discussed, considering their characteristics, advantages and limitations, in order to facilitate researchers in the possible selection of the most suitable tool for their needs.

Published
2021

6. The spatial association of the mathematical symbols «minus and plus»

Author

Marzola G., D'Ascenzo S., Lugli L., Marzola G., D'Ascenzo S., and Lugli L.

Subjects
SNARC effect, Spatial Numerical Association, OSSA effect, spatial attention, Numerical cognition
Abstract

The influence of spatial-numerical associations in number categorization tasks has been widely discussed, while the role of mathematical symbols is less clear. Specifically, it has been demonstrated that subtraction and addition, reducing and increasing the magnitude of numbers, are associated with left and right space, respectively. This result is explained by invoking a mental number line or a semantic association. The present work investigated the role of the mathematical symbols «minus and plus» presented as fixation points in a spatial compatibility task. Results demonstrated an opposite influence of the two symbols: the processing of the «minus» facilitated responses to the target presented on the left, while the «plus» facilitated responses to the target presented on the right.

Published
2021

7. First-episode psychosis in the Ferrara Mental Health Department: Incidence and clinical course within the first 2 years

Author

BELVEDERI MURRI, Martino, Bertelli, Raffaella, Carozza, Paola, Berardi, Lorenzo, Cantarelli, Luca, Croce, Enrico, Antenora, Fabio, Curtarello, Eleonora Maria Alfonsina, Simonelli, Gabriele, Recla, Elisabetta, Girotto, B., Grassi, Luigi, and Ferrara Working Group on First-Episode Psychosis, Callegari, V., Cardelli, R., Emanuelli, F., Garofani, L., Marangoni, C., Mazzoni, P., Nappi, Giulia, Rossi, G., Sacco, M., Turilli, P. D., Vanni, A., Baglini, G., Bandiera, A., Baruffa, R., Beltrami, D., Bongiovanni, L., Canetti, E., Cocchi, B., Di Domizio, C., Guadagnino, C., Laghi, G., Lamponi, C., Marzola, G., Meloncelli, A., Morelli, L., Pavanati, M., Piccolo, E., Polmonari, A., Reali, S., Rizzo, F., Roccati, V., Roncagli, M., Sarela, A. I., Tome, S., Zotos, S., Caracciolo, Stefano, Caruso, Rosangela, Nanni, Maria Giulia, Negrelli, Laura, and Zerbinati, Luigi

Subjects
Adult, Male, Psychosis, Pediatrics, medicine.medical_specialty, untreated, media_common.quotation_subject, NO, Young Adult, 03 medical and health sciences, 0302 clinical medicine, remission, medicine, Humans, first-episode psychosis, Pathological, Biological Psychiatry, media_common, business.industry, Addiction, Incidence (epidemiology), Clinical course, medicine.disease, Mental health, 030227 psychiatry, schizophrenia, Psychiatry and Mental health, Mental Health, Psychotic Disorders, Schizophrenia, dup, incidence, delusions, Female, Schizophrenic Psychology, Pshychiatric Mental Health, business, delusions, first-episode psychosis, incidence, remission, schizophrenia, untreated, 030217 neurology & neurosurgery
Abstract

AIM To examine the incidence of with first-episode psychosis (FEP) in the Integrated Department of Mental Health and Pathological Addictions in Ferrara, Italy, and to examine the association between the Duration of Untreated Psychosis (DUP) and the clinical course. METHODS Participants recruited in 2013-2019 were assessed with the Health of the Nation Outcome Scale (HoNOS) every 6 months for 24 months. Hierarchical growth models analysed changes of global severity (HoNOS total scores) and symptom dimensions. Regression modelled factors associated with remission (HoNOS

Published
2021

8. New scenarios for experiments in Psychology: The online modality

Author

Scerrati, Elisa, Marzola, G., Villani, C., Lugli, L., D'Ascenzo, E. S., Scerrati E. (ORCID:0000-0002-4042-6140), Scerrati, Elisa, Marzola, G., Villani, C., Lugli, L., D'Ascenzo, E. S., and Scerrati E. (ORCID:0000-0002-4042-6140)

Abstract

An increasing number of behavioral studies are conducted online with the aim of including a wider and more heterogeneous sample of participants. this practice was encouraged by the outbreak of the Covid-19 pandemic, which implied social distancing, hence preventing access to laboratories as a measure to contain the infection. in the present work some online platforms will be discussed, considering their characteristics, advantages and limitations, in order to facilitate researchers in the possible selection of the most suitable tool for their needs.

Published
2021

15. 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

24. [Dmt1]N/OFQ(1-13)-NH2: a potent nociceptin/orphanin FQ and opioid receptor universal agonist.

Author

Molinari, S, Camarda, V, Rizzi, A, Marzola, G, Salvadori, S, Marzola, E, Molinari, P, McDonald, J, Ko, MC, Lambert, DG, Calo', G, and Guerrini, R

Subjects
NOCICEPTIN, DRUG synergism, DRUG administration, ANALGESICS, OPIOID receptors, PHARMACOLOGY, GENE expression, LABORATORY rodents
Abstract

Background and Purpose Intrathecally (i.t.) administered nociceptin/orphanin FQ ( N/OFQ) evokes antinociceptive effects in rodents. Recent studies in monkeys demonstrated that i.t. co-application of N/OFQ and morphine elicits synergistic antinociceptive actions suggesting mixed N/OFQ peptide ( NOP) and μ opioid receptor agonists as innovative spinal analgesics. Thus, novel N/OFQ related peptides were synthesized in order to identify and pharmacologically characterize a mixed NOP/ μ opioid receptor agonist. Experimental Approach The following in vitro assays were used: calcium mobilization in cells expressing the human NOP or classical opioid receptors and chimeric G proteins, receptor and [35S]-GTPγS binding, [35S]-GTPγS binding in rat spinal cord membranes, guinea pig ileum bioassay. In vivo experiments were performed in monkeys using the tail withdrawal assay. Key Results From calcium mobilization studies [Dmt1]N/OFQ(1-13)-NH2 was selected as the most potent and least selective compound. The mixed NOP/opioid full agonist activity and high affinity of [Dmt1]N/OFQ(1-13)-NH2 was confirmed at human recombinant receptors in receptor binding, calcium mobilization and/or [35S]-GTPγS binding studies, at rat spinal cord receptors in [35S]-GTPγS binding experiments, and at guinea pig receptors inhibiting neurogenic contractions in the ileum. In vivo in the tail withdrawal assay in monkeys i.t. [Dmt1]N/OFQ(1-13)-NH2 was able to elicit robust and long-lasting antinociceptive effects. Conclusions and Implications Collectively, these results demonstrate that [Dmt1]N/OFQ(1-13)-NH2 behaves as NOP/opioid receptor universal agonist and substantiate the suggestion that such mixed ligands are worthy of development as innovative spinal analgesics. [ABSTRACT FROM AUTHOR]

Published
2013
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26. Pharmacological analysis for mechanisms of GPI-80 release from tumor necrosis factor-α-stimulated human neutrophils.

Author

Rizzi, A., Rizzi, D., Marzola, G., Regoli, D., and Larsen, B.D.

Subjects
PROTEINS, NEUTROPHILS, SYNOVIAL fluid, RHEUMATOID arthritis
Abstract

1 GPI-80, a glycosylphosphatidylinositol (GPI)-anchored protein initially identified on human neutrophils, plays a role(s) in the regulation of β2 integrin function. Previous studies have shown that GPI-80 is sublocated in secretory vesicles. It is also found in soluble form in the synovial fluid of rheumatoid arthritis patients, and in the culture supernatant of formyl-methionyl-leucylphenylalanine-stimulated neutrophils. To understand the behaviour of GPI-80 under conditions of stimulation, we investigated the effects of turnout necrosis factor (TNF)-α on its expression and release. We also probed the mechanism of its release with various pharmacologic tools. 2 TNF-α induced the release of GPI-80 from human neutrophils in a concentration-and timedependent manner (in the range of 1 100 u ml[sup -1] and 30 120 min, respectively), but did not affect surface GPI-80 levels. 3 Cytochalasin B, genistein, and SB203580 but not PD98059 inhibited TNF-α-stimulated GPI-80 release and neutrophil adherence at the same concentration. In addition, TNF-α-induced GPI-80 release was inhibited by blocking monoclonal antibodies specific to components of Mac-1 (CD1lb and CD18). 4 Antioxidants (pyrrolidine dithiocarbamate and N-acetyl-L-cysteine) inhibited GPI-80 release by TNF-α stimulation, but superoxide dismutase did not. Antioxidants but not superoxide dismutase reduced an intracellular oxidation state. 5 These findings indicate that TNF-α-stimulated GPI-80 release from human neutrophils depends upon adherence via β2 integrins. They also suggest that cytochalasin B, genistein, and SB203580 inhibit GPI-80 release by suppressing signals for cell adherence, rather than by a direct effect on its secretion. Finally, we suggest that GPI-80 release involves an intracellular change in a redox state. [ABSTRACT FROM AUTHOR]

Published
2002

31. A study of esophageal reflux following total gastrectomy with hepatobiliary sequential scintigraphy using TC-99m DISIDA

Author

Mario NANO, Castellano G, Coluccia C, Argirò G, Ricci E, Marzola G, Antonacci P, and Gaetini A

Subjects
Adult, Imino Acids, Technetium, Technetium Tc 99m Disofenin, Middle Aged, Postgastrectomy Syndromes, Liver, Stomach Neoplasms, Gastroesophageal Reflux, Methods, Humans, Bile Ducts, Radionuclide Imaging, Aged
Abstract

A new technique to study esophageal reflux by means of hepatobiliary photoscintigraphy using TC-99m DISIDA was examined. The study was undertaken on 19 patients undergoing total gastrectomy without esophageal recurrence or hepatic or pulmonary metastases. The results of hepatobiliary photoscintigraphy were compared with the clinical, endoscopic and radiologic data. From this comparison it was demonstrated that photoscintigraphy is a non-invasive procedure which permits the study of the intestinal loops excluded from the transit of food but not of bile. Hepatobiliary scintigraphy was shown to be a reliable examination and the only one which demonstrates the reflux under physiological conditions, since the 24h. pH test in the absence of the stomach does not clearly prove the presence of alkaline reflux (bile) in an alkaline environment (esophagus). The disadvantages of photoscintigraphy are that the reflux is demonstrated only during the period of examination and in the patients undergoing total gastrectomy it is difficult to identify with accuracy the esophageal anastomosis. In these cases however, the radioactive bolus was used to localize the anastomosis and therefore to assess the esophageal reflux.

Published
1986

32. [Metabolic consequences of total gastrectomy for cancer]

Author

Ricci E, Malfi G, Marzola G, Oliaro A, Coluccia C, and Mario NANO

Subjects
Adult, Aged, 80 and over, Male, Stomach Neoplasms, Humans, Female, Middle Aged, Postgastrectomy Syndromes, Aged, Follow-Up Studies
Published
1986

34. [Nphe 1,Arg 14,Lys 15]Nociceptin-NH 2, a novel potent and selective antagonist of the nociceptin/orphanin FQ receptor

Author

Calo, G., Rizzi, A., Rizzi, D., Bigoni, R., Remo Guerrini, Marzola, G., Marti, M., Mcdonald, J., Morari, M., Lambert, D. G., Salvadori, S., and Regoli, D.

Subjects
Male, Dose-Response Relationship, Drug, Narcotic Antagonists, Guinea Pigs, CHO Cells, In Vitro Techniques, Motor Activity, Peptide Fragments, Nociceptin Receptor, Rats, Rats, Sprague-Dawley, Mice, Opioid Peptides, Cricetinae, Papers, Receptors, Opioid, Animals, Rabbits, Isolated tissues, Locomotor activity, mice, Native and recombinant receptors, Nociceptin/orphanin FQ, NOP receptors, Rat cerebral cortex synaptosomes, Receptor antagonist, Tail withdrawal assay, UFP-101, Pain Measurement
Abstract

1. Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions by activating a specific G-protein coupled receptor (NOP). Few molecules are available that selectively activate or block the NOP receptor. Here we describe the in vitro and in vivo pharmacological profile of a novel NOP receptor ligand, [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101). 2. UFP-101 binds to the human recombinant NOP receptor expressed in Chinese hamster ovary (CHO) cells with high affinity (pK(i) 10.2) and shows more than 3000 fold selectivity over classical opioid receptors. UFP-101 competitively antagonizes the effects of N/OFQ on GTPgamma(35)S binding in CHO(hNOP) cell membranes (pA(2) 9.1) and on cyclic AMP accumulation in CHO(hNOP) cells (pA(2) 7.1), being per se inactive at concentrations up to 10 microM. 3. In isolated peripheral tissues of mice, rats and guinea-pigs, and in rat cerebral cortex synaptosomes preloaded with [(3)H]-5-HT, UFP-101 competitively antagonized the effects of N/OFQ with pA(2) values in the range of 7.3 - 7.7. In the same preparations, the peptide was inactive alone and did not modify the effects of classical opioid receptor agonists. 4. UFP-101 is also active in vivo where it prevented the depressant action on locomotor activity and the pronociceptive effect induced by 1 nmol N/OFQ i.c.v. in the mouse. In the tail withdrawal assay, UFP-101 at 10 nmol produces per se a robust and long lasting antinociceptive effect. 5. UFP-101 is a novel, potent and selective NOP receptor antagonist which appears to be a useful tool for future investigations of the N/OFQ-NOP receptor system.

37. Mirror numbers activate quantity representations, but show no SNARC effect: A working memory explanation.

Author

Marzola G and Cohen DJ

Subjects
Humans, Reaction Time physiology, Judgment physiology, Photic Stimulation methods, Space Perception physiology, Memory, Short-Term
Abstract

The Spatial-Numerical Association of Response Code (SNARC) effect refers to the finding that people respond to small numbers faster with the left hand and to large numbers faster with the right hand. This effect is often explained by hypothesizing that the mental representation of quantities has a spatial component: left to right in ascending order (Mental Number Line). Here we assess the relation between quantity and spatial representation by investigating mirror numbers. Although mirror numbers denote quantity, they are not generally encountered in a left-to-right spatial organization. In Experiments 1 and 2, we assessed whether numerical distance and SNARC effects were present for both mirror and normal numbers when participants were required to process semantic information in a magnitude classification task. In Experiment 3, we assessed whether the SNARC effect was present for both mirror and normal numbers when participants were not required to process semantic information in a mirror judgment task. Results show that participants access the quantity of both normal and mirror numbers, but only normal numbers are spatially organized from left to right. In addition, we show that the physical similarity between numbers successfully predicted the performance of participants. We concluded that the Working Memory account of the SNARC effect best explains our data. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Published
2023
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38. Nociceptin/orphanin FQ receptor knockout rats: in vitro and in vivo studies.

Author

Rizzi A, Molinari S, Marti M, Marzola G, and Calo' G

Subjects
Analysis of Variance, Animals, Dose-Response Relationship, Drug, Electric Stimulation, Male, Opioid Peptides pharmacology, Rats, Rats, Transgenic, Rotarod Performance Test, Vas Deferens drug effects, Vas Deferens physiology, Nociceptin Receptor, Nociceptin, Anxiety genetics, Behavior, Animal physiology, Depression genetics, Motor Activity genetics, Receptors, Opioid genetics
Abstract

Nociceptin/orphanin FQ (N/OFQ) regulates several biological functions via selective activation of the N/OFQ peptide (NOP) receptor. Recently knockout rats for the NOP receptor gene (NOP(-/-)) have been generated; these animals were used in the present study to investigate their emotional (open field, elevated plus maze, and forced swimming test), locomotor (drag and rotarod test), and nociceptive (plantar and formalin test) phenotypes in comparison with their NOP(+/+) littermates. In addition, N/OFQ sensitivity has been assessed in electrically stimulated vas deferens tissues taken from NOP(+/+) and NOP(-/-) rats. In the elevated plus maze and forced swimming tests NOP(-/-) rats showed anxiety- and anti-depressant-like phenotype, respectively. No differences were found in the open field test. NOP(-/-) rats outperformed their NOP(+/+) littermates in two motor behaviour assays. Genetic ablation of the NOP receptor gene produced a statistically significant increase in nociceptive behaviour of the mutant rats in the formalin test. Finally, in the electrically stimulated rat vas deferens taken from NOP(+/+) tissues, N/OFQ inhibited in a concentration-dependent manner the electrically induced twitches while the peptide was inactive in tissues taken from NOP(-/-) animals. These results, in line with previous findings obtained with selective NOP receptor antagonists in mice and rats and with mouse knockout studies, clearly indicate that endogenous N/OFQ-NOP receptor signalling plays an important role in controlling anxiety- and mood-related behaviours, exercise-driven locomotor activity and nociception. These observations are relevant for defining the therapeutic indications (and contraindications) of NOP receptor antagonists., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Published
2011
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39. Anti-inflammatory and analgesic effects displayed by peptides derived from PKI55 protein, an endogenous protein kinase C inhibitor.

Author

Selvatici R, Congestrì F, Marzola G, Guerrini R, Siniscalchi A, and Spisani S

Subjects
Analgesics administration & dosage, Animals, Anti-Inflammatory Agents administration & dosage, Dexamethasone pharmacology, Disease Models, Animal, Dose-Response Relationship, Drug, Edema drug therapy, Edema physiopathology, Humans, Hypothalamo-Hypophyseal System metabolism, Indomethacin pharmacology, Inflammation drug therapy, Inflammation physiopathology, Male, Mice, Pain drug therapy, Pain physiopathology, Peptides administration & dosage, Peptides chemistry, Pituitary-Adrenal System metabolism, Protein Kinase C antagonists & inhibitors, Analgesics pharmacology, Anti-Inflammatory Agents pharmacology, Peptides pharmacology, Proteins chemistry
Abstract

We recently characterized the PKI55 protein as an endogenous protein kinase C (PKC) inhibitor and investigated, in vitro, the potential anti-inflammatory actions of its N-terminal peptides 1-16 (peptide 5), 1-8 (peptide 8) and 1-5 (peptide 9). We showed their ability to inhibit chemotaxis in human polymorphonuclear leukocytes activated by the N-formyl tripeptide for-Met-Leu-Phe-OMe. In this work, we evaluated the anti-inflammatory and the analgesic effects of the selected peptides by in vivo experiments carried out in the mouse. The peptides 5, 8 and 9 (0.1 and 10 nmol i.c.v.) were effective in both the parameters chosen to test the anti-inflammatory activity, i.e., the xylene-induced ear edema and the acetic acid-induced infiltration of neutrophils in the peritoneal cavity. In addition, they displayed analgesic effect, evaluated by the acetic acid-induced writhing test. All the peptides' effects were shared by the reference compounds, dexamethasone and indomethacin (10 mg kg(-1) i.p.), but not by the 9-scramble peptide (10 nmol i.c.v.). The peptide 9, which represents the shortest active sequence of the PKI55 protein, was tested in the ear edema model even following intraperitoneal (i.p.) administration and proved to be effective in the range doses 3-30 mg kg(-1). Moreover, an increase in plasma corticosterone levels was detected in mice treated with the peptide 9, but not with the 9-scramble peptide (both at 10 nmol i.c.v.). The anti-inflammatory and analgesic effects of the PKI55-derived synthetic peptides, possibly related both to PKC inhibition and hypothalamic-pituitary-adrenal axis activation, deserve further investigation in view of potential therapeutic exploitation.

Published
2010
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40. In vitro and in vivo pharmacological characterization of the neuropeptide s receptor antagonist [D-Cys(tBu)5]neuropeptide S.

Author

Camarda V, Rizzi A, Ruzza C, Zucchini S, Marzola G, Marzola E, Guerrini R, Salvadori S, Reinscheid RK, Regoli D, and Calò G

Subjects
Animals, Cell Line, Humans, Male, Mice, Peptides pharmacology, Neuropeptides pharmacology, Receptors, G-Protein-Coupled antagonists & inhibitors
Abstract

Neuropeptide S (NPS) was identified as the endogenous ligand of an orphan receptor now referred to as the NPS receptor (NPSR). In the frame of a structure-activity study performed on NPS Gly5, the NPSR ligand [D-Cys(tBu)(5)]NPS was identified. [D-Cys(tBu)(5)]NPS up to 100 microM did not stimulate calcium mobilization in human embryonic kidney (HEK) 293 cells stably expressing the mouse NPSR; however, in a concentration-dependent manner, the peptide inhibited the stimulatory effects elicited by 10 and 100 nM NPS (pK(B), 6.62). In Schild analysis experiments [D-Cys(tBu)(5)]NPS (0.1-100 microM) produced a concentration-dependent and parallel rightward shift of the concentration-response curve to NPS, showing a pA(2) value of 6.44. Ten micromolar [D-Cys(tBu)(5)]NPS did not affect signaling at seven NPSR unrelated G-protein-coupled receptors. In the mouse righting reflex (RR) recovery test, NPS given at 0.1 nmol i.c.v. reduced the percentage of animals losing the RR in response to 15 mg/kg diazepam and their sleeping time. [d-Cys(tBu)(5)]NPS (1-10 nmol) was inactive per se but dose-dependently antagonized the arousal-promoting action of NPS. Finally, NPSR-deficient mice were similarly sensitive to the hypnotic effects of diazepam as their wild-type littermates. However, the arousal-promoting action of 1 nmol NPS could be detected in wild-type but not in mutant mice. In conclusion, [D-Cys(tBu)(5)]NPS behaves both in vitro and in vivo as a pure and selective NPSR antagonist but with moderate potency. Moreover, using this tool together with receptor knockout mice studies, we demonstrated that the arousal-promoting action of NPS is because of the selective activation of the NPSR protein.

Published
2009
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41. Further studies on the pharmacological features of the nociceptin/orphanin FQ receptor ligand ZP120.

Author

Fischetti C, Rizzi A, Gavioli EC, Marzola G, Trapella C, Guerrini R, Petersen JS, and Calo G

Subjects
Animals, Electric Stimulation, Ligands, Male, Mice, Mice, Knockout, Motor Activity, Narcotic Antagonists, Rats, Rats, Sprague-Dawley, Receptors, Opioid genetics, Receptors, Opioid metabolism, Vas Deferens drug effects, Vasodilator Agents pharmacology, Nociceptin, Oligopeptides pharmacology, Opioid Peptides pharmacology
Abstract

ZP120 is a nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) ligand. In previous studies, the effects of ZP120 were found to be sensitive to J-113397 in mouse tissues while resistant to UFP-101 in rat tissues. The aim of this study was to further investigate the ZP120 pharmacological profile using mouse and rat preparations, J-113397 and UFP-101, as well as NOP receptor knockout (NOP(-/-)) mice. Electrically stimulated mouse and rat vas deferens were used to characterize the pharmacology of ZP120 in vitro. For in vivo studies the tail-withdrawal assay was performed in wild type (NOP(+/+)) and NOP knockout (NOP(-/-)) mice. In the mouse and rat vas deferens ZP120 mimicked the effects of N/OFQ showing higher potency but lower maximal effects. In both preparations, J-113397 antagonized N/OFQ and ZP120 effects showing similar pK(B) values ( approximately 7.8). UFP-101 antagonized the actions of N/OFQ (pK(B) values approximately 7.3) but did not modify the effects of ZP120. The inhibitory effects of N/OFQ and ZP120 were no longer evident in vas deferens tissues taken from NOP(-/-) mice. In NOP(+/+) mice subjected to the tail-withdrawal assay, ZP120 (1 nmol) mimicked the pronociceptive action of N/OFQ (10 nmol), producing longer lasting effects. The effects of both peptides were absent in NOP(-/-) animals. The NOP receptor ligand ZP120 is a high potency NOP selective partial agonist able to evoke long-lasting effects; its diverse antagonist sensitivity in comparison with N/OFQ may derive from different modality of binding to the NOP receptor.

Published
2009
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42. In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist selective for the nociceptin/orphanin FQ receptor.

Author

Rizzi A, Spagnolo B, Wainford RD, Fischetti C, Guerrini R, Marzola G, Baldisserotto A, Salvadori S, Regoli D, Kapusta DR, and Calo G

Subjects
Animals, Blood Pressure drug effects, Dose-Response Relationship, Drug, Eating drug effects, Electric Stimulation, Electrophysiology, Half-Life, Heart Rate drug effects, In Vitro Techniques, Locomotion drug effects, Male, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Knockout, Muscle Contraction drug effects, Opioid Peptides blood, Opioid Peptides urine, Rats, Rats, Sprague-Dawley, Receptors, Opioid drug effects, Sodium urine, Vas Deferens drug effects, Vas Deferens physiology, Nociceptin Receptor, Opioid Peptides pharmacology, Receptors, Opioid agonists
Abstract

[(pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-112) has been designed as a novel ligand for the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) by combining into the same peptide different chemical modifications reported to increase N/OFQ potency. In vitro data obtained in the electrically stimulated mouse vas deferens demonstrated that UFP-112 behaved as a high potency (pEC(50) 9.43) full agonist at the NOP receptor. UFP-112 effects were sensitive to the NOP antagonist UFP-101 but not to naloxone and no longer evident in tissues taken from NOP(-/-) mice. In vitro half life of UFP-112 in mouse plasma and brain homogenate was 2.6- and 3.5-fold higher than that of N/OFQ. In vivo, in the mouse tail withdrawal assay, UFP-112 (1-100pmol, i.c.v.) mimicked the actions of N/OFQ producing pronociceptive effects after i.c.v. administration and antinociceptive effects when given i.t.; in both cases, UFP-112 was approximately 100-fold more potent than the natural peptide and produced longer lasting effects. UFP-112 also mimicked the hyperphagic effect of N/OFQ producing a bell shaped dose response curve with the maximum reached at 10pmol. The hyperphagic effects of N/OFQ and UFP-112 were absent in NOP(-/-) mice. Equi-effective high doses of UFP-112 (0.1nmol) and N/OFQ (10nmol) were injected i.c.v. in mice and spontaneous locomotor activity recorded for 16h. N/OFQ produced a clear inhibitory effect which lasted for 60min while UFP-112 elicited longer lasting effects (>6h). In conscious rats, UFP-112 (0.1 and 10nmol/kg, i.v.) produced a marked and sustained decrease in heart rate, blood pressure, and urinary sodium excretion and a profound increase in urine flow. Collectively, these findings demonstrate that UFP-112 behaves in vitro and in vivo as a highly potent and selective ligand able to produce full and long lasting activation of NOP receptors.

Published
2007
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43. Pharmacological characterization of the nociceptin/orphanin FQ receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol]: in vivo studies.

Author

Rizzi A, Gavioli EC, Marzola G, Spagnolo B, Zucchini S, Ciccocioppo R, Trapella C, Regoli D, and Calò G

Subjects
Animals, Antidepressive Agents pharmacology, Eating drug effects, Hindlimb Suspension, Locomotion drug effects, Male, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Knockout, Pain physiopathology, Pain prevention & control, Pain Measurement methods, Receptors, Opioid genetics, Receptors, Opioid physiology, Swimming, Nociceptin Receptor, Cycloheptanes pharmacology, Narcotic Antagonists pharmacology, Piperidines pharmacology
Abstract

The excellent pharmacological profile displayed by the selective nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol] in vitro prompted us to investigate the actions of this compound in vivo. In the mouse tail withdrawal assay, SB-612111 given i.p. up to 3 mg/kg did not modify per se tail withdrawal latencies but was able to prevent the pronociceptive and the antinociceptive action of 1 nmol of N/OFQ given i.c.v. and i.t., respectively. In food intake studies performed in sated mice, SB-612111 (1 mg/kg i.p.) had no effect on food consumption but fully prevented the orexigenic effect of 1 nmol of N/OFQ i.c.v. In 17-h food-deprived mice, the opioid receptor antagonist naltrexone (1 mg/kg s.c.), but not SB-612111 (1 and 10 mg/kg i.p.), produced a statistically significant reduction of food intake. In the mouse forced swimming and tail suspension tests, SB-612111 (1-10 mg/kg) reduced immobility time. The antidepressant-like effect elicited by SB-612111 in the forced swimming test was reversed by the i.c.v. injection of 1 nmol of N/OFQ and no longer evident in mice knockout for the NOP receptor gene. In conclusion, the present findings demonstrate that SB-612111 behaves in vivo as a potent and selective NOP antagonist and suggest that the N/OFQ-NOP receptor endogenous system plays an important role in regulating mood-related behaviors. The use of SB-612111 in future pathophysiological studies will certainly contribute to define the therapeutic potential of selective NOP receptor antagonists in different disease areas.

Published
2007
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44. Altered anxiety-related behavior in nociceptin/orphanin FQ receptor gene knockout mice.

Author

Gavioli EC, Rizzi A, Marzola G, Zucchini S, Regoli D, and Calo' G

Subjects
Animals, Anxiety Disorders genetics, Crosses, Genetic, Male, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Knockout, Nociceptin Receptor, Anxiety Disorders drug therapy, Behavior, Animal drug effects, Receptors, Opioid agonists, Receptors, Opioid genetics
Abstract

Studies showed that nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) agonists produce anxiolytic-like actions, while little is known about the effects of blockade of NOP receptor signaling in anxiety. To this aim, we investigated the behavioral phenotype of NOP receptor gene knockout mice (NOP(-/-)) in different assays. In the elevated plus-maze and light-dark box, NOP(-/-) mice displayed increased anxiety-related behavior. In the novelty-suppressed feeding behavior and elevated T-maze, NOP(-/-) mice showed anxiolytic-like phenotype, while no differences were found in the open-field, hole-board, marble-burying, and stress-induced hyperthermia. Altogether, these findings suggest that the N/OFQ-NOP receptor system modulates anxiety-related behavior in a complex manner.

Published
2007
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45. Ascorbic and 6-Br-ascorbic acid conjugates as a tool to increase the therapeutic effects of potentially central active drugs.

Author

Dalpiaz A, Pavan B, Vertuani S, Vitali F, Scaglianti M, Bortolotti F, Biondi C, Scatturin A, Tanganelli S, Ferraro L, Marzola G, Prasad P, and Manfredini S

Subjects
Animals, Ascorbic Acid chemistry, Ascorbic Acid metabolism, Cell Line, Central Nervous System Agents metabolism, Dose-Response Relationship, Drug, Drug Synergism, Male, Mice, Seizures chemically induced, Seizures prevention & control, Structure-Activity Relationship, Ascorbic Acid analogs & derivatives, Ascorbic Acid therapeutic use, Central Nervous System Agents therapeutic use
Abstract

Ascorbic acid (AA) or 6-Br-ascorbate (BrAA) conjugation has been investigated as a tool to improve brain drug delivery by the Vitamin C transporter SVCT2. To this aim, the effects of AA- or BrAA-conjugation on drug affinity and uptake have been assessed in vitro, by using human retinal pigment epithelium (HRPE) cells, and compared in vivo on mice. Nipecotic, kynurenic and diclofenamic acids were chosen as model drugs. Kinetic and inhibition experiments referred to [(14)C]AA uptake into HRPE cells showed that nipecotic and kynurenic acids became able to interact with SVCT2, as competitive inhibitors, only when conjugated to AA or BrAA. Surprisingly, diclofenamic acid itself appeared able to interact with SVCT2, with an affinity that was significantly increased or decreased by AA or BrAA conjugation, respectively. HPLC analysis, performed on HRPE cells, confirmed the SVCT2 mediated transport for the BrAA-conjugate of nipecotic acid, whereas kynurenic acids conjugates although interacting with the transporter did not enter the cells. In accordance, only the nipecotic acid conjugates showed anticonvulsant activity after systemic injection in mice.

Published
2005
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46. [(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a highly potent and selective agonist of the nociceptin/orphanin FQ receptor.

Author

Carrà G, Rizzi A, Guerrini R, Barnes TA, McDonald J, Hebbes CP, Mela F, Kenigs VA, Marzola G, Rizzi D, Gavioli E, Zucchini S, Regoli D, Morari M, Salvadori S, Rowbotham DJ, Lambert DG, Kapusta DR, and Calo' G

Subjects
Animals, Binding, Competitive, Blood Pressure drug effects, CHO Cells, Cricetinae, Cyclic AMP metabolism, Guanosine 5'-O-(3-Thiotriphosphate) metabolism, Guinea Pigs, Heart Rate drug effects, Humans, Kidney drug effects, Kidney physiology, Male, Motor Activity drug effects, Rats, Rats, Sprague-Dawley, Serotonin metabolism, Synaptic Transmission, Vas Deferens drug effects, Nociceptin Receptor, Opioid Peptides pharmacology, Receptors, Opioid agonists
Abstract

A novel ligand for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102), has been generated by combining in the N/OFQ-NH(2) sequence two chemical modifications, [Arg(14),Lys(15)] and [(pF)Phe(4)], that have been previously demonstrated to increase potency. In vitro, UFP-102 bound with high affinity to the human NOP receptor, showed at least 200-fold selectivity over classical opioid receptors, and mimicked N/OFQ effects in CHO(hNOP) cells, isolated tissues from various species, and mouse cortical synaptosomes releasing 5-hydroxytryptamine. UFP-102 showed similar maximal effects but higher potency (2- to 48-fold) relative to N/OFQ. The effects of UFP-102 were sensitive to NOP-selective antagonists J-113397 [(+/-)-trans-1-[1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one] (pA(2) = 7.75-8.12) and UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2))(pA(2) = 6.91-7.33) but not to naloxone, and no longer observed in tissues taken from NOP receptor knockout mice (NOP(-/-)). In vivo, UFP-102 (0.01-0.3 nmol i.c.v.) mimicked the pronociceptive action of N/OFQ (0.1-10 nmol i.c.v.) in the mouse tail withdrawal assay, displaying higher potency and longer lasting effects. The action of UFP-102 was not apparent in NOP(-/-) mice. Similar results were obtained measuring locomotor activity in mice. In conscious rats, UFP-102 (0.05 nmol i.c.v.) produced a marked and sustained decrease in heart rate, mean arterial pressure, and urinary sodium excretion and a profound increase in urine flow rate. These effects were comparable with those evoked by N/OFQ at 5 nmol. Collectively, these findings demonstrate that UFP-102 behaves as a highly potent and selective NOP receptor agonist that produces long-lasting effects in vivo.

Published
2005
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47. Pharmacological characterization of the novel nociceptin/orphanin FQ receptor ligand, ZP120: in vitro and in vivo studies in mice.

Author

Rizzi A, Rizzi D, Marzola G, Regoli D, Larsen BD, Petersen JS, and Calo' G

Subjects
Animals, Benzimidazoles pharmacology, Dose-Response Relationship, Drug, Electric Stimulation, In Vitro Techniques, Injections, Intravenous, Ligands, Male, Mice, Motor Activity drug effects, Opioid Peptides pharmacology, Piperidines pharmacology, Receptors, Opioid metabolism, Vas Deferens drug effects, Vas Deferens physiology, Nociceptin Receptor, Nociceptin, Narcotic Antagonists, Oligopeptides pharmacology, Opioid Peptides metabolism
Abstract

1 This study reports on the pharmacological characterization of ZP120, a novel ligand of the nociceptin/orphanin FQ (N/OFQ) peptide receptor, NOP. ZP120 is a structure inducing probes modified NOP ligand: Zealand Pharma proprietary SIP technology was used to increase the enzymatic stability and half-life of peptide. 2 In vitro, ZP120 mimicked the inhibitory effects of N/OFQ in the electrically stimulated mouse vas deferens, showing however higher potency (pEC(50) 8.88 vs 7.74), lower maximal effects (E(max) 69+/-5% vs 91+/-2%), and slower onset of action. Like N/OFQ, the effects of ZP120 were not modified by 1 micro M naloxone, but they were antagonized by the NOP receptor selective antagonist J-113397 (pA(2) 7.80 vs ZP120, 7.81 vs N/OFQ). 3 In vivo, ZP120 mimicked the effects of N/OFQ, producing pronociceptive effects in the tail withdrawal assay and decreased locomotor activity after i.c.v., but not after i.v. administration in mice. ZP120 elicited similar maximal effects as N/OFQ, but it was about 10 fold more potent and its effects lasted longer. 4 In conclusion, the novel NOP receptor ligand ZP120 is a highly potent and selective partial agonist of the NOP receptor with prolonged effects in vivo.

Published
2002
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48. Pharmacological characterisation of [(pX)Phe4]nociceptin(1-13)NH2 analogues. 2. In vivo studies.

Author

Rizzi A, Salis MB, Ciccocioppo R, Marzola G, Bigoni R, Guerrini R, Massi M, Madeddu P, Salvadori S, Regoli D, and Calo' G

Subjects
Animals, Eating drug effects, Eating physiology, Hemodynamics drug effects, Hemodynamics physiology, Male, Mice, Motor Activity drug effects, Motor Activity physiology, Pain Measurement drug effects, Rats, Rats, Wistar, Receptors, Opioid physiology, Structure-Activity Relationship, Nociceptin Receptor, Opioid Peptides chemistry, Opioid Peptides pharmacology, Peptide Fragments chemistry, Peptide Fragments pharmacology
Abstract

As part of a structure-activity study focused on the Phe(4) residue of nociceptin (NC) (1-13)NH(2), we identified two highly potent and selective agonists for the OP(4) receptor, [(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2), whose in vitro pharmacological profiles have been described in the companion paper. In the present study, we investigated the actions of [(pF)Phe(4)]NC(1-13)NH(2) and compared it with those of NC(1-13)NH(2) in a battery of vivo assays. In the locomotor activity test in mice, 1 nmol NC(1-13)NH(2) given intracerebroventricularly (i.c.v.) caused a significant decrease (about 70% inhibition) in activity for the first 15 min following injection; [(pF)Phe(4)]NC(1-13)NH(2), at the same dose, exerted a similar inhibitory effect that continued until the end of the observation period (30 min). This effect was prevented by the selective OP(4) receptor antagonist [Nphe(1)]NC(1-13)NH(2) (10 nmol, i.c.v.). In the tail-withdrawal assay in mice, [(pF)Phe(4)]NC(1-13)NH(2) mimicked the effects of NC(1-13)NH(2) producing pronociceptive and antimorphine effects following i.c.v. administration. In both experimental paradigms, the actions of [(pF)Phe(4)]NC(1-13)NH(2) were longer lasting (>60 min) compared to those of NC(1-13)NH(2) (ca. 30 min). In unanaesthetised normotensive mice, bolus intravenous (i.v.) injection of 100 nmol/kg of [(pF)Phe(4)]NC(1-13)NH(2) decreased mean blood pressure and heart rate; these effects were longer lasting than those elicited by the same dose of NC(1-13)NH(2). I.c.v. administration of [(pF)Phe(4)]NC(1-13)NH(2) dose-dependently stimulated feeding in rats, and was about tenfold more potent than NC(1-13)NH(2).Collectively, the present data demonstrate that, in a variety of in vivo assays, NC(1-13)NH(2) and [(pF)Phe(4)]NC(1-13)NH(2) mimicked the actions of NC. [(pF)Phe(4)]NC(1-13)NH(2) was more potent and its in vivo effects were longer lasting than those of NC(1-13)NH(2) and NC.

Published
2002
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49. [Nphe1,Arg14,Lys15]nociceptin-NH2, a novel potent and selective antagonist of the nociceptin/orphanin FQ receptor.

Author

Calo G, Rizzi A, Rizzi D, Bigoni R, Guerrini R, Marzola G, Marti M, McDonald J, Morari M, Lambert DG, Salvadori S, and Regoli D

Subjects
Animals, CHO Cells, Cricetinae, Dose-Response Relationship, Drug, Guinea Pigs, In Vitro Techniques, Male, Mice, Motor Activity drug effects, Motor Activity physiology, Opioid Peptides chemistry, Pain Measurement drug effects, Peptide Fragments chemistry, Peptide Fragments metabolism, Rabbits, Rats, Rats, Sprague-Dawley, Nociceptin Receptor, Narcotic Antagonists, Opioid Peptides metabolism, Opioid Peptides pharmacology, Peptide Fragments pharmacology, Receptors, Opioid metabolism
Abstract

1. Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions by activating a specific G-protein coupled receptor (NOP). Few molecules are available that selectively activate or block the NOP receptor. Here we describe the in vitro and in vivo pharmacological profile of a novel NOP receptor ligand, [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101). 2. UFP-101 binds to the human recombinant NOP receptor expressed in Chinese hamster ovary (CHO) cells with high affinity (pK(i) 10.2) and shows more than 3000 fold selectivity over classical opioid receptors. UFP-101 competitively antagonizes the effects of N/OFQ on GTPgamma(35)S binding in CHO(hNOP) cell membranes (pA(2) 9.1) and on cyclic AMP accumulation in CHO(hNOP) cells (pA(2) 7.1), being per se inactive at concentrations up to 10 microM. 3. In isolated peripheral tissues of mice, rats and guinea-pigs, and in rat cerebral cortex synaptosomes preloaded with [(3)H]-5-HT, UFP-101 competitively antagonized the effects of N/OFQ with pA(2) values in the range of 7.3 - 7.7. In the same preparations, the peptide was inactive alone and did not modify the effects of classical opioid receptor agonists. 4. UFP-101 is also active in vivo where it prevented the depressant action on locomotor activity and the pronociceptive effect induced by 1 nmol N/OFQ i.c.v. in the mouse. In the tail withdrawal assay, UFP-101 at 10 nmol produces per se a robust and long lasting antinociceptive effect. 5. UFP-101 is a novel, potent and selective NOP receptor antagonist which appears to be a useful tool for future investigations of the N/OFQ-NOP receptor system.

Published
2002
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50. [Arg(14),Lys(15)]nociceptin, a highly potent agonist of the nociceptin/orphanin FQ receptor: in vitro and in vivo studies.

Author

Rizzi D, Rizzi A, Bigoni R, Camarda V, Marzola G, Guerrini R, De Risi C, Regoli D, and Calo' G

Subjects
Animals, Benzimidazoles pharmacology, Electric Stimulation, Guinea Pigs, In Vitro Techniques, Injections, Intraventricular, Male, Mice, Motor Activity drug effects, Naloxone pharmacology, Opioid Peptides administration & dosage, Pain Measurement drug effects, Piperidines pharmacology, Rats, Rats, Sprague-Dawley, Receptors, Opioid agonists, Species Specificity, Nociceptin Receptor, Nociceptin, Narcotic Antagonists pharmacology, Opioid Peptides pharmacology
Abstract

The nociceptin (NC)/orphanin FQ analog, [Arg(14),Lys(15)]NC, has been recently demonstrated to behave as a potent agonist at the human recombinant NC receptors (OP(4)). In this study, we evaluated the pharmacological profile of [Arg(14),Lys(15)]NC in vitro on the native OP(4) receptors expressed in isolated tissues and in vivo in the locomotor activity and the tail-withdrawal assays in mice. On isolated tissues, [Arg(14),Lys(15)]NC mimicked the effects of NC, showing similar maximal effects but higher potencies (17-fold in the mouse vas deferens, 10-fold in the rat vas deferens, and about 5-fold in the guinea pig ileum and mouse colon). In these preparations, the effects of [Arg(14),Lys(15)]NC were not modified by 1 microM naloxone, although antagonized by the OP(4) receptor antagonists [Nphe(1)]NC(1-13)NH(2) (pA(2) congruent with 6) and (+/-)trans-1-[1-cyclooctylmethyl-3hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) (pA(2) congruent with 8). In the rat vas deferens, a cocktail of peptidase inhibitors increased the maximal effects of NC, its analog, and the pEC(50) of NC (by 4-fold); the potency of [Arg(14),Lys(15)]NC was not significantly modified by peptidase inhibitors. In in vivo experiments, [Arg(14),Lys(15)]NC mimicked the effects of NC, producing, after intracerebroventricular administration, pronociceptive effects in the tail-withdrawal assay and inhibiting the locomotor activity of the mice. In both assays, [Arg(14),Lys(15)]NC was about 30-fold more potent than NC and produced longer lasting effects. Taken together, the present data demonstrate that [Arg(14),Lys(15)]NC behaves as a highly potent agonist of the OP(4) receptor and is able to produce long-lasting effects in vivo, compared with the natural ligand NC.

Published
2002
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