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Fyrir marga lyfjaflokka þykir staðbundin lyfjagjöf í augndropaformi ákjósanlegasta leiðin vegna einfaldleika við lyfjagjöf. Eru augndropar algengasta aðferðin til að meðhöndla augnsjúkdóma í fremri hluta augans. Staðbundin lyfjagjöf í augndropaformi yfir hornhimnu er hinsvegar óhagkvæm þegar meðhöndla þarf aftari hluta augans. Hefðbundin lyfjameðferð fyrir aftari hluta augans felur í sér að lyfinu er dælt í glerhlaup augans en með tilheyrandi áhættu á fylgikvillum ásamt tilheyrandi óþægindum fyrir sjúklinga. Sýnt hefur verið fram á að leiðin í gegnum augnslímhúð og augnhvítu hefur hlutfallslega hærra gegndræpi fyrir risasameindir, stærra aðgengilegt yfirborð og meiri nálægð við sjónhimnu samanborið við hornhimnu. Fyrir vikið hafa verið kenningar um að augnslímhúð og augnhvíta sé mögulega leið lyfja í augndropaformi yfir í aftari hluta augans. Meginmarkmið þessarar ritgerðar eru (1) að kanna hversu vel ákveðin lyf í sýklódextrín augndropaformi flytjast yfir í fremri og aftari hluta augans, (2) að ákvarða lyfjafræðileg áhrif angíótensínviðtaka-hamlara á augnþrýsting eftir augndropagjöf, (3) að meta og bera saman in vitro gegndræpi í gegnum hornhimnu og í gegnum augnslímhúð og augnhvítu fyrir staðbundna augndropalyfjagjöf í aftari hluta augans og (4) að bera kennsl á helstu eðlisefnafræðilega eiginleika sem hafa áhrif á gegndræpi lyfja yfir hornhimnu í fullri þykkt og leiðina frá augnslímhúð, í gegnum augnhvítu og æðahimnu að sjónhimnu (augnslímhúð-augnhvítu-æðahimnu-sjónhimnu leið). Aðferðir 1. Framkvæmdar voru tvær in vivo rannsóknir á kanínum þar sem mældur var lyfjastyrkur í augnvefjum eftir stakan skammt af augnlyfjum í sýklódextrín nanóögnum. Í fyrri rannsókninni voru tveir mismunandi angíótensínviðtakahamlarar, 1.5% irbesartan og 0.15% candesartan, gefnir 49 kanínum. Styrkur lyfjanna var mældur í hornhimnu og augnvökva eftir 1, 2, 3, 6 og 12 klukkustundir frá lyfjagjöf. Í seinni rannsókninni var ný γ-sýklódextrín öragna augnlyfjaferja með cediranib maleate (öflugur VEGF hamlari) prófuð á 26 kanínum. Styrkur cediranib maleate var mældur í vefjum fremri og aftari hluta augans eftir 1, 3, og klukkustundir frá lyfjagjöf. 2. Augnþrýstingslækkandi áhrif irbesartan og candesartan voru mæld í 10 kanínum. Algengt glákuaugndropalyf, 0.5% timolol, var síðan notað til samanburðar. Augnþrýstingur var mældur með sérstökum augnþrýstingsmæli á tíma 0, 2 og 4 klukkustundum eftir stakan lyfjaskammt. 3. Framkvæmd var in vitro rannsókn á augnvef úr svínum með Franz-sveimklefa til að bera saman gegndræpi 27 mismunandi efnasambanda yfir hornhimnu og augnslímhúð – augnhvítu – æðahimnu og sjónhimnu. Reiknað var út flæði lyfja og gegndræpisstuðlar fyrir hvert efnasamband og vef. Lýsing á 39 sameindum fyrir efnasamböndin sem voru notuð, voru fengin frá ákveðnum gagnagrunnum á alnetinu og notuð til að reikna út fylgni við gegndræpisstuðul með Spearmans rho fylgnistuðul. Niðurstöður 1. Styrkur irbesartan í augnvökva meðferðarauga fór upp í 282 ± 159 ng/g (meðaltal ± SD, n = 26) og fyrir candesartan 70 ± 73 ng/g. Hæsti styrkur í hornhimnu var 3662,6 ± 987,7 ng/g fyrir irbesartan og 3503,9 ± 801,5 ng/g fyrir candesartan. Cediranib maleate mældist í sjónhimnu í styrkleika 1070 ± 1404 nM og í glerhlaupi 19 ± 9 nM (n = 6). 2. Candesartan hafði mest lækkandi áhrif á augnþrýsting, með breytingu upp á 5,6 mmHg fjórum klukkustundum eftir lyfjagjöf samanborið við 4,0 mmHg fyrir irbesartan og 4,6 mmHg fyrir timolol. 3. 22 af 27 efnasamböndum (81%) sýndu hærra gegndræpi í gegnum augnslímhúð-augnhvítu-æðahimnu-sjónhimnu leiðina, samanborið við hornhimnu. Meðalgegndræpi fyrir augnslímhúð-augnhvítu-æðahimnu-sjónhimnu vefina var 2,9 sinnum hærra en gegndræpi hornhimnunnar. Fylgni var á milli aukins vatnsleysnis og meira gegndræpis yfir bæði hornhimnu í fullri þykkt og augnslímhúð-augnhvítu-æðahimnu-sjónhimnu-leiðina, á meðan hærri fitusækni, mólmassi og fjöldi hringa leiddi til lægri gegndræpisstuðla. Umræða Irbesartan, candesartan og cediranib mældust í styrk af tilætluðum lyfjafræðilegum áhrifum í fremri og aftari hluta augans eftir lyfjagjöf með sýklódextrin augnlyfjaferjum. Niðurstöðurnar gefa til kynna staðbundna dreifingu lyfjanna sem gæti komið í veg fyrir þörf á inngripsmiklum lyfjagjöfum. Irbesartan og candesartan í augndropaformi lækkuðu augnþrýsting hjá kanínum með góðum árangri, sem gæti bent til nýs flokks glákulyfja. In vitro gögn okkar benda til þess að fyrir mörg efnasambönd gæti augnslímhúðaugnhvítu leiðin verið áhrifameiri og mögulega eina leiðin til að skila lyfjum í vefi í aftari hluta augans með staðbundinni augndropalyfjagjöf., Purpose: Topical ocular administration is the preferred route for many classes of drugs because of its ease of administration. It is the most common way of treating eye diseases in the anterior segment. Topical administration through the cornea, however, is inefficient for drug delivery to the back of the eye. Intravitreal injections are the standard drug treatment for posterior segment disorders but are associated with the risk of complications and patient discomfort. The conjunctiva-sclera route has shown a relatively higher permeability to macromolecules, a larger surface of exposed tissue and a closer location to the retina when compared to the cornea. Consequently, it has been suggested as an alternative route for topical drug delivery to the posterior segment. The main goals of this thesis are (1) to test the efficacy of cyclodextrin-based eye drop formulations in delivering certain drugs to the anterior and posterior segments of the eye, (2) to determine the pharmacological effect of angiotensin receptor blockers on intraocular pressure after topical administration, (3) to evaluate and compare the in vitro permeabilities of the corneal and noncorneal routes for topical drug delivery to the posterior segment and (4) to identify the main physicochemical properties affecting the permeation of drugs across full-thickness cornea and conjunctiva-sclera-choroid-retina. Methods: 1. Two separate in vivo studies were performed in rabbits to measure the drug concentration in the intraocular tissues after a single dose administration of cyclodextrin-based nanosuspension eye drops. In the first study, two different angiotensin receptor blockers, 1.5% irbesartan and 0.15% candesartan, were administered to 49 rabbits and the drug concentrations in the cornea and aqueous humour were quantified at 1, 2, 3, 6 and 12 hours after administration. In the second study, a novel γ-cyclodextrin nanoparticle eye drops formulation containing cediranib maleate, was applied to 26 rabbits. The concentration of cediranib maleate in the tissues of both anterior and posterior segments was quantified at 1, 3 and 6 hours after administration. 2. The potential lowering effect of irbesartan and candesartan on intraocular pressure was investigated in 10 rabbits. The IOP was measured at 0, 2 and 4 hours after a single-dose administration using a rebound tonometer and compared with a commercial 0.5% timolol solution. 3. In vitro studies were performed using porcine ocular tissues mounted on Franzdiffusion cells to compare the permeability of 27 different compounds across vi full-thickness cornea and conjunctiva-sclera-choroid-retina. The drug fluxes and permeability coefficients were calculated for each compound and tissue. 39 molecular descriptors were obtained for our compounds from different online databases and correlated with their permeability coefficient using Spearman’s rho. Results: 1. Irbesartan and candesartan reached maximum concentrations in the aqueous humour of the treated eyes three hours after administration. Cediranib maleate was found in all studied tissues, and the highest concentrations in the retina and vitreous were found 1 hour after the administration. 2. Irbesartan and candesartan showed an IOP lowering effect that was equivalent to that of timolol four hours after the administration. 3. Regarding the in vitro permeability data, 22 out of 27 compounds (81%) showed a higher permeability across conjunctiva-sclera-choroid-retina compared with the full-thickness cornea. The mean permeability of the noncorneal route was 2.9 times higher than the cornea. The correlation analysis showed that charge, mass and size, lipophilicity, and the ability to form hydrogen bonds were the most relevant properties for corneal permeability, while lipophilicity and the number of rings and rotatable bonds were more important for the noncorneal route. Discussion: The drugs were found at pharmacologically relevant concentrations in both anterior and posterior segments of the eye after topical administration of cyclodextrinbased formulations. These results indicate a local delivery that could contribute to minimizing systemic drug absorption while replacing the need for invasive drug delivery techniques. Irbesartan and candesartan successfully lowered the IOP in rabbits when topically administered, suggesting the potential for a new class of glaucoma drugs. Our in vitro data suggest that, for many compounds, the noncorneal route could represent a more effective, and possibly the only way of drug delivery to the posterior segment following topical administration.

Desarrollar la validación del instrumento de autoengaño SDQ-12. El presente trabajo pretende validar el instrumento de autoengaño SDQ-12 (cuestionario de manipulación y mixtificación) el cual mide de manera objetiva, adecuada y útil los constructos del autoengaño, la incapacidad de percibir los comportamientos negativos y la forma de actuar en la vida cotidiana en relación con la deseabilidad social. El cuestionario de autoengaño consta de una prueba con 12 ítems que miden dos factores los cuales son: mixtificación y manipulación. Así mismo, el objetivo general de la investigación es desarrollar un proceso de validación de la prueba para la medición del autoengaño en las personas con nacionalidad colombiana adaptada al contexto y a la cultura, comprobando su efectividad en la aplicación a un grupo muestra significativo de la población que permita analizar los resultados y brindar conclusiones que aporten al campo clínico de la psicología y más exactamente al fortalecimiento de los psicólogos colombianos. Abstract This paper aims to validate the self-deception instrument SDQ-12 (manipulation and mixtification questionnaire) which objectively, adequately, and usefully measures the constructs of self-deception, the inability to perceive negative behaviors and the way of acting in daily life in relation to social desirability. This self-deception questionnaire presents a test with 12 items that measure two factors: mixtification and manipulation. The general objective of the research is to develop a test validation process for the measurement of selfdeception in people with Colombian nationality adapted to the context and culture, checking its effectiveness in the application to a significant sample group of the population that leads to conclusions and results contributing to the clinical field of psychology and more precisely to the strengthening of Colombian psychologists.

La etapa gestacional conlleva varios cambios fisiológicos y metabólicos en la madre caracterizadosprincipalmente por el aumento de los requerimientos nutricionales. La anemia en el embarazo, ademásde ser factor de riesgo para la morbilidad fetal-materna, es un problema de salud que afecta al 50% delas mujeres embarazadas. La deficiencia de hierro es la más frecuente, por ello su suplementación,junto a la de ácido fólico, es esencial para prevenir malformaciones y complicaciones en el feto.También cabe destacar la deficiencia de vitamina B12, debido a su relación con un desarrollo ycrecimiento deficiente, que mayormente se debe a la alimentación por lactancia por parte de madresdeficientes. Igual de importante es determinar qué requerimientos se deben cubrir, como aquellassituaciones que no requieren suplementación, como es el caso del calcio, yodo y vitamina D. Elobjetivo de este trabajo de fin de grado será ahondar en cómo los déficits de micronutrientes influyeno qué procesos se alteran durante el embarazo, realizando una revisión bibliográfica que incide en enlas distintas estrategias de suplementación en este grupo de población.

International audience; Zearalenone (ZEN) is a mycotoxin classified as an endocrine disruptor. Many endocrine disruptors are also metabolic disruptors able to modulate energy balance and inflammatory processes in a process often involving a family of protein hormones known as adipokines. The aim of our study was to elucidate the role of ZEN as metabolic disruptor in pigs by investigating the changes in energy balance and adipokines levels in response to different treatment diets. To this end, weaned piglets (n = 10/group) were exposed to either basal feed or feed contaminated with 680 and 1620 µg/kg ZEN for 28 days. Serum samples collected at days 7 and 21 were subjected to biochemistry analysis, followed by determination of adipokine levels using a combined approach of protein array and ELISA. Results indicate that ZEN has an impact on lipid and glucose metabolism that was different depending on the dose and time of exposure. In agreement with these changes, ZEN altered circulating adipokines concentrations, inducing significant changes in adiponectin, resistin, and fetuin B. Our results suggest that ZEN may function as a natural metabolism-disrupting chemical.

International audience

International audience; The molecular basis of male fertility remains unclear, especially in chickens, where decades of genetic selection increased male fertility variability as a side effect. As transcription and translation are highly limited in sperm, proteins are key molecules defining their functionality, making proteomic approaches one of the most adequate methods to investigate sperm capacity. In this context, it is interesting to combine complementary proteomic approaches to maximize the identification of proteins related to sperm-fertilizing ability. In the present study, we aimed at identifying proteins related to fertility in meat-type roosters, showing fertility variability. Fertile roosters (fertility rates higher than 70% after artificial insemination) differed from subfertile roosters (fertility rates lower than 40%) in their sperm mass motility. Fertile and subfertile sperm protein contents were compared using two complementary label-free quantitative proteomic methods: Intact Cell MALDI-TOF-Mass Spectrometry and GeLC-MS/MS. Combining the two strategies, 57 proteins were identified as differentially abundant. Most of them were described for the first time as differentially abundant according to fertility in this species. These proteins were involved in various molecular pathways including flagellum integrity and movement, mitochondrial functions, sperm maturation, and storage in female tract as well as oocyte–sperm interaction. Collectively, our data improved our understanding of chicken sperm biology by revealing new actors involved in the complexity of male fertility that depends on multiple cell functions to reach optimal rates. This explains the inability of reductionist in vitro fertility testing in predicting male fertility and suggests that the use of a combination of markers is a promising approach.

International audience; Human exposure to mycotoxins through our diet is a growing concern in term of both food safety and public health. These toxins, produced by moulds, are very prevalent in our food. Because of their very different chemical structure and mode of action, mycotoxins induce several health effects. At the European level, regulations based on their occurrence in food and/or their toxicity for humans and animals, have been established for seven mycotoxins: aflatoxin B1, deoxynivalenol, fumonisin B1, ochratoxin, patulin, zearalenone and ergot alkaloids. In addition to these “regulated” toxins, new secondary fungal metabolites, described as “modified forms” and “emerging” mycotoxins represent a challenge in term of research. Since our food can be contaminated by many substances, the study of mycotoxin mixtures or the association of mycotoxins with other food contaminants is another challenge for research. This review details the occurrence, metabolization, mode of action and toxicity of each of the regulated mycotoxins, as well as the first answers to both challenges for the coming years.; L;’exposition alimentaire humaine aux mycotoxines est une préoccupation croissante pour la sécurité sanitaire des aliments et la santé publique. Très répandues dans nos aliments, ces toxines ont des modes d’action différents et de nombreux effets sur la santé. Des réglementations, basées sur leur occurrence et/ou leur toxicité chez l’Homme et l’animal, ont été établies pour l’aflatoxine B1, le déoxynivalénol, la fumonisine B1, l’ochratoxine, la patuline, la zéaralénone et les alcaloïdes de l’ergot. Outre ces toxines “réglementées”, de nouveaux métabolites secondaires, les “formes modifiées” et les mycotoxines “émergentes”, représentent un défi pour la recherche. Notre alimentation pouvant être contaminée par de nombreuses substances, l’étude des mélanges de mycotoxines ou de l’association des mycotoxines avec d’autres contaminants alimentaires constitue un autre défi pour la recherche. Cette étude détaille l’occurrence, la métabolisation, le mode d’action et la toxicité des mycotoxines réglementées, ainsi que les premières réponses aux deux défis à relever.

International audience

Aquest treball vol donar resposta, des de l'Economia Social i Solidària, a la necessitat d'aproximar el model d'habitatge cooperatiu en cessió d'ús a les persones joves, les quals actualment no poden accedir-hi degut al preu inicial. Per fer-ho, es desenvolupa una proposta aplicable al model actual per tal de que s'adapti millor a les necessitats i capacitats de les persones joves. Este trabajo quiere dar respuesta, des de la Economía Social y Solidaria, a la necesidad de aproximar el modelo de vivienda cooperativa en cesión de uso a las personas jóvenes, las cuales actualmente no pueden acceder debido al precio inicial. Para hacerlo, se desarrolla una propuesta aplicable al modelo actual para que pueda adaptarse mejor a las necesidades y capacidades de las personas jóvenes. This project aims to respond, from de Social and Solidarity Economy, to the need to bring cooperative housing closer to young people, which now is inaccessible form them due to the initial price. To do so, it has been developed a proposal applicable in the current model for it to be better adapted to the necessities and capacities of young people.

Treball Final de Master en Comunicació Intercultural i d'Ensenyament de Llengües. Codi: SBC042. Curs: 2019/2020 Teniendo en cuenta las características de la sociedad actual y el continuo proceso de globalización en que se encuentra inmersa, las escuelas tratan de renovarse, adaptando los modelos educativos a las necesidades y características del alumnado con tal de potenciar la socialización y, así, potenciar la comunicación. Y, en este sentido, cobra especial importancia la adquisición y desarrollo del lenguaje como principal herramienta de socialización y comunicación. Como consecuencia de todo ello, son muchas las teorías que tratan de responder al proceso de adquisición de la lengua, considerando diferentes variables, como el nivel de estimulación externo recibido, el desarrollo cognitivo, el desarrollo de los órganos bucofaciales o el nivel de socialización. Estas teorías también consideran el aprendizaje de una segunda lengua y el plurilingüismo que podemos encontrar en nuestra sociedad. Es por ello por lo que el presente trabajo se centra en analizar el proceso de adquisición y desarrollo de la lengua durante la etapa de educación primaria y en contrastar el nivel de competencia lingüística adquirido en función del enfoque metodológico utilizado. Considerando los resultados obtenidos del proceso de investigación, se extrae que, por un lado, el tratamiento de las variaciones fonológicas está estrechamente relacionado con el nivel de competencia lingüística adquirido a largo plazo; por otro lado, el aprendizaje de lenguas favorece el desarrollo cognitivo y facilita el aprendizaje de las mismas, ya que las estructuras cognitivas se relacionan entre sí creando estructuras cada vez más complejas.