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2. Multi-feature classifiers for burst detection in single EEG channels from preterm infants

Author

Navarro, X., Porée, F., Kuchenbuch, M., Chavez, M., Beuchée, A., and Carrault, G.

Subjects
Quantitative Biology - Neurons and Cognition, Computer Science - Learning
Abstract

The study of electroencephalographic (EEG) bursts in preterm infants provides valuable information about maturation or prognostication after perinatal asphyxia. Over the last two decades, a number of works proposed algorithms to automatically detect EEG bursts in preterm infants, but they were designed for populations under 35 weeks of post menstrual age (PMA). However, as the brain activity evolves rapidly during postnatal life, these solutions might be under-performing with increasing PMA. In this work we focused on preterm infants reaching term ages (PMA $\geq$ 36 weeks) using multi-feature classification on a single EEG channel. Five EEG burst detectors relying on different machine learning approaches were compared: Logistic regression (LR), linear discriminant analysis (LDA), k-nearest neighbors (kNN), support vector machines (SVM) and thresholding (Th). Classifiers were trained by visually labeled EEG recordings from 14 very preterm infants (born after 28 weeks of gestation) with 36 - 41 weeks PMA. The most performing classifiers reached about 95\% accuracy (kNN, SVM and LR) whereas Th obtained 84\%. Compared to human-automatic agreements, LR provided the highest scores (Cohen's kappa = 0.71) and the best computational efficiency using only three EEG features. Applying this classifier in a test database of 21 infants $\geq$ 36 weeks PMA, we show that long EEG bursts and short inter-bust periods are characteristic of infants with the highest PMA and weights. In view of these results, LR-based burst detection could be a suitable tool to study maturation in monitoring or portable devices using a single EEG channel., Comment: 11 pages, 5 figures. Table 1 in the last page

Published
2017
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6. Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab

Author

Spertino, J., Curto Barredo, L., Rozas Muñoz, E., Figueras Nart, I., Serra Baldrich, E., Bonfill-Ortí, M., Expósito-Serrano, V., Guilabert, A., Melé Ninot, G., Villar Buil, M., Garcias Ladaria, J., García Navarro, X., Vilavella, M., Bielsa Marsol, I., Aparicio Ortiz, G., Baliu Piqué, C., Álvarez Abella, A., Lamas Domenech, N., Mascaró, J.M., Gómez, S., Torné Gutiérrez, J.I., Vicente Villa, A., and Gimenez Arnau, A.

Published
2018
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7. Algoritmo de tratamiento con omalizumab en urticaria crónica espontánea

Author

Spertino, J., Curto Barredo, L., Rozas Muñoz, E., Figueras Nart, I., Gimenez Arnau, A., Serra Baldrich, E., Bonfill-Ortí, M., Expósito-Serrano, V., Guilabert, A., Melé Ninot, G., Villar Buil, M., Garcias Ladaria, J., García Navarro, X., Vilavella, M., Bielsa Marsol, I., Aparicio Ortiz, G., Baliu Piqué, C., Álvarez Abella, A., Lamas Domenech, N., Mascaró, J.M., Gómez, S., Torné Gutiérrez, J.I., and Vicente Villa, A.

Published
2018
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8. Advanced 56 Channels Stimulation System to Drive Intrafascicular Electrodes

Author

Guiho, T., Andreu, D., López-Alvarez, V. M., Cvancara, P., Hiairrassary, A., Granata, G., Wauters, L., Jensen, W., Divoux, J. L., Micera, S., Stieglitz, T., Navarro, X., Guiraud, D., Guglielmelli, Eugenio, Series editor, Ibáñez, Jaime, editor, González-Vargas, José, editor, Azorín, José María, editor, Akay, Metin, editor, and Pons, José Luis, editor

Published
2017
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13. Interobserver variation in the assessment of HER2 low expression in breast cancer: can we improve by adjusting criteria? An international interobserver study

Author

Baez Navarro, X., primary, van Bockstal, M.R., additional, Nawawi, D., additional, Broeckx, G., additional, Colpaert, C.G., additional, Doebar, S.C., additional, Hogenes, M.C.H., additional, Koop, E., additional, Lambein, K., additional, Peeters, D.J.E., additional, Sinke, R.H.J.A., additional, van Brakel, J.B., additional, van der Starre-Gaal, J., additional, van der Vegt, B., additional, van de Vijver, K., additional, Vreuls, C.P.H., additional, Vreuls, W., additional, Westenend, P.J., additional, and van Deurzen, C.H.M., additional

Published
2022
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17. Advanced 56 Channels Stimulation System to Drive Intrafascicular Electrodes

Author

Guiho, T., primary, Andreu, D., additional, López-Alvarez, V. M., additional, Cvancara, P., additional, Hiairrassary, A., additional, Granata, G., additional, Wauters, L., additional, Jensen, W., additional, Divoux, J. L., additional, Micera, S., additional, Stieglitz, T., additional, Navarro, X., additional, and Guiraud, D., additional

Published
2016
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20. EST79232 and EST79376, Two novel sigma-1 receptor ligands, exert neuroprotection on models of motoneuron degeneration

Author

Gaja Capdevila, Núria, Hernández, Neus, Yeste, Sandra, Reinoso, Raquel, Burgueño, Javier, Montero, Ana, Merlos, Manuel, Vela, José M., Herrando-Grabulosa, Mireia, Navarro, X. (Xavier), and Universitat Autònoma de Barcelona. Institut de Neurociències

Subjects
amyotrophic lateral sclerosis, motoneuron degeneration, sigma-1 receptor, SOD1G93A mice, spinal nerve injury, Sigma-1 receptor, Mice, Transgenic, Ligands, Catalysis, Inorganic Chemistry, Mice, Superoxide Dismutase-1, Animals, Receptors, sigma, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Motor Neurons, Superoxide Dismutase, Organic Chemistry, Amyotrophic Lateral Sclerosis, General Medicine, Motoneuron degeneration, Amyotrophic lateral sclerosis, Neuroprotection, Spinal nerve injury, Computer Science Applications, Disease Models, Animal, Spinal Cord
Abstract

Motor neuron diseases (MNDs) include sporadic and hereditary neurological disorders characterized by progressive degeneration of motor neurons (MNs). Sigma-1 receptor (Sig-1R) is a protein enriched in MNs, and mutations on its gene lead to various types of MND. Previous studies have suggested that Sig-1R is a target to prevent MN degeneration. In this study, two novel synthesized Sig-1R ligands, coded EST79232 and EST79376, from the same chemical series, with the same scaffold and similar physicochemical properties but opposite functionality on Sig-1R, were evaluated as neuroprotective compounds to prevent MN degeneration. We used an in vitro model of spinal cord organotypic cultures under chronic excitotoxicity and two in vivo models, the spinal nerve injury and the superoxide dismutase 1 (SOD1)G93A mice, to characterize the effects of these Sig-1R ligands on MN survival and modulation of glial reactivity. The antagonist EST79376 preserved MNs in vitro and after spinal nerve injury but was not able to improve MN death in SOD1G93A mice. In contrast, the agonist EST79232 significantly increased MN survival in the three models of MN degeneration evaluated and had a mild beneficial effect on motor function in SOD1G93A mice. In vivo, Sig-1R ligand EST79232 had a more potent effect on preventing MN degeneration than EST79376. These data further support the interest in Sig-1R as a therapeutic target for neurodegeneration.

Published
2022

21. Pathogenesis of platinum-induced peripheral neurotoxicity: Insights from preclinical studies

Author

Calls, A, Carozzi, V, Navarro, X, Monza, L, Bruna, J, Calls A., Carozzi V., Navarro X., Monza L., Bruna J., Calls, A, Carozzi, V, Navarro, X, Monza, L, Bruna, J, Calls A., Carozzi V., Navarro X., Monza L., and Bruna J.

Abstract

One of the most relevant dose-limiting adverse effects of platinum drugs is the development of a sensory peripheral neuropathy that highly impairs the patients' quality of life. Nowadays there are no available efficacy strategies for the treatment of platinum-induced peripheral neurotoxicity (PIPN), and the only way to prevent its development and progression is by reducing the dose of the cytostatic drug or even withdrawing the chemotherapy regimen. This clinical issue has been the main focus of hundreds of preclinical research works during recent decades. As a consequence, dozens of in vitro and in vivo models of PIPN have been developed to elucidate the molecular mechanisms involved in its development and to find neuroprotective targets. The apoptosis of peripheral neurons has been identified as the main mechanism involved in PIPN pathogenesis. This mechanism of DRG sensory neurons cell death is triggered by the nuclear and mitochondrial DNA platination together with the increase of the oxidative cellular status induced by the depletion of cytoplasmic antioxidant mechanisms. However, since there has been no successful transfer of preclinical results to clinical practise in terms of therapeutic approaches, some mechanisms of PIPN pathogenesis still remain to be elucidated. This review is focused on the pathogenic mechanisms underlying PIPN described up to now, provided by the critical analysis of in vitro and in vivo models.

Published
2020

23. Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases

Author

Català, A., primary, Muñoz-Santos, C., additional, Galván-Casas, C., additional, Roncero Riesco, M., additional, Revilla Nebreda, D., additional, Solá-Truyols, A., additional, Giavedoni, P., additional, Llamas-Velasco, M., additional, González-Cruz, C., additional, Cubiró, X., additional, Ruíz-Villaverde, R., additional, Gómez-Armayones, S., additional, Gil Mateo, M.P., additional, Pesqué, D., additional, Marcantonio, O., additional, Fernández-Nieto, D., additional, Romaní, J., additional, Iglesias Pena, N., additional, Carnero Gonzalez, L., additional, Tercedor-Sanchez, J., additional, Carretero, G., additional, Masat-Ticó, T., additional, Rodríguez-Jiménez, P., additional, Gimenez-Arnau, A.M., additional, Utrera-Busquets, M., additional, Vargas Laguna, E., additional, Angulo Menéndez, A.G., additional, San Juan Lasser, E., additional, Iglesias-Sancho, M., additional, Alonso Naranjo, L., additional, Hiltun, I., additional, Cutillas Marco, E., additional, Polimon Olabarrieta, I., additional, Marinero Escobedo, S., additional, García-Navarro, X., additional, Calderón Gutiérrez, M.J., additional, Baeza-Hernández, G., additional, Bou Camps, L., additional, Toledo-Pastrana, T., additional, and Guilabert, A., additional

Published
2022
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33. New stimulation device to drive multiple transverse intrafascicular electrodes and achieve highly selective and rich neural responses

Author

Guiho, Thomas, López-Álvarez, Victor Manuel, Čvančara, Paul, Hiairrassary, Arthur, Andreu, David, Stieglitz, Thomas, Navarro, X. (Xavier), Guiraud, David, and Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia

Subjects
Stimulation selectivity, Peripheral nerve, Neuroprosthesis, Stimulation device, Intrafascicular electrode
Abstract

Peripheral Nerve Stimulation (PNS) is a promising approach in functional restoration following neural impairments. Although it proves to be advantageous in the number of implantation sites provided compared with intramuscular or epimysial stimulation and the fact that it does not require daily placement, as is the case with surface electrodes, the further advancement of PNS paradigms is hampered by the limitation of spatial selectivity due to the current spread and variations of nerve physiology. New electrode designs such as the Transverse Intrafascicular Multichannel Electrode (TIME) were proposed to resolve this issue, but their use was limited by a lack of innovative multichannel stimulation devices. In this study, we introduce a new portable multichannel stimulator-called STIMEP-and implement different stimulation protocols in rats to test its versatility and unveil the potential of its combined use with TIME electrodes in rehabilitation protocols. We developed and tested various stimulation paradigms in a single fascicle and thereafter implanted two TIMEs. We also tested its stimulation using two different waveforms. The results highlighted the versatility of this new stimulation device and advocated for the parameterizing of a hyperpolarizing phase before depolarization as well as the use of small pulse widths when stimulating with multiple electrodes.

Published
2021

34. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain: Abstracts of Symposia and free communications

Author

Harms, L., Bock, A., JÄnisch, W., Valdueza, J., Weber, J., Link, I., De Keyser, J., Goossens, A., Wilczak, N., Vedeler, C., Bjorge, L., Uvestad, E., Conti, G., Williams, K., Ginsberg, L., Rafique, S., Rapoport, S. I., Gershfeld, N. L., De La Meilleure, G., Crevits, L., Faiss, J. H., Heye, N., Blanke, J., Sackmann, A., Kastrup, O., Doornbos, R., van der Worp, H. B., Kappelle, L. J., Bar, P. R., Davie, C. A., Barker, G. J., Brenton, D., Miller, D. H., Thompson, A. J., Block, F., Schwarz, M., Delodovici, L., Baruzzi, F., Bonaldi, G., Dario, A., Marra, A., Mercuri, A., Dworzak, F., Cavallari, P., Confalonieri, P., Zuffi, M., Antozzi, C., Cornelio, F., Baldissera, F., Chassande, B., Ameri, A., Eymard, B., Poisson, M., Vérier, A., Brunet, P., Congia, S., Murgia, P. L., Cannas, A., Borghero, G., Uselli, S., Mellino, G., Ferrai, R., Lampis, R., Massa, R., Muzzetto, B., Giannini, F., Rossi, S., Cioni, R., d'Aniello, C., Guarneri, A., Battistini, N., Ceriani, F., Del Santo, A., Poloni, M., Campo, J. F., Iglesias, F., Guitera, M. V., Farinas, C., Pascual, J., Leno, C., Berciano, J., Thorpe, I. W., Kendall, B. E., McDonald, W. I., Moulignier, A., Dromer, F., Baudrimont, M., Dupont, B., Gozlan, J., El Amrani, M., Petit, J. C., Roullet, E., Sterzi, R., Causaran, R., Protti, A., Riva, M., Erminio, F., Arena, O., Villa, F., Maccagnano, E., Miletta, M., Spinelli, F., Ben-Hur, T., Weidenfeldl, J., Rao, N. S., Chari, C. C., Laforet, P., Matheron, S., Adams, D., Chemouilli, Ph., Desi, M., Said, G., Davous, P., Lionnet, F., Pulik, M., Genet, P., Rozenberg, F., Cartier, L. M., Castillo, J. L., Cea, J. G., Villagra, R., de Saint Martin, L., Mahieux, F., Manifacier, M. J., Mattos, K., Queiros, C., Publio, L., Vinhas, V., PeÇanha-Martins, A. C., Melo, A., Liska, U., Zifko, U., Budka, H., Drlicek, M., Grisold, W., Kaufmann, R., Kaiser, R., Czygan, M., Gomes, I., Jones, N., Cunha, S., EmbiruÇu, E. Katiane, Vieira, V., Araujo, I., Alexandra, M., Ferreira, A., Goes, J., Chemouilli, P., Israel-Biet, Masson, H., Lacroix, C., Gasnault, J., Hildebrandt-Müller, B., Oschmann, P., Krack, P., Willems, W. R., Dorndorf, W., Freitas, V., Bittencourt, A., Fernandes, D., Nascimento, M. H., Severo, M., Moraes, D., Muller, M., Hasert, K., Merkelbach, S., Schimrigk, K., van Oosten, B. W., Lai, M., Polman, C. H., Bertelsmann, F. W., Hodgkinson, S., Cabre, P. H., Volpe, L., Smadja, D., Vernant, J. P., Villaroya, H., Violleau, K., Younes-Chennoufi, A. Ben, Baumann, N., Villanueva-Hemandez, P., Ballabriga, J., Basart, E., Arbizu, T. X., Perez-Serra, J., Vinuels, F., Giron, J. M., Castilla, J. M., Redondo, L., Izquierdo, G., Lauer, K., Henneberg, A., Bittmann, N., Link, D., Wollinsky, K. H., Mobner, R., Fassbender, K., Kuhnen, J., Schwartz, A., Hennerici, M., Miller, A., Lider, O., Abramsky, O., Weiner, H. L., Offner, H., Vanderbark, A. A., Paoino, E., Fainardi, E., Addonizio, M. C., Ruppi, P., Tola, M. R., Granieri, E., Carreras, M., Sazdovitch, V., Joutel, A., Verdier-taillefer, M. H., Heinzlef, O., Radder, C., Tournier-Lasserve, E., Brenner, R. E., Munro, P. M. G., Williams, S. C. R., Bell, J. D., Hawkins, C. P., Filippi, M., Campi, A., Dousset, V., Canal, N., Comi, G., Zhu, J., Weber, F., Retska, R., List, J., Zhang, L., Brock, M., Taphoorn, M. J. B., Heimans, J. J., van der Veen, E. A., Karim, A. B. M. F., Sarazin, M., Argentino, N., Delattre, J. Y., Derkinderen, P., Buchwald, B., Schroter, G., Serve, G., Franke, C. H., Conrad, B., Kitchen, N. D., Thomas, D. G. T., Forman, A. D., Ang, Kie- Kian, Price, R., Stephens, C., Salmaggi, A., Nermni, R., Silvani, A., Forno, M. G., Luksch, R., Boiardi, A., Grzelec, H., Fryze, C., Nowacki, P., Zdziarska, B., Sanson, M., Merel, P., Richard, S., Rouleau, G., Thomas, G., Olsen, N. K., Pfeiffer, P., Egund, N., Bentzen, S. M., Johannesen, L., Mondrup, K., Rose, C., Zyluk, B., Wondrusch, E., Berger, O., Fast, N., Jellinger, K., Lindner, K., Urman, A., Thibault, J. L., Duyckaerts, Ch., Strik, H., Muller, B., Richter, E., Krauseneck, P., Steinbrecher, A., Schabet, M., Hess, C., Bamberg, M., Dichgans, J., Counsell, C. E., McLeod, M., Grant, R., Creel, G. B., Claus, D., Sieber, E., Engelhardt, A., Rechlin, T., Thierauf, P., Neubauer, U., Peresson, M., Di Giovacchino, G., Romani, G. L., Di Silverio, F., Danek, A., Kuffner, M., Hoermann, R., Schopohl, J., Laska, M., Heye, B., Zangaladze, A. T., Valls-SoIè, J., Cammarota, A., Alvarez, R., Tolosa, E., Hallett, M., Ulbricht, D., Ganslandt, O., Kober, H., Vieth, J., Grummich, P., Pongratz, H., Brigel, C., Fahlbusch, R., Serra, F. P., Palma, V., Nolfe, G., Buscaino, G. A., Rothstein, T. L., Gibson J. M., Morrison P. M., Collins A. D., Eiselt, M., Wagnur, H., Zwiener, U., Schindler, T., Efendi, H., Ertekin, C., Erfas, M., Larsson, L. E., Sirin, H., AraÇ, N., Toygar, A., Demir, Y., Seddigh, S., Vogt, T. H., Hundemer, H., Visbeck, A., Pastena, L., Faralli, F., Mainardi, G., Gagliardi, R., Linden, D., Berlit, P., Lopez, O. L., Becker, J. T., Jungreis, C., Brenner, R., Rezek, D., Dekesky, S. T., Estol, C., Boller, F., Fernandez, J. M., Mederer, S., Batlle, J., Turon, A., Codina, A., Hitzenberger, P., Vila, N., Valls-SolÇ, J., Chamorro, A., Pouget, J., Schmied, A., Morin, D., Azulay, J. Ph., Vedel, J. P., Montalt, J., Escudero, J., Barona, R., Campos, A., Varli, K., Ertem, E., Uludag, B., Yagiz, A., Privorkin, Z., Steinvil, Y., Kott, E., Combarros, O., Sanchez-Pernaute, R., Orizaola, P., Mokrusch, Th., Kutluaye, E., Selcuki, D., Ertikin, C., Zettl, U., Gold, R., Harvey, G. K., Hartung, H. P., Toyka, K. V., Wokke, J. H. J., Oey, P. L., Ippel, P. F., Jansen, G. H., Franssen, H., Toyooka, K., Fujimura, H., Ueno, S., Yoshikawa, H., Yorifuji, S., Yanagihara, T., Talamon, C., Tzourio, C., Kiefer, R., Jung, S., Toyka, K., Ruolt, I., Tranchant, C., Mohr, M., Warter, J. M., Younger, D. S., Rosoklija, G., Hays, A. P., Kurita, R., Hasegawa, O., Matsumto, M., Komiyama, A., Nara, Y., Oueslati, S., Belal, S., Turki, I., Ben Hamida, C., Hentati, F., Ben Hamida, M., Kwiecinski, H., Krolicki, L., Domzal-Stryga, A., Dellemijn, P. L. I., van Deventer, P., van Moll, B., Drogendijk, T., Vecht, Ch. J., Nemni S., Amadio, Fazio, R., Galardin, G., Delodovici, M. L., Peghi, E., Monticelli, M. L., Sessa, A., Viguera, M. L., Palomar, M., Gamez, J., Cervera, C., Navarro, C., Serena, J., Duran, I., Fernandez, A. L., Comabella, M., Nos, C., Rio, J., Montalban, J., Navarro, X., Verdu, E., Darbra, S., Buti, M., Mrabet, A., Fredj, M., Gouider, R., Tounsi, H., Khalfallah, N., Haddad, A., Dbaiss, T., Ghnassia, R., Rouillet, E., Chedru, F., Porsche, H., Strenge, H., Li, S. W., Young, Y. P., Garcia, A. A., Baron, P., Scarpini, E., Bianchi, R., Conti, A., Livraghi, S., Rees, J. H., Gregson, N. A., Hughes, R. A. C., Sedano, M. J., Calleja, J., Canga, E., Bahou, Y., Biary, N., Al Deeb, S. M., Guern, E. L. E., Gugenheim, M., Tardieu, S., Aisonobe, T. M., Agid, Y., Bouche, P., Brice, A., Rautenstrauss, B., Nelis, E., Grehl, H., Van Broeckhoven, C., Pfeiffer, R. A., Liehr, T., Ganzmann, E., Gehring, C., Neundörfer, B., Geremia, L., Doronzo, R., Sacilotto, G., Sergi, P., Pastorino, G. C., Scarlato, G., Planté-Bordeneuve, V., Mantel, A., Baas, F., Moser, H., Antonini, A., Psylla, M., Günther, I., Vontobell, P., Beer, H. F., Leenders, K. L., Chaudhuri, K. Ray, Parker, J., Pye, I. F., Millac, P. A. H., Abbott, R. J., Sutter, M., Albani, C., de Rijk, M. C., Breteler, M. M. B., Graveland, G. A., van der Mechè, F. G. A., Hofman, A., Keipes, M., Hilger, Ch., Diederich, N., Metz, H., Hentges, F., Pollak, P., Benabid, A. L., Limousin, P., Hoffmann, D., Benazzouz, A., Perret, J., Laihinen, A., Rinne, J. O., Ruottinen, H., Nagren, K., Lehikoinen, P., Oikonen, V., Ruotsalainen, U., Rinne, U. K., Cocozza, S., Pizzuti, A., Cavalcanti, F., Monticelli, A., Pianese, L., Redolfi, E., Paiau, F., Di Donato, S., Pandolfo, M., Palau, F., Monros, E., De Michele, G., Smeyers, P., Lopez-ArLandis, J., Uilchez, J., Filla, A., Genis, D., Matilla, T., Volpini, V., Blanchs, M. I., Davalos, A., Molins, A., Rosell, J., Estivill, X., De Jonghe, P., Smeyers, G., Krols, L., Mercelis, R., Hazan, J., Weissenbach, J., Martin, J. J., Warner, T. A. T., Williams, L., Orb, A. S., Harding, A. E., Giunti, P., Sweeney, M. G., Spadaro, M., Jodice, C., Novelletto, A., Malaspina, P., Frontali, M., Salmon, E., Gregoire, Del Fiore, Comar, Franck, G., Scheltens, P. H., Siegfried, K., Dartigues, E., De Deyn, P., Horn, R., Nelson, I., Hanna, M. G., Morgan-Hughes, J. A., Collinge, J., Palmer, M. S., Campbell, T., Mahal, S., Sidle, K., Humphreys, C., Tavitian, B., Pappata, S., Jobert, A., Crouzel, A. M., DiGiamberardino, L., Steimetz, G., Barbanti, P., Fabbrini, G., Salvatore, M., Buzzi, M. G., Di Piero, V., Petraroli, R., Sbriccoli, A., Pocchiari, M., Macchi, G., Lenzi, G. L., Spiegel, R., Maguire, P., Schmid, W., Ott, A., Bots, M. L., Grobbe, D. E., Hofman, A., Howard, R. S., Russell, S., Losseff, N., Hirsch, N. P., Couderc, R., Bailleul, S., Nargeot, M. C., Touchon, J., Picot, M. C., Rizzo, M., Watson, G., McGehee, D., Dingus, T., Kappos, L., Radü, E. W., Haas, J., Hartard, C. H., Spuler, S., Yousry, T., Voltz, R., Scheller, A., Holler, E., Hohlfeld, R., Scolding, N. J., Sussman, J., Kolar, O. J., Farlow, M. R., Rice, P. H., Zipp, F., Sotgiu, S., Weiss, E. H., Wekerle, H., Chalmers, R., Robertson, N., Compston, D. A. S., Martino, G., Clementi, E., Brambilla, E., Moiola, L., Martinelli, V., Colombo, B., Poggi, A., Rovaris, M., Grimaldi, L. M. E., Roth, M. P., Descoins, P., Ballivet, S., Ruidavets, J. B., Waubant, E., Nogueira, L., Cambon-Thomsen, A., Clanet, M., Leppert, D., Hauser, S., Lugaresi, A., Tartaro, A., D'aurelio, P., Befalo, L. L. O., Thomas, A., Malatesta, G., Gambi, D., Benedikz, J. E. G., Magnusson, H., Poser, C. M., Guomundsson, G., Bates, T. E., Davies, S. E. C., Clark, J. B., Landon, D. N., ùther, J. R., Rautenberg, W., Overgaard, K., Sereghy, T., Pedersen, H., Boysen, G., Diez-Tejedor, E., Carceller, F., Gutierrez, M., Lopez-Pajares, R., Roda, J. M., Chandra, B., Ricart, W., Gonzalez-Huix, F., Molina, A., Rundek, T., Demarin, V., De Reuck, J., Boon, P., Decoq, D., Strijckmans, K., Goethals, P., Lemahieu, I., Nibbio, A., Chabriat, H., Vahedi, K., Nagy, T., Verin, M., Mas, J. L., Julien, J., Ducrocq, X., Iba-Zizen, M. T., Cabanis, E. A., Bousser, M. G., Rolland, Y., Landgraf, F., Bompais, B., Lemaitre, M. H., Edan, G., Vorstrup, S., Knudsen, L., Olsen, K. Skovgaard, Videbaek, C., Schroeder, T., van Gijn, J., Jansen, H. M. L., Pruim, J., Paans, A. M. J., Willemsen, A. T. M., Hew, J. M., vd Vliet, A. M., Haaxma, R., Vaalburg, W., Minderhoud, J. M., Korf, J., Soudain, S. E., Ho, T. W., Mishu, B., Li, C. Y., Nachainkin, I., Gao, C. Y., Cornblath, D. R., Griffin, J. W., Asbury, A. K., Blaser, M. J., McKhann, G. M., Ho, T., Macko, C., Xue, P., Stadlan, E. M., Ramos-Alvarez, M., Valenciano, L., Visser, L. H., van der Meché, F. G. A., van Darn, P. A., Meulstee, J., Schmitz, P. I. M., Jacobs, B., Oomes, P. G., Kleyweg, R. P., Jacobs, B. C., Endtz, H. P., van Doorn, P. A., van der Mech, F. G. A., Van den Berg, L. H., Mollee, I., Logtenberg, T., Thomas, P. K., Plant, G., Baxter, P. J., Luis, R. Santiago, Matsumoto, M., Notermans, N. C., Wokke, J. H. J., Lokhorst, H. M., van der Graaf, Y., Jennekens, F. G. I., Azulay, J. P., Bille-Turg, F., Valentin, P., Farnarier, G. G., Pellissier, J. F., Serratrice, G., Quasthoff, S., Schneider, U., Grafe, P., Hilkens, P. H. E., Moll, J. W. B., van der Burg, M. E. L., Planting, A. S. T., van Putten, W. L. J., van den Bent, M. J., Birklein, F., Spitzer, A., Lang, E., Neundorfer, B., Diehl, R. R., Lücke, D., Smith, G. D. P., Mathias, C. J., Serra, J., Campera, M., Ochoa, J. L., Ray Chaudhuri, K., Pavitt, D., Alam, M., Handwerker, H. O., Bleasdale-Barr, K., Smith, G., Murray, N. M. F., Hawkins, P., Pepys, M., Gellera, C., DiDonato, S., Taroni, F., Uncini, A., Di Muzio, A., Servidei, S., Silvestri, G., Lodi, R., Iotti, S., Barbiroli, B., Morrissey, S. P., Borruat, F. X., Francis, D., Mosely, I., Hansen, H. C., Helmke, K., Kunze, K., Sadzot, B., Maquet, P., Lemaire, Plenevaux, Damhaut, Sommer, C., Myers, R. R., Berta, E., Mantegazza, R., Argov, Z., Shapira, Y., Wirguin, I., Beuuer, J., Franke, C., Roberts, M., Willison, H., Vincent, A., Newsom-Davis, J., Morrison, K. E., Damels, R., Francis, M., Campbell, L., Davies, K. E., Kohler, W., Bucka, C., Hertel, G., Kanovsky, P., Auer, D., Ackermann, H., Klose, U., Naegele, Th., Bien, S., Voigt, K., Fink, G. R., Stephan, K. M., Wise, R. J. S., Mullatti, N., Hewer, L., Frackowiak, R. S. J., Weiller, C. S., Rijnites, M., Jueptner, M., Bauermann, T., Krams, M., Diener, H. C., van Walderveen, M. A. A., Barkhof, F., Hommes, O. R., Valk, J., Willmer, J. P., Guzman, D. A., Passingham, R. E., Silbersweig, D., Ceballos-Baumann, A., Frith, C. D., Frackowiak, R., Lucas, C. H., Goullard, L., Marchau, M. J., Godefroy, O., Rondepierre, P. H., Chamas, E., Mounier-Vehier, F., Leys, D., Renato, J., Verdugo, M. S. C., Campero, M., Jose, L., Ochoa, D. S. C., Vivancos, F., Tejedor, E. Diez, Martinez, N., Roda, J., Frank, A., Barreiro, P., Satoh, Y., Nagata, K., Maeda, T., Hirata, Y., YalÇinerner, B., Ozkara, C., Ozer, F., Ozer, S., Hanoglu, L., Zunker, P., Pozo, J. L., Oberwittler, C., Schick, A., Buschmann, H. -Ch., Ringelstein, E. Bernd, Lara, M., Anzola, G. P., Magoni, M., Volta, G. Dalla, Tarasov, A., Feigin, V., Beaudry, M. G., Carrier, S., Chicoutimi, Henriques, I. L., Bogoussslavsky, J., van Melle, G., Mathieu, J., Perusse, L., Allard, P., Prevost, C., Cantin, L., Bouchard, J. M., De Braekeleer, M., Agbo, C., Neau, J. P., Tantot, A. M., Dary-Auriol, M., Ingrand, P., Gil, R., Baltadjiev, D., Zekin, D., Sabey, K., Gennaula, C. P., Pope, B. A., Caparros-Lefebvre, D., Girard-Buttaz, I., Pruvo, J. P., Petit, H., Hipola, D., Martin, M., Giménez-Roldan, S., Ivanez, V., Japaridze, G., Carrasco, J. L., Picomell, I., Herranz, J. L., Macias, J. A., Nieto, M., Noya, M., Oller, L., Kiteva-Trencevska, G., Delgado, M. R., Liu, H., Luengo, A., Parra, J., Colas, J., Fernandez, M. J., Manzanares, R., Kornhuber, M. E., Malashkhia, V., Orkodashili, G., Martinez, M., Bonaventura, I., Porta, G., Martinez, I., Fernandez, A., Aguilar, M., Masnou, P., Drouet, A., Dreyfus, M., Cartron, J., Morel-Kopp, M. C., Tchernia, G., Kaplan, C., Lammers, M. W., Hekster, Y. A., Keyser, A., Meinardi, H., Renier, W. O., Boon, P. A. J. M., Have, M. D., Kint, B., Cruz, P., Cadilha, A., Almeida, R., Goncalves, M., Pimenta, M., Ramos, L. M. P., Polder, T. W., Broere, C. A., Polman, L., Rother, I., Rother, M., Schlaug, G., Arnold, S., Holthausen, H., Wunderlich, G., Ebner, A., Luders, H., Witte, O. W., Seitz, R. J., Serra, L. L., Gallicchio, B., Rotondi, F., Wieshmann, U., Meierkord, H., Sabev, K., Di Carlo, V., Gueguen, B., Derouesné, Ch., Ancri, D., Bourdel, M. C., Guillou, S., Aliaga, R., Chornet, M. A., Rodrigo, A., Pascual, A. Pascual -Leone, Catala, M. D., Pascual-Leone, A., Benbadis, S. R., Dinner, D. S., Chelune, G. J., Lüders, H. O., Piedmonte, M. R., Blanco, T., Lopez, M. P., Romero, B., Deltoro, A., Pascual, A., Pascual, Leone, Bolgert, F., Josse, M. O., Tassan, P., Touze, E., Laplane, D., Godenberg, F., Brizioli, E., Del Gobbo, M., Pelliccioni, G., Scarpino, O., Durak, H., Damlacik, G., Tunca, Z., Fidaner, H., Yurekli, Y., Yemez, B., Kaygisiz, A., Anllo, E. A., Esperet, E., Giovagnoli, A. R., Casazza, M., Spreafico, R., Avanzini, G., Mascheroni, S., Vecchio, I., Tornali, C., Antonuzzo, A., Grasso, A. A., Bella, R., Pennisi, G., Raffaele, R., Broeckx, J., Schildermans, F., Hospers, W., Deberdt, W., Carney, J. M., Aksenova, M., Chen, M. S., Juncadella, M., Busquets, N., De la Fuente, I., Rodriguez, A., Rubio, F., Soler, R., Khati, C., Pillon, B., Deweer, B., Malapani, C., Malichard, N., Dubois, B., Rancurel, G., Lopez, D. L., Jungreia, G., DeKosky, S. T., Boiler, F., Weiller, C., Rijntjes, M., Mueller, S. P., Maguire, E. A., Burke, E. T., Staunton, H., Phillips, J., Rousseaux, M., Pena, J., Bertran, I., Santacruz, P., Lopez, R., Catafau, A., Lomena, F., Blesa, R., Rampello, L., Nicoletti, A., Cabaret, M., Lesoin, F., Steinling, M., Tournev, I., Maier-Hauff, K., Schroeder, M., Wolf, A., Cochin, J. P., Noel, I., Augustin, P., Auzou, P., Hannequin, D., Maria, V., Lopez-Bresnahan, Danielle, D. M., Antin-Ozerkis B. A., Bartels, E., Rodiek, S. O., Flugel, K. A., Campos, D. M., Salas-Puig, J., Del Rio, J. Sanhez, Vidal, J. A., Lahoz, C. H., Eraksoy, M., Barlas, O., Barlas, M., Bayindir, C., Ozcan, H., Birbamer, G., Gerstenbrand, F., Felber, S., Luz, G., Aichner, F., Seidel, G., Kaps, M., Hutzelmann, A., Gerriets, T., Kruggel, F., Martin, P. J., Gaunt, M. E., Abbot, R. J., Naylor, A. R., Meary, E., Dilouya, A., Meder, J. F., De Recondo, J., Lebtahi, R., Neff, K. W., Meairs, S., Viola, S., Matta, E., Aquilone, L., Rise, I. R., Authier, F. J., Kondo, H., Ghnassia, R. T., Degos, J. D., Gherardi, R. K., Bardoni A., Ciafaloni E., Comi G. P., Bresolin N., Robotti M., Moggio M., Rigoletto C., Roses A., Scarlato G., Castelli, E., Turconi, A., Bresolin, N., Perani, D., Felisari, G., Chariot, P., de Pinieux, G., Astier, A., Jacotot, B., Gherardi, R., Fischer-Gagnepain, V., Louboutin, J. P., Crespo, F., Florea-Strat, A., Fromont, G., Sabourin, J. -C., Gonano, E. -F., Moroni, I., Prelle, A., Iannaccone, S., Quattrini, A., deRino, F., Sessa, M., Golzi, V., Smirne, S., Nemni, R., Turpin, J. C., Lucotte, G., Jacobs, S. C. J. M., Willems, P. W. A., Bootsma, A. L., Lasa, A., Calaf, M., Baiget, M., Gallano, B., Fichter-Gagnepain, V., Mazzucchelli, F., D'Angelo, M. G., Velicogna, M., Bet, L., Comi, G. P., Bordoni, A., Gonano, E. F., Bazzi, P., Rapuzzi, S., Moggio, M., Fagiolari, G., Ciscato, P., Messina, A., Battistel, A., Ryniewicz, B., Sangla, I., Desnuelle, C., Paquis, V., Cozzone, P. J., Bendahan, D., Sturenburg, H. J., Kohncke, G., Castellli, E., Linssen, W., Stegeman, D., Binkhorst, R., Notermans, S., Jaspert, A., Fahsold, R., de Munain, A. Lopez, Cobo, A., Martorell, L., Poza, J. J., Navarrete Palau, D., Emparanza, J. I., Sanchez-Roy, R., Vilchez, J. J., Hernandez, M., Tena, J. Garcia, Perla, C., Koutroumanidis, M., Papathanasopoulos, P., Papadimitriou, A., Papapetropoulos, T. H., Divari, R., Hadjigeorgiou, G. M., Anastasopoulos, I., Sansone, V., Rotondo, G., Meola, G., Rigoletto, C., Messina, S., Szwabowska-Orzeszko, E., Jozwiak, S., Michalowicz, R., Szaplyko, W., Petrella, M. A., Della Marca, G., Masullo, G., Mennuni, G. F., Kompf, D., Wascher, E., Verleger, R., Kaido, M., Soga, F., Toyooka, H., Bayon, C., Rubio, J., Carlomagno, S., Parlato, V., Santoro, A., Lavarone, A., Bonavita, V., Pentore, R., Venneri, A., Pasquier, F., Lebert, F., Grymonprez, L., Lefebvre, C., Van der Linden, M., Derouesné, C., Renault, B., Lacomblez, L., Homeyer, P., Ouss, L., Neuman, E., Malbezin, M., Barrandon, S., Guez, D., Stevens, M., van Swieten, J. C., Franke, C. L., Sanchez, A., Castellvirel, S., Mila, M., Jimenez, D., Pallesta, F., Ruiz, P. J. Garcia, Barrio, A., Barroso, T., Benitez, J., de Yebenes, J. Garcia, Manubens, J. M., Martinez-Lage, J. M., Larumbe, R., Muruzabal, J., Lacruz, F., Quesada, Pedro, Gallego, J., Ferini-Strambi, L., Marcone, A., Garancini, P., Tedesi, B., Jacob, B., Rozewicz, L., Langdon, D., Davie, C., Ron, M., Thompson, A., Koepp, M. J., Hansen, M. L., Guldin, B., Pressler, R. M., Ried, S., Scholz, C., Monaco, F., Gianelli, M., Schiavalla, M. P., Naldi, P., Cantello, R., Torta, R., Verze, L., Mutani, R., Knott, H., Ferbert, A., Schulze-Bonhage, A., Aust, W., Di Mascio, R., Marchioli, R., Vitullo, F., Di Pasquale, A., Sciulli, L., Kramer, V., Tognoni, G., Santacruz, P., Lopez, R., Marti, M. J., Charques, I., Catafau, A., Lomeila, F., Peila, J., Bertran, I., Blesa, R., Krendel, D. A., Costiga, D. A., Koeppen, S., Korn, W. M., Brugge, S., Schmitz, D., Scheulen, M. E., King, R. H. M., Robertson, A. M., Thomas, P. K., Kerkhofs, A., Vermersch, P., Dereeper, O., Daems Monpeun, C., Parent, M., Deplanque, D., Petit, H., Campero, M., Serra, J., Ochoa, J. L., Martinez-Matos, J. A., Montero, J., Olivé, M., Rene, R., Vidaller, A., Gugenheim, M., Gouider, R., Le Guern, E., Brice, A., Agid, Y., Bouche, P., Grisold, W., Ziflo, U., Drlicek, M., Budka, H., Jellinger, K., Zielinski, C. H., Ginsberg, L., King, R. H. M., Workman, J., Platts, A. D., Thomas, P. K., Gherardi, R. K., Florea-Strat, A., Poron, F., Sabourin, J. -C., Fazio, R., Nemni, R., Franceschi, M., Lorenzetti, I., Rinaldi, L., Canal, N., Weilbach, F. X., Sennlaub, A., Jung, S., Gold, R., Toyka, K. V., Hartung, H. P., Giegerich, G., Ellie, E., Vital, A., Steck, A. J., Vital, C., Julien, J., Doneda, P., Pizzul, S., Scarpini, E., Chiodi, P., Ramacci, M. T., Livraghi, S., Maimone, D., Annunziata, P., Salvadori, C., Guazzi, G. C., Arne-Bes, M. C., Delisle, M. B., Fabre, N., Hurtevent, J. F., Bes, A., Baudoin-Martin, D., Laborde, E., Viallet, F., Creisson, C., Crespi, V., Bogliun, G., Marzorati, L., Zincone, A., D'Angelo, L., Liberani, A., Merlini, M., Rivolta, R., Creange, A., Sabourin, J. -C., Theodorou, I., Gherardi, R. K., Conti, A. M., Malosio, M. L., Baron, P. L., Scarlato, G., Chorao, R., Rosas, M. J., Leite, I., Callea, L., Donati, E., Bargnani, C., Bud, M., Verdu, E., Navarro, X., Braun, S., Einius, S., Poindron, P., Warier, J. M., Bradley, J., Bekkelund, S. I., Torbergsen, T., Mellgren, S. I., Carlomagno, S., Parlato, V., Santoro, A., Lavarone, A., Boller, F., Bonavita, V., Engelhardt, A., Lörler, H., Robeck, S., Kluglein, C., Comi, G., Avoledo, V., Locatelli, T., Leocani, L., Galardi, G., Magnani, G., Medaglini, S., Chkhikvishvili, T. S., Zangaladze, A., Bratoeva, M., Kovachev, P., Chavdarov, D., Artemis, N., Karacostas, D., Milonas, I., Arpa, J., Lopez-Pajares, R., Cruz-Matinez, A., Sarria, J., Palomo, F., Alonso, M., Rodriguez-Al-barino, A., Lacasa, T., Nos, J., Barreiro, P., Martinez, A. Cruz, Villoslada, C., Alons, M., Taghavy, A., Hamer, H., Kratzer, A., Dethy, S., Pauwels, T., Monclus, M., Luxen, A., Goldman, S., Ziegler, M., Crambes, O., Ragueneau, I., Arnaud, F., Zappia, M., Montesanti, R., Colao, R., Palmieri, A., Branca, D., Nicoletti, G., Rizzo, M., Parlato, G., Quattrone, A., Vanacore, N., Zuchegna, P., Bonifati, V., Meco, G., Scholz, J., Friedrich, H. -J., Rohl, A., Ulm, G., Vieregge, P., Savettieri, G., Rocca, W. A., Meneghini, F., Grigoletto, F., Morgante, L., Reggio, A., Salemi, G., Di Pierri, R., OzckmekÇi, S., Ertan, S., Yeni, N., Apaydin, H., Erkol, G., Kiziltan, G., Denktas, F., Ranoux, D., de Recondo, J., Ostergaard, L., Werdelin, L., Odin, P., Lindvall, O., Dupont, E., Christensen, P. B., Boisen, E., Jensen, N. B., Schmiegelow, M., Ingwersen, S. H., Matias-Guiu, J., Canet, T., Falip, R., Martin, R., Galiano, L., Voloshin, M. Y., Burchinskaya, L. F., Cabrera-Valdivia, F., Jimenez-Jimenez, F. J., Molina, J. A., Fernandez-Calle, P., Vazquez, A., Canizares-Liebana, F., Larumbe-Lobalde, S., Ayuso-Peralta, L., Rabasa, M., Codoceo, R., Arrieta, F. J., Aguilar, M. V., Jorge-Santamaria, A., Martinez-Para, M. C., Alarcon, J., Mateo, D., Gimenez-Roldan, S., Gencheva, E., Tzonev, T. z., Georgiev, G., Petkova, P., Gasparini, M., Vanacore, N., Meco, N. G., de la Sierra, G., Aguado, F., Revilla, M., Varela, L., Rico, H., Feve, A., N'Guyen, J. P., Bathien, N., Fenelon, G., Veroust, J., Cesaro, P., Egersbach, G., Hattig, H., Schelosky, L., Wissel, J., Poewe, W., Durif, F., Albuisson, E., Debilly, B., Tournilhac, M., Magnani, C., Mocellini, C., Soffietti, R., Schiffer, D., Cardozo, A., Cruz-Sanchez, F. F., Falip, L., Potagas, G., Ziegler, M., Rondot, P., Bonifati, V., Fabrizio, E., Meco, G., Bostantjopoulou, S., Katsarou, Z., Kyriazis, G., Baas, H., Demisch, L., Esser, A., Zoeller, F., Burklin, F., Harder, S., Fischer, P. A., Arcusa, M. J., Hermandez, S., Claramonte, F. J., Pascual, A. Pascual- Leone, Alonso, M. D., Catata, M. D., Alessandri, A., Giustini, P., Dufour, A., Ciusani, E., Nespolo, A., Roelcke U., Radu E. W., von Ammon K., Maguire R. P., Leenders K. L., Radionova, M., Chavdarov, D., Bratoeva, M., Tzekov, Ch., Pietrangeli, A., Bove, L., Pace, A., Falqui, L., Jandolo, B., Potemkowski, A., Muller B., Reinhard I., Krone A., Warmuth M., Brocker E. 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M., Pleiffer, G., Kunre, K., Dieterich, M., Brandt, Th., Guarino, M., Stracciari, A., Pazzaglia, P., D'Alessandro, R., Santilli, I., Donato, M., The European Velnacrine Study Group, The Dutch Guillain-Barré study group, The COP-1 Multicenter Clinical and Research Group Study, and European Study Group

Published
1994
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35. Molecular mechanisms involved in Platinum-Induced Peripheral Neuropathy. An exploratory study

Author

Bruna Escuer, Jordi, Udina i Bonet, Esther, Navarro, X. (Xavier), Calls Cobos, Aina, Bruna Escuer, Jordi, Udina i Bonet, Esther, Navarro, X. (Xavier), and Calls Cobos, Aina

Abstract

La neuropatia perifèrica induïda per platins (NPIP) és un dels efectes adversos més freqüents del cisplatí, l'oxaliplatí i el carboplatí, agents quimioteràpics de tipus platins administrats pel tractament de càncers altament prevalents. Degut a la seva severitat, la NPIP pot causar reduccions en la dosis de quimioteràpia o inclús una aturada precoç del tractament, derivant en una disminució de les probabilitats de supervivència dels pacients oncològics. S'ha demostrat que la severitat de la NPIP es correlaciona amb la quantitat de platí acumulat en les neurones sensorials del gangli raquidi de l'arrel dorsal (GRD). Així mateix, s'han descrit varis mecanismes fisiopatològics involucrats en l'aparició de la NPIP, incloent el dany a l'ADN i les mitocòndries de les neurones sensorials, juntament amb alteracions en la funció dels canals iònics, entre altres. Malgrat el gran esforç dels clínics i els investigadors per trobar un tractament per la NPIP, els resultats obtinguts en models experimentals no s'han pogut traslladar a la clínica de forma exitosa. L'objectiu d'aquesta tesi doctoral era determinar els mecanismes moleculars més rellevants involucrats en el desenvolupament de la NPIP i així poder testar noves dianes terapèutiques. Mitjançant seqüenciació de l'ARN de cèl·lules aïllades, hem estudiat el perfil d'expressió gènica de les neurones sensorials del GRD en 2 models de ratolí de NPIP òptimament caracteritzats a nivell neurofisiològic. Un model es va desenvolupar mitjançant l'administració de cisplatí i l'altre, d'oxaliplatí. Hem demostrat que el tractament amb cisplatí causa una lesió permanent a l'ADN de les neurones sensorials, juntament amb un increment de l'expressió del gen Cdkn1a i el seu producte proteic p21. Mentre que les vies d'apoptosis no s'activen en resposta a aquest dany de l'ADN, les neurones sensorials sí expressen una sèrie de marcadors relacionats amb processos de senescència cel·lular, incloent l'enzim beta-galactosidasa, la fosforilació de, La neuropatía periférica inducida por platinos (NPIP) es uno de los efectos adversos mas frecuentes del cisplatino, el oxaliplatino i el carboplatino, fármacos de tipo platino administrados para el tratamiento de neoplasias malignas altamente prevalentes. Debido a su severidad, la NPIP puede causar reducciones en la dosis de quimioterapia e incluso el cese precoz del tratamiento, hecho que influye negativamente en la probabilidad de supervivencia de los pacientes oncológicos. Se ha demostrado que la severidad de la NPIP se correlaciona con la cantidad de platino acumulado en las neuronas sensoriales de los ganglios de la raíz dorsal (GRD). Así mismo, se han descrito varios mecanismos fisiopatológicos involucrados en la aparición de la NPIP, incluyendo la lesión del ADN y las mitocondrias de dichas neuronas, juntamente con una alteración en sus canales iónicos, entre otros. A pesar de los muchos esfuerzos de los clínicos e investigadores para encontrar un tratamiento frente la NPIP, los resultados obtenidos en modelos experimentales no se han podido trasladar a la clínica de forma exitosa. El objetivo de esta tesis doctoral era determinar los mecanismos moleculares mas relevantes involucrados en el desarrollo de la NPIP y así poder encontrar nuevas dianas terapéuticas. Mediante secuenciación del ARN de células aisladas, hemos estudiado el perfil de expresión génica de las neuronas sensoriales del GRD en 2 modelos de ratón de NPIP, óptimamente caracterizados a nivel neurofisiológico. Uno de los modelos se desarrolló a partir de la administración de cisplatino y el otro, de oxaliplatino. Hemos demostrado que el tratamiento con cisplatino causa una lesión permanente en el ADN de las neuronas sensoriales, juntamente con un incremento en la expresión del gen Cdkn1a y su producto proteico p21. Mientras que las vías de apoptosis no se activan en respuesta a la lesión del ADN, las neuronas sensoriales sí expresan marcadores de senescencia celular como la enzima -galactosida, Platinum-Induced Peripheral Neuropathy (PIPN) is a frequent serious dose-limiting adverse event of the platinum-based cytostatic agent cisplatin, oxaliplatin and carboplatin, which are given as a first line treatment against high prevalent cancers. Due to its severity, PIPN often causes cancer treatment reduction or even cessation, thus decreasing the survival probabilities of oncologic patients. It has been extensively reported that PIPN severity correlates with the amount of platinum drugs cumulated in sensory neurons of the dorsal root ganglia (DRG). Several pathophysiological mechanisms have been described for PIPN development, including DNA damage, mytotoxicity and channels dysfunction in DRG sensory neurons, among others. Despite the efforts of clinicians and researchers during the last decades, no successful translation from pre-clinical settings to the clinics has been achieved. The aim of this study was to determine the exact molecular mechanisms involved in the development of PIPN following a non-hypothesis driven methodology to find new therapeutical targets. By single-cell RNA sequencing (scRNA-seq), we studied the transcriptomic profile of DRG sensory neurons from 2 well characterized neurophysiological mice models of PIPN: one induced by cisplatin administration, and the second by oxaliplatin. We demonstrated that cisplatin treatment induced persistent DNA damage and the up-regulation of the Cdkn1a gene and its protein product p21 in the DRG neuronal population. While apoptosis activation pathways were not observed in DRG sensory neurons of cisplatin-treated mice, these neurons did express several senescence hallmarks, including senescence-associated beta-galactosidase (SA-bGAL), phosphor(p)-H2AX and nuclear Nfkb-p65 proteins. The senescent phenotype seen in sensory neurons persisted up to 6 weeks after cisplatin treatment discontinuation. Regarding oxaliplatin study, results of scRNA-seq showed an up-regulation of Lxn and Klk5 genes, and a down-regula, Universitat Autònoma de Barcelona. Programa de Doctorat en Neurociències

Published
2021

39. Integrated CMOS amplifier for ENG signal recording

Author

Uranga, A., Navarro, X., and Barniol, N.

Subjects
Biomedical engineering -- Research, Complementary metal oxide semiconductors -- Research, Biological sciences, Business, Computers, Health care industry
Abstract

The development and in vivo test of a fully integrated differential CMOS amplifier, inplemented with standard 0.7-[micro]m CMOS technology (one poly, two metals, self aligned twin-well CMOS process) intended to record extracellular neural signal is described. In order to minimize the flicker noise generated by the CMOS circuitry, a chopper technique has been chosen. The fabricated amplifier has a gain of 74 dB, a bandwidth of 3 kHz, an input noise of 6.6 nV/[(Hz).sup.0.5], a power dissipation of 1.3 mW, and the active area is 2.7 [mm.sup.2]. An ac coupling has been used to adapt the electrode to the amplifier circuitry for the in vivo testing. Compound muscle action potentials have been recorded in acute experiments with rats, in order to validate the amplifier. Index Terms--Chopper technique, CMOS, neural recording.

Published
2004

44. Diseño y usabilidad de ParaSportAPP: una mHealth destinada a promocionar la actividad física en personas con lesión medular.

Author

Marco-Ahulló, A., Montesinos-Magraner, L., Segura-Navarro, X., Crespo-Rivero, T., González, L. M., and Garcia-Massó, X.

Subjects
PHYSICAL activity, SPINAL cord injuries, PEOPLE with paraplegia, USER-centered system design, MOBILE health
Abstract

Copyright of Revista Andaluza de Medicina del Deporte is the property of Centro Andaluza de Medicina del Deporte and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2022
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48. Methods for in vivo studies in rodents of chemotherapy induced peripheral neuropathy

Author

Bruna, J, Alberti, P, Calls-Cobos, A, Caillaud, M, Damaj, M, Navarro, X, Bruna, Jordi, Alberti, Paola, Calls-Cobos, Aina, Caillaud, Martial, Damaj, M. Imad, Navarro, Xavier, Bruna, J, Alberti, P, Calls-Cobos, A, Caillaud, M, Damaj, M, Navarro, X, Bruna, Jordi, Alberti, Paola, Calls-Cobos, Aina, Caillaud, Martial, Damaj, M. Imad, and Navarro, Xavier

Abstract

Peripheral neuropathy is one of the most common, dose limiting, and long-lasting disabling adverse events of chemotherapy treatment. Unfortunately, no treatment has proven efficacy to prevent this adverse effect in patients or improve the nerve regeneration, once it is established. Experimental models, particularly using rats and mice, are useful to investigate the mechanisms related to axonal or neuronal degeneration and target loss of function induced by neurotoxic drugs, as well as to test new strategies to prevent the development of neuropathy and to improve functional restitution. Therefore, objective and reliable methods should be applied for the assessment of function and innervation in adequately designed in vivo studies of CIPN, taking into account the impact of age, sex and species/strains features. This review gives an overview of the most useful methods to assess sensory, motor and autonomic functions, electrophysiological and morphological tests in rodent models of peripheral neuropathy, focused on CIPN. We include as well a proposal of protocols that may improve the quality and comparability of studies undertaken in different laboratories. It is recommended to apply more than one functional method for each type of function, and to perform parallel morphological studies in the same targets and models.

Published
2020

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