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3. Changes over the years in the indication for heart-lung transplantation in Spain

Author

Lopez Vilella, R., Gomez Bueno, M., Gonzalez Vilchez, F., Sole Jover, S., Laporta Hernandez, R., Vicente Guillen, R., Gonzalez Roman, A. I., Sanchez-Lazaro, I., Hernandez Perez, F., Sales Badia, G., Cordoba Pelaez, M. M., Torregrosa Puerta, S., Luis Martinez, Dolz, Segovia Cubero, J., and Almenar Bonet, L.

Published
2022

5. Short-Term Changes in Left and Right Ventricular Cardiac Magnetic Resonance Feature Tracking Strain Following Ferric Carboxymaltose in Patients With Heart Failure: A Substudy of the Myocardial-IRON Trial

Author

Del Canto I, Santas E, Cardells I, Miñana G, Palau P, Llàcer P, Fácila L, López-Vilella R, Almenar L, Bodí V, López-Lereu MP, Monmeneu JV, Sanchis J, Moratal D, Maceira AM, de la Espriella R, Chorro FJ, Bayés-Genís A, and Núñez J

Subjects
iron deficiency, ventricular strain, heart failure, CMR feature tracking, ferric carboxymaltose, heart failure, iron deficiency, ventricular strain, CMR feature tracking, ferric carboxymaltose
Abstract

Background The mechanisms explaining the clinical benefits of ferric carboximaltose (FCM) in patients with heart failure, reduced or intermediate left ventricular ejection fraction, and iron deficiency remain not fully clarified. The Myocardial-IRON trial showed short-term cardiac magnetic resonance (CMR) changes suggesting myocardial iron repletion following administration of FCM but failed to find a significant increase in left ventricular ejection fraction in the whole sample. Conversely, the strain assessment could evaluate more specifically subtle changes in contractility. In this subanalysis, we aimed to evaluate the effect of FCM on the short-term left and right ventricular CMR feature tracking derived strain. Methods and Results This is a post hoc subanalysis of the double-blind, placebo-controlled, randomized clinical trial that enrolled 53 ambulatory patients with heart failure and left ventricular ejection fraction

Published
2022

11. Impact of intravenous ferric carboxymaltose on heart failure with preserved and reduced ejection fraction

Author

López-Vilella R, Lozano-Edo S, Arenas Martín P, Jover-Pastor P, Ezzitouny M, Sorolla Romero J, Calvo Asensio M, Martínez-Solé J, Guerrero Cervera B, Sánchez Martínez JC, Donoso Trenado V, Sánchez-Lázaro I, Martinez Dolz L, and Almenar Bonet L

Subjects
Ferritin, Reduced ejection fraction, Iron deficiency, Heart failure, Preserved ejection fraction, Ferric carboxymaltose
Abstract

AIMS: Heart failure (HF) is a proinflammatory disease often associated with the onset of iron deficiency (ID). ID alters mitochondrial function, reducing the generation of cellular energy in skeletal muscle and cardiomyocytes. This study aimed to analyse the response of patients with HF to intravenous iron administration according to the type of HF: preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). METHODS AND RESULTS: We conducted a retrospective, single-centre study of 565 consecutive outpatients diagnosed with HF, recruited over 5 years, who were given intravenous ferric carboxymaltose (FCM) for the treatment of ID [defined as ferritin 0.05). CONCLUSIONS: Intravenous iron administration appeared to improve ejection fraction and cardiac functional status in outpatients with ID and HF with both preserved and reduced ejection fraction.

Published
2022

13. Complications After Heart Transplantation According to the Type of Pretransplant Circulatory/Ventricular Support

Author

Lopez-Vilella, R, Sanchez-Lazaro, I, Moncho, AP, Esteban, FP, Guillen, MP, Jauregui, IZ, Costa, RG, Dolz, LM, Puerta, ST, and Bonet, LA

Subjects
surgical procedures, operative, CARDIOGENIC-SHOCK
Abstract

The purpose of the study was to analyze postcardiac transplant complications in patients who received transplants with short-term mechanical ventricular assist devices and to compare complications according to the type of device.

Published
2021

14. Plasma Levels of SERCA2a as a Noninvasive Biomarker of Primary Graft Dysfunction After Heart Transplantation

Author

Lozano-Edo S, Sánchez-Lázaro I, Portolés M, Roselló-Lletí E, Tarazón E, Arnau-Vives MA, Ezzitouny M, Lopez-Vilella R, Almenar-Bonet L, and Martínez-Dolz L

Subjects
cardiovascular system, FAILURE, lipids (amino acids, peptides, and proteins), INTERNATIONAL SOCIETY, respiratory system, circulatory and respiratory physiology
Abstract

Noninvasive detection of primary graft dysfunction (PGD) remains a major challenge. SERCA2a plays an important role in cardiac homeostasis and its dysregulation has been associated with ventricular dysfunction and rejection. This study aimed to determine the potential utility of plasma levels of SERCA2a as a biomarker of PGD.

Published
2021

16. Administration of Subcutaneous Furosemide in Elastomeric Pump vs. Oral Solution for the Treatment of Diuretic Refractory Congestion

Author

Lopez-Vilella R, Sanchez-Lazaro I, Husillos Tamarit I, Monte Boquet E, Nunez Villota J, Donoso Trenado V, Martinez Dolz L, and Almenar Bonet L

Abstract

INTRODUCTION: The most common symptom in heart failure (HF) is congestion, which can be refractory to diuretic treatment. AIM: To verify whether, in patients with advanced HF and diuretic resistance, subcutaneous furosemide or furosemide in an oral solution can improve the clinical-analytical status. METHODS: From 2018 to 2020, 27 consecutive outpatients with diuretic resistance, not candidates for other alternatives, were recruited. Patients were treated either with subcutaneous furosemide in elastomeric pump (n: 10) or with oral solution (n: 17) for 5 days. RESULTS: The functional status (NYHA) improved with subcutaneous administration (predose: 3.8 ± 0.5 vs. postdose: 3.1 ± 0.7; p: 0.02) and oral solution (predose: 3.7 ± 0.3 vs. postdose: 2.5 ± 0.7; p: 0.0001). Weight loss was greater with the oral solution (predose: 85.5 ± 19.5 vs. postdose: 81.3 ± 18.8Kg; p: 0.0001) than subcutaneous (predose: 81.6 ± 15.9 vs. postdose: 80.4 ± 15.1kg; p: 0.16). Creatinine showed a non-significant increase in both groups. The number of hospital visits showed no difference between both options. CONCLUSIONS: The administration of furosemide, both subcutaneously by elastomeric pump or drinking the oral solution, is effective for the treatment of congestion in advanced HF refractory to diuretic treatment.

Published
2021

17. Transient pulmonary nodules with halo sign in patients with advanced heart failure: a report of two cases

Author

López-Vilella R, Muñoz-Núñez CF, Sánchez-Lázaro I, and Bonet LA

Subjects
macromolecular substances, Halo sign, Heart failure, Lung diseases, Tomography, X-ray computed
Abstract

Imaging is important in the diagnosis and follow-up of patients with heart failure (HF). Several thoracic radiological features have been described in these patients. The nodules with halo sign are very rarely reported in HF patients. This sign can appear in several diseases and a clinical context is essential for a final diagnosis.

Published
2020

18. Gender differences in heart transplantation: Twenty-five year trends in the nationwide Spanish heart transplant registry

Author

Garcia-Cosio, MD, Gonzalez-Vilchez, F, Lopez-Vilella, R, Barge-Caballero, E, Gomez-Bueno, M, Martinez-Selles, M, Arizon, JM, Sousa, DR, Gonzalez-Costello, J, Mirabet, S, Perez-Villa, F, Diaz-Molina, B, Rabago, G, Ocampo, AP, de la Fuente-Galan, L, Garrido, I, and Delgado-Jimenez, JF

Subjects
gender, heart transplant, trend, women
Abstract

The study of gender differences may lead into improvement in patient care. We have aimed to identify the gender differences in heart transplantation (HT) of adult HT recipients in Spain and their evolution in a study covering the years 1993-2017 in which 6740 HT (20.6% in women) were performed. HT indication rate per million inhabitants was lower in women, remaining basically unchanged during the 25-year study period. HT rate was higher in men, although this decreased over the 25-year study period. Type of heart disease differed in men versus women (p

Published
2020

19. Spanish Heart Transplant Registry. 31th Official Report of the Heart Failure Association of the Spanish Society of Cardiology

Author

González-Vilchez F, Almenar-Bonet L, Crespo-Leiro MG, Gómez-Bueno M, González-Costello J, Pérez-Villa F, Delgado-Jiménez J, Arizón Del Prado JM, Sobrino-Márquez JM, Sousa Casasnovas I, Spanish Heart Transplant Teams, Segovia-Cubero J, Hernández-Pérez F, Martínez Penades S, Cebrián Pinar M, López Vilella R, Sánchez-Lázaro I, Martínez-Dolz L, Paniagua-Martín MJ, Barge-Caballero E, Barge-Caballero G, Couto-Mallón D, López Granados A, Segura Saintgerons C, Menjíbar Pareja V, Carrasco Ávalos F, Cobo M, Llano-Cardenal M, Vázquez de Prada JA, Nistal Herrera F, Blázquez Z, Jesús Valero M, Ortiz C, Zataraín E, Villa A, Navas P, Martínez-Sellés M, Dolores García Cosío M, Morán Fernández L, Caravaca P, Brossa Loidi V, Roig Minguell E, Mirabet Pérez S, López López L, Zegrí I, Rangel Sousa D, Manito Lorite N, Díez Lopez C, Roca Elias J, García Romero E, Rábago Juan-Aracil G, Castel MÁ, Farrero M, Lambert Rodríguez JL, Díaz Molina B, Bernardo Rodríguez MJ, Fidalgo Muñiz C, Camino López M, Gil Jaurena JM, Gil Villanueva N, Garrido-Bravo I, Pascual Figal DA, Pastor Pérez FJ, Blasco-Peiró T, Portoles Ocampo A, Sanz Julve M, de la Fuente Galán L, Tobar Ruiz J, Recio Platero A, García-Guereta Silva L, González Rocafort Á, Labradero de Lera C, Polo López L, Gran Ipiña F, Albert Brotons DC, Abella Antón R, García Quintana A, and Groba Marco MDV

Subjects
Cardiac transplant, Registro, Registry, Supervivencia, Survival, Trasplante cardiaco
Abstract

The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019.

Published
2020

20. Spanish Heart Transplant Registry. 30th Official Report of the Spanish Society of Cardiology Working Group on Heart Failure (1984-2018)

Author

Gonzalez-Vilchez, F, Almenar-Bonet, L, Crespo-Leiro, MG, Segovia-Cubero, J, Gonzalez-Costello, J, del Prado, JMA, Sousa-Casasnovas, I, Sobrino-Marquez, JM, Delgado-Jimenez, J, Perez-Villa, F, Gomez-Buena, M, Hernandez-Perez, F, Martinez-Penades, S, Cebrian-Pinar, M, Lopez-Vilella, R, Sanchez-Lazaro, I, Martinez-Dolt, L, Paniagua-Martin, MJ, Barge-Caballero, E, Barge-Caballero, G, Couto-Mallon, D, Lopez-Granados, A, Segura-Saintgerons, C, Mesa, D, Ruiz, M, Romo, E, Carrasco, F, Lopez-Aguilera, J, Cobo, M, Llano-Cardenal, M, de Prada, JAV, Nistal-Herrera, F, Martinez-Selles, M, Ortiz, C, Zatarain, E, Valero, MJ, Fernandez-Yanez, J, Navas, P, Castrodeza, J, Garcia-Cosio, MD, Moran-Fernandez, L, Blazquez, Z, Caravaca, P, Roig-Minguell, E, Brossa-Loidi, V, Mirabet-Perez, S, Lopez-Lopez, L, Rangel-Sousa, D, Manito-Lorite, N, Diez-Lopez, C, Roca-Elias, J, Rabago-Aracil, G, Castel, MA, Farrero, M, Garcia-Alvarez, A, Lambert-Rodriguez, JL, Diaz-Molina, B, Bernardo-Rodriguez, MJ, Camino-Lopez, M, Gil-Jaurena, JM, Gil-Villanueva, N, Garrido-Bravo, I, Pascual-Figal, DA, Pastor-Perez, FJ, Blasco-Peiro, T, Portoles-Ocampo, A, Sanz-Julve, M, de La Fuente-Galan, L, Tobar-Ruiz, J, Correa-Fernandez, AM, Garcia-Guereta-Silva, L, Gonzalez-Rocafort, A, de Lera, CL, Polo-Lopez, L, Albert-Brotons, DC, Gran-Ipina, F, and Abella-Anton, R

Subjects
Registry, Survival, Heart transplant
Abstract

Introduction and objectives: The present report updates the clinical characteristics and outcomes of heart transplant in Spain to 2018. Methods: Prospective registry of all the heart transplants performed between 1984 and 2018 in Spain. Specifically, temporal trends in clinical characteristics and outcomes are described for the period from 2009 to 2017. Results: In 2018, 321 transplants were performed (8494 since 1984; 2719 between 2009 and 2018). Compared with the previous year, the number of transplants performed in 2018 rose by 52% in recipients younger than 16 years and by 42% in those older than 60 years. In the last decade, significant temporal trends were observed in recipient characteristics (better pretransplant renal function, higher rates of diabetes, more urgent transplants, and greater use of pretrasplant circulatory support, particularly ventricular assist devices), donor characteristics (higher donor age, more female donors, and higher frequencies of cerebrovascular cause of death and predonation cardiac arrest and lower ischemia time). Survival significantly improved in the last decade, mainly due to lower mortality due to primary graft failure. Conclusions: The number of heart transplants is increasing in Spain, with a progressive improvement in survival. (C) 2019 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Published
2019

21. Use of Idarucizumab to reverse the anticoagulant effect of dabigatran in cardiac transplant surgery. A multicentric experience in Spain

Author

Crespo-Leiro, M. G. Maria G., Raquel Lopez-Vilella, R. L. V., Lopez Granados, A. L. G. Amador, Mirabet-Perez, S., Diez-Lopez, C., Barge-Caballero, E., Segovia-Cubero, J., Gonzalez-Vilchez, F., Rangel-Sousa, D., Blasco-Peiro, T., La Fuente-Galan, L., Beatriz Diaz Molina, Zatarain-Nicolas, E., Carrasco Avalos, F., and Almenar-Bonet, L.

Subjects
idarucizumab, Dabigatran, Heart Transplant, Idarucizumab, cardiovascular system, dabigatran, cardiovascular diseases, heart transplant
Abstract

Background Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin inhibitor, is increasingly used for anticoagulation in patients with non-valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab. Aim To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT. Methods Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery. Results Fifty-three patients were included (81.1% male). 7.5% required re-operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30-day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post-HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post-HT death was associated with bleeding. Conclusions These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations.

Published
2019

22. Idarucizumab in High-risk Thoracic Surgery

Author

López-Vilella R, Sanz-Sánchez J, Sánchez-Lázaro I, Elena Marqués Sulé, Rueda-Soriano J, and Almenar-Bonet L

Subjects
lcsh:R, Idarucizumab, lcsh:Medicine, Anticoagulants, Case Report, Heart-lung transplantation
Abstract

Direct oral anticoagulants have suggested a favorable profile compared with vitamin K antagonists. However, the lack of treatment to reverse the effect of direct oral anticoagulants has limited its use in some patients who require rapid reversal of anticoagulation, as those included in the transplant waiting list. Idarucizumab is a recently approved drug to reverse the anticoagulant effect of dabigatran. However, the clinical experience when using this drug is scarce. Herein, we present a clinical case on anticoagulation reversal with idarucizumab to perform heart and lung transplantation in a patient with Eisenmenger syndrome.

Published
2018

23. Spanish Heart Transplant Registry. 29th Official Report of the Spanish Society of Cardiology Working Group on Heart Failure

Author

Gonzalez-Vilchez, F, Almenar-Bonet, L, Crespo-Leiro, MG, Alonso-Pulpon, L, Gonzalez-Costelo, J, Sobrino-Marquez, JM, del Prado, JMA, Sousa-Casasnovas, I, Jimenez, JD, Perez-Villa, F, Segovia-Cubero, J, Gomez-Buena, M, Hernandez-Perez, F, Martinez-Penades, S, Cebrian-Pinar, M, Lopez-Vilella, R, Sanchez-Lazaro, I, Martinez-Dolz, L, Paniagua-Martin, MJ, Barge-Caballero, E, Barge-Caballero, G, Couto-Mallon, D, Lopez-Granados, A, Segura-Saintgerons, C, Mesa, D, Ruiz, M, Romo, E, Carrasco, F, Lopez-Aguilera, J, Cobo, M, Llano-Cardenal, M, de Prada, JAV, Nistal-Herrera, F, Valero, MJ, Fernandez-Yanez, J, Navas, P, Ortiz, C, Villa, A, Zatarain, E, Martinez-Selles, M, Garcia-Cosio, MD, Moran-Fernandez, L, Blazquez, Z, Roig-Minguell, E, Brossa-Loidi, V, Mirabet-Perez, S, Lopez-Lopez, L, Lage-Galle, E, Rangel-Sousa, D, Manito-Lorite, N, Diez-Lopez, C, Roca-Elias, J, Rabago-Aracil, G, Castel, MA, Farrero, M, Garcia-Alvarez, A, Lambert-Rodriguez, JL, Diaz-Molina, B, Bernardo-Rodriguez, MJ, Camino-Lopez, M, Gil-Jaurena, JM, Gil-Villanueva, N, Garrido-Bravo, I, Blasco-Peiro, T, Portoles-Ocampo, A, Sanz-Julve, M, de la Fuente-Galan, L, Tobar-Ruiz, J, Correa-Fernandez, AM, Silva, LGG, Gonzalez-Rocafort, A, Labradero-de Lera, C, Polo-Lopez, L, Albert-Brotons, DC, Gran-Ipna, F, Abella-Anton, R, and Representation Equipos Espanoles T

Subjects
Registry, Survival, Heart transplant
Abstract

Introduction y objetivos: The present report updates the characteristics and results of heart transplantation in Spain, mainly focused in the 2008-2017 period. Methods: We describe the recipient and donor characteristics, surgical procedures, and outcomes of heart transplants performed in 2017. The 2017 data were compared with those obtained from 2008 to 2016. Results: A total of 304 cardiac transplants were performed in 2017. Between 1984 and 2017, 8173 procedures were performed, 2689 of them after 2008. Significant temporal trends were observed in recipient characteristics (lower pulmonary vascular resistance, lower use of mechanical ventilation, and a higher percentage of diabetic patients and those with previous cardiac surgery), donor characteristics (older donor age and a higher percentage of female donors and those with a prior cardiac arrest) and Palabras procedures (lower ischemia time). In 2017, 27% of patients were transplanted after undergoing mechanical ventricular assistance (P < .001 for trend). In the last decade, there was a trend to better survival. Conclusions: Around 300 transplants per year were performed in Spain in the last decade. There was a significant increase in the use of pretransplant mechanical circulatory support and a trend to improved survival. (C) 2018 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Published
2018

24. Genome-wide association study identifies novel loci predisposing to cutaneous melanoma†

Author

Amos, Ci, Wang, Le, Lee, Je, Gershenwald, Je, Chen, Wv, Fang, S, Kosoy, R, Zhang, M, Qureshi, Aa, Vattathil, S, Schacherer, Cw, Gardner, Jm, Wang, Y, Bishop, Dt, Barrett, Jh, Macgregor, S, Hayward, Nk, Martin, Ng, Duffy, Dl, Mann, Gj, Cust, A, Hopper, J, Brown, Km, Grimm, Ea, Xu, Y, Han, Y, Jing, K, Mchugh, C, Laurie, Cc, Doheny, Kf, Pugh, Ew, Seldin, Mf, Han, J, Wei, Q, Genomel, Investigators, Mega Investigators, Q., AMFS Investigators Mann GJ, Hopper, Jl, Aitken, Jf, Armstrong, Bk, Giles, Gg, Kefford, Rf, Cust, Ae, Jenkins, Ma, Schmid, H, Aguilera, P, Badenas, C, Carrera, C, Cuellar, F, Gabriel, D, Martinez, E, Gonzalez, M, Iglesias, P, Malvehy, J, Marti Laborda, R, Mila, M, Ogbah, Z, Butille, Ja, Puig, S, Alós, L, Arance, A, Arguís, P, Campo, A, Castel, T, Conill, C, Palou, J, Rull, R, Sánchez, M, Vidal Sicart, S, Vilalta, A, Vilella, R, Montgomery, Gw, Whiteman, Dc, Whiteman, D, Webb, P, Green, A, Parsons, P, Purdie, D, Hayward, N, Landi, Mt, Calista, D, Landi, G, Minghetti, P, Arcangeli, F, Bertazzi, Pa, Bianchi, Giovanna, Ghiorzo, Paola, Pastorino, Lorenza, Bruno, William, Battistuzzi, Linda, Gargiulo, Sara, Nasti, Sabina, Gliori, S, Origone, Paola, Andreotti, V, Queirolo, P, Mackie, R, Lang, J, Bishop, Ja, Affleck, P, Harrison, J, Iles, Mm, Randerson Moor, J, Harland, M, Taylor, Jc, Whittaker, L, Kukalizch, K, Leake, S, Karpavicius, B, Haynes, S, Mack, T, Chan, M, Taylor, Y, Davies, J, King, P, Gruis, Na, van Nieuwpoort FA, Out, C, van der Drift, C, Bergman, W, Kukutsch, N, Bavinck, Jn, Bakker, B, van der Stoep, N, ter Huurne, J, van der Rhee, H, Bekkenk, M, Snels, D, van Praag, M, Brochez, L, Gerritsen, R, Crijns, M, Vasen, H, Olsson, H, Ingvar, C, Jönsson, G, Borg, Å, Måsbäck, A, Lundgren, L, Baeckenhorn, K, Nielsen, K, Casslén, As, Helsing, P, Andresen, Pa, Rootwelt, H, Akslen, La, Molven, A, Avril, Mf, Bressac de Paillerets, B, Chaudru, V, Chateigner, N, Corda, E, Jeannin, P, Lesueur, F, de Lichy, M, Maubec, E, Mohamdi, H, Demenais, F, Andry Benzaquen, P, Bachollet, B, Bérard, F, Berthet, P, Boitier, F, Bonadona, V, Bonafé, Jl, Bonnetblanc, Jm, Cambazard, F, Caron, O, Caux, F, Chevrant Breton, J, Chompret, A, Dalle, S, Demange, L, Dereure, O, Doré, Mx, Doutre, Ms, Dugast, C, Faivre, L, Grange, F, Humbert, P, Joly, P, Kerob, D, Lasset, C, Leccia, Mt, Lenoir, G, Leroux, D, Levang, J, Lipsker, D, Mansard, S, Martin, L, Martin Denavit, T, Mateus, C, Michel, Jl, Morel, P, Olivier Faivre, L, Perrot, Jl, Robert, C, Ronger Savle, S, Sassolas, B, Souteyrand, P, Stoppa Lyonnet, D, Thomas, L, Vabres, P, Wierzbicka, E, Elder, D, Kanetsky, P, Knorr, J, Ming, M, Mitra, N, Ruffin, A, Van Belle, P, Debniak, T, Lubiński, J, Mirecka, A, Ertmański, S, Novakovic, S, Hocevar, M, Peric, B, Cerkovnik, P, Höiom, V, Hansson, J, Holland, Ea, Azizi, E, Galore Haskel, G, Friedman, E, Baron Epel, O, Scope, A, Pavlotsky, F, Yakobson, E, Cohen Manheim, I, Laitman, Y, Milgrom, R, Shimoni, I, and Kozlovaa, E.

Subjects
Genetic Markers, Candidate gene, Skin Neoplasms, Ubiquitin-Protein Ligases, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Genetics, Eye color, Guanine Nucleotide Exchange Factors, Humans, SNP, Genetic Predisposition to Disease, Melanoma, Molecular Biology, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Pigmentation, Association Studies Articles, General Medicine, 3. Good health, Chromosomes, Human, Pair 1, Genetic Loci, Genetic marker, Case-Control Studies, 030220 oncology & carcinogenesis, Cutaneous melanoma, Genome-Wide Association Study
Abstract

We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.

Published
2011
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25. Phase II randomised trial of autologous tumour lysate dendritic cell plus best supportive care compared with best supportive care in pre-treated advanced colorectal cancer patients

Author

Caballero-Banos, M, Benitez-Ribas, D, Tabera, J, Varea, S, Vilana, R, Bianchi, L, Ayuso, JR, Pages, M, Carrera, G, Cuatrecasas, M, Martin-Richard, M, Cid, J, Lozano, M, Castells, A, Garcia-Albeniz, X, Maurel, J, and Vilella, R

Subjects
Immunotherapy, Dendritic cells, Vaccine, Colorectal, Cancer
Abstract

Background: Autologous tumour lysate dendritic cell vaccine (ADC) has T-cell stimulatory capacity and, therefore, potential antitumour activity. We designed a phase II randomised trial of ADC + best supportive care (BSC) (experimental arm [EA]) compared with BSC (control arm [CA]), in pre-treated metastatic colorectal cancer (mCRC) patients. Patients and methods: Patients with progressive mCRC, at least to two chemotherapy regimens and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, were randomised to EA versus CA. Stratification criteria: ECOG PS (0-1 versus 2) and lactate dehydrogenase (ULN). EA was administered subcutaneously till progressive disease. Primary end-point was progression-free survival (PFS) at 4 months. Results: Fifty-two patients were included (28 EA/24 CA). An interim analysis recommended early termination for futility. No objective radiological response was observed in EA. Median PFS in EA was 2.7 months (95% confidence interval [CI], 2.3-3.2 months) versus 2.3 months (95% CI, 2.1-2.5 months) in CA (p = 0.628). Median overall survival (OS) was 6.2 months (95% CI, 4.4-7.9 months) in EA versus 4.7 months (95% CI, 2.3-7 months) in CA (p = 0.41). No ADC-related adverse events were reported. Immunization induces tumour-specific T-cell response in 21 of 25 (84%) patients. Responder patients have an OS of 7.3 months (95% CI, 5.2-9.4 months) versus 3.8 months (95% CI, 0.6-6.9 months) in non-responders; p = 0.026). Conclusion: Our randomised clinical trial comparing ADC + BSC versus BSC in mCRC demonstrates that ADC generates a tumour-specific immune response but not benefit on PFS and OS. Our results do not support the use of ADC alone, in a phase III trial. (C) 2016 Elsevier Ltd. All rights reserved.

Published
2016

29. Differential expression of 2-6 sialylated polylactosamine structures by human B and T cells

Author

Reinhard Schwartz-Albiez, Nimtz M, Gramatzki M, Vilella R, Marc Schmitz, Ernst Peter Rieber, Bernhard Kniep, Hinnak Northoff, and Knut Schäkel

Subjects
Glycan, medicine.drug_class, T-Lymphocytes, CD3, Molecular Sequence Data, Monoclonal antibody, Biochemistry, chemistry.chemical_compound, Antigen, Polysaccharides, medicine, Humans, B-Lymphocytes, biology, CD24, Antibodies, Monoclonal, Amino Sugars, Carbohydrate, Molecular biology, Sialic acid, Carbohydrate Sequence, chemistry, Antigens, Surface, Sialic Acids, biology.protein, Glycolipids, Antibody
Abstract

We found that human peripheral B and T cells differed in the surface expression of alpha2-6 sialylated type 2 chain glycans. In contrast to B cells, T cells expressed only sialoglycans with repeated N-acetyllactosamine (Galss1-4GlcNAc) disaccharides. This finding was based on the specificity of the monoclonal antibodies HB6, HB9 (CD24), HD66 (CDw76), FB21, and CRIS4 (CDw76) with the alpha2-6 sialylated model gangliosides IV6NeuAcnLc4Cer (2-6 SPG), VI6NeuAcnLc6Cer (2-6 SnHC), VIII6NeuAcnLc8Cer (2-6 SnOC), and X6NeuAcnLc10Cer (2-6 SnDC). We found that, in addition to their common requirement of an alpha2-6 bound terminal sialic acid for binding, the antibodies displayed preferences for the length of the carbohydrate backbones. Some of them bound mainly to 2-6 SPG with one N-acetyllactosamine (LacNAc) unit (HB9, HD66); others preferentially to 2-6 SnHC and 2-6 SnOC, with two and three LacNAc units, respectively (HB6 and FB21); and one of them exclusively to very polar alpha2-6 sialylated type 2 chain antigens (CRIS4) such as to 2-6 SnOC and even more polar gangliosides with three and more LacNAc units. These specificities could be correlated with the cellular binding of the antibodies as follows: whereas all antibodies bound to human CD 19 positive peripheral B cells, their reactivity with CD3 positive T cells was either nearly lacking (HD66, HB9), intermediate (about 65%: HB6, FB21) or strongly positive (CRIS4, 95%). Thus, the binding of the antibodies to 2-6 sialylated glycans with multiple lactosamine units appeared to determine their binding to T-cells.

Published
1999
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30. Sensitisation to Act 2d in patientsallergic to Alternaria alternanta: an epiphenomenom without clinical significance?

Author

Sánchez López, J., Pascal, M., Gomez Casado, Cristina, Rueda, M., Vilella, R., Valero, A., Diaz Perales, Araceli, and Bartra, Joan

Subjects
Biología
Abstract

In the last few years, the introduction of microarrays in the diagnosis of type I allergy is allowing the clinicians to have a much more accurate picture of their allergenic profile. However, the simultaneous measurement of specific IgE to multiple molecules can show unexpected sensitisations, without knowing their clinical relevance. For instance, we have been observing a high prevalence (74%) of sensitisation to Act d 2 (the thaumatin of kiwifruit) in patients sensitised to Alt a 1 (major allergen of Alternaria alternata) with a confirmed allergy to this mould. The aim of the present study was to clarify if there was any clinical relevance in this finding.

Published
2013

31. CD148 is a membrane protein tyrosine phosphatase present in all hematopoietic lineages and is involved in signal transduction on lymphocytes

Author

Ma, La Fuente-García, Jm, Nicolás, Jh, Freed, Eduard Palou, Ap, Thomas, Vilella R, Vives J, and Gayá A

Subjects
T-Lymphocytes, COS Cells, Molecular Sequence Data, Receptor-Like Protein Tyrosine Phosphatases, Class 3, Animals, Humans, Cell Lineage, Amino Acid Sequence, Protein Tyrosine Phosphatases, Hematopoietic Stem Cells, Sequence Analysis, Hematopoiesis, Signal Transduction
Abstract

Evidence is presented showing that a protein tyrosine phosphatase different from CD45 is present on the membrane of human hematopoietic cells. The molecule recognized by the monoclonal antibody 143-41, which has been classified as CD148 in the VI International Workshop on Leukocyte Differentiation Antigens, was immunopurified and sequenced. The sequence obtained from N-terminus as well as from two different CNBr-digested peptides showed a close identity with a previously described tyrosine phosphatase named HPTP-eta/DEP-1. CD148 is present on all hematopoietic lineages, being expressed with higher intensity on granulocytes than on monocytes and lymphocytes. Interestingly, whereas it is clearly present on peripheral blood lymphocytes, it is poorly expressed on different lymphoid cell lines of T and B origin. When this protein tyrosine phosphatase was cocrosslinked with CD3, an inhibition of the normally observed calcium mobilization was observed. This inhibition correlates with a decrease in phospholipase C-gamma (PLC-gamma) phosphorylation and is similar to the one observed with CD45. In addition, it is shown that the crosslinking of the CD148 alone is also able to induce an increase in [Ca2+]i. This increase is abolished in the presence of genistein and by cocrosslinking with CD45. These data, together with the induction of tyrosine phosphorylation on several substrates, including PLC-gamma, after CD148 crosslinking, suggest the involvement of a tyrosine kinase-based signaling pathway in this process. In conclusion, the data presented show that CD148 corresponds to a previously described protein tyrosine phosphatase HPTP-eta/DEP-1 and that this molecule is involved in signal transduction in lymphocytes.

Published
1998

32. CD27 induction on thymocytes

Author

Martorell J, Rojo I, Vilella R, Eva Martínez-Cáceres, and Vives J

Subjects
Antigens, Differentiation, T-Lymphocyte, Dipeptidyl Peptidase 4, Ionomycin, T-Lymphocytes, Immunology, Antibodies, Monoclonal, Cyclosporins, Thymus Gland, Flow Cytometry, Lymphocyte Activation, Antigens, Differentiation, Precipitin Tests, Tumor Necrosis Factor Receptor Superfamily, Member 7, Antigens, CD, Concanavalin A, Immunology and Allergy, Humans, Leukocyte Common Antigens, Tetradecanoylphorbol Acetate
Abstract

CD27 mAb recognize a disulfide-linked homodimer of 55 kDa present in the majority of T cells and in a minor subpopulation of thymocytes. Although an increase of CD27 expression has been described in activated T cells, this Ag is poorly expressed in long term growing T cells. It has been also reported that CD27- becomes CD27+ upon activation. In the aim to better know the relationship between CD27 expression and the activation and maturation processes, the induction of this Ag in thymocytes was analyzed. The results obtained in this work show that: 1) CD27 is expressed only in thymocytes with high CD3 Ag density. 2) Its expression can be induced in low density CD3 CD4+ CD8+ cells by Con A and in low CD3 Ag density by PMA+ionomycin. 3) PMA alone or in combination with rIL-2 induces CD25 and CD71 expression but not CD27. 4) Unlike CD27, the Ag CD45RA, CD26, and CD76, which are present only in a minor thymocyte subpopulation, are not induced in double positive thymocytes. Because it has been reported that cyclosporin A interferes with thymocytes maturation and blocks the transition from double to single positive cells, its effect was measured on CD27 induction. Cyclosporin A did not inhibit CD25 expression induced by both Con A and PMA+ionomycin, but under these conditions it inhibited the induction of CD27. In this paper we discuss whether CD27 could be implicated in T cell maturation.

35. Activation of human phagocytes through carbohydrate antigens (CD15, sialyl-CD15, CDw17, and CDw65)

Author

Fridtjof Lund-Johansen, Olweus J, Horejsi V, Km, Skubitz, Js, Thompson, Vilella R, and Fw, Symington

Subjects
Cytoplasm, Phagocytes, Membrane Glycoproteins, Receptors, IgG, Antibodies, Monoclonal, Lewis X Antigen, Macrophage-1 Antigen, Receptors, Fc, Antigens, Differentiation, N-Formylmethionine Leucyl-Phenylalanine, Antigens, CD, Antigens, Neoplasm, Humans, Calcium, Cell Adhesion Molecules, Cells, Cultured, Respiratory Burst
Abstract

The leukocyte carbohydrate (CHO) Ag CD15, sialyl-CD15, and CDw65 have recently been found to function as ligands for CD62 and ELAM-1 cell adhesion molecules on platelets and endothelium, respectively. Cell adhesion ligands also may act as receptors capable of signal transduction. We therefore investigated the possibility that these CHO Ag and CDw17, a glycolipid Ag whose expression is regulated by leukocyte activation, may have receptor-like characteristics. The effects of antibody cross-linking of CHO Ag on phagocyte activation were measured by using flow cytometry and fluorescent indicators for cytoplasmic calcium ions, oxidative burst, and the granule-associated proteins CD11b and CD67. Cross-linking of CD15, sialyl-CD15, CDw65, or CDw17 induced a moderate release of calcium ions into the cytoplasm of granulocytes, a strong activation of oxidative burst, and a low up-regulation of CD11b and CD67 compared to the effects of treatment with 4 microM FMLP. The results suggest a role for CHO Ag in leukocyte signal transduction and support the view that these molecules are involved in phagocyte activation.

38. Nasal challenge test in the diagnosis of latex-related systemic reactions

Author

Rosa Munoz Cano, Pascal, M., Lombardero, M., Sánchez-López, J., Bartra, J., Vilella, R., Picado, C., and Valero, A.

Subjects
Adult, Nasal Provocation Tests, Basophil Degranulation Test, Allergens, Immunoglobulin E, Postoperative Complications, Latex Hypersensitivity, Uterine Myomectomy, Humans, Female, Immunization, Rubber, Anaphylaxis, Skin Tests

40. The use erythrocyte glutathione as a predictive marker for malignant melanoma

Author

Moral, A., Lafuente, M. J., Lafuente, A., Castel, T., Balesta, A. M., Lecha, M., Trias, M., Mascaro, J. M., Castro, J., Puig, S., Malvehy, J., Soler, J., Yachi, E., Piulachs, J., Barruiso, C., Vilalta, A., Martin, E., Mellado, B., DOLORS COLOMER, Estape, J., Gonzalez, L., Estivill, X., Ruiz, A., Mila, M., Casterad, X., Laso, N., Molina, R., Vilella, R., Mila, J., and Vidal, J.

42. Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Author

Schoof, N, Iles, Mm, Bishop, Dt, Newton Bishop JA, Barrett, Jh, Mann, Gj, Hopper, Jl, Aitken, Jf, Armstrong, Bk, Giles, Gg, Kefford, Rf, Cust, A, Jenkins, M, Aguilera, P, Badenas, C, Carrera, C, Cuellar, F, Gabriel, D, Martinez, E, Gonzalez, M, Iglesias, P, Malvehy, J, Marti Laborda, R, Mila, M, Ogbah, Z, Butille, Ja, Puig, S, Alós, L, Arance, A, Arguís, P, Campo, A, Castel, T, Conill, C, Palou, J, Rull, R, Sánchez, M, Vidal Sicart, S, Vilalta, A, Vilella, R, Martin, Ng, Montgomery, Gw, Duffy, D, Whiteman, D, Macgregor, S, Hayward, Nk, Webb, P, Parsons, P, Purdie, D, Hayward, N, Landi, Mt, Calista, D, Landi, G, Minghetti, P, Arcangeli, F, Bertazzi, Pa, Bianchi, Giovanna, Ghiorzo, Paola, Pastorino, Lorenza, Bruno, William, Battistuzzi, Linda, Gargiulo, Sara, Nasti, Sabina, Gliori, S, Origone, Paola, Queirolo, P, Mackie, R, Lang, J, Bishop, Ja, Affleck, P, Harrison, J, Randerson Moor, J, Harland, M, Taylor, Jc, Whittaker, L, Kukalizch, K, Leake, S, Karpavicius, B, Haynes, S, Mack, T, Chan, M, Taylor, Y, Davies, J, King, P, Gruis, Na, van Nieuwpoort FA, Out, C, van der Drift, C, Bergman, W, Kukutsch, N, Bavinck, Jn, Bakker, B, van der Stoep, N, ter Huurne, J, van der Rhee, H, Bekkenk, M, Snels, D, van Praag, M, Brochez, L, Gerritsen, R, Crijns, M, Vasen, H, Olsson, H, Ingvar, C, Jönsson, G, Borg, Å, Måsbäck, A, Lundgren, L, Baeckenhorn, K, Nielsen, K, Casslén, As, Helsing, P, Andresen, Pa, Rootwelt, H, Akslen, La, Molven, A, Avril, Mf, Bressac de Paillerets, B, Chaudru, V, Chateigner, N, Corda, E, Jeannin, P, Lesueur, F, de Lichy, M, Maubec, E, Mohamdi, H, Demenais, F, Andry Benzaquen, P, Bachollet, B, Bérard, F, Berthet, P, Boitier, F, Bonadona, V, Bonafé, Jl, Bonnetblanc, Jm, Cambazard, F, Caron, O, Caux, F, Chevrant Breton, J, Chompret, A, Dalle, S, Demange, L, Dereure, O, Doré, Mx, Doutre, Ms, Dugast, C, Faivre, L, Grange, F, Humbert, P, Joly, P, Kerob, D, Lasset, C, Leccia, Mt, Lenoir, G, Leroux, D, Levang, J, Lipsker, D, Mansard, S, Martin, L, Martin Denavit, T, Mateus, C, Michel, Jl, Morel, P, Olivier Faivre, L, Perrot, Jl, Robert, C, Ronger Savle, S, Sassolas, B, Souteyrand, P, Stoppa Lyonnet, D, Thomas, L, Vabres, P, Wierzbicka, E, Elder, D, Kanetsky, P, Knorr, J, Ming, M, Mitra, N, Ruffin, A, Van Belle, P, Dębniak, T, Lubiński, J, Mirecka, A, Ertmański, S, Novakovic, S, Hocevar, M, Peric, B, Cerkovnik, P, Höiom, V, Hansson, J, Schmid, H, Holland, Ea, Azizi, E, Galore Haskel, G, Friedman, E, Baron Epel, O, Scope, A, Pavlotsky, F, Yakobson, E, Cohen Manheim, I, Laitman, Y, Milgrom, R, Shimoni, I, Kozlovaa, E., Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Martí Laborda, Rosa Ma., and Universitat de Barcelona

Subjects
Melanomas, Skin Neoplasms, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, Genome-wide association study, 0302 clinical medicine, Polymorphism (computer science), Genetics of the Immune System, lcsh:Science, Melanoma, Genetics, 0303 health sciences, Multidisciplinary, Cancer Risk Factors, Statistics, Immunosuppression, Genomics, Oncology, Genetic Epidemiology, 030220 oncology & carcinogenesis, Medicine, Research Article, medicine.medical_specialty, Immunology, Genetic Causes of Cancer, Malignant Skin Neoplasms, Single-nucleotide polymorphism, Dermatology, Biostatistics, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Genome Analysis Tools, Molecular genetics, Genome-Wide Association Studies, medicine, Humans, SNP, Genetic Predisposition to Disease, Statistical Methods, Gene, 030304 developmental biology, Immunosuppression Therapy, Evolutionary Biology, Population Biology, Immunosupressió, lcsh:R, Computational Biology, Human Genetics, medicine.disease, Genetic Polymorphism, Clinical Immunology, lcsh:Q, Population Genetics, Mathematics, Genome-Wide Association Study
Abstract

Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.

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43. Melanoma inhibiting activity protein (MIA), beta-2 microglobulin and lactate dehydrogenase (LDH) in metastatic melanoma

Author

González Cao, M., Auge, J. M., Molina, R., Martí, R., Carrera, C., Castel, T., Vilella, R., Conill, C., Sánchez, M., Malvehy, J., and Susana Puig

Subjects
Adult, Male, Extracellular Matrix Proteins, L-Lactate Dehydrogenase, S100 Proteins, Kaplan-Meier Estimate, Middle Aged, Prognosis, Neoplasm Proteins, Multivariate Analysis, Biomarkers, Tumor, Disease Progression, Humans, Female, Neoplasm Metastasis, beta 2-Microglobulin, Melanoma, Aged
Abstract

Serum levels of melanoma markers may have a role in monitoring disease evolution in metastatic melanoma.Serial measurements of melanoma inhibiting activity protein (MIA), lactate dehydrogenase (LDH), S-100 and beta2-microglubulin were obtained from 42 metastatic melanoma patients during their biochemotherapy treatment.High pre-treatment serum levels of S-100, LDH, MIA and P2-microglobulin were detected in 50%, 57%, 50% and 24% of the patients, respectively. Only S-100 had prognostic significance for both disease-free (p=0.011) and overall survival (p=0.021). In patients who responded to treatment, S-100 levels decreased significantly from pre-treatment to the time of response (p = 0.050). When patients progressed, levels of MIA and P2-microglobulin increased significantly (p =0.028 and p =0.030, respectively).Correlation with disease evolution was found for S-100, MIA and P2-microglobulin levels. Despite the small sample size of the study, S-100 was a significant prognostic marker for overall survival and disease-free survival.

44. Comorbidity and emergency visits explain home care patients hospital admissions | Comorbilidad y visitas a urgencias explican los ingresos hospitalarios de los pacientes incluidos en programas de atención domiciliaria

Author

Gené Badia, J., Hidalgo García, A., Contel Segura, J. C., Borràs Santos, A., Carlos Ascaso Terren, Piñeiro González, M., Ortiz Molina, J., Martín Royo, J., Gonzalez Martinez, S., Camprubí Casellas, Ma D., Cegri Lombardo, F., Limón Ramírez, E., Aranzana Martínez, A., Heras Tebar, A., Noguera Rodríguez, R., Oliver Olius, A., Rivas Zuazo, S., Porta Borges, M., Adell Aguiló, N., Borrell Muñoz, M., Rodríguez, R. N., Riera, N., Polis, S. V., Martín, S. D., Gené, J., Martin, A. B. I. J., Haro, S. P., Arderiu, E. S., Ubiedo, Ma A. M., León, S. P., Rosalen, A. P., González, M. N., Artigas, N. G., Ruano, N. S., Planas, N. G., Huertas, I. C., López, R. S., Amat, G., Navarro, B. V., Hosta, M. M., Soldevila, J. C., Soriano, I. B., Docon, A. H., Vilaseca, J. M., Molina, J. O., Martinez, S. G., Sotoca, J. M., Almirall, A. S., Pascual, I. M., Navas, G. P., Martos, Ma J. G., García, P. A., Moliner, E. M., Sas, S. S. M., Salami, D. C., Esteban, Ma L. M., Beuter, B. D. A., Poyato, M. L., Asensio, Ma L. S., Chillida, S. B., Rodríguez, A. M., Fusté, S. C., Cucurny, A. Ma P. D. M., Muñoz, M. B., García, M. P. A., Sánchez, P. M., Pallarés, M. P. -M, Baldrich, M. C., Viñas, R. B., Ramírez, B. A., Fusalba, A. R., Espinosa, J. A., Schmab, A. P., Baró, T. M., Pujol, L. E., Santandreu, C. N., Monfort, G. M., Olius, A. O., Borges, M. P., Zuazo, S. R., Arcos, C. A., Bastardes, C. C., Solsona, I. H., Gaitero, C. M., Del Valle, S. R., Villuendas, A. S., Arus, M. S., López, C. V., López, C. Z., Casas, R. B., Marco, G. P., Casado, M. S., Santamaría, M. G., González, Ma C. G., Tutusaus, I. C., Juliano, F. D., Balasch, J., Martinez, R. Ma A., Elizondo, E. A., Ciordia, B. A., Godia, J. L. C., Rivero, J. C., Ibáñez, B. D. M., Ruiz, F. J. G., González, E. S., Miguel, L. G., Manrique, P. N., Saiz, G. M., Vergel, R. F., Maña, M. P., Sánchez, C. C., Andreu, L. C., Mendoza, R. D., Robledo, S. C., García, D. G., Castillo, Á S., Sesma, F. F., Suárez, E. Q., Piquero, H. P., García, C. P., López, P. S., Marsal, A. P., Jacas, Ma C. S., Fernández, Ma E. B., López, S. Á, Antón, I. E., Casamada, N., Llauradó, R. M., Mata, J., Colominas, J., Gómez, A., Bargalló, G., Mora, E. V., González, I. A., Ferrer, O. M., Carrión, F. G., Carrión, B. G., Font, M. M., Juan, M. P., Cuxart, J. G., Castro, E. D., Canovas, A. N., Ferrer, J. L. G., Perea, S. G., González, I. V., Pujolras, T. A., Nogueras, R. G., Morillo, E. V., Lorenzo, P. F., Gelabert, J. T., Mifsud, A. A., Gutiérrez, M. D. C. G., Lasheras, M., Fernandez, E. A., López, F., Yánez, R. F., Brau, C. V., Soria, C. G., Sánchez, G. S., Salafranca, R. Ma F., Ortiz, M. I. P., Recio, P. E., Cantó, A., Rebullida, M. C., Sillero, L., Esteve, M., Rodrigo, F., Lasaosa, L., Lombardo, F. C., Martínez, A. A., Pinadell, N. A., Schornstein, M. D. O., Carretero, M. M., Enguidanos, J. P., Gómez, A. M., Miralles, C. B., Osuna, G. B., Ellacuria, M. P., Villena, I. G., Santiago, Y. C., Mayor, I. T., González, P. M., Pujol, J. A., Gallart, E. B., Ortega, M. T. T., Agorritz, R. U., Reig, N. R., Dausa, M. L. D., García, A. J. B., Jiménez, A. D., García, R. C., Aponte, T. L., Reig, C. V., Barbero, T. I., Soriano, L. M., Gomez, C. U., Bellera, L. R., Pañella, S. C., Arévalo, A., Palies, A. R. G., Rocarias, M. G., Bueno, J. L. L., Olivera, L. D., Rosselló, Ma A. L., Jiménez, Ma A. P., Alborch, J. F., Canal, Ma T. F., Pérez, Ma P. H., Priego, D. G., Salvans, Ma C. Q., Villanueva, C. F., Martín, Ma L. M., Radial, Ma A. M. D. E., Ibáñez, M. C., Moreno, P. V., Cortes, T. P., Beltrán, M. B., Caba, P. M., Exposito, A. B., Bellido, E. D., Alonso, E. B., Baena, M. M., Andres, E. C., Cerdà, N. B., Aguadé, M. M., Busquets, A. R., Piñeiro, M. C. S., Salla, E. N., Gual, R. P., Ricart, A. J., Pujol, N. R., Vidal, E. F., Rodríguez, M. B. S., Vilella, R. A., Delcor, C. M., García, M. D. S., Bartroli, M. R., Arcos, E. G., Larroy, E. L., Matas, R. M., Martinez, P. G., Novella, R. M., Freixanet, C. V., Pipió, C. M., Albí, N., Nogués, J., Martinez, Ma J. R., Heras, J. N., Pérez, Ma L. T., Clotet, E. C., Ramirez, E. L., Chuscas, G. M., Galbana, M. R., López, N. B., Onievai, F. C., Garrido, J. M. S., Morales, E. M., Pérez, M. V., Navarro, A. B., Álvarez, C. G., González, Y. G., Cabañero, C. C., Martínez, L. C. A., Macias, D. S., Ballabriga, M. R., Ramos, J. B., Serrabasa, E. G., Torras, A. B., Torné, C. G., Viladrich, G. C., Martinez, Ma J. F., Abella, M. Á, Segundo, D. G., Cortes, A. P., Herrero, M. M., Segués, N. V., Albert, A. C., Continente, M. P., Álvarez, E. O., Gomez, Ma J. L., Boadella, F. V., Jimeno, K. M., Valls, N. J., García, A. M., Aguiló, N. A., Martí, E., Jacob, M. H., Munté, M., Nolla, M., Cort, I., Peralta, L., Tost, J. S., Jornet, R. F., Pérez, R. G., Gavalda, M. S., Corbella, R. R., Andujar, J. P., Tudo, G. C., Perol, F. P., Perpiñà, C. A., Ferrer, C., Garriga, D., Piñol, C., Caro, R., Llaberia, R. P., Reina, A., Ferrater, Ma J., Duran, J. Ma, Puig, D. J., Pellicer, Ma L. P., Burgeño, M. L., Palies, R. C., Margalef, M. S., Coll, R. B., Pedrosa, T. L., Pedrosa, A. L., Ferrer, A. D., Cortinas, T. M., Pavón, I. L., Mompó, C. L., Aloy, M. G., Mas, M. T., Parrón, M. F., Vilalta, A. V., Sarra, J. R. G., San Celestino, P. P., Casagran, A. V., Soler, T. S., Pagès, D. O., Granada, R. M., Borregan, M. D., Cortés, O. P., Tebar, A. H., Iglesias, A. G., Gomez, V. M., Becardi, R. G., Tejero, J. R., Montañés, C. G., Laborda, A. F., Fontané, J. C., Molina, Ma C. G., Talavera, R. H., Antó, A. C., Milozzi, J., Hernández, L. G., Herrando, L. P., Pérez, A. L., Velásquez, C. A., Sánchez, Ma B. M., Lorente, R. F., Silvero, I. M., Jodar, R. M., Cabrera, A. C., Borque, M. O., Benito, A. G., Burillo, R. S., Broz, M. L. F., Potrony, L. S., Aguiló, I. P., Rubio, J. I. B., Hernández, M. M., Navó, D. G., Morón, M. S., Casellas, M. D. C., Peral, M. A., Fernández, A. B., Milagro, P. C., Crusat, G. M., Prat, F. S., Sabaté, E. S., Porras, I. S., Bacardit, N. S., Hidalgo, I. P., Vancell Varonil, R. M., Marcé, D. 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46. Long-Term Oral Administration of Theaphenon-E Improves Cardiomyocyte Mechanics and Calcium Dynamics by Affecting Phospholamban Phosphorylation and ATP Production

Author

Giancarlo Solaini, Federica Rizzi, Leonardo Bocchi, Alessandra Baracca, Saverio Bettuzzi, Rocchina Vilella, Gianluca Sgarbi, Donatella Stilli, Monia Savi, Valeria Naponelli, and Bocchi L., Savi M., Naponelli V., Vilella R., Sgarbi G., Baracca A., Solaini G., Bettuzzi S., Rizzi F., Stilli D.

Subjects
Male, 0301 basic medicine, Physiology, Administration, Oral, chemistry.chemical_element, Pharmacology, Calcium, 01 natural sciences, Ryanodine receptor 2, Calcium dynamics, lcsh:Physiology, Calcium in biology, Catechins, Sarcoplasmic Reticulum Calcium-Transporting ATPases, lcsh:Biochemistry, 03 medical and health sciences, Adenosine Triphosphate, In vivo, Calcium-binding protein, Animals, lcsh:QD415-436, Myocytes, Cardiac, Calcium Signaling, Phosphorylation, Rats, Wistar, Phospholamban, lcsh:QP1-981, Tea, 010405 organic chemistry, Chemistry, SERCA2 activity, Calcium-Binding Proteins, Green tea extracts, Catechins, Cardiomyocyte mechanics, Calcium dynamics, SERCA2 activity, Phospholamban, Mitochondrial respiration, Polyphenols, Green tea extracts, Rats, 0104 chemical sciences, 030104 developmental biology, Cardiomyocyte mechanics, Energy Metabolism, Intracellular, Ex vivo, Mitochondrial respiration
Abstract

Background/Aims: Dietary polyphenols from green tea have been shown to possess cardio-protective activities in different experimental models of heart diseases and age-related ventricular dysfunction. The present study was aimed at evaluating whether long term in vivo administration of green tea extracts (GTE), can exert positive effects on the normal heart, with focus on the underlying mechanisms. Methods: The study population consisted of 20 male adult Wistar rats. Ten animals were given 40 mL/day tap water solution of GTE (concentration 0.3%) for 4 weeks (GTE group). The same volume of water was administered to the 10 remaining control rats (CTRL). Then, in vivo and ex vivo measurements of cardiac function were performed in the same animal, at the organ (hemodynamics) and cellular (cardiomyocyte mechanical properties and intracellular calcium dynamics) levels. On cardiomyocytes and myocardial tissue samples collected from the same in vivo studied animals, we evaluated: (1) the intracellular content of ATP, (2) the endogenous mitochondrial respiration, (3) the expression levels of the Sarcoplasmic Reticulum Ca2+-dependent ATPase 2a (SERCA2), the Phospholamban (PLB) and the phosphorylated form of PLB, the L-type Ca2+ channel, the Na+-Ca2+ exchanger, and the ryanodine receptor 2. Results: GTE cardiomyocytes exhibited a hyperdynamic contractility compared with CTRL (the rate of shortening and re-lengthening, the fraction of shortening, the amplitude of calcium transient, and the rate of cytosolic calcium removal were significantly increased). A faster isovolumic relaxation was also observed at the organ level. Consistent with functional data, we measured a significant increase in the intracellular ATP content supported by enhanced endogenous mitochondrial respiration in GTE cardiomyocytes, as well as higher values of the ratios phosphorylated-PLB/PLB and SERCA2/PLB. Conclusions: Long-term in vivo administration of GTE improves cell mechanical properties and intracellular calcium dynamics in normal cardiomyocytes, by increasing energy availability and removing the inhibitory effect of PLB on SERCA2.

Published
2018
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