Hydroxytyrosol targets extracellular matrix remodeling by endothelial cells and inhibits both ex vivo and in vivo angiogenesis

This is the preprint version of our manuscript, corresponding to the article that has been 
published in final form at FOOD CHEMISTRY with DOI: 10.1016/j.foodchem.2016.10.111The health benefits of olive oil are attributed to their bioactive compounds, such as hydroxytyrosol. Previously, we demonstrated that hydroxytyrosol inhibits angiogenesis in vitro. The present study aimed to: i) get further insight into the effects of hydroxytyrosol on extracellular matrix remodeling; and ii) test whether hydroxytyrosol is able to inhibit angiogenesis ex vivo and in vivo. Hydroxytyrosol induced a shift toward inhibition of proteolysis in endothelial cells, with decreased expression of extracellular matrix remodeling-enzyme coding genes and increased levels of some of their inhibitors. Furthermore, this work demonstrated that hydroxytyrosol, at concentrations within the range of its content in virgin olive oil that can be absorbed from moderate and sustained virgin olive oil consumption, is a strong inhibitor of angiogenesis ex vivo and in vivo. These results suggest the need for translational studies to evaluate the potential use of hydroxytyrosol for angio-prevention and angiogenesis inhibition in clinical setting.This work was supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER). The “CIBER de Enfermedades Raras” is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

The relation between firms and translation within the agro-food sector in Andalusia

En una época dominada por una crisis económica que se prolonga en el tiempo, las empresas optan por diversificar riesgos y mercados entrando en nuevos países, con el principal objetivo de complementar una demanda local fuertemente sacudida por la escasez de ingresos. En este estudio presentamos los primeros resultados de una investigación empírica en la que las empresas agroalimentarias andaluzas son preguntadas sobre sus estrategias frente a las necesidades lingüísticas que les surgen en los procesos de internacionalización en que se encuentran inmersas. El estudio arroja conclusiones sobre la relación entre el tamaño y las características de las empresas y el uso que estas hacen de los servicios de traducción e interpretación, así como sobre las situaciones en las que se contratan los servicios de traducción o el uso del inglés como lengua franca.Nowadays, with a long crisis that seems to have no end, many firms find in other countries the way to diversify risks and markets, with the main goal of serving as a back-up for a weakened domestic demand, triggered by low income. This paper shows the first results of an empirical research on agri-food firms in Andalusia and how they meet verbal and written needs arising from their internationalisation process. This study sheds light on the relations between size and characteristics of the firms and how they use translation and interpreting services; on the situations where firms use these services, or on the use of English as “lingua franca”

La crisis del sector eléctrico en california 2000–2001: reformas y desintegración vertical

El objetivo en este artículo es mostrar cómo se dio el proceso de desintegración vertical del sector eléctrico de California. Además de examinar el papel que desempeñó la regulación en este proceso y determinar los efectos de la reforma implementada en 1996 en este mercado. La crisis del mercado eléctrico en California finalizando la década de los noventa y principios de 2000, ha sido para muchas economía mundiales, un buen ejemplo de lo que no se debe hacer, dado el efecto negativo que esto tiene sobre la eficiencia económica.This paper seeks to analyze what factors determine the capital structure of the banking firms in Colombia. With this purpose, the existing literatura about the subject is reviewed and, assuming that the hypothesis of the existence of an optimal capital structure holds, an optimization model of a representative banking firm is implemented to observe how these factors affect the optimal capital structure. Additionally, a panel data model is run to contrast the theoretical results with the empirical evidence for the Colombian banking firms. Finally, some conclusions about the found results are postulated

La retribución emocional ofrecida por la empresa a los empleados. Medidas para facilitar la conciliación de la vida laboral-personal.

Con este proyecto pretendo investigar por una parte los efectos negativos que causa en Europa la falta de conciliación, y de otra estudiar los diferentes tipos de conciliación que se dan en los países nórdicos, Suecia Finlandia y Noruega, y compararlos con los que se dan en España. Para ello diferenciaremos entre medidas de conciliación obligatorias (estipuladas por los gobiernos nacionales) y medidas de conciliación voluntarias (medidas que toman las empresas mejorando las ayudas ya creadas o impulsando nuevas). La elección de estos tres países nórdicos para realizar el análisis comparativo, se debe a dos motivos; por un lado, que los tres países son pioneros en conciliación laboral. De otro lado, todos ellos tienen en común, el que a pesar de trabajar menos horas son más productivos y en menos tiempo pueden realizar el mismo trabajo que otros empleados de otros países con jornadas más largasGrado en Administración y Dirección de Empresa

“MORBI-MORTALIDAD EN PACIENTES DEL SERVICIO DE NEONATOLOGÍA DEL HOSPITAL PARA EL NIÑO, IMIEM, DE ENERO 2006 A DICIEMBRE 2010”

INTRODUCCIÓN La morbilidad y mortalidad perinatal representa uno de los principales indicadores del desarrollo socio-cultural y del nivel de salud de un país, es un parámetro para medir la efectividad y calidad de los sistemas de salud y la calidad de vida de una población, y de esta manera plantear estrategias con la finalidad de mejorarla. OBJETIVO GENERAL 1. Determinar la tasa de morbilidad y mortalidad en los recién nacidos hospitalizados en el Servicio de Neonatología, en el Hospital para el Niño, IMIEM, de enero 2006 a diciembre 2010, con la finalidad de conocer las patologías mas frecuentes y realizar propuestas para brindar una mejor atención medica, tomar las medidas necesarias y disminuir la mortalidad en los recién nacidos ingresados en este servicio. OBJETIVOS ESPECÍFICOS 1. Describir las 10 principales causas de ingreso al servicio de Neonatología. 2. Conocer el género de los recién nacidos hospitalizados en el Servicio de Neonatología. MATERIAL Y MÉTODO Se revisaron todos los expedientes de los recién nacidos hospitalizados en el Servicio de Neonatología del Hospital para el Niño, IMIEM, durante enero 2006 a diciembre del 2010. RESULTADOS Durante los cinco años estudiados encontramos que las principales causas de morbilidad son la hiperbilirrubinemia, en primer lugar, continuando en frecuencia sepsis y neumonía, presentándose con mayor frecuencia en el género masculino y que las principales causas de mortalidad son sepsis, choque séptico y SDR, siendo la mortalidad más frecuente en el género masculino. CONCLUSIONES El presente estudio, nos aporta información acerca de la morbilidad y mortalidad en el Servicio de Neonatología del Hospital para el Niño, IMIEM, ya que el conocimiento oportuno del comportamiento epidemiológico de la morbilidad y mortalidad neonatal es de vital importancia, debido a que esto nos permite estar más preparados para brindar una mejor atención tanto en el diagnóstico como en el manejo terapéutico, y de tal forma disminuir los costos hospitalarios, obteniendo una mayor sobrevida y menos morbilidad. Así mismo de disminuir el número de pacientes con secuelas que pueden ser incapacitantes en diverso grado afectando al núcleo familiar y a nuestra sociedad. Concluyendo que con el conocimiento de los mismos, podemos prevenir y disminuir en la manera de lo posible los factores de riesgo en los paciente hospitalizados, implementando medidas de prevención y control que aseguren la identificación de factores de riesgo, mejorando la capacitación continua del personal medico y de enfermería, reforzando los programas de detección oportuna de pacientes de alto riesgo, fortaleciendo las medidas hospitalarias para prevenir las infecciones nosocomiales, con el fin de abatir la incidencia de morbilidad-mortalidad neonatal

Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF-C/VEGFR-3 signalling pathway

BACKGROUND AND PURPOSE Lymphangiogenesis is an important biological process associated with the pathogenesis of several diseases, including metastatic dissemination, graft rejection, lymphoedema and other inflammatory disorders. The development of new drugs that block lymphangiogenesis has become a promising therapeutic strategy. In this study, we investigated the ability of toluquinol, a 2-methyl-hydroquinone isolated from the culture broth of the marine fungus Penicillium sp. HL-85-ALS5-R004, to inhibit lymphangiogenesis in vitro, ex vivo and in vivo. EXPERIMENTAL APPROACH We used human lymphatic endothelial cells (LECs) to analyse the effect of toluquinol in 2D and 3D in vitro cultures and in the ex vivo mouse lymphatic ring assay. For in vivo approaches, the transgenic Fli1:eGFPy1 zebrafish, mouse ear sponges and cornea models were used. Western blotting and apoptosis analyses were carried out to search for drug targets. KEY RESULTS Toluquinol inhibited LEC proliferation,migration, tubulogenesis and sprouting of new lymphatic vessels. Furthermore, toluquinol induced apoptosis of LECs after 14 h of treatment in vitro, blocked the development of the thoracic duct in zebrafish and reduced the VEGF-C-induced lymphatic vessel formation and corneal neovascularization in mice. Mechanistically, we demonstrated that this drug attenuates VEGF-C-induced VEGFR-3 phosphorylation in a dose-dependentmanner and suppresses the phosphorylation of Akt and ERK1/2. CONCLUSIONS AND IMPLICATIONS Based on these findings, we propose toluquinol as a new candidate with pharmacological potential for the treatment of lymphangiogenesis-related pathologies. Notably, its ability to suppress corneal neovascularization paves the way for applications in vascular ocular pathologies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work has been supported by personal funding by FP7-PEOPLE-2013-IEF Marie Curie Postdoctoral Fellowship (MGC). Acknowledged are the supporting grants from the Action de Recherche Concertée (ARC) (Université de Liège), the Fonds de la Recherche Scientifique-FNRS (F.R.S.-FNRS), the Foundation Against Cancer (foundation of public interest), the Centre Anticancéreux près l’Université de Liège, the Fonds Léon Fredericq (University of Liège), the Interuniversity Attraction Poles Programme-Belgian Science Policy (all from Belgium) and the Plan National Cancer (« Service Public Federal » from Belgium). Research in the lab of A.R.Q. and M.A.M. was supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER)

The noni anthraquinone damnacanthal is a multi-kinase inhibitor with potent anti-angiogenic effects

Este es el manuscrito que fue aceptado y que finalmente se publicó en Cancer Letters con el DOI: 10.1016/j.canlet.2016.10.037The natural bioactive compound damnacanthal inhibits several tyrosine kinases. Herein, we show that -in fact- damancanthal is a multi kinase inhibitor. A docking and molecular dynamics simulation approach allows getting further insight on the inhibitory effect of damnacanthal on three different kinases: vascular endothelial growth factor receptor-2, c-Met and focal adhesion kinase. Several of the kinases targeted and inhibited by damnacanthal are involved in angiogenesis. Ex vivo and in vivo experiments clearly demonstrate that, indeed, damnacanthal is a very potent inhibitor of angiogenesis. A number of in vitro assays contribute to determine the specific effects of damnacanthal on each of the steps of the angiogenic process, including inhibition of tubulogenesis, endothelial cell proliferation, survival, migration and production of extracellular matrix remodeling enzyme. Taken altogether, these results suggest that damancanthal could have potential interest for the treatment of cancer and other angiogenesisdependent diseases.Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). JAGV had the financial support of Vicerrectorado de Investigación y Transferencia (University of Málaga, Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Screening of Synergistic Interactions of Epigallocatechin-3-gallate with Antiangiogenic and Antitumor Compounds

This is the accepted manuscript of the article that finally was published in Synergy with DOI: 10.1016/j.synres.2016.05.001Purpose: To screen for possible synergistic interactions of epigallocatechin-3-gallate (EGCG) with a selection of 10 anti-angiogenic or anti-tumor compounds on the survival of endothelial and tumor cells. Methods: Human HMEC endothelial and MDA-MB231 breast cancer cells were treated with different concentrations of EGCG and the 10 tested compounds either as single agents or in paired combinations with EGCG for 3 days and final survival of cells was determined by the MTT assay. IC50 values, sensitization factors and combination indexes were calculated. Results; IC50 values of 140±2 and 45±6 μM were determined for EGCG-treated endothelial and tumor cells, respectively. IC50 values for all tested compounds were within the micromolar and the submillimolar range. The values of the sensitization factor increased and those of the combination index decreased for paired combinations of EGCG with 4-methylumbelliferone. The opposite was true for the combination of EGCG with vitamin D3. Other tested combinations did not exhibit a clear monotonic effect but rather a biphasic behaviour. Conclusion: Combinations of EGCG and 4-methylumbelliferone synergistically decrease endothelial and tumor cell survival. In contrast, the presence of EGCG antagonizes with the antiproliferative effect exerted by vitamin D3 on endothelial and tumor cells.Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). JAGV has the financial support of Vicerrectorado de Investigación y Transferencia (University of Málaga, Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Plan de cuidados en paciente con infarto agudo de miocardio

El infarto agudo de miocardio (IAM) es una patología con una gran incidencia sobre la población. En la actualidad, es una de las principales causas de muerte en España y en el mundo. Además, el envejecimiento de la población solo indica que seguirá aumentado. Para minimizar su incidencia, mortalidad y mejorar la calidad de vida tras el tratamiento, es imprescindible una rápida y buena identificación de la patología para su posterior tratamiento. Este trabajo expone los puntos principales para su sospecha según los factores de riesgo, sintomatología, herramientas de diagnóstico y tratamiento. A continuación, se realiza un proceso de atención de enfermería desarrollando un plan de cuidados basándonos en las 14 necesidades de Virginia Henderson. Por último, se termina con la importancia de la enfermería en el cuidado de los pacientes que han sufrido un IAM, así como la imprescindible formación para proporcionar unos cuidados adecuados y de calidad

The enzymatic determination of glucose in carbonated beverages: a useful tool for the undergraduate students to learn the basis of enzymatic analysis and the comparison of two analytical methods

The importance of enzymatic analysis in biochemistry, clinical chemistry and food chemistry is undoubted. The course "Applied Biochemistry" in our Faculty is aimed to undergraduate students of Chemistry and Biochemistry. In this subject, the principles and applications of enzymatic analysis are presented to the students, who receive a theoretical introductory lecture in the classroom before they carry out an experiment that should be feasible to be solved in a short laboratory period. The experimental protocol here presented, based on the enzymatic determination of glucose in carbonated beverages, has been implemented at the University of Málaga and it has been optimized according to the students’ results and commentaries along the last years. It aims to illustrate basic issues relating enzymatic analysis, including its potential application to food chemistry. Although there are several enzymatic methods that can be used for the determination of glucose, we selected the one based on the coupled reactions of glucose oxidase (GOD; EC 1.1.3.4.) and peroxidase (POD; EC 1.11.1.7.) because the kinetic constants of glucose oxidase allow the mentioned enzymatic reactions to be used in both, the end point and the kinetic enzymatic analysis methods. In this way, data for two different protocols for the determination of glucose concentration are obtained by the students from a single reaction mixture. Students construct a calibration curve for each method using a glucose standard solution, and use them to determine the glucose concentration in the problem solutions. The inclusion of replicate samples in the determination of the glucose concentration of an “ideal problem” (glucose in purified water) is used to illustrate the principles of statistics in the lab, and comparison with the “real value” allows an estimation of the accuracy of each method. The evaluation of glucose concentration in four carbonated beverages: coloured coke and uncoloured tonic sodas (regular or sugarless in both cases) makes student to recognise the appearance of interferences that should be either avoided or eliminated. Since all samples are analysed by means of end-point and kinetic methods, students can discuss the applicability of each method to these specific analytical problems. They are also encouraged to compare both analytical methods in terms of sensitivity, selectivity, accuracy, and time consumed. Chemistry and Biochemistry undergraduate students having performed this experiment in our laboratories have found it formative, interesting and challenging.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech