85 results on '"Lione L"'
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2. A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19
- Author
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Aurisicchio, L, Brambilla, N, Cazzaniga, M, Bonfanti, P, Milleri, S, Ascierto, P, Capici, S, Vitalini, C, Girolami, F, Giacovelli, G, Caselli, G, Visintin, M, Fanti, F, Ghirri, M, Conforti, A, Compagnone, M, Lione, L, Salvatori, E, Pinto, E, Muzi, A, Marra, E, Palombo, F, Roscilli, G, Manenti, A, Montomoli, E, Cadossi, M, Rovati, L, Aurisicchio, Luigi, Brambilla, Nadia, Cazzaniga, Marina E, Bonfanti, Paolo, Milleri, Stefano, Ascierto, Paolo A, Capici, Serena, Vitalini, Cristina, Girolami, Federica, Giacovelli, Giampaolo, Caselli, Gianfranco, Visintin, Michela, Fanti, Francesca, Ghirri, Matteo, Conforti, Antonella, Compagnone, Mirco, Lione, Lucia, Salvatori, Erika, Pinto, Eleonora, Muzi, Alessia, Marra, Emanuele, Palombo, Fabio, Roscilli, Giuseppe, Manenti, Alessandro, Montomoli, Emanuele, Cadossi, Matteo, Rovati, Lucio C, Aurisicchio, L, Brambilla, N, Cazzaniga, M, Bonfanti, P, Milleri, S, Ascierto, P, Capici, S, Vitalini, C, Girolami, F, Giacovelli, G, Caselli, G, Visintin, M, Fanti, F, Ghirri, M, Conforti, A, Compagnone, M, Lione, L, Salvatori, E, Pinto, E, Muzi, A, Marra, E, Palombo, F, Roscilli, G, Manenti, A, Montomoli, E, Cadossi, M, Rovati, L, Aurisicchio, Luigi, Brambilla, Nadia, Cazzaniga, Marina E, Bonfanti, Paolo, Milleri, Stefano, Ascierto, Paolo A, Capici, Serena, Vitalini, Cristina, Girolami, Federica, Giacovelli, Giampaolo, Caselli, Gianfranco, Visintin, Michela, Fanti, Francesca, Ghirri, Matteo, Conforti, Antonella, Compagnone, Mirco, Lione, Lucia, Salvatori, Erika, Pinto, Eleonora, Muzi, Alessia, Marra, Emanuele, Palombo, Fabio, Roscilli, Giuseppe, Manenti, Alessandro, Montomoli, Emanuele, Cadossi, Matteo, and Rovati, Lucio C
- Abstract
The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Sixty-eight healthy adults received two doses of 0.5, 1, or 2 mg 28 days apart, or a single 2-mg dose, via intramuscular injection followed by electroporation, and they were monitored for 6 months. All participants completed the primary safety and immunogenicity assessments after 8 weeks. COVID-eVax was well tolerated, with mainly mild to moderate solicited adverse events (tenderness, pain, bruising, headache, and malaise/fatigue), less frequent after the second dose, and it induced an immune response (binding antibodies and/or T cells) at all prime-boost doses tested in up to 90% of the volunteers at the highest dose. However, the vaccine did not induce neutralizing antibodies, while particularly relevant was the T cell-mediated immunity, with a robust Th1 response. This T cell-skewed immunological response adds significant information to the DNA vaccine platform and should be assessed in further studies for its protective capacity and potential usefulness also in other therapeutic areas, such as oncology.
- Published
- 2023
3. P08.03 Neoantigen cancer vaccine auguments anti CTLA-4 efficacy
- Author
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Palombo, F, primary, Salvatori, E, additional, Lione, L, additional, Compagnone, M, additional, Conforti, A, additional, and Aurisicchio, L, additional
- Published
- 2021
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4. Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation. COVID-eVax, an electroporated plasmid DNA vaccine candidate encoding the SARS-CoV-2 Receptor Binding Domain, elicits protective immune responses in animal models of COVID-19
- Author
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Conforti A, Marra E, Palombo F, Roscilli G, Ravà M, Fumagalli V, Muzi A, Maffei M, Luberto L, Lione L, Salvatori E, Compagnone M, Pinto E, Pavoni E, Bucci F, Vitagliano G, Stoppoloni D, Pacello ML, Cappelletti M, Ferrara FF, D'Acunto E, Chiarini V, Arriga R, Nyska A, Di Lucia P, Marotta D, Bono E, Giustini L, Sala E, Perucchini C, Paterson J, Ryan KA, Challis AR, Matusali G, Colavita F, Caselli G
- Published
- 2021
- Full Text
- View/download PDF
5. Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes 11 Medical and Health Sciences 1103 Clinical Sciences
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Mirijello, A, Viazzi, F, Fioretto, P, Giorda, C, Ceriello, A, Russo, G, Guida, P, Pontremoli, R, De Cosmo, S, Cimino, A, Fava, D, Meloncelli, I, Nicolucci, A, Pellegrini, F, Rossi, M, Turco, S, Vespasiani, G, Graziano, G, Lucisano, G, Memmo, R, Pellicciotta, E, Paciotti, V, Pupillo, M, Armentano, G, Giovannini, C, Armentano, V, Laudato, M, Acquati, S, Ciardullo, A, Laffi, G, Felace, G, Taboga, C, Tortul, C, Santantonio, G, Suraci, C, Ghisoni, G, Raffa, M, Genovese, S, Lovagnini-Scher, C, Rampini, P, Rocca, A, Ruggeri, P, Tortato, E, Cotti, L, Cristofaro, M, Tagliaferri, M, Comoglio, M, Fornengo, R, Gentile, F, Gigante, A, Mastinu, F, Di Benedetto, A, Pata, P, Arcangeli, A, Orsini, P, Acler, P, De Blasi, G, Cicioni, G, Pocciati, S, Marangoni, A, Nogara, A, Lanero, M, Bertero, M, Damassino, R, Bergonzini, C, Schumtz, L, Seksich, L, Pipitone, A, Boaretto, M, Manfroi, I, Parmesan, L, Conte, B, Soccol, F, Pagano, A, Papini, E, Rinaldi, R, Petrucci, L, Graziano, F, Chianelli, M, Silvagni, S, Rosco, M, Ansaldi, E, Malvicino, F, Battezzati, M, Maresca, P, Palenzona, C, Boemi, M, Rabini, R, Brandoni, G, Lanari, L, Gatti, C, Testa, I, Cherubini, V, Doveri, G, Pecorelli, L, Ciccarelli, A, Gallardini, M, Courthoud, R, Sara Bredy, S, Ricciardi, G, Vitalone, G, Setti, D, Contrini, P, Corsi, A, Ghigliotti, V, Oddone, G, Ponzani, P, Valbonesi, G, Mazzini, V, Di Berardino, P, Colleluori, P, Montani, V, Trosini, V, Velussi, M, Alfidi, P, Verdecchia, B, Baliva, L, Di Pietro, A, Franchi, G, Luce, R, Pianta, A, Ferrari, M, Balzano, S, Beltranello, G, Dal Fabbro, S, Arico, C, Cervo, L, Zanon, R, Rossa, S, Di Pace, M, Ciavarella, A, Giangiulio, S, Grimaldi, M, Mustacchio, A, Fattor, B, Monauni, T, Cristini, M, Orion, G, Crazzolara, D, Amor, F, Eisath, J, Lintner, S, Garavelli, S, Calari, T, Marini, P, Sandri, O, Scala, M, Stroppa, C, Trentin, A, Carlin, R, Carli, B, Sandona, M, Zortea, C, Bonet, L, Pradel, L, Reato, S, Buschini, M, Bonfiglioli, D, Mones, D, Beldi, F, Morea, A, Bondesan, L, Perbellini, S, Valentini, U, Agosti, B, Corsini, R, Girelli, A, Zarra, E, Rocca, L, Bergmann, M, Pradi, I, Unterkircher, S, Piok, M, Pichler, M, Trinchera, A, Palama, G, Palma, P, Carboni, L, Murtas, M, Mudadu, T, Turco, M, Floris, M, Delogu, A, Farris, L, Songini, M, Piras, G, Seguro, R, Floris, R, Corona, G, Lai, M, Piras, E, Contini, P, Cocco, S, Pilosu, R, Sannia, M, Spanu, F, Busciantella Ricci, N, Cartechini, M, Agostinelli, G, Fiorelli, C, Nuzzi, A, Ballauri, C, Lesina, A, Romeo, F, Giudici, G, Maciejewska, E, Deroma, A, Paduano, M, Rossi, L, Vagnini, C, Dolci, M, Mori, M, Baccetti, F, Gregori, G, Straface, E, Pozzuoli, G, Barone, M, Stasio, G, Tondini, S, Borgoni, F, Grosso, J, Scarsellato, C, Sciulli, A, De Marco, F, Confortin, L, Marin, N, Lamonica, M, Gialdino, S, Borzi, V, Gatta, C, Rapisard, R, Strano, S, Calabro, M, Puccio, L, Zolli, M, Coracina, A, Starnone, V, Del Buono, A, Terracciano, A, Monda, M, Castro, F, Guaglianone, A, Maccari, V, Corsi, L, Versari, G, Falivene, M, Boletto, N, Corsi, S, Marafetti, L, Vitacolonna, E, Capani, F, Caputo, L, Di Nisio, L, Simonetti, F, Boscolo Bariga, A, Ballarin, G, De Boni, S, Di Benedetto, S, Chiambretti, A, Di Vito, L, Pascuzzo, M, Urli, P, Rumi, P, Balzarini, B, Galli, P, Castellan, M, Giannetti, A, Russotti, C, De Blasi, A, Perna, A, Campanelli, C, Ranchelli, A, Biccheri, D, Dadi, G, Massa, L, Baldi, G, Sciacca, F, Costanzo, E, Spada, M, Paolini, G, Ziller, P, Portolan, F, Pasolini, G, Ghilardi, G, Fiorina, P, Grata, M, Capretti, L, Speroni, G, Fugazza, L, Massafra, C, Lovagnini Scher, A, Cimicchi, M, Percudani, C, Risolo, T, Sacco, P, Gidoni Guarnieri, G, Piccolo, D, Bravin, C, De Noni, E, Scarpel, M, Marcon, M, Giacon, F, Panebianco, G, Tadiotto, F, Da Tos, V, D'Ambrosio, M, Pellizzola, D, Zampini, M, Frezzati, E, Mari, E, Raminelli, E, Gaiti, D, Bosi, E, Chierici, G, Pilla, S, Copelli, M, Zanichelli, P, Bertelli, L, Caretta, P, Vezzani, V, Bodecchi, S, Longobucco, A, Di Lembo, S, Spotti, E, Carrai, E, Degli Innocenti, A, Manini, L, Persico, R, Rossi, C, Magro, G, Marelli, G, Vilei, V, Andrioli, M, Bellato, L, Fedeli, M, Merlini, A, Pinelli, G, Marin, G, Contin, M, Gallo, A, Parlato, P, Pecchielan, W, Jacovacci, J, Placentino, G, Richini, D, Molinari, S, Strazzeri, R, Fabbri, T, Di Bartolo, P, Garrapa, G, D'Incau, F, Lagomanzini, P, Conte, P, Todesco, F, Foglini, P, Pantanetti, P, Bedetta, C, Maricotti, R, Tomasi, F, Monesi, M, Graziani, R, Beretta, F, Penna, L, Guberti, A, Dazzi, D, Forte, E, Gasbarrone, A, Marrocco, T, Moschetta, R, Tuccinardi, F, De Meo, F, Coppola, A, Pirolozzi, P, Placitelli, E, Vallefuoco, R, Catone, B, Ceschia, S, Urban, M, Fabbri, F, Torresani, M, Crovetto, R, Battistini, M, Carosia, P, Viviani, G, Durante, A, Pais, F, Lilliu, V, Quieto, C, D'Ugo, E, Squadrone, M, Amenduni, T, Iovannisci, M, Della Penna, L, Potente, F, Delle Donne, T, Massa, C, Ulisse, M, De Berardinis, S, Guarnieri, I, Pace, S, Splendiani, M, Di Giuseppe, R, Brunato, B, Assaloni, R, Muraro, R, Loro, R, Bucciol, S, Lavacca, C, Sabbatini, G, Quadri, F, Sambuco, L, Santacroce, C, Paola Caretta, D, Marino, C, Micheletti, A, Petrelli, A, Corda, A, Pisano, L, Guaita, G, Deias, C, Trevisan, G, Coletti, I, Iannarelli, R, De Luca, A, Minnucci, A, Antenucci, D, Di Florio, C, Angelicola, G, Bosco, A, Fresco, R, Di Marco, G, Ugolotti, D, Cadossi, T, Di Caro, P, Mazzocchetti, M, Buzzetti, R, Leto, G, Gnessi, C, Cipolloni, L, Foffi, C, Moretti, C, Venditti, C, Meniconi, R, Bertoli, S, Cosimi, S, Di Cianni, G, Turco, A, Richini, A, Marconi, S, Sannino, C, Lemmi, P, Giuntoli, S, Manfre, N, Giannini, F, Di Carlo, A, Casadidio, I, Melandri, P, Maolo, G, Polenta, B, Piccinini, N, Vincenti, C, Pastore, N, Mega, P, Magurano, E, Cananiello, A, Francescutto, C, Brussa Toi, E, Gaspardo, G, Angeli, L, Ronchese, L, Sciangula, L, Ciucci, A, Contartese, A, Banfi, E, Castelli, E, Tatti, P, Bloise, D, Di Mauro, P, Masselli, L, Lo Presti, A, Scarpitta, A, Gambina, F, Venezia, A, Morea, R, Lagonigro, G, Copeta, G, Iannucci, V, Milano, V, Trupo, M, Lochmann, A, Marchetto, P, Incelli, G, De Paola, G, Steiger, M, Gamper, M, Breitenberger, S, Holzner, M, Frischmann, J, Lambiase, C, Di Vece, T, D'Aniello, M, Fezza, M, Giordano, C, Leo, F, Saitta, G, Cucinotta, D, Di Vieste, G, Pintaudi, B, Mancuso, T, Musacchio, N, Giancaterini, A, Pessina, L, Salis, G, Schivalocchi, F, Testori, G, Cerutti, N, Morpugo, P, Cavaletto, M, Bonino, G, Morreale, F, Mariani, G, Ragonesi, P, Bollati, P, Colapinto, P, Falqui, L, Bortolato, L, Cosma, A, Pistolato, P, Centenaro, B, Ceccato, A, Campobasso, G, Zaurino, F, Mazzotta, G, Manti, R, Da Ros, R, Carlucci, S, Narduzzi, L, Bortolotto, D, D'Acunto, L, Stanic, L, Volpi, A, Cospite, A, Manicardi, V, Michelini, M, Finardi, L, Borghi, F, Manicardi, E, Lombardi, S, Tommasi, C, Iaccarino, M, Cozza, S, Binotto, M, Marini, F, Mecenero, I, Massignani, S, Stecco, P, Urbani, E, Massariol, W, Parolin, R, Gatti, A, Bonavita, M, Creso, E, Giannettino, R, Gobbo, M, Iovine, C, Riccardi, G, Iazzetta, N, Giannattasio, C, Egione, O, Galdieri, S, Velotti, A, Azzolina, A, Annicelli, G, Sorrentino, T, Gaeta, I, Zenari, L, Bertolini, L, Sorgato, C, Grippaldi, F, Stroppiana, M, Popolizio, R, Carbone, N, Grasso, S, Abate, S, Gaggero, G, Strazzabosco, M, Brun, E, Carlesi, G, Garrone, S, Cicalo, A, Clausi, C, Cau, R, Manconi, A, Carboni, A, Angius, M, Pinna, A, Caria, S, Filigheddu, G, Tonolo, G, Carta, I, Calebich, S, Burlotti, C, Saglietti, G, Schellino, A, Madau, G, Cossu, M, Mulas, F, Zoccheddu, S, Balsanelli, M, Fetonti, M, Rotolo, A, Sambo, P, Secchi, E, Angotzi, M, Loddoni, S, Brundu, I, Careddu, F, Becciu, A, Gabriella Piras, G, Novara, F, Cipro, F, Torchio, G, Palumbo, P, Bianchi, A, Colucci, G, La Motta, G, Tiengo, A, Avogaro, A, Bruttomesso, D, Crepaldi, C, Fadini, G, Guarnieri, G, Lavagnini, M, Maran, A, Vedovato, M, De Kreutzenberg, V, Fedele, D, Lapolla, A, Sartore, G, Bax, G, Cardone, C, Dalfra, M, Masin, M, Toniato, R, Piarulli, F, Mattina, G, Fulantelli, M, Gioia, D, Conti, M, Ridola, G, D'Agati, F, Grossi, G, Zavaroni, I, Dei Cas, A, Franzini, L, Usberti, E, Antonimi, M, Anelli, N, Poli, R, Ridolfi, V, Michela, M, Haddoub, S, Prampolini, G, Muoio, A, Filippi, D, Bucci, F, Tardio, S, Calderini, M, Magotti, M, Quarantelli, C, Vernazza, M, Carolfi, A, Saracca, R, Picchio, E, Del Sindaco, P, Spalluto, A, Maggiulli, L, Torreggiani, V, Rastelletti, S, Ugolini, C, Pucci, N, Magi, S, Muratori, S, La Penna, G, Consoli, A, Galeone, F, Magiar, A, Gherardini, V, Moretti, L, Bientinesi, M, Landi, L, Bernardi, A, Del Prato, S, Miccoli, R, Bianchi, C, Penno, G, Venditti, F, Anichini, R, De Bellis, A, Bruschi, T, Butelli, L, Gioffredi, M, Gori, R, Picciafuochi, R, Malagoli, R, Bernini, A, Gelisio, R, Zanon, M, Del Bianco, A, Bamiston, A, Signorato, M, Citro, G, Calabrese, M, Ianni, L, Lorenzetti, M, Marsocci, A, Guizzotti, S, Memoli, G, Cabasino, F, Farci, F, Atzori, A, Sanna, A, Ghiani, M, Siotto, I, Sedda, M, Manis, A, Loddo, C, Loddo, I, Seguro, P, Cuomo, A, Orlando, L, Olanda, G, Pucci, A, Massenzo, M, Sardu, C, Perrone, G, Corazziere, F, La Puzza, I, Tripodi, P, Riggio, S, Giampaolo, A, Mannino, D, Aleandri, A, Guidi, M, Battisti, B, Faraglia, M, Lilli, V, Leotta, S, Visalli, N, Gagliardi, A, Fontana, L, Altomare, M, Carletti, S, Abbruzzese, S, Chiaramonte, F, Giordano, R, Rossini, M, Migneco, G, Cappelloni, D, Urbani, A, Piergiovanni, F, Simonetta, A, Massimiani, F, Bulzomi, R, Giuliano, M, Pennafina, M, Di Perna, P, D'Accinni, M, Paolucci, D, D'Ubaldi, A, D'Angelo, M, Masaro, G, Pietrantoni, M, Fratini, M, La Rosa, R, Poggi, M, Piccirilli, F, Pisano, R, Saponara, C, Conforti, I, Penza, A, Scalpone, R, Lo Pinto, S, Iacovella, L, Caccamo, C, Sposito, S, Teodonio, C, Restuccia, M, Mirto, G, Girardello, R, Gennaro, R, De Moliner, L, Bettini, E, Mattuzzi, A, Speese, K, Frisinghelli, F, Locatelli, F, Nicoletti, M, Trojan, N, Centis, R, L Volsi, P, Levis, E, Zanette, G, Comba, G, Ballatore, L, Cattaneo, A, Aglialoro, A, Guido, R, Patrone, M, Zecchini, M, Clementi, L, Galetta, M, Marconi, V, Bordin, P, Perale, L, Vinci, C, Sira Zanon, M, Geretto, L, Toffolo, C, Furlan, M, Mazzanti, G, Vinci, M, Sica, V, Armeni, M, Derai, R, Ennas, O, Mamusa, S, Pisano, M, Carreras, L, Rauseo, A, Cervone, S, Leggieri, A, Pontonio, M, Sturaro, R, Quattrocchi, F, Molinaro, M, Trasatti, M, Ferretti, B, Labarile, G, Baule, G, Gentilini, A, Spanu, M, Fancellu, A, Bianco, P, Lione, L, Massazza, G, Bocchio, G, Bosco, E, Monachesi, M, Carta, G, Boschetti, M, Ceresola, E, Venier, E, Calcaterra, F, Cataldi, F, Miola, M, Manfrini, S, Lai, A, Locci, B, Putzu, D, Tanganelli, I, Leonini, M, Egger, K, Marchiotto, W, Vincis, L, Orlandini, V, Pilloni, C, Farci, R, Pelligra, I, Renier, G, Mameli, M, Pala, A, Devigus, E, Fumagalli, I, Lalli, C, Leandri, M, Agliani, M, De Pascalis, L, Malci, F, De Ciocchis, A, Diodati, M, Macerola, B, Davi, S, Caccavale, A, Brocato, L, Pognant Gros, M, Borla, S, Lattanzi, E, Piersanti, C, Piersanti, A, Spinelli, I, Tuzzoli, L, Tulini, V, Quaranta, G, Iorio, V, Tirabovi, M, De Terlizi, C, Massarelli, M, Venturi, S, Travaglini, A, Draghi, P, Pomante, P, Richiardi, L, Clerico, A, Bruno, A, Cavallo Perin, P, Ghigo, E, Porta, M, Scuntero, P, Arcari, R, Bertaina, S, Bo, S, Broglio, F, Bruno, G, Degiovanni, M, Fornengo, P, Grassi, G, Inglese, V, Maccario, M, Maghenzani, G, Marena, S, Martina, V, Passera, P, Ruiu, G, Tagliabue, M, Zanone, M, Monge, M, Boffano, G, Macri, K, Maio, P, Ozzello, A, Pergolizzi, E, Gaia, D, Gennari, P, Micali, G, Rossetto, E, Dalmazzo, C, Oreglia, M, Stefani, T, Dossena, C, Paglia, P, Bosoni, S, Romanelli, T, Inchiostro, S, Dauriz, M, Bossi, C, Meregalli, G, Balini, A, Berzi, D, Filippini, B, Crotto, G, Paccagnella, A, Orrasch, M, Sambataro, M, Citro, T, Kiwanuka, E, Bagolin, E, Almoto, B, Macchia, A, Branca, M, Filesi, M, Candido, R, Caroli, E, Manca, E, Petrucco, A, Tommasi, E, Jagodnik, G, Baskar, B, Daris, N, Dal Col, P, Pellegrini, M, Tonutti, L, Venturini, G, Andreani, M, Turchi, F, Fedrighelli, F, Martinelli, G, Rongioletti, R, Candidi, M, Pais, M, Moro, E, Cervellino, F, Sinisi, R, Zampino, A, Mingardi, R, Lora, L, Reitano, R, Stocchiero, C, Simoncini, M, Mesturino, C, Zen, F, Di Pietro, S, Scoponi, C, Tilaro, L, Pelliccioni, S, Slongo, R, Vita, E, Garofalo, A, Vitale, F, Campanella, B, Mastrilli, V, Borrelli, T, D'Avino, A, Perbellini, A, Mirijello A., Viazzi F., Fioretto P., Giorda C. B., Ceriello A., Russo G. T., Guida P., Pontremoli R., De Cosmo S., Cimino A., Fava D., Meloncelli I., Nicolucci A., Pellegrini F., Rossi M. C., Turco S., Vespasiani G., Graziano G., Lucisano G., Memmo R., Pellicciotta E., Paciotti V., Pupillo M., Armentano G., Giovannini C., Armentano V., Laudato M., Acquati S., Ciardullo A. V., Laffi G., Felace G., Taboga C., Tortul C., Santantonio G., Suraci C., Ghisoni G., Raffa M., Genovese S., Lovagnini-Scher C. A., Rampini P., Rocca A., Ruggeri P., Tortato E., Cotti L., Cristofaro M. R., Tagliaferri M., Comoglio M., Fornengo R., Gentile F. M., Gigante A., Mastinu F., Di Benedetto A., Pata P., Arcangeli A., Orsini P., Acler P., De Blasi G., Cicioni G., Pocciati S., Marangoni A., Nogara A., Lanero M., Bertero M. G., Damassino R., Bergonzini C., Schumtz L., Seksich L., Pipitone A., Boaretto M., Manfroi I., Parmesan L., Conte B., Soccol F., Pagano A., Papini E., Rinaldi R., Petrucci L., Graziano F., Chianelli M., Silvagni S., Rosco M., Ansaldi E., Malvicino F., Battezzati M., Maresca P., Palenzona C., Boemi M., Rabini R. A., Brandoni G., Lanari L., Gatti C., Testa I., Cherubini V., Doveri G., Pecorelli L., Ciccarelli A., Gallardini M. B., Courthoud R., Sara Bredy S., Ricciardi G. P., Vitalone G., Setti D., Contrini P., Corsi A., Ghigliotti V., Oddone G., Ponzani P., Valbonesi G., Mazzini V., Di Berardino P., Colleluori P., Montani V., Trosini V., Velussi M., Alfidi P., Verdecchia B., Baliva L., Di Pietro A., Franchi G., Luce R. P., Pianta A., Ferrari M., Balzano S., Beltranello G., Dal Fabbro S., Arico C. N., Cervo L., Zanon R., Rossa S., Di Pace M. C., Ciavarella A., Giangiulio S., Grimaldi M., Mustacchio A., Fattor B., Monauni T., Cristini M., Orion G., Crazzolara D., Amor F., Eisath J. E., Lintner S., Garavelli S., Calari T., Marini P., Sandri O., Scala M., Stroppa C., Trentin A., Carlin R., Carli B., Sandona M., Zortea C., Bonet L., Pradel L., Reato S., Buschini M., Bonfiglioli D., Mones D., Beldi F., Morea A., Bondesan L., Perbellini S., Valentini U., Agosti B., Corsini R., Girelli A., Zarra E., Rocca L., Bergmann M., Pradi I., Unterkircher S., Piok M., Pichler M., Trinchera A., Palama G., Palma P., Carboni L., Murtas M. G., Mudadu T., Turco M. P., Floris M., Delogu A., Farris L., Songini M., Piras G., Seguro R., Floris R., Corona G., Lai M., Piras E., Contini P. P., Cocco S., Pilosu R. M., Sannia M. C., Spanu F., Busciantella Ricci N., Cartechini M. G., Agostinelli G., Fiorelli C., Nuzzi A., Ballauri C., Lesina A., Romeo F., Giudici G., Maciejewska E. G., Deroma A., Paduano M., Rossi L., Vagnini C., Dolci M., Mori M., Baccetti F., Gregori G., Straface E., Pozzuoli G., Barone M., Stasio G. B., Tondini S., Borgoni F., Grosso J., Scarsellato C., Sciulli A., De Marco F., Confortin L., Marin N., Lamonica M., Gialdino S., Borzi V., Gatta C., Rapisard R., Strano S., Calabro M., Puccio L., Zolli M., Coracina A., Starnone V., Del Buono A., Terracciano A. M., Monda M. V., Castro F., Guaglianone A., Maccari V., Corsi L., Versari G., Falivene M. R., Boletto N., Corsi S., Marafetti L., Vitacolonna E., Capani F., Caputo L., Di Nisio L., Simonetti F., Boscolo Bariga A., Ballarin G., De Boni S., Di Benedetto S., Chiambretti A. M., Di Vito L., Pascuzzo M. D., Urli P., Rumi P., Balzarini B., Galli P., Castellan M., Giannetti A., Russotti C., De Blasi A., Perna A., Campanelli C., Ranchelli A., Biccheri D., Dadi G., Massa L., Baldi G. P., Sciacca F., Costanzo E., Spada M., Paolini G., Ziller P., Portolan F., Pasolini G., Ghilardi G., Fiorina P., Grata M. L., Capretti L., Speroni G., Fugazza L., Massafra C., Lovagnini Scher A., Cimicchi M. C., Percudani C., Risolo T., Sacco P., Gidoni Guarnieri G. L., Piccolo D., Bravin C., De Noni E., Scarpel M., Marcon M., Giacon F., Panebianco G., Tadiotto F., Da Tos V., D'Ambrosio M., Pellizzola D., Zampini M. A., Frezzati E., Mari E., Raminelli E., Gaiti D., Bosi E. A., Chierici G., Pilla S., Copelli M., Zanichelli P., Bertelli L., Caretta P., Vezzani V., Bodecchi S., Longobucco A., Di Lembo S., Spotti E., Carrai E., Degli Innocenti A., Manini L., Persico R., Rossi C., Magro G., Marelli G., Vilei V., Andrioli M., Bellato L., Fedeli M., Merlini A., Pinelli G., Marin G., Contin M. L., Gallo A., Parlato P., Pecchielan W., Jacovacci J., Placentino G., Richini D., Molinari S., Strazzeri R., Fabbri T., Di Bartolo P., Garrapa G., D'Incau F., Lagomanzini P., Conte P., Todesco F., Foglini P., Pantanetti P., Bedetta C., Maricotti R., Tomasi F., Monesi M., Graziani R., Beretta F., Penna L., Guberti A., Dazzi D., Forte E., Gasbarrone A., Marrocco T., Moschetta R., Tuccinardi F., De Meo F., Coppola A., Pirolozzi P., Placitelli E., Vallefuoco R., Catone B., Ceschia S., Urban M., Fabbri F., Torresani M., Crovetto R., Battistini M., Carosia P., Viviani G. L., Durante A., Pais F., Lilliu V., Quieto C., D'Ugo E., Squadrone M., Amenduni T., Iovannisci M. M., Della Penna L., Potente F., Delle Donne T., Massa C., Ulisse M. A., De Berardinis S., Guarnieri I., Pace S., Splendiani M., Di Giuseppe R., Brunato B., Assaloni R., Muraro R., Loro R., Bucciol S., Lavacca C., Rossi M., Sabbatini G., Quadri F., Sambuco L., Santacroce C., Paola Caretta D., Marino C., Micheletti A., Petrelli A., Corda A., Pisano L., Guaita G., Deias C., Trevisan G., Coletti I., Iannarelli R., De Luca A., Minnucci A., Antenucci D., Di Florio C., Angelicola G., Bosco A., Fresco R., Di Marco G., Ugolotti D., Cadossi T., Di Caro P., Mazzocchetti M., Buzzetti R., Leto G., Gnessi C., Cipolloni L., Foffi C., Moretti C., Venditti C., Meniconi R., Bertoli S., Cosimi S., Di Cianni G., Turco A., Richini A., Marconi S., Sannino C., Lemmi P., Giuntoli S., Manfre N., Giannini F., Di Carlo A., Casadidio I., Melandri P., Maolo G., Polenta B., Piccinini N., Vincenti C., Pastore N., Mega P., Magurano E., Cananiello A., Francescutto C. A., Brussa Toi E., Gaspardo G., Angeli L., Ronchese L., Sciangula L., Ciucci A., Contartese A., Banfi E., Castelli E., Tatti P., Bloise D., Di Mauro P., Masselli L., Lo Presti A., Scarpitta A. M., Gambina F., Venezia A., Morea R., Lagonigro G., Copeta G., Iannucci V., Milano V., Trupo M., Lochmann A., Marchetto P. E., Incelli G., De Paola G., Steiger M. M., Gamper M. A., Breitenberger S., Holzner M., Frischmann J., Lambiase C., Di Vece T., D'Aniello M., Fezza M., Giordano C., Leo F., Saitta G., Cucinotta D., Di Vieste G., Pintaudi B., Mancuso T., Musacchio N., Giancaterini A., Pessina L., Salis G., Schivalocchi F., Testori G., Cerutti N., Morpugo P. S., Cavaletto M. L., Bonino G., Morreale F., Mariani G., Ragonesi P. D., Bollati P., Colapinto P., Falqui L., Bortolato L., Cosma A., Pistolato P., Centenaro B., Ceccato A., Campobasso G., Zaurino F., Mazzotta G., Manti R., Da Ros R., Carlucci S., Narduzzi L., Bortolotto D., D'Acunto L., Stanic L., Volpi A., Cospite A. M., Manicardi V., Michelini M., Finardi L., Borghi F., Manicardi E., Lombardi S., Tommasi C., Iaccarino M., Cozza S., Binotto M., Marini F., Mecenero I., Massignani S., Stecco P., Urbani E., Massariol W., Parolin R., Gatti A., Bonavita M., Creso E., Giannettino R., Gobbo M., Iovine C., Riccardi G., Iazzetta N., Giannattasio C., Egione O., Galdieri S., Velotti A., Azzolina A., Annicelli G., Sorrentino T., Gaeta I., Zenari L., Bertolini L., Sorgato C., Grippaldi F., Stroppiana M., Popolizio R., Carbone N., Grasso S., Abate S., Gaggero G. C., Strazzabosco M., Brun E., Carlesi G. P., Garrone S., Cicalo A. M., Clausi C., Cau R., Manconi A., Carboni A., Angius M. F., Pinna A. A., Caria S., Filigheddu G. D., Tonolo G., Carta I., Calebich S., Burlotti C., Saglietti G., Schellino A., Madau G., Cossu M., Mulas F., Zoccheddu S., Balsanelli M., Fetonti M., Rotolo A., Sambo P., Secchi E., Angotzi M. A., Loddoni S., Brundu I., Careddu F., Becciu A., Gabriella Piras G., Novara F., Cipro F., Torchio G., Palumbo P., Bianchi A., Colucci G., La Motta G., Tiengo A., Avogaro A., Bruttomesso D., Crepaldi C., Fadini G., Guarnieri G., Lavagnini M. T., Maran A., Vedovato M., De Kreutzenberg V., Fedele D., Lapolla A., Sartore G., Bax G., Cardone C., Dalfra M. G., Masin M., Toniato R., Piarulli F., Mattina G., Fulantelli M. A., Gioia D., Conti M., Ridola G., D'Agati F., Grossi G., Zavaroni I., Dei Cas A., Franzini L., Usberti E., Antonimi M., Anelli N., Poli R., Ridolfi V., Michela M., Haddoub S., Prampolini G., Muoio A., Filippi D., Bucci F., Tardio S. M., Calderini M. C., Magotti M. G., Quarantelli C., Vernazza M. A., Carolfi A., Saracca R., Picchio E., Del Sindaco P., Spalluto A., Maggiulli L., Torreggiani V., Rastelletti S., Ugolini C., Pucci N., Magi S., Muratori S., La Penna G., Consoli A., Galeone F., Magiar A. V., Gherardini V., Moretti L., Bientinesi M., Landi L., Bernardi A., Del Prato S., Miccoli R., Bianchi C., Penno G., Venditti F., Anichini R., De Bellis A., Bruschi T., Butelli L., Gioffredi M., Gori R., Picciafuochi R., Malagoli R., Bernini A., Gelisio R., Zanon M., Del Bianco A., Bamiston A., Signorato M., Citro G., Calabrese M., Ianni L., Lorenzetti M., Marsocci A., Guizzotti S., Memoli G., Cabasino F., Farci F., Atzori A., Sanna A., Ghiani M., Siotto I., Sedda M., Manis A., Loddo C., Loddo I., Seguro P., Cuomo A., Orlando L., Olanda G. B., Pucci A., Massenzo M., Sardu C., Perrone G., Corazziere F., La Puzza I., Tripodi P. F., Riggio S., Giampaolo A., Mannino D., Aleandri A. R., Guidi M. V., Battisti B., Faraglia M. R., Lilli V., Leotta S., Visalli N., Gagliardi A., Fontana L., Altomare M., Carletti S., Abbruzzese S., Chiaramonte F., Giordano R., Rossini M., Migneco G., Cappelloni D., Urbani A., Piergiovanni F., Simonetta A., Massimiani F., Bulzomi R., Giuliano M., Pennafina M. G., Di Perna P., D'Accinni M. P., Paolucci D., D'Ubaldi A., D'Angelo M. T., Masaro G., Pietrantoni M., Fratini M., La Rosa R., Poggi M., Piccirilli F., Pisano R., Saponara C., Conforti I., Penza A., Scalpone R., Lo Pinto S., Iacovella L., Caccamo C., Sposito S., Teodonio C., Restuccia M. G., Mirto G., Girardello R., Gennaro R., De Moliner L., Bettini E., Mattuzzi A., Speese K., Frisinghelli F., Locatelli F., Nicoletti M., Trojan N., Centis R., L Volsi P., Levis E., Zanette G., Comba G., Ballatore L., Cattaneo A., Aglialoro A., Guido R., Patrone M., Zecchini M., Clementi L., Galetta M., Marconi V., Bordin P., Perale L., Vinci C., Sira Zanon M., Geretto L., Toffolo C., Furlan M. G., Mazzanti G., Vinci M., Sica V., Armeni M., Derai R., Ennas O., Mamusa S., Pisano M. A., Carreras L., Rauseo A., Cervone S., Leggieri A., Pontonio M., Sturaro R., Quattrocchi F., Molinaro M., Trasatti M., Ferretti B., Labarile G., Baule G. M., Gentilini A., Spanu M. A., Fancellu A., Bianco P., Lione L., Massazza G., Bocchio G., Bosco E., Monachesi M., Carta G., Boschetti M., Ceresola E., Venier E., Calcaterra F., Cataldi F., Miola M., Manfrini S., Lai A., Locci B., Putzu D., Tanganelli I., Leonini M., Egger K., Marchiotto W., Vincis L., Orlandini V., Pilloni C., Farci R., Pelligra I., Renier G., Mameli M., Pala A., Devigus E., Fumagalli I., Lalli C., Leandri M., Agliani M., De Pascalis L., Malci F., De Ciocchis A., Diodati M. B., Macerola B., Davi S., Caccavale A., Brocato L., Pognant Gros M., Borla S., Lattanzi E., Piersanti C., Piersanti A., Spinelli I., Tuzzoli L., Tulini V., Quaranta G., Iorio V., Tirabovi M., De Terlizi C., Massarelli M. G., Venturi S., Travaglini A., Draghi P., Pomante P., Richiardi L., Clerico A., Bruno A., Cavallo Perin P., Ghigo E., Porta M., Scuntero P., Arcari R., Bertaina S., Bo S., Broglio F., Bruno G., Degiovanni M., Fornengo P., Grassi G., Inglese V., Maccario M., Maghenzani G., Marena S., Martina V., Passera P., Ruiu G., Tagliabue M., Zanone M., Monge M., Boffano G. M., Macri K., Maio P., Ozzello A., Pergolizzi E., Gaia D., Gennari P., Micali G., Rossetto E., Dalmazzo C., Oreglia M., Stefani T., Dossena C., Paglia P., Bosoni S., Romanelli T., Inchiostro S., Dauriz M., Bossi C. A., Meregalli G., Balini A., Berzi D., Filippini B., Crotto G., Paccagnella A., Orrasch M., Sambataro M., Citro T., Kiwanuka E., Bagolin E., Almoto B., Macchia A., Branca M. T., Filesi M., Candido R., Caroli E., Manca E., Petrucco A., Tommasi E., Jagodnik G., Baskar B., Daris N., Dal Col P., Pellegrini M. A., Tonutti L., Venturini G., Andreani M., Turchi F., Fedrighelli F., Martinelli G., Rongioletti R., Candidi M., Pais M., Moro E., Cervellino F., Sinisi R., Zampino A., Mingardi R., Lora L., Reitano R., Stocchiero C., Simoncini M., Mesturino C. 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G., Di Perna P., D'Accinni M. P., Paolucci D., D'Ubaldi A., D'Angelo M. T., Masaro G., Pietrantoni M., Fratini M., La Rosa R., Poggi M., Piccirilli F., Pisano R., Saponara C., Conforti I., Penza A., Scalpone R., Lo Pinto S., Iacovella L., Caccamo C., Sposito S., Teodonio C., Restuccia M. G., Mirto G., Girardello R., Gennaro R., De Moliner L., Bettini E., Mattuzzi A., Speese K., Frisinghelli F., Locatelli F., Nicoletti M., Trojan N., Centis R., L Volsi P., Levis E., Zanette G., Comba G., Ballatore L., Cattaneo A., Aglialoro A., Guido R., Patrone M., Zecchini M., Clementi L., Galetta M., Marconi V., Bordin P., Perale L., Vinci C., Sira Zanon M., Geretto L., Toffolo C., Furlan M. G., Mazzanti G., Vinci M., Sica V., Armeni M., Derai R., Ennas O., Mamusa S., Pisano M. A., Carreras L., Rauseo A., Cervone S., Leggieri A., Pontonio M., Sturaro R., Quattrocchi F., Molinaro M., Trasatti M., Ferretti B., Labarile G., Baule G. M., Gentilini A., Spanu M. A., Fancellu A., Bianco P., Lione L., Massazza G., Bocchio G., Bosco E., Monachesi M., Carta G., Boschetti M., Ceresola E., Venier E., Calcaterra F., Cataldi F., Miola M., Manfrini S., Lai A., Locci B., Putzu D., Tanganelli I., Leonini M., Egger K., Marchiotto W., Vincis L., Orlandini V., Pilloni C., Farci R., Pelligra I., Renier G., Mameli M., Pala A., Devigus E., Fumagalli I., Lalli C., Leandri M., Agliani M., De Pascalis L., Malci F., De Ciocchis A., Diodati M. B., Macerola B., Davi S., Caccavale A., Brocato L., Pognant Gros M., Borla S., Lattanzi E., Piersanti C., Piersanti A., Spinelli I., Tuzzoli L., Tulini V., Quaranta G., Iorio V., Tirabovi M., De Terlizi C., Massarelli M. G., Venturi S., Travaglini A., Draghi P., Pomante P., Richiardi L., Clerico A., Bruno A., Cavallo Perin P., Ghigo E., Porta M., Scuntero P., Arcari R., Bertaina S., Bo S., Broglio F., Bruno G., Degiovanni M., Fornengo P., Grassi G., Inglese V., Maccario M., Maghenzani G., Marena S., Martina V., Passera P., Ruiu G., Tagliabue M., Zanone M., Monge M., Boffano G. M., Macri K., Maio P., Ozzello A., Pergolizzi E., Gaia D., Gennari P., Micali G., Rossetto E., Dalmazzo C., Oreglia M., Stefani T., Dossena C., Paglia P., Bosoni S., Romanelli T., Inchiostro S., Dauriz M., Bossi C. A., Meregalli G., Balini A., Berzi D., Filippini B., Crotto G., Paccagnella A., Orrasch M., Sambataro M., Citro T., Kiwanuka E., Bagolin E., Almoto B., Macchia A., Branca M. T., Filesi M., Candido R., Caroli E., Manca E., Petrucco A., Tommasi E., Jagodnik G., Baskar B., Daris N., Dal Col P., Pellegrini M. A., Tonutti L., Venturini G., Andreani M., Turchi F., Fedrighelli F., Martinelli G., Rongioletti R., Candidi M., Pais M., Moro E., Cervellino F., Sinisi R., Zampino A., Mingardi R., Lora L., Reitano R., Stocchiero C., Simoncini M., Mesturino C. A., Zen F., Di Pietro S., Scoponi C., Tilaro L., Pelliccioni S., Slongo R., Vita E., Garofalo A., Vitale F., Campanella B., Mastrilli V., Borrelli T., D'Avino A., and Perbellini A.
- Abstract
Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage ≥3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage ≥3 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage ≥3 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 ± 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage ≥3 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage ≥3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening.
- Published
- 2018
6. Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes 11 Medical and Health Sciences 1103 Clinical Sciences
- Author
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Mirijello, Antonio, Viazzi, Francesca, Fioretto, Paola, Giorda, C. B., Ceriello, Antonio, Russo, Giuspina T., Guida, Pietro, Pontremoli, Roberto, De Cosmo, S., Cimino, Antonino, Fava, Danila, Meloncelli, Illidio, Nicolucci, Antonio, Pellegrini, Fabio, Rossi, Maria Chiara, Turco, Salvatore, Vespasiani, Giacomo, Graziano, G., Lucisano, G., Memmo, R., Pellicciotta, E., Paciotti, V., Pupillo, M., Armentano, G., Giovannini, C., Armentano, V., Laudato, M., Acquati, S., Ciardullo, A. V., Laffi, G., Felace, G., Taboga, C., Tortul, C., Santantonio, G., Suraci, C., Ghisoni, G., Raffa, M., Genovese, S., Lovagnini-Scher, C. A., Rampini, P., Rocca, A., Ruggeri, P., Tortato, E., Cotti, L., Cristofaro, M. R., Tagliaferri, M., Comoglio, M., Fornengo, R., Gentile, F. M., Gigante, Antonio, Mastinu, F., Di Benedetto, A., Pata, P., Arcangeli, A., Orsini, P., Acler, P., De Blasi, G., Cicioni, G., Pocciati, S., Marangoni, A., Nogara, A., Lanero, M., Bertero, M. 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- Subjects
Albuminuria ,Diabetic kidney disease ,GFR ,Albuminuria, Diabetic kidney disease, GFR ,Nephrology - Abstract
Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage ≥3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage ≥3 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage ≥3 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 ± 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage ≥3 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage ≥3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening.
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- 2018
7. Isolation of pig pancreatic islets by a new method with hydraulic shaking: preliminary report
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Viviani, G. L., Fontana, I., Zecchi, A., Bottino, R., Sanna, R., Lione, L., Sacchi, G., Falzetti, G., Valente, U., Adezati, L., Kootstra, Gauke, editor, Opelz, Gerhard, editor, Buurman, W. A., editor, van Hooff, J. P., editor, MacMaster, P., editor, and Wallwork, J., editor
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- 1992
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8. Novel Selective Compounds for the Investigation of Imidazoline Receptorsa
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HUDSON, A. L., GOUGH, R., TYACKE, R., LIONE, L., LALIES, M., LEWIS, J., HUSBANDS, S., KNIGHT, P., MURRAY, F., HUTSON, P., and NUTT, D. J.
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- 1999
9. Isolation of pig pancreatic islets by a new method with hydraulic shaking: preliminary report
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Giorgio Luciano Viviani, Fontana, I., Zecchi, A., Bottino, R., Sanna, R., Lione, L., Sacchi, G., Falzetti, G., Valente, U., and Adezati, L.
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Transplantation - Published
- 2018
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10. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International diabetes Federation and the European Federation of Periodontology
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Sanz, M. Ceriello, A. Buysschaert, M. Chapple, I. Demmer, R.T. Graziani, F. Herrera, D. Jepsen, S. Lione, L. Madianos, P. Mathur, M. Montanya, E. Shapira, L. Tonetti, M. Vegh, D.
- Abstract
Background: Diabetes and periodontitis are chronic non-communicable diseases independently associated with mortality and have a bidirectional relationship. Aims: To update the evidence for their epidemiological and mechanistic associations and re-examine the impact of effective periodontal therapy upon metabolic control (glycated haemoglobin, HbA1C). Epidemiology: There is strong evidence that people with periodontitis have elevated risk for dysglycaemia and insulin resistance. Cohort studies among people with diabetes demonstrate significantly higher HbA1C levels in patients with periodontitis (versus periodontally healthy patients), but there are insufficient data among people with type 1 diabetes. Periodontitis is also associated with an increased risk of incident type 2 diabetes. Mechanisms: Mechanistic links between periodontitis and diabetes involve elevations in interleukin (IL)-1-β, tumour necrosis factor-α, IL-6, receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio, oxidative stress and Toll-like receptor (TLR) 2/4 expression. Interventions: Periodontal therapy is safe and effective in people with diabetes, and it is associated with reductions in HbA1C of 0.27–0.48% after 3 months, although studies involving longer-term follow-up are inconclusive. Conclusions: The European Federation of Periodontology (EFP) and the International Diabetes Federation (IDF) report consensus guidelines for physicians, oral healthcare professionals and patients to improve early diagnosis, prevention and comanagement of diabetes and periodontitis. © 2017 John Wiley & Sons A/S and Elsevier B.V.
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- 2018
11. Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes
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Mirijello, Antonio, Viazzi, Francesca, Fioretto, Paola, Giorda, Carlo, Ceriello, Antonio, Russo, Giuspina T., Guida, Pietro, Pontremoli, Roberto, De Cosmo, Salvatore, Cimino, Antonino, Fava, Danila, Giorda, Carlo Bruno, Meloncelli, Illidio, Nicolucci, Antonio, Pellegrini, Fabio, Rossi, Maria Chiara, Turco, Salvatore, Vespasiani, Giacomo, Pellegrini, F., Graziano, G., Lucisano, G., Memmo, R., Pellicciotta, E., Paciotti, V., Pupillo, M., Armentano, G., Giovannini, C., Armentano, V., Laudato, M., Turco, S., Acquati, S., Ciardullo, A. V., Laffi, G., Felace, G., Taboga, C., Tortul, C., Santantonio, G., Suraci, C., Ghisoni, G., Raffa, M., Genovese, S., Lovagnini-Scher, C. A., Rampini, P., Rocca, A., Ruggeri, P., Tortato, E., Cotti, L., Cristofaro, M. R., Tagliaferri, M., Comoglio, M., Fornengo, R., De Cosmo, S., Gentile, F. M., Gigante, A., Mastinu, F., Di Benedetto, A., Pata, P., Arcangeli, A., Orsini, P., Acler, P., De Blasi, G., Cicioni, G., Pocciati, S., Marangoni, A., Nogara, A., Lanero, M., Bertero, M. G., Damassino, R., Bergonzini, C., Schumtz, L., Seksich, L., Pipitone, A., Boaretto, M., Manfroi, I., Parmesan, L., Conte, B., Soccol, F., Pagano, A., Papini, E., Rinaldi, R., Petrucci, L., Graziano, F., Chianelli, M., Silvagni, S., Rosco, M., Ansaldi, E., Malvicino, F., Battezzati, M., Maresca, P., Palenzona, C., Boemi, M., Rabini, R. A., Brandoni, G., Lanari, L., Gatti, C., Testa, I., Cherubini, V., Doveri, G., Pecorelli, L., Ciccarelli, A., Gallardini, M. B., Courthoud, R., Sara Bredy, S., Ricciardi, G. P., Vitalone, G., Setti, D., Contrini, P., Corsi, A., Ghigliotti, V., Oddone, G., Ponzani, P., Valbonesi, G., Mazzini, V., Di Berardino, P., Colleluori, P., Montani, V., Trosini, V., Velussi, M., Alfidi, P., Verdecchia, B., Baliva, L., Di Pietro, A., Franchi, G., Luce, R. 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D., Urli, P., Rumi, P., Balzarini, B., Galli, P., Castellan, M., Giannetti, A., Russotti, C., De Blasi, A., Perna, A., Campanelli, C., Ranchelli, A., Biccheri, D., Dadi, G., Massa, L., Baldi, G. P., Sciacca, F., Costanzo, E., Spada, M., Paolini, G., Ziller, P., Portolan, F., Pasolini, G., Ghilardi, G., Fiorina, P., Grata, M. L., Capretti, L., Speroni, G., Fugazza, L., Massafra, C., Lovagnini Scher, A., Cimicchi, M. C., Percudani, C., Risolo, T., Saccò, P., Gidoni Guarnieri, G. L., Piccolo, D., Bravin, C., De Noni, E., Scarpel, M., Marcon, M., Giacon, F., Panebianco, G., Tadiotto, F., Da Tos, V., D'Ambrosio, M., Pellizzola, D., Zampini, M. A., Frezzati, E., Mari, E., Raminelli, E., Gaiti, D., Bosi, E. A., Chierici, G., Pilla, S., Copelli, M., Zanichelli, P., Bertelli, L., Caretta, P., Vezzani, V., Bodecchi, S., Longobucco, A., Di Lembo, S., Spotti, E., Carrai, E., Degli Innocenti, A., Manini, L., Persico, R., Rossi, C., Magro, G., Marelli, G., Vilei, V., Andrioli, M., Bellato, L., Fedeli, M., Merlini, A., Pinelli, G., Marin, G., Contin, M. L., Gallo, A., Parlato, P., Pecchielan, W., Jacovacci, J., Placentino, G., Richini, D., Molinari, S., Strazzeri, R., Fabbri, T., Di Bartolo, P., Garrapa, G., D'Incau, F., Lagomanzini, P., Conte, P., Todesco, F., Foglini, P., Pantanetti, P., Bedetta, C., Maricotti, R., Tomasi, F., Monesi, M., Graziani, R., Beretta, F., Penna, L., Guberti, A., Dazzi, D., Forte, E., Gasbarrone, A., Marrocco, T., Moschetta, R., Tuccinardi, F., De Meo, F., Coppola, A., Pirolozzi, P., Placitelli, E., Vallefuoco, R., Catone, B., Ceschia, S., Urban, M., Fabbri, F., Torresani, M., Crovetto, R., Battistini, M., Carosia, P., Viviani, G. L., Durante, A., Pais, F., Lilliu, V., Quieto, C., D'Ugo, E., Squadrone, M., Amenduni, T., Iovannisci, M. M., Della Penna, L., Potente, F., Delle Donne, T., Massa, C., Ulisse, M. A., De Berardinis, S., Guarnieri, I., Pace, S., Splendiani, M., Di Giuseppe, R., Brunato, B., Assaloni, R., Muraro, R., Loro, R., Bucciol, S., Lavacca, C., Rossi, M., Sabbatini, G., Quadri, F., Sambuco, L., Santacroce, C., Paola Caretta, D., Marino, C., Micheletti, A., Petrelli, A., Corda, A., Pisano, L., Guaita, G., Deias, C., Trevisan, G., Coletti, I., Iannarelli, R., De Luca, A., Minnucci, A., Antenucci, D., Di Florio, C., Angelicola, G., Bosco, A., Fresco, R., Di Marco, G., Ugolotti, D., Cadossi, T., Di Caro, P., Mazzocchetti, M., Buzzetti, R., Leto, G., Gnessi, C., Cipolloni, L., Foffi, C., Moretti, C., Venditti, C., Meniconi, R., Bertoli, S., Cosimi, S., Di Cianni, G., Turco, A., Richini, A., Marconi, S., Sannino, C., Lemmi, P., Giuntoli, S., Manfrè, N., Giannini, F., Di Carlo, A., Casadidio, I., Melandri, P., Maolo, G., Polenta, B., Piccinini, N., Vincenti, C., Pastore, N., Mega, P., Magurano, E., Cananiello, A., Francescutto, C. A., Brussa Toi, E., Gaspardo, G., Angeli, L., Ronchese, L., Sciangula, L., Ciucci, A., Contartese, A., Banfi, E., Castelli, E., Tatti, P., Bloise, D., Di Mauro, P., Masselli, L., Lo Presti, A., Scarpitta, A. M., Gambina, F., Venezia, A., Morea, R., Lagonigro, G., Copeta, G., Iannucci, V., Milano, V., Trupo, M., Lochmann, A., Marchetto, P. E., Incelli, G., De Paola, G., Steiger, M. M., Gamper, M. A., Breitenberger, S., Holzner, M., Frischmann, J., Lambiase, C., Di Vece, T., D'Aniello, M., Fezza, M., Giordano, C., Leo, F., Saitta, G., Cucinotta, D., Di Vieste, G., Pintaudi, B., Mancuso, T., Musacchio, N., Giancaterini, A., Pessina, L., Salis, G., Schivalocchi, F., Testori, G., Rampini, P. A., Cerutti, N., Morpugo, P. S., Cavaletto, M. L., Bonino, G., Morreale, F., Mariani, G., Ragonesi, P. D., Bollati, P., Colapinto, P., Bosi, E., Falqui, L., Bortolato, L., Cosma, A., Pistolato, P., Centenaro, B., Ceccato, A., Campobasso, G., Zaurino, F., Mazzotta, G., Manti, R., Da Ros, R., Carlucci, S., Narduzzi, L., Bortolotto, D., D'Acunto, L., Stanic, L., Volpi, A., Cospite, A. M., Manicardi, V., Michelini, M., Finardi, L., Borghi, F., Manicardi, E., Lombardi, S., Tommasi, C., Iaccarino, M., Cozza, S., Binotto, M., Marini, F., Mecenero, I., Massignani, S., Stecco, P., Urbani, E., Massariol, W., Parolin, R., Gatti, A., Bonavita, M., Creso, E., Giannettino, R., Gobbo, M., Iovine, C., Turco, A. A., Riccardi, G., Iazzetta, N., Giannattasio, C., Egione, O., Galdieri, S., Velotti, A., Azzolina, A., Annicelli, G., Sorrentino, T., Gaeta, I., Zenari, L., Bertolini, L., Sorgato, C., Grippaldi, F., Stroppiana, M., Popolizio, R., Carbone, N., Grasso, S., Abate, S., Gaggero, G. C., Strazzabosco, M., Brun, E., Carlesi, G. P., Garrone, S., Cicalò, A. M., Clausi, C., Cau, R., Manconi, A., Carboni, A., Angius, M. F., Pinna, A. A., Caria, S., Filigheddu, G. D., Tonolo, G., Carta, I., Calebich, S., Burlotti, C., Saglietti, G., Schellino, A., Madau, G., Cossu, M., Mulas, F., Zoccheddu, S., Balsanelli, M., Fetonti, M., Rotolo, A., Sambo, P., Secchi, E., Angotzi, M. A., Loddoni, S., Brundu, I., Careddu, F., Becciu, A., Gabriella Piras, G., Novara, F., Cipro, F., Torchio, G., Palumbo, P., Bianchi, A., Colucci, G., La Motta, G., Tiengo, A., Avogaro, A., Bruttomesso, D., Crepaldi, C., Fadini, G., Guarnieri, G., Lavagnini, M. T., Maran, A., Vedovato, M., De Kreutzenberg, V., Fedele, D., Lapolla, A., Sartore, G., Bax, G., Cardone, C., Dalfrà, M. G., Masin, M., Toniato, R., Piarulli, Francesco, Mattina, G., Fulantelli, M. A., Gioia, D., Conti, M., Ridola, G., D'Agati, F., Grossi, G., De Berardinis, F., Zavaroni, I., Dei Cas, A., Franzini, L., Usberti, E., Antonimi, M., Anelli, N., Poli, R., Ridolfi, V., Michela, M., Haddoub, S., Prampolini, G., Muoio, A., Filippi, D., Bucci, F., Tardio, S. M., Calderini, M. C., Magotti, M. G., Quarantelli, C., Vernazza, M. A., Carolfi, A., Saracca, R., Picchio, E., Del Sindaco, P., Spalluto, A., Maggiulli, L., Torreggiani, V., Rastelletti, S., Ugolini, C., Pucci, N., Magi, S., Muratori, S., La Penna, G., Consoli, A., Galeone, F., Magiar, A. V., Gherardini, V., Moretti, L., Bientinesi, M., Landi, L., Bernardi, A., Del Prato, S., Miccoli, R., Bianchi, C., Penno, G., Venditti, F., Anichini, R., De Bellis, A., Bruschi, T., Butelli, L., Gioffredi, M., Gori, R., Picciafuochi, R., Malagoli, R., Bernini, A., Gelisio, R., Zanon, M., Del Bianco, A., Bamiston, A., Signorato, M., Citro, G., Calabrese, M., Ianni, L., Lorenzetti, M., Marsocci, A., Guizzotti, S., Memoli, G., Cabasino, F., Farci, F., Atzori, A., Sanna, A., Ghiani, M., Siotto, I., Sedda, M., Manis, A., Loddo, C., Loddo, I., Seguro, P., Cuomo, A., Orlando, L., Olanda, G. B., Pucci, A., Massenzo, M., Sardu, C., Perrone, G., Corazziere, F., La Puzza, I., Tripodi, P. F., Riggio, S., Giampaolo, A., Mannino, D., Aleandri, A. R., Guidi, M. V., Battisti, B., Faraglia, M. R., Lilli, V., Leotta, S., Visalli, N., Gagliardi, A., Fontana, L., Altomare, M., Carletti, S., Abbruzzese, S., Chiaramonte, F., Giordano, R., Rossini, M., Migneco, G., Cappelloni, D., Urbani, A., Piergiovanni, F., Fava, D., Simonetta, A., Massimiani, F., Bulzomì, R., Giuliano, M., Pennafina, M. G., Di Perna, P., D'Accinni, M. P., Paolucci, D., D'Ubaldi, A., D'Angelo, M. T., Masaro, G., Pietrantoni, M., Fratini, M., La Rosa, R., Poggi, M., Piccirilli, F., Pisano, R., Saponara, C., Conforti, I., Penza, A., Scalpone, R., Lo Pinto, S., Iacovella, L., Caccamo, C., Sposito, S., Teodonio, C., Restuccia, M. G., Mirto, G., Girardello, R., Gennaro, R., De Moliner, L., Bettini, E., Mattuzzi, A., Speese, K., Frisinghelli, F., Locatelli, F., Nicoletti, M., Trojan, N., Centis, R., L Volsi, P., Levis, E., Zanette, G., Comba, G., Ballatore, L., Cattaneo, A., Aglialoro, A., Guido, R., Patrone, M., Zecchini, M., Vespasiani, G., Meloncelli, I., Clementi, L., Galetta, M., Marconi, V., Bordin, P., Perale, L., Vinci, C., Sira Zanon, M., Geretto, L., Toffolo, C., Furlan, M. G., Mazzanti, G., Vinci, M., Sica, V., Armeni, M., Derai, R., Ennas, O., Mamusa, S., Pisano, M. A., Carreras, L., Rauseo, A., Cervone, S., Leggieri, A., Pontonio, M., Sturaro, R., Quattrocchi, F., Molinaro, M., Trasatti, M., Ferretti, B., Labarile, G., Baule, G. M., Gentilini, A., Spanu, M. A., Fancellu, A., Bianco, P., Lione, L., Massazza, G., Bocchio, G., Bosco, E., Monachesi, M., Carta, G., Boschetti, M., Ceresola, E., Venier, E., Calcaterra, F., Cataldi, F., Miola, M., Manfrini, S., Lai, A., Locci, B., Putzu, D., Tanganelli, I., Leonini, M., Egger, K., Marchiotto, W., Vincis, L., Orlandini, V., Pilloni, C., Farci, R., Pelligra, I., Renier, G., Mameli, M., Pala, A., Devigus, E., Fumagalli, I., Lalli, C., Leandri, M., Agliani, M., De Pascalis, L., Malci, F., De Ciocchis, A., Diodati, M. B., Macerola, B., Davì, S., Caccavale, A., Brocato, L., Pognant Gros, M., Borla, S., Lattanzi, E., Piersanti, C., Piersanti, A., Spinelli, I., Tuzzoli, L., Tulini, V., Quaranta, G., Iorio, V., Tirabovi, M., De Terlizi, Candia, Massarelli, M. G., Venturi, S., Travaglini, A., Draghi, P., Pomante, P., Richiardi, L., Clerico, A., Bruno, A., Cavallo Perin, P., Ghigo, E., Porta, M., Scuntero, P., Arcari, R., Bertaina, S., Bo, S., Broglio, F., Bruno, G., Degiovanni, M., Fornengo, P., Grassi, G., Inglese, V., Maccario, M., Maghenzani, G., Marena, S., Martina, V., Passera, P., Ruiu, G., Tagliabue, M., Zanone, M., Monge, M., Boffano, G. M., Macrì, K., Maio, P., Ozzello, A., Pergolizzi, E., Gaia, D., Gennari, P., Micali, G., Rossetto, E., Dalmazzo, C., Oreglia, M., Stefani, T., Dossena, C., Paglia, P., Bosoni, S., Romanelli, T., Inchiostro, S., Dauriz, M., Bossi, C. A., Meregalli, G., Balini, A., Berzi, D., Filippini, B., Crotto, G., Paccagnella, A., Orrasch, M., Sambataro, M., Citro, T., Kiwanuka, E., Bagolin, E., Almoto, B., Macchia, A., Branca, M. T., Filesi, M., Candido, R., Caroli, E., Manca, E., Petrucco, A., Tommasi, E., Jagodnik, G., Baskar, B., Daris, N., Dal Col, P., Pellegrini, M. A., Tonutti, L., Venturini, G., Andreani, M., Turchi, F., Fedrighelli, F., Martinelli, G., Rongioletti, R., Candidi, M., Pais, M., Moro, E., Cervellino, F., Sinisi, R., Zampino, A., Mingardi, R., Lora, L., Reitano, R., Stocchiero, C., Simoncini, M., Mesturino, C. A., Zen, F., Di Pietro, S., Scoponi, C., Tilaro, L., Pelliccioni, S., Slongo, R., Vita, E., Garofalo, A., Vitale, F., Campanella, B., Mastrilli, V., Borrelli, T., D'Avino, A., Perbellini, A., Mirijello, Antonio, Viazzi, Francesca, Fioretto, Paola, Giorda, Carlo, Ceriello, Antonio, Russo, Giuspina T, Guida, Pietro, Pontremoli, Roberto, and De Cosmo, Salvatore, Giordano, Carla
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Adult ,Male ,Nephrology ,medicine.medical_specialty ,endocrine system diseases ,Renal function ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,lcsh:RC870-923 ,Kidney ,urologic and male genital diseases ,GFR ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Albuminuria ,Diabetic kidney disease ,Type 1 diabetes ,urogenital system ,business.industry ,Incidence (epidemiology) ,Middle Aged ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,female genital diseases and pregnancy complications ,Albuminuria, Diabetic kidney disease, GFR, Nephrology ,Diabetes Mellitus, Type 1 ,medicine.anatomical_structure ,Italy ,Disease Progression ,Female ,medicine.symptom ,business ,Research Article ,Follow-Up Studies ,Glomerular Filtration Rate ,Kidney disease - Abstract
Background Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage ≥3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage ≥3 CKD in a large cohort of patients affected by T1DM. Methods A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage ≥3 CKD (eGFR 30% from baseline was evaluated. Results The mean estimated GFR was 98 ± 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions Albuminuria and eGFR reduction represent independent risk factors for incident stage ≥3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening. Electronic supplementary material The online version of this article (10.1186/s12882-018-1136-6) contains supplementary material, which is available to authorized users.
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- 2018
12. An overview of anti-diabetic plants used in Gabon: Pharmacology and toxicology
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Bading Taika, B., primary, Bouckandou, M., additional, Souza, A., additional, Bourobou Bourobou, H.P., additional, MacKenzie, L.S., additional, and Lione, L., additional
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- 2018
- Full Text
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13. AMD Annals: a model of continuous monitoring and improvement of the quality of diabetes care
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Cimino A, de Bigontina G, Fava D, Giorda C, Meloncelli I, Nicolucci A, Pellegrini F, Rossi MC, Arcangeli A, Vespasiani G, Graziano G, Memmo R, Pellicciotta E, Pipitone A, Bodner E, Bonanome A, Testa I, Boemi M, Giansanti R, Romagnoli F, Testa R, Rabini R, Brandoni G, Paciotti V, Alfidi P, Verdecchia B, Marangoni A, Pianta A, Ferrari M, Bertone V, Capellini C, Camozzi D, Remondini E, Laffi G, Ciavarella A, Giangiulio S, Grimaldi M, Mustacchio A, Santacroce G, Marini F, Bondesan L, Valentini U, Rocca L, Girelli A, Zarra E, Agosti B, Corsini R, De Blasi G, Bergmann M, Trinchera A, Masi G, Macchitella V, Mancuso C, Trisciuzzi L, Viehweider B, Carboni L, Turco MP, Delogu A, Floris M, Murtas MG, Farris L, Manai M, Spanu F, Songini M, Piras G, Seguro R, Floris R, Corona R, Lai M, Lostia S, Piras E, Dolci M, Mori M, Baccetti F, Gregori G, Capretti L, Speroni G, Carbone A, Fugazza L, Pozzuoli G, Laudato M, Barone M, Stasio G, Grosso J, Di Nardo B, Rossi L, Sciulli A, Confortin L, Marin N, Lamonica M, Lorenti I, Starnone V, Del Buono A, Terracciano AM, Boscolo Bariga A, Ballarin G, Nogara A, De Boni S, Chiambretti A, Fornengo R, Mularoni EM, Rocca A, Rumi P, Balzarini B, Pellegrini MA, Noacco C, Tonutti L, Venturini G, Santantonio G, Baldi G, Massa L, Ghilardi G, Fiorina P, Massafra C, Lovagnini Scher A, Panebianco G, Tadiotto F, Gaiti D, Bosi EA, Chierici G, Pilla S, Copelli M, Zanichelli P, Bertelli L, Caretta P, Vezzani V, Bodecchi S, Longobucco A, Ruggeri P, Mondani A, Persico R, Rossi C, Magro G, Musacchio N, Giancaterini A, Marelli G, Placentino G, Richini D, Molinari S, Strazzeri R, D'Ambrosio M, Da Tos V, Cotti L, Garrapa G, Foglini P, Bedetta C, Tortato E, Pantanetti P, Manicotti R, Forte E, Marrocco C, Torri A, Sommariva D, Taboga C, Catone B, Ghisoni G, Fabbri F, Torresan M, Marina R, Campobasso G, D'Ugo E, Merni M, Brunato B, Rossi M, Sabbatini G, Quadri F, Sambuco L, Iannarelli R, Pupillo M, De Luca A, Antenucci D, Minnucci A, Di Florio C, Carnevale A, Angelicola G, Bosco A, Fresco R, Di Marco G, Cogo L, Meniconi R, Bertoli S, Cosimi S, Giannini F, di Carlo A, Casadidio I, Maolo G, Polenta B, Bruglia M, Vincenti C, Sciangula L, Banfi E, Ciucci A, Contartese A, Menicatti L, Tatti P, Bloise D, Di Mauro P, Masselli L, Lo Presti A, Scarpitta AM, Gambina F, Venezia A, Morea R, Lagonigro G, Saitta G, Cucinotta D, Di Benedetto A, Pata P, Mancuso T, Zocca A, Aiello B, Picca M, Testori G, Rampini P, Cerutti N, Mariani G, Ragonesi PD, Bollati P, Colapinto P, Comoglio M, Manti G, Cernigoi AM, Tortul C, Volpi A, Coracina A, Cospite AM, Manicardi V, Michelini M, Finardi L, Galliani S, Cilloni R, Iemmi M, Lombardi S, Mattarello MJ, Gatti A, Giannettina R, Gobbo M, Bonavita M, Creso E, Turco S, Turco AA, Iovine C, De Natale C, Zenari L, Bertulini L, Sorgato C, Saglietti G, Schellino A, Mastinu F, Cossu M, Madau G, Mulas MF, Zuccheddu S, Torchio G, Palumbo P, Bianchi A, Mattina G, Zavaroni I, Dei Cas I, Franzini L, Usberti E, Antonimi M, Anelli N, Poli R, Picchio E, Del Sindaco P, Spalluto A, Maggiulli L, Ricciardelli L, La Penna G, Gelisio R, Vinci C, Ianni L, Lorenzetti M, Marsocci A, Di Bartolo P, Scaramuzza A, Melandri P, Giovannini C, Rastelli E, Leotta S, Suraci C, Visalli N, Gagliardi A, Fontana L, Altomare M, Carletti S, Abbruzzese S, Chiaramonte F, Giordano R, Rossini M, Migneco G, Piergiovanni F, Simonetta A, Massimiani F, Bulzomì R, Armentano G, Restuccia MG, Genovese S, Locatelli F, Croato T, Nicoletti M, Trojan N, Li Volsi P, Zanette G, Clementi L, Galetta M, Santangelo M, Bordin P, Perale L, Zanon M, Sica V, Sturaro R, Raffa M, Lione L, Calcaterra F, Cataldi F, Miola M, Manfrini S, Rilli S, Tanganelli I, Felace G, Fumagalli I, Divizia G, Agliani M, Travaglini A, Draghi P, Acler P, Romanelli T, Inchiostro S, Candido R, Caroli E, Manca E, Petrucco A, Da Ros R, Da Col P, Tommasi E, Daris N, Cogliatti MG, Pianca A, Fragiacomo E, Vasta M, Sudano M, Pronti MG, Martinelli G, Andreani M, Ciandrini G, Lani S, Bogazzi AR, Bendinelli G, Pais M, Moro E, Cervellino F, Zampino A, Sinisi R, Mingardi R, Lora L, Stocchiero C, Basso A, Brun E, Strazzabosco M, Simoncini M, Grigoletto C, Zen F, Mesturino C.A., GENTILE, Sandro, Cimino, A, de Bigontina, G, Fava, D, Giorda, C, Meloncelli, I, Nicolucci, A, Pellegrini, F, Rossi, Mc, Gentile, Sandro, Arcangeli, A, Vespasiani, G, Graziano, G, Memmo, R, Pellicciotta, E, Pipitone, A, Bodner, E, Bonanome, A, Testa, I, Boemi, M, Giansanti, R, Romagnoli, F, Testa, R, Rabini, R, Brandoni, G, Paciotti, V, Alfidi, P, Verdecchia, B, Marangoni, A, Pianta, A, Ferrari, M, Bertone, V, Capellini, C, Camozzi, D, Remondini, E, Laffi, G, Ciavarella, A, Giangiulio, S, Grimaldi, M, Mustacchio, A, Santacroce, G, Marini, F, Bondesan, L, Valentini, U, Rocca, L, Girelli, A, Zarra, E, Agosti, B, Corsini, R, De Blasi, G, Bergmann, M, Trinchera, A, Masi, G, Macchitella, V, Mancuso, C, Trisciuzzi, L, Viehweider, B, Carboni, L, Turco, Mp, Delogu, A, Floris, M, Murtas, Mg, Farris, L, Manai, M, Spanu, F, Songini, M, Piras, G, Seguro, R, Floris, R, Corona, R, Lai, M, Lostia, S, Piras, E, Dolci, M, Mori, M, Baccetti, F, Gregori, G, Capretti, L, Speroni, G, Carbone, A, Fugazza, L, Pozzuoli, G, Laudato, M, Barone, M, Stasio, G, Grosso, J, Di Nardo, B, Rossi, L, Sciulli, A, Confortin, L, Marin, N, Lamonica, M, Lorenti, I, Starnone, V, Del Buono, A, Terracciano, Am, Boscolo Bariga, A, Ballarin, G, Nogara, A, De Boni, S, Chiambretti, A, Fornengo, R, Mularoni, Em, Rocca, A, Rumi, P, Balzarini, B, Pellegrini, Ma, Noacco, C, Tonutti, L, Venturini, G, Santantonio, G, Baldi, G, Massa, L, Ghilardi, G, Fiorina, P, Massafra, C, Lovagnini Scher, A, Panebianco, G, Tadiotto, F, Gaiti, D, Bosi, Ea, Chierici, G, Pilla, S, Copelli, M, Zanichelli, P, Bertelli, L, Caretta, P, Vezzani, V, Bodecchi, S, Longobucco, A, Ruggeri, P, Mondani, A, Persico, R, Rossi, C, Magro, G, Musacchio, N, Giancaterini, A, Marelli, G, Placentino, G, Richini, D, Molinari, S, Strazzeri, R, D'Ambrosio, M, Da Tos, V, Cotti, L, Garrapa, G, Foglini, P, Bedetta, C, Tortato, E, Pantanetti, P, Manicotti, R, Forte, E, Marrocco, C, Torri, A, Sommariva, D, Taboga, C, Catone, B, Ghisoni, G, Fabbri, F, Torresan, M, Marina, R, Campobasso, G, D'Ugo, E, Merni, M, Brunato, B, Rossi, M, Sabbatini, G, Quadri, F, Sambuco, L, Iannarelli, R, Pupillo, M, De Luca, A, Antenucci, D, Minnucci, A, Di Florio, C, Carnevale, A, Angelicola, G, Bosco, A, Fresco, R, Di Marco, G, Cogo, L, Meniconi, R, Bertoli, S, Cosimi, S, Giannini, F, di Carlo, A, Casadidio, I, Maolo, G, Polenta, B, Bruglia, M, Vincenti, C, Sciangula, L, Banfi, E, Ciucci, A, Contartese, A, Menicatti, L, Tatti, P, Bloise, D, Di Mauro, P, Masselli, L, Lo Presti, A, Scarpitta, Am, Gambina, F, Venezia, A, Morea, R, Lagonigro, G, Saitta, G, Cucinotta, D, Di Benedetto, A, Pata, P, Mancuso, T, Zocca, A, Aiello, B, Picca, M, Testori, G, Rampini, P, Cerutti, N, Mariani, G, Ragonesi, Pd, Bollati, P, Colapinto, P, Comoglio, M, Manti, G, Cernigoi, Am, Tortul, C, Volpi, A, Coracina, A, Cospite, Am, Manicardi, V, Michelini, M, Finardi, L, Galliani, S, Cilloni, R, Iemmi, M, Lombardi, S, Mattarello, Mj, Gatti, A, Giannettina, R, Gobbo, M, Bonavita, M, Creso, E, Turco, S, Turco, Aa, Iovine, C, De Natale, C, Zenari, L, Bertulini, L, Sorgato, C, Saglietti, G, Schellino, A, Mastinu, F, Cossu, M, Madau, G, Mulas, Mf, Zuccheddu, S, Torchio, G, Palumbo, P, Bianchi, A, Mattina, G, Zavaroni, I, Dei Cas, I, Franzini, L, Usberti, E, Antonimi, M, Anelli, N, Poli, R, Picchio, E, Del Sindaco, P, Spalluto, A, Maggiulli, L, Ricciardelli, L, La Penna, G, Gelisio, R, Vinci, C, Ianni, L, Lorenzetti, M, Marsocci, A, Di Bartolo, P, Scaramuzza, A, Melandri, P, Giovannini, C, Rastelli, E, Leotta, S, Suraci, C, Visalli, N, Gagliardi, A, Fontana, L, Altomare, M, Carletti, S, Abbruzzese, S, Chiaramonte, F, Giordano, R, Rossini, M, Migneco, G, Piergiovanni, F, Simonetta, A, Massimiani, F, Bulzomì, R, Armentano, G, Restuccia, Mg, Genovese, S, Locatelli, F, Croato, T, Nicoletti, M, Trojan, N, Li Volsi, P, Zanette, G, Clementi, L, Galetta, M, Santangelo, M, Bordin, P, Perale, L, Zanon, M, Sica, V, Sturaro, R, Raffa, M, Lione, L, Calcaterra, F, Cataldi, F, Miola, M, Manfrini, S, Rilli, S, Tanganelli, I, Felace, G, Fumagalli, I, Divizia, G, Agliani, M, Travaglini, A, Draghi, P, Acler, P, Romanelli, T, Inchiostro, S, Candido, R, Caroli, E, Manca, E, Petrucco, A, Da Ros, R, Da Col, P, Tommasi, E, Daris, N, Cogliatti, Mg, Pianca, A, Fragiacomo, E, Vasta, M, Sudano, M, Pronti, Mg, Martinelli, G, Andreani, M, Ciandrini, G, Lani, S, Bogazzi, Ar, Bendinelli, G, Pais, M, Moro, E, Cervellino, F, Zampino, A, Sinisi, R, Mingardi, R, Lora, L, Stocchiero, C, Basso, A, Brun, E, Strazzabosco, M, Simoncini, M, Grigoletto, C, Zen, F, and Mesturino, C. A.
- Published
- 2011
14. Application of the hydraulic shaking system to isolation of human pancreatic islets
- Author
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Viviani, GIORGIO LUCIANO, Bottino, R., Zecchi, A., Sanna, R., Cavo, M., Fontana, I., Arcuri, V., Lione, L., Valente, U., and Adezati, L.
- Published
- 1994
15. Indipendence of morphological and functional aspects of pseudoislets from gel collagen matrix. cell
- Author
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Cavo, M., Lione, L., Falzetti, G., Adezati, L., and Viviani, GIORGIO LUCIANO
- Published
- 1993
16. OC3.03.1 T-CELL SELECTIVE INHIBITION OF GUT PRO-INFLAMMATORY CYTOKINE PRODUCTION BY A CA2+ RELEASE-ACTIVATED CA2+ CHANNEL (CRAC) BLOCKER IN INFLAMMATORY BOWEL DISEASE (IBD)
- Author
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Di Sabatino, A., primary, Kruidenier, L., additional, Rovedatti, L., additional, Leakey, N., additional, Wilson, M., additional, Lione, L., additional, Knowles, C., additional, Lee, K., additional, Corazza, G.R., additional, Mc Lean, P., additional, and Mac Donald, T.T., additional
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- 2008
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17. Isolation of pig pancreatic islets by a new method with hydraulic shaking
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Viviani, GIORGIO LUCIANO, Fontana, I., Zecchi, A., Bottino, R., Sanna, R., Lione, L., Sacchi, G., Falzetti, G., Valente, U., and Adezati, L.
- Published
- 1992
18. Oral Tolerance and Allografts: Can Multiple Oral Administrations of Low Doses of Highly Purified Islets Induce Peripheral Tolerance in Pancreatic Islet Allografts?
- Author
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Senesi, B, primary, Curiale, V, additional, Lione, L, additional, Puddu, A, additional, Pedemonte, A, additional, Pastorino, A, additional, and Viviani, G.L, additional
- Published
- 1998
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19. Imidazoline receptors: CNS pharmacology and clinical relevance
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Nutt, D.J., primary, Hudson, A., additional, Husbands, S., additional, Jackson, H.C., additional, Lione, L., additional, Lalies, M.D., additional, Lewis, J., additional, and Reynolds, G., additional
- Published
- 1996
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- View/download PDF
20. Functional Studies of Specific Imidazoline-2 Receptor Ligands
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NUTT, D. J., primary, FRENCH, N., additional, HANDLEY, S., additional, HUDSON, A., additional, HUSBANDS, S., additional, JACKSON, H., additional, JORDAN, S., additional, LALIES, M. D., additional, LEWIS, J., additional, LIONE, L., additional, MALLARD, N., additional, and PRATT, J., additional
- Published
- 1995
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21. Novel Selective Compounds for the Investigation of Imidazoline Receptorsa.
- Author
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HUDSON, A. L., GOUGH, R., TYACKE, R., LIONE, L., LALIES, M., LEWIS, J., HUSBANDS, S., KNIGHT, P., MURRAY, F., HUTSON, P., and NUTT, D. J.
- Published
- 1999
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22. Characterisation and localisation of [^3H]2-(2-benzofuranyl)-2-imidazoline binding in rat brain: a selective ligand for imidazoline I~2 receptors
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Lione, L. A., Nutt, D. J., and Hudson, A. L.
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- 1998
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23. Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation
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Lione, L. A., Carter, R. J., Hunt, M. J., Bates, G. P., Morton, A. J., and Stephen Dunnett
24. Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation
- Author
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Murphy, K. P. S. J., Carter, R. J., Lione, L. A., Mangiarini, L., Mahal, A., Bates, G. P., Stephen Dunnett, and Jennifer Morton, A.
25. Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation
- Author
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Carter, R. J., Lione, L. A., Humby, T., Mangiarini, L., Mahal, A., Gillian Bates, Dunnett, S. B., and Jennifer Morton, A.
- Subjects
RC0321 ,BF - Abstract
Transgenic mice expressing exon 1 of the human Huntington’s disease (HD) gene carrying a 141–157 CAG repeat (line R6/2) develop a progressive neurological phenotype with motor symptoms resembling those seen in HD. We have characterized the motor deficits in R6/2 mice using a battery of behavioral tests selected to measure motor aspects of swimming, fore- and hindlimb coordination, balance, and sensorimotor gating [swimming tank, rotarod, raised beam, fore- and hindpaw footprinting, and acoustic startle/prepulse inhibition (PPI)]. Behavioral testing was performed on female hemizygotic R6/2 transgenic mice (n = 9) and female wild-type littermates (n = 22) between 5 and 14 weeks of age. Transgenic mice did not show an overt behavioral phenotype until around 8 weeks of age. However, as early as 5–6 weeks of age they had significant difficulty swimming, traversing the narrowest square (5 mm) raised beam, and maintaining balance on the rotarod at rotation speeds of 33–44 rpm. Furthermore, they showed significant impairment in prepulse inhibition (an impairment also seen in patients with HD). Between 8 and 15 weeks, R6/2 transgenic mice showed a progressive deterioration in performance on all of the motor tests. Thus R6/2 mice show measurable deficits in motor behavior that begin subtly and increase progressively until death. Our data support the use of R6/2 mice as a model of HD and indicate that they may be useful for evaluating therapeutic strategies for HD, particularly those aimed at reducing the severity of motor symptoms or slowing the course of the disease.
26. Rat serum improves rat pseudoislet formation and insulin gene expression
- Author
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Lione, L., Alessandra Puddu, Pedemonte, A., and Viviani, G. L.
27. Application of the hydraulic shaking system method to isolation of human pancreatic islets
- Author
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Giorgio Luciano Viviani, Bottino, R., Zecchi, A., Sanna, R., Cavo, M., Fontana, I., Arcuri, V., Lione, L., Stubinski, R., Falzetti, G., Valente, U., and Adezati, L.
28. S-27-2 - Imidazoline receptors: CNS pharmacology and clinical relevance
- Author
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Nutt, D.J., Hudson, A., Husbands, S., Jackson, H.C., Lione, L., Lalies, M.D., Lewis, J., and Reynolds, G.
- Published
- 1996
- Full Text
- View/download PDF
29. COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models
- Author
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Abraham Nyska, Alessia Muzi, Fabio Palombo, Luigi Aurisicchio, Mirela Kuka, Nicola Clementi, Concetta Castilletti, Valerio Chiarini, Erika Salvatori, Emanuele Marra, Alina Seidel, Francesca Colavita, Roberto Arriga, Valeria Fumagalli, Giulia Matusali, Laura Luberto, Lorena Donnici, Maria Lucrezia Pacello, Davide Marotta, Fabiana Fosca Ferrara, Eleonora Sala, Amy Rose Challis, Nicasio Mancini, Mariano Maffei, Eleonora Pinto, Gennaro Ciliberto, Emiliano Pavoni, Daniela Stoppoloni, Giuseppe Roscilli, Matteo Iannacone, Emanuela D’Acunto, Lucia Lione, Rüdiger Groß, Lukas Wettstein, Antonella Conforti, Federica Bucci, Elisa Bono, Jemma Paterson, Maria Rosaria Capobianchi, Gianfranco Caselli, Kathryn A. Ryan, Grazia Vitagliano, Jan Münch, Lucio C. Rovati, Matteo Conti, Giuseppe Ippolito, Elena Criscuolo, Chiara Perucchini, Micol Ravà, Manuela Cappelletti, Pietro Di Lucia, Leonardo Giustini, Raffaele De Francesco, Luca G. Guidotti, Mirco Compagnone, Conforti, A., Marra, E., Palombo, F., Roscilli, G., Rava, M., Fumagalli, V., Muzi, A., Maffei, M., Luberto, L., Lione, L., Salvatori, E., Compagnone, M., Pinto, E., Pavoni, E., Bucci, F., Vitagliano, G., Stoppoloni, D., Pacello, M. L., Cappelletti, M., Ferrara, F. F., D'Acunto, E., Chiarini, V., Arriga, R., Nyska, A., Di Lucia, P., Marotta, D., Bono, E., Giustini, L., Sala, E., Perucchini, C., Paterson, J., Ryan, K. A., Challis, A. -R., Matusali, G., Colavita, F., Caselli, G., Criscuolo, E., Clementi, N., Mancini, N., Gross, R., Seidel, A., Wettstein, L., Munch, J., Donnici, L., Conti, M., De Francesco, R., Kuka, M., Ciliberto, G., Castilletti, C., Capobianchi, M. R., Ippolito, G., Guidotti, L. G., Rovati, L., Iannacone, M., and Aurisicchio, L.
- Subjects
Genetically modified mouse ,DNA vaccine ,COVID-19 Vaccines ,Mice, Transgenic ,Antibodies, Viral ,DNA vaccination ,Rats, Sprague-Dawley ,Mice ,Plasmid ,Protein Domains ,Complementary DNA ,Drug Discovery ,Genetics ,Vaccines, DNA ,Animals ,Humans ,Neutralizing antibody ,Molecular Biology ,Pharmacology ,Mice, Inbred BALB C ,biology ,SARS-CoV-2 ,Electroporation ,Immunogenicity ,Ferrets ,COVID-19 ,protection ,Virology ,Antibodies, Neutralizing ,animal models ,antiviral immunity ,Mice, Inbred C57BL ,Viral replication ,Models, Animal ,Spike Glycoprotein, Coronavirus ,biology.protein ,Molecular Medicine ,Female ,Immunization ,Original Article - Abstract
The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax—a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein receptor-binding domain (RBD)—induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function, and lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started., Graphical abstract, We report the development, characterization, and preclinical evaluation of COVID-eVax, a novel COVID-19 vaccine candidate with improved supply and logistics profiles. The technology is based on the electroporation of engineered, synthetic cDNA encoding a secreted monomeric form of the receptor-binding domain of the SARS-CoV-2 spike protein.
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30. A new vessel filled and heart-beating human corpse model for VATS lobectomy training.
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Verzeletti V, Lione L, Bonis A, Sella N, Cannone G, Melan L, Rebusso A, Faccioli E, Porzionato A, Comacchio GM, Nicotra S, Dell'Amore A, and Rea F
- Subjects
- Humans, Simulation Training methods, Models, Anatomic, Clinical Competence, Pulmonary Artery surgery, Internship and Residency methods, Thoracic Surgery, Video-Assisted education, Thoracic Surgery, Video-Assisted methods, Pneumonectomy methods, Pneumonectomy education, Cadaver
- Abstract
Background: Nowadays, video-assisted thoracic surgery (VATS) lobectomy represents the treatment of choice for early-stage lung cancer. Over the years, different methods for VATS training have evolved. The aim of this study is to present an innovative beating-heart filled-vessel cadaveric model to simulate VATS lobectomies., Methods: Via selective cannulation of the cadaver heart, the pulmonary vessels were filled with a gel to improve their haptic feedback. An endotracheal tube with a balloon on its tip then allowed movement of the heart chambers, transmitting a minimum of flow to the pulmonary vessels. A simulated OR was created, using all instrumentation normally available during surgery on living patients, with trainees constantly mentored by experienced surgeons. At the end of each simulation, the participants were asked 5 questions on a scale of 1 to 10 to evaluate the effectiveness of the training method ("1" being ineffective and "10" being highly effective)., Results: Eight models were set up, each with a median time of 108 min and a cost of €1500. Overall, 50 surgeons were involved, of which 39 (78%) were consultants and 11 (22%) were residents (PGY 3-5). The median scores for the 5 questions were 8.5 (Q1; IQR
1-3 8-9), 8 (Q2; IQR1-3 7-9), 9 (Q3; IQR1-3 8-10), 9 (Q4; IQR1-3 8-10), and 9 (Q5; IQR1-3 8-10). Overall, the model was most appreciated by young trainees even though positive responses were also provided by senior surgeons., Conclusions: We introduce a new beating-heart filled-vessel cadaveric model to simulate VATS lobectomies. From this initial experience, the model is cost effective, smooth to develop, and realistic for VATS simulation., (© 2024. The Author(s).)- Published
- 2024
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31. Tumor inflammatory microenvironment contribution to survival in resected upstaged adenocarcinomas.
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Bonis A, Verzeletti V, Lunardi F, Lione L, Cannone G, Faccioli E, Mammana M, Nicotra S, Calabrese F, Dell'Amore A, and Rea F
- Subjects
- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Neoplasm Staging, Adenocarcinoma of Lung surgery, Adenocarcinoma of Lung pathology, Adenocarcinoma of Lung immunology, Adenocarcinoma of Lung mortality, Survival Rate, Pneumonectomy, Adenocarcinoma surgery, Adenocarcinoma pathology, Adenocarcinoma mortality, Adenocarcinoma immunology, Tumor Microenvironment immunology, Lung Neoplasms pathology, Lung Neoplasms surgery, Lung Neoplasms mortality, Lung Neoplasms immunology, Lymphocytes, Tumor-Infiltrating immunology, B7-H1 Antigen metabolism
- Abstract
Introduction: Tumor Inflammatory microenvironment (TIME) encompasses several immune pathways modulating cancer development and escape that are not entirely uncoded. The results achieved with immunotherapy elicited the scientific debate on TIME also in non-small cell lung cancer (NSCLC). We aimed to investigate whether TIME (in terms of PD-L1 expression and/or Tumor Infiltrating Lymphocytes - TILs) played a separate role in terms of survival (OS) in resected upstaged lung adenocarcinomas (ADCs), excluding other perioperative variables as confounders., Materials and Methods: This retrospective study included 50 patients with a clinically resectable lung ADC, undergoing surgery (lobectomy or segmentectomy) at the Thoracic Unit of Padova University Hospital between 2016 and 2022 and receiving an unexpected pathological upstaging (IIB or higher)., Results: Despite microscopical variables increasing from IIB to IIIB, survival was not significantly related to them. OS was better in TIME-active patients (defined as the presence of positive PD-L1 and/or TILs>10 %) than double negatives (PD-L1-/TILs-) (p = 0.01). In IIB or higher ADCs, TIME-active patients showed an improved survival compared to double negatives, merging the current TIME theories., Conclusion: TIME seems to be associated with survival independently from other microscopical parameter, even in case of resected upstaged adenocarcinomas., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)
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- 2024
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32. Thoracic Ultrasound as an Alternative to Chest X-ray in Thoracic Surgery Patients: A Single-Center Experience.
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Lione L, Busetto A, Verzeletti V, Cannone G, Bonis A, Berni A, Gasparini D, Mammana M, Rebusso A, Nicotra S, Gregori D, Dell'Amore A, and Rea F
- Abstract
Background/Objectives : Chest X-ray (CXR) is currently the most used investigation for clinical follow-up after major noncardiac thoracic surgery. This study explores the use of lung ultrasound (LUS) as an alternative to CXR in the postoperative management of patients who undergo major thoracic procedures. Methods : The patients in our cohort were monitored with both a CXR and a lung ultrasonography after surgery and the day after chest drain removal. The LUS was performed by a member of the medical staff of our unit who was blinded to both the images and the radiologist's report of the CXR. Findings were compared between the two methods. Results : In the immediate postoperative evaluation, 280 patients were compared, finding general agreement between the two procedures at 84% (kappa statistic, 0.603). The LUS showed a sensibility of 84.1%, a specificity of 84.3%, a positive predictive value (PPV) of 60.9%, and a negative predictive value (NPV) of 94.8%. We evaluated 219 out of 280 patients in the postdrainage-removal setting due to technical issues. Concordance between the methods in the postdrainage-removal setting was 89% (kappa statistic, 0.761) with the LUS demonstrating an 82.2% sensibility, a 93.2% specificity, a PPV of 85.7%, and an NPV of 91.3%. Conclusions : The results of this study showed a substantial agreement between LUS and CXR, suggesting that the LUS could reduce the number of X rays in certain conditions. The high NPV allows for the exclusion of PNX and pleural effusion without the need to expose patients to radiation. Discrepancies were noted in cases of mild pneumothorax or modest pleural effusion, without altering the clinical approach.
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- 2024
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33. Right re-redo video-assisted thoracoscopic surgery lower lobectomy with middle lobe preservation for recurrent and metachronous lung adenocarcinoma.
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Nicotra S, Verzeletti V, Cannone G, Lione L, and Rea F
- Abstract
Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
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- 2023
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34. Three-Dimensional Imaging-Guided Lung Anatomic Segmentectomy: A Single-Center Preliminary Experiment.
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Cannone G, Verzeletti V, Busetto A, Lione L, Bonis A, Nicotra S, Rebusso A, Mammana M, Schiavon M, Dell'Amore A, and Rea F
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- Male, Female, Humans, Pneumonectomy, Imaging, Three-Dimensional methods, Lung pathology, Retrospective Studies, Lung Neoplasms diagnostic imaging, Lung Neoplasms surgery, Lung Neoplasms pathology, Carcinoma, Non-Small-Cell Lung surgery
- Abstract
Background and objectives : VATS segmentectomy has been proven to be effective in the treatment of stage I NSCLC, but its technical complexity remains one of the most challenging aspects for thoracic surgeons. Furthermore, 3D-CT reconstruction images can help in planning and performing surgical procedures. In this paper, we present our personal experience of 11 VATS anatomical resections performed after accurate pre-operative planning with 3D reconstructions. Materials and methods : A 3D virtual model of the lungs, airways, and vasculature was obtained, starting from a 1.25 mm 3-phase contrast CT scan, and the original images were used for the semi-automatic segmentation of the lung parenchyma, airways, and tumor. Results : Six males and five females were included in this study. The median diameter of the pulmonary lesion at the pre-operative chest CT scan was 20 mm. The surgical indication was confirmed in seven patients: in three cases, a lobectomy, instead of a segmentectomy, was needed due to intraoperative findings of nodal metastasis. Meanwhile, only in one case, we performed a lobectomy because of inadequate surgical resection margins. Skin-to-skin operative average time was 142 (IQR 1-3 105-182.5) min. The median post-operative stay was 6 (IQR 1-3 3.5-7) days. The mean value of the closest surgical margin was 13.7 mm. Conclusion : Image-guided reconstructions are a useful tool for surgeons to perform complex resections in order to spare healthy parenchyma and to ensure disease-free margins. Nevertheless, human skill and surgeon experience still remain fundamental for the final decisions regarding the proper resection to perform.
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- 2023
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35. Ketamine supresses REM sleep and markedly increases EEG gamma oscillations in the Wistar Kyoto rat model of treatment-resistant depression.
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Kantor S, Lanigan M, Giggins L, Lione L, Magomedova L, de Lannoy I, Upton N, and Duxon M
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- Rats, Animals, Male, Rats, Inbred WKY, Depression, Rats, Sprague-Dawley, Electroencephalography, Antidepressive Agents pharmacology, Sleep physiology, Sleep, REM physiology, Ketamine pharmacology
- Abstract
Wistar-Kyoto (WKY) rats exhibit depression-like characteristics and decreased sensitivity to monoamine-based antidepressants, making them a suitable model of treatment-resistant depression (TRD). Ketamine has emerged recently as a rapidly acting antidepressant with high efficacy in TRD. Our aim was to determine whether subanaesthetic doses of ketamine can correct sleep and electroencephalogram (EEG) alterations in WKY rats and whether any ketamine-induced changes differentially affect WKY rats compared to Sprague-Dawley (SD) rats. Thus, we surgically implanted 8 SD and 8 WKY adult male rats with telemetry transmitters and recorded their EEG, electromyogram, and locomotor activity after vehicle or ketamine (3, 5 or 10 mg/kg, s.c.) treatment. We also monitored the plasma concentration of ketamine and its metabolites, norketamine and hydroxynorketamine in satellite animals. We found that WKY rats have an increased amount of rapid eye movement (REM) sleep, fragmented sleep-wake pattern, and increased EEG delta power during non-REM sleep compared to SD rats. Ketamine suppressed REM sleep and increased EEG gamma power during wakefulness in both strains, but the gamma increase was almost twice as large in WKY rats than in SD rats. Ketamine also increased beta oscillations, but only in WKY rats. These differences in sleep and EEG are unlikely to be caused by dissimilarities in ketamine metabolism as the plasma concentrations of ketamine and its metabolites were similar in both strains. Our data suggest an enhanced antidepressant-like response to ketamine in WKY rats, and further support the predictive validity of acute REM sleep suppression as a measure of antidepressant responsiveness., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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36. New perspectives in management of diabetes in long-term care facilities.
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Sampietro L, Cirone M, Lione L, Gonella D, Testino G, Bottaro LC, and Torre E
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- Humans, Skilled Nursing Facilities, Health Facilities, Long-Term Care, Diabetes Mellitus epidemiology, Diabetes Mellitus therapy
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- 2023
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37. Relevance of Spike/Estrogen Receptor-α interaction for endothelial-based coagulopathy induced by SARS-CoV-2.
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Barbieri SS, Cattani F, Sandrini L, Grillo MM, Amendola A, Valente C, Talarico C, Iaconis D, Turacchio G, Lucariello M, Lione L, Salvatori E, Amadio P, Garoffolo G, Maffei M, Galli F, Beccari AR, Sberna G, Marra E, Zoppi M, Michaelides M, Roscilli G, Aurisicchio L, Bertini R, Allegretti M, and Pesce M
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- Humans, Receptors, Estrogen, Binding Sites, Spike Glycoprotein, Coronavirus genetics, SARS-CoV-2, COVID-19
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- 2023
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38. A linear SARS-CoV-2 DNA vaccine candidate reduces virus shedding in ferrets.
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Martins M, do Nascimento GM, Conforti A, Noll JCG, Impellizeri JA, Sanchez E, Wagner B, Lione L, Salvatori E, Pinto E, Compagnone M, Viscount B, Hayward J, Shorrock C, Aurisicchio L, and Diel DG
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- Humans, Animals, COVID-19 Vaccines, SARS-CoV-2, Ferrets, Virus Shedding, Antibodies, Viral, Antibodies, Neutralizing, DNA, Spike Glycoprotein, Coronavirus genetics, Immunogenicity, Vaccine, COVID-19 prevention & control, Vaccines, DNA genetics, Viral Vaccines
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 760 million cases and over 6.8 million deaths as of March 2023. Vaccination has been the main strategy used to contain the spread of the virus and to prevent hospitalizations and deaths. Currently, two mRNA-based vaccines and one adenovirus-vectored vaccine have been approved and are available for use in the U.S. population. The versatility, low cost, and rapid production of DNA vaccines provide important advantages over other platforms. Additionally, DNA vaccines efficiently induce both B- and T-cell responses by expressing the antigen within transfected host cells, and the antigen, after being processed into peptides, can associate with MHC class I or II of antigen-presenting cells (APCs) to stimulate different T cell responses. However, the efficiency of DNA vaccination needs to be improved for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been used successfully in the field of veterinary oncology, resulting in high rates of response after electrochemotherapy. Here, we evaluate the safety, immunogenicity, and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate delivered by intramuscular injection followed by electroporation (Vet-ePorator™) in ferrets. The linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects. Additionally, the vaccine elicited neutralizing antibodies and T cell responses on day 42 post-immunization using a low dose of the linear DNA construct in a prime-boost regimen. Most importantly, vaccination significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
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- 2023
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39. Immunogenicity of COVID-eVax Delivered by Electroporation Is Moderately Impacted by Temperature and Molecular Isoforms.
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D'Alessio F, Lione L, Salvatori E, Bucci F, Muzi A, Roscilli G, Compagnone M, Pinto E, Battistuzzi G, Conforti A, Aurisicchio L, and Palombo F
- Abstract
DNA integrity is a key issue in gene therapy and genetic vaccine approaches based on plasmid DNA. In contrast to messenger RNA that requires a controlled cold chain for efficacy, DNA molecules are considered to be more stable. In this study, we challenged this concept by characterizing the immunological response induced by a plasmid DNA vaccine delivered using electroporation. As a model, we used COVID-eVax, a plasmid DNA-based vaccine that targets the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Increased nicked DNA was produced by using either an accelerated stability protocol or a lyophilization protocol. Surprisingly, the immune response induced in vivo was only minimally affected by the percentage of open circular DNA. This result suggests that plasmid DNA vaccines, such as COVID-eVax that have recently completed a phase I clinical trial, retain their efficacy upon storage at higher temperatures, and this feature may facilitate their use in low-/middle-income countries.
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- 2023
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40. A linear DNA encoding the SARS-CoV-2 receptor binding domain elicits potent immune response and neutralizing antibodies in domestic cats.
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Conforti A, Sanchez E, Salvatori E, Lione L, Compagnone M, Pinto E, Palombo F, D'Acunto E, Muzi A, Roscilli G, Sun Y, Viscount B, Hayward J, Shorrock C, Diel DG, Impellizeri JA, and Aurisicchio L
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, has been shown to infect a wide range of animal species, especially mammals, and besides human-to-human transmission, human-to-animal transmission has also been observed in some wild animals and pets, especially in cats. It has been demonstrated that cats are permissive to COVID-19 and are susceptible to airborne infections. Given the high transmissibility potential of SARS-CoV-2 to different host species and the close contact between humans and animals, it is crucial to find mechanisms to prevent the transmission chain and reduce the risk of spillover to susceptible species. Here, we show results from a clinical trial conducted in domestic cats to assess safety and immunogenicity of a linear DNA (linDNA) vaccine encoding the receptor-binding domain (RBD) from SARS-CoV-2 (Lin-COVID-eVax). Lin-COVID-eVax proved to be safe, with no significant adverse events, and was able to elicit both RBD-specific antibodies and T cells. Also, the linDNA vaccine induced neutralizing antibody titers against ancestral SARS-CoV-2 virus and its variants. These findings demonstrate the safety and immunogenicity of a genetic vaccine against COVID-19 administered to cats and strongly support the development of vaccines for preventing viral spread in susceptible species, especially those in close contact with humans., Competing Interests: Evvivax, Takis, and NeoMatrix are currently developing proprietary nucleic-acid vaccines based on DNA-EGT. Applied DNA and LineaRx are commercializing LinearDNA, its proprietary, large-scale PCR-based manufacturing platform that allows for the large-scale production of specific DNA sequences for biotherapeutic applications. The company’s common stock is listed on NASDAQ under ticker symbol “APDN,” and its publicly traded warrants are listed on OTC under ticker symbol “APPDW.”, (© 2023 The Authors.)
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- 2023
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41. Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells.
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Manco R, D'Apice L, Trovato M, Lione L, Salvatori E, Pinto E, Compagnone M, Aurisicchio L, De Berardinis P, and Sartorius R
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- Humans, Mice, Animals, CD8-Positive T-Lymphocytes, Galactosylceramides metabolism, Antigens, Neoplasm, Peptides, Mice, Transgenic, Antibodies metabolism, Membrane Proteins metabolism, Neoplasms
- Abstract
Tumor-associated antigens (TAAs) represent attractive targets in the development of anti-cancer vaccines. The filamentous bacteriophage is a safe and versatile delivery nanosystem, and recombinant bacteriophages expressing TAA-derived peptides at a high density on the viral coat proteins improve TAA immunogenicity, triggering effective in vivo anti-tumor responses. To enhance the efficacy of the bacteriophage as an anti-tumor vaccine, we designed and generated phage particles expressing a CD8+ peptide derived from the human cancer germline antigen NY-ESO-1 decorated with the immunologically active lipid alpha-GalactosylCeramide (α-GalCer), a potent activator of invariant natural killer T (iNKT) cells. The immune response to phage expressing the human TAA NY-ESO-1 and delivering α-GalCer, namely fdNY-ESO-1/α-GalCer, was analyzed either in vitro or in vivo, using an HLA-A2 transgenic mouse model (HHK). By using NY-ESO-1-specific TCR-engineered T cells and iNKT hybridoma cells, we observed the efficacy of the fdNY-ESO-1/α-GalCer co-delivery strategy at inducing activation of both the cell subsets. Moreover, in vivo administration of fdNY-ESO-1 decorated with α-GalCer lipid in the absence of adjuvants strongly enhances the expansion of NY-ESO-1-specific CD8+ T cells in HHK mice. In conclusion, the filamentous bacteriophage delivering TAA-derived peptides and the α-GalCer lipid may represent a novel and promising anti-tumor vaccination strategy.
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- 2023
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42. A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19.
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Aurisicchio L, Brambilla N, Cazzaniga ME, Bonfanti P, Milleri S, Ascierto PA, Capici S, Vitalini C, Girolami F, Giacovelli G, Caselli G, Visintin M, Fanti F, Ghirri M, Conforti A, Compagnone M, Lione L, Salvatori E, Pinto E, Muzi A, Marra E, Palombo F, Roscilli G, Manenti A, Montomoli E, Cadossi M, and Rovati LC
- Subjects
- Adult, Humans, Antibodies, Neutralizing, Antibodies, Viral, COVID-19 Vaccines adverse effects, Double-Blind Method, Pandemics prevention & control, SARS-CoV-2, COVID-19 prevention & control, Vaccines, DNA adverse effects
- Abstract
The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Sixty-eight healthy adults received two doses of 0.5, 1, or 2 mg 28 days apart, or a single 2-mg dose, via intramuscular injection followed by electroporation, and they were monitored for 6 months. All participants completed the primary safety and immunogenicity assessments after 8 weeks. COVID-eVax was well tolerated, with mainly mild to moderate solicited adverse events (tenderness, pain, bruising, headache, and malaise/fatigue), less frequent after the second dose, and it induced an immune response (binding antibodies and/or T cells) at all prime-boost doses tested in up to 90% of the volunteers at the highest dose. However, the vaccine did not induce neutralizing antibodies, while particularly relevant was the T cell-mediated immunity, with a robust Th1 response. This T cell-skewed immunological response adds significant information to the DNA vaccine platform and should be assessed in further studies for its protective capacity and potential usefulness also in other therapeutic areas, such as oncology., Competing Interests: Declaration of interests L.A., E.Marra, F.P., G.R., A.C., M.Compagnone, L.L., E.S., E.P., and A.Muzi are Takis employees. L.C.R., F.G., N.B., G.G., G.C., M.V., F.F., M.G., and C.V. are Rottapharm Biotech employees. Takis and Rottapharm Biotech are jointly developing COVID-eVax. M.E.C., P.B., S.M., P.A.A., and S.C. are investigators in this study, and their institutions received fees for participation., (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2023
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43. DNA-Vaccine-Induced Immune Response Correlates with Lower Viral SARS-CoV-2 Titers in a Ferret Model.
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Compagnone M, Pinto E, Salvatori E, Lione L, Conforti A, Marchese S, Ravà M, Ryan K, Hall Y, Rayner E, Salguero FJ, Paterson J, Iannacone M, De Francesco R, Aurisicchio L, and Palombo F
- Abstract
The COVID-19 pandemic is entering a new era with the approval of many SARS-CoV-2 vaccines. In spite of the restoration of an almost normal way of life thanks to the immune protection elicited by these innovative vaccines, we are still facing high viral circulation, with a significant number of deaths. To further explore alternative vaccination platforms, we developed COVID- e Vax-a genetic vaccine based on plasmid DNA encoding the RBD domain of the SARS-CoV-2 spike protein. Here, we describe the correlation between immune responses and the evolution of viral infection in ferrets infected with the live virus. We demonstrate COVID- e Vax immunogenicity as means of antibody response and, above all, a significant T-cell response, thus proving the critical role of T-cell immunity, in addition to the neutralizing antibody activity, in controlling viral spread.
- Published
- 2022
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44. Linear DNA amplicons as a novel cancer vaccine strategy.
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Conforti A, Salvatori E, Lione L, Compagnone M, Pinto E, Shorrock C, Hayward JA, Sun Y, Liang BM, Palombo F, Viscount B, and Aurisicchio L
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- Animals, Antigens, Neoplasm, DNA, HeLa Cells, Humans, Immunotherapy methods, Mice, Cancer Vaccines, Neoplasms drug therapy, Neoplasms therapy, Vaccines, DNA
- Abstract
Background: DNA-based vaccines represent a simple, safe and promising strategy for harnessing the immune system to fight infectious diseases as well as various forms of cancer and thus are considered an important tool in the cancer immunotherapy toolbox. Nonetheless, the manufacture of plasmid DNA vaccines has several drawbacks, including long lead times and the need to remove impurities from bacterial cultures. Here we report the development of polymerase chain reaction (PCR)-produced amplicon expression vectors as DNA vaccines and their in vivo application to elicit antigen-specific immune responses in animal cancer models., Methods: Plasmid DNA and amplicon expression was assessed both in vitro, by Hela cells transfection, and in vivo, by evaluating luciferase expression in wild-type mice through optical imaging. Immunogenicity induced by DNA amplicons was assessed by vaccinating wild-type mice against a tumor-associated antigen, whereas the antitumoral effect of DNA amplicons was evaluated in a murine cancer model in combination with immune-checkpoint inhibitors (ICIs)., Results: Amplicons encoding tumor-associated-antigens, such as telomerase reverse transcriptase or neoantigens expressed by murine tumor cell lines, were able to elicit antigen-specific immune responses and proved to significantly impact tumor growth when administered in combination with ICIs., Conclusions: These results strongly support the further exploration of the use of PCR-based amplicons as an innovative immunotherapeutic approach to cancer treatment., (© 2022. The Author(s).)
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- 2022
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45. Neoantigen cancer vaccine augments anti-CTLA-4 efficacy.
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Salvatori E, Lione L, Compagnone M, Pinto E, Conforti A, Ciliberto G, Aurisicchio L, and Palombo F
- Abstract
Immune checkpoint inhibitors (ICI) based on anti-CTLA-4 (αCTLA-4) and anti-PD1 (αPD1) are being tested in combination with different therapeutic approaches including other immunotherapies such as neoantigen cancer vaccines (NCV). Here we explored, in two cancer murine models, different therapeutic combinations of ICI with personalized DNA vaccines expressing neoantigens and delivered by electroporation (EP). Anti-cancer efficacy was evaluated using vaccines with or without CD4 epitopes. Therapeutic DNA vaccines showed synergistic effects in different therapeutic protocols including established large tumors. Flow cytometry (FC) was utilized to measure CD8, CD4, Treg, and switched B cells as well as neoantigen-specific immune responses, which were also measured by IFN-γ ELIspot. Immune responses were augmented in combination with αCTLA4 but not with αPD1 in the MC38 tumor-bearing mice, significantly impacting tumor growth. Similarly, neoantigen-specific T cell immune responses were enhanced in combined treatment with αCTLA-4 in the CT26 tumor model where large tumors regressed in all mice, while monotherapy with αCTLA-4 was less efficacious. In line with previous evidence, we observed an increased switched B cells in the spleen of mice treated with αCTLA-4 alone or in combination with NCV. These results support the use of NCV delivered by DNA-EP with αCTLA-4 and suggest a new combined therapy for clinical testing., (© 2022. The Author(s).)
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- 2022
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46. COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models.
- Author
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Conforti A, Marra E, Palombo F, Roscilli G, Ravà M, Fumagalli V, Muzi A, Maffei M, Luberto L, Lione L, Salvatori E, Compagnone M, Pinto E, Pavoni E, Bucci F, Vitagliano G, Stoppoloni D, Pacello ML, Cappelletti M, Ferrara FF, D'Acunto E, Chiarini V, Arriga R, Nyska A, Di Lucia P, Marotta D, Bono E, Giustini L, Sala E, Perucchini C, Paterson J, Ryan KA, Challis AR, Matusali G, Colavita F, Caselli G, Criscuolo E, Clementi N, Mancini N, Groß R, Seidel A, Wettstein L, Münch J, Donnici L, Conti M, De Francesco R, Kuka M, Ciliberto G, Castilletti C, Capobianchi MR, Ippolito G, Guidotti LG, Rovati L, Iannacone M, and Aurisicchio L
- Subjects
- Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 genetics, COVID-19 virology, Female, Ferrets, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Protein Domains, Rats, Sprague-Dawley, Rats, COVID-19 prevention & control, COVID-19 Vaccines administration & dosage, Immunization methods, Models, Animal, SARS-CoV-2 isolation & purification, Spike Glycoprotein, Coronavirus immunology, Vaccines, DNA administration & dosage
- Abstract
The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax-a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein receptor-binding domain (RBD)-induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function, and lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started., Competing Interests: Declaration of interests A.C. and M.M. are Evvivax employees. E.M., F.P., G.R., A.M., L.L., L.L., E. Salvatori, M. Cappalletti, F.F.F., E.D., V.C., and L.A. are Takis employees. G. Caselli and L.R. are Rottapharm Biotech employees. Takis and Rottapharm Biotech are jointly developing COVID-eVax. M.I. participates in advisory boards/consultancies for or receives funding from Gilead Sciences, Roche, Third Rock Ventures, Amgen, Allovir, Asher Bio. L.G.G is a member of the board of directors at Genenta Science and Epsilon Bio and participates in advisory boards/consultancies for Gilead Sciences, Roche, and Arbutus Biopharma., (Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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47. Consensus report of the joint workshop of the Italian Society of Diabetology, Italian Society of Periodontology and Implantology, Italian Association of Clinical Diabetologists (SID-SIdP-AMD).
- Author
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Adda G, Aimetti M, Citterio F, Consoli A, Di Bartolo P, Landi L, Lione L, and Luzi L
- Subjects
- Biomarkers blood, Blood Glucose drug effects, Blood Glucose metabolism, Consensus, Glycated Hemoglobin metabolism, Humans, Hypoglycemic Agents therapeutic use, Prevalence, Prognosis, Risk Assessment, Risk Factors, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 epidemiology, Periodontitis diagnosis, Periodontitis epidemiology, Periodontitis therapy, Rheumatology standards
- Abstract
Periodontitis has been defined as the Sixth complication of Diabetes Mellitus. Since both diabetes mellitus and periodontitis have a high prevalence in the general population, the Italian Society of Diabetology, the Italian Society of Periodontology and Implantology and the Italian Association of Clinical Diabetologists revised the present scientific literature in the present consensus report. A bi-directional interaction was demonstrated: Patients affected by type 1 and type 2 diabetes have a higher prevalence of periodontitis than the general population, due to several metabolic factors (e.g. chronic hyperglycemia, autoimmunity, dietary and life-style factors); similarly, periodontitis predisposes to type 2 diabetes mellitus mainly via the increase of systemic cytokines release. Conversely, improvement of metabolic control of diabetic patients delay the progression of periodontitis as well as periodontitis treatment reduces glycosylated hemoglobin levels in blood. Due to the bi-directional causal interaction between periodontitis and diabetes mellitus, a strict collaboration among dentists and diabetologists is required and strongly recommended. The inter-societies consensus proposes specific flow-diagrams to improve the treatment of patients and management of the general population regarding the issue of periodontitis and diabetes., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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48. Antitumor efficacy of a neoantigen cancer vaccine delivered by electroporation is influenced by microbiota composition.
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Lione L, Salvatori E, Petrazzuolo A, Massacci A, Maggio R, Confroti A, Compagnone M, Aurisicchio L, Ciliberto G, and Palombo F
- Subjects
- Antigens, Neoplasm, Electroporation, Immunotherapy, Cancer Vaccines, Microbiota, Neoplasms drug therapy
- Abstract
Cancer is a heterogeneous disease and its treatment remains unsatisfactory with inconstant therapeutic responses. This variability could be related, at least in part, to different and highly personalized gut microbiota compositions. Different studies have shown an impact of microbiota on antitumor therapy. It has been demonstrated that some gut bacteria influences the development and differentiation of immune cells, suggesting that different microbiota compositions could affect the efficacy of the antitumor vaccine. Emerging data suggest that recognition of neoantigens for the generation of neoantigen cancer vaccines (NCVs) could have a key role in the activity of clinical immunotherapies. However, it is still unknown whether there is a crosstalk between microbiota and NCV. This study aimed to understand the possible mechanisms of interaction between gut microbiota and NCV delivered by DNA-electroporation (DNA-EP). We found that decreased microbiota diversity induced by prolonged antibiotic (ATB) treatment is associated with higher intratumor specific immune responses and consequently to a better antitumor effect induced by NCV delivered by DNA-EP., Competing Interests: Authors do not have a conflict of interest to be declared., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)
- Published
- 2021
- Full Text
- View/download PDF
49. Nature of Amorphous Hydrophilic Block Affects Self-Assembly of an Artificial Viral Coat Polypeptide.
- Author
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Willems L, van Westerveld L, Roberts S, Weitzhandler I, Calcines Cruz C, Hernandez-Garcia A, Chilkoti A, Mastrobattista E, van der Oost J, and de Vries R
- Subjects
- Amino Acid Motifs, Capsid Proteins chemistry, Collagen chemistry, Crystallization, Elastin chemistry, Hydrophobic and Hydrophilic Interactions, Silk chemistry, Capsid chemistry, DNA, Viral chemistry, Peptides chemistry, Protein Multimerization
- Abstract
Consensus motifs for sequences of both crystallizable and amorphous blocks in silks and natural structural analogues of silks vary widely. To design novel silklike polypeptides, an important question is therefore how the nature of either the crystallizable or the amorphous block affects the self-assembly and resulting physical properties of silklike polypeptides. We address herein the influence of the amorphous block on the self-assembly of a silklike polypeptide that was previously designed to encapsulate single DNA molecules into rod-shaped viruslike particles. The polypeptide has a triblock architecture, with a long N-terminal amorphous block, a crystallizable midblock, and a C-terminal DNA-binding block. We compare the self-assembly behavior of a triblock with a very hydrophilic collagen-like amorphous block (GXaaYaa)
132 to that of a triblock with a less hydrophilic elastin-like amorphous block (GSGVP)80 . The amorphous blocks have similar lengths and both adopt a random coil structure in solution. Nevertheless, atomic force microscopy revealed significant differences in the self-assembly behavior of the triblocks. If collagen-like amorphous blocks are used, there is a clear distinction between very short polypeptide-only fibrils and much longer fibrils with encapsulated DNA. If elastin-like amorphous blocks are used, DNA is still encapsulated, but the polypeptide-only fibrils are now much longer and their size distribution partially overlaps with that of the encapsulated DNA fibrils. We attribute the difference to the more hydrophilic nature of the collagen-like amorphous block, which more strongly opposes the growth of polypeptide-only fibrils than the elastin-like amorphous blocks. Our work illustrates that differences in the chemical nature of amorphous blocks can strongly influence the self-assembly and hence the functionality of engineered silklike polypeptides.- Published
- 2019
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50. Inducible Fibril Formation of Silk-Elastin Diblocks.
- Author
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Willems L, Roberts S, Weitzhandler I, Chilkoti A, Mastrobattista E, van der Oost J, and de Vries R
- Abstract
Silk-elastin block copolymers have such physical and biological properties that make them attractive biomaterials for applications ranging from tissue regeneration to drug delivery. Silk-elastin block copolymers that only assemble into fibrils at high concentrations can be used for a template-induced fibril assembly. This can be achieved by additionally including template-binding blocks that promote high local concentrations of polymers on the template, leading to a template-induced fibril assembly. We hypothesize that template-inducible silk-fibril formation, and hence high critical concentrations for fibril formation, requires careful tuning of the block lengths, to be close to a critical set of block lengths that separates fibril forming from nonfibril forming polymer architectures. Therefore, we explore herein the impact of tuning block lengths for silk-elastin diblock polypeptides on fibril formation. For silk-elastin diblocks E
S m -SQ n , in which the elastin pentamer repeat is ES = GSGVP and the crystallizable silk octamer repeat is SQ = GAGAGAGQ, we find that no fibril formation occurs for n = 6 but that the n = 10 and 14 diblocks do show concentration-dependent fibril formation. For n = 14 diblocks, no effect is observed of the length m (with m = 40, 60, 80) of the amorphous block on the lengths of the fibrils. In contrast, for the n = 10 diblocks that are closest to the critical boundary for fibril formation, we find that long amorphous blocks ( m = 80) oppose the growth of fibrils at low concentrations, making them suitable for engineering template-inducible fibril formation., Competing Interests: The authors declare no competing financial interest.- Published
- 2019
- Full Text
- View/download PDF
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