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In vitro biotransformation of 3-methylmethcathinone (3-MMC) through incubation with human liver microsomes and cytosol and application to in vivo samples
Synthetic cathinones are the second largest group of new psychoactive substances (NPS) monitored by the European Monitoring Centre for Drugs and Drug Addiction. Although 3-methylmethcathinone (3-MMC, C11H15NO) is legally banned in many countries, it is readily available for purchase online and on the street. Due to the scarcity of information regarding the pharmacokinetic and toxicological profile of 3-MMC, understanding its biotransformation pathways is crucial in determining its potential toxicity in humans and in the development of analytical methods for screening of human matrices. To gain more insight, Phase I and Phase II in vitro biotransformation of 3-MMC was investigated using human liver microsomes and human liver cytosol. Suspect and non-target screening approaches were employed to identify metabolites. To confirm in vitro results in an in vivo setting, human matrices (i.e., plasma, urine, saliva and hair) positive for 3-MMC (n=31) were screened. In total three biotransformation products were identified in vitro: C11H15NO2 (a hydroxylated derivate), C11H17NO (a keto-reduced derivate) and C10H13NO (an N-desmethyl derivate). All three were confirmed as human metabolites in respectively 16 %, 52 % and 42 % of the analysed human samples. In total, 61 % of the analysed samples were positive for at least one of the three metabolites. Interestingly, three urine samples were positive for all three metabolites. The presence of 3-MMC in saliva and hair indicates its potential applicability in specific settings, e.g., roadside testing or chronic consumption analysis. To our knowledge, C11H17NO was not detected before in vivo. Although some of these metabolites have been previously suggested in vitro or in a single post mortem case report, a wide in vivo confirmation including the screening of four different human matrices was performed for the first time. These metabolites could serve as potential human biomarkers to monitor human 3-MMC consumption effectively.Lidia Belova, Maarten Roggeman, Tim Boogaerts and Maarten Quireyns acknowledge the Research Foundation – Flanders (project number: 11G1821N, 1133223N, 1225924N and G060920N, respectively) for funding. Fatima den Ouden was funded by the Interuniversity Special Research Fund from Flanders (GISMO 01IB1320, Flexigut project). Rani Robeyns acknowledges the BOF-GOA project of the University of Antwerp (PS ID 494 41667). Authors from the University of Santiago de Compostela further acknowledge funding through Consellería de Cultura de Galicia, Educación e Universidades Xunta de Galicia (ED481A-2020/258 & ED431C 2021/06) and Instituto de Salud Carlos III-Next Generation EU/PRTR (RD21/0009/0012 – RIAPAd Network).2026-07-03S
Eco-Innovations For Advanced Pulmonary Drug Delivery: Beclomethasone Dipropionate- Loaded Alginate Particles By Supercritical and Aerogel Technologies
Addressing current challenges with DPIs calls for the
development of innovative inhaled formulations. Achieving
enhanced formulation efficacy demands the use of advanced
technologies and the design of suitable carriers. Furthermore, a
key consideration is the development of novel inhalers that
actively contribute to minimizing environmental impact.
In this PhD Thesis, aerogels, renowned as the world's lightest
materials due to their high porosity and surface area, along
with environmentally friendly approaches, were explored for
their potential in pulmonary drug delivery. This research aims
to contribute to overcoming existing challenges in DPIs by
leveraging the unique properties of aerogels and adopting
sustainable practices in pharmaceutical development
The introduction of insect meal as a supplement in ruminant rations: a strategy to be adopted in the short term in the face of raw material scarcity. A review
El crecimiento demográfico mundial está provocando un aumento en la demanda de alimentos de ori gen animal, entre la que se encuentra la carne y leche de rumiantes. Pero esta necesidad se enfrenta a
una ideología que denuesta este sector por considerar su alimentación en clara competencia con los re cursos destinados al consumo humano, al tiempo que contribuye a la degradación de los suelos y es pacios naturales. Ante esta situación, es urgente buscar nuevas fuentes que puedan suplir en parte de terminados componentes de la ración, al tiempo que aporten un valor añadido al producto final
(carne/leche). El consumo de harina de insectos, debidamente procesados y bajo una estricta regla mentación que asegure su seguridad, emerge como una posibilidad que podría extenderse al ganado
bovino, ovino y caprino.
En esta revisión pretendemos ofrecer los últimos estudios en lo que respecta a la legislación europea,
los insectos que están permitidos, así como todos aquellos estudios realizados in vivo e in vitro en es tas especies. La bibliografía citada demuestra que, si bien la calidad de la harina de insectos depende
de la especie y forma de cría, su introducción como suplemento en la ración, no causa ningún perjui cio en dinámica ruminal ni la producción, pudiendo constituir una solución rentable y respetuosa con
el medio ambiente.World population growth is causing an increase in the demand for food of animal origin, including ruminant meat and milk. But this need is confronted by an ideology rejecting this sector because it considers its food to be in direct competition with the resources destined for human consumption while contributing to the degradation of soils and natural spaces. Faced with this situation, it is urgent to look for new sources that can partly supply some components of the ration, while providing an added value to
the final product (meat/milk). The consumption of insect meal, duly processed and under strict regulations that ensure its safety, emerges as a possibility that could be extended to cattle, sheep and goats.
In this revision, we intend to offer the latest studies regarding European legislation, the allowed insects,
and all those studies carried out in vivo and in vitro in these species. All of them show that, although
the quality of insect meal depends on the species and rearing method, its introduction as a supplement
in the ration, does not cause any damage in ruminal dynamics or production and can be a profitable
and environmentally friendly solutionS
Resolución Reitoral, do 6 de xuño de 2024, pola que se establece o procedemento de xestión dos certificados negativos de delitos sexuais para persoal con contacto habitual con persoas menores de idade
Nuevas estrategias de análisis en radiogenómica del cáncer de próstata
Aproximadamente el 50% de los pacientes con cáncer recibirán radioterapia como parte de su tratamiento. A pesar de que los avances tecnológicos en radioterapia permiten aplicar el tratamiento de forma cada vez más precisa en el tumor, parte del tejido sano será inevitablemente irradiado, lo que puede dar lugar al desarrollo de efectos adversos. Estos efectos impactarán negativamente en la calidad de vida del paciente. Se ha descrito que los factores genéticos desempeñan un papel muy importante en el desarrollo y severidad de los efectos adversos a la radioterapia. Así, el propósito de esta tesis es la identificación de marcadores genéticos asociados con el sangrado rectal, uno de los efectos adversos más relevantes en el tratamiento radioterápico de pacientes con cáncer de próstata.2025-01-2
Fabric phase sorptive extraction as a sustainable sample preparation procedure to determine synthetic musks in water
A rapid sample preparation fabric phase sorptive extraction (FPSE) methodology followed by gas chromatography coupled to tandem mass spectrometry is proposed for the first time to determine 12 synthetic musks including nitro-, polycyclic and macrocyclic musk in environmental water and wastewater. An asymmetric screening design of experiments was used to evaluate the influence of nine parameters affecting FPSE in only 16 experiments. The factors included the sol–gel sorbent coating, stirring mode (both extraction and desorption), extraction and desorption time, salting-out effect, sample volume, type of solvent, and desorption solvent volume. The selected conditions imply the use of the sol–gel PDMS sorbent coating, 15 min extraction by ultrasound energy employing 10 mL of sample and 0.5 mL of ethanol as desorption solvent during 5 min. Accuracy and precision were assessed in different real water samples. Matrix effects were evaluated performing recovery studies in several aqueous matrices: river, sea, spring, laundry washing place, and wastewater at different concentration levels (0.1, 2, 10 µg L−1) demonstrating method accuracy (results ranged between 82 and 110%) and good precision (relative standard deviation, RSD < 12% in all cases). Limits of detection (LODs) were below 8 ng L−1 for the analyzed synthetic musks. As extraction was quantitative (exhaustive extraction), calibration was carried out using solvent standards without the need of repeating the extraction step, which is required in most microextraction methods, improving sample throughput, and reducing costs. Finally, the analysis of real contaminated samples revealed the presence of 11 out of the 12 target synthetic musks at concentrations up to 30 µg L−1, three of them banned in cosmetic regulation (musk tibetene, ambrette, and moskene). The developed FPSE based methodology uses low volume (0.5 mL) of a Generally Recognized as Safe (GRAS) solvent (ethanol), as well as minimum energy and time consumption, demonstrating to be a sustainable alternative to detect these microcontaminants in environmental waters and wastewaters.S
Introdución á programación lineal: resolución de problemas de programación lineal mediante "software" libre
Preséntase unha introdución á programación e lineal e dúas ferramentas informáticas gratuítas que permiten a resolución dos problemas de programación lineal. Efectúase unha ilustración das ferramentas por medio de exemplos
Qué es la calidad y cómo medirla en los proyectos de aprendizaje-servicio universitario
El origen de esta Tesis Doctoral es el análisis de la calidad en los
proyectos de aprendizaje-servicio (ApS). A tal efecto, planteamos un
diseño cuasiexperimental y estudiamos las variables que intervienen en
la configuración de los proyectos y cómo estas median en los beneficios
que puede obtener el alumnado, en términos de adquisición de
competencias transversales, pero también prestando atención a la mejora
de la relación entre inserción laboral y la formación que reciben en la
universidad. Con base en los resultados, se aporta una Guía de
Verificación d e la Calidad de los Proyectos de ApS, susceptible de servir
como apoyo al profesorado dispuesto a sacar el adecuado provecho
pedagógico a su experiencia y contribuir así a la calidad de la institución
como tal.2025-03-2
Carga de mortalidad atribuida al consumo de tabaco en España y sus comunidades autónomas
El consumo de tabaco es uno de los factores de riesgo que
mayor mortalidad produce a nivel mundial y es el principal
factor de riesgo del cáncer de pulmón. El radón es el segundo
factor de riesgo en el desarrollo de cáncer de pulmón en
fumadores y el primero en nunca fumadores. Los resultados de
esta tesis permiten caracterizar la epidemia tabáquica en
España al estudiar la evolución de la prevalencia y la
mortalidad atribuida a su consumo. Además, se estima por
primera vez la mortalidad atribuida al consumo de tabaco y a
la exposición a radón residencial en las 17 comunidades
autónomas de España y al consumo de tabaco en las siete
regiones de Portugal. Por último, se presenta una guía
metodológica que permite aumentar la calidad de las
estimaciones de mortalidad atribuida a diferentes factores de
riesgo.2025-01-2
Main characteristics of preventive postural hygiene training programs in the educational field
Objective: To determine the state of the art regarding preventive training programs on postural hygiene and back health in an educational context. Introduction: The prevalence of non-specific back pain in population reaches alarming figures and its causes are largely preventable. Adequate training in postural education is necessary along students' academic career. Method: Retrospective descriptive study, using the PRISMA method. Results: 61 original articles published from 2017 to 2021 have been analysed. Discussion: Postural education programs have demonstrated their effectiveness and have provided benefits for the participating studentsS