Complejos metalosupramoleculares de Cu(I), Ag(I), Au(I), Pd(II) y Pt(II): síntesis, caracterización estructural y propiedades biológicas

En esta tesis se han desarrollado compuestos metalosupramoleculares de Cu(I), Ag(I), Au(I), Pd(II) y Pt(II) a partir de ligandos funcionalizados con fosfinas (bases de Schiff, tiosemicarbazonas y semicarbazona), que han permitido obtener información valiosa para la comprensión de los procesos de autoensamblaje en sistemas de esta naturaleza. Particularmente, se ha estudiado en detalle el proceso de desulfurización de un helicato clúster doble derivado de Ag(I) y tiosemicarbazona. La gran relevancia de algunos de estos iones metálicos a nivel biológico ha permitido evaluar de forma preliminar la aplicación de alguno de los complejos como posibles metalofármacos

Supramolecular self-assembly of a symmetric imine ligand functionalized with a dansyl fluorophore moiety

The 20th International Electronic Conference on Synthetic Organic Chemistry session Polymer and Supramolecular ChemistryWe report the synthesis and characterization of a symmetric [N4] tetradentate imine-type ligand H2L that incorporates a dansyl fluorophore group in both ligand arms. Two binding domains separated by a short arene spacer and two bulky arms with an anti conformation make this organic molecule suitable as precursor of metallosupramolecular species such as helicates. The molecular structure of H2L has been analyzed by X-ray diffraction. This technique has revealed the formation of intermolecular hydrogen bond interactions that lead to the supramolecular self-assembly of ligand molecules in the solid state and the generation of oval-shaped channels in the 3D crystal packin

Perspectives of Therapeutic Drug Monitoring of Biological Agents in Non-Infectious Uveitis Treatment: A Review

Biological drugs, especially those targeting anti-tumour necrosis factor alpha (TNF alpha) molecule, have revolutionized the treatment of patients with non-infectious uveitis (NIU), a sight-threatening condition characterized by ocular inflammation that can lead to severe vision threatening and blindness. Adalimumab (ADA) and infliximab (IFX), the most widely used anti-TNF alpha drugs, have led to greater clinical benefits, but a significant fraction of patients with NIU do not respond to these drugs. The therapeutic outcome is closely related to systemic drug levels, which are influenced by several factors such as immunogenicity, concomitant treatment with immunomodulators, and genetic factors. Therapeutic drug monitoring (TDM) of drug and anti-drug antibody (ADAbs) levels is emerging as a resource to optimise biologic therapy by personalising treatment to bring and maintain drug concentration within the therapeutic range, especially in those patients where a clinical response is less than expected. Furthermore, some studies have described different genetic polymorphisms that may act as predictors of response to treatment with anti-TNF alpha agents in immune-mediated diseases and could be useful in personalising biologic treatment selection. This review is a compilation of the published evidence in NIU and in other immune-mediated diseases that support the usefulness of TDM and pharmacogenetics as a tool to guide clinicians' treatment decisions leading to better clinical outcomes. In addition, findings from preclinical and clinical studies, assessing the safety and efficacy of intravitreal administration of anti-TNF alpha agents in NIU are discussed

Design, optimization, and in vitro characterization of idebenone-loaded PLGA microspheres for LHON treatment

Biodegradable poly(lactic-co-glycolic acid) microspheres (PLGA MSs) are attractive delivery systems for site-specific maintained release of therapeutic active substances into the intravitreal chamber. The design, development, and characterization of idebenone-loaded PLGA microspheres by means of an oil-in-water emulsion/solvent evaporation method enabled the obtention of appropriate production yield, encapsulation efficiency and loading values. MSs revealed spherical shape, with a size range of 10–25 μm and a smooth and non-porous surface. Fourier-transform infrared spectroscopy (FTIR) spectra demonstrated no chemical interactions between idebenone and polymers. Solid-state nuclear magnetic resonance (NMR), X-ray diffractometry, differential scanning calorimetry (DSC) and thermogravimetry (TGA) analyses indicated that microencapsulation led to drug amorphization. In vitro release profiles were fitted to a biexponential kinetic profile. Idebenone-loaded PLGA MSs showed no cytotoxic effects in an organotypic tissue model. Results suggest that PLGA MSs could be an alternative intraocular system for long-term idebenone administration, showing potential therapeutic advantages as a new therapeutic approach to the Leber's Hereditary Optic Neuropathy (LHON) treatment by intravitreal administrationThis research was partially supported by the Spanish Ministry of Science, Innovation and Universities (RTI2018-099597-B-100)S

Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging

Aging is characterized by a gradual functional decline of tissues with age. Adult stem and progenitor cells are responsible for tissue maintenance, repair, and regeneration, but during aging, this population of cells is decreased or its activity is reduced, compromising tissue integrity and causing pathologies that increase vulnerability, and ultimately lead to death. The causes of stem cell exhaustion during aging are not clear, and whether a reduction in stem cell function is a cause or a consequence of aging remains unresolved. Here, we took advantage of a mouse model of induced adult Sox2+ stem cell depletion to address whether accelerated stem cell depletion can promote premature aging. After a short period of partial repetitive depletion of this adult stem cell population in mice, we observed increased kyphosis and hair graying, and reduced fat mass, all of them signs of premature aging. It is interesting that cellular senescence was identified in kidney after this partial repetitive Sox2+ cell depletion. To confirm these observations, we performed a prolonged protocol of partial repetitive depletion of Sox2+ cells, forcing regeneration from the remaining Sox2+ cells, thereby causing their exhaustion. Senescence specific staining and the analysis of the expression of genetic markers clearly corroborated that adult stem cell exhaustion can lead to cellular senescence induction and premature agingWork in the laboratory of M.C. is funded by an ISCIII and EU‐FEDER grant (PI14/00554)S

Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop

Uveitis is a vision inflammatory disorder with a high prevalence in developing countries. Currently, marketed treatments remain limited and reformulation is usually performed to obtain a tacrolimus eye drop as a therapeutic alternative in corticosteroid-refractory eye disease. The aim of this work was to develop a mucoadhesive, non-toxic and stable topical ophthalmic formulation that can be safely prepared in hospital pharmacy departments. Four different ophthalmic formulations were prepared based on the tacrolimus/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes’ formation. Phase solubility diagrams, Nuclear Magnetic Resonance (NMR) and molecular modeling studies showed the formation of 1:1 and 1:2 tacrolimus/HPβCD inclusion complexes, being possible to obtain a 0.02% (w/v) tacrolimus concentration by using 40% (w/v) HPβCD aqueous solutions. Formulations also showed good ophthalmic properties in terms of pH, osmolality and safety. Stability studies proved these formulations to be stable for at least 3 months in refrigeration. Ex vivo bioadhesion and in vivo ocular permanence showed good mucoadhesive properties with higher ocular permanence compared to the reference pharmacy compounding used in clinical settings (t1/2 of 86.2 min for the eyedrop elaborated with 40% (w/v) HPβCD and Liquifilm® versus 46.3 min for the reference formulation). Thus, these novel eye drops present high potential as a safe alternative for uveitis treatment, as well as a versatile composition to include new drugs intended for topical ophthalmic administrationThis research was partially supported by the Spanish Ministry of Science, Innovation and Universities (RTI2018-099597-B-100), the ISCIII (PI17/00940, RETICS Oftared, RD16/0008/0003 and RD12/0034/0017) and by Xunta de Galicia, grant numbers GPC2013/015 and GRC2017/015S

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics

Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit–risk balance and, consequently, patients’ quality of lifeThis project was partially supported by Fundación Española de Farmacia Hospitalaria “Convocatoria de ayudas de proyectos para grupos de trabajo de la SEFH 2021-2022”, Plan Galego de Saude Mental (SERGAS) and Axencia Galega Innovación (Grupos de Potencial Crecimiento IN607B2020/11). Bandín-Vilar E.: Mondelo-García C. and Fernández-Ferreiro A. are grateful to the Carlos III Health Institute for financing their personnel contracts: CM20/00135, JR20/00026 and JR18/00014S

Slavery and the african cultural legacy in the Caribbean

Con autorización de la editorial para este libro.[EN] The purpose of this book is to raise awareness among a wide audience of one of the most significant and shameful phenomena for humanity, as was the enslavement of over twelve and a half million Africans who were brought to America and forced to work and live as slaves. Many countries participated in the slave trade at different times and withvaried intensity (Great Britain, Portugal, France, Spain, Denmark, Netherlands, Germany, United States...).[ES] El propósito de esta obra es dar a conocer a un público amplio uno de los fenómenos de mayor trascendencia y vergüenza para la humanidad como fue la esclavización de más de doce millones y medio de africanos que fueron trasladados a América, obligados a trabajar y vivir como esclavos. Muchos países participaron en la trata de esclavos en distintos momentos y con diferente intensidad (Gran Bretaña, Portugal, Francia, España, Dinamarca, Países Bajos, Alemania, Estados Unidos…).Connected Worlds: The Caribbean, Origin of Modern World. This project has received funding from the European Union´s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement Nº 823846. This project is directed by professor Consuelo Naranjo Orovio, Institute of History-CSIC.Peer reviewe

VI Encontro da Mocidade Investigadora: Libro de resumos

Libro de resumos correspondentes ás presentacións durante o VI Encontro da Mocidade Investigadora - CienciasUniversidade de Santiago de Compostela. Centro Internacional de Estudos de Doutoramento e Estudos Avanzado