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1. Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention

Author

Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., Protti G., Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., and Protti G.

Abstract

Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's

Published
2023

3. Umbilical Cord Mesenchymal Stromal Cells for Cartilage Regeneration Applications

Author

Russo, E., Caprnda, M., Kruzliak, P., Conaldi, P. G., Borlongan, C. V., and La Rocca, G.

Subjects
Article Subject
Abstract

Chondropathies are increasing worldwide, but effective treatments are currently lacking. Mesenchymal stromal cell (MSCs) transplantation represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA) and rheumatoid arthritis (RA). Umbilical cord- (UC-) MSCs gained increasing interest due to their multilineage differentiation potential, immunomodulatory, and anti-inflammatory properties as well as higher proliferation rates, abundant supply along with no risks for the donor compared to adult MSCs. In addition, UC-MSCs are physiologically adapted to survive in an ischemic and nutrient-poor environment as well as to produce an extracellular matrix (ECM) similar to that of the cartilage. All these characteristics make UC-MSCs a pivotal source for a stem cell-based treatment of chondropathies. In this review, the regenerative potential of UC-MSCs for the treatment of cartilage diseases will be discussed focusing on in vitro, in vivo, and clinical studies.

Published
2022
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11. Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats

Author

Pietrosi, G., Fernandez-Iglesias, A., Pampalone, M., Ortega-Ribera, M., Lozano, J. J., Garcia-Caldero, H., Abad-Jorda, L., Conaldi, P. G., Parolini, O., Vizzini, G., Luca, A., Bosch, J., Gracia-Sancho, J., Parolini O. (ORCID:0000-0002-5211-6430), Pietrosi, G., Fernandez-Iglesias, A., Pampalone, M., Ortega-Ribera, M., Lozano, J. J., Garcia-Caldero, H., Abad-Jorda, L., Conaldi, P. G., Parolini, O., Vizzini, G., Luca, A., Bosch, J., Gracia-Sancho, J., and Parolini O. (ORCID:0000-0002-5211-6430)

Abstract

Background and Aims: Portal hypertension is the main consequence of cirrhosis, responsible for the complications defining clinical decompensation. The only cure for decompensated cirrhosis is liver transplantation, but it is a limited resource and opens the possibility of regenerative therapy. We investigated the potential of primary human amniotic membrane-derived mesenchymal stromal (hAMSCs) and epithelial (hAECs) stem cells for the treatment of portal hypertension and decompensated cirrhosis. Methods: In vitro: Primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) from cirrhotic rats (chronic CCl4 inhalation) were co-cultured with hAMSCs, hAECs or vehicle for 24 hours, and their RNA profile was analysed. In vivo: CCl4-cirrhotic rats received 4x106 hAMSCs, 4x106 hAECs, or vehicle (NaCl 0.9%) (intraperitoneal). At 2-weeks we analysed: a) portal pressure (PP) and hepatic microvascular function; b) LSECs and HSCs phenotype; c) hepatic fibrosis and inflammation. Results: In vitro experiments revealed sinusoidal cell phenotype amelioration when co-cultured with stem cells. Cirrhotic rats receiving stem cells, particularly hAMSCs, had significantly lower PP than vehicle-treated animals, together with improved liver microcirculatory function. This hemodynamic amelioration was associated with improvement in LSECs capillarization and HSCs de-activation, though hepatic collagen was not reduced. Rats that received amnion derived stem cells had markedly reduced hepatic inflammation and oxidative stress. Finally, liver function tests significantly improved in rats receiving hAMSCs. Conclusions: This preclinical study shows that infusion of human amniotic stem cells effectively decreases PP by ameliorating liver microcirculation, suggesting that it may represent a new treatment option for advanced cirrhosis with portal hypertension.

Published
2020

13. Zika virus infection induces MiR34c expression in glioblastoma stem cells: new perspectives for brain tumor treatments

Author

Iannolo, G., Sciuto, M. R., Cuscino, N., Pallini, R., Douradinha, B., Ricci Vitiani, L., De Maria, R., Conaldi, P. G., Pallini R. (ORCID:0000-0002-4611-8827), De Maria R. (ORCID:0000-0003-2255-0583), Iannolo, G., Sciuto, M. R., Cuscino, N., Pallini, R., Douradinha, B., Ricci Vitiani, L., De Maria, R., Conaldi, P. G., Pallini R. (ORCID:0000-0002-4611-8827), and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Zika virus (ZIKV) is a flavivirus with a marked effect on fetal nervous system development. ZIKV treatment has recently been found to also have a benefit against glioblastoma, a highly aggressive brain tumor with a poor prognosis. The reported data do not completely explain the mechanism beyond this effect. Nevertheless, in the majority of the cases no adverse effect has been found in healthy adult humans. In this study, we characterized the ZIKV infection mechanism on glioblastoma stem cells, which are considered responsible for the tumor progression and resistance to conventional therapies. Moreover, we explain why the action of this virus is directed to the stem cells in the nervous system counterpart. Our results confirm the effectiveness of ZIKV treatment against glioblastoma, indicating novel molecular targets that can be introduced for more powerful therapies.

Published
2019

14. Collaborative national multicenter for the identification of conversion factors from copies/mL to international units/mL for the normalization of HCMV DNA load

Author

Sidoti, F., Piralla, A., Costa, C., Scarasciulli, M. L., Calvario, A., Conaldi, P. G., Paba, P., Perno, C. F., Gaeta, A., Antonelli, G., Sodano, G., Santangelo, Rosaria, Sanguinetti, Maurizio, Vatteroni, M. L., Barzon, L., Palu, G., Abbate, I., Capobianchi, M. R., Piccirilli, G., Lazzarotto, T., Baldanti, F., Cavallo, R., Santangelo R. (ORCID:0000-0002-8056-218X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Sidoti, F., Piralla, A., Costa, C., Scarasciulli, M. L., Calvario, A., Conaldi, P. G., Paba, P., Perno, C. F., Gaeta, A., Antonelli, G., Sodano, G., Santangelo, Rosaria, Sanguinetti, Maurizio, Vatteroni, M. L., Barzon, L., Palu, G., Abbate, I., Capobianchi, M. R., Piccirilli, G., Lazzarotto, T., Baldanti, F., Cavallo, R., Santangelo R. (ORCID:0000-0002-8056-218X), and Sanguinetti M. (ORCID:0000-0002-9780-7059)

Abstract

The present multicentric (n = 11 laboratories) study aimed to identify conversion factors from copies/mL to international units (IU)/mL for the normalization of HCMV DNA load using the first WHO International Standard for HCMV nucleic acid amplification techniques and to enhance interlaboratory agreement of HCMV DNA quantification methods. Study protocols for whole blood and plasma (extraction and amplification) were performed to calculate conversion factors from HCMV DNA copy number to IU. The greatest variability was observed in samples with lower HCMV concentrations (3.0 Log10) in both biological matrices. Overall, 73.1% (206/282) of whole blood and 82.2% (324/394) of plasma samples analyzed fell within an acceptable variation range (±0.5 Log10 difference). An average of 0.64 (range 0.21–1.17) was the conversion factor calculated for the HCMV whole blood panel and 0.82 (range 0.39–2.2) for the HCMV plasma panel.

Published
2019

15. Infections in liver and lung transplant recipients. A national prospective cohort

Author

Gagliotti, Carlo, Morsillo, Filomena, Moro, Maria Luisa, Masiero, Lucia, Procaccio, Francesco, Vespasiano, Francesca, Pantosti, Annalisa, Monaco, Monica, Errico, Giulia, Ricci, Andrea, Grossi, Paolo, Nanni Costa, Alessandro, Adorno, D., Ambretti, S., Amoroso, A., Arghittu, M., Berloco, P., Bertani, A., Bonizzoli, M., Cambieri, P., Canzonieri, M., Caprio, M., Carrara, E., Carrinola, R., Cibelli, E., Cillo, U., Colledan, M., Colombo, R., Coluccio, E., Conaldi, P. G., Cusi, M., D’Armini, A. M., da Riva, A., D’Auria, B., de Carlis, L., de Cillia, C., de Gasperi, A., Di Caro, A., Di Ciaccio, P., Dondossola, D., Farina, C., Feltrin, G., Finarelli, A. C., Fossati, L., Gaibani, P., Garcia Fernandez, A., Gesu, G., Giacometti, R., Gona, F., Gridelli, B., Henrici de Angelis, L., Landini, M. P., Maldarelli, F., Mancini, C., Marone, P., Mularoni, A., Paglialunga, G., Paladini, P., Palù, G., Parisi, S., Peris, A., Pinna, A. D., Platto, M., Pugliese, F., Puoti, F., Rago, C., Ravini, M., Rea, F., Rinaldi, M., Rossi, G., Rossi, L., Rossi, M., Salizzoni, M., Sangiorgi, G., Santambrogio, L., Spada, M., Sparacino, V., Stella, F., Torelli, R., Torresani, E., Tosi, D., Vailati, F., Valeri, M., Venuta, F., Vesconi, S., Viale, P., Vismara, C., Gagliotti, C, Morsillo, F, Moro, M, Masiero, L, Procaccio, F, Vespasiano, F, Pantosti, A, Monaco, M, Errico, G, Ricci, A, Grossi, P, Nanni Costa, A, Adorno, D, Ambretti, S, Amoroso, A, Arghittu, M, Berloco, P, Bertani, A, Bonizzoli, M, Cambieri, P, Canzonieri, M, Caprio, M, Carrara, E, Carrinola, R, Cibelli, E, Cillo, U, Colledan, M, Colombo, R, Coluccio, E, Conaldi, P, Cusi, M, D’Armini, A, da Riva, A, D’Auria, B, de Carlis, L, de Cillia, C, de Gasperi, A, Di Caro, A, Di Ciaccio, P, Dondossola, D, Farina, C, Feltrin, G, Finarelli, A, Fossati, L, Gaibani, P, Garcia Fernandez, A, Gesu, G, Giacometti, R, Gona, F, Gridelli, B, Henrici de Angelis, L, Landini, M, Maldarelli, F, Mancini, C, Marone, P, Mularoni, A, Paglialunga, G, Paladini, P, Palù, G, Parisi, S, Peris, A, Pinna, A, Platto, M, Pugliese, F, Puoti, F, Rago, C, Ravini, M, Rea, F, Rinaldi, M, Rossi, G, Rossi, L, Rossi, M, Salizzoni, M, Sangiorgi, G, Santambrogio, L, Spada, M, Sparacino, V, Stella, F, Torelli, R, Torresani, E, Tosi, D, Vailati, F, Valeri, M, Venuta, F, Vesconi, S, Viale, P, Vismara, C, Gagliotti, Carlo, Morsillo, Filomena, Moro, Maria Luisa, Masiero, Lucia, Procaccio, Francesco, Vespasiano, Francesca, Pantosti, Annalisa, Monaco, Monica, Errico, Giulia, Ricci, Andrea, Grossi, Paolo, Costa, Alessandro Nanni, Adorno, Domenico, Ambretti, Simone, Amoroso, Antonio, Arghittu, Milena, Berloco, Pasquale, Bertani, Alessandro, Bonizzoli, Manuela, Cambieri, Patrizia, Canzonieri, Marco, Caprio, Mario, Carrara, Elena, Carrinola, Rosaria, Cibelli, Eva, Cillo, Umberto, Colledan, Michele, Colombo, Rosaria, Coluccio, Elena, Conaldi, Pier Giulio, Cusi, Mariagrazia, D’Armini, Andrea Maria, Da Riva, Adelaide, D'Auria, Bianca, De Carlis, Luciano, De Cillia, Carlo, De Gasperi, Andrea, Di Caro, Antonino, Di Ciaccio, Paola, Dondossola, Daniele, Farina, Claudio, Feltrin, Giuseppe, Finarelli, Alba Carola, Fossati, Lucina, Gaibani, Paolo, Fernandez, Aurora Garcia, Gesu, Giovanni, Giacometti, Raffaella, Gona, Floriana, Gridelli, Bruno, De Angelis, Lucia Henrici, Landini, Maria Paola, Maldarelli, Federica, Mancini, Carlo, Marone, Piero, Mularoni, Alessandra, Paglialunga, Giulia, Paladini, Piero, Palù, Giorgio, Parisi, Saverio, Peris, Adriano, Pinna, Antonio Daniele, Platto, Marco, Pugliese, Francesco, Puoti, Francesca, Rago, Claudio, Ravini, Mario, Rea, Federico, Rinaldi, Mauro, Rossi, Giorgio, Rossi, Lucia, Rossi, Massimo, Salizzoni, Mauro, Sangiorgi, Gabriela, Santambrogio, Luigi, Spada, Marco, Sparacino, Vito, Stella, Franco, Torelli, Rosanna, Torresani, Erminio, Tosi, Davide, Vailati, Francesca, Valeri, Maurizio, Venuta, Federico, Vesconi, Sergio, Viale, Pierluigi, and Vismara, Chiara

Subjects
Microbiology (medical), Infectious Diseases, Male, 0301 basic medicine, medicine.medical_treatment, Drug Resistance, Transplant Recipient, 030230 surgery, Liver transplantation, Postoperative Complications, 0302 clinical medicine, Drug Resistance, Multiple, Bacterial, Medicine, Cumulative incidence, Prospective Studies, Prospective cohort study, Incidence, Incidence (epidemiology), Mortality rate, Bacterial, Bacterial Infections, General Medicine, Middle Aged, lung transplant, Anti-Bacterial Agents, infectious, Italy, Female, Multiple, Adult, Bacteria, Humans, Transplant Recipients, Liver Transplantation, Lung Transplantation, Human, medicine.medical_specialty, 030106 microbiology, Bacterial Infection, Infectious Diseases, transplantation, 03 medical and health sciences, Internal medicine, Anti-Bacterial Agent, Lung transplantation, business.industry, lung transplant, liver transplant, infectious, Transplantation, Prospective Studie, liver transplant, Etiology, Postoperative Complication, business, transplantation
Abstract

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients’ characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.

Published
2018

19. Epidemic diffusion of OXA-23-producing Acinetobacter baumannii isolates in Italy: results of the first cross-sectional countrywide survey

Author

Principe, Luigi, Piazza, Aurora, Giani, Tommaso, Bracco, Silvia, Caltagirone, Maria Sofia, Arena, Fabio, Nucleo, Elisabetta, Tammaro, Federica, Rossolini, Gian Maria, Pagani, Laura, Luzzaro, Francesco, DI GESU', VERONICA GAETANA, Toniolo, A., Serra, MASSIMO RAFFAELE, Pini, B., Fortina, G., Mori, M., Dusi, P. A., Fontana, R., Aschbacher, R., Sarti, M., Rumpianesi, F., Pecile, P., Mencacci, A., Manso, E., Tronci, M., Fazii, P., Labonia, M., Pizzolante, M., Amato, G., Buonopane, P., Giraldi, C., Conaldi, P. G., and Stefani, S.

Subjects
Microbiology (medical), Acinetobacter baumannii, Genotype, Sequence analysis, Epidemiology, Drug Resistance, Microbial Sensitivity Tests, Biology, Polymerase Chain Reaction, beta-Lactamases, Microbiology, law.invention, law, Drug Resistance, Multiple, Bacterial, Genetic variation, medicine, Prevalence, Cluster Analysis, Humans, Epidemics, Polymerase chain reaction, Acinetobacter Infections, Anti-Bacterial Agents, Cross-Sectional Studies, Genes, Bacterial, Genetic Variation, Italy, Molecular Epidemiology, Molecular Typing, Sequence Analysis, DNA, Molecular epidemiology, Bacterial, DNA, biology.organism_classification, Genes, Colistin, Multilocus sequence typing, Multiple, Sequence Analysis, medicine.drug
Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAb) is emerging worldwide as a public health problem in various settings. The aim of this study was to investigate the prevalence of CRAb isolates in Italy and to characterize their resistance mechanisms and genetic relatedness. A countrywide cross-sectional survey was carried out at 25 centers in mid-2011. CRAb isolates were reported from all participating centers, with overall proportions of 45.7% and 22.2% among consecutive nonreplicate clinical isolates of A. baumannii from inpatients ( n = 508) and outpatients ( n = 63), respectively. Most of them were resistant to multiple antibiotics, whereas all remained susceptible to colistin, with MIC 50 and MIC 90 values of ≤0.5 mg/liter. The genes coding for carbapenemase production were identified by PCR and sequencing. OXA-23 enzymes (found in all centers) were by far the most common carbapenemases (81.7%), followed by OXA-58 oxacillinases (4.5%), which were found in 7 of the 25 centers. In 6 cases, CRAb isolates carried both bla OXA-23-like and bla OXA-58-like genes. A repetitive extragenic palindromic (REP)-PCR technique, multiplex PCRs for group identification, and multilocus sequence typing (MLST) were used to determine the genetic relationships among representative isolates ( n = 55). Two different clonal lineages were identified, including a dominant clone of sequence type 2 (ST2) related to the international clone II (sequence group 1 [SG1], SG4, and SG5) and a clone of ST78 (SG6) previously described in Italy. Overall, our results demonstrate that OXA-23 enzymes have become the most prevalent carbapenemases and are now endemic in Italy. In addition, molecular typing profiles showed the presence of international and national clonal lineages in Italy.

Published
2014

32. Antibody response to fibronectin-binding adhesin FnbpA in patients with Staphylococcus aureus infections.

Author

Casolini, F, Visai, L, Joh, D, Conaldi, P G, Toniolo, A, Höök, M, and Speziale, P

Abstract

We have analyzed antibody reactivity to a fibronectin-binding microbial surface component that recognizes adhesive matrix molecules (MSCRAMM) in blood plasma collected from patients with staphylococcal infections. All patients had elevated levels of anti-MSCRAMM antibodies compared to those of young children who, presumably, had not been exposed to staphylococcal infections. The anti-MSCRAMM antibodies preferentially reacted with the ligand-binding repeat domain of the adhesin. However, these antibodies did not inhibit fibronectin binding. Essentially, all patients had antibodies which specifically recognized the fibronectin-MSCRAMM complex but not the isolated components. Epitopes recognized by these anti-ligand-induced binding sites antibodies were found in each repeat unit of the MSCRAMM. These results demonstrate that staphylococci have bound fibronectin some time during infection and that each repeat unit in the MSCRAMM can engage in ligand binding. Furthermore, our previously proposed model, suggesting that an unordered structure in the MSCRAMM undergoes a conformational change upon ligand binding (K. House-Pompeo, Y. Xu, D. Joh, P. Speziale, and M. Höök, J. Biol. Chem. 271:1379-1384, 1996), is presumably operational in patients during infections.

Published
1998

35. Pandemic influenza A/H1N1 virus in a swine farm house in Sicily, Italy

Author

Annalisa Guercio, Purpari, G., Conaldi, P. G., Pagano, V., Moreno, A., Giambruno, P., Di Trani, L., Vaccari, G., Falcone, E., Boni, A., Cordioli, P., Guercio, A., Purpari, G., Conaldi, P., Pagano, V., Moreno, A., Giambruno, P., Di Trani, L., Vaccari, G., Falcone, E., Boni, A., and Cordioli, P.

Subjects
Swine Diseases, Reverse Transcriptase Polymerase Chain Reaction, Swine, A/H1N1 viru, Real-Time Polymerase Chain Reaction, Disease Outbreaks, Zoonosis, Influenza A Virus, H1N1 Subtype, Orthomyxoviridae Infections, Influenza, Human, Animals, Humans, Sequencing, Female, Pandemics, Sicily, Pandemic influenza
Abstract

This report describes a pandemic A/H1N1 (H1N1 pdm) virus outbreak occurred in December, 2009 in a swine farm used as research facility (Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione) for preclinical studies, located in Sicily, Italy. All the 13 pigs of the farm, showed cough, fever, inappetence and weakness. At the same time, an unvaccinated worker of the stabling showed influenza-like symptoms. RNAv extracted from two swabs collected from infected pigs resulted positive by Real Time RT-PCR for Influenza A virus. Furthermore, after growth on embryonated eggs, viral isolates were identified by Real Time RT-PCR specific for H1N1 pdm virus and characterized antigenically. Sequencing of the whole genome was also performed. All sera taken from animals and from the worker were tested by a competitive Influenza A ELISA and by the haemoagglutination inhibition test. Serological findings confirmed the circulation of influenza virus H1N1 pdm in pigs and the presence of specific antibodies against H1N1 pdm in human serum. The results of this study seem to support a H1N1 pdm transmission from man to animals showing the importance of serological and virological investigation to control the pig farms and the importance of close cooperation between the different authorities like veterinarian and human public. © 2012 Triveni Enterprises.

36. Trapianto di fegato

Author

Gridelli, B., Gruttadauria, Salvatore Giovanni, Spada, M., Luca, A., Conaldi, P. G., Pagano, D., and Vizzini, G. B.

41. Expression of and response to interleukin 6 (IL6) in human mammary tumors

Author

FULVIO BASOLO, Fiore, L., Fontanini, G., Conaldi, P. G., Calvo, S., Falcone, V., and Toniolo, A.

Subjects
Interleukin-6, Reference Values, Tumor Cells, Cultured, Cytokines, Humans, Breast Neoplasms, Female, Breast, Immunohistochemistry, Cells, Cultured, Epithelium
Abstract

Multifunctional cytokines play important and only partially defined roles in mammary tumor development and progression. Normal human mammary epithelia] cells (MECs) constitutively produce interleukin (IL) 6, IL8, and a nonsecreted form of tumor necrosis factor. MEC transformation by different oncogenes is frequently associated with alterations of cytokine/growth factor production and responsiveness. This seems particularly true in the case of IL6. Histochemical studies showed that expression of immunoreactive IL6, as compared to normal tissue and to in situ lesions, is significantly reduced in invasive ductal carcinoma. Conversely, the expression of IL6 in invasive lobular carcinoma was enhanced. Expression of TGF-beta1 in mammary neoplasia was in general less intense than that seen in the normal mammary gland. In vitro studies partially supported the in vivo findings: expression of IL6 and TGF-beta1 was significantly down-regulated in cultures derived from both ductal carcinoma and peritumoral tissue. Similarly, responsiveness to IL6 and TGF-beta1 was significantly reduced in neoplastic MECs. The data suggest that alterations of cytokine pathways are present not only in mammary neoplasia, but also in pathologically unaffected breast tissues.

44. In vivo multiclonal transfer of bla KPC-3 from Klebsiella pneumoniae to Escherichia coli in surgery patients.

Author

Gona, F., Barbera, F., Pasquariello, A. C., Grossi, P., Gridelli, B., Mezzatesta, M. L., Caio, C., Stefani, S., and Conaldi, P. G.

Subjects
*KLEBSIELLA pneumoniae, *ESCHERICHIA coli, *DRUG resistance in bacteria, *DRUG resistance in microorganisms, *NUCLEOTIDE sequencing
Abstract

During active surveillance at the Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT, Palermo, Italy) with the CARBA screening medium, five pairs of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae and Escherichia coli strains were isolated in each of five colonized patients. In each patient, lateral gene transfer was demonstrated by comparing K. pneumoniae and E. coli strains, both possessing KPC-3, Tn 4401a and pKpQIL-IT elements. The isolates were found to be multiclonal by multilocus sequence typing (sequence type (ST) 512 related to ST258, and ST307 belonging to a clonal complex different from the habitual sequence clone ST258 isolated in Italy) and pulsed-field gel electrophoresis. The results of our study highlight the easy transfer of KPC among Enterobacteriaceae colonizing the human intestine, and the active and careful surveillance required to identify and prevent the spread of these multidrug-resistant microorganisms. [ABSTRACT FROM AUTHOR]

Published
2014
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45. Role of non-coding RNAs in age-related vascular cognitive impairment: An overview on diagnostic/prognostic value in Vascular Dementia and Vascular Parkinsonism.

Author

Miceli V, Russelli G, Iannolo G, Gallo A, Lo Re V, Agnese V, Sparacia G, Conaldi PG, and Bulati M

Subjects
Humans, Aging metabolism, Cerebrovascular Circulation, Cognitive Dysfunction diagnosis, Cognitive Dysfunction metabolism, Cognitive Dysfunction physiopathology, Dementia, Vascular diagnosis, Dementia, Vascular metabolism, Dementia, Vascular physiopathology, Parkinsonian Disorders diagnosis, Parkinsonian Disorders metabolism, Parkinsonian Disorders physiopathology, RNA, Untranslated metabolism
Abstract

Age is the pivotal risk factor for different common medical conditions such as cardiovascular diseases, cancer and dementia. Among age-related disorders, cardiovascular and cerebrovascular diseases, represent the leading causes of premature mortality strictly related to vascular ageing, a pathological condition characterized by endothelial dysfunction, atherosclerosis, hypertension, heart disease and stroke. These features negatively impact on the brain, owing to altered cerebral blood flow, neurovascular coupling and impaired endothelial permeability leading to cerebrovascular diseases (CVDs) as Vascular Dementia (VD) and Parkinsonism (VP). It is an increasing opinion that neurodegenerative disorders and cerebrovascular diseases are associated from a pathogenetic point of view, and in this review, we discuss how cerebrovascular dysfunctions, due to epigenetic alterations, are linked with neuronal degeneration/dysfunction that lead to cognitive impairment. The relation between neurodegenerative and cerebrovascular diseases are reviewed with a focus on role of ncRNAs in age-related vascular diseases impairing the endothelium in the blood-brain barrier with consequent dysfunction of cerebral blood flow. In this review we dissert about different regulatory mechanisms of gene expression implemented by ncRNAs in the pathogenesis of age-related neurovascular impairment, aiming to highlight the potential use of ncRNAs as biomarkers for diagnostic/prognostic purposes as well as novel therapeutic targets., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Published
2020
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46. Infant colonisation with Escherichia coli and Klebsiella pneumoniae strains co-harbouring bla OXA-48 and bla NDM-1 carbapenemases genes: a case report.

Author

Monaco F, Mento GD, Cuscino N, Conaldi PG, and Douradinha B

Subjects
Drug Resistance, Multiple, Bacterial, Escherichia coli drug effects, Escherichia coli Infections drug therapy, Escherichia coli Proteins genetics, Humans, Infant, Klebsiella Infections drug therapy, Klebsiella pneumoniae drug effects, Male, Microbial Sensitivity Tests, beta-Lactamases genetics, Escherichia coli genetics, Escherichia coli Infections microbiology, Klebsiella Infections microbiology, Klebsiella pneumoniae genetics
Published
2018
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47. Emergence of a Klebsiella pneumoniae ST392 clone harbouring KPC-3 in an Italian transplantation hospital.

Author

Di Mento G, Cuscino N, Carcione C, Cardinale F, Conaldi PG, and Douradinha B

Subjects
Adult, Anti-Bacterial Agents pharmacology, Cross Infection microbiology, Female, Hospitals, Humans, Italy, Klebsiella Infections microbiology, Klebsiella pneumoniae enzymology, Klebsiella pneumoniae genetics, Klebsiella pneumoniae isolation & purification, Microbial Sensitivity Tests, Bacterial Proteins analysis, Cross Infection diagnosis, Genotype, Klebsiella Infections diagnosis, Klebsiella pneumoniae classification, Molecular Typing, beta-Lactamases analysis
Published
2018
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48. Pandemic influenza A/H1N1 virus in a swine farm house in Sicily, Italy.

Author

Guercio A, Purpari G, Conaldi PG, Pagano V, Moreno A, Giambruno P, Di Trani L, Vaccari G, Falcone E, Istituto AB, and Cordioli P

Subjects
Animals, Disease Outbreaks veterinary, Female, Humans, Influenza, Human epidemiology, Influenza, Human virology, Orthomyxoviridae Infections epidemiology, Orthomyxoviridae Infections virology, Pandemics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Sicily epidemiology, Swine, Swine Diseases epidemiology, Influenza A Virus, H1N1 Subtype classification, Orthomyxoviridae Infections veterinary, Swine Diseases virology
Abstract

This report describes a pandemic A/H1N1 (H1N1 pdm) virus outbreak occurred in December, 2009 in a swine farm used as research facility (Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione) for preclinical studies, located in Sicily, Italy. All the 13 pigs of the farm, showed cough, fever, inappetence and weakness. At the same time, an unvaccinated worker of the stabling showed influenza-like symptoms. RNAv extracted from two swabs collected from infected pigs resulted positive by Real Time RT-PCR for Influenza A virus. Furthermore, after growth on embryonated eggs, viral isolates were identified by Real Time RT-PCR specific for H1N1 pdm virus and characterized antigenically. Sequencing of the whole genome was also performed. All sera taken from animals and from the worker were tested by a competitive influenza A ELISA and by the haemoagglutination inhibition test. Serological findings confirmed the circulation of influenza virus H1N1 pdm in pigs and the presence of specific antibodies against H1N1 pdm in human serum. The results of this study seem to support a H1N1 pdm transmission from man to animals showing the importance of serological and virological investigation to control the pig farms and the importance of close cooperation between the different authorities like veterinarian and human public.

Published
2012

49. [HIV-1 and renal cells: pathogenesis of HIV-associated nephropathy].

Author

Conaldi PG and Camussi G

Subjects
Animals, Humans, AIDS-Associated Nephropathy etiology, HIV-1, Kidney cytology, Kidney virology
Abstract

Kidney is one of the organs, as haematopoietic tissue and central nervous system, representing a reservoir of HIV-1, where the virus can exert a direct pathogenic activity. HIV-associated nephropathy (HIVAN) is the prominent illness among the numerous renal injuries occurring in HIV-1 infection. It is characterized by heavy proteinuria and rapid progression to end stage renal disease. Histopathologically, HIVAN is a collapsing form of focal segmental glomerulosclerosis with podocyte hyperplasia and dedifferentiation, associated with severe tubulopathy which is characterized by tubular apoptosis, microcysts, and interstitial fibrosis. Several clinical and experimental data point to a direct role of HIV-1 in kidney damage. In renal biopsies of HIVAN cases viral transcripts have been found in glomerular and tubular epithelial cells. Transgenic mice expressing replication-defective HIV proviral constructs develop a renal disease similar to HIVAN both from the histopathological and clinical point of view. In vitro studies using cultures of human renal cells have shown that HIV-1 can induce in glomerular and tubular cells distinct pathogenic effects, which mimic the pathological features of HIVAN in vivo. A large body of evidence suggests that an abnormal response of podocytes to HIV-1 infection and/or HIV-1 proteins is the key event in HIVAN pathogenesis. Since the highly-active antiretroviral therapy has demonstrated scant beneficial effects on the development of HIVAN, the elucidation of the pathogenic mechanisms activated by HIV-1 in the renal cells might allow designing specific therapeutic strategies.

Published
2005

50. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome.

Author

Doublier S, Ruotsalainen V, Salvidio G, Lupia E, Biancone L, Conaldi PG, Reponen P, Tryggvason K, and Camussi G

Subjects
Adolescent, Adult, Aged, Blotting, Western, Cells, Cultured, Female, Fluorescent Antibody Technique, Gene Expression, Glomerulonephritis, Membranous genetics, Glomerulonephritis, Membranous metabolism, Glomerulonephritis, Membranous pathology, Humans, Kidney Glomerulus cytology, Male, Membrane Proteins, Middle Aged, Nephrotic Syndrome genetics, Nephrotic Syndrome metabolism, Proteins metabolism, Proteinuria genetics, Proteinuria metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Kidney Glomerulus metabolism, Nephrotic Syndrome pathology, Proteins genetics, Proteinuria pathology
Abstract

We investigated the distribution of nephrin by immunofluorescence microscopy in renal biopsies of patients with nephrotic syndrome: 13 with membranous glomerulonephritis (GN), 10 with minimal change GN, and seven with focal segmental glomerulosclerosis. As control, six patients with IgA GN without nephrotic syndrome and 10 normal controls were studied. We found an extensive loss of staining for nephrin and a shift from a podocyte-staining pattern to a granular pattern in patients with nephrotic syndrome, irrespective of the primary disease. In membranous GN, nephrin was co-localized with IgG immune deposits. In the attempt to explain these results, we investigated in vitro whether stimuli acting on the cell cytoskeleton, known to be involved in the pathogenesis of GN, may induce redistribution of nephrin on the surface of human cultured podocytes. Aggregated but not disaggregated human IgG(4), plasmalemmal insertion of membrane attack complex of complement, tumor necrosis factor-alpha, and puromycin, induced the shedding of nephrin with a loss of surface expression. This phenomenon was abrogated by cytochalasin and sodium azide. These results suggest that the activation of cell cytoskeleton may modify surface expression of nephrin allowing a dislocation from plasma membrane to an extracellular site.

Published
2001
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