138 research outputs found

    Neonatal Hypoglycemia - Current Concepts

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    Enseñanza de la Biología y la Geología en la Educación Secundaria: evolución, tendencias y resultados.

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    Ha pasado mucho tiempo desde que comenzara el Máster para Profesorado en Educación Secundaria Obligatoria, Bachillerato, Formación Profesional y Enseñanza de Idiomas. En todo este tiempo hemos abordado contenidos de muchas disciplinas diferentes, hemos estudiado modelos, teorías, metodologías y recursos diferentes (aplicados a la enseñanza de la Biología y la Geología, y de las Ciencias Naturales en general) y hemos vivido experiencias en centros escolares. Sin embargo, siempre se han tratado de manera muy compartimentada e individualizada en asignaturas como Didáctica de la Biología y la Geología, Diseño Curricular en Biología y Geología, Metodología y Evaluación en Biología y Geología, Innovación Docente en Biología y Geología e Iniciación a la Investigación Educativa en Biología y Geología. En definitiva, de una manera ligeramente estanca y sin terminar de interrelacionar los contenidos. Por todo ello, este Trabajo Fin de Máster pretende relacionar todos estos aspectos (metodología, contenidos, estructuración, organización, actividades, recursos, etc.) en el marco de la Biología y la Geología y actuar como análisis de su evolución y resultados a lo largo de los últimos años.Didáctica de las Ciencias Experimentales, Sociales y de la MátematicaMáster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idioma

    Current status of terpenoids as inflammasome inhibitors

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    Increasing evidence supports NLRP3 inflammasome as a new target to control inflammation. Dysregulation of NLRP3 inflammasome has been reported to be involved in the pathogenesis of several human inflammatory diseases. However, no NLRP3 inflammasome inhibitors are available in clinic. Terpenoids are natural products with multi-target activities against inflammation. Recent studies have revealed that these compounds are capable of inhibiting the activation of NLRP3 inflammasome in several mouse models of NLRP3 inflammasome-related pathogenesis. Thus, terpenoids represent an interesting pharmacological approach for the treatment of inflammatory diseases as they are endowed with a dual mechanism of inhibition of NF-KB transcription factor and inflammasome activation, both critically involved in their anti-inflammatory effects. This work provides an overview of the current knowledge on the therapeutic potential of terpenoids as NLRP3 inflammasome inhibitors.This work was supported by grant PI11/00036, PI14/00055, and PI17/00012 from the FIS, MPY 1410/09 from ISCIII and Spanish Ministry of Health (Instituto de Salud Carlos III; RD12/0036/0059) to SH and grant RTI2018-094356-B-C21 from Ministerio de Economía y Competitividad to LGC, IC and BH. LGC received a predoctoral fellowship award from the Spanish Ministry of Education, Culture and Sports (FPU17/03519).S

    Non-vitamin K antagonist oral anticoagulants and antiphospholipid syndrome

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    The current treatment of thrombotic APS patients includes long-term anticoagulation with oral vitamin K antagonists (VKAs), with warfarin being the one most commonly used. However, the use of VKAs can be challenging, especially in patients with APS. VKAs monitoring in patients with aPL is complicated by the heterogeneous responsiveness to LAs of reagents used in the International Normalized Ratio test, potentially resulting in instability of anticoagulation. For decades, VKAs were the only available oral anticoagulants. However, non-VKA oral anticoagulants, including a direct thrombin inhibitor (dabigatran etexilate) and direct anti-Xa inhibitors (rivaroxaban, apixaban and edoxaban), are currently available. The use of these agents may represent a major step forward since, unlike VKAs, they have few reported drug interactions and they do not interact with food or alcohol intake, thereby resulting in more stable anticoagulant intensity. Most importantly, monitoring their anticoagulant intensity is not routinely required due to their predictable anticoagulant effects. In this review, we discuss the clinical and laboratory aspects of non-VKA oral anticoagulants, focusing on the available evidence regarding their use in patients with APS

    Slow thermo-optomechanical pulsations in suspended 1D photonic crystal nanocavities

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    We investigate the nonlinear optical response of suspended 1D photonic crystal nanocavities fabricated on a silicon nitride chip. Strong thermo-optical nonlinearities are demonstrated for input powers as low as 2μW2\,\mu\text{W} and a self-sustained pulsing regime is shown to emerge with periodicity of several seconds. As the input power and laser wavelength are varied the temporal patterns change in period, duty cycle and shape. This dynamics is attributed to the multiple timescale competition between thermo-optical and thermo-optomechanical effects and closely resembles the relaxation oscillations states found in mathematical models of neuronal activity. We introduce a simplified model that reproduces all the experimental observations and allows us to explain them in terms of the properties of a 1D critical manifold which governs the slow evolution of the system.Comment: 9 pages, 6 figure

    Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity

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    The cardiovascular side effects associated with doxorubicin (DOX), a wide spectrum anticancer drug, have limited its clinical application. Therefore, to explore novel strategies with cardioprotective effects, a series of new labdane conjugates were prepared (6a-6c and 8a-8d) from the natural diterpene labdanodiol (1). These hybrid compounds contain anti-inflammatory privileged structures such as naphthalimide, naphthoquinone, and furanonaphthoquinone. Biological activity of these conjugates against DOX-induced cardiotoxicity was tested in vitro and the potential molecular mechanisms of protective effects were explored in H9c2 cardiomyocytes. Three compounds 6c, 8a, and 8b significantly improved cardiomyocyte survival, via inhibition of reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways (extracellular signal-regulated kinase and c-Jun N-terminal kinase) and autophagy mediated by Akt activation. Some structure-activity relationships were outlined, and the best activity was achieved with the labdane-furonaphthoquinone conjugate 8a having an N-cyclohexyl substituent. The findings of this study pave the way for further investigations to obtain more compounds with potential cardioprotective activity.This study was supported by Grant RTI2018‐094356‐BC21 from the Ministerio de Ciencia, Innovación y Universidades (MICIU) to A. E.‐B., I. C., L. G.‐C., and B. H.; Grant PI17/00012 and PI20/00018 from the Instituto de Salud Carlos III to S. H. These projects are also cofunded by the European Regional Development Fund (FEDER). A. A. and S. O.‐R. thank the Cabildo de Tenerife (Agustín de Betancourt Program).S

    Semisynthesis and Inhibitory Effects of Solidagenone Derivatives on TLR-Mediated Inflammatory Responses

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    A series of nine derivatives (2⁻10) were prepared from the diterpene solidagenone (1) and their structures were elucidated by means of spectroscopic studies. Their ability to inhibit inflammatory responses elicited in peritoneal macrophages by TLR ligands was investigated. Compounds 5 and 6 showed significant anti-inflammatory effects, as they inhibited the protein expression of nitric oxide synthase (NOS-2), cyclooxygenase-2 (COX-2), and cytokine production (TNF-α, IL-6, and IL-12) induced by the ligand of TLR4, lipopolysaccharide (LPS), acting at the transcriptional level. Some structure⁻activity relationships were outlined. Compound 5 was selected as a representative compound and molecular mechanisms involved in its biological activity were investigated. Inhibition of NF-κB and p38 signaling seems to be involved in the mechanism of action of compound 5. In addition, this compound also inhibited inflammatory responses mediated by ligands of TLR2 and TLR3 receptors. To rationalize the obtained results, molecular docking and molecular dynamic studies were carried out on TLR4. All these data indicate that solidagenone derivative 5 might be used for the design of new anti-inflammatory agents.S

    Synthesis of Quinoline and Dihydroquinoline Embelin Derivatives as Cardioprotective Agents

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    A set of new dihydroquinoline embelin derivatives was obtained from the reaction of the natural benzoquinone embelin (1) with anilines and aromatic aldehydes in the presence of AgOTf. The synthesis of these compounds involves the formation of a Knoevenagel adduct, followed by nucleophilic addition of aniline and subsequent electrocyclic ring closure. The scope of the reaction regarding the aldehydes and anilines was determined. Quinoline derivatives were also obtained from the corresponding dihydroquinolines under oxidation with DDQ. The cardioprotective activity of the synthesized compounds was screened using a doxorubicin-induced cardiotoxicity model in H9c2 cardiomyocytes. Some structure-activity relationships were outlined, and the best activities were achieved with quinoline-embelin derivatives having a 4-nitrophenyl group attached at the pyridine ring. The obtained results indicated that embelin derivatives 4i, 6a, 6d, 6k, and 6m could have potential as cardioprotective agents, as they attenuated a DOX-induced cardiotoxicity effect acting on oxidative stress and apoptosis.We gratefully acknowledge the financial support from the Spanish MICIU RTI2018-094356-B-C21 to A.E.B., I.C., and B.H. and Agencia Canaria de Investigación, Innovación y Sociedad de la Información Pro ID 2021010037 to A.E.B. These projects are also cofunded by the European Regional Development Fund (FEDER). We thank Dr. A. Tapia and G. Feresin for providing the natural embeline. We are grateful to Instituto de Salud Carlos III for financial support to S.H.S

    Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.

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    Inhibition of Extracellular Matrix degradation by nitric oxide (NO) induces cardiac protection against coronary ischemia/reperfusion (IR). Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) stimulates enzymatic activation of matrix metalloproteinases (MMPs) in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood. We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN) in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2) knockout (KO) mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO) in the drinking water, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9), in expression of matrix metalloproteinases, and cardiac performance was improved (left ventricular ejection fraction (LVEF). NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6). The role of Caveolin-3/EMMPRIN in NO-mediated cardiac protection was further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7±5), or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR.Ministerio de Economía y CompetitividadInstituto de Salud Carlos II
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