Nanosistemas de administración oftálmica para el tratamiento de patologías crónicas e inflamatorias

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 14-07-2022Chronic ocular diseases that involve inflammatory conditions affects both the anterior and posterior segments of the eye, which in many cases lack of effective and well tolerated treatments at the same time. These types of pathologies can be subdivided into two welldifferentiated groups: those induced by inflammatory processes that end up developing a vicious cycle, such as uveitis or conjunctivitis, and those generated by pathophysiological transformations, or modifications that evolve towards inflammatory and degenerative processes. This last instance would be the case of prevalent pathologies such as dry eye disease (DED) and glaucoma. In DED, changes on the ocular surface occur such as tear evaporation, change in the lipid or aqueous profile of the precorneal tear film among others. Meanwhile, in glaucoma a damage in the nervous fibers of the retina is produced associated in most cases to an IOP increment. In both cases a chronic inflammation is induced giving rise rise to chronic and degenerative processes of both the anterior segment (fibrosis, abrasion, corneal ulcerations, and vision loss) and the posterior segment of the eye (neuroinflammation, excitotoxicity and retinal neurodegeneration). In fact, there is growing evidence about the relation between neurodegenerative diaseases and inflammatory events...Las enfermedades oculares crónicas, que cursan con inflamación, afectan tanto al segmento anterior como al posterior y, en muchas ocasiones carecen de tratamientos quesean efectivos y que al mismo tiempo resulten bien tolerados. Este tipo de patologías se pueden dividir en dos categorías bien diferenciadas: aquellas inducidas por eventos inflamatorios que acaban generando un círculo vicioso, como la uveítis o la conjuntivitis, y las generadas por transformaciones o modificaciones fisiopatológicas que evolucionan hacia procesos inflamatorios y degenerativos. Esta última categoría sería el caso de patologías prevalentes como la enfermedad de ojo seco (EOS) y el glaucoma. En la EOS se producen, entre otros procesos, evaporación de la lágrima y/o alteraciones en el perfil lipídico o acuoso de la película precorneal. En el glaucoma se produce un daño en la capa de fibras nerviosas de la retina que se asocia, en la mayoría de los casos, a un aumento dela presión intraocular (PIO). En ambos casos se genera gradualmente una inflamación crónica, dando lugar a procesos degenerativos tanto del segmento anterior (fibrosis, abrasión y ulceraciones corneales) como posterior (neuroinflamación, excitotoxicidad y otros procesos neurodegenerativos de la retina). De hecho, cada vez hay más evidencia de que las enfermedades neurodegenerativas se asocian a eventos inflamatorios...Fac. de FarmaciaTRUEunpu

Long‑term efect of a dietary intervention with two‑healthy dietary approaches on food intake and nutrient density in coronary patients: results from the CORDIOPREV trial

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. N.C.-I. is a recipient of the Juan de la Cierva Formación Programme. E.M.Y-S is a recipient of the Nicolás Monardes Programme (C1-0005–2019, Servicio Andaluz de Salud, Junta de Andalucía, Spain). A.P.A-L is supported by a Río-Hortega Programme (Instituto de Salud Carlos III). The CORDIOPREV study is supported by the Fundacion Patrimonio Comunal Olivarero. The sponsor was not involved in the design or carrying out the study, and its participation was limited to funding and providing the olive oil used in the study. CORDIOPREV trial also received additional funding from CITOLIVA, CEAS, Junta de Andalucia (Consejeria de Salud, Consejeria de Agricultura y Pesca, Consejeria de Innovacion, Ciencia y Empresa), Diputaciones de Jaen y Cordoba, Centro de Excelencia en Investigacion sobre Aceite de Oliva y Salud and Ministerio de Medio Ambiente, Medio Rural y Marino and the Spanish Government. It was also partly supported by research grants from the Ministerio de Ciencia e Innovacion (AGL2009-122270 to J L-M, FIS PI10/01041 to P. P.-M, FIS PI13/00023 to J. D.-L); Ministerio de Economia y Competitividad (AGL2012/39615 to J L-M); Consejeria de Salud, Junta de Andalucia (PI0193/09 to J. L.-M, PI-0252/09 to J. D.-L, and PI-0058/10 to P. P.-M, PI-0206–2013 to A. G.-R); Proyecto de Excelencia, Consejería de Economía, Innovación, Ciencia y Empleo (CVI-7450 to J. L.-M).Background Cardiovascular disease (CVD) is the leading cause of disease burden in the world by non-communicable diseases. Nutritional interventions promoting high-quality dietary patterns with low caloric intake value and high nutrient density (ND) could be linked to a better control of CVD risk and recurrence of coronary disease. This study aims to assess the efects of a dietary intervention based on MedDiet or Low-Fat dietary intervention over changes in ND and food intake after 1 and 7 years of follow-up of the CORDIOPREV study. Methods We prospectively analyzed the results of the 802 coronary patients randomized to two healthy dietary patterns (MedDiet=425, Low-Fat Diet=377) who completed the 7 years of follow-up and had all the dietary data need. Dietary intake information obtained from a validated 137-item Food Frequency Questionnaire was used to calculate 1- and 7-year changes in dietary intake and ND (measured as nutrient intake per 1000 kcal). T test was used to ascertain diferences in food intake and ND between groups across follow-up time. Within-subject (dietary allocation group) diferences were analyzed with ANOVA repeated measures. Results From baseline to 7 years of follow-up, signifcant increases of vegetables, fruits, and whole cereals within groups (p<0.001) was found. We found a higher increase in dietary intake of certain food groups with MedDiet in comparison with Low-Fat Diet for vegetables (46.1 g/day vs. 18.1 g/day, p<00.1), fruits (121.3 g/day vs. 72.9 g/day), legumes (4.3 g/day vs. 0.16 g/day) and nuts (7.3 g/day vs. − 3.7 g/day). There was a decrease in energy intake over time in both groups, slightly higher in Low-Fat Diet compared to MedDiet group (− 427.6 kcal/day vs. − 279.8 kcal/day at 1st year, and − 544.6 kcal/ day vs. − 215.3 kcal/day after 7 years of follow-up). ND of all the nutrients increased within group across follow-up time, except for Saturated Fatty Acids (SFA), cholesterol and sodium (p<0.001). Conclusions A comprehensive dietary intervention improved quality of diet, reducing total energy intake and increasing the intake of healthy food groups and overall ND after 1 year and maintaining this trend after 7 years of follow-up. Our results reinforce the idea of the participation in trials, enhance nutrition literacy and produces better nutritional outcomes in adult patients with established CVD. Clinical trial registry The trial was registered in 2009 at ClinicalTrials.gov (number NCT00924937)CITOLIVACentro de Excelencia en Investigacion sobre Aceite de Oliva y SaludConsejeria de Agricultura y PescaConsejeria de InnovacionConsejeria de SaludConsejeria de Salud, Junta de Andalucia PI-0058/10, PI-0206–2013, PI-0252/09, PI0193/09Consejería de Economía, Innovación, Ciencia y Empleo CVI-7450Diputaciones de Jaen y CordobaFundacion Patrimonio Comunal OlivareroMedio Rural y MarinoMinisterio de Ciencia e Innovacion AGL2009-122270, FIS PI10/01041, FIS PI13/00023Spanish GovernmentCenter for East Asian Studies, Stanford UniversityMinisterio de Economía y Competitividad AGL2012/39615Instituto de Salud Carlos IIIMinistério do Meio AmbienteJunta de Andalucí

The role of relief, perceived control, and prospective intolerance of uncertainty in excessive avoidance in uncertain-threat environments

Excessive avoidance is a key feature of pathological anxiety. However, the precise mechanisms underlying the development of excessive avoidance are still unknown. In the present study, we tested the hypothesis that excessive avoidance, especially in individuals with high Intolerance of Uncertainty (IU) is aimed at distress reduction via the enhancement of subjective perceived control in uncertain-threat environments. In our experiment, participants learned to avoid an uncertain aversive sound through a discriminated free operant procedure. In a later test phase in extinction, we manipulated the amount of avoidance responses available per trial by creating a limited and an unrestricted response condition. Nonetheless, the aversive sound could be effectively avoided in both conditions. We measured response frequency, avoidance confidence ratings and anxiety-predisposing traits such as intolerance of uncertainty, trait anxiety and distress tolerance. The degree of distress suffered during trials was inferred from post-trial relief ratings that were requested after trials in which the aversive sound had been omitted. In the avoidance acquisition phase, we found a positive association between prospective intolerance of uncertainty (P-IU) and the decline rate of distress. This relationship was not significant, however, when inhibitory intolerance of uncertainty (I-IU) was controlled for. At test, we found that the increase in avoidance responses led to distress reduction through the enhancement of avoidance confidence. Finally, we found a significant modulating role of P-IU in the effect of response limit on distress reduction that lends further support to our hypothesis. Specifically, P-IU was positively associated with the effect of response limit on distress. However, such modulating role was not significant when controlling for trait anxiety or I-IU.Preparation of this manuscript was supported by a KU Leuven C1 project (C16/19/02), and by Grants PGC2018-096863-B-I00 and UMA18-FEDERJA-051 from the Spanish Ministerio de Economía y Competitividad and the Spanish regional government Junta de Andalucía, respectively. María J. Quintero has been awarded a PhD fellowship from the Spanish Ministry of Science, Innovation, and Universities (FPU Programme, FPU18/00917. Funding for open access charge: Universidad de Málaga / CBU

Electrodes based on nafion and epoxy-graphene composites for improving the performance and durability of open cathode fuel cells, prepared by electrospray deposition

Fabrication of electrodes for polymer electrolyte fuel cells is a intriguing process in which a balance between gas transport, electrical conductivity, proton transport and water managing must be optimized. In this work four different electrodes prepared by electrospray deposition have been studied using different catalytic inks, in which Nafion and epoxy doped with Graphene-Nanoplatelets were used as binders. After studying the behavior of those electrodes in a single open cathode fuel cell proton electrolyte membrane, it is clear that the addition of epoxy as binder doped with graphene, improves the performance of the fuel cell and increase the mechanical stability of the electrode avoiding the loose of catalyst during the electrode manipulation in the fuel cell assembly process and the durability of the fuel cell. To explain this behavior, an ex-situ study was carried out, in which properties such as its surface morphology, hydrophobicity and electrical and thermal conductivity of those electrodes were studied. From the results of this study, such improvement in the performance of the fuel cell was justified on the basis of the increase in the electrical conductivity, a diminution in its thermal conductivity and an enhancement of hydrophobicity (surface morphology) of the deposited catalyst layer, when an optimum quantity of epoxy is added to the catalytic ink that makes to improve the mechanical properties of those electrodesAJN and MAG are actually working on this project with a contract funded by the Comunidad Atonoma de la Región de Murcia, Conserjería de Desarrollo Económico, Turismo y Empleo, and the European Union, through the program RIS3- MUR, grant number 2I20SAE00079. This work has also been funded by the Spanish Ministry of Science and Innovation (AEI, Spain,PID2020-112744GB-I00/AEI/10.13039/501100011033 and RTI2018-095844-B-I00), Fundacion Seneca (Región de Murcia, Spain), grant number: 20985/PI/18 and Agencia estatal española de Investigación, grant number PID2019-104272RBC55/AEI/10.13039/501100011033. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper

Correlations between acoustic and electrochemical measurements for metallic corrosion on steel strings used in guitars

The corrosion state of steel guitar strings and their morphology were evaluated according to exposure time to artificial human sweat solution. The instantaneous corrosion rate was evaluated using polarization resistance. Electrochemical impedance spectroscopy was used to measure the strings' state due to corrosion in artificial human sweat solution. Modification of vibroacoustic parameters was analyzed: changes in harmonic content of sound were studied by means of the Fast Fourier Transform and spectrograms. The correlation between corrosion and acoustic measurements was established in the successive stages of corrosion. Thus, the strings' acoustic properties could be modified by means of controlled corrosion processes. (C) 2015 Elsevier Ltd. All rights reserved.The authors wish to thank to the Spanish Ministerio de Ciencia e Innovacion (contract CTM2011-23583) for the financial support.López Muelas, JL.; Bonastre Cano, JA.; Segura Alcaraz, JG.; Gadea Borrell, JM.; Juliá Sanchis, E.; Cases Iborra, FJ. (2015). Correlations between acoustic and electrochemical measurements for metallic corrosion on steel strings used in guitars. Engineering Failure Analysis. 57:270-281. https://doi.org/10.1016/j.engfailanal.2015.07.014S2702815

Modelos de volumen específicos y regionales para 12 especies forestales en el estado de Durango, México

Introduction: Estimating the volume of individual trees is an important aspect in dendrometry and in the conducting of forest inventories. Objective: Significant differences were evaluated in additive equation systems for estimating the total volume of individual trees in nine species of the genus Pinus (P. cooperi, P.durangensis, P. arizonica, P. leiophylla, P. teocote, P. engelmannii, P. lumholtzii, P.strobiformisand P. herrerae), and three of the genus Quercus (Q. sideroxyla, Q. durifoliaand Q. rugosa), and among regional forest management units (UMAFOR) when dealing with the same species. Materials and methods: To evaluate whether equation systems are different among tree species of the same genus and among the UMAFORs for the same species, two complementary statistical analyzes were used based on the fitting of a reduced and a full equation system: the F test of nonlinear extra sum of squares method, and the parameter significance analysis. Results and discussion: For most of the species studied, equation systems are significantly different. The need to use regional models in 10 of the 12 tree species, except for P. strobiformis and Q. rugosa, is also reported. Conclusion: The use of a state model for P. strobiformis and Q. rugosa is recommended.Introducción: La estimación del volumen de árboles individuales es un aspecto relevante en la dendrometría y en la realización de inventarios forestales. Objetivo: Se evaluaron diferencias significativas en sistemas de ecuaciones aditivas para la estimación de volumen total de árboles individuales en nueve especies de Pinus (P. cooperi, P. durangensis, P. arizonica, P. leiophylla, P. teocote, P. engelmannii, P. lumholtzii, P. strobiformis y P. herrerae), y tres de Quercus (Q. sideroxyla, Q. durifolia y Q. rugosa), y entre unidades de manejo forestal regional (UMAFOR) cuando se trata de una misma especie. Materiales y métodos: Para evaluar si el sistema de ecuaciones difiere entre especies de un mismo género y entre las UMAFOR para una misma especie, se utilizaron dos análisis estadísticos complementarios basados en el ajuste de un sistema reducido y un sistema completo de ecuaciones: la prueba F asociada al método de la suma adicional de cuadrados no lineales y el análisis de significancia de los parámetros. Resultados y discusión: Para la mayoría de las especies estudiadas, los sistemas de ecuaciones son significativamente diferentes. Se reporta la necesidad de utilizar modelos regionales en 10 de las 12 especies, exceptuando a P. strobiformis y Q. rugosa. Conclusiones: Se recomienda el empleo de un modelo estatal para P. strobiformis y Q. rugosa.We thank the Program Fomento a la Organización Social,Planeación y Desarrollo Regional Forestal (PROFOS) of CONAFOR for funding the collection of the data used in this studyS

CALHM1 and its polymorphism P86L differentially control Ca²⁺ homeostasis, mitogen-activated protein kinase signaling, and cell vulnerability upon exposure to amyloid β

The mutated form of the Ca2+ channel CALHM1 (Ca2+ homeostasis modulator 1), P86L-CALHM1, has been correlated with early onset of Alzheimer’s disease (AD). P86L-CALHM1 increases production of amyloid beta (Ab) upon extracellular Ca2+ removal and its subsequent addback. The aim of this study was to investigate the effect of the overexpression of CALHM1 and P86L-CALHM, upon Ab treatment, on the following: (i) the intracellular Ca2+ signal pathway; (ii) cell survival proteins ERK1/2 and Ca2+/cAMP response element binding (CREB); and (iii) cell vulnerability after treatment with Ab. Using aequorins to measure the effect of nuclear Ca2+ concentrations ([Ca2+]n) and cytosolic Ca2+ concentrations ([Ca2+]c) on Ca2+ entry conditions, we observed that baseline [Ca2+]n was higher in CALHM1 and P86L-CALHM1 cells than in control cells. Moreover, exposure to Ab affected [Ca2+]c levels in HeLa cells overexpressing CALHM1 and P86L-CALHM1 compared with control cells. Treatment with Ab elicited a significant decrease in the cell survival proteins p-ERK and p-CREB, an increase in the activity of caspases 3 and 7, and more frequent cell death by inducing early apoptosis in P86L-CALHM1- overexpressing cells than in CALHM1 or control cells. These results suggest that in the presence of Ab, P86L-CALHM1 shifts the balance between neurodegeneration and neuronal survival toward the stimulation of pro-cytotoxic pathways, thus potentially contributing to its deleterious effects in AD.This work was partly supported by the following grants: Ministerio de Economía y Competitividad, FPU Program, Refs. AP2009/0343 (AJMO) and AP2010/1219 (IB). ARN: FIS PI10/01426. MGL: Ministerio de Economía y Competitividad, Ref. SAF2012-23332. MFCA: Consolidación de grupos de investigación UAM-CAM 1004040047. We also thank Fundación Teófilo Hernando, Madrid, Spain, for their continued suppor

An effective polymeric nanocarrier that allows for active targeting and selective drug delivery in cell coculture systems

In this manuscript, we report the development of a versatile, robust, and stable targeting nanocarrier for active delivery. This nanocarrier is based on bifunctionalized polymeric nanoparticles conjugated to a monoclonal antibody that allows for active targeting of either (i) a fluorophore for tracking or (ii) a drug for monitoring specific cell responses. This nanodevice can efficiently discriminate between cells in coculture based on the expression levels of cell surface receptors. As a proof of concept, we have demonstrated efficient delivery using a broadly established cell surface receptor as the target, the epidermal growth factor receptor (EGFR), which is overexpressed in several types of cancers. Additionally, a second validation of this nanodevice was successfully carried out using another cell surface receptor as the target, the cluster of differentiation 147 (CD147). Our results suggest that this versatile nanocarrier can be expanded to other cell receptors and bioactive cargoes, offering remarkable discrimination efficiency between cells with different expression levels of a specific marker. This work supports the ability of nanoplatforms to boost and improve the progress towards personalized medicine.Health Institute Carlos III (ISCIII) DTS18/00121Junta de Andalucia-FEDER, Ministry of Economy, Knowledge, Companies and University (University of Granada) B-FQM-475-UGR18 PT18-TP-1490 AT17_6096- OTRISpanish State Research Agency RED2018-102469-TFundación Benéfica Anticáncer San Francisco Javier y Santa CándidaSpanish Ministry of Economy and Competitiveness PTQ-16- 08597Spanish Government FPU 16/0206

Upgrade of the edge Charge Exchange Recombination Spectroscopy system at the High Field Side of ASDEX Upgrade

The upgrade of the high field side (HFS) edge charge exchange recombination spectroscopy (CXRS) system of ASDEX Upgrade is presented. This diagnostic provides temperature, rotation and radiance measurements of impurity species by taking advantage of the gas puff based CXRS technique (GP-CXRS). The system is formed by a fast piezoelectric valve, that injects thermal neutrals into the plasma, and two optical heads. The localized gas injection together with properly aligned lines of sights (LOS) lead to a high spatial resolution of 5–19 mm. Fast gas puff modulation allows a precise subtraction of the passive part of the signal. The existing poloidal optical head has been replaced with a new one to increase the radial resolution. The number of lines of sight (LOS) of the poloidal optical head has been increased from 8 to 16 covering around 7 cm of the plasma edge at the HFS. The same radial range is also viewed by a toroidal optical head. The neutral deposition, needed to calculate the impurity density profile, has been modelled using the FIDASIM code. A realistic gas puff geometry has been implemented in the code. The first measurements of impurity temperature, rotation and radiance utilizing the upgraded diagnostic are presented.Universidad de Sevilla PPITUS 2017EUROfusion Consortium 633053H2020 Marie-Skłodowska Curie programme (Grant No. 708257)Spanish Ministry of Economy and Competitiveness (Grant No. FJCI-201422139