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1. Gender-differences in disease distribution and outcome in hospitalized elderly: Data from the REPOSI study

Author: Corrao, S, Santalucia, P, Argano, C, Djade, C, Barone, E, Tettamanti, M, Pasina, L, Franchi, C, Kamal Eldin, T, Marengoni, A, Salerno, F, Marcucci, M, Mannucci, P, Nobili, A, Mannucci, M, Sparacio, E, Alborghetti, S, Di Costanzo, R, Djignefa Djade, C, Prisco, D, Silvestri, E, Cenci, C, Barnini, T, Delitala, G, Carta, S, Atzori, S, Guarnieri, G, Zanetti, M, Spalluti, A, Serra, M, Bleve, M, Vanoli, M, Grignani, G, Casella, G, Gasbarrone, L, Maniscalco, G, Gunelli, M, Tirotta, D, Brucato, A, Ghidoni, S, Bernardi, M, Bassi, S, Santi, L, Agnelli, G, Iorio, A, Marchesini, E, Mannarino, E, Lupattelli, G, Rondelli, P, Paciullo, F, Fabris, F, Carlon, M, Turatto, F, Baroni, M, Zardo, M, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Paolisso, G, Rizzo, M, Laieta, M, Salvatore, T, Sasso, F, Utili, R, Durante Mangoni, E, Pinto, D, Olivieri, O, Stanzial, A, Fellin, R, Volpato, S, Fotini, S, Barbagallo, M, Dominguez, L, Plances, L, D'Angelo, D, Rini, G, Mansueto, P, Pepe, I, Licata, G, Calvo, L, Valenti, M, Borghi, C, Strocchi, E, Rinaldi, E, Zoli, M, Fabbri, E, Magalotti, D, Auteri, A, Pasqui, A, Puccetti, L, Laghi Pasini, F, Capecchi, P, Bicchi, M, Sabbà, C, Vella, F, Marseglia, A, Luglio, C, Palasciano, G, Modeo, M, Aquilino, A, Raffaele, P, Pugliese, S, Capobianco, C, Postiglione, A, Barbella, M, De Stefano, F, Fenoglio, L, Brignone, C, Bracco, C, Giraudo, A, Musca, G, Cuccurullo, O, Cricco, L, Fiorentini, A, Cappellini, M, Fabio, G, Seghezzi, S, De Amicis, M, Fargion, S, Bonara, P, Bulgheroni, M, Lombardi, R, Magrini, F, Massari, F, Tonella, T, Peyvandi, F, Tedeschi, A, Rossio, R, Moreo, G, Ferrari, B, Roncari, L, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Mari, D, Rossi, P, Damanti, S, Prolo, S, Lilleri, M, Micale, G, Podda, M, Selmi, C, Meda, F, Accordino, S, Conca, A, Monti, V, Corazza, G, Miceli, E, Lenti, M, Padula, D, Balduini, C, Bertolino, G, Provini, S, Quaglia, F, Murialdo, G, Bovio, M, Dallegri, F, Ottonello, L, Quercioli, A, Barreca, A, Secchi, M, Ghelfi, D, Chin, W, Carassale, L, Caporotundo, S, Anastasio, L, Carbone, M, Traisci, G, De Feudis, L, Davì, G, Guagnano, M, Sestili, S, Bergami, E, Rizzioli, E, Cagnoni, C, Bertone, L, Manucra, A, Buratti, A, Tognin, T, Liberato, N, Bernasconi, G, Nardo, B, Bianchi, G, Benetti, G, Quagliolo, M, Centenaro, G, Purrello, F, Di Pino, A, Piro, S, Mancuso, G, Calipari, D, Bartone, M, Gullo, F, Cortellaro, M, Magenta, M, Perego, F, Meroni, M, Cicardi, M, Magenta, A, Sacco, A, Bonelli, A, Dentamaro, G, Rozzini, R, Falanga, L, Giordano, A, Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Montrucchio, G, Greco, E, Tizzani, P, Fera, G, Di Luca, M, Renna, D, Perciccante, A, Coralli, A, Tassara, R, Melis, D, Rebella, L, Menardo, G, Bottone, S, Sferrazzo, E, Ferri, C, Striuli, R, Scipioni, R, Salmi, R, Gaudenzi, P, Gamberini, S, Ricci, F, Morabito, C, Fava, R, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Bolondi, L, Rasciti, L, Serio, I, Masala, C, Mammarella, A, Raparelli, V, Rossi Fanelli, F, Delfino, M, Amoroso, A, Violi, F, Basili, S, Perri, L, Serra, P, Fontana, V, Falcone, M, Landolfi, R, Grieco, A, Gallo, A, Zuccalà, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, Bellusci, M, Setti, D, Pedrazzoli, F, Romanelli, G, Pirali, C, Amolini, C, Rosei, E, Rizzoni, D, Castoldi, L, Picardi, A, Gentilucci, U, Mazzarelli, C, Gallo, P, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Contini, S, Molaro, M, Annoni, G, Corsi, M, Zazzetta, S, Bertolotti, M, Mussi, C, Scotto, R, Ferri, M, Veltri, F, Arturi, F, Succurro, E, Sesti, G, Gualtieri, U, Perticone, F, Sciacqua, A, Quero, M, Bagnato, C, Loria, P, Becchi, M, Martucci, G, Fantuzzi, A, Maurantonio, M, Corinaldesi, R, De Giorgio, R, Grasso, V, Ruggeri, E, Carozza, L, Pignatti, F, Mannucci M, Nobili A, Tettamanti M, Pasina L, Franchi C, Salerno F, Corrao S, Marengoni A, Marcucci M, Sparacio E, Alborghetti S, Di Costanzo R, Djignefa Djade C, Prisco D, Silvestri E, Cenci C, Barnini T, Delitala G, Carta S, Atzori S, Guarnieri G, Zanetti M, Spalluti A, Serra MG, Bleve MA, Vanoli M, Grignani G, Casella G, Gasbarrone L, Maniscalco G, Gunelli M, Tirotta D, Brucato A, Ghidoni S, Bernardi M, Bassi SL, Santi L, Agnelli G, Iorio A, Marchesini E, Mannarino E, Lupattelli G, Rondelli P, Paciullo F, Fabris F, Carlon M, Turatto F, Baroni MC, Zardo M, Manfredini R, Molino C, Pala M, Fabbian F, Nuti R, Valenti R, Ruvio M, Cappelli S, Paolisso G, Rizzo MR, Laieta MT, Salvatore T, Sasso FC, Utili R, Durante Mangoni E, Pinto D, Olivieri O, Stanzial AM, Fellin R, Volpato S, Fotini S, Barbagallo M, Dominguez L, Plances L, D'Angelo D, Rini G, Mansueto P, Pepe I, Licata G, Calvo L, Valenti M, Borghi C, Strocchi E, Rinaldi ER, Zoli M, Fabbri E, Magalotti D, Auteri A, Pasqui AL, Puccetti L, Laghi Pasini F, Capecchi PL, Bicchi M, Sabbà C, Vella FS, Marseglia A, Luglio CV, Palasciano G, Modeo ME, Aquilino A, Raffaele P, Pugliese S, Capobianco C, Postiglione A, Barbella MR, De Stefano F, Fenoglio L, Brignone C, Bracco C, Giraudo A, Musca G, Cuccurullo O, Cricco L, Fiorentini A, Cappellini MD, Fabio G, Seghezzi S, De Amicis MM, Fargion S, Bonara P, Bulgheroni M, Lombardi R, Magrini F, Massari F, Tonella T, Peyvandi F, Tedeschi A, Rossio R, Moreo G, Ferrari B, Roncari L, Monzani V, Savojardo V, Folli C, Magnini M, Mari D, Rossi PD, Damanti S, Prolo S, Lilleri MS, Micale G, Podda M, Selmi C, Meda F, Accordino S, Conca A, Monti V, Corazza GR, Miceli E, Lenti MV, Padula D, Balduini CL, Bertolino G, Provini S, Quaglia F, Murialdo G, Bovio M, Dallegri F, Ottonello L, Quercioli A, Barreca A, Secchi MB, Ghelfi D, Chin WS, Carassale L, Caporotundo S, Anastasio L, Carbone M, Traisci G, De Feudis L, Davì G, Guagnano MT, Sestili S, Bergami E, Rizzioli E, Cagnoni C, Bertone L, Manucra A, Buratti A, Tognin T, Liberato NL, Bernasconi G, Nardo B, Bianchi GB, Benetti G, Quagliolo M, Centenaro GR, Purrello F, Di Pino A, Piro S, Mancuso G, Calipari D, Bartone M, Gullo F, Cortellaro M, Magenta M, Perego F, Meroni MR, Cicardi M, Magenta AG, Sacco A, Bonelli A, Dentamaro G, Rozzini R, Falanga L, Giordano A, Perin PC, Lorenzati B, Gruden G, Bruno G, Montrucchio G, Greco E, Tizzani P, Fera G, Di Luca ML, Renna D, Perciccante A, Coralli A, Tassara R, Melis D, Rebella L, Menardo G, Bottone S, Sferrazzo E, Ferri C, Striuli R, Scipioni R, Salmi R, Gaudenzi P, Gamberini S, Ricci F, Morabito C, Fava R, Semplicini A, Gottardo L, Vendemiale G, Serviddio G, Forlano R, Bolondi L, Rasciti L, Serio I, Masala C, Mammarella A, Raparelli V, Rossi Fanelli F, Delfino M, Amoroso A, Violi F, Basili S, Perri L, Serra P, Fontana V, Falcone M, Landolfi R, Grieco A, Gallo A, Zuccalà G, Franceschi F, De Marco G, Chiara C, Marta S, Bellusci M, Setti D, Pedrazzoli F, Romanelli G, Pirali C, Amolini C, Rosei EA, Rizzoni D, Castoldi L, Picardi A, Gentilucci UV, Mazzarelli C, Gallo P, Guasti L, Castiglioni L, Maresca A, Squizzato A, Contini S, Molaro M, Corsi M, Bertolotti M, Mussi C, Scotto R, Ferri MA, Veltri F, Arturi F, Succurro E, Sesti G, Gualtieri U, Perticone F, Sciacqua A, Quero M, Bagnato C, Loria P, Becchi MA, Martucci G, Fantuzzi A, Maurantonio M, Corinaldesi R, De Giorgio R, Serra M, Grasso V, Ruggeri E, Carozza LM, Pignatti F., ANNONI, GIORGIO, ZAZZETTA, SARA, Corrao, S, Santalucia, P, Argano, C, Djade, C, Barone, E, Tettamanti, M, Pasina, L, Franchi, C, Kamal Eldin, T, Marengoni, A, Salerno, F, Marcucci, M, Mannucci, P, Nobili, A, Mannucci, M, Sparacio, E, Alborghetti, S, Di Costanzo, R, Djignefa Djade, C, Prisco, D, Silvestri, E, Cenci, C, Barnini, T, Delitala, G, Carta, S, Atzori, S, Guarnieri, G, Zanetti, M, Spalluti, A, Serra, M, Bleve, M, Vanoli, M, Grignani, G, Casella, G, Gasbarrone, L, Maniscalco, G, Gunelli, M, Tirotta, D, Brucato, A, Ghidoni, S, Bernardi, M, Bassi, S, Santi, L, Agnelli, G, Iorio, A, Marchesini, E, Mannarino, E, Lupattelli, G, Rondelli, P, Paciullo, F, Fabris, F, Carlon, M, Turatto, F, Baroni, M, Zardo, M, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Paolisso, G, Rizzo, M, Laieta, M, Salvatore, T, Sasso, F, Utili, R, Durante Mangoni, E, Pinto, D, Olivieri, O, Stanzial, A, Fellin, R, Volpato, S, Fotini, S, Barbagallo, M, Dominguez, L, Plances, L, D'Angelo, D, Rini, G, Mansueto, P, Pepe, I, Licata, G, Calvo, L, Valenti, M, Borghi, C, Strocchi, E, Rinaldi, E, Zoli, M, Fabbri, E, Magalotti, D, Auteri, A, Pasqui, A, Puccetti, L, Laghi Pasini, F, Capecchi, P, Bicchi, M, Sabbà, C, Vella, F, Marseglia, A, Luglio, C, Palasciano, G, Modeo, M, Aquilino, A, Raffaele, P, Pugliese, S, Capobianco, C, Postiglione, A, Barbella, M, De Stefano, F, Fenoglio, L, Brignone, C, Bracco, C, Giraudo, A, Musca, G, Cuccurullo, O, Cricco, L, Fiorentini, A, Cappellini, M, Fabio, G, Seghezzi, S, De Amicis, M, Fargion, S, Bonara, P, Bulgheroni, M, Lombardi, R, Magrini, F, Massari, F, Tonella, T, Peyvandi, F, Tedeschi, A, Rossio, R, Moreo, G, Ferrari, B, Roncari, L, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Mari, D, Rossi, P, Damanti, S, Prolo, S, Lilleri, M, Micale, G, Podda, M, Selmi, C, Meda, F, Accordino, S, Conca, A, Monti, V, Corazza, G, Miceli, E, Lenti, M, Padula, D, Balduini, C, Bertolino, G, Provini, S, Quaglia, F, Murialdo, G, Bovio, M, Dallegri, F, Ottonello, L, Quercioli, A, Barreca, A, Secchi, M, Ghelfi, D, Chin, W, Carassale, L, Caporotundo, S, Anastasio, L, Carbone, M, Traisci, G, De Feudis, L, Davì, G, Guagnano, M, Sestili, S, Bergami, E, Rizzioli, E, Cagnoni, C, Bertone, L, Manucra, A, Buratti, A, Tognin, T, Liberato, N, Bernasconi, G, Nardo, B, Bianchi, G, Benetti, G, Quagliolo, M, Centenaro, G, Purrello, F, Di Pino, A, Piro, S, Mancuso, G, Calipari, D, Bartone, M, Gullo, F, Cortellaro, M, Magenta, M, Perego, F, Meroni, M, Cicardi, M, Magenta, A, Sacco, A, Bonelli, A, Dentamaro, G, Rozzini, R, Falanga, L, Giordano, A, Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Montrucchio, G, Greco, E, Tizzani, P, Fera, G, Di Luca, M, Renna, D, Perciccante, A, Coralli, A, Tassara, R, Melis, D, Rebella, L, Menardo, G, Bottone, S, Sferrazzo, E, Ferri, C, Striuli, R, Scipioni, R, Salmi, R, Gaudenzi, P, Gamberini, S, Ricci, F, Morabito, C, Fava, R, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Bolondi, L, Rasciti, L, Serio, I, Masala, C, Mammarella, A, Raparelli, V, Rossi Fanelli, F, Delfino, M, Amoroso, A, Violi, F, Basili, S, Perri, L, Serra, P, Fontana, V, Falcone, M, Landolfi, R, Grieco, A, Gallo, A, Zuccalà, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, Bellusci, M, Setti, D, Pedrazzoli, F, Romanelli, G, Pirali, C, Amolini, C, Rosei, E, Rizzoni, D, Castoldi, L, Picardi, A, Gentilucci, U, Mazzarelli, C, Gallo, P, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Contini, S, Molaro, M, Annoni, G, Corsi, M, Zazzetta, S, Bertolotti, M, Mussi, C, Scotto, R, Ferri, M, Veltri, F, Arturi, F, Succurro, E, Sesti, G, Gualtieri, U, Perticone, F, Sciacqua, A, Quero, M, Bagnato, C, Loria, P, Becchi, M, Martucci, G, Fantuzzi, A, Maurantonio, M, Corinaldesi, R, De Giorgio, R, Grasso, V, Ruggeri, E, Carozza, L, Pignatti, F, Mannucci M, Nobili A, Tettamanti M, Pasina L, Franchi C, Salerno F, Corrao S, Marengoni A, Marcucci M, Sparacio E, Alborghetti S, Di Costanzo R, Djignefa Djade C, Prisco D, Silvestri E, Cenci C, Barnini T, Delitala G, Carta S, Atzori S, Guarnieri G, Zanetti M, Spalluti A, Serra MG, Bleve MA, Vanoli M, Grignani G, Casella G, Gasbarrone L, Maniscalco G, Gunelli M, Tirotta D, Brucato A, Ghidoni S, Bernardi M, Bassi SL, Santi L, Agnelli G, Iorio A, Marchesini E, Mannarino E, Lupattelli G, Rondelli P, Paciullo F, Fabris F, Carlon M, Turatto F, Baroni MC, Zardo M, Manfredini R, Molino C, Pala M, Fabbian F, Nuti R, Valenti R, Ruvio M, Cappelli S, Paolisso G, Rizzo MR, Laieta MT, Salvatore T, Sasso FC, Utili R, Durante Mangoni E, Pinto D, Olivieri O, Stanzial AM, Fellin R, Volpato S, Fotini S, Barbagallo M, Dominguez L, Plances L, D'Angelo D, Rini G, Mansueto P, Pepe I, Licata G, Calvo L, Valenti M, Borghi C, Strocchi E, Rinaldi ER, Zoli M, Fabbri E, Magalotti D, Auteri A, Pasqui AL, Puccetti L, Laghi Pasini F, Capecchi PL, Bicchi M, Sabbà C, Vella FS, Marseglia A, Luglio CV, Palasciano G, Modeo ME, Aquilino A, Raffaele P, Pugliese S, Capobianco C, Postiglione A, Barbella MR, De Stefano F, Fenoglio L, Brignone C, Bracco C, Giraudo A, Musca G, Cuccurullo O, Cricco L, Fiorentini A, Cappellini MD, Fabio G, Seghezzi S, De Amicis MM, Fargion S, Bonara P, Bulgheroni M, Lombardi R, Magrini F, Massari F, Tonella T, Peyvandi F, Tedeschi A, Rossio R, Moreo G, Ferrari B, Roncari L, Monzani V, Savojardo V, Folli C, Magnini M, Mari D, Rossi PD, Damanti S, Prolo S, Lilleri MS, Micale G, Podda M, Selmi C, Meda F, Accordino S, Conca A, Monti V, Corazza GR, Miceli E, Lenti MV, Padula D, Balduini CL, Bertolino G, Provini S, Quaglia F, Murialdo G, Bovio M, Dallegri F, Ottonello L, Quercioli A, Barreca A, Secchi MB, Ghelfi D, Chin WS, Carassale L, Caporotundo S, Anastasio L, Carbone M, Traisci G, De Feudis L, Davì G, Guagnano MT, Sestili S, Bergami E, Rizzioli E, Cagnoni C, Bertone L, Manucra A, Buratti A, Tognin T, Liberato NL, Bernasconi G, Nardo B, Bianchi GB, Benetti G, Quagliolo M, Centenaro GR, Purrello F, Di Pino A, Piro S, Mancuso G, Calipari D, Bartone M, Gullo F, Cortellaro M, Magenta M, Perego F, Meroni MR, Cicardi M, Magenta AG, Sacco A, Bonelli A, Dentamaro G, Rozzini R, Falanga L, Giordano A, Perin PC, Lorenzati B, Gruden G, Bruno G, Montrucchio G, Greco E, Tizzani P, Fera G, Di Luca ML, Renna D, Perciccante A, Coralli A, Tassara R, Melis D, Rebella L, Menardo G, Bottone S, Sferrazzo E, Ferri C, Striuli R, Scipioni R, Salmi R, Gaudenzi P, Gamberini S, Ricci F, Morabito C, Fava R, Semplicini A, Gottardo L, Vendemiale G, Serviddio G, Forlano R, Bolondi L, Rasciti L, Serio I, Masala C, Mammarella A, Raparelli V, Rossi Fanelli F, Delfino M, Amoroso A, Violi F, Basili S, Perri L, Serra P, Fontana V, Falcone M, Landolfi R, Grieco A, Gallo A, Zuccalà G, Franceschi F, De Marco G, Chiara C, Marta S, Bellusci M, Setti D, Pedrazzoli F, Romanelli G, Pirali C, Amolini C, Rosei EA, Rizzoni D, Castoldi L, Picardi A, Gentilucci UV, Mazzarelli C, Gallo P, Guasti L, Castiglioni L, Maresca A, Squizzato A, Contini S, Molaro M, Corsi M, Bertolotti M, Mussi C, Scotto R, Ferri MA, Veltri F, Arturi F, Succurro E, Sesti G, Gualtieri U, Perticone F, Sciacqua A, Quero M, Bagnato C, Loria P, Becchi MA, Martucci G, Fantuzzi A, Maurantonio M, Corinaldesi R, De Giorgio R, Serra M, Grasso V, Ruggeri E, Carozza LM, Pignatti F., ANNONI, GIORGIO, and ZAZZETTA, SARA
Abstract: Background and purpose Women live longer and outnumber men. On the other hand, older women develop more chronic diseases and conditions such as arthritis, osteoporosis and depression, leading to a greater number of years of living with disabilities. The aim of this study was to describe whether or not there are gender differences in the demographic profile, disease distribution and outcome in a population of hospitalized elderly people. Methods Retrospective observational study including all patients recruited for the REPOSI study in the year 2010. Analyses are referred to the whole group and gender categorization was applied. Results A total of 1380 hospitalized elderly subjects, 50.5% women and 49.5% men, were considered. Women were older than men, more often widow and living alone or in nursing homes. Disease distribution showed that malignancy, diabetes, coronary artery disease, chronic kidney disease and chronic obstructive pulmonary disease were more frequent in men, but hypertension, osteoarthritis, anemia and depression were more frequent in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment evaluated by the Short Blessed Test (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3-month mortality rates were higher in men. Conclusions Our study showed a gender dimorphism in the demographic and morbidity profiles of hospitalized elderly people, emphasizing once more the need for a personalized process of healthcare. © 2014 European Federation of Internal Medicine.
Published: 2014

2. Implementation of the Frailty Index in hospitalized older patients: Results from the REPOSI register

Author: Matteo, Cesari, Carlotta, Franchi, Laura, Cortesi, Alessandro, Nobili, Ilaria, Ardoino, Pier Mannuccio Mannucci, Mauro, Tettamanti, Luca, Pasina, Francesco, Perticone, Francesco, Salerno, Salvatore, Corrao, Alessandra, Marengoni, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Tarek Kamal Eldin, Maria Pia Donatella Di Blanca, Giovanna, Lanzo, Sarah, Astuto, Prisco, Domenico, Elena, Silvestri, Caterina, Cenci, Giacomo, Emmi, Gianni, Biolo, Gianfranco, Guarnieri, Michela, Zanetti, Giovanni, Fernandes, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Gianluca, Casella, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Teresa, Salvatore, Ferdinando Carlo Sasso, Domenico, Girelli, Olivieri, Oliviero, Thomas, Matteazzi, Mario, Barbagallo, Lidia, Plances, Roberta, Alcamo, Luigi, Calvo, Maria, Valenti, Marco, Zoli, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Maurizio, Bicchi, Giuseppe, Palasciano, Maria Ester Modeo, Maria, Peragine, Fabrizio, Pappagallo, Stefania, Pugliese, Carla Di Gennaro, Alfredo, Postiglione, Maria Rosaria Barbella, Francesco De Stefano, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Sonia, Seghezzi, Margherita Migone De Amicis, Marta, Mancarella, Daniela, Mari, Paolo Dionigi Rossi, Sarah, Damanti, Barbara Brignolo Ottolini, Giulia, Bonini, Emanuela, Miceli, Marco Vincenzo Lenti, Donatella, Padula, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Giovanni, Davì, Maria Teresa Guagnano, Simona, Sestili, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Maria Rachele Meroni, Paolo Cavallo Perin, Bartolomeo, Lorenzati, Gabriella, Gruden, Graziella, Bruno, Cristina, Amione, Paolo, Fornengo, Rodolfo, Tassara, Deborah, Melis, Lara, Rebella, Giuseppe, Delitala, Vincenzo, Pretti, Maristella Salvatora Masala, Chiara, Pes, Luigi, Bolondi, Leonardo, Rasciti, Ilaria, Serio, Filippo Rossi Fanelli, Antonio, Amoroso, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Francesco, Franceschi, Guido De Marco, Cordischi, Chiara, Sabbatini, Marta, Gabriella, D'Aurizio, Giuseppe, Romanelli, Claudia, Amolini, Deborah, Chiesa, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giorgio, Annoni, Maurizio, Corsi, Sara, Zazzetta, Giuseppe, Bellelli, Hajnalka, Szabo, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Giorgio, Sesti, Paola, Loria, Maria Angela Becchi, Gianfranco, Martucci, Alessandra, Fantuzzi, Mauro, Maurantonio, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Paola Di Corato, Agnelli, Giancarlo, Marchesini, Emanuela, Fabrizio, Fabris, Michela, Carlon, Francesca, Turatto, Aldo, Baritusso, Annalisa, Amabile, Elisabetta, Omenetto, Paolo, Scarinzi, Roberto, Manfredini, Christian, Molino, Marco, Pala, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Giuseppe, Paolisso, Maria Rosaria Rizzo, Maria Teresa Laieta, Giovanbattista, Rini, Pasquale, Mansueto, Ilenia, Pepe, Claudio, Borghi, Enrico, Strocchi, Valeria De Sando, Ilaria, Pareo, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Raffaella, Valerio, Pasquale, Agosti, Flavia, Fontana, Francesca, Loparco, Caterina, Capobianco, Luigi, Fenoglio, Christian, Bracco, Alessia Valentina Giraudo, Elisa, Testa, Cristina, Serraino, Silvia, Fargion, Paola, Bonara, Giulia, Periti, Marianna, Porzio, Slivia, Tiraboschi, Flora, Peyvandi, Alberto, Tedeschi, Raffaella, Rossio, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Maria, Magnini, Alessio, Conca, Giulia, Gobbo, Giada, Pallini, Miriam, Valenti, Balduini, Carlo L., Giampiera, Bertolino, Stella, Provini, Federica, Quaglia, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Wu Sheng Chin, Laura, Carassale, Silvia, Caporotundo, Giancarlo, Traisci, Lucrezia De Feudis, Silvia Di Carlo, Nicola Lucio Liberato, Alberto, Buratti, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Giuseppe, Montrucchio, Elisabetta, Greco, Pietro, Tizzani, Paolo, Petitti, Antonio, Perciccante, Alessia, Coralli, Raffaella, Salmi, Piergiorgio, Gaudenzi, Susanna, Gamberini, Andrea, Semplicini, Lucia, Gottardo, Gianluigi, Vendemiale, Gaetano, Serviddio, Roberta, Forlano, Cesare, Masala, Antonio, Mammarella, Valeria, Raparelli, Stefania, Basili, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Carla, Vallone, Martino, Bellusci, Donatella, Setti, Filippo, Pedrazzoli, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Marta, Molaro, Bertolotti, Marco, Chiara, Mussi, Maria Vittoria Libbra, DI MICELI, Andrea, Pellegrini, Elisa, Lucia, Carulli, Francesca, Veltri, Angela, Sciacqua, Michele, Quero, Chiara, Bagnato, Lidia, Colangelo, Tania, Falbo, Roberto De Giorgio, DALLA SERRA, Mauro, Valentina, Grasso, Eugenio, Ruggeri, Benzoni, Ilaria, Andrea, Salvi, Leonardi, Roberto, Chiara, Grassini, Ilenia, Mascherona, Minelli, Giorgio, Francesca, Maltese, Giampaolo, Damiani, William, Capeci, Mattioli, Massimo, Giuseppe Pio Martino, Biondi, Lorenzo, Monica, Ormas, Pietro, Pettinari, Roberto, Romiti, Silvia, Messina, Federica, Cavallaro, Riccardi, Ghio, Serena, Favorini, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Antonella, Afeltra, Pamela, Alemanno, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Julien, Blanco, Luca, Zanoli, Cattaneo, Marco Natale, Paola, Fracasso, Amoruso, MARIA VALENTINA, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Vittorio, Durante, Giovanna, Eusebi, Daniela, Tirotta, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Carlo, Vigorito, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesco, Scopelliti, Francesca, Gasparini, Melissa, Cocca, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Giuseppe, Scattolin, Sergio, Martinelli, Mauro, Turrin, Leonardo, Sechi, Cristina, Catena, Gianluca, Colussi, Ramirez Duque Nieves, Muela Molinero Alberto, Abad Requejo Pedro, Lopez Pelaez Vanessa, Tamargo, Lara, Corbella Viros Xavier, Formiga, Francesc, Diez Manglano Jesus, Bejarano Tello Esperanza, Del Corral Behamonte Esther, Sevil Puras Maria, Manuel, Romero, Pinilla Llorente Blanca, Lopez Gonzalez-Cobos Cristina, Victoria, Villalba Garcia M., Lopez, Saez, Juan, Bosco, Sanz Baena Susana, Arroyo Gallego Marta, Gonzalez Becerra Concepcion, Fernandez Moyano Antonio, Mercedes Gomez Hernandez, Manuel Poyato Borrego, Pacheco Cuadros Raquel, Perez Rojas Florencia, Garcia Olid Beatriz, Carrascosa Garcia Sara, Gonzalez-Cruz Cervellera Alfonso, Peinado Martinez Marta, Sara Carrascosa Garcia, Ruiz Cantero Alberto, Albarracín Arraigosa Antonio, Godoy Guerrero Montserrat, Barón Ramos Miguel Ángel, Machin Jose Manuel, Novo Veleiro Ignacio, Alvela Suarez Lucía, Lopez, Alfonso, Rubal Bran David, Iñiguez Vazquez Iria, Rios Prego Monica, Cesari M., Franchi C., Cortesi L., Nobili A., Ardoino I., Mannucci P.M., Tettamanti M., Pasina L., Perticone F., Salerno F., Corrao S., Marengoni A., Licata G., Violi F., Corazza G.R., Eldin T.K., Di Blanca M.P.D., Lanzo G., Astuto S., Prisco D., Silvestri E., Cenci C., Emmi G., Biolo G., Guarnieri G., Zanetti M., Fernandes G., Chiuch M., Vanoli M., Grignani G., Casella G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Mannarino E., Lupattelli G., Bianconi V., Paciullo F., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Salvatore T., Sasso F.C., Girelli D., Olivieri O., Matteazzi T., Barbagallo M., Plances L., Alcamo R., Calvo L., Valenti M., Zoli M., Arno R., Pasini F.L., Capecchi P.L., Bicchi M., Palasciano G., Modeo M.E., Peragine M., Pappagallo F., Pugliese S., Gennaro C.D., Postiglione A., Barbella M.R., De Stefano F., Cappellini M.D., Fabio G., Seghezzi S., De Amicis M.M., Mancarella M., Mari D., Rossi P.D., Damanti S., Ottolini B.B., Bonini G., Miceli E., Lenti M.V., Padula D., Murialdo G., Marra A., Cattaneo F., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Davi G., Guagnano M.T., Sestili S., Mancuso G., Calipari D., Bartone M., Meroni M.R., Perin P.C., Lorenzati B., Gruden G., Bruno G., Amione C., Fornengo P., Tassara R., Melis D., Rebella L., Delitala G., Pretti V., Masala M.S., Pes C., Bolondi L., Rasciti L., Serio I., Fanelli F.R., Amoroso A., Molfino A., Petrillo E., Zuccala G., Franceschi F., De Marco G., Chiara C., Marta S., D'aurizio G., Romanelli G., Amolini C., Chiesa D., Picardi A., Gentilucci U.V., Gallo P., Annoni G., Corsi M., Zazzetta S., Bellelli G., Szabo H., Arturi F., Succurro E., Rubino M., Sesti G., Loria P., Becchi M.A., Martucci G., Fantuzzi A., Maurantonio M., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Di Corato P., Agnelli G., Marchesini E., Fabris F., Carlon M., Turatto F., Baritusso A., Amabile A., Omenetto E., Scarinzi P., Manfredini R., Molino C., Pala M., Fabbian F., Boari B., De Giorgi A., Paolisso G., Rizzo M.R., Laieta M.T., Rini G., Mansueto P., Pepe I., Borghi C., Strocchi E., De Sando V., Pareo I., Sabba C., Vella F.S., Suppressa P., Valerio R., Agosti P., Fontana F., Loparco F., Capobianco C., Fenoglio L., Bracco C., Giraudo A.V., Testa E., Serraino C., Fargion S., Bonara P., Periti G., Porzio M., Tiraboschi S., Peyvandi F., Tedeschi A., Rossio R., Monzani V., Savojardo V., Folli C., Magnini M., Conca A., Gobbo G., Pallini G., Balduini C.L., Bertolino G., Provini S., Quaglia F., Dallegri F., Ottonello L., Liberale L., Chin W.S., Carassale L., Caporotundo S., Traisci G., De Feudis L., Di Carlo S., Liberato N.L., Buratti A., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Montrucchio G., Greco E., Tizzani P., Petitti P., Perciccante A., Coralli A., Salmi R., Gaudenzi P., Gamberini S., Semplicini A., Gottardo L., Vendemiale G., Serviddio G., Forlano R., Masala C., Mammarella A., Raparelli V., Basili S., Perri L., Landolfi R., Montalto M., Mirijello A., Vallone C., Bellusci M., Setti D., Pedrazzoli F., Guasti L., Castiglioni L., Maresca A., Squizzato A., Molaro M., Bertolotti M., Mussi C., Libbra M.V., Miceli A., Pellegrini E., Carulli L., Veltri F., Sciacqua A., Quero M., Bagnato C., Colangelo L., Falbo T., De Giorgio R., Serra M., Grasso V., Ruggeri E., Ilaria B., Salvi A., Leonardi R., Grassini C., Mascherona I., Minelli G., Maltese F., Damiani G., Capeci W., Mattioli M., Martino G.P., Biondi L., Ormas M., Pettinari P., Romiti R., Messina S., Cavallaro F., Ghio R., Favorini S., Col A.D., Minisola S., Afeltra A., Alemanno P., Marigliano B., Pipita M.E., Castellino P., Blanco J., Zanoli L., Cattaneo M., Fracasso P., Amoruso M.V., Saracco V., Fogliati M., Bussolino C., Durante V., Eusebi G., Tirotta D., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Scopelliti F., Gasparini F., Cocca M., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Nieves R.D., Alberto M.M., Pedro A.R., Vanessa L.P., Lara T., Xavier C.V., Francesc F., Jesus D.M., Esperanza B.T., Esther D.C.B., Maria S.P., Romero M., Blanca P.L., Cristina L.G.-C., Victoria V.G.M., Saez L., Bosco J., Susana S.B., Marta A.G., Concepcion G.B., Antonio F.M., Hernandez M.G., Borrego M.P., Raquel P.C., Florencia P.R., Beatriz G.O., Sara C.G., Alfonso G.-C.C., Marta P.M., Garcia S.C., Alberto R.C., Antonio A.A., Montserrat G.G., Angel B.R.M., Manuel M.J., Ignacio N.V., Lucia A.S., Alfonso L., David R.B., Iria I.V., Monica R.P., Cesari, M., Franchi, C., Cortesi, L., Nobili, A., Ardoino, I., Mannucci, P. M., Tettamanti, M., Pasina, L., Perticone, F., Salerno, F., Corrao, S., Marengoni, A., Licata, G., Violi, F., Corazza, G. R., Eldin, T. K., Di Blanca, M. P. D., Lanzo, G., Astuto, S., Prisco, D., Silvestri, E., Cenci, C., Emmi, G., Biolo, G., Guarnieri, G., Zanetti, M., Fernandes, G., Chiuch, M., Vanoli, M., Grignani, G., Casella, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Mannarino, E., Lupattelli, G., Bianconi, V., Paciullo, F., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Salvatore, T., Sasso, F. C., Girelli, D., Olivieri, O., Matteazzi, T., Barbagallo, M., Plances, L., Alcamo, R., Calvo, L., Valenti, M., Zoli, M., Arno, R., Pasini, F. L., Capecchi, P. L., Bicchi, M., Palasciano, G., Modeo, M. E., Peragine, M., Pappagallo, F., Pugliese, S., Gennaro, C. D., Postiglione, A., Barbella, M. R., De Stefano, F., Cappellini, M. D., Fabio, G., Seghezzi, S., De Amicis, M. M., Mancarella, M., Mari, D., Rossi, P. D., Damanti, S., Ottolini, B. B., Bonini, G., Miceli, E., Lenti, M. V., Padula, D., Murialdo, G., Marra, A., Cattaneo, F., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Davi, G., Guagnano, M. T., Sestili, S., Mancuso, G., Calipari, D., Bartone, M., Meroni, M. R., Perin, P. C., Lorenzati, B., Gruden, G., Bruno, G., Amione, C., Fornengo, P., Tassara, R., Melis, D., Rebella, L., Delitala, G., Pretti, V., Masala, M. S., Pes, C., Bolondi, L., Rasciti, L., Serio, I., Fanelli, F. R., Amoroso, A., Molfino, A., Petrillo, E., Zuccala, G., Franceschi, F., De Marco, G., Chiara, C., Marta, S., D'Aurizio, G., Romanelli, G., Amolini, C., Chiesa, D., Picardi, A., Gentilucci, U. V., Gallo, P., Annoni, G., Corsi, M., Zazzetta, S., Bellelli, G., Szabo, H., Arturi, F., Succurro, E., Rubino, M., Sesti, G., Loria, P., Becchi, M. A., Martucci, G., Fantuzzi, A., Maurantonio, M., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Di Corato, P., Agnelli, G., Marchesini, E., Fabris, F., Carlon, M., Turatto, F., Baritusso, A., Amabile, A., Omenetto, E., Scarinzi, P., Manfredini, R., Molino, C., Pala, M., Fabbian, F., Boari, B., De Giorgi, A., Paolisso, G., Rizzo, M. R., Laieta, M. T., Rini, G., Mansueto, P., Pepe, I., Borghi, C., Strocchi, E., De Sando, V., Pareo, I., Sabba, C., Vella, F. S., Suppressa, P., Valerio, R., Agosti, P., Fontana, F., Loparco, F., Capobianco, C., Fenoglio, L., Bracco, C., Giraudo, A. V., Testa, E., Serraino, C., Fargion, S., Bonara, P., Periti, G., Porzio, M., Tiraboschi, S., Peyvandi, F., Tedeschi, A., Rossio, R., Monzani, V., Savojardo, V., Folli, C., Magnini, M., Conca, A., Gobbo, G., Pallini, G., Balduini, C. L., Bertolino, G., Provini, S., Quaglia, F., Dallegri, F., Ottonello, L., Liberale, L., Chin, W. S., Carassale, L., Caporotundo, S., Traisci, G., De Feudis, L., Di Carlo, S., Liberato, N. L., Buratti, A., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Montrucchio, G., Greco, E., Tizzani, P., Petitti, P., Perciccante, A., Coralli, A., Salmi, R., Gaudenzi, P., Gamberini, S., Semplicini, A., Gottardo, L., Vendemiale, G., Serviddio, G., Forlano, R., Masala, C., Mammarella, A., Raparelli, V., Basili, S., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Vallone, C., Bellusci, M., Setti, D., Pedrazzoli, F., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Molaro, M., Bertolotti, M., Mussi, C., Libbra, M. V., Miceli, A., Pellegrini, E., Carulli, L., Veltri, F., Sciacqua, A., Quero, M., Bagnato, C., Colangelo, L., Falbo, T., De Giorgio, R., Serra, M., Grasso, V., Ruggeri, E., Ilaria, B., Salvi, A., Leonardi, R., Grassini, C., Mascherona, I., Minelli, G., Maltese, F., Damiani, G., Capeci, W., Mattioli, M., Martino, G. P., Biondi, L., Ormas, M., Pettinari, P., Romiti, R., Messina, S., Cavallaro, F., Ghio, R., Favorini, S., Col, A. D., Minisola, S., Afeltra, A., Alemanno, P., Marigliano, B., Pipita, M. E., Castellino, P., Blanco, J., Zanoli, L., Cattaneo, M., Fracasso, P., Amoruso, M. V., Saracco, V., Fogliati, M., Bussolino, C., Durante, V., Eusebi, G., Tirotta, D., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Scopelliti, F., Gasparini, F., Cocca, M., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Nieves, R. D., Pedro, A. R., Vanessa, L. P., Lara, T., Xavier, C. V., Francesc, F., Jesus, D. M., Esperanza, B. T., Esther, D. C. B., Maria, S. P., Romero, M., Blanca, P. L., Cristina, L. G. -C., Victoria, V. G. M., Saez, L., Bosco, J., Susana, S. B., Marta, A. G., Concepcion, G. B., Antonio, F. M., Hernandez, M. G., Borrego, M. P., Raquel, P. C., Florencia, P. R., Beatriz, G. O., Sara, C. G., Alfonso, G. -C. C., Marta, P. M., Garcia, S. C., Alberto, R. C., Antonio, A. A., Montserrat, G. G., Angel, B. R. M., Manuel, M. J., Ignacio, N. V., Lucia, A. S., Alfonso, L., David, R. B., Iria, I. V., Monica, R. P., Cesari, M, Franchi, C, Cortesi, L, Nobili, A, Ardoino, I, Mannucci, P, Tettamanti, M, Pasina, L, Perticone, F, Salerno, F, Corrao, S, Marengoni, A, Licata, G, Violi, F, Corazza, G, Eldin, T, Di Blanca, M, Lanzo, G, Astuto, S, Prisco, D, Silvestri, E, Cenci, C, Emmi, G, Biolo, G, Guarnieri, G, Zanetti, M, Fernandes, G, Chiuch, M, Vanoli, M, Grignani, G, Casella, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Mannarino, E, Lupattelli, G, Bianconi, V, Paciullo, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Salvatore, T, Sasso, F, Girelli, D, Olivieri, O, Matteazzi, T, Barbagallo, M, Plances, L, Alcamo, R, Calvo, L, Valenti, M, Zoli, M, Arno, R, Pasini, F, Capecchi, P, Bicchi, M, Palasciano, G, Modeo, M, Peragine, M, Pappagallo, F, Pugliese, S, Gennaro, C, Postiglione, A, Barbella, M, De Stefano, F, Cappellini, M, Fabio, G, Seghezzi, S, De Amicis, M, Mancarella, M, Mari, D, Rossi, P, Damanti, S, Ottolini, B, Bonini, G, Miceli, E, Lenti, M, Padula, D, Murialdo, G, Marra, A, Cattaneo, F, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Davi, G, Guagnano, M, Sestili, S, Mancuso, G, Calipari, D, Bartone, M, Meroni, M, Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Amione, C, Fornengo, P, Tassara, R, Melis, D, Rebella, L, Delitala, G, Pretti, V, Masala, M, Pes, C, Bolondi, L, Rasciti, L, Serio, I, Fanelli, F, Amoroso, A, Molfino, A, Petrillo, E, Zuccala, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, D'Aurizio, G, Romanelli, G, Amolini, C, Chiesa, D, Picardi, A, Gentilucci, U, Gallo, P, Annoni, G, Corsi, M, Zazzetta, S, Bellelli, G, Szabo, H, Arturi, F, Succurro, E, Rubino, M, Sesti, G, Loria, P, Becchi, M, Martucci, G, Fantuzzi, A, Maurantonio, M, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Di Corato, P, Agnelli, G, Marchesini, E, Fabris, F, Carlon, M, Turatto, F, Baritusso, A, Amabile, A, Omenetto, E, Scarinzi, P, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Boari, B, De Giorgi, A, Paolisso, G, Rizzo, M, Laieta, M, Rini, G, Mansueto, P, Pepe, I, Borghi, C, Strocchi, E, De Sando, V, Pareo, I, Sabba, C, Vella, F, Suppressa, P, Valerio, R, Agosti, P, Fontana, F, Loparco, F, Capobianco, C, Fenoglio, L, Bracco, C, Giraudo, A, Testa, E, Serraino, C, Fargion, S, Bonara, P, Periti, G, Porzio, M, Tiraboschi, S, Peyvandi, F, Tedeschi, A, Rossio, R, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Conca, A, Gobbo, G, Pallini, G, Balduini, C, Bertolino, G, Provini, S, Quaglia, F, Dallegri, F, Ottonello, L, Liberale, L, Chin, W, Carassale, L, Caporotundo, S, Traisci, G, De Feudis, L, Di Carlo, S, Liberato, N, Buratti, A, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Montrucchio, G, Greco, E, Tizzani, P, Petitti, P, Perciccante, A, Coralli, A, Salmi, R, Gaudenzi, P, Gamberini, S, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Masala, C, Mammarella, A, Raparelli, V, Basili, S, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Vallone, C, Bellusci, M, Setti, D, Pedrazzoli, F, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Molaro, M, Bertolotti, M, Mussi, C, Libbra, M, Miceli, A, Pellegrini, E, Carulli, L, Veltri, F, Sciacqua, A, Quero, M, Bagnato, C, Colangelo, L, Falbo, T, De Giorgio, R, Grasso, V, Ruggeri, E, Ilaria, B, Salvi, A, Leonardi, R, Grassini, C, Mascherona, I, Minelli, G, Maltese, F, Damiani, G, Capeci, W, Mattioli, M, Martino, G, Biondi, L, Ormas, M, Pettinari, P, Romiti, R, Messina, S, Cavallaro, F, Ghio, R, Favorini, S, Col, A, Minisola, S, Afeltra, A, Alemanno, P, Marigliano, B, Pipita, M, Castellino, P, Blanco, J, Zanoli, L, Cattaneo, M, Fracasso, P, Amoruso, M, Saracco, V, Fogliati, M, Bussolino, C, Durante, V, Eusebi, G, Tirotta, D, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Scopelliti, F, Gasparini, F, Cocca, M, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Nieves, R, Alberto, M, Pedro, A, Vanessa, L, Lara, T, Xavier, C, Francesc, F, Jesus, D, Esperanza, B, Esther, D, Maria, S, Romero, M, Blanca, P, Cristina, L, Victoria, V, Saez, L, Bosco, J, Susana, S, Marta, A, Concepcion, G, Antonio, F, Hernandez, M, Borrego, M, Raquel, P, Florencia, P, Beatriz, G, Sara, C, Alfonso, G, Marta, P, Garcia, S, Alberto, R, Antonio, A, Montserrat, G, Angel, B, Manuel, M, Ignacio, N, Lucia, A, Alfonso, L, David, R, Iria, I, Monica, R, Franchi, Carlotta, Cortesi, Laura, Nobili, Alessandro, Ardoino, Ilaria, Mannucci, Pier Mannuccio, Tettamanti, Mauro, Pasina, Luca, Perticone, Francesco, Salerno, Francesco, Corrao, Salvatore, Marengoni, Alessandra, Licata, Giuseppe, Violi, Francesco, Corazza, Gino Roberto, Eldin, Tarek Kamal, Di Blanca, Maria Pia Donatella, Lanzo, Giovanna, Astuto, Sarah, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Guarnieri, Gianfranco, Zanetti, Michela, Fernandes, Giovanni, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Salvatore, Teresa, Sasso, Ferdinando Carlo, Girelli, Domenico, Olivieri, Oliviero, Matteazzi, Thoma, Barbagallo, Mario, Plances, Lidia, Alcamo, Roberta, Calvo, Luigi, Valenti, Maria, Zoli, Marco, Arnò, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Palasciano, Giuseppe, Modeo, Maria Ester, Peragine, Maria, Pappagallo, Fabrizio, Pugliese, Stefania, Gennaro, Carla Di, Postiglione, Alfredo, Barbella, Maria Rosaria, De Stefano, Francesco, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, De Amicis, Margherita Migone, Mancarella, Marta, Mari, Daniela, Rossi, Paolo Dionigi, Damanti, Sarah, Ottolini, Barbara Brignolo, Bonini, Giulia, Miceli, Emanuela, Lenti, Marco Vincenzo, Padula, Donatella, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Meroni, Maria Rachele, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Amione, Cristina, Fornengo, Paolo, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Delitala, Giuseppe, Pretti, Vincenzo, Masala, Maristella Salvatora, Pes, Chiara, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Fanelli, Filippo Rossi, Amoroso, Antonio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, Franceschi, Francesco, De Marco, Guido, Chiara, Cordischi, Marta, Sabbatini, D'Aurizio, Gabriella, Romanelli, Giuseppe, Amolini, Claudia, Chiesa, Deborah, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bellelli, Giuseppe, Szabo, Hajnalka, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Sesti, Giorgio, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Di Corato, Paola, Agnelli, Giancarlo, Marchesini, Emanuela, Fabris, Fabrizio, Carlon, Michela, Turatto, Francesca, Baritusso, Aldo, Amabile, Annalisa, Omenetto, Elisabetta, Scarinzi, Paolo, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Borghi, Claudio, Strocchi, Enrico, De Sando, Valeria, Pareo, Ilaria, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Valerio, Raffaella, Agosti, Pasquale, Fontana, Flavia, Loparco, Francesca, Capobianco, Caterina, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Testa, Elisa, Serraino, Cristina, Fargion, Silvia, Bonara, Paola, Periti, Giulia, Porzio, Marianna, Tiraboschi, Slivia, Peyvandi, Flora, Tedeschi, Alberto, Rossio, Raffaella, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Conca, Alessio, Gobbo, Giulia, Pallini, Giada, Valenti, Miriam, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Traisci, Giancarlo, De Feudis, Lucrezia, Di Carlo, Silvia, Liberato, Nicola Lucio, Buratti, Alberto, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Petitti, Paolo, Perciccante, Antonio, Coralli, Alessia, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Masala, Cesare, Mammarella, Antonio, Raparelli, Valeria, Basili, Stefania, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Vallone, Carla, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Miceli, Andrea, Pellegrini, Elisa, Carulli, Lucia, Veltri, Francesca, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Colangelo, Lidia, Falbo, Tania, De Giorgio, Roberto, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Ilaria, Benzoni, Salvi, Andrea, Leonardi, Roberto, Grassini, Chiara, Mascherona, Ilenia, Minelli, Giorgio, Maltese, Francesca, Damiani, Giampaolo, Capeci, William, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Ormas, Monica, Pettinari, Pietro, Romiti, Roberto, Messina, Silvia, Cavallaro, Federica, Ghio, Riccardi, Favorini, Serena, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Alemanno, Pamela, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Cattaneo, Marco, Fracasso, Paola, Amoruso, Maria Valentina, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Durante, Vittorio, Eusebi, Giovanna, Tirotta, Daniela, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Scopelliti, Francesco, Gasparini, Francesca, Cocca, Melissa, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffrè, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viro, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Esther, Del Corral Behamonte, Maria, Sevil Pura, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez-Cobo, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadro, Florencia, Perez Roja, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Alfonso, Gonzalez-Cruz Cervellera, Marta, Peinado Martinez, Garcia, Sara Carrascosa, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Ángel, Barón Ramos Miguel, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, Monica, Rios Prego, and Alberto, M. M.
Subjects: Gerontology, Male, Multivariate analysis, Frailty, Internal medicine and geriatric wards, Multimorbidity, Physical and cognitive impairment, Internal Medicine, Psychological intervention, Predictive Value of Test, Severity of Illness Index, 0302 clinical medicine, Interquartile range, Frailty, Internal medicine and geriatric wards, Multimorbidity, Physical and cognitive impairment, 80 and over, Medicine, 030212 general & internal medicine, Prospective Studies, Hospital Mortality, Prospective cohort study, Multivariate Analysi, Aged, 80 and over, Prognosis, Aged, Female, Geriatric Assessment, Hospitalization, Humans, Italy, Multivariate Analysis, Predictive Value of Tests, Regression Analysis, Survival Analysis, Frail Elderly, Predictive value of tests, Survival Analysi, Cohort study, Human, Prognosi, Socio-culturale, Regression Analysi, 03 medical and health sciences, Severity of illness, Survival analysis, business.industry, Internal medicine and geriatric ward, Prospective Studie, business, 030217 neurology & neurosurgery
Abstract: Background Frailty is a state of increased vulnerability to stressors, associated to poor health outcomes. The aim of this study was to design and introduce a Frailty Index (FI; according to the age-related accumulation of deficit model) in a large cohort of hospitalized older persons, in order to benefit from its capacity to comprehensively weight the risk profile of the individual. Methods Patients aged 65 and older enrolled in the REPOSI register from 2010 to 2016 were considered in the present analyses. Variables recorded at the hospital admission (including socio-demographic, physical, cognitive, functional and clinical factors) were used to compute the FI. The prognostic impact of the FI on in-hospital and 12-month mortality was assessed. Results Among the 4488 patients of the REPOSI register, 3847 were considered eligible for a 34-item FI computation. The median FI in the sample was 0.27 (interquartile range 0.21–0.37). The FI was significantly predictive of both in-hospital (OR 1.61, 95%CI 1.38–1.87) and overall (HR 1.46, 95%CI 1.32–1.62) mortality, also after adjustment for age and sex. Conclusions The FI confirms its strong predictive value for negative outcomes. Its implementation in cohort studies (including those conducted in the hospital setting) may provide useful information for better weighting the complexity of the older person and accordingly design personalized interventions.
Published: 2018

3. Targeting the αVβ3/NgR2 pathway in neuroendocrine prostate cancer.

Author: Testa A, Quaglia F, Naranjo NM, Verrillo CE, Shields CD, Lin S, Pickles MW, Hamza DF, Von Schalscha T, Cheresh DA, Leiby B, Liu Q, Ding J, Kelly WK, Hooper DC, Corey E, Plow EF, Altieri DC, and Languino LR
Subjects: Male, Humans, Androgen Antagonists, Signal Transduction, Antibodies, Monoclonal, Integrins, Integrin alphaVbeta3 genetics, Integrin alphaVbeta3 metabolism, Cell Line, Tumor, Prostatic Neoplasms drug therapy, Prostatic Neoplasms genetics, Prostatic Neoplasms metabolism
Abstract: Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in vitro functional assays, we here demonstrate that NgR2 is crucial in promoting cell adhesion to αVβ3 ligands. Moreover, we describe for the first time co-fractionation of αVβ3 integrin and NgR2 in small extracellular vesicles derived from metastatic prostate cancer patients' plasma. These prostate cancer patient-derived small extracellular vesicles have a functional impact on human monocytes, increasing their adhesion to fibronectin. The monocytes incubated with small extracellular vesicles do not show an associated change in conventional polarization marker expression and appear to be in an early stage that may be defined as "adhesion competent". Overall, these findings allow us to better understand integrin-directed signaling and cell-cell communication during cancer progression. Furthermore, our results pave the way for new diagnostic and therapeutic perspectives for patients affected by neuroendocrine prostate cancer., Competing Interests: Declaration of Competing Interest FQ is an employee/contractor at Janssen Pharmaceutical. EC is a consultant of Dotquant and received funding under institutional SRA from Janssen Research, Bayer Pharmaceuticals, Forma Therapeutics, Foghorn, Kronos Bios, Genentech, Astra Zeneca, and MacroGenics. No potential conflict of interest was reported by the other authors., (Copyright © 2023. Published by Elsevier B.V.)
Published: 2023
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4. A molecular dyad delivered by biodegradable polymeric nanoparticles for combined PDT and NO-PDT in cancer cells.

Author: Parisi C, Longobardi G, Graziano ACE, Fraix A, Conte C, Quaglia F, and Sortino S
Subjects: Cell Line, Tumor, Nitric Oxide, Photosensitizing Agents chemistry, Photosensitizing Agents pharmacology, Photosensitizing Agents therapeutic use, Polymers chemistry, Water, Nanoparticles chemistry, Neoplasms, Photochemotherapy
Abstract: The design, synthesis, photochemical properties, and biological evaluation of a novel molecular dyad with double photodynamic action and its formulation within biodegradable polymeric nanoparticles (NPs) are reported. A BODIPY-based singlet oxygen ( 1 O 2 ) photosensitizer (PS) and a nitric oxide (NO) photodonor (NOPD) based on an amino-nitro-benzofurazan moiety have been covalently joined in a new molecular dyad, through a flexible alkyl spacer. Excitation of the dyad with visible light in the range 400-570 nm leads to the concomitant generation of the cytotoxic 1 O 2 and NO with effective quantum yields, being Φ Δ = 0.49 ± 0.05 and Φ NO = 0.18 ± 0.01, respectively. Besides, the non-fluorescent NOPD unit becomes highly fluorescent after the NO release, acting as an optical reporter for the NO photogenerated. The dyad is not soluble in water medium but can be effectively entrapped in water-dispersible, biodegradable polymeric NPs made of mPEG-PCL, ca. 66 nm in diameter. The polymeric nano-environment affects in an opposite way the photochemical performances of the dyad, reducing Φ Δ to 0.16 ± 0.02 and increasing Φ NO to 0.92 ± 0.03, respectively. The NPs effectively deliver the photoactive cargo into the cytoplasm of HepG2 hepatocellular carcinoma cells. A remarkable level of cell mortality is observed for the loaded NPs at very low concentrations of the dyad (1-5 µM) and very low light doses (≤0.8 J cm -2 ) more likely as the result of the combined photodynamic action of 1 O 2 and NO., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)
Published: 2022
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5. PEGylated mucus-penetrating nanocrystals for lung delivery of a new FtsZ inhibitor against Burkholderia cenocepacia infection.

Author: Costabile G, Provenzano R, Azzalin A, Scoffone VC, Chiarelli LR, Rondelli V, Grillo I, Zinn T, Lepioshkin A, Savina S, Miro A, Quaglia F, Makarov V, Coenye T, Brocca P, Riccardi G, Buroni S, and Ungaro F
Subjects: Bacterial Proteins metabolism, Bronchi metabolism, Bronchi pathology, Burkholderia Infections metabolism, Burkholderia Infections pathology, Cell Line, Tumor, Cystic Fibrosis metabolism, Cystic Fibrosis microbiology, Cystic Fibrosis pathology, Cytoskeletal Proteins metabolism, Epithelial Cells metabolism, Epithelial Cells pathology, Humans, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Bacterial Proteins antagonists & inhibitors, Bronchi microbiology, Burkholderia Infections drug therapy, Burkholderia cenocepacia growth & development, Cystic Fibrosis drug therapy, Cytoskeletal Proteins antagonists & inhibitors, Drug Delivery Systems, Epithelial Cells microbiology, Nanoparticles chemistry, Nanoparticles therapeutic use
Abstract: C109 is a potent but poorly soluble FtsZ inhibitor displaying promising activity against Burkholderia cenocepacia, a high-risk pathogen for cystic fibrosis (CF) sufferers. To harness C109 for inhalation, we developed nanocrystal-embedded dry powders for inhalation suspension consisting in C109 nanocrystals stabilized with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) embedded in hydroxypropyl-β-cyclodextrin (CD). The powders could be safely re-dispersed in water for in vitro aerosolization. Owing to the presence of a PEG shell, the rod shape and the peculiar aspect ratio, C109 nanocrystals were able to diffuse through artificial CF mucus. The promising technological features were completed by encouraging in vitro/in vivo effects. The formulations displayed no toxicity towards human bronchial epithelial cells and were active against planktonic and sessile B. cenocepacia strains. The efficacy of C109 nanosuspensions in combination with piperacillin was confirmed in a Galleria mellonella infection model, strengthening their potential for combined therapy of B. cenocepacia lung infections., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2020
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6. Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity.

Author: Conte C, Moret F, Esposito D, Dal Poggetto G, Avitabile C, Ungaro F, Romanelli A, Laurienzo P, Reddi E, and Quaglia F
Subjects: Angiogenesis Inhibitors pharmacology, Animals, Cell Death drug effects, Cell Line, Tumor, Cell Membrane drug effects, Cell Membrane metabolism, Chickens, Chorioallantoic Membrane drug effects, Chorioallantoic Membrane metabolism, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells metabolism, Humans, Neovascularization, Physiologic drug effects, Polyesters chemical synthesis, Polyesters chemistry, Polyethylene Glycols chemical synthesis, Polyethylene Glycols chemistry, Vascular Endothelial Growth Factor Receptor-1 metabolism, Antineoplastic Agents pharmacology, Biocompatible Materials pharmacology, Docetaxel pharmacology, Nanoparticles chemistry, Peptides chemistry
Abstract: Inhibition of tumor angiogenesis is considered as a valuable clinical strategy to treat some tumors, although benefits in term of progression-free and overall survival have been modest. Recent findings have pushed toward the use of antiangiogenic drugs in combination with chemotherapy regimens to potentiate therapeutic outcome. Herein, we propose a novel type of biodegradable antiangiogenic core-shell polymeric nanoparticles (NPs) for the delivery of poorly water-soluble chemotherapeutics. An amphiphilic diblock copolymer of poly(ethyleneglycol)-poly(ε-caprolactone) (PEG-PCL) was conjugated with an anti-FLT1 hexapeptide (aFLT1) at -OH PEG end, mixed in appropriate ratios with a monomethoxy-PEG-PCL and nanoprecipitated to form core-shell aFLT1-bearing NPs (DBL aFLT1 ). DBL aFLT1 were <100 nm, exposed aFLT1 on the surface and showed a higher thickness of the external hydrophilic shell as compared to NPs that do not bear aFLT1 (DBL). Very interestingly, DBL aFLT1 showed an antiangiogenic activity in the human umbilical endothelial cells (HUVEC) tube formation assay three-fold higher than an equivalent dose of free aFLT1. To provide a proof-of-concept of DBL aFLT1 potential in the delivery of conventional chemotherapeutics, docetaxel (DTX) was selected as model drug. DBL aFLT1 entrapped DTX with high efficiency and sustained its release along time in simulated biological conditions. At a non-cytotoxic dose, DTX-loaded DBL aFLT1 almost completely abolished tube formation in HUVEC while inhibition of DTX loaded DBL was significantly lower. The cytotoxicity of DTX-loaded NPs in HUVEC and triple negative breast cancer cells (MDA-MB-231) was not significantly different from that of the free drug in a wide range of concentrations and up to 72 h. Studies carried out in MDA-MB-231 cells implanted in chicken embryo chorioallantoic membranes (CAMs) evidenced an antiangiogenic activity of DTX-loaded DBL aFLT1 higher as compared with that of both DTX-loaded DBL and free DTX. While cancer cell migration from the tumor site was unaffected, the anticancer activity of DTX-loaded NPs was higher than that of free DTX and maximized for DTX-DBL aFLT1 . In perspective, these results suggest that the delivery approach proposed here can be applied to other lipophilic chemotherapeutics devoid of relevant antiangiogenic properties to improve the final therapeutic response., (Copyright © 2019. Published by Elsevier B.V.)
Published: 2019
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7. Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid in Postextractive Alveolar Wounds.

Author: Catanzano O, D'Esposito V, Formisano P, Boateng JS, and Quaglia F
Subjects: Bandages, Freeze Drying methods, Glucuronic Acid chemistry, Hexuronic Acids chemistry, Humans, Porosity, Alginates chemistry, Hyaluronic Acid chemistry, Tranexamic Acid chemistry, Wound Healing drug effects
Abstract: The management of wounds in patients on anticoagulant therapy who require oral surgical procedures is problematic and often results in a nonsatisfactory healing process. Here, we report a method to prepare an advanced dressing able to avoid uncontrolled bleeding by occluding the postextractive alveolar wounds, and simultaneously, capable of a fast release of tranexamic acid (TA). Composite alginate/hyaluronan (ALG/HA) sponge dressings loaded with TA were prepared by a straightforward internal gelation method followed by a freeze-drying step. Both blank and drug-loaded sponges were soft, flexible, and elegant in appearance and nonbrittle in nature. Scanning electron microscopy analysis confirmed the porous nature of these dressings. The integration of HA influenced the microstructure, reducing the porosity, modifying the water uptake kinetic, and increasing the resistance to compression. TA release from ALG/HA sponges showed a controlled release up to 3 h, and it was faster in the presence of HA. Finally, an in vitro clotting test performed on human whole blood confirmed that the TA-loaded sponges significantly reduce the blood clotting index by 30% compared with ALG/HA 20 sponges. These results suggest that, if placed in a socket cavity, these dressings could give a relevant help to the blood hemostasis after dental extractions, especially in patients with coagulation disorders., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)
Published: 2018
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8. Multifunctional theranostic Pluronic mixed micelles improve targeted photoactivity of Verteporfin in cancer cells.

Author: Pellosi DS, Calori IR, de Paula LB, Hioka N, Quaglia F, and Tedesco AC
Subjects: Female, Humans, MCF-7 Cells, Male, Neoplasms metabolism, Neoplasms pathology, Verteporfin, Drug Carriers chemistry, Drug Carriers pharmacokinetics, Drug Carriers pharmacology, Micelles, Nanoparticles chemistry, Neoplasms drug therapy, Photochemotherapy, Poloxalene chemistry, Poloxalene pharmacokinetics, Poloxalene pharmacology, Poloxamer chemistry, Poloxamer pharmacokinetics, Poloxamer pharmacology, Porphyrins chemistry, Porphyrins pharmacokinetics, Porphyrins pharmacology, Theranostic Nanomedicine methods
Abstract: Nanotechnology development provides new strategies to treat cancer by integration of different treatment modalities in a single multifunctional nanoparticle. In this scenario, we applied the multifunctional Pluronic P123/F127 mixed micelles for Verteporfin-mediated photodynamic therapy in PC3 and MCF-7 cancer cells. Micelles functionalization aimed the targeted delivery by the insertion of biotin moiety on micelle surface and fluorescence image-based through rhodamine-B dye conjugation in the polymer chains. Multifunctional Pluronics formed spherical nanoparticulated micelles that efficiently encapsulated the photosensitizer Verteporfin maintaining its favorable photophysical properties. Lyophilized formulations were stable at least for 6months and readily reconstituted in aqueous media. The multifunctional micelles were stable in protein-rich media due to the dual Pluronic mixed micelles characteristic: high drug loading capacity provided by its micellar core and high kinetic stability due its biocompatible shell. Biotin surface functionalized micelles showed higher internalization rates due biotin-mediated endocytosis, as demonstrated by competitive cellular uptake studies. Rhodamine B-tagged micelles allowed monitoring cellular uptake and intracellular distribution of the formulations. Confocal microscopy studies demonstrated a larger intracellular distribution of the formulation and photosensitizer, which could drive Verteporfin to act on multiple cell sites. Formulations were not toxic in the dark condition, but showed high Verteporfin-induced phototoxicity against both cancer cell lines at low drug and light doses. These results point Verteporfin-loaded multifunctional micelles as a promising tool to further developments in photodynamic therapy of cancer., (Copyright © 2016 Elsevier B.V. All rights reserved.)
Published: 2017
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9. Nanoassemblies based on non-ionic amphiphilic cyclodextrin hosting Zn(II)-phthalocyanine and docetaxel: Design, physicochemical properties and intracellular effects.

Author: Conte C, Scala A, Siracusano G, Sortino G, Pennisi R, Piperno A, Miro A, Ungaro F, Sciortino MT, Quaglia F, and Mazzaglia A
Subjects: Cell Survival drug effects, Docetaxel, HeLa Cells, Humans, Indoles pharmacology, Isoindoles, Organometallic Compounds pharmacology, Taxoids pharmacology, Zinc Compounds, Cyclodextrins chemistry, Indoles chemistry, Organometallic Compounds chemistry, Surface-Active Agents chemistry, Taxoids chemistry
Abstract: The combination of conventional anticancer therapy with other treatment modalities such as photodynamic therapy (PDT) is paving the way to novel more effective treatment of solid tumors via light exposure. With this idea in mind, in this paper, nanoparticles (NPs) based on Heptakis (2-oligo(ethyleneoxide)-6-hexadecylthio-)-β-CD (SC16OH) for dual delivery of Zinc-Phthalocyanine (ZnPc) and Docetaxel (DTX) were developed pointing to their potential application as nanomedicine for the combined photodynamic and chemo-therapy of solid tumors. NPs prepared by the emulsion-solvent evaporation technique displayed a hydrodynamic diameter of ≅ 200nm, a negative zeta potential (≅ -27mV) and a satisfactory entrapment efficiency of both drugs at a specific mass ratio. On these bases, NPs containing DTX and ZnPc with theoretical loading of 5% and 0.2% respectively (ZnPc/DTX5-NPs) were selected for further investigations. The allocation of ZnPc and DTX into the colloid was investigated by complementary spectroscopic techniques. In particular, fluorescence emission studies showed the entrapment of ZnPc as a monomer in the carrier, with a low tendency to self-aggregate and consequently a fairly high propensity to photogenerate singlet oxygen. The interaction of SC16OH with DTX, co-entrapped with ZnPc, was elucidated by (1)H NMR and 2D ROESY, which suggested the presence of the chemotherapeutic in the hydrophobic portion of SC16OH. ZnPc/DTX5-NPs were fairly stable in different biological relevant media within 24h. Finally, in vitro potential of the nanoassembly was evaluated in HeLa cancer cells by cell viability exploring both effects of DTX and ZnPc. Overall, results suggest the suitability of NPs based on SC16OH for delivering a combination of DTX with ZnPc to cancer cells, thus inducing photodynamic and antimitotic effects., (Copyright © 2016 Elsevier B.V. All rights reserved.)
Published: 2016
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10. Cyclodextrin-assisted assembly of PEGylated polyester nanoparticles decorated with folate.

Author: Conte C, Fotticchia I, Tirino P, Moret F, Pagano B, Gref R, Ungaro F, Reddi E, Giancola C, and Quaglia F
Subjects: A549 Cells, Calorimetry methods, Caproates chemistry, Cell Line, Tumor, Drug Carriers chemistry, Endocytosis, Folate Receptors, GPI-Anchored metabolism, Folic Acid metabolism, Folic Acid pharmacokinetics, Humans, Lactones chemistry, Particle Size, Proton Magnetic Resonance Spectroscopy, Folic Acid chemistry, Nanoparticles chemistry, Polyesters chemistry, Polyethylene Glycols chemistry, beta-Cyclodextrins chemistry
Abstract: In the last decades, nano-oncologicals bearing a polyethylene glycol (PEG) coating are being emerging as biomimetic devices able to drive their drug cargo to solid tumors through passive mechanisms. To improve selectivity toward cancer cells, nanocarriers decorated with the small ligand folate have been widely investigated. Nevertheless, a great challenge remains the effective exposition of folate on nanoparticles (NPs), which is a key prerequisite to ensure the correct binding to receptor and the following endocytic uptake. On these premises, in this study we propose a novel strategy to produce core-shell folate-targeted NPs based on diblock copolymers of poly(ε-caprolactone) (PCL) and PEG through the aid of (2-hydroxypropyl)-β-cyclodextrin (HPβCD). PCL4300-PEG2000 and PCL4300-PEG2000-Fol copolymers were synthesized, characterized and employed to produce NPs without and with HPβCD by a melting/sonication procedure. Colloidal properties of targeted NPs produced with HPβCD demonstrated a highly extended conformation of PEG chains in the shell, an enhanced interaction with a specific antibody against folate and a higher uptake in cells overexpressing folate receptor. Overall, these results suggest that proper manipulation of PEG shell conformation through HPβCD can represent a novel non-covalent strategy to modify shell features., (Copyright © 2016 Elsevier B.V. All rights reserved.)
Published: 2016
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11. Overcoming barriers in Pseudomonas aeruginosa lung infections: Engineered nanoparticles for local delivery of a cationic antimicrobial peptide.

Author: d'Angelo I, Casciaro B, Miro A, Quaglia F, Mangoni ML, and Ungaro F
Subjects: Cations, Cystic Fibrosis complications, Drug Carriers, Humans, Respiratory Tract Infections etiology, Respiratory Tract Infections microbiology, Anti-Bacterial Agents administration & dosage, Nanoparticles, Peptides administration & dosage, Pseudomonas Infections drug therapy, Pseudomonas aeruginosa pathogenicity, Respiratory Tract Infections drug therapy
Abstract: Cationic antimicrobial peptides (CAMPs) are very promising in the treatment of multi-drug resistant Pseudomonas aeruginosa lung infections experienced by cystic fibrosis (CF) patients. Nevertheless, there is an urgent need of inhalable formulations able to deliver the intact CAMP in conductive airways and to shield its interactions with airway mucus/bacterial biofilm, thus enhancing CAMP/bacteria interactions. Along these lines, the aim of this work was the design and development of nano-embedded microparticles (NEM) for sustained delivery of CAMPs in the lung. To this purpose, nanoparticles (NPs) made of poly(lactide-co-glycolide) (PLGA) containing a model CAMP, colistin (Col), were produced by emulsion/solvent diffusion technique. Engineering NPs with chitosan (CS) and poly(vinyl alcohol) (PVA) allowed to modulate surface properties and, in so doing, to improve NP transport through artificial CF mucus. In order to achieve a long-term stable dosage form useful for NP inhalation, NPs were spray-dried in different carriers (lactose or mannitol), thus producing NEM. The most promising NEM formulations were selected on the basis of bulk and flow properties, distribution of NPs in the carrier and aerosolization performance upon delivery through a breath-actuated dry powder inhaler. Of note, selected Col-loaded NEM were found to kill P. aeruginosa biofilm and to display a prolonged efficacy in biofilm eradication compared to the free Col. This effect was likely ascribable to the ability of NPs to penetrate into bacterial biofilm, as demonstrated by confocal analysis, and to sustain Col release inside it. Taken all together, our results indicate that adequate engineering of PLGA NPs represents an enticing technological approach to harness novel antimicrobials for P. aeruginosa lung infection, such as CAMPs, especially in CF., (Copyright © 2015 Elsevier B.V. All rights reserved.)
Published: 2015
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12. β-cyclodextrin nanosponges as multifunctional ingredient in water-containing semisolid formulations for skin delivery.

Author: Conte C, Caldera F, Catanzano O, D'Angelo I, Ungaro F, Miro A, Pellosi DS, Trotta F, and Quaglia F
Subjects: Animals, Chemistry, Pharmaceutical methods, Gels administration & dosage, Gels chemistry, Permeability, Skin Absorption, Swine, Nanostructures administration & dosage, Nanostructures chemistry, Skin metabolism, Water chemistry, beta-Cyclodextrins administration & dosage, beta-Cyclodextrins chemistry
Abstract: A β-cyclodextrin nanosponge cross-linked with pyromellitic dianhydride (βNS-PYRO) is reported for the first time as multifunctional ingredient in semisolid formulations for drug delivery to the skin. The role of βNS-PYRO on solubilization and stabilization of the photosensitizer benzoporphyrin-derivative monoacid ring A (BPDMA) and all-trans retinoic acid (atRA) as well as its effect on skin permeation of diclofenac (DIC) was investigated. Aqueous solutions, gels, and cream-gels were prepared from mixtures of βNS-PYRO with a conventional gelling agent at specific ratios. The incorporation of BPDMA in βNS-PYRO water solutions prevented its aggregation and gave kinetically stable complexes with high photostability and singlet oxygen generation upon irradiation. atRA incorporated in the βNS-PYRO-containing gel demonstrated a remarkable stability as compared with the formulation without βNS-PYRO, resulting in an eightfold increase of its lifetime. Skin permeation studies highlighted that βNS-PYRO in gels and cream-gels containing DIC significantly decreased the amount of drug permeated through the skin while increasing its amount in stratum corneum and viable epidermis. Overall, swellable βNS-PYRO turns to be a multifunctional coingredient with potential in topical monophasic and biphasic formulations to stabilize light-sensitive drugs and to localize the action of highly penetrating drugs in the external layers of skin., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)
Published: 2014
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13. Melt-spun bioactive sutures containing nanohybrids for local delivery of anti-inflammatory drugs.

Author: Catanzano O, Acierno S, Russo P, Cervasio M, Del Basso De Caro M, Bolognese A, Sammartino G, Califano L, Marenzi G, Calignano A, Acierno D, and Quaglia F
Subjects: Animals, In Vitro Techniques, Male, Mice, Microscopy, Electron, Scanning, Spectrometry, X-Ray Emission, Anti-Inflammatory Agents administration & dosage, Drug Carriers, Nanostructures, Sutures
Abstract: In this work, a novel concept is introduced in drug-eluting fibres to ensure a good control of drug delivery features and wide applicability to different bioactive compounds. Composite bioactive sutures based on fibre grade poly(ε-caprolactone) (PCL) and loaded with the anti-inflammatory drug Diclofenac (Dic) or a Dic nanohybrid where the drug is intercalated in a synthetic hydrotalcite (Mg/Al hydroxycarbonate) (HT-Dic) were developed. Fibres were prepared by melt-spinning at different PCL/HT-Dic/Dic ratios and analysed in terms of morphology, mechanical properties and drug release features. Results emphasized that tensile properties of fibres are clearly affected by Dic or HT-Dic addition, while the presence of knots has limited influence on the mechanical behaviour of the sutures. Release of Dic strongly depends on how Dic is loaded in the fibre (as free or nanohybrid) whereas the combination of free Dic and HT-Dic can allow a further tuning of release profile. In vivo experiments show a reduction of inflammatory responses associated with Dic-loaded fibers. Thus, a proof of principle is provided for a novel class of bioactive sutures integrating advanced controlled-release technologies., (Copyright © 2014 Elsevier B.V. All rights reserved.)
Published: 2014
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14. Engineering strategies to control vascular endothelial growth factor stability and levels in a collagen matrix for angiogenesis: the role of heparin sodium salt and the PLGA-based microsphere approach.

Author: d'Angelo I, Oliviero O, Ungaro F, Quaglia F, and Netti PA
Subjects: Angiogenesis Inducing Agents administration & dosage, Angiogenesis Inducing Agents chemistry, Capsules administration & dosage, Capsules chemical synthesis, Cell Proliferation drug effects, Cells, Cultured, Diffusion, Drug Implants chemistry, Drug Stability, Endothelial Cells cytology, Endothelial Cells drug effects, Humans, Materials Testing, Microspheres, Neovascularization, Physiologic drug effects, Polylactic Acid-Polyglycolic Acid Copolymer, Salts, Tissue Scaffolds, Vascular Endothelial Growth Factor A chemistry, Collagen chemistry, Drug Implants administration & dosage, Endothelial Cells physiology, Heparin chemistry, Lactic Acid chemistry, Neovascularization, Physiologic physiology, Polyglycolic Acid chemistry, Vascular Endothelial Growth Factor A administration & dosage
Abstract: New vessel formation is the result of the complex orchestration of various elements, such as cells, signalling molecules and extracellular matrix (ECM). In order to establish the suitable conditions for an effective cell response, the influence of vascular endothelial growth factor (VEGF) complexation with heparin sodium salt (Hp) on its pro-angiogenic activity has been evaluated by an in vitro capillary-like tube formation assay. VEGF with or without Hp was embedded into collagen gels, and the activated matrices were characterized in terms of VEGF activity and release kinetics. Taking into account the crucial role of Hp in VEGF stability and activity, VEGF/Hp complex was then encapsulated into microspheres based on poly(lactide-co-glycolide) (PLGA), and microsphere properties, VEGF/Hp release kinetics and VEGF in vitro activity over time were evaluated. Integrated microsphere/collagen matrices were developed in order to provide a continuous release of active VEGF/Hp inside the matrix but also a VEGF gradient at the boundary, which is an essential condition for endothelial cell attraction and scaffold invasion. The results confirmed a strong influence of Hp on VEGF configuration and, consequently, on its activity, while the encapsulation of VEGF/Hp complex in PLGA-microspheres guaranteed a sustained release of active VEGF for more than 30days. This paper confirms the importance of VEGF stability and signal presentation to cells for an effective proangiogenic activity and highlights how the combination of two stabilizing approaches, namely VEGF/Hp complexation and entrapment within PLGA-based microspheres, may be a very effective strategy to achieve this goal., (Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
Published: 2013
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15. Core-shell biodegradable nanoassemblies for the passive targeting of docetaxel: features, antiproliferative activity and in vivo toxicity.

Author: Ungaro F, Conte C, Ostacolo L, Maglio G, Barbieri A, Arra C, Misso G, Abbruzzese A, Caraglia M, and Quaglia F
Subjects: Animals, Cell Line, Tumor, Cell Proliferation, Docetaxel, Drug Delivery Systems adverse effects, Drug Delivery Systems methods, Erythrocytes drug effects, Freezing, Hemolysis drug effects, Humans, Mice, Mice, Inbred BALB C, Sonication methods, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Nanoparticles administration & dosage, Nanoparticles chemistry, Polyesters administration & dosage, Polyesters chemistry, Polyethylene Glycols administration & dosage, Polyethylene Glycols chemistry, Taxoids administration & dosage, Taxoids adverse effects
Abstract: Amphiphilic block copolymers of poly(ɛ-caprolactone) and poly(ethylene oxide) were assembled in core-shell nanoparticles (NPs) by a melting-sonication technique (MeSo). The entrapment of the poorly water-soluble anticancer drug docetaxel (DTX), nanocarrier cytotoxicity toward different cells and toxicity in mice were investigated. The encapsulation mechanism was rationalized and related to copolymer properties such as crystallinity and drug solubility in the copolymer phase. DTX release from NPs occurred in 2 drug pulses over 30 days. DTX entrapment in NPs strongly decreased haemolysis of erythrocytes in comparison with a commercial DTX formulation. In comparison with free DTX, NPs were both more efficient in inhibiting cell growth of breast and prostate cancer cells and less toxic in experimental animal models. The results of this study indicate that MeSo is an interesting technique for the achievement of peculiar core-shell nanocarriers for the passive targeting and sustained release of poorly water-soluble anticancer drugs., From the Clinical Editor: In this study, stealth nanoparticles of PEO/PCL block copolymers for passive targeting of docetaxel to solid tumors were developed using a novel technique. The studied properties of NPs suggest strong potential as anticancer drug-delivery system., (Copyright © 2012 Elsevier Inc. All rights reserved.)
Published: 2012
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16. Oligonucleotide decoy to NF-kappaB slowly released from PLGA microspheres reduces chronic inflammation in rat.

Author: De Stefano D, De Rosa G, Maiuri MC, Ungaro F, Quaglia F, Iuvone T, Cinelli MP, La Rotonda MI, and Carnuccio R
Subjects: Animals, Blotting, Western, Chronic Disease, Disease Models, Animal, Electrophoretic Mobility Shift Assay, Granulation Tissue drug effects, Granulation Tissue metabolism, Inflammation metabolism, Male, Microspheres, Nitric Oxide biosynthesis, Nitric Oxide Synthase Type II biosynthesis, Phosphorothioate Oligonucleotides administration & dosage, Polylactic Acid-Polyglycolic Acid Copolymer, Rats, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Tumor Necrosis Factor-alpha biosynthesis, Drug Carriers chemistry, Inflammation drug therapy, Lactic Acid chemistry, NF-kappa B metabolism, Phosphorothioate Oligonucleotides therapeutic use, Polyglycolic Acid chemistry
Abstract: Nuclear factor-kappaB (NF-kappaB) plays a key role in the expression of several genes involved in the immune and inflammatory process. Previously, we demonstrated that NF-kappaB activation can be significantly inhibited by a double stranded oligodeoxynucleotide (ODN). Nevertheless, the therapeutic use of ODN requires a delivery system able to improve poor crossing of cell membranes and rapid in vivo enzymatic degradation. Poly(D,L-lactide-co-glycolide) (PLGA) microspheres can increase ODN stability in biological environment and release the encapsulated drug in long time frames. Here, we used a decoy ODN against NF-kappaB and we investigated its effect, when administered in naked form or when delivered by PLGA microspheres, in a rat model of chronic inflammation. The subcutaneous implant of lambda-carrageenin-soaked sponges caused leukocyte infiltration and formation of granulation tissue which were inhibited up to 15 days by co-injection of microspheres releasing decoy ODN whereas naked decoy ODN showed this effect only up to 5 days. Molecular analysis performed on granulation tissue demonstrated an inhibition of NF-kappaB activation correlated to a decrease of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) expression. Our results suggest that microspheres could be an useful tool to improve pharmacokinetics of decoy ODN and may represent a strategy to inhibit NF-kappaB activation in chronic inflammation.
Published: 2009
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17. Poly(lactide-co-glycolide) microspheres for the controlled release of oligonucleotide/polyethylenimine complexes.

Author: De Rosa G, Quaglia F, La Rotonda MI, Appel M, Alphandary H, and Fattal E
Subjects: Biocompatible Materials, Cell Membrane Permeability drug effects, Cell Survival drug effects, Delayed-Action Preparations, Drug Compounding, Drug Delivery Systems, HeLa Cells, Humans, Microscopy, Confocal, Microscopy, Electron, Scanning, Microspheres, Oligonucleotides chemistry, Particle Size, Polyethyleneimine chemistry, Polylactic Acid-Polyglycolic Acid Copolymer, Solubility, Lactic Acid chemistry, Oligonucleotides administration & dosage, Polyethyleneimine administration & dosage, Polyglycolic Acid chemistry, Polymers chemistry
Abstract: In this article, microspheres able to induce the controlled release of oligonucleotide/polyethylenimine complexes are proposed. A model oligonucleotide (the oligothymidilate pdT16) was encapsulated within poly(lactide-co-glycolide) microspheres alone or associated with polyethylenimine (PEI) at different nitrogen/phospate (N/P) ratios. Microspheres were prepared by the multiple emulsion-solvent evaporation technique and characterized for morphology, diameter, encapsulation efficiency, and release kinetics. The introduction of PEI in the internal aqueous phase resulted in the formation of a soluble complex with pdT16 and in a strong increase of the oligonucleotide encapsulation efficiency. PEI affected microsphere morphology inducing the formation of very porous particles yielding to an accelerated release of pdT16. When incubated with HeLa cells, microspheres encapsulating pdT16/PEI complexes allowed both a reduction of the complex toxicity and an improvement of the intracellular penetration of the released oligonucleotide. We conclude that biodegradable microspheres encapsulating oligonucleotides/PEI complexes have a great potential as controlled release system because they allow the sustained release of an oligonucleotide carrier that crosses biological membranes and locates in nucleus., (Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association.)
Published: 2002
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18. Chromatographic indexes on immobilized artificial membranes for the prediction of transdermal transport of drugs.

Author: Barbato F, Cappello B, Miro A, La Rotonda MI, and Quaglia F
Subjects: Administration, Cutaneous, Chromatography, High Pressure Liquid, Humans, Linear Models, Membranes, Artificial, Permeability, Pharmaceutical Preparations administration & dosage, Pharmaceutical Preparations chemistry, Structure-Activity Relationship, Pharmacokinetics, Skin Absorption
Abstract: A set of 12 drugs, consisting of structurally unrelated neutral, basic, acidic and amphoteric compounds, was examined by high performance liquid chromatrography (HPLC) on a model of fluid membrane bilayers, the immobilized artificial membrane (IAM) column. The logarithms of chromatographic capacity factors extrapolated to 100% aqueous phase at pH 5.5 (log kw) were measured and compared to the n-octanol/water partition coefficients (log P). The scale derived from the IAM system was different from the lipophilicity scale expressed by the log P, due to the peculiar capability of phospholipids to well accommodate the ionized form of some molecules and show additive or repulsive extra-interactions when particular structural motifs on the molecule are present. The relationship between log P and log kw previously obtained for compounds interacting on IAM phase by a uniquely lipophilicity-based mechanism, allowed us to calculate, from log P, the values of log kw expected for the drugs considered. These values were subtracted from the log kw experimentally determined and the differences were assumed to quantify the amount of extra-interactions (hydrogen bond and electrostatic interactions) with phospholipids (delta log kw). The coefficients of permeability through the human skin (Kp) for the compounds considered did not correlate with either log kw or log P values. However, the Kp values correlated well with the delta log kw values indicating that the higher the ability of a molecule to cross the skin barrier, the lower its component of interaction with phospholipids not accounted for by lipophilicity-based interactions.
Published: 1998
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19. Interactions of nonsteroidal antiinflammatory drugs with phospholipids: comparison between octanol/buffer partition coefficients and chromatographic indexes on immobilized artificial membranes.

Author: Barbato F, La Rotonda MI, and Quaglia F
Subjects: Buffers, Chromatography, High Pressure Liquid, Octanols chemistry, Anti-Inflammatory Agents, Non-Steroidal chemistry, Membranes, Artificial, Phospholipids chemistry
Abstract: A set of seventeen nonsteroidal antiinflammatory drugs (NSAIDs), consisting of structurally unrelated carboxylic acids and piroxicam, was examined by high-performance liquid chromatography (HPLC) on an immobilized artificial membrane (IAM) column that is a solid-phase model of fluid membranes. The chromatographic capacity factors extrapolated to 100% aqueous phase (log KWIAM) were compared with n-octanol/buffer lipophilicity parameters. The interactions with phospholipids were much better predicted from the intrinsic partition coefficient, log P, than from the apparent partition value, log D7.4, indicating that phospholipids can counteract the influence of electrically charged functions of analytes on lipophilic interactions. The log KWIAM and log P values for both NSAIDs and structurally unrelated neutral compounds result in unique scale if uniquely partition-based mechanisms take place. However, an electrostatic repulsion component was observed for the NSAIDs bearing the carboxylic function directly linked to the aromatic ring, and for ibuprofen. Hence, the IAM-derived scale is distinctive from the one obtained by lipophilic parameters. The IC50 values on cyclooxygenase 2 (COX-2) in intact cells determined by different authors have been successfully correlated with respective IAM parameters, whereas no correlation was found with COX-1 activity data. These results suggest that membrane affinity may represent an important prerequisite for the specific binding NSAIDs/COX-2.
Published: 1997
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20. Retention behaviour of anti-emetic serotonin antagonists in reversed phase high performance liquid chromatography.

Author: Barbato F, La Rotonda MI, and Quaglia F
Subjects: Chromatography, High Pressure Liquid, Tropisetron, Antiemetics analysis, Granisetron analysis, Indoles analysis, Ondansetron analysis, Serotonin Antagonists analysis
Abstract: Granisetron, Ondansetron and Tropisetron, three 5-HT3 antagonists showing anti-emetic activity, were analysed by HPLC on lipophilic stationary phases. The addition of an amine or quaternary ammonium salt to the eluents was a powerful tool in the analysis of these basic substances. The influence on chromatographic parameters of pH, ionic strength and various counter-ions in the aqueous phase as well as of different organic modifiers is discussed. Some of the proposed experimental conditions allow a more strictly partition-based separation mechanism and can produce chromatographic parameters suitable for structure-activity studies. These experimental conditions are also suitable for analysis of the considered compounds in pharmaceutical dosage forms or in biological fluids.
Published: 1995

21. Analysis of ACE inhibitor drugs by high performance liquid chromatography.

Author: Barbato F, Morrica P, and Quaglia F
Subjects: Chromatography, High Pressure Liquid, Angiotensin-Converting Enzyme Inhibitors analysis
Abstract: Seven angiotensin-converting-enzyme (ACE) inhibitors have been analyzed by HPLC. The influence of different organic modifiers and counter-ions in the eluent at different pH values have been investigated allowing the identification of the best experimental conditions for the analysis of these compounds. The sinergic effect of TEA and propanol in the eluents resulted as a critical factor to obtain satisfactory peak shapes and resolution.
Published: 1994

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21 results on '"Quaglia F"'

1. Gender-differences in disease distribution and outcome in hospitalized elderly: Data from the REPOSI study

2. Implementation of the Frailty Index in hospitalized older patients: Results from the REPOSI register

3. Targeting the αVβ3/NgR2 pathway in neuroendocrine prostate cancer.

4. A molecular dyad delivered by biodegradable polymeric nanoparticles for combined PDT and NO-PDT in cancer cells.

5. PEGylated mucus-penetrating nanocrystals for lung delivery of a new FtsZ inhibitor against Burkholderia cenocepacia infection.

6. Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity.

7. Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid in Postextractive Alveolar Wounds.

8. Multifunctional theranostic Pluronic mixed micelles improve targeted photoactivity of Verteporfin in cancer cells.

9. Nanoassemblies based on non-ionic amphiphilic cyclodextrin hosting Zn(II)-phthalocyanine and docetaxel: Design, physicochemical properties and intracellular effects.

10. Cyclodextrin-assisted assembly of PEGylated polyester nanoparticles decorated with folate.

11. Overcoming barriers in Pseudomonas aeruginosa lung infections: Engineered nanoparticles for local delivery of a cationic antimicrobial peptide.

12. β-cyclodextrin nanosponges as multifunctional ingredient in water-containing semisolid formulations for skin delivery.

13. Melt-spun bioactive sutures containing nanohybrids for local delivery of anti-inflammatory drugs.

14. Engineering strategies to control vascular endothelial growth factor stability and levels in a collagen matrix for angiogenesis: the role of heparin sodium salt and the PLGA-based microsphere approach.

15. Core-shell biodegradable nanoassemblies for the passive targeting of docetaxel: features, antiproliferative activity and in vivo toxicity.

16. Oligonucleotide decoy to NF-kappaB slowly released from PLGA microspheres reduces chronic inflammation in rat.

17. Poly(lactide-co-glycolide) microspheres for the controlled release of oligonucleotide/polyethylenimine complexes.

18. Chromatographic indexes on immobilized artificial membranes for the prediction of transdermal transport of drugs.

19. Interactions of nonsteroidal antiinflammatory drugs with phospholipids: comparison between octanol/buffer partition coefficients and chromatographic indexes on immobilized artificial membranes.

20. Retention behaviour of anti-emetic serotonin antagonists in reversed phase high performance liquid chromatography.

21. Analysis of ACE inhibitor drugs by high performance liquid chromatography.

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