Influencia del género en la farmacocinética y la seguridad de los estudios de bioequivalencia

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Farmacología. Fecha de lectura: 14-12-201

Cómo seguir construyendo soberanía

En marzo del 2022 se llevó a cabo la XXVIII Semana de la Memoria, en la facultad de Trabajo Social. El eje de este año se centró en los 40 años de Malvinas, con el fin de seguir construyendo la memoria de manera colectiva. La actividad de cierre, entre tantas que se llevaron a cabo, tuvo como eje principal la entrega de la Distinción “Liliana Ross”, la cual es otorgada por la Facultad de Trabajo Social desde el año 2015 a los distintos referentes/ as de los Derechos Humanos en reconocimiento a su compromiso con la lucha por la memoria, la verdad y la justicia. En esta ocasión, en el marco del cumplimiento de los 40 años de la Guerra de las Islas Malvinas, la distinción fue otorgada al Centro de Ex Combatientes Islas Malvinas La Plata (C.E.C.I.M) creado en 1982 por ex soldados conscriptos.Facultad de Trabajo Socia

Juventud peligrosa

El siguiente escrito reúne la experiencia de las prácticas abordadas en el año 2019, en el marco de la Facultad de Trabajo Social. Se desarrollaron en la Comisión Provincial por la Memoria, específicamente en el Programa de Juicios por Delitos de Lesa Humanidad. Nuestro objetivo principal consistió en la elaboración de una propuesta teórico-metodológica desde el Programa de Justicia por Delitos de Lesa Humanidad para el abordaje de los talleres de La Escuela va a los Juicios, donde desde el trabajo sobre la construcción de la juventud como la otredad peligrosa pueda establecerse una relación entre el presente y nuestro pasado reciente.Facultad de Trabajo Socia

Study of PMT target specificity in Ustilago maydis

Ustilago maydis is a pathogenic fungi responsible for the corn smut fungus disease, which causes a significant loss in mayze production every year. The PMT is a family of well-conserved O-mannosylating proteins. In Ustilago maydis, the deletion of Pmt2 has been shown to be deleterious and the deletion of Pmt4 disrupts completely the infectious process; on the other hand, the deletion of Pmt1 doesn't manifest any phenotype. All PMT proteins have three domains, named PMT, MIR and 4TMC, and several transmembrane regions. We hipothesized that one of these domains of Pmt4 is responsable for the substrate specificity that confers the virulence phenotype in Ustilago maydis Pmt4 and, if this would be the case, we could develop an antifungal drug specific to this domain. To check this, we built three chimerical protein strains, chanching one domain in Pmt4 for the same domain of Pmt1 at a time, and measure the tumor formation in 3 independent experiments. We also built a full Pmt4 length strain as a positive control. The results indicate that either the protein requires all three Pmt4 domains to infect or the chimerical protein is not working properly.Furthermore, we also wanted to check what region gives Pmt2 its specificity for growth. In Schizosaccharomyces pombe, a ortholog of Pmt2, named Ogm2, present the same essencial-for-growth phenotype than in U. maydis. Since U. maydis doesn't have any repressable promoter, we built a S. pombe strain with the shut-off promoter nmt81 in the endougenous Ogm2 gene and will complement the phenotype with mutagenized plasmids containing the U. maydis Pmt2 and measure its viability.Finally, we also plan to build other three strains interchanching Pmt4 domains in the Pmt1 protein

Efectividad de una intervención educativa de enfermería en los estilos de vida en adultos con Diabetes tipo II, San José - Chiclayo - 2012

La diabetes tipo II, una enfermedad de salud pública representa el 90% de casos mundiales y se debe en gran medida a un sobrepeso e inactividad física. La investigación tuvo como objetivo medir la efectividad de una intervención educativa de enfermería en los estilos de vida en adultos con diabetes tipo II, San José - Chiclayo - 2012. Cuya finalidad fue concientizar a la población en el control de sus estilos de vida en dieta y ejercicio, aportando a la ciencia de enfermería en el trabajo comunitario mediante programas extramurales; fue de tipo cuantitativo cuasi experimental, la población fue de 32 adultos, se tuvieron en cuenta criterios de exclusión e inclusión; finalmente la muestra estuvo integrada por 18 adultos con diabetes tipo II, con edades mayor a 40 años; el muestreo fue no probabilístico de tipo intencional. Los datos se recolectaron pre y post-intervención educativa, a través de la escala Likert de 26 items sobre dieta y ejercicio, y la lista de cotejo con 4 indicadores (IMC, presión arterial, perímetro abdominal y glicemia capilar). La intervención educativa duró 4 meses, donde se aplicaron 3 sesiones educativas a cada participante con una hora de duración cada una. Para el procesamiento y análisis, se creó una base de datos en el programa SPSS versión 20 para el análisis estadístico descriptivo y análisis estadístico inferencial. Los resultados mostraron que la intervención educativa de enfermería en dieta y ejercicio solamente fue efectiva en el índice de masa corporal (p=0.00049) y presión arterial (p=0.00016)

Effect of truncating AUC at 12, 24 and 48 hr when evaluating the bioequivalence of drugs with a Long Half-Life

This is the peer reviewed version of the following article: Basic an Clinical Pharmacology and Toxicology 118.1 (2016): 53-7 which has been published in final form at http://dx.doi.org/10.1111/bcpt.12432. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalentThis study was partially funded by the Fundación Teófilo Hernando and Foundation for Biomedical Research at Hospital Universitario de La Princesa F Abad-Santos and D Ochoa have been consultants or investigators in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Farmalíder, Ferrer, GlaxoSmithKline, Janssen-Cilag, Kern, Normon, Servier, Teva, and Zambon

Individual and Joint Effect of Alpha-Tocopherol and Hydroxytyrosol Acetate on the Oxidation of Sunflower Oil Submitted to Oxidative Conditions: A Study by Proton Nuclear Magnetic Resonance

[EN] This study tackles the individual and joint effect of alpha-tocopherol and hydroxytyrosol acetate on the oxidation of sunflower oil submitted to accelerated storage conditions at intermediate temperature, in order to deepen the understanding of antioxidant–prooxidant behaviour. This was accomplished by 1H Nuclear Magnetic Resonance. For this purpose, the evolution of the degradation of both the main components of the oil and the aforementioned added compounds was monitored by this technique throughout the storage time. Furthermore, the formation of a very large number of oxylipins and the evolution of their concentration up to a very advanced stage of oil oxidation, as well as the occurrence of lipolysis, were also simultaneously studied. The results obtained show very clearly and thoroughly that in the oxidation process of the oil enriched in binary mixtures, interactions occur between alpha-tocopherol and hydroxytyrosol acetate that notably reduce the antioxidant effect of the latter compound with the corresponding negative consequences that this entails. The methodology used here has proved to be very efficient to evaluate the antioxidant power of mixtures of compoundsThis work has been funded by the Spanish Ministry of Science and Innovation (MINECO, AGL2015-65450-R, AEI/FEDER-EU) and by the Basque Government and its Departments of Univer- sities and Research (EJ-GV, IT-916-16

Influence of Hydroxytyrosol Acetate Enrichment of an Oil Rich in Omega-6 Groups on the Evolution of Its Oxidation and Oxylipin Formation When Subjected to Accelerated Storage. A Global Study by Proton Nuclear Magnetic Resonance

Sunflower oil samples, both unenriched and enriched with four different concentrations of hydroxytyrosol acetate, were subjected to accelerated storage at 70 °C until a very advanced oxidation stage and the process was monitored by 1H NMR spectroscopy. The aim of the study is to know the effect that the presence of this antioxidant has on the oxidation process of sunflower oil under the aforementioned conditions, as well as on the formation and evolution of the concentration of a significant number of oxylipins. The oxidation process was studied globally by monitoring, during storage time, the degradation of both the linoleic acyl group of sunflower oil, which is the main component of sunflower oil, and the added hydroxytyrosol acetate. Simultaneously, the identification of up to twenty-six different types of oxylipins formed in the oxidation process and the monitoring of the evolution of their concentration over the storage time were carried out. In this way, essential information about the effect that hydroxytyrosol acetate provokes on the oxidation of this oil rich in omega-6 polyunsaturated acyl groups, has been obtained. It has also been shown that the enrichment of sunflower oil with this antioxidant under the conditions tested does not prevent the oxidation process but slows it down, affecting the entire oxidation process.This work has been funded by the Spanish Ministry of Science and Innovation (MINECO, AGL2015-65450-R, AEI/FEDER-EU) and by the Basque Government and its Departments of Universities and Research (EJ-GV, IT-916-16

Alpha-Tocopherol, a Powerful Molecule, Leads to the Formation of Oxylipins in Polyunsaturated Oils Differently to the Temperature Increase: A Detailed Study by Proton Nuclear Magnetic Resonance of Walnut Oil Oxidation

Lipid oxidation causes food degradation and the formation of toxic compounds. Therefore, the addition to foods of compounds able to avoid, delay or minimize this degradative process is a commonly used strategy. Nevertheless, neither the identity of most of the formed compounds in this complex process nor the way in which their formation is affected by the strategy used are well known. In this context, the effect the temperature increase and the enrichment level in alpha-tocopherol on the evolution of the walnut oil oxidation, as a model of an oil rich in polyunsaturated omega-6 acyl groups, submitted to storage conditions, are tackled by 1H NMR. The study has allowed knowing the degradation kinetic of both the oil acyl groups and alpha-tocopherol, the identification of a very high number of oxylipins and the kinetic of their formation. The temperature increase accelerates the formation of all oxylipins, favouring the formation of hydroperoxy conjugated E,E-dienes and related derivatives versus that of the Z,E-isomers. The enrichment in alpha-tocopherol accelerates the formation of hydroperoxy conjugated Z,E-dienes and related derivatives, and delays in relation to the formation of the former that of the E,E-isomers and related derivatives, hindering, to a certain extent, the formation of the latter in line with the enrichment level.This work has been funded by the Spanish Ministry of Science and Innovation (MINECO, AGL2015-65450-R, AEI/FEDER-EU) and by the Basque Government and its Departments of Universities and Research (EJ-GV, IT-916-16)