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1. Management of cutaneous melanoma: Comparison of the leading international guidelines updated to the 8th American Joint Committee on Cancer staging system and workup proposal by the Italian Society of Dermatology

Author

Argenziano, G., Brancaccio, G., Moscarella, E., Dika, E., Fargnoli, Maria Concetta, Ferrara, Giovanna, Longo, C., Pellacani, G., Peris, Ketty, Pimpinelli, N., Quaglino, P., Rongioletti, F., Simonacci, Matteo, Zalaudek, Iri, Calzavarapinton, P., Fargnoli M. C., Ferrara G., Peris K. (ORCID:0000-0002-5237-0463), Simonacci M., Zalaudek I., Argenziano, G., Brancaccio, G., Moscarella, E., Dika, E., Fargnoli, Maria Concetta, Ferrara, Giovanna, Longo, C., Pellacani, G., Peris, Ketty, Pimpinelli, N., Quaglino, P., Rongioletti, F., Simonacci, Matteo, Zalaudek, Iri, Calzavarapinton, P., Fargnoli M. C., Ferrara G., Peris K. (ORCID:0000-0002-5237-0463), Simonacci M., and Zalaudek I.

Abstract

The melanoma care landscape is changing fast in the last years. As a result of new insights in melanoma biology, prognosis and therapeutic options, both the American Joint Committee on Cancer (AJCC) and the World Health OrgaÂnization (WHO) Classification of Skin Tumors underwent substantial changes in 2018. Consequently, all the leading guidelines on melanoma management have been updated. Most of the recommendations derive from systematic reÂviews, while others are based on expert opinion, due to the lack of high-level evidence in some aspects of melanoma management. We provide a revision of all the available guidelines that have been updated to the 8th version of the AJCC classification system. Comparison is not provided for topics on which there is agreement on the standard of care.

Published
2020

2. Pruritus characteristics in a large Italian cohort of psoriatic patients

Author

Damiani, G., Cazzaniga, S., Conic, R. R. Z., Naldi, L., Griseta, V., Miracapillo, A., Azzini, M., Mocci, L., Michelini, M., Offidani, A., Bernardini, Lucia, Campanati, A., Ricotti, G., Giacchetti, A., Norat, M., Gualco, F., Castelli, A., Cuccia, A., Diana, A., Roncarolo, G., Belli, M. A., Baldassarre, M. A., Santoro, G., Vena, G. A., Lo Console, F., Filotico, R., Mastrandrea, V., Brunetti, B., Musumeci, F., Carrabba, E., Dal Mas, P., Annicchiarico, F., Benvegnu, B., Spaziani, G., Cusano, F., Saletta Iannazzone, S., Galluccio, A., Pezza, M., Marchesi, L., Imberti, G., Reseghetti, A., Barbera, C., Reggiani, M., Lanzoni, A., Patrizi, A., Bardazzi, F., Antonucci, Anna Maria, De Tommaso, S., Wallnofer, W., Ingannamorte, F., Calzavara-Pinton, P., Iannazzi, S., Zane, C., Capezzera, R., Bassisi, S., Rossi, M. T., Altamura, V., Vigl, W., Nobile, C., Aste, N., Murgia, S., Mugheddu, C., Scuderi, G., Baglieri, F., Di Dio, C., Cilioni Grilli, E., Mastronardi, C., Agnusdei, C. P., Antrilli, A., Aulisa, L., Raimondo, U., Scotto di Luzio, G., Battarra, V. C., Farro, P., Plaitano, R., Micali, G., Musumeci, M. L., Massimino, D., Li Calzi, M., La Greca, S., Pettinato, M., Sapienza, G., Valenti, Gianfranco, De Giacomo, P. F., Amico, Arcangeli, F., Brunelli, D., Ghetti, E., Tulli, A., Assi, G., Amerio, P., Laria, G., Prestinari, F., Spadafora, S., Coppola, Maria, Caresana, G., Pezzarossa, E., Felisi, C., Donato, L., Bertero, M., Musso, Luisa Giulia, Pa lazzini, S., Bruscino, P., Agozzino, U. C., Ottaviani, M., Simoncini, C., Virgili, A., Osti, F., Fabbri, P., Volpi, W., Caproni, M., Lotti, T., Prignano, F., Buggiani, G., Troiano, M., Fenizi, G., Altobella, A., Amoruso, A., Condello, M., Goffredo, A., Righini, M. G., Alessandrini, Francesco, Satolli, F., Zampetti, M., Bertani, E., Fossati, S., Parodi, A., Burlando, M., Fiorucci, C., Nigro, A., Ghigliotti, G., Massone, L., Moise, G. M., Serrai, M., Cannata, G., Campagnoli, A. M., Daly, M., Leporati, C., Peila, R., Filosa, G., Bugatti, L., Nicolini, M., Nazzari, G., Cestari, R., Anastasio, F., Larussa, F. M., Pollice, N., De Francesco, F., Mazzocchetti, G., Peris, Ketty, Fargnoli, Maria Concetta, Di Cesare, Andrea, De Angelis, Livio, Flati, G., Biamonte, A. S., Quarta, G., Congedo, Maria Teresa, Carcaterra, A., Strippoli, D., Fideli, D., Marsili, Francesca, Celli, M., Ceccarini, Martina, Bachini, L., D'Oria, M., Schirripa, V., De Filippi, C., Martini, P., Lapucci, E., Mazzatenta, C., Ghilardi, A., Simonacci, Matteo, Bettacchi, A., Gasco, R., Zanca, A., Battistini, S., Dattola, S., Vernaci, R., Postorino, F., Zampieri, P. F., Padovan, C., Gonzalez Intchaurraga, M. A., Ladurner, J., Guarneri, B., Cannavo, S., Manfre, C., Borgia, F., Puglisi Guerra, A., Cattaneo, A., Carrera, C., Fracchiolla, C., Mozzanica, N., Prezzemolo, L., Menni, S., Lodi, A., Martino, P., Monti, M., Mancini, L., Sacrini, F., Altomare, G. F., Taglioni, M., Lovati, C., Mercuri, S. R., Schiesari, G., Giannetti, A., Conti, A., Lasagni, C., Greco, M., Ronsini, G., Schianchi, S., Fiorentini, Cecilia, Niglietta, S., Maglietta, R., Padalino, C., Crippa, D., Pini, M., Rossi, E., Tosi, D., Armas, M., Ruocco, V., Ayala, F., Balato, N., Gaudiello, F., Cimmino, G. F., Monfrecola, G., Gallo, L., Argenziano, G., Fulgione, E., Berruti, G., Ceparano, S., De Michele, I., Giorgiano, D., Leigheb, G., Deledda, S., Peserico, A., Alaibac, M., Piaserico, S., Schiesari, L., Dan, G., Mattei, I., Oro, E., Arico, M., Bongiorno, M. R., Angileri, R., Amato, S., Todaro, F., Milioto, M., Bellastro, R., Di Nuzzo, S., De Panfilis, G., Zanni, M., Borroni, G., Cananzi, Raffaele, Brazzelli, V., Lisi, P., Stingeni, L., Hansel, K., Pierfelice, V., Donelli, S., Rastelli, Debora, Gasperini, M., Barachini, P., Cecchi, R., Bartoli, L., Pavesi, M., De Paola, S., Corradin, M. T., Ricciuti, F., Piccirillo, A., Viola, L., Tataranni, M., Mautone, M. G., Lo Scocco, G., Niccoli, M. C., Brunasso Vernetti, A. M. G., Gaddoni, G., Resta, F., Casadio, M. C., Arcidiaco, M. C., Luvara, M. C., Albertini, G., Di Lernia, V., Guareschi, E., Catrani, S., Morri, M., De Simone, Clara, D'Agostino, M., Agostino, Ilaria Maria, Calvieri, S., Cantoresi, F., Richetta, A., Sorgi, P., Carnevale, C., Nicolucci, F., Berardesca, E., Ardigo, M., De Felice, C., Gubinelli, E., Talamonti, M., Camplone, G., Cruciani, G., Riccardi, F., Barbati, R., Zumiani, G., Pagani, W., Malagoli, P. G., Pellicano, R., Donadio, D., Di Vito, C., Cottoni, F., Montesu, M. A., Pirodda, C., Addis, G., Marongiu, P., Farris, A., Cacciapuoti, M., Verrini, A., Desirello, G., Gnone, M., Fimiani, M., Pellegrino, Maria Gabriella, Castelli, G., Zappala, L., Sesana, G., Ingordo, V., Vozza, E., Di Giuseppe, D., Fasciocco, D., Nespoli, P., Papini, M., Cicoletti, M., Bernengo, M. G., Ortoncelli, M., Bonvicino, A., Capella, G., Doveil, G. C., Forte, Mario, Peroni, Antonia, Salomone, B., Savoia, P., Pippione, M., Zichichi, L., Frazzitta, M., De Luca, G., Tasin, L., Simonetto, D., Ros, S., Trevisan, G., Patamia, Maria, Miertusova, S., Patrone, P., Frattasio, A., Piccirillo, F., La Spina, S., Di Gaetano, L., Marzocchi, V., Motolese, A., Venturi, C., Gai, F., Pasquinucci, S., Bellazzi, R. M., Silvestri, T., Girolomoni, G., Gisondi, P., Veller Fornasa, C., Trevisan, G. P., Bernardini L., Antonucci A., Valenti G., Coppola M., Musso L., Alessandrini F., Peris K. (ORCID:0000-0002-5237-0463), Fargnoli M. C., Di Cesare A., De Angelis L., Congedo M., Marsili F., Ceccarini M., Simonacci M., Fiorentini C., Cananzi R., Rastelli D., De Simone C. (ORCID:0000-0002-0898-0045), Agostino I., Pellegrino M., Forte M., Peroni A., Patamia M., Damiani, G., Cazzaniga, S., Conic, R. R. Z., Naldi, L., Griseta, V., Miracapillo, A., Azzini, M., Mocci, L., Michelini, M., Offidani, A., Bernardini, Lucia, Campanati, A., Ricotti, G., Giacchetti, A., Norat, M., Gualco, F., Castelli, A., Cuccia, A., Diana, A., Roncarolo, G., Belli, M. A., Baldassarre, M. A., Santoro, G., Vena, G. A., Lo Console, F., Filotico, R., Mastrandrea, V., Brunetti, B., Musumeci, F., Carrabba, E., Dal Mas, P., Annicchiarico, F., Benvegnu, B., Spaziani, G., Cusano, F., Saletta Iannazzone, S., Galluccio, A., Pezza, M., Marchesi, L., Imberti, G., Reseghetti, A., Barbera, C., Reggiani, M., Lanzoni, A., Patrizi, A., Bardazzi, F., Antonucci, Anna Maria, De Tommaso, S., Wallnofer, W., Ingannamorte, F., Calzavara-Pinton, P., Iannazzi, S., Zane, C., Capezzera, R., Bassisi, S., Rossi, M. T., Altamura, V., Vigl, W., Nobile, C., Aste, N., Murgia, S., Mugheddu, C., Scuderi, G., Baglieri, F., Di Dio, C., Cilioni Grilli, E., Mastronardi, C., Agnusdei, C. P., Antrilli, A., Aulisa, L., Raimondo, U., Scotto di Luzio, G., Battarra, V. C., Farro, P., Plaitano, R., Micali, G., Musumeci, M. L., Massimino, D., Li Calzi, M., La Greca, S., Pettinato, M., Sapienza, G., Valenti, Gianfranco, De Giacomo, P. F., Amico, Arcangeli, F., Brunelli, D., Ghetti, E., Tulli, A., Assi, G., Amerio, P., Laria, G., Prestinari, F., Spadafora, S., Coppola, Maria, Caresana, G., Pezzarossa, E., Felisi, C., Donato, L., Bertero, M., Musso, Luisa Giulia, Pa lazzini, S., Bruscino, P., Agozzino, U. C., Ottaviani, M., Simoncini, C., Virgili, A., Osti, F., Fabbri, P., Volpi, W., Caproni, M., Lotti, T., Prignano, F., Buggiani, G., Troiano, M., Fenizi, G., Altobella, A., Amoruso, A., Condello, M., Goffredo, A., Righini, M. G., Alessandrini, Francesco, Satolli, F., Zampetti, M., Bertani, E., Fossati, S., Parodi, A., Burlando, M., Fiorucci, C., Nigro, A., Ghigliotti, G., Massone, L., Moise, G. M., Serrai, M., Cannata, G., Campagnoli, A. M., Daly, M., Leporati, C., Peila, R., Filosa, G., Bugatti, L., Nicolini, M., Nazzari, G., Cestari, R., Anastasio, F., Larussa, F. M., Pollice, N., De Francesco, F., Mazzocchetti, G., Peris, Ketty, Fargnoli, Maria Concetta, Di Cesare, Andrea, De Angelis, Livio, Flati, G., Biamonte, A. S., Quarta, G., Congedo, Maria Teresa, Carcaterra, A., Strippoli, D., Fideli, D., Marsili, Francesca, Celli, M., Ceccarini, Martina, Bachini, L., D'Oria, M., Schirripa, V., De Filippi, C., Martini, P., Lapucci, E., Mazzatenta, C., Ghilardi, A., Simonacci, Matteo, Bettacchi, A., Gasco, R., Zanca, A., Battistini, S., Dattola, S., Vernaci, R., Postorino, F., Zampieri, P. F., Padovan, C., Gonzalez Intchaurraga, M. A., Ladurner, J., Guarneri, B., Cannavo, S., Manfre, C., Borgia, F., Puglisi Guerra, A., Cattaneo, A., Carrera, C., Fracchiolla, C., Mozzanica, N., Prezzemolo, L., Menni, S., Lodi, A., Martino, P., Monti, M., Mancini, L., Sacrini, F., Altomare, G. F., Taglioni, M., Lovati, C., Mercuri, S. R., Schiesari, G., Giannetti, A., Conti, A., Lasagni, C., Greco, M., Ronsini, G., Schianchi, S., Fiorentini, Cecilia, Niglietta, S., Maglietta, R., Padalino, C., Crippa, D., Pini, M., Rossi, E., Tosi, D., Armas, M., Ruocco, V., Ayala, F., Balato, N., Gaudiello, F., Cimmino, G. F., Monfrecola, G., Gallo, L., Argenziano, G., Fulgione, E., Berruti, G., Ceparano, S., De Michele, I., Giorgiano, D., Leigheb, G., Deledda, S., Peserico, A., Alaibac, M., Piaserico, S., Schiesari, L., Dan, G., Mattei, I., Oro, E., Arico, M., Bongiorno, M. R., Angileri, R., Amato, S., Todaro, F., Milioto, M., Bellastro, R., Di Nuzzo, S., De Panfilis, G., Zanni, M., Borroni, G., Cananzi, Raffaele, Brazzelli, V., Lisi, P., Stingeni, L., Hansel, K., Pierfelice, V., Donelli, S., Rastelli, Debora, Gasperini, M., Barachini, P., Cecchi, R., Bartoli, L., Pavesi, M., De Paola, S., Corradin, M. T., Ricciuti, F., Piccirillo, A., Viola, L., Tataranni, M., Mautone, M. G., Lo Scocco, G., Niccoli, M. C., Brunasso Vernetti, A. M. G., Gaddoni, G., Resta, F., Casadio, M. C., Arcidiaco, M. C., Luvara, M. C., Albertini, G., Di Lernia, V., Guareschi, E., Catrani, S., Morri, M., De Simone, Clara, D'Agostino, M., Agostino, Ilaria Maria, Calvieri, S., Cantoresi, F., Richetta, A., Sorgi, P., Carnevale, C., Nicolucci, F., Berardesca, E., Ardigo, M., De Felice, C., Gubinelli, E., Talamonti, M., Camplone, G., Cruciani, G., Riccardi, F., Barbati, R., Zumiani, G., Pagani, W., Malagoli, P. G., Pellicano, R., Donadio, D., Di Vito, C., Cottoni, F., Montesu, M. A., Pirodda, C., Addis, G., Marongiu, P., Farris, A., Cacciapuoti, M., Verrini, A., Desirello, G., Gnone, M., Fimiani, M., Pellegrino, Maria Gabriella, Castelli, G., Zappala, L., Sesana, G., Ingordo, V., Vozza, E., Di Giuseppe, D., Fasciocco, D., Nespoli, P., Papini, M., Cicoletti, M., Bernengo, M. G., Ortoncelli, M., Bonvicino, A., Capella, G., Doveil, G. C., Forte, Mario, Peroni, Antonia, Salomone, B., Savoia, P., Pippione, M., Zichichi, L., Frazzitta, M., De Luca, G., Tasin, L., Simonetto, D., Ros, S., Trevisan, G., Patamia, Maria, Miertusova, S., Patrone, P., Frattasio, A., Piccirillo, F., La Spina, S., Di Gaetano, L., Marzocchi, V., Motolese, A., Venturi, C., Gai, F., Pasquinucci, S., Bellazzi, R. M., Silvestri, T., Girolomoni, G., Gisondi, P., Veller Fornasa, C., Trevisan, G. P., Bernardini L., Antonucci A., Valenti G., Coppola M., Musso L., Alessandrini F., Peris K. (ORCID:0000-0002-5237-0463), Fargnoli M. C., Di Cesare A., De Angelis L., Congedo M., Marsili F., Ceccarini M., Simonacci M., Fiorentini C., Cananzi R., Rastelli D., De Simone C. (ORCID:0000-0002-0898-0045), Agostino I., Pellegrino M., Forte M., Peroni A., and Patamia M.

Abstract

Background: Psoriasis (Ps) is a chronic systemic autoimmune disease associated with pruritus in 64–98% of patients. However, few modestly sized studies assess factors associated with psoriatic pruritus. Objective: To investigate factors associated with Ps pruritus intensity. Methods: Psoriasis patients 18 years or older seen in one of 155 centres in Italy between September 2005 and 2009 were identified from the Italian PsoCare registry. Patients without cutaneous psoriasis and those with missed information on pruritus were excluded. Results: We identified 10 802 patients, with a mean age 48.8 ± 14.3 years. Mild itch was present in 33.2% of patients, moderate in 34.4%, severe in 18.7% and very severe in 13.7%. Higher itch intensity was associated with female gender, lower educational attainment compared to university degree, pustular psoriasis, psoriasis on the head, face, palmoplantar areas, folds and genitalia, more severe disease, disease duration <15 years, and no or few prior systemic treatments. Limitations: Effects of specific medication on itch were not assessed. Conclusions: Pruritus should be evaluated during psoriasis visits, and physicians should be aware of patients at higher risk for itch. Further studies are needed to assess the effects of medications on itch, and establish therapy for psoriasis patients with persistent itch.

Published
2019

3. Improving the disease awareness: how a communication campaign brings hidradenitis suppurativa to the light

Author

Ribero, S., Dapavo, P., Casalegno, C., Alaibac, M., Argenziano, G., Arpaia, N. G., Bagnoni, G., Berti, Emanuele, Bianchi, L., Bianchini, D., Calzavara Pinton, P., Cannavo, S. P., Congedo, Maria Teresa, Corrao, S., Costanzo, Rosa Maria Alba, Cusano, F., Dattola, S., Dattoli, S., Deledda, S., Donini, M., Fabbrocini, G., Teresa Fierro, M., Foti, C., Galluccio, A. G., Gatti, A., Rene Girardelli, C., Girolomoni, G., Lemme, G., Malagoli, P., Malara, G., Mercuri, S. R., Micali, G., Montesu, M. A., Offidani, A., Papini, M., Parodi, A., Patrizi, A., Pellacani, G., Peris, Ketty, Piccirillo, A., Pigatto, P., Pimpinelli, N., Potenza, C., Provenzano, Katia Elisabetta, Romanelli, Margherita, Rongioletti, F., Savoia, P., Simonacci, Matteo, Sirna, R., Stinco, G., Valenti, Gianfranco, Zalaudek, Iris, Berti E., Congedo M., Costanzo A., Peris K. (ORCID:0000-0002-5237-0463), Provenzano E., Romanelli M., Simonacci M., Valenti G., Zalaudek I., Ribero, S., Dapavo, P., Casalegno, C., Alaibac, M., Argenziano, G., Arpaia, N. G., Bagnoni, G., Berti, Emanuele, Bianchi, L., Bianchini, D., Calzavara Pinton, P., Cannavo, S. P., Congedo, Maria Teresa, Corrao, S., Costanzo, Rosa Maria Alba, Cusano, F., Dattola, S., Dattoli, S., Deledda, S., Donini, M., Fabbrocini, G., Teresa Fierro, M., Foti, C., Galluccio, A. G., Gatti, A., Rene Girardelli, C., Girolomoni, G., Lemme, G., Malagoli, P., Malara, G., Mercuri, S. R., Micali, G., Montesu, M. A., Offidani, A., Papini, M., Parodi, A., Patrizi, A., Pellacani, G., Peris, Ketty, Piccirillo, A., Pigatto, P., Pimpinelli, N., Potenza, C., Provenzano, Katia Elisabetta, Romanelli, Margherita, Rongioletti, F., Savoia, P., Simonacci, Matteo, Sirna, R., Stinco, G., Valenti, Gianfranco, Zalaudek, Iris, Berti E., Congedo M., Costanzo A., Peris K. (ORCID:0000-0002-5237-0463), Provenzano E., Romanelli M., Simonacci M., Valenti G., and Zalaudek I.

Abstract

Background: Hidradenitis suppurativa is an inflammatory skin disease that presents a recurrence of painful and suppurating lesions in the apocrine gland-bearing regions, with a strong impact on the patients’ life quality. Despite its peculiar presentation, early forms are often underestimated by patients and this would inevitably result in late diagnosis and delayed therapy. Objectives: Improved communication around the disease could facilitate self-diagnosis and a quicker response from healthcare practitioners, especially in this moment when we dispose of effective treatment against this disease. Methods: A HS awareness campaign was conducted for 2 years with the help of a media agency and a patients’ association. Results: Results confirm that a better communication has a strong impact on the disease awareness. Conclusions: This paper demonstrates that the more this disease awareness is carried on, the more quick, effective and efficient the patient's management could be.

Published
2019

5. Modulation of TRPM6 and Na+/Mg2+ exchange in mammary epithelial cells in response to variations of magnesium availability.

Author

Wolf, Federica, Trapani, Valentina, Simonacci, Matteo, Mastrototaro, Lucia, Cittadini, Achille, Wolf, Federica (ORCID:0000-0003-1361-1049), Trapani, Valentina (ORCID:0000-0002-0259-6624), Wolf, Federica, Trapani, Valentina, Simonacci, Matteo, Mastrototaro, Lucia, Cittadini, Achille, Wolf, Federica (ORCID:0000-0003-1361-1049), and Trapani, Valentina (ORCID:0000-0002-0259-6624)

Published
2010

6. Magnesium deficiency affects mammary epithelial cell proliferation: involvement of oxidative stress.

Author

Wolf, Federica, Trapani, Valentina, Simonacci, Matteo, Boninsegna Lucarelli, Alma, Mazur, A, Maier, J., Wolf, Federica (ORCID:0000-0003-1361-1049), Trapani, Valentina (ORCID:0000-0002-0259-6624), Wolf, Federica, Trapani, Valentina, Simonacci, Matteo, Boninsegna Lucarelli, Alma, Mazur, A, Maier, J., Wolf, Federica (ORCID:0000-0003-1361-1049), and Trapani, Valentina (ORCID:0000-0002-0259-6624)

Published
2009

10. Modulation of TRPM6 and Na+/Mg2+ exchange in mammary epithelial cells in response to variations of magnesium availability.

Author

WOLF, FEDERICA I., TRAPANI, VALENTINA, SIMONACCI, MATTEO, MASTROTOTARO, LUCIA, CITTADINI, ACHILLE, and SCHWEIGEL, MONIKA

Subjects
EPITHELIAL cells, CELLS, MAGNESIUM in the body, BODY composition, WESTERN immunoblotting
Abstract

Mammary epithelial cells (HC11) chronically adapted to grow in a low-magnesium (0.05 mM vs. 0.5 mM) or in a high-magnesium (40 mM) medium were used to investigate on the mechanisms of cell magnesium transport under conditions of non-physiological magnesium availability. Magnesium influx was higher in low-magnesium cells compared to control or high-magnesium cells, whereas magnesium efflux was higher in high-magnesium cells compared to control and low-magnesium cells. Magnesium efflux was partially inhibited by imipramine, inhibitor of the Na+/Mg2+ exchange. Using a monoclonal antibody detecting a ∼70 kDa protein associated with Na+/Mg2+ exchange activity, we found that the expression levels of this protein were proportional to magnesium efflux capacity, that is, high-magnesium cells > control cells > low-magnesium cells. As for magnesium influx, this was abolished by Co(III)hexaammine, inhibitor of magnesium channels. Surprisingly, we found that cells grown in low magnesium upregulated mRNA for the magnesium channel TRPM6, but not for other channels like TRPM7 or MagT1. TRPM6 mRNA was also rapidly upregulated or downregulated in HC11 cells deprived of magnesium or in low-magnesium cells re-added with magnesium, respectively. TRPM6 protein levels, as assessed by Western blot and immunofluorescence, underwent similar changes under comparable conditions. We propose that mammary epithelial cells adapt to decreased magnesium availability by upregulating magnesium influx via TRPM6, and counteract increased magnesium availability by increasing magnesium efflux primarily via Na+/Mg2+ exchange. These results show, for the first time, that TRPM6 contributes to regulating magnesium influx in mammary epithelial cells, similar to what is known for intestine and kidney. J. Cell. Physiol. 222: 374–381, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Published
2010
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11. Modulation of TRPM6 and Na(+)/Mg(2+) exchange in mammary epithelial cells in response to variations of magnesium availability.

Author

Wolf FI, Trapani V, Simonacci M, Mastrototaro L, Cittadini A, and Schweigel M

Subjects
Adaptation, Physiological, Animals, Antiporters antagonists & inhibitors, Biological Transport, Blotting, Western, Cell Line, Cobalt pharmacology, Epithelial Cells drug effects, Female, Fluorescent Antibody Technique, Imipramine pharmacology, Kinetics, Mammary Glands, Animal cytology, Mammary Glands, Animal drug effects, Mice, Microscopy, Confocal, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, TRPM Cation Channels antagonists & inhibitors, TRPM Cation Channels genetics, Antiporters metabolism, Epithelial Cells metabolism, Magnesium metabolism, Mammary Glands, Animal metabolism, Sodium metabolism, TRPM Cation Channels metabolism
Abstract

Mammary epithelial cells (HC11) chronically adapted to grow in a low-magnesium (0.05 mM vs. 0.5 mM) or in a high-magnesium (40 mM) medium were used to investigate on the mechanisms of cell magnesium transport under conditions of non-physiological magnesium availability. Magnesium influx was higher in low-magnesium cells compared to control or high-magnesium cells, whereas magnesium efflux was higher in high-magnesium cells compared to control and low-magnesium cells. Magnesium efflux was partially inhibited by imipramine, inhibitor of the Na(+)/Mg(2+) exchange. Using a monoclonal antibody detecting a approximately 70 kDa protein associated with Na(+)/Mg(2+) exchange activity, we found that the expression levels of this protein were proportional to magnesium efflux capacity, that is, high-magnesium cells > control cells > low-magnesium cells. As for magnesium influx, this was abolished by Co(III)hexaammine, inhibitor of magnesium channels. Surprisingly, we found that cells grown in low magnesium upregulated mRNA for the magnesium channel TRPM6, but not for other channels like TRPM7 or MagT1. TRPM6 mRNA was also rapidly upregulated or downregulated in HC11 cells deprived of magnesium or in low-magnesium cells re-added with magnesium, respectively. TRPM6 protein levels, as assessed by Western blot and immunofluorescence, underwent similar changes under comparable conditions. We propose that mammary epithelial cells adapt to decreased magnesium availability by upregulating magnesium influx via TRPM6, and counteract increased magnesium availability by increasing magnesium efflux primarily via Na(+)/Mg(2+) exchange. These results show, for the first time, that TRPM6 contributes to regulating magnesium influx in mammary epithelial cells, similar to what is known for intestine and kidney., ((c) 2009 Wiley-Liss, Inc.)

Published
2010
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12. Magnesium deficiency and endothelial dysfunction: is oxidative stress involved?

Author

Wolf FI, Trapani V, Simonacci M, Ferré S, and Maier JA

Subjects
Cells, Cultured, Endothelial Cells cytology, Endothelial Cells drug effects, Endothelial Cells metabolism, Endothelium pathology, Endothelium physiopathology, Humans, Hydrogen Peroxide pharmacology, Immunohistochemistry, Reactive Oxygen Species metabolism, Endothelium metabolism, Magnesium Deficiency physiopathology, Oxidative Stress physiology
Abstract

Low magnesium (Mg) has been associated with oxidative stress, an important player in aging, atherosclerosis and other vascular diseases. In vivo, low Mg and immune system activation seem to cooperate to promote endothelial dysfunction. We therefore evaluated whether exposure of human endothelial cells to low Mg in vitro determines oxidative stress features. We therefore measured intracellular reactive oxygen species (ROS) by dichlorofluorescein (DCF) fluorescence after Mg deprivation with or without treatment with H2O2 While we did not observe any alteration of DCF-detectable intracellular ROS under basal conditions, we show that, early after exposure to low Mg (2 h), endothelial cells are more sensitive to the oxidant action of H2O2 than the controls cultured in physiologic concentrations of Mg. This increase of ROS in Mg deprived cells is transient and followed by a stable reduction of DCF-fluorescence below the levels measured in the controls. We also evaluated oxidative DNA damage and observed higher 8-hydroxy-deoxyguanine levels early (2 h) after Mg deprivation in respect to the controls, both in basal conditions and after treatment with H2O2 Mg deficiency in vivo associates with the onset of an inflammatory response leading to increased circulating levels of cytokines, which trigger an oxidative response in endothelial cells. We here show that exposure to IL-1 and IL-6 significantly increased the levels of DCF-detectable ROS in cells cultured in physiologic concentrations of Mg, but not in Mg-deprived cells. We conclude that low Mg transiently leads to pro-oxidant effects. We suggest that different molecules, including pro-inflammatory cytokines, might be involved in promoting endothelial dysfunction.

Published
2008

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