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13. CLINICAL, BIOMOLECULAR AND IMMUNOLOGICAL INVESTIGATION OF KNEE OSTEOARTHRITIS

Author

Cammarata, FP, Minafra, L, Forte, GI, Sonnino, S, Gilardi, MC, BRAVATA', Valentina, Cammarata, FP, Minafra, L, Bravatà, V, Forte, GI, Sonnino, S, and Gilardi, MC

Subjects
Osteoarthritis, SNPs, IL
Abstract

Introduction. Osteoarthritis (OA) is a slowly progressive disorder characterized by a gradual loss of articular cartilage. The OA classification is mainly based on clinical and radiographic evaluations, using the Knee Society Score (AKSS) and the Kellgren and Lawrence (KL) scale. Single nucleotide polymorphisms (SNPs) in frzb, matn3,aspn, pthr2, gdf5 and dvwa genes are involved in OA susceptibility. However, very few studies in Caucasian people describe the association between KL grading scale and genetical alterations. In this study we assessed the associations between KL grade, clinical features,SNPs and inflammatory mediators in Sicilian individuals Methods. We enrolled 66 patients with primary OA, classified into 3 groups: A, B, C (mild, medium and severe OA) using AKSS and KL scale. Human Gene Mutation and dbSNP Short Genetic Variations databases were used to analyze the selected SNPs.The roles of cytokines was analyzed in synovial fluids by Luminex technology Results. In our patients cohort we observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function. The severity of symptoms increases with age. A significant association has been observed between KL grading and GDF5 and DVWA, displaying their predictive role as OA marker progression. IL 6/8/10/13 levels were associated with KL grading Conclusions. This work represents a multidisciplinary approach to better define OA grading and progression. Genetic background could have a significant role in the OA pathogenesis. SNPs and biochemical markers could be potentially used as OA progression markers in association with clinical and radiological feature

Published
2014

20. Evidence that ganglioside enriched domains are distinct from caveolae in MDCK II and human fibroblast cells in culture

Author

Chigorno, V, Palestini, P, Sciannambolo, M, Dolo, V, Pavan, Antonio, Tettamanti, G, Sonnino, S., Chigorno, V, Palestini, P, Sciannamblo, M, Dolo, V, Pavan, A, Tettamanti, G, and Sonnino, S

Subjects
GM3, caveolin-1, ganglioside, Cell Membrane, Fibroblasts, sphingolipid domain, Molecular Weight, Sphingosine, Gangliosides, caveolae, Animals, Humans, Electrophoresis, Polyacrylamide Gel, Cells, Cultured
Abstract

Cultures of MDCK II and human fibroblast cells were fed radioactive sphingosine and a radioactive GM3 ganglioside derivative containing a photoactivable group. The derived cell homogenates were treated with Triton X-100 and fractionated by sucrose-gradient centrifugation to prepare a detergent-insoluble membrane fraction known to be enriched in sphingolipid and caveolin-1, i.e. of caveolae. The detergent-insoluble membrane fraction prepared after feeding [1-3H]sphingosine to cells, was found to be highly enriched, with respect to protein content, in metabolically radiolabeled sphingomyelin and glycosphingolipids (about 18-fold). By feeding cells photoactivable radioactive GM3, after 2 h-chase, caveolin-1, CAV1, and proteins of high molecular mass became cross-linked to GM3, the cross-linking complexes being highly concentrated in the detergent-insoluble membrane fraction. The interaction between the ganglioside derivative and CAV1 was a time-dependent, transient process so that CAV1 cross-linking to GM3 was hardly detectable after a 24-h chase followed the pulse time. After a 24-h chase, only the high molecular mass proteins cross-linked to GM3 could be clearly observed. These results suggest that a portion of the GM3 administered to cells enters caveolae and moves to the glycosphingolipid domains, or enters caveolae that are then rapidly catabolized. Electron microscopy of cells in a culture immunostained with a monoclonal antibody to GM3 and a secondary gold-conjugated antibody detected several clusters of gangliosides on the plasma membranes separate from caveolae; gangliosides located inside the caveolae could not be detected. Scanning confocal microscopy of cells immunostained with anti-GM3 and anti-CAV1 Ig showed only a very small overlap with the CAV1 and GM3 signals. Thus, the biochemical and microscopic studies suggest that caveolae contain at most a low level of gangliosides and are separate from the GM3 ganglioside enriched domains.

Published
2000

22. Ceramide production at the plasma membrane

Author

Aureli, M., Loberto, N., Masilamani, A.P., Illuzzi, G., Prinetti, A.E.G., Chigorno, V.L., and Sonnino, S.

Subjects
Settore BIO/10 - Biochimica, Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Published
2009

30. N-glycolyl GM1 ganglioside as a receptor for Simian virus 40 (SV40)

Author

Campanero-Rhodes, M.A., Smith, A., Chai, W., Sonnino, S., Mauri, L., Childs, R.A., Zhang, Y., Ewers, H., Helenius, A., Imberty, A., Feizi, T., Centre de Recherches sur les Macromolécules Végétales (CERMAV), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)

Subjects
ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

45. Gene Therapy of Tay-Sachs disease

Author

Martino, Sabata, Emiliani, Carla, Severini, G. M., Tancini, Brunella, Chigorno, V., Consiglio, A., Dolcetta, D., Trojani, A., Sonnino, S., Orlacchio, Aldo, and Bordignon, C.

Subjects
gene therapy lysosomal storage disorders review
Published
2000

47. MEDICAL SCIENCE. GISSI-2: A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction

Author

Feruglio, G. A., Lotto, A., Rovelli, F., Solinas, P., Tavazzi, L., Tognoni, G., De Vita, C., Franzosi, M. G., Maggiom, A. P., Mauri, F., Volpi, A., Selvini, A., Donato, L., Garattmi, S., Loi, U., Sirchia, G., Ambrosioni, E., Camerini, F., Campolo, L., Donati, M. B., Ferrari, M., Farchi, G., Geraci, E., Mannucci, P. M., Marubini, E., Neri Semeri, G. G., Peto, R., Prati, P. L., Specchia, G., Vecchio, C., Visani, L., Yusuf, S., Mezzanotte, G., Santoro, E., Bruno, M., Cappello, T., Coppini, A., Fincati, F., Mantovani, G., Pangrazzi, J., Pogna, M., Turazza, F. M., Ansehni, M., Barbonaglia, L., Bigi, R., Cavalli, A., Frigerio, M., Giordano, A., Gualtierotti, C., Torta, D., Vinci, P., Bossi, M., Furlanello, F., Braito, E., Giulia, V., Palmieri, M., Majoimo, P., Pinelli, G., Papi, L., Nardelli, A., Capestro, F., Rossi, A., Ricci, D., Mininni, N., Bianco, G., Barbuzzi, S., Plastina, F., Di Giovanna, F., Mereu, D., Giordano, F., Barlotti, R., Loparco, G., Boscarino, S., Ruggeri, G., Anastasi, R., Paciaroni, E., Tomassini, P. F., Purcaro, A., Francesconi, M., Figliolia, S., Tesse, S., Devoti, G., Giometti, R., Teoni, P., Burali, A., Zucconelli, V., Iervoglini, A., Amabili, S., Caratti, C. A., Zola, G., Ferraguto, P., Sagci, G., Rotiroti, D., Genovese, M., Da€™amato, N., Taurino, L., Colonna, L., Bovenzi, F., Messina, D., Sarcina, G., Compostella, L., Cucchini, F., Malacrida, R., Gradel, C., Bridda, A., Pellegrini, P., Acone, L., Bruno, A., Tespili, M., Guaghurrii, G., Casari, A., Bobba, F., Scaramuzzino, G., Berardi, C., De Castro, U., Fulvi, M., Lintner, W., Erlicher, A., Pitscheider, W., Scola Gagliardi, R., Bonizzato, G., Roggero, C., Perrini, A., Tsialtas, D., Straneo, U., Storelli, A., Verrienti, A., Albonico, B., Corradi, L., De Petra, V., Villani, C., Maxia, P., Bianco, A., Crabu, E., Centamore, G., Di Stefano, G., Vancheri, F., Amico, C., Baldini, F., Santopuoli, G., Pantaleoni, A., Contessotto, F., Terlizzi, R., Turchi, E., Teglio, V., Pignatti, F., Aletto, C., Gozzelino, G., Pettinati, G., De Santis, F., Correale, E., Romano, S., Perrotta, R., Tritto, C., May, L., Achilli, G., Suzzi, G., Cemetti, C., Longobardi, R., Somma, G., Palumbo, C., Gallone, P., Sorrentino, F., Dato, A., Della Monica, R., Pagano, L., Alberti, A., Orselli, L., Negrini, M., De Ponti, C., Acito, P., Capelletti, D., Bortolini, F., Coppola, V., Ciglia, C., De Cesare, M., De Lio, U., Maiolino, P., Giannini, R., Niccolini, A., Marinoni, C., Guasconi, C., Sonnino, S., Pagliei, M., Ferrari, G., Politi, A., Galli, M., De Rinaldis, G., Calcagnile, A., Bendinelli, S., Lusetti, L., Mollaioli, M., Cosmi, F., Venneri, N., Feraco, E., Lauro, A., Catelli, P., Poluzzi, C., Distante, S., Pedroni, P., Zampaglione, G., Lumare, R., Bruna, C., De Benedictis, N., Ziacchi, V., Lomanto, B., Riva, D., Bertocchi, P., Tirella, G., Tessitori, M., Bini, A., Peruzzi, F., Maresta, A., Pirazzini, L., Gaggi, S., Frausini, G., Malacame, C., Codeca, L., Cappato, R., Andreoli, L., Bastoni, L. A., Pucci, P., Sarro, F., Vergassola, R., Barchielli, M., De Matteis, D., Carrone, M., Liberati, R., Meniconi, L., Radogna, M., Tallone, M., Ieri, A., Ferreri, A., Guidali, P., Canziani, R., Mariello, F., Minelli, C., Muzio, L., Rota Baldini, M., Lupi, G., Cecchi, A., Giuliano, G., Bellotti, S., Livi, S., Corti, E., Rossi, P., Delfino, R., Iannetti, M., Pastorini, C., Pennesi, A., Di Giacinto, N., Bertolo, L., Slomp, L., Cresti, A., Svetoni, N., Distefano, S., Veneri, L., Moretti, S., Palermo, R., Giovanelli, N., Parchi, C., Dethomads, M., Paparella, N., Carrino, C., Aquaro, G., Idone, P., Marsili, P., Sideri, F., Valerio, A., Tullio, D., Ragazzini, G., Gramenzi, S., De Pasquale, B., Gelfo, P. G., Rosselli, P., De Marchi, E., Greco, M. R., Fazio, A. M., Savoia, M. T., Gerosa, C., Barbiero, M., Barbaresi, F., Volta, G., Da€™urbano, M., Passoni, F., Parola, G., Lanzini, A., Baldini, U., Del Bene, P., Orlandi, M., Oddone, A., Lazzari, M., Ballerini, B., Bozzi, L., Moccetti, T., Bemasconi, E., Sanguinetti, M., Tognoli, T., Bardelli, G., Maggi, A., Turato, R., Piva, M., Izzo, A., Tantalo, L., Rizzi, A., Scilabra, G., Varvaro, F., Colombo, G., Grieco, A., Dovico, E., Belluzzi, F., Casellato, F., Lecchi, G., Maugeri Sacci, C., Consolo, A., Piccolo, E., Zuin, G., Zappa, C., Sanna, G. P., Dossena, M. G., Corsini, C., Lettino, M., Marconi, M., Mafrici, A., Leonardi, G., Moreo, A., Seregni, R., Pastine, I., Casazza, F., Regalia, F., Maggiolini, S., Benenati, P. M., Rigo, R., Pascotto, P., Zanocco, A., Artusi, L., Cappelli, C., Bernardi, C., Pahnieri, M., Zilio, G., Sandri, R., Neri, G., Valagussa, F., Osculati, G., Cira, A., Da€™aniello, L., Piantadosi, F. R., Improta, M., Severino, S., Bisconti, C., Mostacci, M., Randon, L., Boschello, M., Allegri, M., Freggiaro, V., Mureddu, V., Soro, F., Marras, E., Marchi, S. M., De Luca, C., Manetta, M., Dalla Volta, S., Maddalena, F., Donzelli, M., Vitrano, M. G., Canonico, A., Ledda, A., Bellomare, D., Carrubba, A., Da€™antonio, E., Scardulla, C., Raineri, A., Traina, M., La Calce, C., Cirincione, V., Montanar, F., Strizzolo, L., Di Gregorio, D., Mantini, L., Chiriatti, G., Gazzola, U., Rosi, A., Mellini, M., Piazza, R., Micheli, G., Bechi, S., Martines, C., Marchese, D., Bigalli, A., Davini, P., Boem, A., Del Citerna, F., Giomi, A., Codeluppi, P., Negrelli, M., Brieda, M., Charmet, P. A., Petrella, A., Bardazzi, L., Bianco, G. A., Marco, A., Licitra, R., Lettica, G. V., Tumiotto, G., Bosi, S., Spitali, G., Casali, G., Bottoni, N., Parenti, G. F., Triulzi, E., Brighi, F., Benati, A., De Sanctis, A., Mene, A., Pesaresi, A., Bologna, F., Lumia, F., Barbato, G., Milazzotto, F., Proietti, F., Angrisani, G., Azzolini, P., Coppola, E., Trani, Carlo, Masini, V., Rocchi, M., Borgia, M. C., Luciani, C., Vitucci, N. C., Giuliani, P., Tugnoli, F., Vetta, C., Altieri, T., Gimigliano, F., Striano, U., Salituri, S., Zanazzi, G., Zonzin, P., Bugatti, U., Ravera, B., Allemano, P., Reynaud, S., Sanson, A., Milani, L., De Simone, M. V., Villella, A., Grazzini, M., Amidei, S., Ansehni, L., Benza, G., Tagliamonte, A., Messina, V., Etro, M. D., Vivaldi, F., Cortese, R., Ibba, G. V., Sannia, L., Pedrazzini, F., Gazzotti, G. L., Pizzuti, A., Antonielli, E., Becchi, G., Filice, A., Salmoiraghi, A., Caramanno, G., Caporicci, D., Brun, M., Ferrario, G., Giani, P., Ronconi, G., Douglas, S., Bianchi, C., Cucchi, G., Marieni, M., Marcellini, G., Speca, G., Beato, E., Serabni, N., Bazzucchi, M., Coronelli, R., Rossi, L., Basso, G., Presbitero, P., Bevilacqua, R., Pallisco, O., Di Leo, M., Golzio, P. G., Parigi, A., Belli, R., Trinchero, R., Gaschino, G., Barenghi, M., Poggio, G. L., Braschi, G. B., Sciacca, R., Sammartano, A., Braito, G., Cuzzato, V., Frigo, G., Perissinono, F., Galati, A., Accogli, M., Morgera, T., Barbieri, L., Slavich, G. A., Fresco, C., Cuda, A., Liguori, A., Cozzi, A., Caico, S., Alberio, M., Di Marco, G., De Vito, G., Valente, S., Zagatti, G., Zardini, P., Nidasio, G. P., Girardi, P., Mazzini, C., Nava, S., Achilli, A., Bisogno, A., Pasotti, C., Ballestra, A. M., and Giustarini, C.

Subjects
Aspirin, medicine.medical_specialty, business.industry, Streptokinase, acute myocardial infarction, General Medicine, Heparin, medicine.disease, Atenolol, Surgery, Anistreplase, Anesthesia, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, medicine, Myocardial infarction, business, Stroke, medicine.drug, Killip class
Abstract

A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1·5 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12 500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study was the combined estimate of death plus severe left ventricular damage. 12 490 patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA alone, tPA plus heparin). No specific differences between the two thrombolytic agents were detected as regards the combined end-point (tPA 23·1%; SK 22·5%; relative risk 1·04, 95% Cl 0·95-1·13), nor after the addition of heparin to the aspirin treatment (hep 22·7%, no hep 22·9%; RR 0·99, 95% Cl 0·91-1·08). The outcome of patients allocated to the four treatment groups was similar with respect to baseline risk factors such as age, Killip class, hours from onset of symptoms, and site and type of infarct. The rates of major in-hospital cardiac complications (reinfarction, post-infarction angina) were also similar. The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0·5%, SK 1·0%, RR 0·57, 95% Cl 0·38-0·85; hep 1·0%, no hep 0·6%, RR 1·64, 95% Cl 1·09-2·45), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8·8% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI.

Published
1990

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