Search

Your search keyword '"Ragonese, F"' showing total 73 results
Start Over Author "Ragonese, F"
73 results on '"Ragonese, F"'

1. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial

Author

Vaccaro, O, Masulli, M, Nicolucci, A, Bonora, E, Del Prato, S, Maggioni, A, Rivellese, A, Squatrito, S, Giorda, C, Sesti, G, Mocarelli, P, Lucisano, G, Sacco, M, Signorini, S, Cappellini, F, Perriello, G, Babini, A, Lapolla, A, Gregori, G, Giordano, C, Corsi, L, Buzzetti, R, Clemente, G, Di Cianni, G, Iannarelli, R, Cordera, R, La Macchia, O, Zamboni, C, Scaranna, C, Boemi, M, Iovine, C, Lauro, D, Leotta, S, Dall'Aglio, E, Cannarsa, E, Tonutti, L, Pugliese, G, Bossi, A, Anichini, R, Dotta, F, Di Benedetto, A, Citro, G, Antenucci, D, Ricci, L, Giorgino, F, Santini, C, Gnasso, A, De Cosmo, S, Zavaroni, D, Vedovato, M, Consoli, A, Calabrese, M, di Bartolo, P, Fornengo, P, Riccardi, G, D'Angelo, F, Giansanti, R, Tanase, L, Lanari, L, Testa, I, Pancani, F, Ranchelli, A, Vagheggi, P, Scatona, A, Fontana, L, Laviola, L, Tarantino, L, Ippolito, C, Gigantelli, V, Manicone, M, Conte, E, Trevisan, R, Rota, R, Dodesini, A, Reggiani, G, Montesi, L, Mazzella, N, Forlani, G, Caselli, C, Di Luzio, R, Mazzotti, A, Aiello, A, Barrea, A, Musto, A, D'Amico, F, Sinagra, T, Longhitano, S, Trowpea, V, Sparti, M, Italia, S, Lisi, E, Grasso, G, Pezzino, V, Insalaco, F, Carallo, C, Scicchitano, C, De Franceschi, M, Calbucci, G, Ripani, R, Cuneo, G, Corsi, S, Romeo, F, Lesina, A, Comoglio, M, Bonetto, C, Robusto, A, Nada, E, Asprino, V, Cetraro, R, Impieri, M, Lucchese, G, Donnarumma, G, Tizio, B, Lenza, L, Paraggio, P, Tomasi, F, Dozio, N, Scalambra, E, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, O, Fariello, S, Sorrentino, M, Franzetti, I, Radin, R, Annunziata, F, Bonabello, L, Durante, A, Dolcino, M, Gallo, F, Mazzucchelli, C, Aleo, A, Melga, P, Briatore, L, Maggi, D, Storace, D, Cecoli, F, D'Ugo, E, Pupillo, M, Baldassarre, M, Salvati, F, Minnucci, A, De Luca, A, Zugaro, A, Santarelli, L, Bosco, A, Petrella, V, La Verghetta, G, D'Andrea, S, Giuliani, A, Polidoro, W, Sperandio, A, Sciarretta, F, Pezzella, A, Carlone, A, Potenziani, S, Venditti, C, Foffi, C, Carbone, S, Cipolloni, L, Moretti, C, Leto, G, Serra, R, Petrachi, F, Romano, I, Lacaria, E, Russo, L, Goretti, C, Sannino, C, Dolci, M, Bruselli, L, Mori, M, Baccetti, F, Del Freo, M, Cucinotta, D, Giunta, L, Ruffo, M, Cannizzaro, D, Pintaudi, B, Perrone, G, Pata, P, Ragonese, F, Lettina, G, Mancuso, T, Coppolino, A, Piatti, P, Monti, L, Stuccillo, M, Lucotti, P, Setola, M, Crippa, G, Loi, C, Oldani, M, Bottalico, M, Pellegata, B, Bonomo, M, Menicatti, L, Resi, V, Bertuzzi, F, Disoteo, E, Pizzi, G, Annuzzi, G, Capaldo, B, Nappo, R, Auciello, S, Turco, A, Costagliola, L, Corte, G, Vallefuoco, P, Nappi, F, Vitale, M, Cocozza, S, Ciano, O, Massimino, E, Garofalo, N, Avogaro, A, Guarneri, G, Fedele, D, Sartore, G, Chilelli, N, Burlina, S, Bonsembiante, B, Galluzzo, A, Torregrossa, V, Mancastroppa, G, Arsenio, L, Cioni, F, Caronna, S, Papi, M, Santeusanio, F, Calagreti, G, Timi, A, Tantucci, A, Marino, C, Ginestra, F, Di Biagio, R, Taraborelli, M, Miccoli, R, Bianchi, C, Garofolo, M, Politi, K, Penno, G, Livraga, S, Calzoni, F, Corsini, E, Tedeschi, A, Gagliano, M, Ippolito, G, Salutini, E, Cervellino, F, Natale, M, Salvatore, V, Zampino, A, Sinisi, R, Arcangeli, A, Zogheri, A, Guizzotti, S, Longo, R, Pellicano, F, Scolozzi, P, Termine, S, Luberto, A, Ballardini, G, Trojani, C, Mazzuca, P, Bruglia, M, Ciamei, M, Genghini, S, Zannoni, C, Rangel, G, Salvi, L, Zappaterreno, A, Cordone, S, Simonelli, P, Meggiorini, M, Frasheri, A, Di Pippo, C, Maglio, C, Mazzitelli, G, Rinaldi, M, Galli, A, Romano, M, D'Angelo, P, Suraci, C, Bacci, S, Palena, A, Genovese, S, Mancino, M, Rondinelli, M, Capone, F, Calabretto, E, Bulgheroni, M, Bucciarelli, L, Ceccarelli, E, Fondelli, C, Santacroce, C, Guarino, E, Nigi, L, Lalli, C, Di Vizia, G, Scarponi, M, Montani, V, Di Bernardino, P, Romagni, P, Dolcetti, K, Forte, E, Tamburo, L, Perin, P, Prinzis, T, Gruden, G, Bruno, G, Zucco, C, Perotta, M, Marena, S, Monsignore, S, Panero, F, Ponzi, F, Carpinteri, R, Casagrande, M, Coletti, M, Balini, A, Filopanti, M, Madaschi, S, Pulcina, A, Grimaldi, F, Venturini, G, Agus, S, Pagnutti, S, Guidotti, F, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Fainelli, G, Tomasetto, E, Zoppini, G, Galletti, A, Perrone, D, Capra, C, Bianchini, F, Ceseri, M, Di Nardo, B, Sasso, E, Bartolomei, B, Suliman, I, Fabbri, G, Romano, G, Maturo, N, Nunziata, G, Capobianco, G, De Simone, G, Villa, V, Rota, G, Pentangelo, C, Carbonara, O, Caiazzo, G, Cutolo, M, Sorrentino, T, Mastrilli, V, Amelia, U, Masi, S, Corigliano, G, Gaeta, I, Armentano, V, Calatola, P, Capuano, G, Angiulli, B, Auletta, P, Petraroli, E, Iodice, C, Agrusta, M, Vaccaro O., Masulli M., Nicolucci A., Bonora E., Del Prato S., Maggioni A. P., Rivellese A. A., Squatrito S., Giorda C. B., Sesti G., Mocarelli P., Lucisano G., Sacco M., Signorini S., Cappellini F., Perriello G., Babini A. C., Lapolla A., Gregori G., Giordano C., Corsi L., Buzzetti R., Clemente G., Di Cianni G., Iannarelli R., Cordera R., La Macchia O., Zamboni C., Scaranna C., Boemi M., Iovine C., Lauro D., Leotta S., Dall'Aglio E., Cannarsa E., Tonutti L., Pugliese G., Bossi A. C., Anichini R., Dotta F., Di Benedetto A., Citro G., Antenucci D., Ricci L., Giorgino F., Santini C., Gnasso A., De Cosmo S., Zavaroni D., Vedovato M., Consoli A., Calabrese M., di Bartolo P., Fornengo P., Riccardi G., D'Angelo F., Giansanti R., Tanase L., Lanari L., Testa I., Pancani F., Ranchelli A., Vagheggi P., Scatona A., Fontana L., Laviola L., Tarantino L., Ippolito C., Gigantelli V., Manicone M., Conte E., Trevisan R., Rota R., Dodesini A. R., Reggiani G. M., Montesi L., Mazzella N., Forlani G., Caselli C., Di Luzio R., Mazzotti A., Aiello A., Barrea A., Musto A., D'Amico F., Sinagra T., Longhitano S., Trowpea V., Sparti M., Italia S., Lisi E., Grasso G., Pezzino V., Insalaco F., Carallo C., Scicchitano C., De Franceschi M. S., Calbucci G., Ripani R., Cuneo G., Corsi S., Romeo F., Lesina A., Comoglio M., Bonetto C., Robusto A., Nada E., Asprino V., Cetraro R., Impieri M., Lucchese G., Donnarumma G., Tizio B., Lenza L., Paraggio P., Tomasi F., Dozio N., Scalambra E., Mannucci E., Lamanna C., Cignarelli M., Macchia O. L., Fariello S., Sorrentino M. R., Franzetti I., Radin R., Annunziata F., Bonabello L. A., Durante A., Dolcino M., Gallo F., Mazzucchelli C., Aleo A., Melga P., Briatore L., Maggi D., Storace D., Cecoli F., D'Ugo E., Pupillo M., Baldassarre M. P. A., Salvati F., Minnucci A., De Luca A., Zugaro A., Santarelli L., Bosco A., Petrella V., La Verghetta G. G., D'Andrea S., Giuliani A. E., Polidoro W. L., Sperandio A., Sciarretta F., Pezzella A., Carlone A., Potenziani S., Venditti C., Foffi C., Carbone S., Cipolloni L., Moretti C., Leto G., Serra R., Petrachi F., Romano I., Lacaria E., Russo L., Goretti C., Sannino C., Dolci M., Bruselli L., Mori M. L., Baccetti F., Del Freo M., Cucinotta D., Giunta L., Ruffo M. C., Cannizzaro D., Pintaudi B., Perrone G., Pata P., Ragonese F., Lettina G., Mancuso T., Coppolino A., Piatti P. M., Monti L., Stuccillo M., Lucotti P., Setola M., Crippa G. V., Loi C., Oldani M., Bottalico M. L., Pellegata B., Bonomo M., Menicatti L. S. M., Resi V., Bertuzzi F., Disoteo E. O., Pizzi G., Annuzzi G., Capaldo B., Nappo R., Auciello S. M., Turco A. A., Costagliola L., Corte G. D., Vallefuoco P., Nappi F., Vitale M., Cocozza S., Ciano O., Massimino E., Garofalo N., Avogaro A., Guarneri G., Fedele D., Sartore G., Chilelli N. C., Burlina S., Bonsembiante B., Galluzzo A., Torregrossa V., Mancastroppa G., Arsenio L., Cioni F., Caronna S., Papi M., Santeusanio F., Calagreti G., Timi A., Tantucci A., Marino C., Ginestra F., Di Biagio R., Taraborelli M., Miccoli R., Bianchi C., Garofolo M., Politi K. S., Penno G., Livraga S., Calzoni F., Mancastroppa G. L. F., Corsini E., Tedeschi A., Gagliano M. S., Ippolito G., Salutini E., Cervellino F., Natale M., Salvatore V., Zampino A., Sinisi R., Arcangeli A., Zogheri A., Guizzotti S., Longo R., Pellicano F., Scolozzi P., Termine S., Luberto A., Ballardini G., Trojani C., Mazzuca P., Bruglia M., Ciamei M., Genghini S., Zannoni C., Rangel G., Salvi L., Zappaterreno A., Cordone S., Simonelli P., Meggiorini M., Frasheri A., Di Pippo C., Maglio C., Mazzitelli G., Rinaldi M. E., Galli A., Romano M., D'Angelo P., Suraci C., Bacci S., Palena A. P., Genovese S., Mancino M., Rondinelli M., Capone F., Calabretto E., Bulgheroni M., Bucciarelli L., Ceccarelli E., Fondelli C., Santacroce C., Guarino E., Nigi L., Lalli C., Di Vizia G., Scarponi M., Montani V., Di Bernardino P., Romagni P., Dolcetti K., Forte E., Tamburo L., Perin P. C., Prinzis T., Gruden G., Bruno G., Zucco C., Perotta M., Marena S., Monsignore S., Panero F., Ponzi F., Carpinteri R., Casagrande M. L., Coletti M. F., Balini A., Filopanti M., Madaschi S., Pulcina A., Grimaldi F., Venturini G., Agus S., Pagnutti S., Guidotti F., Cavarape A., Cigolini M., Pichiri I., Brangani C., Fainelli G., Tomasetto E., Zoppini G., Galletti A., Perrone D., Capra C., Bianchini F., Ceseri M., Di Nardo B., Sasso E., Bartolomei B., Suliman I., Fabbri G., Romano G., Maturo N., Nunziata G., Capobianco G., De Simone G., Villa V., Rota G., Pentangelo C., Carbonara O., Caiazzo G., Cutolo M., Sorrentino T., Mastrilli V., Amelia U., Masi S., Corigliano G., Gaeta I., Armentano V., Calatola P., Capuano G., Angiulli B., Auletta P., Petraroli E., Iodice C. E., Agrusta M., Vaccaro, O, Masulli, M, Nicolucci, A, Bonora, E, Del Prato, S, Maggioni, A, Rivellese, A, Squatrito, S, Giorda, C, Sesti, G, Mocarelli, P, Lucisano, G, Sacco, M, Signorini, S, Cappellini, F, Perriello, G, Babini, A, Lapolla, A, Gregori, G, Giordano, C, Corsi, L, Buzzetti, R, Clemente, G, Di Cianni, G, Iannarelli, R, Cordera, R, La Macchia, O, Zamboni, C, Scaranna, C, Boemi, M, Iovine, C, Lauro, D, Leotta, S, Dall'Aglio, E, Cannarsa, E, Tonutti, L, Pugliese, G, Bossi, A, Anichini, R, Dotta, F, Di Benedetto, A, Citro, G, Antenucci, D, Ricci, L, Giorgino, F, Santini, C, Gnasso, A, De Cosmo, S, Zavaroni, D, Vedovato, M, Consoli, A, Calabrese, M, di Bartolo, P, Fornengo, P, Riccardi, G, D'Angelo, F, Giansanti, R, Tanase, L, Lanari, L, Testa, I, Pancani, F, Ranchelli, A, Vagheggi, P, Scatona, A, Fontana, L, Laviola, L, Tarantino, L, Ippolito, C, Gigantelli, V, Manicone, M, Conte, E, Trevisan, R, Rota, R, Dodesini, A, Reggiani, G, Montesi, L, Mazzella, N, Forlani, G, Caselli, C, Di Luzio, R, Mazzotti, A, Aiello, A, Barrea, A, Musto, A, D'Amico, F, Sinagra, T, Longhitano, S, Trowpea, V, Sparti, M, Italia, S, Lisi, E, Grasso, G, Pezzino, V, Insalaco, F, Carallo, C, Scicchitano, C, De Franceschi, M, Calbucci, G, Ripani, R, Cuneo, G, Corsi, S, Romeo, F, Lesina, A, Comoglio, M, Bonetto, C, Robusto, A, Nada, E, Asprino, V, Cetraro, R, Impieri, M, Lucchese, G, Donnarumma, G, Tizio, B, Lenza, L, Paraggio, P, Tomasi, F, Dozio, N, Scalambra, E, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, O, Fariello, S, Sorrentino, M, Franzetti, I, Radin, R, Annunziata, F, Bonabello, L, Durante, A, Dolcino, M, Gallo, F, Mazzucchelli, C, Aleo, A, Melga, P, Briatore, L, Maggi, D, Storace, D, Cecoli, F, D'Ugo, E, Pupillo, M, Baldassarre, M, Salvati, F, Minnucci, A, De Luca, A, Zugaro, A, Santarelli, L, Bosco, A, Petrella, V, La Verghetta, G, D'Andrea, S, Giuliani, A, Polidoro, W, Sperandio, A, Sciarretta, F, Pezzella, A, Carlone, A, Potenziani, S, Venditti, C, Foffi, C, Carbone, S, Cipolloni, L, Moretti, C, Leto, G, Serra, R, Petrachi, F, Romano, I, Lacaria, E, Russo, L, Goretti, C, Sannino, C, Dolci, M, Bruselli, L, Mori, M, Baccetti, F, Del Freo, M, Cucinotta, D, Giunta, L, Ruffo, M, Cannizzaro, D, Pintaudi, B, Perrone, G, Pata, P, Ragonese, F, Lettina, G, Mancuso, T, Coppolino, A, Piatti, P, Monti, L, Stuccillo, M, Lucotti, P, Setola, M, Crippa, G, Loi, C, Oldani, M, Bottalico, M, Pellegata, B, Bonomo, M, Menicatti, L, Resi, V, Bertuzzi, F, Disoteo, E, Pizzi, G, Annuzzi, G, Capaldo, B, Nappo, R, Auciello, S, Turco, A, Costagliola, L, Corte, G, Vallefuoco, P, Nappi, F, Vitale, M, Cocozza, S, Ciano, O, Massimino, E, Garofalo, N, Avogaro, A, Guarneri, G, Fedele, D, Sartore, G, Chilelli, N, Burlina, S, Bonsembiante, B, Galluzzo, A, Torregrossa, V, Mancastroppa, G, Arsenio, L, Cioni, F, Caronna, S, Papi, M, Santeusanio, F, Calagreti, G, Timi, A, Tantucci, A, Marino, C, Ginestra, F, Di Biagio, R, Taraborelli, M, Miccoli, R, Bianchi, C, Garofolo, M, Politi, K, Penno, G, Livraga, S, Calzoni, F, Corsini, E, Tedeschi, A, Gagliano, M, Ippolito, G, Salutini, E, Cervellino, F, Natale, M, Salvatore, V, Zampino, A, Sinisi, R, Arcangeli, A, Zogheri, A, Guizzotti, S, Longo, R, Pellicano, F, Scolozzi, P, Termine, S, Luberto, A, Ballardini, G, Trojani, C, Mazzuca, P, Bruglia, M, Ciamei, M, Genghini, S, Zannoni, C, Rangel, G, Salvi, L, Zappaterreno, A, Cordone, S, Simonelli, P, Meggiorini, M, Frasheri, A, Di Pippo, C, Maglio, C, Mazzitelli, G, Rinaldi, M, Galli, A, Romano, M, D'Angelo, P, Suraci, C, Bacci, S, Palena, A, Genovese, S, Mancino, M, Rondinelli, M, Capone, F, Calabretto, E, Bulgheroni, M, Bucciarelli, L, Ceccarelli, E, Fondelli, C, Santacroce, C, Guarino, E, Nigi, L, Lalli, C, Di Vizia, G, Scarponi, M, Montani, V, Di Bernardino, P, Romagni, P, Dolcetti, K, Forte, E, Tamburo, L, Perin, P, Prinzis, T, Gruden, G, Bruno, G, Zucco, C, Perotta, M, Marena, S, Monsignore, S, Panero, F, Ponzi, F, Carpinteri, R, Casagrande, M, Coletti, M, Balini, A, Filopanti, M, Madaschi, S, Pulcina, A, Grimaldi, F, Venturini, G, Agus, S, Pagnutti, S, Guidotti, F, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Fainelli, G, Tomasetto, E, Zoppini, G, Galletti, A, Perrone, D, Capra, C, Bianchini, F, Ceseri, M, Di Nardo, B, Sasso, E, Bartolomei, B, Suliman, I, Fabbri, G, Romano, G, Maturo, N, Nunziata, G, Capobianco, G, De Simone, G, Villa, V, Rota, G, Pentangelo, C, Carbonara, O, Caiazzo, G, Cutolo, M, Sorrentino, T, Mastrilli, V, Amelia, U, Masi, S, Corigliano, G, Gaeta, I, Armentano, V, Calatola, P, Capuano, G, Angiulli, B, Auletta, P, Petraroli, E, Iodice, C, Agrusta, M, Vaccaro O., Masulli M., Nicolucci A., Bonora E., Del Prato S., Maggioni A. P., Rivellese A. A., Squatrito S., Giorda C. B., Sesti G., Mocarelli P., Lucisano G., Sacco M., Signorini S., Cappellini F., Perriello G., Babini A. C., Lapolla A., Gregori G., Giordano C., Corsi L., Buzzetti R., Clemente G., Di Cianni G., Iannarelli R., Cordera R., La Macchia O., Zamboni C., Scaranna C., Boemi M., Iovine C., Lauro D., Leotta S., Dall'Aglio E., Cannarsa E., Tonutti L., Pugliese G., Bossi A. C., Anichini R., Dotta F., Di Benedetto A., Citro G., Antenucci D., Ricci L., Giorgino F., Santini C., Gnasso A., De Cosmo S., Zavaroni D., Vedovato M., Consoli A., Calabrese M., di Bartolo P., Fornengo P., Riccardi G., D'Angelo F., Giansanti R., Tanase L., Lanari L., Testa I., Pancani F., Ranchelli A., Vagheggi P., Scatona A., Fontana L., Laviola L., Tarantino L., Ippolito C., Gigantelli V., Manicone M., Conte E., Trevisan R., Rota R., Dodesini A. R., Reggiani G. M., Montesi L., Mazzella N., Forlani G., Caselli C., Di Luzio R., Mazzotti A., Aiello A., Barrea A., Musto A., D'Amico F., Sinagra T., Longhitano S., Trowpea V., Sparti M., Italia S., Lisi E., Grasso G., Pezzino V., Insalaco F., Carallo C., Scicchitano C., De Franceschi M. S., Calbucci G., Ripani R., Cuneo G., Corsi S., Romeo F., Lesina A., Comoglio M., Bonetto C., Robusto A., Nada E., Asprino V., Cetraro R., Impieri M., Lucchese G., Donnarumma G., Tizio B., Lenza L., Paraggio P., Tomasi F., Dozio N., Scalambra E., Mannucci E., Lamanna C., Cignarelli M., Macchia O. L., Fariello S., Sorrentino M. R., Franzetti I., Radin R., Annunziata F., Bonabello L. A., Durante A., Dolcino M., Gallo F., Mazzucchelli C., Aleo A., Melga P., Briatore L., Maggi D., Storace D., Cecoli F., D'Ugo E., Pupillo M., Baldassarre M. P. A., Salvati F., Minnucci A., De Luca A., Zugaro A., Santarelli L., Bosco A., Petrella V., La Verghetta G. G., D'Andrea S., Giuliani A. E., Polidoro W. L., Sperandio A., Sciarretta F., Pezzella A., Carlone A., Potenziani S., Venditti C., Foffi C., Carbone S., Cipolloni L., Moretti C., Leto G., Serra R., Petrachi F., Romano I., Lacaria E., Russo L., Goretti C., Sannino C., Dolci M., Bruselli L., Mori M. L., Baccetti F., Del Freo M., Cucinotta D., Giunta L., Ruffo M. C., Cannizzaro D., Pintaudi B., Perrone G., Pata P., Ragonese F., Lettina G., Mancuso T., Coppolino A., Piatti P. M., Monti L., Stuccillo M., Lucotti P., Setola M., Crippa G. V., Loi C., Oldani M., Bottalico M. L., Pellegata B., Bonomo M., Menicatti L. S. M., Resi V., Bertuzzi F., Disoteo E. O., Pizzi G., Annuzzi G., Capaldo B., Nappo R., Auciello S. M., Turco A. A., Costagliola L., Corte G. D., Vallefuoco P., Nappi F., Vitale M., Cocozza S., Ciano O., Massimino E., Garofalo N., Avogaro A., Guarneri G., Fedele D., Sartore G., Chilelli N. C., Burlina S., Bonsembiante B., Galluzzo A., Torregrossa V., Mancastroppa G., Arsenio L., Cioni F., Caronna S., Papi M., Santeusanio F., Calagreti G., Timi A., Tantucci A., Marino C., Ginestra F., Di Biagio R., Taraborelli M., Miccoli R., Bianchi C., Garofolo M., Politi K. S., Penno G., Livraga S., Calzoni F., Mancastroppa G. L. F., Corsini E., Tedeschi A., Gagliano M. S., Ippolito G., Salutini E., Cervellino F., Natale M., Salvatore V., Zampino A., Sinisi R., Arcangeli A., Zogheri A., Guizzotti S., Longo R., Pellicano F., Scolozzi P., Termine S., Luberto A., Ballardini G., Trojani C., Mazzuca P., Bruglia M., Ciamei M., Genghini S., Zannoni C., Rangel G., Salvi L., Zappaterreno A., Cordone S., Simonelli P., Meggiorini M., Frasheri A., Di Pippo C., Maglio C., Mazzitelli G., Rinaldi M. E., Galli A., Romano M., D'Angelo P., Suraci C., Bacci S., Palena A. P., Genovese S., Mancino M., Rondinelli M., Capone F., Calabretto E., Bulgheroni M., Bucciarelli L., Ceccarelli E., Fondelli C., Santacroce C., Guarino E., Nigi L., Lalli C., Di Vizia G., Scarponi M., Montani V., Di Bernardino P., Romagni P., Dolcetti K., Forte E., Tamburo L., Perin P. C., Prinzis T., Gruden G., Bruno G., Zucco C., Perotta M., Marena S., Monsignore S., Panero F., Ponzi F., Carpinteri R., Casagrande M. L., Coletti M. F., Balini A., Filopanti M., Madaschi S., Pulcina A., Grimaldi F., Venturini G., Agus S., Pagnutti S., Guidotti F., Cavarape A., Cigolini M., Pichiri I., Brangani C., Fainelli G., Tomasetto E., Zoppini G., Galletti A., Perrone D., Capra C., Bianchini F., Ceseri M., Di Nardo B., Sasso E., Bartolomei B., Suliman I., Fabbri G., Romano G., Maturo N., Nunziata G., Capobianco G., De Simone G., Villa V., Rota G., Pentangelo C., Carbonara O., Caiazzo G., Cutolo M., Sorrentino T., Mastrilli V., Amelia U., Masi S., Corigliano G., Gaeta I., Armentano V., Calatola P., Capuano G., Angiulli B., Auletta P., Petraroli E., Iodice C. E., and Agrusta M.

Abstract

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50–75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2–3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15–45 mg) or a sulfonylurea (5–15 mg glibenclamide, 2–6 mg glimepiride, or 30–120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 p

Published
2017

7. Effect of nitrogen fertilisation on the overall quality of minimally processed globe artichoke heads

Author

Lombardo, S., Restuccia, Cristina, Muratore, Giuseppe, Barbagallo, Riccardo Nunzio, Licciardello, Fabio, Pandino, G., Scifo', G. O., Mazzaglia, A., Ragonese, F., and Mauromicale, Giovanni

Subjects
Crops, Agricultural, Nitrogen Fertiliser Rate, Food Handling, Surface Properties, Cell Respiration, Sensation, Flowers, Gram-Positive Bacteria, Refrigeration, Cynara scolymus, Gram-Negative Bacteria, Dietary Carbohydrates, Food Quality, Fertilizers, Plant Proteins, Inulin, Pigments, Biological, Nitrogen Cycle, Bacterial Load, Crop Production, Food Storage, Nutritional Quality, Minimal Processing, Nutritive Value, Catechol Oxidase
Abstract

Although nitrogen (N) fertilisation is essential for promoting crop yield, it may also affect the produce quality. Here, the influence of three N fertiliser rates (0 kg haThroughout the storage time, N fertilised samples had higher inulin contents than those unfertilised. In addition, the respiratory quotient of NA fertiliser level of 200 kg N ha

Published
2017

8. Hyperinsulinism, Insulin Resistance and Insulin Receptors in Obese Patients

Author

G. D’Andrea, Ragonese F, Consolo F, Forte F, G. Saitta, G. Perrone, O. Guerrisi, and A. Carducci Artenisio

Subjects
medicine.medical_specialty, Insulin, medicine.medical_treatment, Biology, medicine.disease, Obesity, Insulin receptor, Endocrinology, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Hyperinsulinemia, biology.protein, Hyperinsulinism
Published
2015
Full Text
View/download PDF

9. Addition of either pioglitazone or a sulfonylurea in type 2 diabetic patients inadequately controlled with metformin alone: impact on cardiovascular events. A randomized controlled trial

Author

Vaccaro, O, Masulli, M, Bonora, E, Del Prato, S, Giorda, Cb, Maggioni, Ap, Mocarelli, P, Nicolucci, A, Rivellese, Aa, Squatrito, S, Riccardi, G, IT study group, T. O. S. C. A., Sud, Cm, Imbaro, S, Garofalo, N, Ferrannini, E, Howard, B, Gerdts, E, Imperatore, G, Tavazzi, L, Pellegrini, F, Fabbri, G, Levantesi, G, Turazza, F, Gentile, S, Panico, S, Brambilla, P, Signorini, S, Cappellini, F, Parma, C, D'Alonzo, D, Di Nardo, B, Ferrari, S, Franciosi, M, Pecce, R, Valentini, M, Ceseri, M, Bianchini, F, Baldini, E, Atzori, A, Boemi, M, D'Angelo, F, Giansanti, R, Ricci, L, Ranchelli, A, Di Berardino, P, Cannarsa, E, Giorgino, F, Manicone, M, Tarantino, L, Trevisan, R, Scaranna, C, Forlani, G, Montesi, L, Aiello, A, Barrea, A, Sinagra, T, Longhitano, S, Sesti, G, Gnasso, A, Carallo, C, Scicchitano, C, Santini, C, Calbucci, G, Ripani, R, Corsi, L, Corsi, S, Romeo, F, Asprino, V, Donnarumma, G, Tizio, B, Clemente, G, Tomasi, F, Dozio, N, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, Ol, Fariello, S, Cordera, R, Mazzucchelli, C, Pupillo, M, Zugaro, A, Bosco, A, De Luca, A, Iannarelli, R, Giuliani, A, Polidoro, L, Sperandio, A, Sciarretta, F, Raffaella, B, Venditti, C, Di Cianni, G, Goretti, C, Dolci, Ma, Bruselli, L, Mori, M, Baccetti, F, Gregori, G, Venezia, A, Cucinotta, D, Pintaudi, B, Ragonese, F, Pata, P, Piatti, Pm, Luccotti, P, Orsi, E, Bonomo, M, Menicatti, L, Turco, Aa, Ciano, O, Vallefuoco, P, Corigliano, G, Pentangelo, C, Petraroli, E, Auletta, P, Carbonara, O, Capobianco, G, Caiazzo, G, Angiulli, B, De Simone, G, Michele, C, Mastrilli, V, Nunziata, G, Romano, G, Gaeta, I, Sorrentino, T, Iovine, C, Nappi, F, Paolisso, G, Rizzo, Mr, Avogaro, A, Vedovato, M, Lapolla, A, Sartore, G, Burlina, S, Chilelli, Nc, Galluzzoy, A, Giordano, C, Torregrossa, V, Arsenio, L, Dall'Aglio, E, Cioni, F, Babini, M, Moncastroppa, G, Perriello, G, Timi, A, Consoli, A, Ginestra, F, Zavaroni, D, Calzoni, F, Miccoli, R, Bianchi, C, Politi, S, Anichini, R, Tedeschi, A, Citro, G, Zampino, A, Rosa, S, Natale, M, Giocoli, Cl, Caruso, E, Tramontano, L, Imbroinise, A, Perna, Cd, Calabrese, M, Zogheri, A, Luberto, A, Ballardini, G, Babini, Ac, Zannoni, C, Pugliese, G, Salvi, L, Mazzitelli, G, Zappaterreno, A, Frontoni, S, Ventricini, A, Lauro, D, Galli, A, Rinaldi, Me, Leotta, S, Fontana, L, Goretti, S, Pozzilli, P, Leonetti, F, Morano, S, Filetti, S, Cosmo, Sd, Bacci, S, Palena, Ap, Calatola, P, Capuano, G, Amelia, U, Dotta, Francesco, Guarino, E, Ceccarelli, E, Lalli, C, Scarponi, M, Forte, E, Potenziani, S, Perin, Pc, Marena, S, Zucco, C, Perotto, M, Bossi, A, Filopanti, M, Grimaldi, F, Tonutti, L, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Tomasetto, E, Capra, C, Cigolini, M., Vaccaro, O1, Masulli, M, Bonora, E, Del Prato, S, Giorda, Cb, Maggioni, Ap, Mocarelli, P, Nicolucci, A, Rivellese, Aa, Squatrito, S, Riccardi, G, Collaborators Riccardi G, T. O. S. C. A. IT study g. r. o. u. p., Sud, Cm, Imbaro, S, Vaccaro, O, Garofalo, N, Ferrannini, E, Howard, B, Gerdts, E, Imperatore, G, Tavazzi, L, Pellegrini, F, Fabbri, G, Levantesi, G, Turazza, F, Gentile, Sandro, Panico, S, Brambilla, P, Signorini, S, Cappellini, F, Parma, C, D'Alonzo, D, Di Nardo, B, Ferrari, S, Franciosi, M, Pecce, R, Valentini, M, Ceseri, M, Bianchini, F, Baldini, E, Atzori, A, Boemi, M, D'Angelo, F, Giansanti, R, Ricci, L, Ranchelli, A, Di Berardino, P, Cannarsa, E, Giorgino, F, Manicone, M, Tarantino, L, Trevisan, R, Scaranna, C, Forlani, G, Montesi, L, Aiello, A, Barrea, A, Sinagra, T, Longhitano, S, Sesti, G, Gnasso, A, Carallo, C, Scicchitano, C, Santini, C, Calbucci, G, Ripani, R, Corsi, L, Corsi, S, Romeo, F, Asprino, V, Donnarumma, G, Tizio, B, Clemente, G, Tomasi, F, Dozio, N, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, Ol, Fariello, S, Cordera, R, Mazzucchelli, C, Pupillo, M, Zugaro, A, Bosco, A, De Luca, A, Iannarelli, R, Giuliani, A, Polidoro, L, Sperandio, A, Sciarretta, F, Raffaella, B, Venditti, C, Di Cianni, G, Goretti, C, Dolci, Ma, Bruselli, L, Mori, M, Baccetti, F, Gregori, G, Venezia, A, Cucinotta, D, Pintaudi, B, Ragonese, F, Pata, P, Piatti, Pm, Luccotti, P, Orsi, E, Bonomo, M, Menicatti, L, Turco, Aa, Ciano, O, Vallefuoco, P, Corigliano, G, Pentangelo, C, Petraroli, E, Auletta, P, Carbonara, O, Capobianco, G, Caiazzo, G, Angiulli, B, De Simone, G, Michele, C, Mastrilli, V, Nunziata, G, Romano, G, Gaeta, I, Sorrentino, T, Iovine, C, Nappi, F, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Avogaro, A, Vedovato, M, Lapolla, A, Sartore, G, Burlina, S, Chilelli, Nc, Galluzzoy, A, Giordano, C, Torregrossa, V, Arsenio, L, Dall'Aglio, E, Cioni, F, Babini, M, Moncastroppa, G, Perriello, G, Timi, A, Consoli, A, Ginestra, F, Zavaroni, D, Calzoni, F, Miccoli, R, Bianchi, C, Politi, S, Anichini, R, Tedeschi, A, Citro, G, Zampino, A, Rosa, S, Natale, M, Giocoli, Cl, Caruso, E, Tramontano, L, Imbroinise, A, Perna, Cd, Calabrese, M, Zogheri, A, Luberto, A, Ballardini, G, Babini, Ac, Zannoni, C, Pugliese, G, Salvi, L, Mazzitelli, G, Zappaterreno, A, Frontoni, S, Ventricini, A, Lauro, D, Galli, A, Rinaldi, Me, Leotta, S, Fontana, L, Goretti, S, Pozzilli, P, Leonetti, F, Morano, S, Filetti, S, Cosmo, Sd, Bacci, S, Palena, Ap, Calatola, P, Capuano, G, Amelia, U, Dotta, F, Guarino, E, Ceccarelli, E, Lalli, C, Scarponi, M, Forte, E, Potenziani, S, Perin, Pc, Marena, S, Zucco, C, Perotto, M, Bossi, A, Filopanti, M, Grimaldi, F, Tonutti, L, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Tomasetto, E, Capra, C, Cigolini M., Author information, Vaccaro, Olga, Masulli, Maria, Rivellese, ANGELA ALBAROSA, Riccardi, Gabriele, Giorda, C, Maggioni, A, Rivellese, A, Giorda, CB, Maggioni, AP, and Rivellese, AA

Subjects
Blood Glucose, Male, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Endocrinology, Diabetes and Metabolism, pioglitazone, sulfonylurea, type 2 diabetes, metformin, cardiovascular events, Medicine (miscellaneous), Type 2 diabetes, Settore MED/13 - Endocrinologia, Body Mass Index, law.invention, Randomized controlled trial, Risk Factors, law, Surveys and Questionnaires, Cardiovascular Disease, pioglitazone, piogllitazone, Stroke, Diabetes, Therapy, Pioglitazone, Nutrition and Dietetics, Diabetes, Thiazolidinedione, cardiovascular events, Type 2 Diabetes Mellitus, sulphonylureas, Middle Aged, Metformin, Sulfonylurea Compound, Treatment Outcome, Tolerability, Cardiovascular Diseases, Drug Therapy, Combination, Female, type 2 diabetes, Cardiology and Cardiovascular Medicine, Human, medicine.drug, medicine.medical_specialty, Endpoint Determination, sulfonylurea, cardiovascualr event, Sudden death, Follow-Up Studie, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, sulfonylureas, interventio trial, randomized controlled trial, Aged, Hypoglycemic Agent, Questionnaire, business.industry, Risk Factor, medicine.disease, Surgery, Sulfonylurea Compounds, Diabetes Mellitus, Type 2, Quality of Life, Thiazolidinediones, Therapy, business, metformin, Pioglitazone, Follow-Up Studies
Abstract

Background and aims Metformin is the first-line therapy in type 2 diabetes. In patients inadequately controlled with metformin, the addition of a sulfonylurea or pioglitazone are equally plausible options to improve glycemic control. However, these drugs have profound differences in their mechanism of action, side effects, and impact on cardiovascular risk factors. A formal comparison of these two therapies in terms of cardiovascular morbidity and mortality is lacking. The TOSCA.IT study was designed to explore the effects of adding pioglitazone or a sulfonylurea on cardiovascular events in type 2 diabetic patients inadequately controlled with metformin. Methods Multicentre, randomized, open label, parallel group trial of 48 month duration. Type 2 diabetic subjects, 50–75 years, BMI 20–45 Kg/m 2 , on secondary failure to metformin monotherapy will be randomized to add-on a sulfonylurea or pioglitazone. The primary efficacy outcome is a composite endpoint of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned coronary revascularization. Principal secondary outcome is a composite ischemic endpoint of sudden death, fatal and non-fatal myocardial infarction and stroke, endovascular or surgical intervention on the coronary, leg or carotid arteries, major amputations. Side effects, quality of life and economic costs will also be evaluated. Efficacy, safety, tolerability, and study conduct will be monitored by an independent Data Safety Monitoring Board. End points will be adjudicated by an independent external committee. Conclusions TOSCA.IT is the first on-going study investigating the head-to-head comparison of adding a sulfonylurea or pioglitazone to existing metformin treatment in terms of hard cardiovascular outcomes. Registration: Clinicaltrials.gov ID NCT00700856.

Published
2012

18. Insulin receptors and insulin sensitivity in normo and hyperinsulinemic obese patients

Author

Ragonese F, G. Saitta, R. Campisi, G. Lettina, G. Perrone, A. Carducci Artenisio, Forte F, and Consolo F

Subjects
Adult, Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Biology, Glucagon, chemistry.chemical_compound, Endocrinology, Insulin resistance, Hyperinsulinism, Internal medicine, medicine, Hyperinsulinemia, Humans, Insulin, Obesity, Glucose tolerance test, C-Peptide, medicine.diagnostic_test, C-peptide, Glucose Tolerance Test, Middle Aged, medicine.disease, Receptor, Insulin, Insulin receptor, chemistry, biology.protein, Insulin Resistance
Abstract

The authors have studied insulin receptors on peripheral blood monocytes and insulin sensitivity, evaluated by simultaneous infusion of glucose, insulin and somatostatin in 10 control subjects and in 20 obese patients with normal glucose tolerance. The obese patients have been divided into two groups, normo (NO) and hyperinsulinemic (HO), according to the total insulin response during OGTT. We considered HO patients with insulin response higher than M + 2DS of controls. Obese patients showed, in comparison to the controls, a lower specific binding and higher degree of insulin resistance. The subdivision of obese patients allowed us to distinguish two groups. The first was characterized by basal hyperinsulinemia, normal insulin response to the stimulus, reduced number of insulin receptors and normal or slightly reduced sensitivity. The second group showed high basal and after stimulus insulinemic values, reduced number of insulin receptors and high level of insulin resistance. When we compared the two groups of obeses we found that the first has a shorter duration of obesity and lower blood glucose values after OGTT. However both groups show the same reduction of insulin bound and the same degree of basal hyperinsulinemia. These data suggest that a reduction of insulin receptors is not the main factor responsible for insulin resistance in obesity. Furthermore, the presence of basal hyperinsulinemia and normal insulin sensitivity in our first group suggests that the modification of basal insulin concentrations is not dependent on the presence of insulin resistance.

Published
1985
Full Text
View/download PDF

19. Behaviour of HPL and GH Plasmatic Rate in Pregnant Women at Different Times of Their Pregnancy during Dynamic Tests

Author

Forte F, Maccarrone G, Volpe A, Ragonese F, Artenisio Ac, and Consolo F

Subjects
Blood Glucose, medicine.medical_specialty, Arginine, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Deoxyglucose, Hypoglycemia, Biochemistry, Endocrinology, blood, Pregnancy, Internal medicine, diagnostic use, Blood Glucose, Deoxyglucose, diagnostic use, Female, Glucose Tolerance Test, Glucose, diagnostic use, Growth Hormone, blood, Humans, Insulin, diagnostic use, Placental Lactogen, blood, Pregnancy, Humans, Insulin, Medicine, Placental lactogen, business.industry, Biochemistry (medical), General Medicine, Glucose Tolerance Test, Placental Lactogen, medicine.disease, Non pregnant, Glucose, Intravenous glucose, Growth Hormone, Female, diagnostic use, business, Hormone
Abstract

The authors have studied the effects of an oral or intravenous glucose load, of insulinic hypoglycemia, of arginine and the effects of the 2-deoxi-glucose on the plasmatic concentration of HPL and GH on pregnant women at different times during their pregnancy. None of the used tests seemed able to modify in any way the plasmatic concentration of the placental lactogen hormone; the somatotropinic response to the different stimuli happens to be lower than that found in non pregnant women of the same age. We and by asserting that unlike what happens with the GH, there does not exist a direct "feedback" between the modifications of plasmatic concentration of the main underlayers and HPL.

Published
1980
Full Text
View/download PDF

22. Effects of Propranolol on HGH Secretion after Endovenous Tolbutamide Load in Obese Subjects

Author

Albanese Mc, Ragonese F, V Corsi, Sprovieri M, A Carducci Artenisio, and V Allegra

Subjects
Adult, Blood Glucose, medicine.medical_specialty, Time Factors, Tolbutamide, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Radioimmunoassay, Propranolol, Fatty Acids, Nonesterified, Growth hormone, Biochemistry, Endocrinology, Internal medicine, medicine, Humans, Secretion, Obesity, Aged, Fatty acids.nonesterified, business.industry, Biochemistry (medical), General Medicine, Middle Aged, medicine.disease, Growth Hormone, Obese subjects, business, medicine.drug
Published
1973
Full Text
View/download PDF

23. Electrophysiological Impact of SARS-CoV-2 Envelope Protein in U251 Human Glioblastoma Cells: Possible Implications in Gliomagenesis?

Author

Monarca L, Ragonese F, Biagini A, Sabbatini P, Pacini M, Zucchi A, Spaccapelo R, Ferrari P, Nicolini A, and Fioretti B

Subjects
Humans, HEK293 Cells, Cell Line, Tumor, Coronavirus Envelope Proteins metabolism, Coronavirus Envelope Proteins genetics, Apoptosis, Brain Neoplasms metabolism, Brain Neoplasms virology, Brain Neoplasms pathology, Brain Neoplasms genetics, Glioblastoma metabolism, Glioblastoma virology, Glioblastoma pathology, Glioblastoma genetics, SARS-CoV-2 physiology, COVID-19 virology, COVID-19 metabolism, Membrane Potential, Mitochondrial
Abstract

SARS-CoV-2 is the causative agent of the COVID-19 pandemic, the acute respiratory disease which, so far, has led to over 7 million deaths. There are several symptoms associated with SARS-CoV-2 infections which include neurological and psychiatric disorders, at least in the case of pre-Omicron variants. SARS-CoV-2 infection can also promote the onset of glioblastoma in patients without prior malignancies. In this study, we focused on the Envelope protein codified by the virus genome, which acts as viroporin and that is reported to be central for virus propagation. In particular, we characterized the electrophysiological profile of E-protein transfected U251 and HEK293 cells through the patch-clamp technique and FURA-2 measurements. Specifically, we observed an increase in the voltage-dependent (Kv) and calcium-dependent (KCa) potassium currents in HEK293 and U251 cell lines, respectively. Interestingly, in both cellular models, we observed a depolarization of the mitochondrial membrane potential in accordance with an alteration of U251 cell growth. We, therefore, investigated the transcriptional effect of E protein on the signaling pathways and found several gene alterations associated with apoptosis, cytokines and WNT pathways. The electrophysiological and transcriptional changes observed after E protein expression could explain the impact of SARS-CoV-2 infection on gliomagenesis.

Published
2024
Full Text
View/download PDF

24. Electro-Metabolic Coupling of Cumulus-Oocyte Complex.

Author

Del Bianco D, Gentile R, Sallicandro L, Biagini A, Quellari PT, Gliozheni E, Sabbatini P, Ragonese F, Malvasi A, D'Amato A, Baldini GM, Trojano G, Tinelli A, and Fioretti B

Subjects
Humans, Animals, Female, Mitochondria metabolism, Adenosine Triphosphate metabolism, Gap Junctions metabolism, Oxidative Phosphorylation, Calcium metabolism, Potassium Channels metabolism, Cell Communication, Oocytes metabolism, Cumulus Cells metabolism, Cumulus Cells cytology
Abstract

Oocyte-cumulus cell interaction is essential for oocyte maturation and competence. The bidirectional crosstalk network mediated by gap junctions is fundamental for the metabolic cooperation between these cells. As cumulus cells exhibit a more glycolytic phenotype, they can provide metabolic substrates that the oocyte can use to produce ATP via oxidative phosphorylation. The impairment of mitochondrial activity plays a crucial role in ovarian aging and, thus, in fertility, determining the success or failure of assisted reproductive techniques. This review aims to deepen the knowledge about the electro-metabolic coupling of the cumulus-oocyte complex and to hypothesize a putative role of potassium channel modulators in order to improve fertility, promote intracellular Ca 2+ influx, and increase the mitochondrial biogenesis and resulting ATP levels in cumulus cells.

Published
2024
Full Text
View/download PDF

25. Synthesis and Characterization of ZIF-90 Nanoparticles as Potential Brain Cancer Therapy.

Author

Monarca L, Ragonese F, Sabbatini P, Caglioti C, Stamegna M, Palazzetti F, Sportoletti P, Costantino F, and Fioretti B

Abstract

Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood-brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system.

Published
2024
Full Text
View/download PDF

26. Therapeutic Targeting Potential of Novel Silver Nanoparticles Coated with Anti-CD20 Antibody against Chronic Lymphocytic Leukemia.

Author

Adamo FM, Silva Barcelos EC, De Falco F, Dorillo E, Rompietti C, Sorcini D, Stella A, Del Papa B, Baldoni S, Esposito A, Geraci C, Arcaleni R, Pennetta C, Ragonese F, Moretti L, Mameli M, Di Ianni M, Rosati E, Fioretti B, and Sportoletti P

Abstract

Background: Chronic lymphocytic leukemia (CLL) is an incurable disorder associated with alterations in several pathways essential for survival and proliferation. Despite the advances made in CLL therapy with the new target agents, in some cases, relapses and resistance could occur, making the discovery of new alternatives to manage CLL refractoriness necessary. To provide new therapeutic strategies for CLL, we investigated the anti-leukemic activity of silver nanoparticles (AgNPs), whose impact on CLL cells has been poorly explored., Methods: We studied the action mechanisms of AgNPs in vitro through flow cytometry and molecular analyses. To improve the bioavailability of AgNPs, we generated AgNPs coated with the anti-CD20 antibody Rituximab (AgNPs@Rituximab) and carried out imaging-based approaches and in vivo experiments to evaluate specificity, drug uptake, and efficacy., Results: AgNPs reduced the viability of primary CLL cells and the HG-3 cell line by inducing an intrinsic apoptotic pathway characterized by Bax/Bcl-2 imbalance, caspase activation, and PARP degradation. Early apoptotic events triggered by AgNPs included enhanced Ca 2+ influx and ROS overproduction. AgNPs synergistically potentiated the cytotoxicity of Venetoclax, Ibrutinib, and Bepridil. In vitro, the AgNPs@Rituximab conjugates were rapidly internalized within CLL cells and strongly prolonged the survival of CLL xenograft models compared to each unconjugated single agent., Conclusions: AgNPs showed strong anti-leukemic activity in CLL, with the potential for clinical translation in combination with agents used in CLL. The increased specificity of AgNPs@Rituximab toward CLL cells could be relevant for overcoming in vivo AgNPs' non-specific distribution and increasing their efficacy.

Published
2023
Full Text
View/download PDF

27. LY294002 Inhibits Intermediate Conductance Calcium-Activated Potassium (KCa3.1) Current in Human Glioblastoma Cells.

Author

Caglioti C, Palazzetti F, Monarca L, Lobello R, Ceccarini MR, Iannitti RG, Russo R, Ragonese F, Pennetta C, De Luca A, Codini M, and Fioretti B

Abstract

Glioblastomas (GBs) are among the most common tumors with high malignancy and invasiveness of the central nervous system. Several alterations in protein kinase and ion channel activity are involved to maintain the malignancy. Among them, phosphatidylinositol 3-kinase (PI3K) activity and intermediate conductance calcium-activated potassium (KCa3.1) current are involved in several aspects of GB biology. By using the electrophysiological approach and noise analysis, we observed that KCa3.1 channel activity is LY294002-sensitive and Wortmannin-resistant in accordance with the involvement of PI3K class IIβ (PI3KC2β). This modulation was observed also during the endogenous activation of KCa3.1 current with histamine. The principal action of PI3KC2β regulation was the reduction of open probability in intracellular free calcium saturating concentration. An explanation based on the "three-gate" model of the KCa3.1 channel by PI3KC2β was proposed. Based on the roles of KCa3.1 and PI3KC2β in GB biology, a therapeutic implication was suggested to prevent chemo- and radioresistance mechanisms., Competing Interests: RL was employed by the company Relab S.r.l. RI was employed by the company S&R Farmaceutici S.p.A Bastia Umbra. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Caglioti, Palazzetti, Monarca, Lobello, Ceccarini, Iannitti, Russo, Ragonese, Pennetta, De Luca, Codini and Fioretti.)

Published
2022
Full Text
View/download PDF

28. Resveratrol depolarizes the membrane potential in human granulosa cells and promotes mitochondrial biogenesis.

Author

Ragonese F, Monarca L, De Luca A, Mancinelli L, Mariani M, Corbucci C, Gerli S, Iannitti RG, Leonardi L, and Fioretti B

Subjects
Cell Line, Tumor, Cell Survival drug effects, Cell Survival physiology, Cells, Cultured, Female, Granulosa Cells physiology, Humans, Membrane Potential, Mitochondrial physiology, Mitochondria physiology, Antioxidants pharmacology, Granulosa Cells drug effects, Membrane Potential, Mitochondrial drug effects, Mitochondria drug effects, Organelle Biogenesis, Resveratrol pharmacology
Abstract

Objective: To study the biological effects of resveratrol on the growth, electrophysiology, and mitochondrial function of human granulosa cells (h-GCs)., Design: Preclinical study., Setting: Electrophysiology laboratory and in vitro fertilization unit., Patient(s): This study included h-GCs from seven infertile women undergoing assisted reproductive techniques., Intervention(s): Human ovarian Granulosa Cell Tumor (GCT) cell line COV434 and h-GCs obtained after oocyte retrieval were cultured in the absence or presence of resveratrol., Main Outcome Measure(s): Granulosa cells were evaluated for cell viability and mitochondrial activity. Electrophysiological recordings and evaluation of potassium current (IKur) and Ca 2+ concentration were also performed., Result(s): Resveratrol induced mitochondrial activity in a bell-shaped, dose-effect-dependent manner. Specifically, resveratrol treatment (3 μM, 48 hours) increased ATP production and cell viability and promoted the induction of cellular differentiation. These biological changes were associated with mitochondrial biogenesis. Electrophysiological recordings showed that resveratrol reduced the functional expression of an ultra rapid activating, slow inactivating, delayed rectifier potassium current (IKur) that is associated with a plasma membrane depolarization and that promotes an increase in intracellular Ca 2 + . CONCLUSION(S): The effects of resveratrol on potassium current and mitochondrial biogenesis in h-GCs could explain the beneficial effects of this polyphenol on the physiology of the female reproductive system. These findings suggest there are therapeutic implications of resveratrol in a clinical setting., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Published
2021
Full Text
View/download PDF

29. Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Represents an Oral Formulation of Resveratrol With Better Gastric Absorption and Bioavailability Respect to Pure Resveratrol.

Author

Iannitti RG, Floridi A, Lazzarini A, Tantucci A, Russo R, Ragonese F, Monarca L, Caglioti C, Spogli R, Leonardi L, De Angelis M, Palazzetti F, and Fioretti B

Abstract

Resveratrol attracts great interest because of the plethora of in vitro effects at the micromolar concentration range. Unfortunately, these effects are difficult to establish in vivo , due to the low concentration of resveratrol reached. This discrepancy is due to the molecules low solubility in water that favors the propensity for an intestinal absorption rather than in the gastric compartment. To address these challenges, we developed a Solid Dispersion of Resveratrol Supported by Magnesium Di Hydroxide formulation (Resv@MDH). This formulation displays increased water solubility and better bioavailability relative to pure resveratrol in the rabbit animal model. In our study, we evaluated the pharmacokinetics profile of resveratrol in six healthy human subjects following 180 mg of oral resveratrol administration, derived from Resv@MDH or pure resveratrol. Free resveratrol was evaluated in the whole blood sample by using HPLC - MS/MS. In comparison with pure resveratrol that displays an increase of the maximum plasma concentration, Cmax at about 90 min and 2 μM, Resv@MDH displays an earlier peak of resveratrol concentration with an increase of Cmax at about 30 min and 6 μM. The different kinetics suggest a main gastric route for resveratrol absorption from Resv@MDH, where, because of its improved dissolution rate, there seems to be a higher propensity for an acidic environment, as opposed to that with pure resveratrol. This conclusion is also supported by the numerical simulation analysis, which considers the principal steps during the oral route administration. Moreover, there is a 2-fold increase in the amount of free resveratrol with respect to pure resveratrol confirming a better bioavailability observed in the animal model. The characteristic feature of the pharmacokinetic profile of Resv@MDH implies that the beneficial properties of resveratrol in human health should be capitalized on it., (Copyright © 2020 Iannitti, Floridi, Lazzarini, Tantucci, Russo, Ragonese, Monarca, Caglioti, Spogli, Leonardi, De Angelis, Palazzetti and Fioretti.)

Published
2020
Full Text
View/download PDF

30. Effect of 1α,25(OH) 2 Vitamin D 3 in Mutant P53 Glioblastoma Cells: Involvement of Neutral Sphingomyelinase1.

Author

Cataldi S, Arcuri C, Lazzarini A, Nakashidze I, Ragonese F, Fioretti B, Ferri I, Conte C, Codini M, Beccari T, Curcio F, and Albi E

Abstract

Glioblastoma is one the most aggressive primary brain tumors in adults, and, despite the fact that radiation and chemotherapy after surgical approaches have been the treatments increasing the survival rates, the prognosis of patients remains poor. Today, the attention is focused on highlighting complementary treatments that can be helpful in improving the classic therapeutic approaches. It is known that 1α,25(OH) 2 vitamin D 3 , a molecule involved in bone metabolism, has many serendipidy effects in cells. It targets normal and cancer cells via genomic pathway by vitamin D3 receptor or via non-genomic pathways. To interrogate possible functions of 1α,25(OH) 2 vitamin D3 in multiforme glioblastoma, we used three cell lines, wild-type p53 GL15 and mutant p53 U251 and LN18 cells. We demonstrated that 1α,25(OH) 2 vitamin D3 acts via vitamin D receptor in GL15 cells and via neutral sphingomyelinase1, with an enrichment of ceramide pool, in U251 and LN18 cells. Changes in sphingomyelin/ceramide content were considered to be possibly responsible for the differentiating and antiproliferative effect of 1α,25(OH) 2 vitamin D in U251 and LN18 cells, as shown, respectively, in vitro by immunofluorescence and in vivo by experiments of xenotransplantation in eggs. This is the first time 1α,25(OH) 2 vitamin D3 is interrogated for the response of multiforme glioblastoma cells in dependence on the p53 mutation, and the results define neutral sphingomyelinase1 as a signaling effector.

Published
2020
Full Text
View/download PDF

31. New Insights on KCa3.1 Channel Modulation.

Author

Manfroni G, Ragonese F, Monarca L, Astolfi A, Mancinelli L, Iannitti RG, Bastioli F, Barreca ML, Cecchetti V, and Fioretti B

Subjects
Binding Sites, Calcium metabolism, Humans, Calcium Signaling, Intermediate-Conductance Calcium-Activated Potassium Channels metabolism
Abstract

The human intermediate conductance calcium-activated potassium channel, KCa3.1, is involved in several pathophysiological conditions playing a critical role in cell secretory machinery and calcium signalling. The recent cryo-EM analysis provides new insights for understanding the modulation by both endogenous and pharmacological agents. A typical feature of this channel is the low open probability in saturating calcium concentrations and its modulation by potassium channel openers (KCOs), such as benzo imidazolone 1-EBIO, without changing calcium-dependent activation. In this paper, we proposed a model of KCOs action in the modulation of channel activity. The KCa3.1 channel has a very rich pharmacological profile with several classes of molecules that selectively interact with different binding sites of the channel. Among them, benzo imidazolones can be openers (positive modulators such as 1-EBIO, DC-EBIO) or blockers (negative modulators such as NS1619). Through computation modelling techniques, we identified the 1,4-benzothiazin-3-one as a promising scaffold to develop new KCa3.1 channel modulators. Further studies are needed to explore the potential use of 1-4 benzothiazine- 3-one in KCa3.1 modulation and its pharmacological application., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Published
2020
Full Text
View/download PDF

32. Focus on the Use of Resveratrol as an Adjuvant in Glioblastoma Therapy.

Author

Dionigi L, Ragonese F, Monarca L, Covino S, de Luca A, Iannitti RG, Bastioli F, Moulas AN, Allegretti M, and Fioretti B

Subjects
Antineoplastic Agents, Alkylating therapeutic use, Humans, Matrix Metalloproteinase 2, Phosphatidylinositol 3-Kinases, Resveratrol pharmacology, Brain Neoplasms drug therapy, Glioblastoma drug therapy
Abstract

Glioblastoma (GB) represents the most common and malignant form of glioma cancer. The Gold Standard in Glioblastoma is neurosurgical tumor removal and radiotherapy treatment in concomitant with temozolomide (TMZ). Unfortunately, because of tumor chemo and radio-resistance during this therapy, the patient's outcome remains very poor, with a median overall survival of about 14.6 months. Resveratrol is a natural polyphenol with a stilbene structure with chemopreventive and anticancer properties. In the present review, we evaluated data from preclinical studies conducted with resveratrol as a possible adjuvant during the standard protocol of GB. Resveratrol can reach the brain parenchyma at sub-micromolar concentrations when administrated through conventional routes. In this way, resveratrol reduces cell invasion and increases the efficacy of radiotherapy (radiosensitizer effects) and temozolomide. The molecular mechanism of the adjuvant action of resveratrol may depend upon the reduction of PI3K/AKT/NF-κB axis and downstream targets O-6-methylguanine-DNA methyltransferase (MGMT) and metalloproteinase-2 (MMP-2). It has been reported that redox signaling plays an important role in the regulation of autophagy. Resveratrol administration by External Carotid Artery (ECA) injection or by Lumbar Puncture (LP) can reach micromolar concentrations in tumor mass where it would inhibit tumor growth by STAT-3 dependent mechanisms. Preclinical evidences indicate a positive effect on the use of resveratrol as an adjuvant in anti-GB therapy. Ameliorated formulations of resveratrol with a favorable plasmatic profile for a better brain distribution and timing sequences during radio and chemotherapy could represent a critical aspect for resveratrol use as an adjuvant for a clinical evaluation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Published
2020
Full Text
View/download PDF

33. Silver ions promote blebs growth in U251 glioblastoma cell by activating nonselective cationic currents.

Author

Ragonese F, Monarca L, Bastioli F, Arcuri C, Mancinelli L, and Fioretti B

Subjects
Calcium metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Humans, Hydrostatic Pressure, Intracellular Space drug effects, Intracellular Space metabolism, Sodium metabolism, Cell Membrane drug effects, Cell Membrane pathology, Electrophysiological Phenomena drug effects, Glioblastoma pathology, Silver chemistry, Silver pharmacology
Abstract

Glioblastoma (GBM) is the most common and aggressive human brain cancer with low prognosis and therefore the discovery of new anticancer agents is needful. Sulfydryl reagents, such as silver, have been shown to induce membrane vesiculation in several cellular models through a mechanism that has not been yet completely clarified. Using U251 glioblastoma cells, we observed that silver induced irreversible bleb formation of the plasma membrane. This morphological event was anticipated by an increase of intracellular Ca 2+ associated to extracellular Ca 2+ influx. Accordingly, using patch-clamp whole cell recording during silver ion application, inward current/s (IAg) at -90 mV were detected and cells were permeable to Ca 2+ and monovalent ions such as Na + . IAg activation and the intracellular Ca 2+ increase promoted by silver ions (Ag + ) were prevented by co-application of 20 µM cysteine and 300 µM DIDS (4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid), suggesting a critical role of thiol groups in the biological effects of silver ions. IAg was partially inhibited by 1 mM Gd 3+ , an unspecific inhibitor of cationic currents. Cysteine, Gd 3+ and extracellular free Ca 2+ solution completely abolished blebbing formation promoted by Ag + . Furthermore, extracellular Na + ion replacement with TEA or an increase of extracellular tonicity by sucrose (100 mM) reduced both size and growth of membrane blebbing. Our data suggest that Ag + promotes the formation necrotic blebs as consequence of the increase of intracellular Ca 2+ and intracellular hydrostatic pressure associated to the activation of cationic currents. Since silver-induced blebs were less evident in benign glial human Müller MIO-M1 cells, silver compounds could represent new adjuvant to anticancer agents to improve GBM therapies.

Published
2019
Full Text
View/download PDF

34. Solid Dispersion of Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Microparticles Improves Oral Bioavailability.

Author

Spogli R, Bastianini M, Ragonese F, Iannitti RG, Monarca L, Bastioli F, Nakashidze I, Brecchia G, Menchetti L, Codini M, Arcuri C, Mancinelli L, and Fioretti B

Subjects
Administration, Oral, Animals, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Anti-Inflammatory Agents, Non-Steroidal chemistry, Biological Availability, Chemistry, Pharmaceutical, Particle Size, Rabbits, Resveratrol administration & dosage, Resveratrol chemistry, Anti-Inflammatory Agents, Non-Steroidal pharmacokinetics, Magnesium Hydroxide chemistry, Resveratrol pharmacokinetics
Abstract

Resveratrol, because of its low solubility in water and its high membrane permeability, is collocated in the second class of the biopharmaceutical classification system, with limited bioavailability due to its dissolution rate. Solid dispersion of resveratrol supported on Magnesium DiHydroxide (Resv@MDH) was evaluated to improve solubility and increase bioavailability of resveratrol. Fluorimetric microscopy analysis displays three types of microparticles with similar size: Type 1 that emitted preferably fluorescence at 445 nm with bandwidth of 50 nm, type 2 that emitted preferably fluorescence at 605 nm with bandwidth of 70 nm and type 3 that is non-fluorescent. Micronized pure resveratrol displays only microparticles type 1 whereas type 3 are associated to pure magnesium dihydroxide. Dissolution test in simulated gastric environment resveratrol derived from Resv@MDH in comparison to resveratrol alone displayed better solubility. A 3-fold increase of resveratrol bioavailability was observed after oral administration of 50 mg/kg of resveratrol from Resv@MDH in rabbits. We hypothesize that type 2 microparticles represent magnesium dihydroxide microparticles with a resveratrol shell and that they are responsible for the improved resveratrol solubility and bioavailability of Resv@MDH.

Published
2018
Full Text
View/download PDF

35. Probing Internalization Effects and Biocompatibility of Ultrasmall Zirconium Metal-Organic Frameworks UiO-66 NP in U251 Glioblastoma Cancer Cells.

Author

Arcuri C, Monarca L, Ragonese F, Mecca C, Bruscoli S, Giovagnoli S, Donato R, Bereshchenko O, Fioretti B, and Costantino F

Abstract

The synthesis of ultrasmall UiO-66 nanoparticles (NPs) with an average size of 25 nm, determined by X-ray powder diffraction and electron microscopies analysis, is reported. The NPs were stabilized in water by dialyzing the NP from the DMF used for the synthesis. DLS measurements confirmed the presence of particles of 100 nm, which are spherical aggregates of smaller particles of 20⁻30 nm size. The NP have a BET surface area of 700 m²/g with an external surface area of 300 m²/g. UiO-66_N (UiO-66 nanoparticles) were loaded with acridine orange as fluorescent probe. UV-vis spectroscopy analysis revealed no acridine loss after 48 h of agitation in simulated body fluid. The biocompatibility of UiO-66_N was evaluated in human glioblastoma (GBM) cell line U251, the most malignant (IV grade of WHO classification) among brain tumors. In U251 cells, UiO-66_N are inert since they do not alter the cell cycle, the viability, migration properties, and the expression of kinases involved in cancer cell growth. The internalization process was evident after a few hours of incubation. After 24 h, UiO-66_N@Acr (UiO-66_N loaded with acridine orange) were detectable around the nuclei of the cells. These data suggest that small UiO-66 are biocompatible NP and could represent a potential carrier for drug delivery in glioblastoma therapies.

Published
2018
Full Text
View/download PDF

36. Antitumor activity and expression profiles of genes induced by sulforaphane in human melanoma cells.

Author

Arcidiacono P, Ragonese F, Stabile A, Pistilli A, Kuligina E, Rende M, Bottoni U, Calvieri S, Crisanti A, and Spaccapelo R

Subjects
Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Melanoma therapy, Sulfoxides, Thiocyanates, Anticarcinogenic Agents pharmacology, Apoptosis drug effects, Brassicaceae chemistry, Cell Survival, Isothiocyanates pharmacology
Abstract

Purpose: Human melanoma is a highly aggressive incurable cancer due to intrinsic cellular resistance to apoptosis, reprogramming, proliferation and survival during tumour progression. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, plays a role in carcinogenesis in many cancer types. However, the cytotoxic molecular mechanisms and gene expression profiles promoted by SFN in human melanoma remain unknown., Methods: Three different cell lines were used: two human melanoma A375 and 501MEL and human epidermal melanocytes (HEMa). Cell viability and proliferation, cell cycle analysis, cell migration and invasion and protein expression and phosphorylation status of Akt and p53 upon SFN treatment were determined. RNA-seq of A375 was performed at different time points after SFN treatment., Results: We demonstrated that SFN strongly decreased cell viability and proliferation, induced G 2 /M cell cycle arrest, promoted apoptosis through the activation of caspases 3, 8, 9 and hampered migration and invasion abilities in the melanoma cell lines. Remarkably, HEMa cells were not affected by SFN treatment. Transcriptomic analysis revealed regulation of genes involved in response to stress, apoptosis/cell death and metabolic processes. SFN upregulated the expression of pro-apoptotic genes, such as p53, BAX, PUMA, FAS and MDM2; promoted cell cycle inhibition and growth arrest by upregulating EGR1, GADD45B, ATF3 and CDKN1A; and simultaneously acted as a potent inhibitor of genotoxicity by launching the stress-inducible protein network (HMOX1, HSPA1A, HSPA6, SOD1)., Conclusion: Overall, the data show that SFN cytotoxicity in melanoma derives from complex and concurrent mechanisms during carcinogenesis, which makes it a promising cancer prevention agent.

Published
2018
Full Text
View/download PDF

37. Glioblastoma single-cell microRaman analysis under stress treatments.

Author

Ricci M, Ragonese F, Gironi B, Paolantoni M, Morresi A, Latterini L, Fioretti B, and Sassi P

Subjects
Apoptosis drug effects, Brain Neoplasms metabolism, Cell Line, Tumor, Dimethyl Sulfoxide pharmacology, Glioblastoma metabolism, Glucose metabolism, Humans, Brain Neoplasms pathology, Glioblastoma pathology, Hydrogen Peroxide pharmacology, Oxidative Stress drug effects, Oxidative Stress physiology, Single-Cell Analysis methods, Spectrum Analysis, Raman methods
Abstract

Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor characterized by highly heterogeneous subpopulations. In order to reveal the heterogeneous cell response, single cell analysis is an essential requirement. In this study, optical microscopy and Raman microspectroscopy were used to follow the stress response of U251 single cells adherent on a silicon substrate. Cultured cells on silicon substrate were treated with hydrogen peroxide to promote apoptosis. Under these conditions expected changes occurred after a few hours and were revealed by the reduction of cytochrome c, lipid, nucleic acid and protein Raman signals: this ensured the possibility to analyse U251 cell line as grown on Si substrate, and to monitor the response of single cells to stress conditions. As a consequence, we used microRaman to monitor the effects induced by nutrient depletion: a fast change of Raman spectra showed two different sub-populations of sensible and resistant U251 cells. Furthermore, spectral variations after DMSO addition were associated to volume changes and confirmed by morphological analysis. Thus, our results highlight the sensitivity of Raman microspectroscopy to detect rapid variations of macromolecule concentration due to oxidative stress and/or cell volume changes at the single cell level.

Published
2018
Full Text
View/download PDF

38. Anticarcinogenic activities of sulforaphane are influenced by Nerve Growth Factor in human melanoma A375 cells.

Author

Arcidiacono P, Stabile AM, Ragonese F, Pistilli A, Calvieri S, Bottoni U, Crisanti A, Spaccapelo R, and Rende M

Subjects
Apoptosis, Caspase 3 metabolism, Cell Cycle physiology, Cell Line, Tumor, Cell Movement physiology, Cell Survival physiology, Humans, Melanoma pathology, Nerve Tissue Proteins metabolism, Proto-Oncogene Proteins c-akt metabolism, Real-Time Polymerase Chain Reaction, Receptor, trkA metabolism, Receptors, Nerve Growth Factor metabolism, Skin Neoplasms pathology, Sulfoxides, Anticarcinogenic Agents pharmacology, Isothiocyanates pharmacology, Melanoma metabolism, Nerve Growth Factor physiology, Skin Neoplasms metabolism
Abstract

Melanoma is a severe form of cancer, resistant to conventional therapies. According to in vitro studies, sulforaphane, a dietary component, has been considered a promising antineoplastic candidate. The present study analyzes the in vitro biological effects of sulforaphane in A375 melanoma cell line with or without the addition of Nerve Growth Factor. For the first time, our results show that a supplementation of Nerve Growth Factor partially reverses the sulforaphane-induced: i) inhibition of cell migration, ii) pro apoptotic changes in cell cycle and iii) modulation of active caspase-3. Furthermore, we report the sulforaphane-induced modulation in the expression of Nerve Growth Factor receptors TrKA and p75NTR, shifting their ratio from pro survival to pro apoptotic. In conclusion, the present study evidences that in vivo the antineoplastic effects of sulforaphane may be reduced by the contemporaneous presence of other biological elements such as Nerve Growth Factor and it contributes to a better definition of the real in vivo potentiality of sulforaphane as antineoplastic candidate., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
Full Text
View/download PDF

39. Effect of nitrogen fertilisation on the overall quality of minimally processed globe artichoke heads.

Author

Lombardo S, Restuccia C, Muratore G, Barbagallo RN, Licciardello F, Pandino G, Scifò GO, Mazzaglia A, Ragonese F, and Mauromicale G

Subjects
Bacterial Load, Catechol Oxidase metabolism, Cell Respiration, Crops, Agricultural growth & development, Crops, Agricultural metabolism, Crops, Agricultural microbiology, Cynara scolymus growth & development, Cynara scolymus metabolism, Cynara scolymus microbiology, Dietary Carbohydrates analysis, Flowers growth & development, Flowers metabolism, Flowers microbiology, Food Handling, Food Storage, Gram-Negative Bacteria growth & development, Gram-Negative Bacteria isolation & purification, Gram-Positive Bacteria growth & development, Gram-Positive Bacteria isolation & purification, Inulin analysis, Inulin biosynthesis, Nutritive Value, Pigments, Biological analysis, Pigments, Biological biosynthesis, Pigments, Biological metabolism, Plant Proteins metabolism, Refrigeration, Sensation, Surface Properties, Crop Production, Crops, Agricultural chemistry, Cynara scolymus chemistry, Fertilizers, Flowers chemistry, Food Quality, Nitrogen Cycle
Abstract

Background: Although nitrogen (N) fertilisation is essential for promoting crop yield, it may also affect the produce quality. Here, the influence of three N fertiliser rates (0 kg ha -1 as a control, 200 kg ha -1 and 400 kg ha -1 referred to as N 0 , N 200 and N 400 , respectively) on the overall quality of minimally processed globe artichoke heads was investigated during refrigerated storage for 12 days., Results: Throughout the storage time, N fertilised samples had higher inulin contents than those unfertilised. In addition, the respiratory quotient of N 200 and N 400 samples was 2-fold and 2.5-fold lower than N 0 ones, whose values were close to the normal range for vegetables. All the samples reported good microbiological standards, although N 200 and N 400 achieved lower mesophilic and psychotropic counts than N 0 throughout the storage time. After 8 and 12 days of refrigerated storage, the N 200 samples showed the highest scores of positive sensory descriptors., Conclusion: A fertiliser level of 200 kg N ha -1 is suitable for obtaining minimally processed globe artichoke heads with good nutritional, sensory and microbiological quality, characterised by low endogenous oxidase activities. Proper packaging systems and procedures are, however, crucial for extending the product shelf-life and, thus, promoting its exportation on a wider scale. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Published
2017
Full Text
View/download PDF

40. Development of novel cyclic peptides as pro-apoptotic agents.

Author

Brindisi M, Maramai S, Brogi S, Fanigliulo E, Butini S, Guarino E, Casagni A, Lamponi S, Bonechi C, Nathwani SM, Finetti F, Ragonese F, Arcidiacono P, Campiglia P, Valenti S, Novellino E, Spaccapelo R, Morbidelli L, Zisterer DM, Williams CD, Donati A, Baldari C, Campiani G, Ulivieri C, and Gemma S

Subjects
Animals, Cell Cycle drug effects, Cell Line, Tumor, Drug Screening Assays, Antitumor, Humans, Mice, Microtubules metabolism, Peptides, Cyclic chemistry, Peptidomimetics chemistry, Peptidomimetics pharmacology, Structure-Activity Relationship, Tubulin drug effects, Apoptosis drug effects, Peptides, Cyclic pharmacology
Abstract

Our recent finding that paclitaxel behaves as a peptidomimetic of the endogenous protein Nur77 inspired the design of two peptides (PEP1 and PEP2) reproducing the effects of paclitaxel on Bcl-2 and tubulin, proving the peptidomimetic nature of paclitaxel. Starting from these peptide-hits, we herein describe the synthesis and the biological investigation of linear and cyclic peptides structurally related to PEP2. While linear peptides (2a,b, 3a,b, 4, 6a-f) were found inactive in cell-based assays, biological analysis revealed a pro-apoptotic effect for most of the cyclic peptides (5a-g). Cellular permeability of 5a (and also of 2a,b) on HL60 cells was assessed through confocal microscopy analysis. Further cellular studies on a panel of leukemic cell lines (HL60, Jurkat, MEC, EBVB) and solid tumor cell lines (breast cancer MCF-7 cells, human melanoma A375 and 501Mel cells, and murine melanoma B16F1 cells) confirmed the pro-apoptotic effect of the cyclic peptides. Cell cycle analysis revealed that treatment with 5a, 5c, 5d or 5f resulted in an increase in the number of cells in the sub-G0/G1 peak. Direct interaction with tubulin (turbidimetric assay) and with microtubules (immunostaining experiments) was assessed in vitro for the most promising compounds., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Published
2016
Full Text
View/download PDF

41. [Behavior of HGH after oral administration of L-dopa in normal and obese subjects].

Author

Carducci Artenisio A, Ragonese F, Albanese MC, Alibrando S, and Allegra V

Subjects
Administration, Oral, Adolescent, Adult, Blood Glucose biosynthesis, Fatty Acids, Nonesterified metabolism, Growth Hormone biosynthesis, Humans, Insulin blood, Levodopa administration & dosage, Middle Aged, Obesity blood, Pituitary Gland physiopathology, Growth Hormone blood, Levodopa pharmacology, Obesity physiopathology
Published
1974

44. [Effects of intravenous lipid loading on HGH secretion after administration of L-DOPA].

Author

Carducci Artenisio A, Ragonese F, Alibrando A, Forte F, Mancuso T, and Consolo F

Subjects
Adult, Blood Glucose biosynthesis, Fatty Acids, Nonesterified blood, Female, Humans, Male, Parenteral Nutrition, Triglycerides blood, Dietary Fats administration & dosage, Growth Hormone metabolism, Levodopa pharmacology, Lipids blood
Published
1979

45. [Effects of nicotinic acid on the secretion of HGH in normal and obese subjects].

Author

Carducci Artenisio A, Albanese MC, Ragonese F, Allegra V, and Alibrando S

Subjects
Adult, Blood Glucose biosynthesis, Fatty Acids, Nonesterified blood, Growth Hormone blood, Humans, Insulin blood, Middle Aged, Pituitary Gland physiopathology, Growth Hormone metabolism, Nicotinic Acids pharmacology, Obesity physiopathology, Pituitary Gland metabolism
Published
1974

46. [Levodopa and somatotropic hormone in diabetes].

Author

Carducci Artenisio A, Ragonese F, Martelli G, Forte F, Campisi R, and Consolo F

Subjects
Humans, Middle Aged, Pituitary Gland, Anterior drug effects, Pituitary Gland, Anterior physiopathology, Stimulation, Chemical, Diabetes Mellitus physiopathology, Growth Hormone metabolism, Levodopa pharmacology
Published
1978

47. [Effects of adrenergic blocking agents on HGH secretion after administration of L-Dopa].

Author

Ragonese F, Melluso K, Campisi R, and Carducci Artenisio A

Subjects
Adolescent, Adult, Blood Glucose analysis, Fatty Acids, Nonesterified blood, Humans, Middle Aged, Growth Hormone metabolism, Levodopa pharmacology, Phentolamine pharmacology, Pituitary Gland metabolism, Pituitary Gland, Anterior metabolism, Propranolol pharmacology
Published
1975

50. Insulin receptors and insulin sensitivity in normo and hyperinsulinemic obese patients.

Author

Carducci Artenisio A, Ragonese F, Forte F, Saitta G, Perrone G, Lettina G, Campisi R, and Consolo F

Subjects
Adult, Blood Glucose metabolism, C-Peptide blood, Glucagon blood, Glucose Tolerance Test, Humans, Hyperinsulinism complications, Insulin blood, Middle Aged, Obesity complications, Hyperinsulinism metabolism, Insulin Resistance, Obesity metabolism, Receptor, Insulin metabolism
Abstract

The authors have studied insulin receptors on peripheral blood monocytes and insulin sensitivity, evaluated by simultaneous infusion of glucose, insulin and somatostatin in 10 control subjects and in 20 obese patients with normal glucose tolerance. The obese patients have been divided into two groups, normo (NO) and hyperinsulinemic (HO), according to the total insulin response during OGTT. We considered HO patients with insulin response higher than M + 2DS of controls. Obese patients showed, in comparison to the controls, a lower specific binding and higher degree of insulin resistance. The subdivision of obese patients allowed us to distinguish two groups. The first was characterized by basal hyperinsulinemia, normal insulin response to the stimulus, reduced number of insulin receptors and normal or slightly reduced sensitivity. The second group showed high basal and after stimulus insulinemic values, reduced number of insulin receptors and high level of insulin resistance. When we compared the two groups of obeses we found that the first has a shorter duration of obesity and lower blood glucose values after OGTT. However both groups show the same reduction of insulin bound and the same degree of basal hyperinsulinemia. These data suggest that a reduction of insulin receptors is not the main factor responsible for insulin resistance in obesity. Furthermore, the presence of basal hyperinsulinemia and normal insulin sensitivity in our first group suggests that the modification of basal insulin concentrations is not dependent on the presence of insulin resistance.

Published
1985
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results