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2. Cytochalasin D restores nuclear size acting on F-actin and IZUMO1 localization in low-quality spermatozoa

Author

Martinez G, Cappetta D, Telesca M, Urbanek K, Castaldo G, Dhellemmes M, Mele VG, Chioccarelli T, Porreca V, Barbotin AL, Boursier A, Guillou F, Coutton C, Brouillet S, De Angelis A, Berrino L, Pierantoni R, Cobellis G, Chianese R, Manfrevola F, Martinez, G, Cappetta, D, Telesca, M, Urbanek, K, Castaldo, G, Dhellemmes, M, Mele, Vg, Chioccarelli, T, Porreca, V, Barbotin, Al, Boursier, A, Guillou, F, Coutton, C, Brouillet, S, De Angelis, A, Berrino, L, Pierantoni, R, Cobellis, G, Chianese, R, and Manfrevola, F

Subjects
Cell Biology, Molecular Biology, Applied Microbiology and Biotechnology, Ecology, Evolution, Behavior and Systematics, F actin, IZUMO1, sperm quality, chromosomes territories, histone acetylation, Developmental Biology
Abstract

In spermatozoa, the nuclear F-actin supports the acroplaxome, a subacrosomal structure involved in the correct exposure of several acrosomal membrane proteins; among them, the glycoprotein IZUMO1 is the major protein involved in sperm-oocyte fusion. Nuclear F-actin is also involved in sperm head shaping and chromosome compartmentalization. To date, few notions regarding the bivalent role of F-actin on sperm chromatin organization and IZUMO1 positioning have been reported. In our work, we characterized subcellular organization of F-actin in human high- and low-quality spermatozoa (A- and B-SPZ), respectively, showing that F-actin over-expression in sperm head of B-SPZ affected IZUMO1 localization. A correct IZUMO1 repositioning following in vitro induction of F-actin depolymerization, by cytochalasin D treatment, occurred. Interestingly, F-actin depolymerization was also associated with a correct acrosome repositioning, thus to favor a proper acrosome reaction onset, with changes in sperm nuclear size parameters and histone acetylation rate reaching high-quality conditions. In conclusion, the current work shows a key role of F-actin in the control of IZUMO1 localization as well as chromatin remodeling and acetylation events.

Published
2023
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5. Atrial fibrillation: Epigenetic aspects and role of sodium-glucose cotransporter 2 inhibitors

Author

Donniacuo, M., primary, De Angelis, A., additional, Telesca, M., additional, Bellocchio, G., additional, Riemma, M.A., additional, Paolisso, P., additional, Scisciola, L., additional, Cianflone, E., additional, Torella, D., additional, Castaldo, G., additional, Capuano, A., additional, Urbanek, K., additional, Berrino, L., additional, Rossi, F., additional, and Cappetta, D., additional

Published
2023
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6. Il ruolo primario dell'indennizzo (L. 210/92) per un'adeguata campagna vaccinale in tempo di COVID-19

Author

Capuano, A, Cupelli, C, Militerni, M, Riccardi, C, Mascolo, A, Berrino, L, Ferrari, M, La Torre, M, Attademo, G, Maccaro, A, Fulgeri, G, Paesano, G, Palazzani, L, Militerni, M., Capuano, A., Riccardi, C., Mascolo, A., Berrino, L., Ferrari, M., Cupelli, C., La Torre, M. A., Attademo, G., Maccaro, A., Fulgeri, G., Paesano, G., Palazzani, L., Capuano, A, Cupelli, C, Militerni, M, Riccardi, C, Mascolo, A, Berrino, L, Ferrari, M, La Torre, M, Attademo, G, Maccaro, A, Fulgeri, G, Paesano, G, Palazzani, L, Militerni, M., Capuano, A., Riccardi, C., Mascolo, A., Berrino, L., Ferrari, M., Cupelli, C., La Torre, M. A., Attademo, G., Maccaro, A., Fulgeri, G., Paesano, G., and Palazzani, L.

Abstract

Dall'introduzione della legge 210/92 con la previsione di un indennizzo per lesioni o menomazioni permanenti a seguito di una vaccinazione obbligatoria per legge, la Corte Costituzionale ha ampliato, con specifiche analisi caso per caso e decisioni, anche a eventi avversi derivanti da vaccinazioni soltanto raccomandate, come il vaccino anti-COVID 19. L'Autrice auspica il riconoscimento diretto dell'indennizzo da parte del giudice ordinario competente anche in assenza di pronuncia della Corte Costituzionale, vista l'innegabilità della funzione pubblica e socialmente utile di ogni vaccinazione raccomandata, che velocizzerebbe i tempi di ristoro e conforterebbe la popolazione restia a sottoporsi al vaccino in tempi di pandemia.

Published
2021

9. Increased Programmed Death Ligand 1 (PD-L1) Expression Profile in Structural and Immune Cells from Mild COPD Patients and Lung Cancer

Author

Mirra, D., primary, Esposito, R., additional, Spaziano, G., additional, Sgambato, M., additional, Piegari, E., additional, Cozzolino, A., additional, Cione, E., additional, Gallelli, L., additional, Capuozzo, A., additional, Santoriello, C., additional, Berrino, L., additional, D'Agostino, B., additional, and Polverino, F., additional

Published
2022
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11. Il ruolo primario dell'indennizzo (L. 210/92) per un'adeguata campagna vaccinale in tempo di COVID-19

Author

Militerni, M., Capuano, A., Riccardi, C., Mascolo, A., Berrino, L., Ferrari, M., Cupelli, C., La Torre, M. A., Attademo, G., Maccaro, A., Fulgeri, G., Paesano, G., Palazzani, L., Capuano, A, Cupelli, C, Militerni, M, Riccardi, C, Mascolo, A, Berrino, L, Ferrari, M, La Torre, M, Attademo, G, Maccaro, A, Fulgeri, G, Paesano, G, and Palazzani, L

Subjects
tutela salute pubblica collettiva, vaccinazione obbligatoria raccomandata, risarcimento, indennizzo, IUS/01 - DIRITTO PRIVATO, vaccinazione obbligatoria raccomandata, indennizzo, risarcimento, tutela salute pubblica collettiva, Vaccino anti Covid-19
Abstract

Dall'introduzione della legge 210/92 con la previsione di un indennizzo per lesioni o menomazioni permanenti a seguito di una vaccinazione obbligatoria per legge, la Corte Costituzionale ha ampliato, con specifiche analisi caso per caso e decisioni, anche a eventi avversi derivanti da vaccinazioni soltanto raccomandate, come il vaccino anti-COVID 19. L'Autrice auspica il riconoscimento diretto dell'indennizzo da parte del giudice ordinario competente anche in assenza di pronuncia della Corte Costituzionale, vista l'innegabilità della funzione pubblica e socialmente utile di ogni vaccinazione raccomandata, che velocizzerebbe i tempi di ristoro e conforterebbe la popolazione restia a sottoporsi al vaccino in tempi di pandemia.

Published
2021

14. Correction to: Angiotensin II and angiotensin 1–7: which is their role in atrial fibrillation? (Heart Failure Reviews, (2020), 10.1007/s10741-020-09961-9)

Author

Mascolo A., Urbanek K., De Angelis A., Sessa M., Scavone C., Berrino L., Rosano G. M. C., Capuano A., Rossi F., Mascolo, A., Urbanek, K., De Angelis, A., Sessa, M., Scavone, C., Berrino, L., Rosano, G. M. C., Capuano, A., and Rossi, F.

Abstract

There was a mistake in Prof. Giuseppe Massimo Claudio Rosano’s affiliation.

Published
2020

15. ABCA1, TCF7, NFATC1, PRKCZ and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis

Author

Infante, T, primary, Franzese, M, additional, Ruocco, A, additional, Schiano, C, additional, Affinito, O, additional, Pane, K, additional, Memoli, D, additional, Rizzo, F, additional, Weisz, A, additional, Bontempo, P, additional, Grimaldi, V, additional, Berrino, L, additional, Soricelli, A, additional, Mauro, C, additional, and Napoli, C, additional

Published
2021
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16. Circulating CD4+T/methylation signatures of network-oriented SOCS3, ITGAL, NFIC, NCOR2, PGK1 genes associate with hemodynamics in pulmonary arterial hypertension patients

Author

Benincasa, G, primary, Maron, B A, additional, Affinito, O, additional, D'Alto, M, additional, Franzese, M, additional, Argiento, P, additional, Schiano, C, additional, Romeo, E, additional, Bontempo, P, additional, Golino, P, additional, Berrino, L, additional, Loscalzo, J, additional, and Napoli, C, additional

Published
2021
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18. Neuron-specific enolase serum levels in COVID-19 are related to the severity of lung injury

Author

Cione E., Siniscalchi A., Gangemi P., Cosco L., Colosimo M., Longhini F., Luciani F., De Sarro G., G, SP Working Group, Giuseppe Spaziano, Berrino L., D'Agostino B., Gallelli L., Cione, E., Siniscalchi, A., Gangemi, P., Cosco, L., Colosimo, M., Longhini, F., Luciani, F., De Sarro, G., G&amp, SP Working Group, Spaziano, Giuseppe, Berrino, L., D'Agostino, B., and Gallelli, L.

Subjects
RNA viruses, Male, Viral Diseases, Pulmonology, Coronaviruses, Biochemistry, Severity of Illness Index, Gastroenterology, Lung and Intrathoracic Tumors, Procalcitonin, Small Cell Lung Cancer, Medical Conditions, Epidemiology, Immunologic Test, Pathology and laboratory medicine, Multidisciplinary, Lung Injury, Medical microbiology, Middle Aged, C-Reactive Proteins, Infectious Diseases, medicine.anatomical_structure, Oncology, Italy, Viruses, Medicine, Tuberculosis Diagnosis and Management, Female, SARS CoV 2, Pathogens, Research Article, Human, Adult, medicine.medical_specialty, SARS coronavirus, Coronavirus disease 2019 (COVID-19), Science, Enolase, Immunologic Tests, Lung injury, Microbiology, Respiratory Disorders, Diagnostic Medicine, Internal medicine, Severity of illness, medicine, Humans, Medicine and health sciences, Chemiluminescence assay, Lung, Biology and life sciences, SARS-CoV-2, business.industry, Organisms, Viral pathogens, Proteins, Cancers and Neoplasms, COVID-19, Covid 19, Biomarker, Microbial pathogens, Dyspnea, Phosphopyruvate Hydratase, Respiratory Infections, business, Biomarkers
Abstract

The multifunctional role of neuron-specific enolase (NSE) in lung diseases is well established. As the lungs are greatly affected in COVID-19, we evaluated serum NSE levels in COVID-19 patients with and without dyspnea. In this study, we evaluated both SARS-CoV-2-infected and uninfected patients aged >18 years who were referred to hospitals in Catanzaro, Italy from March 30 to July 30, 2020. Epidemiological, clinical, and radiological characteristics, treatment, and outcome data were recorded and reviewed by a trained team of physicians. In total, 323 patients (178 men, 55.1% and 145 women, 44.9%) were enrolled; of these, 128 were COVID-19 patients (39.6%) and 195 were control patients (60.4%). Westergren’s method was used to determine erythroid sedimentation rate. A chemiluminescence assay was used for measurement of interleukin-6, procalcitonin, C-reactive protein, and NSE. We detected significantly higher NSE values (P

Published
2021
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19. Amelioration of diastolic dysfunction by dapagliflozin in a non-diabetic model involves coronary endothelium

Author

Cappetta, D., De Angelis, A., Ciuffreda, L. P., Coppini, R., Cozzolino, A., Micciche, A., Dell'Aversana, C., D'Amario, D., Cianflone, E., Scavone, C., Santini, L., Palandri, C., Naviglio, S., Crea, F., Rota, M., Altucci, L., Rossi, F., Capuano, A., Urbanek, K., Berrino, L., De Angelis A., D'Amario D., Crea F. (ORCID:0000-0001-9404-8846), Capuano A., Cappetta, D., De Angelis, A., Ciuffreda, L. P., Coppini, R., Cozzolino, A., Micciche, A., Dell'Aversana, C., D'Amario, D., Cianflone, E., Scavone, C., Santini, L., Palandri, C., Naviglio, S., Crea, F., Rota, M., Altucci, L., Rossi, F., Capuano, A., Urbanek, K., Berrino, L., De Angelis A., D'Amario D., Crea F. (ORCID:0000-0001-9404-8846), and Capuano A.

Abstract

The results of trials with sodium-glucose cotransporter 2 (SGLT2) inhibitors raised the possibility that this class of drugs provides cardiovascular benefits independently from their anti-diabetic effects, although the mechanisms are unknown. Therefore, we tested the effects of SGLT2 inhibitor dapagliflozin on the progression of experimental heart disease in a non-diabetic model of heart failure with preserved ejection fraction. Dahl salt-sensitive rats were fed a high-salt diet to induce hypertension and diastolic dysfunction and were then treated with dapagliflozin for six weeks. Dapagliflozin ameliorated diastolic function as documented by echo-Doppler and heart catheterization, while blood pressure remained markedly elevated. Chronic in vivo treatment with dapagliflozin reduced diastolic Ca2+ and Na+ overload and increased Ca2+ transient amplitude in ventricular cardiomyocytes, although no direct action of dapagliflozin on isolated cardiomyocytes was observed. Dapagliflozin reversed endothelial activation and endothelial nitric oxide synthase deficit, with reduced cardiac inflammation and consequent attenuation of pro-fibrotic signaling. The potential involvement of coronary endothelium was supported by the endothelial upregulation of Na+/H+ exchanger 1in vivo and direct effects on dapagliflozin on the activity of this exchanger in endothelial cells in vitro. In conclusions, several mechanisms may cumulatively play a significant role in the dapagliflozin-associated cardioprotection. Dapagliflozin ameliorates diastolic function and exerts a positive effect on the myocardium, possibly targeting coronary endothelium. The lower degree of endothelial dysfunction, inflammation and fibrosis translate into improved myocardial performance.

Published
2020

28. Abstracts of posters

Author

Suffisseau L., Taugourdeau M. C., Goldstein F. W., Mainardi J. L., Larrouturou Ph., Romero, M., Cervino, A. R., Albertone, G., Di Pasquale, R., Venturini, F., Congedo, R., Benettolo, F., Pistolesi, C., Olivato, R., Casasin T., Agusti C., Gurrera M. T., Fabregas X., Rizo A., Badia J. M., Santa-Olalla M., Marini, P., Rampazzo, R., Scroccaro, G., Dell'Aera, M., Luzzi, R., Ciccarone, G., Martinet, N., Beney, J., Marty, S., Reymond, J. -Ph., Cairns, Chris, Morgutti M., Posco M., Moltempi M., Lonqhini P., Rossignoli A., Rihet, P., Carles, G., Braguer, D., Azulay, J. P., Pouget, J., Pelletier, J., Crevat, A., Past.o, L., Barroso, E., Pujol, R., Ferrer, I., Ibars, M., Llop, J. M., Frankfort, Ellen, van Dongen, Robert T. M., Hekster, Yechiel A., Kart, T., Rasmussen, M., Horn, A., Wested, L., Gagyi, O., Markó, E., Regazzi M. B., Martinelli L., Goggi C., Bellotti E., Molinaro M., Rinaldi M., Gavazzi A., Buggia I., Daneri A., Guarnone E., Bascapē V., Viganô M., Lazzaro, A., Palozzo, A., Banfi R., Borselli G., Fabbiani P., Marinai C., Delorme, J., Tubiana, N., Buck, M., Chinot, O., De Wever, C., Robays, H., Montoro J. B., Flores G., Juárez J. C., Juste C., Jardí R., Altisent C., Tusell J. M., Arpinelli, F., De Carli, G., Olivieri, A., Recchia, G., Rossignoli A., Longhini P., La Guidara C., Russo B., Moltempi M., Tamés, M. J., Cajaraville, G., Ponz, L., Echaniz, E., Garcia, B., van Mil, J. W. Foppe, Leufkens, Hubert G., v. Haelst, Ingrid M. M., Parel, Piet C. M., Scholten, Wim K., Sessink, F. G. M., Raschatt, R., Traversa, G., Donini, G., Arpino, C., Da Cas, R., Pasquin, P., Bernadotte af Wisborg G., Claesson C., Lundberg O., Thorslund M., Ferraro L., Marrazzo E., Ostino G., Tognoni G., Heerdink, Eibert R., Koppedraaijer, Corrie, Bakker, Albert, Bidoli E., Battistin M., Troncon M. G., Franceschi S., Serraino D., Marino, M., Matera, M. G., Berrino, L., Contaldi, C., Piucci, B., Rossi, F., Rolle C., Marrazzo E. 0., Murgia, V., Bussi, R., Schievano, P., Pedrini, A., Baraghini, M., Benini, A., Cataldo, M. M., Galletti, P., Magnani, M., Manzoli, M., Novi, M. V., Pezzi, O., Font M., Salmaso A. B., Mezzalira L., Braybrook, Saran, Walker, Roger, van Mil, J. W. F., Tromp, F. T. J., de Jong-v.d. Berg, L. T. W., Bakker, A., Paes, A. H. P., Soe-Agnie, C., Llopis, P., Tortajada, J. J., Font, I., Climente, M., Real, J. V., Almenar, D., Molins, C., Jiménez, N. V., Bellés Medall MD, Casterá Melchor DE, Marco Sena MA, Cantarinz Marti I., Abad Gimeno FJ, Török, J., Thurzó, L., Juárez J. C., Oliveras M., Hidalgo E., Cabañas M. J., Barroso C., Moraga F. A., Sánchez de Toledo J., Kollöffel, W. J., Driessen, F. G. W. H. M., Goldhoorn, P. B., Moral, M. A., Roglan, A., Mangues, M. A., Bonal, J., Clopés, A., Badell, I., Fraga, G., Deinum, J. T., van Lingen, R. A., Quak, J. M. E., Kuizenga, A. J., van Dam, J. G., Villani P., Maserati R., Viale P., Alberici F., Iacona I., Wasieczko, A., Szymura-Oleksiak, J., Wyska, E., Magulova, L., Sirotiakova, J., Letkovicova, M., Branger, E., Besse, D., Blin, O., Bille, F., Serratrice, G., Desnuelle, C., Grassin, J., Reben, I., Meunier, Ph., Antier, D., Berthet, M., Søndergaard B., Herborg H., Frøkjær B., Hepler C., Steckner, H., Bergold, A., Drings, P., Märkel, A., Manegold, C., Venning, Mary, Pazzagli, Luciana, Semmola, Maria Vittoria, Mannoni, Alessandro, Tersen I., Huchet J., Sevilla, E., Ferrari, J. M., Herreros de Tejada, A., Congedo, R., Font, M., Fraccaro, A., Osti, M., Pappagallo, G., Spolaor, A., Terrazzani, G., Vezzani, M., Edouard B., Laine G., Geeraerts D., Robays H., Carrera-Hueso, F. J., Font, B., Marquina, C., Idoate, A., Giráldez, J., Fernández, E., Lacasa, C., Guzzo, D., Martini, N., Boya, P. Giner, González, M. M. Negredo, Agulló, J. Muñoz, Mansilla, L. Lorente, Nahata, Milap C., Troncon, M. G., Cattaruzzi, C., Bilbao G., Galende I., Atañé C., Bermudez de Castro A., Delgado O., Escribano B., Frías J., Gabriel R., Gómez J. A., Gracia D., Gutiérrez E., Hellín T., Izquierdo J. L., Moreno A., Requena T., Sainz-Terreros M., Tejedor J. C., Torralba A., Vigil D., Scuffi, C., Trallori, G., Messori, A., Bardazzi, G., Bonanomi, A., Silvano, R., D'Albasio, G., Bardelli, F., Verona, Firenzee, Bardelli, F., Corrado, A., Ferriols R., Aleixander M. J., Garcia J., Faus M., Ibañez E., Alós M., Rinaldi, M., Pharmacy & Therapeutic Committee (Ps&TC), Collaborative Group, SIFO-Veneto Working Group on Clinical Trials, Working Group on the Elaboration of an Approval Conditions Document to certify the Clinical Trials Ethics Committees in the Autonomous Community of Madrid, and Area SIFO di Metanalisi

Published
1994
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33. Effects of ranolazine in a model of doxorubicin-induced left ventricle diastolic dysfunction

Author

Cappetta D, Esposito G, Coppini R, Piegari E, Russo R, Ciuffreda LP, Rivellino A, Santini L, Rafaniello C, Scavone C, Rossi F, Berrino L, Urbanek K, De Angelis A, Cappetta, D, Esposito, G, Coppini, R, Piegari, E, Russo, R, Ciuffreda, Lp, Rivellino, A, Santini, L, Rafaniello, C, Scavone, C, Rossi, F, Berrino, L, Urbanek, K, and De Angelis, A

Published
2017

36. Doxorubicin cardiotoxicity and target cells: a broader perspective

Author

De Angelis A, Urbanek K, Cappetta D, Piegari E, Ciuffreda LP, Rivellino A, Russo R, Esposito G, Rossi F, Berrino L, De Angelis, A, Urbanek, K, Cappetta, D, Piegari, E, Ciuffreda, Lp, Rivellino, A, Russo, R, Esposito, G, Rossi, F, and Berrino, L

Published
2016

37. Treatment of HFpEF: An unresolved enigma

Author

Urbanek, K., primary, Cappetta, D., additional, Coppini, R., additional, Ciuffreda, L.P., additional, Esposito, G., additional, Rossi, F., additional, Berrino, L., additional, and De Angelis, A., additional

Published
2018
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43. Neutralization of IL-18 inhibits injury-induced neointima formation

Author

MAFFIA, PASQUALE, GRASSIA, GIANLUCA, CARNUCCIO, ROSA, IANARO, ANGELA, IALENTI, ARMANDO, DI MEGLIO P, BERRINO L, GARSIDE P, Maffia, Pasquale, Grassia, Gianluca, DI MEGLIO, P, Carnuccio, Rosa, Berrino, L, Garside, P, Ianaro, Angela, and Ialenti, Armando

Published
2006

44. Epigenetics in Cardiac Health and Disease225miR-218 and mi-R34a drive persistent myocardial oxidative stress by targeting chromatin remodelers DNMT3b and SIRT1: new mechanistic insights in diabetic cardiomyopathy226Effects of miRNAs modulated by endurance training on cardiomyocyte excitability227Differential transcriptome and microRNA expression signatures in the healthy heart (RV vs. LV) and the failing, pressure-overloaded right ventricle (SuHx model)

Author

Costantino, S, primary, Bonzanni, M, primary, Legchenko, E, primary, Paneni, F, additional, Mitchell, K, additional, Berrino, L, additional, Schwarzwald, C, additional, Volpe, M, additional, Luscher, TF, additional, Cosentino, F, additional, Napoli, A, additional, Landi, S, additional, Bucchi, A, additional, Vernillo, G, additional, Baruscotti, M, additional, La Torre, A, additional, Difrancesco, D, additional, Barbuti, A, additional, Kueffner, R, additional, and Hansmann, G, additional

Published
2016
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45. Moderatore

Author

Riccardi, Carlo and Berrino, L.

Published
2012

46. Cytokines and VEGF Induction in Orthodontic Movement in Animal Models

Author

Di Domenico, M., D'apuzzo, F., Feola, A., Cito, L., Monsurrò, A., Pierantoni, G. M., Berrino, L., De Rosa, A., Polimeni, A., and Perillo, L.

Subjects
stomatognathic diseases, stomatognathic system, Article Subject
Abstract

Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1β and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor.

Published
2012
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48. Atenolol vs enalapril in young hypertensive patients after successful repair of aortic coarctation

Author

Di Salvo, G, primary, Castaldi, B, additional, Gala, S, additional, Baldini, L, additional, Del Gaizo, F, additional, D'Aiello, F A, additional, Mormile, A, additional, Rea, A, additional, Scognamiglio, G, additional, Pacileo, G, additional, Keating, S, additional, Fadel, B M, additional, Berrino, L, additional, Perna, A, additional, Russo, M G, additional, and Calabrò, R, additional

Published
2015
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