Prevention of the memory deficits induced by intensive ethanol exposure in mice by the neuroprotective compound 3,3’-diindolylmethane

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 03-02-2023El alcohol es la droga de abuso más consumida en el mundo, estimándose que un 5 % de las muertes totales a nivel global están ligadas directa o indirectamente al consumo de esta sustancia adictiva, lo que genera un elevado coste socioeconómico y supone una importante amenaza para los sistemas de salud pública. Los perfiles de consumo difieren en función de diversos aspectos, como la cultura social, el estatus económico, el sexo y la edad. El consumo tipo binge drinking, que se define como un consumo abusivo y excesivo de alcohol en un periodo corto de tiempo, es el más practicado por adolescentes y jóvenes adultos, edades altamente susceptibles a los efectos perjudiciales del consumo de alcohol. Es especialmente preocupante que las consecuencias inducidas por el consumo de alcohol en estas etapas tempranas de la vida se pueden perpetuar en la edad adulta y la vejez...Alcohol is the most widely consumed drug of abuse worldwide, with an estimated 5 % of all deaths globally being directly or indirectly linked to the use of this addictive substance, generating a high socioeconomic cost and posing a major threat to public health systems. Consumption profiles differ according to various aspects, such as social culture, economic status, sex and age. Binge drinking, which is defined as an abusive and excessive alcohol consumption in a short period of time, is most commonly practiced by adolescents and young adults, ages that are highly susceptible to the harmful effects of alcohol consumption. Of particular concern is the fact that the consequences induced by alcohol consumption in these early stages of life can be perpetuated into adulthood and old age...Fac. de MedicinaTRUEunpu

Influx of kynurenine into the brain is involved in the reduction of ethanol consumption induced by Ro 61‐8048 after chronic intermittent ethanol in mice

Background and Purpose: The kynurenine pathway has been proposed as a target for modulating drug abuse. We previously demonstrated that inhibition of kynurenine 3-monooxygenase (KMO), using Ro 61-8048, reduces ethanol consumption in a binge drinking model. Here, we investigate the effect of the kynurenine pathway modulation in ethanol-dependent mice. Experimental Approach: Adult male and female mice were subjected to a Chronic Intermittent Ethanol (CIE) paradigm. On the last day of CIE, mice were treated with Ro 61-8048, Ro 61-8048 + PNU-120596, a positive allosteric modulator of α7nAChR, and Ro 61-8048 + L-leucine or probenecid, which blocks the influx or efflux of kynurenine from the brain, respectively. Ethanol, water consumption and preference were measured and kynurenine levels in plasma and limbic forebrain were determined. Key Results: Ro 61-8048 decreases consumption and preference for ethanol in both sexes exposed to the CIE model, an effect that was prevented by PNU-120596. The Ro 61-8048-induced decrease in ethanol consumption depends on the influx of kynurenine into the brain. Conclusion and Implications: Inhibition of KMO reduces ethanol consumption and preference in both male and female mice subjected to CIE model by a mechanism involving α7nAChR. Moreover, this centrally-mediated effect depends on the influx of peripheral kynurenine to the brain and can be prolonged by blocking the efflux of kynurenine from the brain. Here, for the first time, we demonstrate that the modulation of the kynurenine pathway is an effective strategy for the treatment of ethanol dependence in both sexe

Base de datos de preguntas y actualización del software. Herramientas para la generación de exámenes presenciales u online

Depto. de Farmacología y ToxicologíaFac. de MedicinaFALSEsubmitte

Gestión de exámenes online. Base de datos de preguntas y desarrollo de software

Depto. de Farmacología y ToxicologíaFac. de MedicinaFALSEsubmitte

Periodic table screening for enhanced positive contrast in MRI and in vivo uptake in glioblastoma

The quest for nanomaterial-based imaging probes that can provide positive contrast in MRI is fueled by the necessity of developing novel diagnostic applications with potential for clinical translation that current gold standard probes cannot provide. Although interest in nanomaterials for positive contrast has increased in recent years, their study is less developed than that of traditional negative contrast probes in MRI. In our search for new magnetic materials with enhanced features as positive contrast probes for MRI, we decided to explore the chemical space to comprehensively analyze the effects of different metals on the performance of iron oxide nanomaterials already able to provide positive contrast in MRI. To this end, we synthesized 30 different iron-oxide-based nanomaterials. Thorough characterization was performed, including multivariate analysis, to study the effect of different variables on their relaxometric properties. Based on these results, we identified the best combination of metals for in vivo imaging and tested them in different experiments. First, we tested its performance on magnetic resonance angiography using a concentration ten times lower than that clinically approved for Gd. Finally, we studied the capability of these nanomaterials to cross the affected blood-brain barrier in a glioblastoma model. The results showed that the selected nanomaterials provided excellent positive contrast at large magnetic field and were able to accumulate at the tumor site, highlighting the affected tissue

Educando de otras maneras. Hijos de la tierra : rompe tu silencio

El trabajo obtuvo un premio de la Modalidad B de los Premios Tomás García Verdejo a las buenas prácticas educativas en la Comunidad Autónoma de Extremadura para el curso 2011/2012Se presenta un proyecto que pretende enseñar valores y fomentar el gusto por la lectura con el soporte de las nuevas tecnologías. Se describe la Jornada interdisciplinar 'Hijos de la tierra: rompe tu silencio' que consistió en realizar actividades y talleres relacionados con los temas transversales trabajados a lo largo del curso desde las distintas asignaturas y desde actividades generadas desde la biblioteca del centro, aunque tuvieron como tema central el medioambiente y el fomento de valores como la solidaridad, el respeto, la tolerancia, etcExtremaduraES

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field