Fondos de inversión. El value investing

A lo largo de la historia, hemos presenciado como la evolución e importancia de los fondos de inversión como instrumentos financieros de ahorro se han ido intensificando. Consecuencia de ello, es la ventaja que proporcionan al pequeño ahorrador de acceder a un mercado más amplio, consiguiendo así obtener una mayor diversificación del riesgo. El principal objetivo de este trabajo es proporcionar una visión general de los fondos de inversión, así como una filosofía llevada a cabo por diversos gestores, el Value Investing. Para llevar a cabo este estudio, se ha realizado una clasificación sobre los tipos de fondos de inversión y su vocación inversora, consiguiendo de este modo conocer los riesgos asociados a la misma que debería asumir el inversor, los diferentes criterios a seguir en la elección del fondo, así como los estilos de gestión del mismo. Finalmente se presenta una visión general de la filosofía del value investing, señalando los conceptos más importantes de ésta, como es el margen de seguridad.Universidad de Sevilla. Doble Grado en Derecho y en Economí

Diseño de un sistema de garantía de calidad de producto en entorno farmacéutico

El present treball de fi de màster consisteix en dissenyar un sistema de garantia de qualitat per a la fabricació de medicaments en entorn farmacèutic. Per a dur-ho a terme, es defineixen les regulacions aplicables que han de complir-se, es proporciona un cas problema amb GAPs detectats de potencials incompliments en relació a les NCF i es proposa un pla de remediació per mitigar aquests GAPs i així obtenir un sistema de garantia de qualitat robust que pugui assegurar la qualitat del producte fabricat abans d’arribar al pacient.El presente trabajo de final de máster consiste en diseñar un sistema de garantía de calidad para la fabricación de medicamentos en entorno farmacéutico. Para ello, se definen las regulaciones aplicables que deben cumplirse, se proporciona un caso problema con GAPs detectados de potenciales incumplimientos en relación a las NCF y se propone un plan de remediación para mitigar dichos GAPs, para así obtener un sistema de garantía de calidad robusto que pueda asegurar la calidad del producto fabricado antes de llegar al paciente.The current final master’s degree project consists in designing a quality assurance system for the manufacturing of medicines in a pharmaceutical environment. For that, the applicable regulations that must be complied are defined. In addition, a problem case is presented with GAPs detected about non-compliances of GMPs and a remediation plan is proposed to mitigate these GAPs in order to obtain a robust quality assurance system that assures the product quality prior to arrive to the patient

Differentiation Restricted Endocytosis of Cell Penetrating Peptides in MDCK Cells Corresponds with Activities of Rho-GTPases

Purpose: Cellular entry of biomacromolecules is restricted by the barrier function of cell membranes. Tethering such molecules to cell penetrating peptides (CPPs) that can translocate cell membranes has opened new horizons in biomedical research. Here, we investigate the cellular internalization of hCT(9-32)-br, a human calcitonin derived branched CPP, and SAP, a γ-zein related sequence. Methods: Internalization of fluorescence labelled CPPs was performed with both proliferating and confluent MDCK cells by means of confocal laser scanning microscopy (CLSM) and fluorescence activated cell sorting (FACS) using appropriate controls. Internalization was further elaborated in an inflammatory, IFN-γ/TNF-αa induced confluent MDCK model mimicking inflammatory epithelial pathologies. Activities of active form Rho-GTPases (Rho-A and Rac-1) in proliferating and confluent MDCK cells were monitored by pull-down assay and Western blot analysis. Results: We observed marked endocytic uptake of the peptides into proliferating MDCK by a process suggesting both lipid rafts and clathrin-coated pits. In confluent MDCK, however, we noted a massive but compound-unspecific slow-down of endocytosis. This corresponded with a down-regulation of endocytosis by Rho-GTPases, previously identified to be intimately involved in endocytic traffic. In fact, we found endocytic internalization to relate with active Rho-A; vice versa, MDCK cell density, degree of cellular differentiation and endocytic slow-down were found to relate with active Rac-1. To our knowledge, this is the first study to cast light on the previously observed differentiation restricted internalization of CPPs into epithelial cell models. In the inflammatory IFN-γ/TNF-αa induced confluent MDCK model mimicking inflammatory epithelial pathologies, CPP internalization was enhanced in a cytokine concentration-dependent way resulting in maximum enhancement rates of up to 90%. We suggest a cytokine induced redistribution of lipid rafts in confluent MDCK to cause this enhancement. Conclusion: Our findings emphasize the significance of differentiated cell models in the study of CPP internalization and point towards inflammatory epithelial pathologies as potential niche for the application of CPPs for cellular deliver

Antimony in Polyethylene Terephthalate-Bottled Beverages: The Migration Puzzle

A novel strategy to assess the main variables that potentially affect the migration of antimony from PET bottles to beverages, including mineral waters and juices, is herein proposed. In a preliminary step, an LC-ICP-MS method previously used for water analysis was optimized to correct identify Sb species present in the studied matrices using HRMS. Subsequently, the influence of temperature and storage time up to 30 days on Sb migration from PET bottles into peach and pineapple juices of the same brand was studied. Storing PET bottled drinks at elevated temperatures (i.e., in a hot car or in summer) can cause antimony migration to exceed the limits allowed in the EU or USA. Because the behavior observed differed from the results reported for Sb migration in mineral waters, a second approach was proposed: three mineral water and two juice samples were kept in different PET containers and stored at an elevated temperature (up to 60 °C) to understand the role of the PET type and matrix simultaneously. This study demonstrated that both matrix characteristics and type of PET bottle greatly influence antimony leaching, highlighting the need to consider these variables together when conducting migration experiments. The obtained results can be helpful for developing future legislation concerning migration of pollutants from packing to food commodities

Migration of antimony from polyethylene terephthalate used in mineral water bottles.

The influence of storage time and temperature on Sb migration from PET bottles into mineral water was studied in short-term tests lasting up to 15 days and long-term studies lasting up to 220 days. Samples purchased were stored in three different coloured bottles: clear (CL), light blue (LB) and dark blue (DB). Sb migration was assayed by HG-AFS for total determination and HPLC-ICP-MS for speciation analysis. Migration studies showed that waters stored at 4 and 20 oC were not subject to Sb migration. At 40 oC there was a significant increase in Sb concentration, although the maximum limit established by the European Union (5.0 ug/L) was not exceeded, whereas at 60 oC samples were subject to considerable Sb migration after 30 days of storage. In this case, the maximum limit established by the European Union was exceeded and both Sb (V) and Sb (III) were detected

Metabolic Cleavage and Translocation Efficiency of Selected Cell Penetrating Peptides: A Comparative Study with Epithelial Cell Cultures

We investigated the metabolic stability of four cell penetrating peptides (CPPs), namely SAP, hCT(9-32)-br, [Pα] and [Pβ], when in contact with either subconfluent HeLa, confluent MDCK or Calu-3 epithelial cell cultures. Additionally, through analysis of their cellular translocation efficiency, we evaluated possible relations between metabolic stability and translocation efficiency. Metabolic degradation kinetics and resulting metabolites were assessed using RP-HPLC and MALDI-TOF mass spectrometry. Translocation efficiencies were determined using fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM). Between HeLa, MDCK and Calu-3 we found the levels of proteolytic activities to be highly variable. However, for each peptide, the individual degradation patterns were quite similar. The metabolic stability of the investigated CPPs was in the order of CF-SAP = CF-hCT(9-32)-br > [Pβ]−IAF > [Pα] and we identified specific cleavage sites for each of the four peptides. Throughout, we observed higher translocation efficiencies into HeLa cells as compared to MDCK and Calu-3, corresponding to the lower state of differentiation of HeLa cell cultures. No direct relation between metabolic stability and translocation efficiency was found, indicating that metabolic stability in general is not a main limiting factor for efficient cellular translocation. Nevertheless, translocation of individual CPPs may be improved by structural modifications aiming at increased metabolic stabilit

Antimony speciation in spirits stored in PET bottles: identification of a novel antimony complex

Total antimony and its +V and +III oxidation state species were determined in twelve spirit samples (Greek raki and tsipouro) stored in polyethylene terephthalate bottles. Reliable and reproducible results were obtained following direct analysis by using ICP-MS providing total Sb concentrations between 0.4-4 mu g L-1. Antimony speciation analysis by LC-ICP-MS was also assessed, showing the presence of both inorganic Sb species along with an unknown Sb complex, which was the predominant species in all samples analysed. The structure of this complex was investigated by using liquid chromatography with high-resolution tandem mass spectrometry. The analysis gave evidence for an acetaldehyde-bisulphite pyruvate Sb complex with the formula: C7H14O12S2Sb. The proposed ligands are organic substances expected to be present in the raki matrix. In addition, the influence of high temperature storage conditions and extended exposure times up to two weeks, on Sb migration from PET bottles into raki samples was investigated. Total Sb and Sb species content was determined by ICP-MS and LC-ICP-MS, respectively. The concentrations determined were in the range of 5.6 to 28 mu g Sb per L spirit after a week of storage at 60 degrees C. In which case, inorganic Sb(V) and Sb(III) became the predominant species in comparison to the 'novel' organic Sb complex

Topical Administration of Somatostatin Prevents Retinal Neurodegeneration in Experimental Diabetes

Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). Somatostatin (SST) is an endogenous neuroprotective peptide that is downregulated in the diabetic eye. The aim of the study was to test the usefulness of topical administration of SST in preventing retinal neurodegeneration. For this purpose, rats with streptozotocin-induced diabetes mellitus (STZ-DM) were treated with either SST eye drops or vehicle for 15 days. Nondiabetic rats treated with vehicle served as a control group. Functional abnormalities were assessed by electroretinography (ERG), and neurodegeneration was assessed by measuring glial activation and the apoptotic rate. In addition, proapoptotic (FasL, Bid, and activation of caspase-8 and caspase-3) and survival signaling pathways (BclxL) were examined. Intraretinal concentrations of glutamate and its main transporter glutamate/aspartate transporter (GLAST) were also determined. Treatment with SST eye drops prevented ERG abnormalities, glial activation, apoptosis, and the misbalance between proapoptotic and survival signaling detected in STZ-DM rats. In addition, SST eye drops inhibited glutamate accumulation in the retina and GLAST downregulation induced by diabetes mellitus. We conclude that topical administration of SST has a potent effect in preventing retinal neurodegeneration induced by diabetes mellitus. In addition, our findings open up a new preventive pharmacological strategy targeted to early stages of DR