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- Estudio mediante dHPLC del perfil mutacional de los genes SYK y ZAP70 en pacientes con Síndromes Mieloproliferativos Crónicos BCR-ABL negativos(Editorial Doyma, 2007-10-25) Ormazábal, C. (Cristina); Hurtado, C. (Cristina); Novo-Villaverde, F. J. (Francisco Javier); Vizmanos-Pérez, J.L. (José Luis); García-Delgado, M. (Marina); Aranaz-Oroz, P. (Paula); Calasanz-Abinzano, M.J. (Maria Jose)
- A simple and a reliable method to quantify antioxidant activity in vitro(2019) Cavero-Remon, R.Y. (Rita Yolanda); Calvo, M.I. (María Isabel); Vizmanos-Pérez, J.L. (José Luis); Torre, M.P. (María Pilar) deThe characterization of compounds with antioxidant activity is of great interest due to their ability to reduce reactive oxygen species production and, therefore, prevent some age-related diseases. Its antioxidant capacity can be analyzed by different methods both in vitro and in vivo. Caenorhabditis elegans is an in vivo model widely used in ageing research. Until now, available tests analyze functional effects in the worms, so the antioxidant activity of the compound is indirectly monitored. We have developed a simple and a reliable method to quantify internal antioxidant activity in vivo. To validate this method, we analyzed an aqueous green tea extract and two other compounds with a well-known antioxidant activity and without this activity. The results obtained (EC50 green tea = 21.76 ± 1.28 µg/mL; EC50 positive control = 8.50 ± 0.33 µg/mL; negative control EC50 > 500 µg/mL) can help in the design of further in vivo experiments. Thus, our method can be used as a previous screening capable of reducing the gap between in vitro and in vivo assays.
- FISH and mutational screening of the ABL, SYK and JAK tirosine kinase family genes in BCR-ABL1 negative and V617FJAK2 negative chronic myeloproliferative neoplasms (CMPNs)(Ferrata-Storti Foundation, 2009-06-04) Ormazábal, C. (Cristina); Hurtado, C. (Cristina); Novo-Villaverde, F. J. (Francisco Javier); Vizmanos-Pérez, J.L. (José Luis); Erquiaga, I. (Ignacio); Aranaz-Oroz, P. (Paula); Calasanz-Abinzano, M.J. (Maria Jose)
- Methylation status of SOCS1 and SOCS3 in BCR-ABL negative and JAK2V617F negative chronic myeloproliferative neoplasms(Elsevier Ltd., 2008-10-01) Cebrián, V. (Virginia); Fernandez-Mercado, M. (Marta); Euba, B. (Begoña); Garcia-Granero, M. (Marta); Novo-Villaverde, F. J. (Francisco Javier); Vizmanos-Pérez, J.L. (José Luis); García-Delgado, M. (Marina); Calasanz-Abinzano, M.J. (Maria Jose)
- ¿Existen más mutaciones en JAK2 en pacientes con Síndromes Mieloproliferativos Crónicos BCR-ABL negativos?(Editorial Doyma, 2007-10-25) Ormazábal, C. (Cristina); Hurtado, C. (Cristina); Novo-Villaverde, F. J. (Francisco Javier); Vizmanos-Pérez, J.L. (José Luis); García-Delgado, M. (Marina); Aranaz-Oroz, P. (Paula); Calasanz-Abinzano, M.J. (Maria Jose)
- Mucus‑penetrating and permeation enhancer albumin‑based nanoparticles for oral delivery of macromolecules: Application to bevacizumab(Springer, 2023) Pangua-Irigaray, C. (Cristina); Espuelas, S. (Socorro); Vizmanos-Pérez, J.L. (José Luis); Irache, J.M. (Juan Manuel); Martinez-Oharriz, C. (Cristina)The oral administration of therapeutic proteins copes with important challenges (mainly degradation and poor absorption) making their potential therapeutic application extremely difficult. The aim of this study was to design and evaluate the potential of the combination between mucus-permeating nanoparticles and permeation enhancers as a carrier for the oral delivery of the monoclonal antibody bevacizumab, used as a model of therapeutic protein. For this purpose, bevacizumab was encapsulated in PEG-coated albumin nanoparticles as a hydrophobic ion-pairing complex with either sodium deoxycholate (DS) or sodium docusate (DOCU). In both cases, complex formation efficiencies close to 90% were found. The incorporation of either DS or DOCU in PEG-coated nanoparticles significantly increased their mean size, particularly when DOCU was used. Moreover, the diffusion in mucus of DOCU-loaded nanoparticles was significantly reduced, compared with DS ones. In a C. elegans model, DS or DOCU (free or nanoencapsulated) disrupted the intestinal epithelial integrity, but the overall survival of the worms was not affected. In rats, the relative oral bioavailability of bevacizumab incorporated in PEG-coated nanoparticles as a complex with DS (B-DS-NP-P) was 3.7%, a 1000-fold increase compared to free bevacizumab encapsulated in nanoparticles (B-NP-P). This important effect of DS may be explained not only by its capability to transiently disrupt tight junctions but also to their ability to increase the fluidity of membranes and to inhibit cytosolic and brush border enzymes. In summary, the current strategy may be useful to allow the therapeutic use of orally administered proteins, including monoclonal antibodies.
- Citogenética y biología molecular en la leucemia aguda linfoblástica(Doyma, 2002) Novo-Villaverde, F. J. (Francisco Javier); Vizmanos-Pérez, J.L. (José Luis); Larrayoz, M.J. (María J.); Calasanz-Abinzano, M.J. (Maria Jose); Odero, M.D. (Maria Dolores)
- Análisis de la expresión diferencial de distintos transcritos de PDGFRA en neoplasias hematológicas con eosinofilia(Editorial Doyma, 2009-11-12) Ormazábal, C. (Cristina); Hurtado, C. (Cristina); Novo-Villaverde, F. J. (Francisco Javier); Vizmanos-Pérez, J.L. (José Luis); García-Delgado, M. (Marina); Erquiaga, I. (Ignacio); Aranaz-Oroz, P. (Paula); Calasanz-Abinzano, M.J. (Maria Jose)
- Phenolic compounds inhibit 3T3-L1 adipogenesis depending on the stage of differentiation and their binding affinity to PPAR gamma(2019) Martinez, J.A. (José Alfredo); Miguéliz-Basterra, I. (Itziar); Milagro-Yoldi, F.I. (Fermín Ignacio); Gonzalez-Navarro, C.J. (Carlos Javier); Vizmanos-Pérez, J.L. (José Luis); Aranaz-Oroz, P. (Paula); Romo‐Hualde, A. (Ana); Zabala-Navó, M. (María); López-Yoldi, M. (Miguel); Navarro-Herrera, D. (David)Phenolic compounds might modulate adiposity. Here, we report our observation that polyphenols and phenolic acids inhibit adipogenesis in 3T3-L1 with different intensity depending on the family and the stage of differentiation. While quercetin and resveratrol inhibited lipid accumulation along the whole process of differentiation, apigenin and myricetin were active during the early and latest stages, but not intermediate, contrary to hesperidin. The activity of phenolic acids was limited to the early stages of the differentiation process, except p-coumaric and ellagic acids. This anti-adipogenic effect was accompanied by down-regulation of Scd1 and Lpl. Molecular docking analysis revealed that the inhibitory activity of these phenolic compounds over the early stages of adipogenesis exhibits a significant correlation (r = 0.7034; p = 0.005) with their binding affinity to the ligand-binding domain of PPAR¿. Results show that polyphenols and phenolic acids would interact with specific residues of the receptor, which could determine their potential anti-adipogenic activity during the early stages of the differentiation. Residues Phe264, His266, Ile281, Cys285 and Met348 are the most frequently involved in these interactions, which might suggest a crucial role for these amino acids modulating the activity of the receptor. These data contribute to elucidate the possible mechanisms of phenolic compounds in the control of adipogenesis.
- Improvement of antioxidant activity of oregano (Origanum vulgare L.) with an oral pharmaceutical form(2020) Cavero-Remon, R.Y. (Rita Yolanda); Calvo, M.I. (María Isabel); Vizmanos-Pérez, J.L. (José Luis); Torre, M.P. (María Pilar) deAging-related diseases can be triggered by multiple factors such as oxidative stress. Oxidative stress is an imbalance between free radicals and antioxidants, so today, compounds capable of reducing or neutralizing free radicals are being studied for a therapeutic use. Origanum vulgare L. is a traditional medicinal plant used for a wide number of health problems due to its antimicrobial, carminative and antioxidant activities. However, when administered orally, gastrointestinal digestion can modify some of therapeutical properties. To avoid this, two different solid oral formulations have been designed for an O. vulgare extract evaluating their antioxidant behaviours in vitro and in vivo after a simulation of gastrointestinal digestion. The results showed that the divided powder has a lower antioxidant activity both in vitro and in vivo than the encapsulated extract. The quantitative difference of polyphenols found on HPLC-DAD (especially luteolin, apigenin and caffeic acid) may explain the differences in pharmacological activity. Thus, we propose that the best form to administrate O. vulgare extracts to maintain the antioxidant properties is the encapsulated form, that is, two capsules of 250mg of a hydroalcoholic extract of O. vulgare with a minimum of 33 % of rosmarinic acid as a daily dose.