Tesis doctorales y Tesinas
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- Improvement of the bioavailability of quercetin encapsulated in zein-based nanoparticles. Effects on a Diet-Induced Obesity model.(Universidad de Navarra, 2022-11-28) Raquel; Gonzalez-Navarro, C.J. (Carlos Javier); Irache, J.M. (Juan Manuel)Flavonoids are a subclass of polyphenols, the most common and widespread group of substances in plants. They have been demonstrated to exert several beneficial health effects, such as anti-obesity or anti-diabetic ones. However, they present low water solubility and low oral bioavailability, what produces a reduction of the efficacy. For that reason, some strategies must be followed, such as the nanoencapsulation of these bioactive compounds. Thus, this doctoral thesis was focused on the development and characterization of nanoparticles made of a vegetal protein intended for the oral delivery of flavonoids, and its evaluation in in vivo models of obesity. In this work, the development of nanospheres made of a vegetal protein was performed. Two strategies were followed to improve the characteristics of these nanospheres. First, a hydrophilic polymer was used to coat the device, in order to improve its intestinal mucus-permeating characteristics. Second, nanocapsules (containing an oily core) were developed, with the aim of improving the loading of the flavonoid and the in vitro release properties in simulated gastric and intestinal fluids. Once the nanoparticles were developed, a flavonoid was loaded. Empty and flavonoid-loaded nanoparticles were characterized by measuring the size, zeta potential, morphology, hydrophobicity of the surface, diffusion in intestinal mucus, and the in vitro release. As a first approach, nanoparticles were evaluated in a model of increased fat accumulation in the nematode Caenorhabditis elegans. Results showed that the flavonoid decreased the fat accumulation compared to the control, even more when encapsulated in nanospheres (bare or coated ones). On the contrary, nanocapsules did not have an effect. The in vivo gastrointestinal transit and biodistribution of nanoparticles were also analyzed in Wistar rats, using radiolabelled or fluorescently marked nanoparticles. Nanocapsules were the fastest formulation, and the mucus-permeating properties of coated nanospheres were confirmed. In addition, a pharmacokinetic assay was carried out, showing that the nanoencapsulation of the flavonoid improved the pharmacokinetic parameters and relative oral bioavailability. Finally, nanoparticles and free flavonoid were evaluated in a model of diet-induced obesity (DIO) in Wistar rats. The DIO model was successfully achieved by feeding rats with a high fat/high sucrose diet, and coated nanospheres displayed more positive effects than other treatments; some white fat depots and size of adipocytes, serum triglycerides and glucose, plasma monocyte chemoattractant protein-1 (MCP-1), hepatic steatosis, and hepatic triglycerides were reduced. Also, in the retroperitoneal fat, the treatment with coated nanospheres overexpressed genes involved in the β-oxidation of fatty acids, genes encoding two adipokines, and a gene involved in the browning of fat. In summary, nanoparticles made of a vegetal protein were successfully prepared and characterized. A flavonoid was loaded, and the anti-obesity effect of the free and encapsulated compound was confirmed in the nematode C. elegans and in a diet-induced obesity model in rats.
- La belleza de las organizaciones. Una perspectiva semiótica(Universidad de Navarra, 2022-03-21) Raquel; Alonso-del-Val, M.Á. (Miguel Ángel); Nubiola, J. (Jaime)Este trabajo aspira a abrir una línea novedosa de investigación al concentrar la atención en la creatividad y los procesos creativos en el ámbito organizacional. Este tema fue ampliamente abordado por la disciplina de la Administración o Management, desde muy diversas perspectivas. En las últimas dos décadas, los autores relacionados con las teorías de la creatividad organizacional señalaron cómo los entornos organizacionales pueden favorecer el desarrollo de la creatividad. Los estudios mencionados parecen coincidir en el hecho de que la creatividad en las organizaciones requiere un determinado ambiente organizacional que la propicie. De modo que en esta investigación se decidió desplazar el foco de atención de la creatividad a las cuestiones previas que facilitan y posibilitan la creatividad; es decir, los aspectos estéticos de las organizaciones, responsables de generar en las personas un mayor compromiso con su trabajo. Este Trabajo de Investigación, entonces, se propone tomar como objeto de estudio la estética de las organizaciones y aspira a identificar, desde una perspectiva semiótica, cuáles son las dimensiones y las percepciones que tienen las personas sobre la estética de las organizaciones en las que trabajan. La perspectiva semiótica triádica del signo, tal como lo propuso el científico, lógico y filósofo estadounidense Charles Sanders Peirce [1893 (1931)], ofrece un nivel más amplio de análisis de las categorías que integran el fenómeno. Para dar cumplimiento a sus objetivos, este Trabajo de Investigación tiene un enfoque metodológico mixto. Por un lado, el enfoque es cualitativo, con un diseño retrospectivo, transversal y no experimental que utiliza la técnica del análisis exploratorio de significado a partir de los datos obtenidos de la matriz semiótica construida sobre la base del Método para el Análisis de las Investigaciones en Administración (MAIA). Por otro lado, es cuantitativo, ya que los resultados obtenidos de las encuestas realizadas son expuestos en forma numérica en la matriz semiótica armada con el método MAIA. Así, los resultados son sometidos a un análisis multivariado, como técnicas de regresión múltiple, correlación o análisis factorial. Los resultados de este Trabajo, resumidos en las conclusiones finales, dilucidan varias nociones en las organizaciones que contribuyen a la formación de los profesionales en arquitectura, por un lado, aspectos de diseño, estructura y funcionalidad de las organizaciones y, por otro, facetas que conciernen al dominio de las capacidades, las relaciones y los propósitos. La confluencia de estas dimensiones pone de manifiesto la fisonomía de la organización formal, la organización informal, las estrategias, las acciones, la cultura y sus logros productivos, así como también plantean las valoraciones estéticas, éticas y lógicas en el ámbito organizacional. El trabajo finaliza esbozando una teoría sobre la belleza en las organizaciones y presentando 10 tipos de belleza organizacional.
- New Epigenetic Targets in Multiple Myeloma(2019-02-06) Raquel; Prosper-Cardoso, F. (Felipe); Prosper, F. (Felipe); Aguirre-Ena, X. (Xabier)
- Building City Resilience through Collaboration.(Servicio de Publicaciones. Universidad de Navarra., 2017) Raquel; Hernantes-Apezetxea, J. (Josune); Labaka-Zubieta, L. (Leire)Nowadays, the majority of the world’s population lives in cities and, according to projections, this number will increase over the coming decades. Accelerated globalization has dramatically increased the complexity and perceived unpredictability of threats and hazards. As cities continue to grow and grapple with uncertainties, cities across the world face an increasing variety of challenges ranging from short-term disasters such as floods, droughts, and earthquakes, to long-term disasters such as climate change. In most cities, the approach to managing disasters has limited to top-down initiatives directed by disjointed departments and entities of the local government who adopted a reactive response to disasters. In this context, city stakeholders such as volunteer organizations, citizens, media, academic, educational and scientific entities, and private and public companies were informed without becoming actively involved in the resilience-building process. The capacity of a city to adapt to disasters requires a resilience approach that not only takes into consideration the contribution of each stakeholder independently but also tackles the functioning of a city in a comprehensive and holistic manner. The approach to building resilience focuses on the innate strengths of city stakeholders and the need to collaborate to maximize efforts and existing resources. Building city resilience therefore, requires analyzing the needs of the different city stakeholders and empowering them to take actions. Currently, however, frameworks that help governments to improve collaboration with city stakeholders in the resilience-building process remain undeveloped. Therefore, frameworks that help local governments to understand and assess how to engage stakeholders at the most appropriate time and in a manner that contributes to the resilience-building process need to be developed. The contribution of this research is the development of a stakeholder-collaboration maturity model. The stakeholder-collaboration maturity model defines five sequential maturity stages to help local governments to improve progressively the collaboration with city stakeholders in the resilience-building process. Each maturity stage indicates the stakeholders that need to be involved, the policies that need to be implemented, and the indicators that evaluate the implementation of the policies. The stakeholder-collaboration maturity model was developed as a result of an iterative process that included semi-structured interviews with representatives from six different cities committed to improving their level of city resilience. Furthermore, two case studies were carried out in two cities in order to implement the stakeholder-collaboration maturity model. These case studies aimed at gathering evidence of the evolution of the collaboration between the local government and city stakeholders and to validate the sequence of stages and policies presented in the maturity model. Moreover, the stakeholder-collaboration maturity model made it possible to assess the current maturity stage of the cities under study and to provide recommendations for improving collaboration with different city stakeholders.