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Authors contribution: Hanfei Wang: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Conceptualization. Yingying Yang: Writing – original draft, Visualization, Supervision, Investigation, Formal analysis, Conceptualization. Simeng Wang: Writing – original draft, Methodology, Investigation, Formal analysis, Conceptualization. Sara Badawy: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Conceptualization. Irma Ares: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Conceptualization. Marta Martínez: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Conceptualization. Bernardo Lopez-Torres: Writing – original draft, Visualization, Supervision, Methodology, Investigation, Formal analysis, Conceptualization. María-Rosa Martínez-Larranaga: ˜ Writing – original draft, Visualization, Supervision, Methodology, Investigation, Formal analysis, Conceptualization. Xu Wang: Writing – review & editing, Writing – original draft, Visualization, Supervision, Project administration, Methodology, Investigation, Formal analysis, Conceptualization. Arturo Anadon: ´ Writing – review & editing, Writing – original draft, Supervision, Project administration, Investigation, Conceptualization. María-Aranzazu ´ Martínez: Writing – review & editing, Writing – original draft, Validation, Supervision, Project administration, Methodology, Investigation, Formal analysis, Conceptualization., The resistance of multidrug-resistant bacteria to existing antibiotics forces the continued development of new antibiotics and antibacterial agents, but the high costs and long timeframe involved in the development of new agents renders the hope that existing antibiotics may again play a part. The “antibiotic adjuvant” is an indirect antibacterial strategy, but its vague concept has, in the past, limited the development speed of related drugs. In this review article, we put forward an accurate concept of a “non-self-antimicrobial sensitisers (NSAS)”, to distinguish it from an “antibiotic adjuvant”, and then discuss several scientific methods to restore bacterial sensitivity to antibiotics, and the sources and action mechanism of existing NSAS, in order to guide the development and further research of NSAS., Major Special Science and Technology Plan (202302AA310020), National Natural Science Foundation of China (NSFC) (32072925), Project Ref. PID2020-115979RR-C33 from Ministerio de Ciencia e Innovación, Spain (Project/AEI/10.13039/501100011033), Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

A lo largo de varias ediciones, el proyecto de innovación docente Espacio NEWSHUB ha tratado de ser un punto de encuentro académico y profesional. En entregas anteriores, se presentó como una solución para cubrir necesidades específicas de formación tanto para el profesorado como para el alumnado en materia de comunicación. En ese sentido, ha servido para diseñar actividades de aprendizaje basadas en proyectos orientadas a generar productos comunicativos de calidad profesional, que sirvan a un tiempo como herramienta eficiente de aprendizaje en el entorno académico además de recurso destacado en el portfolio del alumnado para la búsqueda de empleo o la formalización de proyectos emprendedores Ha funcionado igualmente como incubadora de proyectos. Con esta orientación, ha buscado rediseñar las actividades y prácticas de clase para que se ajusten a una aplicación eficaz de la metodología de aprendizaje basado en proyectos. Al tiempo, se ha ofrecido asesoría y acompañamiento a docentes y estudiantes para que desarrollen su actividad académica integrando estrategias y procesos de calidad propios del ámbito profesional. En todo momento, se ha buscado compartir con la comunidad educativa contenidos formativos sobre comunicación, gracias a recursos abiertos, como una web que agrupa materiales del proyecto. Por otro lado, este proyecto de innovación docente tiene una vertiente tecnológica muy importante. Se ha tratado de ir construyendo un notable arsenal de materiales y herramientas para edición de contenidos audiovisuales y digitales. Todo ese material, incluyendo un espacio físico dotado de un pequeño plató de grabación, está a disposición de la comunidad educativa. Así, en esta edición del proyecto, se ha querido ampliar esta dimensión física, ampliando la dotación tecnológica y ofreciendo mejores herramientas a profesores y estudiantes. Aunque no se ha logrado la ayuda económica solicitada, se han hecho avances en este sentido y, hoy, el Espacio NewsHub es una referenc

El objetivo del proyecto es la mejora de la enseñanza virtual a los alumnos del Grado en Farmacia mediante la realización de diversos recursos educativos abiertos virtuales, como vídeos o cuestionarios, que faciliten el aprendizaje.

Natamycin is a polyene macrolide antibiotic widely used in the food industry as a feed additive to prevent mold contamination of foods. There are many contradictory results on the genotoxic effects of macrolides which could suggest a potential risk for humans. In the present study, the effects of natamycin on the activities of some drug metabolizing enzymes in rat liver microsomes were determined in vivo. Rats were treated orally with natamycin at doses of 0.3, 1, 3 and 10 mg/kg body weight (bw)/day for 6 days. Determinations of cytochrome P450 (CYP) enzyme activities were carried out in hepatic microsomes isolated from rats treated. The activities of CYP2E1, CYP1A1/2 CYP2B1/2 and CYP4A1/2 enzymes significantly decreased after treatment with 1, 3 and 10 mg/kg bw/day, in a dose-dependent manner as compared to control. This effect was not observed after natamycin treatment at dose of 0.3 mg/kg bw/day. Our results suggest that natamycin may not potentiate the toxicity of many xenobiotics via metabolic activation and/or accumulation of reactive metabolites but also might affect the clearance of other xenobiotics detoxified by the studied CYP enzymes., Universidad Complutense de Madrid, Comunidad de Madrid, Ministerio de Educación y Ciencia (MEC). España, Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

Chickens were used to investigate plasma disposition of florfenicol after single intravenous (i.v.) and oral dose (20 mg kg-1 body weight) and to study residue depletion of florfenicol and its major metabolite florfenicol-amine after multiple oral doses (40 mg kg-1 body weight, daily for 3 days). Plasma and tissue samples were analyzed using a high-performance liquid chromatography (HPLC) method. After i.v. and oral administration, plasma concentration-time curves were best described by a two-compartment open model. The mean [ +/- standard deviation (SD)] elimination half-life (t1/2beta) of florfenicol in plasma was 7.90 +/- 0.48 and 8.34 +/- 0.64 h after i.v. and oral administration, respectively. The maximum plasma concentration was 10.23 +/- 1.67 microg mL-1, and the interval from oral administration until maximal concentration was 0.63 +/- 0.07 h. Oral bioavailability was found to be 87 +/- 16%. Florfenicol was converted to florfenicol-amine. After multiple oral dose (40 mg kg-1 body weight, daily for 3 days), in kidney and liver, concentrations of florfenicol (119.34 +/- 31.81 and 817.34 +/- 91.65 microg kg-1, respectively) and florfenicol-amine (60.67 +/- 13.05 and 48.50 +/- 13.07 microg kg-1, respectively) persisted for 7 days. The prolonged presence of residues of florfenicol and florfenicol-amine in edible tissues can play an important role in human food safety, because the compounds could give rise to a possible health risk. A withdrawal time of 6 days was necessary to ensure that the residues of florfenicol were less than the maximal residue limits or tolerance established by the European Union., Comunidad de Madrid, Ministerio de Educación y Ciencia, Consolider-Ingenio 2010, Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

Credit author statement: Xiaoqing Xu, Yixin Yu, Min Ling, Irma Ares, Marta Martínez, Bernardo Lopez-Torres, Jorge-Enrique Maximiliano, María-Rosa MartínezLarranaga: ˜ Conceptualization, Methodology, Investigation, Data curation, Writing - original draft, Visualization. Xu Wang, Arturo Anadon and María-Aranzazu ´ Martínez: Conceptualization, Supervision, Writing – original draft, Writing – review & editing, Project administration. All authors have approved the final version of this manuscript., Lambda-cyhalothrin, also known as cyhalothrin, is an efficient, broad-spectrum, quick-acting pyrethroid insecticide and acaricide and the most powerful pyrethroid insecticide in the world. However, there is increasing evidence that lambda-cyhalothrin is closely related to a variety of toxicity drawbacks (hepatotoxicity, nephrotoxicity, neurotoxicity and reproductive toxicity, among others) in non-target organisms, and oxidative stress seems to be the main mechanism of toxicity. This manuscript reviews the oxidative and mitochondrial damage induced by lambda-cyhalothrin and the signalling pathways involved in this process, indicating that oxidative stress occupies an important position in lambda-cyhalothrin toxicity. The mechanism of antioxidants to alleviate the toxicity of lambda-cyhalothrin is also discussed. In addition, the metabolites of lambda-cyhalothrin and the major metabolic enzymes involved in metabolic reactions are summarized. This review article reveals a key mechanism of lambda-cyhalothrin toxicity-oxidative damage and suggests that the use of antioxidants seems to be an effective method for preventing toxicity., Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

We attempted to identify cellular mechanisms as an approach to screen chemicals for the potential to cause developmental neurotoxicity. We examine, in SH-SY5Y cells, whether apoptosis and oxidative stress via reactive oxygen species (ROS) generation, caspase 3/7 activation, gene expression (Bax, Bcl-2, Casp-3, BNIP3, p53 and Nrf2) alterations and necrosis by release of cytosolic adenylate kinase (AK), underlie direct effects of the pyrethroids cyfluthrin and alpha-cypermethrin. We also determined transcriptional alterations of genes (TUBB3, NEFL, NEFH, GAP43, CAMK2A, CAMK2B, WNT3A, WNT5A, WNT7A, SYN1 and PIK3C3) linked to neuronal development and maturation. Our results indicate that cyfluthrin and alpha-cypermethrin have the ability to elicit concentration-dependent increases in AK release, cellular ROS production, caspase 3/7 activity and gene expression of apoptosis and oxidative stress mediators. Both pyrethroids caused changes in mRNA expression of key target genes linked to neuronal development. These changes might reflect in a subsequent neuronal dysfunction. Our study shows that SH-SY5Y cell line is a valuable in vitro model for predicting development neurotoxicity. Our research provides evidence that cyfluthrin and alpha-cypermethrin have the potential to act as developmental neurotoxic compounds. Additional information is needed to improve the utility of this in vitro model and/or better understand its predictive capability., Ministerio de Economía, Industria y Competitividad, Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

The effects of cyfluthrin oral exposure (1, 5, 10 and 20mg/kg bw, 6 days) on brain region monoamine levels of male rats were examined. Cyfluthrin-treated rats (1, 5 and 10mg/kg bw, orally 6 days), had no visible injury, i.e., no clinical signs of dysfunction were observed. However, rats treated with cyfluthrin at the highest dose (20mg/kg bw, orally 6 days) showed skeletal muscle contraction in the hind limbs, slight movement incoordination without any signs of dyskinesia and tremor after 1-2h of treatment. These signs were reversible at 6h after dose. After last dose of cyfluthrin, dopamine (DA) and serotonin (5-HT) and its metabolites levels were determined in brain regions hypothalamus, midbrain, hippocampus, striatum and prefrontal cortex by HPLC. Cyfluthrin (1mg/kg bw, orally 6 days) did not affect the DA, 5-HT and metabolites levels in the brain regions studied. Cyfluthrin (5, 10 and 20mg/kg bw, orally 6 days) caused a statistically significant decrease in DA and its metabolites DOPAC and HVA levels and in 5-HT and its metabolite 5-HIAA levels in a brain region- and dose-related manner. Moreover, cyfluthrin (20mg/kg bw, orally 6 days) evoked a statistically significant increase in 5-HT turnover in striatum and midbrain, and in DA turnover in striatum and prefrontal cortex. These findings indicate that serotoninergic and dopaminergic neurotransmission is affected by exposure to cyfluthrin and may contribute to the overall spectrum of neurotoxicity caused by this pyrethroid, Universidad Complutense de Madrid, Comunidad de Madrid, Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

All authors contributed in performing data curation, investigation, validation, and writing original draft. Xu Wang, Arturo Anadon and María-Aranzazu Martínez were responsible for critically reading the manuscript, revision the original draft, review and editing. All authors read and approved the final version of the manuscript., Conjugated linoleic acid (CLA) has attracted great attention in recent years as a popular class of functional food that is broadly used. It refers to a group of geometric and positional isomers of linoleic acid (LA) with a conjugated double bond. The main natural sources of CLA are dairy products, beef and lamb, whereas only trace amounts occur naturally in plant lipids. CLA has been shown to improve various health issues, having effects on obesity, inflammatory, anti-carcinogenicity, atherogenicity, immunomodulation, and osteosynthesis. Also, compared to studies on humans, many animal researches reveal more positive benefits on health. CLA represents a nutritional avenue to improve lifestyle diseases and metabolic syndrome. Most of these effects are attributed to the two major CLA isomers [conjugated linoleic acid cis-9,trans-11 isomer (c9,t11), and conjugated linoleic acid trans-10,cis-12 isomer (t10,c12)], and their mixture (CLA mix). In contrast, adverse effects of CLA have been also reported, such as glucose homeostasis, insulin resistance, hepatic steatosis and induction of colon carcinogenesis in humans, as well as milk fat inhibition in ruminants, lowering chicken productivity, influencing egg quality and altering growth performance in fish. This review article aims to discuss the health benefits of CLA as a nutraceutical supplement and highlight the possible mechanisms of action that may contribute to its outcome. It also outlines the feasible adverse effects of CLA besides summarizing the recent peer-reviewed publications on CLA to ensure its efficacy and safety for proper application in humans., Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

Glyphosate (GLYP) is a widely used pesticide; it is considered to be a safe herbicide for animals and humans because it targets 5-enolpyruvylshikimate-3-phosphate synthase. However, there has been increasing evidence that GLYP causes varying degrees of toxicity. Moreover, oxidative stress and metabolism are highly correlated with toxicity. This review provides a comprehensive introduction to the toxicity of GLYP and, for the first time, systematically summarizes the toxicity mechanism of GLYP from the perspective of oxidative stress, including GLYP-mediated oxidative damage, changes in antioxidant status, altered signaling pathways, and the regulation of oxidative stress by exogenous substances. In addition, the metabolism of GLYP is discussed, including metabolites,metabolic pathways, metabolic enzymes, and the toxicity of metabolites. This review provides new ideas for the toxicity mechanism of GLYP and proposes effective strategies for reducing its toxicity., Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

Authorship contribution statement: Jorge-Enrique Maximiliano: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Irma Ares: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Marta Martínez: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Bernardo Lopez-Torres: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. María-Rosa Martínez-Larranaga: ˜ Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Arturo Anadon: ´ Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. María-Aranzazu ´ Martínez: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization., The monoaminergic systems dopamine (DA) and serotonin (5-HT) play important roles in neuromodulation, such as motor control, cognitive, affective, and neuroendocrine functions. In the present research study, we addressed the hypothesis that exposure to Type I pyrethroid tefluthrin may specifically target the dopaminergic and serotoninergic systems. Tefluthrin could modify brain monoamine neurotransmitters, DA and 5-HT levels as well as dopaminergic and serotoninergic signaling pathways. Adult male Wistar rats were treated with tefluthrin [2.2, 4.4 and 5.5 mg/kg bw, equivalent to 1/10, 1/5 and 1/4 of the acute oral rat lethal dose 50 (LD50) value] by oral gavage, six days. After last dose of tefluthrin, DA and 5-HT and metabolites levels were determined in brain regions (striatum, hippocampus, prefrontal cortex and hypothalamus). Tefluthrin induced a decrease of DA, 5-HT and metabolites contents, in a brain regional- and dose-related manner. The major decreases in DA and 5-HT contents were observed in prefrontal cortex tissue. Here, we studied that in vivo exposure to tefluthrin may alter DA and 5-HT neurotransmission in prefrontal cortex. Transcripts related to (i) dopaminergic [dopamine transporter 1 (Dat1), tyrosine hydroxylase (TH), dopamine receptors (Drd1, Drd2)], (ii) serotoninergic [serotonin transporter (SERT), tryptophan hydroxylase 2 (TPH2), serotonin receptors (5-HT1A, 5-HT2A)] and (iii) DA and 5-HT degradation [monoamine oxidases (MAOA, MAOB)] signaling pathways were investigated. Results showed that tefluthrin induced down-regulation of transcripts responsible for the synthesis and action of DA (TH, Drd1, Drd2) and 5-HT (SERT, TPH2). In contrast, tefluthrin treatment induced up-regulation of genes involved in DA transporter (Dat1), 5-HT receptors (5-HT1A, 5-HT2A) and monoamine oxidases (MAOA, MAOB). Given the integral roles of mitochondrial dysfunction and dopaminergic and serotoninergic alterations as hallmarks of neurodegenerative diseases, our data s, Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

Chloramine-T is an antimicrobial agent recognized for its disinfectant properties widely used in food industry. As an N-chloro-compound, chloramine-T contains electrophilic chlorine and in water it hydrolyses to hypochlorite. Chlorine as hypochlorous acid or hypochlorite is a very reactive chemical which can function as both an oxidant and halogenating agent. Because chloramine-T could be involved in the metabolic activation of drugs, in the present study the effects of chloramine-T on the activities of some drug metabolizing enzymes in rat liver microsomes and peroxisome proliferation were determined in vivo. Rats were treated orally with chloramine-T at doses of 1.25, 2.50, 5 and 10 mg/kg body weight (bw)/day for 6 days. The activities of CYP2E1, CYP1A1/2 CYP2B1/2, CYP3A4 and CYP4A1/2 enzymes significantly increased after treatment with 2.50, 5 and 10 mg/kg bw/day, in a dose-dependent manner as compared to control. This effect was not observed after chloramine-T treatment at dose of 1.25 mg/kg bw/day. Our results suggest that chloramine-T may potentiate the toxicity of many xenobiotics via metabolic activation and/or accumulation of reactive metabolites, Comunidad de Madrid, Ministerio de Economía y Competitividad (España), Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

The effects of glyphosate oral exposure (35, 75, 150 and 800 mg/kg bw, 6 days) on brain region monoamine levels of male Wistar rats were examined. Glyphosate-treated rats (35, 75, 150 and 800 mg/kg bw, 6 days), had no visible injury, i.e., no clinical signs of dysfunction were observed. After last dose of glyphosate, serotonin (5-HT), dopamine (DA) and norepinephrine (NE) and its metabolites levels were determined in the brain regions striatum, hippocampus, prefrontal, cortex, hypothalamus and midbrain, by HPLC. Glyphosate caused statistically significant changes in the 5-HT and its metabolite 5-hydroxy-3-indolacetic acid (5-HIAA), DA and its metabolites 3,4-hydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and NE and its metabolite 3-metoxy-4-hydroxyphenylethyleneglycol (MHPG) levels in a brain regional- and dose-related manner. Moreover, glyphosate, dose-dependent, evoked a statistically significant increase in 5-HT turnover in striatum and hypothalamus and in DA turnover in prefrontal cortex and hippocampus, and a statistically significant decrease in NE turnover in prefrontal cortex and hypothalamus. The present findings indicate that glyphosate significantly altered central nervous system (CNS) monoaminergic neurotransmitters in a brain regional- and dose-related manner, effects that may contribute to the overall spectrum of neurotoxicity caused by this herbicide., Comunidad de Madrid, Ministerio de Economía y Competitividad (España), Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

Chickens were used to investigate plasma disposition of chlortetracycline after single IV (15 mg/kg) and multiple oral administration (60 mg/kg, 5 days) and residue depletion of chlortetracycline after multiple oral doses (60 mg/kg, 5 days). Plasma and tissue samples were analyzed by HPLC. Mean elimination half-lives in plasma were 7.96 and 13.15 h after IV and multiple oral administration. Maximum plasma concentration was 4.33 lg/ml and the interval from oral administration until maximal concentration was 1.79 h. Oral bioavailability was 17.76%. After multiple oral dose, mean kidney, liver and muscle tissue concentrations of chlortetracycline + 4-epi-chlortetracycline of 835.3, 192.7, and 126.3 ug/kg, respectively, were measured 1 day after administration of the final dose of chlortetracycline. Chlortetracycline residues were detected in kidney and liver (205.4 and 81.7 ug/kg, respectively), but not in muscle, 3 days after the end of chlortetracycline treatment. The mean chlortetracycline + 4-epi-chlortetracycline concentrations were below LOQ at 3 and 5 days after cessation of medication in muscle and liver, respectively. A withdrawal time of 3 days was necessary to ensure that the chlortetracycline residues were less than the maximal residue limits (MRLs) established by the European Union (100, 300, and 600 ug/kg in muscle, liver, and kidney, respectively)., Universidad Complutense de Madrid, Comunidad de Madrid, Ministerio de Educación y Ciencia, Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

Chickens were used to investigate kinetic properties including metabolism of flumequine after single IV and oral dose, and to study tissue depletion of flumequine after multiple oral doses. Plasma and tissue (muscle, kidney, liver and skin plus fat) concentrations of flumequine and its metabolite 7-hydroxyflumequine were determined using a HPLC method. After IV and oral administration (single-dose of 12 mg flumequine/kg bw), plasma concentration-time curves were best described by a two-compartment open model. Elimination half-life and mean residence time of flumequine in plasma were 6.91 and 5.90 h, respectively, after IV administration and 10.32 and 8.95 h after oral administration. Maximum plasma concentration was 3.62 microg/ml and interval from oral administration until maximum concentration was 1.43 h. Oral bioavailability was found to be 57%. Flumequine was converted to 7-hydroxyflumequine. After oral administration (24 mg/kg bw every 24 h for 5 days), renal and hepatic concentrations of flumequine (18-25 microg/kg) persisted for 4 days; however, at that time, flumequine residues were not detected in skin plus fat and muscle tissues. Flumequine administered at a dosage of 24 mg/kg bw every 24h for 5 days, with a withdrawal time of 2d ays, resulted in flumequine concentrations in target tissues that were less than the European Union maximal residue limits., Comisión Interministerial de Ciencia y Tecnología, Programa Nacional de Investigación y Desarrollo Farmacéutico, Comunidad de Madrid, Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

The toxicokinetics of lambda-cyhalothrin after single 20 mg kg(-1) oral and 3 mg kg(-1) intravenous doses were studied in rats. Serial blood samples were obtained after oral and intravenous administration. Liver, brain, spinal cord, sciatic nerve, vas deferens, anococcygeus and myenteric plexus tissue samples were also collected. Plasma, liver, hypothalamus, cerebellum, medulla oblongata, frontal cortex, striatum, hippocampus, midbrain, spinal cord, vas deferens, anococcygeus, myenteric plexus and sciatic nerve concentrations of lambda-cyhalothrin were determined by HPLC. The plasma and tissue concentration-time data for lambda-cyhalothrin were found to fit a two-compartment open model. For lambda-cyhalothrin, the elimination half-life (T1/2beta) and the mean residence time from plasma were 7.55 and 8.55 h after i.v. and 10.27 and 14.43 h after oral administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.060l h(-1)kg(-1). After i.v. administration, the apparent volume of distribution and at steady state were 0.68 and 0.53l kg(-1), suggesting a diffusion of the pyrethroid into tissue. After oral administration, lambda-cyhalothrin was extensively but slowly absorbed (Tmax, 2.69 h). The oral bioavailability was found to be 67.37%. Significant differences in the kinetic parameters between nervous tissues and plasma was observed. The maximum concentrations in hypothalamus (Cmax, 24.12 microg g(-1)) and myenteric plexus (Cmax, 25.12 microg g(-1)) were about 1.5 times higher than in plasma (Cmax, 15.65 microg ml(-1)) and 1.3 times higher than in liver (Cmax, 18.42 microg ml(-1)). Nervous tissue accumulation of lambda-cyhalothrin was also reflected by the area under the concentration curve ratios of tissue/plasma (liver). The T1/2beta for lambda-cyhalothrin was significantly greater for the nerve tissues, including neuromuscular fibres, (range 12-26 and 15-34 h, after i.v. and oral doses) than for plasma (7.55 an, Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

Aflatoxin B1 (AFB1), fumonisin B1 (FB1), ochratoxin A (OTA) and T-2 toxin (T2) are mycotoxins that commonly contaminate the food chain and cause various toxicological effects. Their global occurrence is regarded as an important risk factor for human and animal health. In this study, the results demonstrate that, in human Caco-2 cells, AFB1, FB1, OTA and T2 origin cytotoxic effects, determining cell viability through MTT assay and LDH leakage, and decrease trans-epithelial electrical resistance (TEER). The decrease in barrier properties is concomitant with a reduction in the expression levels of the tight junction constituents claudin-3, claudin-4 and occludin. The protective effect of mineral clays (diosmectite, montmorillonite and illite) on alterations in cell viability and epithelial barrier function induced by the mycotoxins was also evaluated. Illite was the best clay to prevent the mycotoxin effects. Illite plus mycotoxin co-treatment completely abolished AFB1 and FB1-induced cytotoxicity. Also, the decreases in the gene expression of claudins and the reduction of TEER induced by mycotoxins were reversed by the illite plus mycotoxin co-treatment. In conclusion, these results demonstrated that mycotoxins AFB1, FB1, T2 and OTA disrupt the intestinal barrier permeability by a mechanism involving reduction of claudin isoform expressions, and illite counteracts this disruption., Universidad Complutense de Madrid, Comunidad de Madrid, Depto. de Farmacología y Toxicología, Fac. de Veterinaria, TRUE, pub

In Classical Antiquity, where theatre was an exclusively male sphere, there was a gender split: a male playwright wrote a female character, giving her a conventionalised speech in order to project, from a masculine perspective, the idea of femininity predominating in society. This character was later performed by a male actor, who embraced the contradiction of said female character showing a negative vision of patriarchal society. This article analyses a staging with a contemporary aesthetics, Prometeo (2010) by Carme Portaceli, and another one with a timeless aesthetics, Antígona (2015) by Miguel del Arco. In particular, emphasis is placed on studying the transgression of the dramatic conventions about gender in Greek tragedy, as well as the dramaturgical transformation of male characters into female ones, to observe what happens nowadays, and what is intended to be communicated on stage, when there are women playing traditionally masculine roles. This gender perspective can be used to modernise tragedy by adding a feminist and vindictive lens, as in Prometeo, or else the main character can be feminised in order to reformulate the gender conflict, underlining other ones, as in Antígona., En la Antigüedad clásica, donde el teatro era un ámbito masculino, se producía un desdoblamiento de género: un dramaturgo varón escribía un personaje femenino, con un discurso convencionalizado para reflejar, desde una perspectiva masculina, la idea de la feminidad imperante en la sociedad. Dicho personaje era luego interpretado por un actor varón, que abrazaba la contradicción de que dicho personaje femenino proyectara una visión negativa de la sociedad patriarcal. En este artículo se analiza un montaje de estética contemporánea, Prometeo (2010) de Carme Portaceli, y otro de ambientación atemporal, Antígona (2015) de Miguel del Arco. Se estudia, en particular, la transgresión de las convenciones dramáticas sobre género en la tragedia griega, y la transformación dramatúrgica de personajes masculinos en personajes femeninos, para observar qué sucede en la actualidad, y qué se quiere transmitir desde el escenario, cuando hay mujeres interpretando papeles tradicionalmente masculinos. Puede usarse esta perspectiva de género para actualizar la tragedia introduciendo una lente feminista reivindicativa, como en Prometeo, o se puede feminizar el personaje para reformular, como en Antígona, el conflicto de género, subrayando otros.

Creación de nuevo recurso educativo virtual para estudiantes de grado en Farmacia. El presente proyecto es continuación de un proyecto concedido con financiación el año 2019 y en él se continuarán desarrollando nuevos recursos educativos virtuales como los que ya se han hecho este curso, y que han tenido excelente acogida por los alumnos, para facilitar la adquisición del conocimiento de los estudiantes de Farmacia especialmente de aquellos temas en los que la bibliografía disponible es escasa como en el caso de la Asignatura de Tecnología Farmacéutica III en los temas dedicados a la industria farmacéutica.

NEWSHUB es un espacio de encuentro académico y profesional. Su principal función es cubrir necesidades específicas de formación tanto para el profesorado como para el alumnado en materia de comunicación. La finalidad es facilitar que se diseñen actividades de aprendizaje basado en proyectos orientadas a generar productos comunicativos de calidad profesional, que sirvan a un tiempo como herramienta eficiente de aprendizaje en el entorno académico además de recurso destacado en el portfolio del alumnado para la búsqueda de empleo o la formalización de proyectos emprendedores. Asímismo, nuestro grupo es una incubadora de proyectos en el que rediseñamos actividades y prácticas de clase para que se ajusten a una aplicación eficaz de la metodología de aprendizaje basado en proyectos. Ofrecemos asesoría y acompañamiento a docentes y estudiantes para que desarrollen su actividad académica integrando estrategias y procesos de calidad propios del ámbito profesional. Como plataforma de formación ponemos contenidos formativos sobre comunicación eficiente a disposición de la comunidad educativa e investigadora y del sector de la orientación laboral y el fomento del emprendimiento. Ofrecemos recursos educativos abiertos a través de una plataforma web modular, interoperable y accesible, que alberga contenidos digitales de producción propia y un banco de buenas prácticas. Intentamos servir como plataforma de coaching digital. Con la irrupción de la Inteligencia Artificial los profesores tenemos que adaptar nuestra manera de enseñar y de aprender entendiendo e incorporando las nuevas tecnologías en nuestra docencia. Para ello acompañaremos a los docentes y contaremos con la opinión directa de los alumnos/as que participan en nuestro proyecto. Además, dada el área de Tecnología de la Información que comparten la mayor parte de los profesores que formamos NEWSHUB creemos necesario ayudar mediante esta plataforma a nuestros compañeros en su formación tecnológica mediante la impartición

Little is known about feeding and eating disorders (FED) in the community of Latino origin in the Caribbean. The purpose of this study is to identify the published research on the FED with the Spanish-speaking Latino population from the Caribbean islands. The narrative systemic review was focused on Cuba, Dominican Republic, and Puerto Rico. For the narrative systematic review, we used the Covidence program in eight databases (i.e., PubMed, Scopus, Scielo, LILACS, Global Health, CINAHL, Psych Info, REDIB) using the Preferred reporting items for systematic review and meta-analyses-PRISMA guidelines. We used the keywords in both languages Spanish and English (i.e., eating disorders, anorexia nervosa, bulimia nervosa, binge eating disorder, disordered eating), combined with keywords for the identification of the Caribbean geographic area (i.e., Caribbean, Dominican Republic, Cuba, Puerto Rico, Latinos, Latinas, Latinxs) for the literature search. Out of 398 articles, 13 articles were included in the final review (Cuba n=4; Puerto Rico n=8; combined Cuba, Puerto Rico and Dominican Republic, n=1). Published topics include prevalence of FED in youth, college students, and gay men, and body image, bigorexia, scale development for orthorexia, genetic factors, and the role of the family in the treatment of FED., Poco conocemos sobre los trastornos de la ingesta y de la conducta alimentaria (TICA) en la comunidad de origen latino en el Caribe. El propósito de este estudio es documentar los trabajos publicados sobre el TICA con población latina hispanoparlante en el Caribe. La revisión narrativa sistemática estuvo centrada en Cuba, Puerto Rico y República Dominicana. Para la revisión, utilizamos el programa Covidence en ocho bases de datos (p.ej. PubMed, Scopus, Scielo, LILACS, Global Health, CINAHL, Psych Info, REDIB) usando las guías “Preferred reporting items for systematic reviews and meta‐analyses” (PRISMA). Identificamos los artículos con palabras clave en español e inglés (p.ej. trastornos de la conducta alimentaria, anorexia nerviosa, bulimia nerviosa, trastorno por atracón, trastornos alimentarios, desórdenes alimentarios), combinado con palabras clave para la identificación de la zona geográfica del Caribe (p.ej. Caribe, República Dominicana, Cuba, Puerto Rico, latinos, latinas, latinxs). De 398 artículos revisados, 13 artículos se incluyeron en la revisión final (Cuba n=4; Puerto Rico n= 8; Combinado, Cuba, Puerto Rico y República Dominicana n=1). Los temas incluyen: prevalencia de conductas de TICA en jóvenes y hombres gais, imagen corporal, vigorexia, desarrollo de escala para identificar ortorexia, factores genéticos y el rol de la familia en el tratamiento de TICA.

Understanding audiovisual works and the quality of the viewing experience are two of the main challenges faced by people with visual impairments. This article addresses the importance of media literacy plans for this group and proposes the design of a training program that facilitates knowledge of the codes of language and audiovisual narrative as a tool to achieve an improvement in their critical capacity, facilitating learning more in line with the technological transformations of today's society. Through a review of the scientific literature and a cross-sectional mixed methodological model that combines the use of surveys with interviews with experts, their needs, interests, and training demands have been identified in relation to audiovisual media, contributing to optimizing the program's design. The analysis of the data obtained confirms that this type of proposal contributes to a significant improvement in the lives of people at risk of social exclusion, facilitates their interaction with the world, and collaborates in the elimination of barriers that interfere with the improvement of their digital and media skills., A compreensão das obras audiovisuais e a qualidade da experiência de visualização são dois dos principais desafios enfrentados por pessoas com deficiência visual. Este artigo aborda a importância dos planos de alfabetização midiática para este grupo e propõe o design de um programa educacional que facilite o conhecimento dos códigos da linguagem e da narrativa audiovisual como ferramenta para alcançar uma melhoria em sua capacidade crítica, permitindo uma aprendizagem mais alinhada com as transformações tecnológicas da sociedade atual. Por meio de uma revisão da literatura científica e de um modelo metodológico misto transversal que combina o uso de pesquisas com entrevistas a especialistas, suas necessidades, interesses e demandas de treinamento em relação aos meios audiovisuais foram identificados, contribuindo para otimizar o design do programa. A análise dos dados obtidos confirma que esse tipo de proposta contribui para uma melhoria significativa na vida de pessoas em risco de exclusão social, facilita sua interação com o mundo e colabora na eliminação de barreiras que interferem na melhoria de suas habilidades digitais e midiáticas., La comprensión de las obras audiovisuales y la calidad de la experiencia de su visionado, son dos de dos de los principales desafíos a los que se enfrentan las personas con discapacidad visual. El presente artículo aborda la importancia de los planes de alfabetización mediática para este colectivo y propone el diseño de un programa formativo que facilite el conocimiento de los códigos del lenguaje y la narrativa audiovisual como herramienta para lograr una mejora en su capacidad crítica, facilitando un aprendizaje más acorde a las transformaciones tecnológicas de la sociedad actual. Mediante una revisión de la literatura científica y un modelo metodológico mixto transversal que combina el uso de encuestas, con entrevistas a expertos, se han identificado sus necesidades, intereses y demandadas formativas en relación con los medios audiovisuales, contribuyendo a optimizar el diseño del programa. El análisis de los datos obtenidos nos confirma que este tipo de propuestas contribuyen a una mejora significativa en la vida de las personas en riesgo de exclusión social, facilitan su interacción con el mundo y colaboran en la eliminación de barreras que interfieren en la mejora de sus habilidades digitales y mediáticas.

The hippocampus hosts the continuous addition of new neurons throughout life—a phenomenon named adult hippocampal neurogenesis (AHN). Here we revisit the occurrence of AHN in more than 110 mammalian species, including humans, and discuss the further validation of these data by single-cell RNAseq and other alternative techniques. In this regard, our recent studies have addressed the long-standing controversy in the field, namely whether cells positive for AHN markers are present in the adult human dentate gyrus (DG). Here we review how we developed a tightly controlled methodology, based on the use of high-quality brain samples (characterized by short postmortem delays and ≤24 h of fixation in freshly prepared 4% paraformaldehyde), to address human AHN. We review that the detection of AHN markers in samples fixed for 24 h required mild antigen retrieval and chemical elimination of autofluorescence. However, these steps were not necessary for samples subjected to shorter fixation periods. Moreover, the detection of labile epitopes (such as Nestin) in the human hippocampus required the use of mild detergents. The application of this strictly controlled methodology allowed reconstruction of the entire AHN process, thus revealing the presence of neural stem cells, proliferative progenitors, neuroblasts, and immature neurons at distinct stages of differentiation in the human DG. The data reviewed here demonstrate that methodology is of utmost importance when studying AHN by means of distinct techniques across the phylogenetic scale. In this regard, we summarize the major findings made by our group that emphasize that overlooking fundamental technical principles might have consequences for any given research field.

Adult hippocampal neurogenesis (AHN) gives rise to new neurons throughout life. This phenomenon takes place in more than 120 mammalian species, including humans, yet its occurrence in the latter was questioned after one study proposed the putative absence of neurogenesis markers in the adult human hippocampus. In this regard, we showed that prolonged fixation impedes the visualization of Doublecortin immature neurons in this structure, whereas other authors have suggested that a dilated post-mortem delay (PMD) underlies these discrepancies. Nevertheless, the individual and/or additive contribution of fixation and the PMD to the detection (or lack thereof) of other AHN markers has not been studied to date. To address this pivotal question, we used a tightly controlled experimental design in mice, which allowed the dissection of the relative contribution of the aforementioned factors to the visualization of markers of individual AHN stages. Fixation time emerged as the most prominent factor globally impeding the study of this process in mice. Moreover, the visualization of other particularly sensitive epitopes was further prevented by prolonged PMD. These results are crucial to disambiguate current controversies related to the occurrence of AHN not only in humans but also in other mammalian species.