985 resultados para Receptores NMDA


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El objetivo de este artículo es abordar dentro de un contexto general aspectos relacionados con las migraciones, la globalización y los derechos humanos en la región latinoamericana. En ese sentido, se pretende destacar que las migraciones son positivas tanto en los países de destino como de origen. En los países receptores se constituyen en un componente importante para los procesos de desarrollo económico, según la sectorización y dinámica de sus economías y de conformidad con el proceso de globalización que se está viviendo, como en los países de origen, en razón del envío de remesas que significa un aporte importante para sus familias que viven en condiciones

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El “enfoque de Derechos” constituye un marco conceptual para el proceso de desarrollo humano que está basado normativamente en principios y estándares internacionales de Derechos Humanos y operacionalmente dirigido a respetarlos, protegerlos y satisfacerlos. Ahora bien, a pesar de ciertos avances en materia de reconocimiento de derechos o la incorporación en los últimos años de cierta retórica de “derechos” en las políticas sociales aún queda un largo camino por recorrer en la implementación de esta perspectiva (tanto en la región como en particular en la argentina). Todavía persisten un esquema político caracterizado por oferta de beneficios asistenciales, multiplicidad de programas otorgados discrecionalmente y bajo lógica de clientelismo político, soluciones basadas en el supuesto de la “responsabilización individual” por parte de los receptores de las políticas, falta de participación de los sectores vulnerables en la construcción de la política, permanente re-denominación de viejos programas, falta de control y accountability y con falencias en materia de información pública (tanto en términos de producción como de acceso). En este marco, este trabajo se propone primero indagar sobre algunos de los principios que deben guiar políticas públicas pensadas en términos del “enfoque de Derechos”. Luego, se señalan algunos aspectos que pueden ser útiles a la hora de comprender por que este enfoque dista de implementarse en la argentina. Cabe destacar que a fin de iluminar los diferentes puntos se tomarán como referencias ejemplos extraídos de programas sociales de transferencia de ingreso implementados en Argentina y que se convirtieron en respuestas estatales protagónicas a partir de la crisis de 2001-2002.

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Durante los últimos años las exportaciones no tradicionales han sufrido un incremento significativo, mientras que las exportaciones tradicionales han sufrido reducciones, teniendo como principales destinos a los EE.UU. y la CAN, siendo los países que conforman el bloque regional los principales receptores de producción industrial. Que en el caso del intercambio con Ecuador se realiza en su mayoría por vía terrestre a través del puente internacional de Rumichaca, que en los tres años anteriores ha tenido una participación promedio del 28% de las exportaciones terrestres de Colombia. El país posee una guerrilla que data de entre 1948 y 1966, a raíz de la violencia partidista, con el tiempo ha adquirido posiciones importantes en algunas zonas y han desplazado su accionar hacia aquellas que les pueden brindar ventajas en su accionar frente al estado: cada uno de los frentes posee tareas especificas en pro de la organización general. Hay además presencia de grupos de autodefensa cuya localización coincide con los grupos guerrilleros debido a su naturaleza y estos a su vez coinciden con la presencia de cultivos ilícitos en los departamentos que se unen por la vía panamericana, lo cual lleva a establecer la existencia de una relación estrecha entre los beneficios obtenidos por los grupos al margen de la ley y la actividad del narcotráfico. Por la aplicación del Plan Colombia y los nexos entre narcotráfico y grupos al margen de la ley, los recursos del primero son empleados en realizar acciones en contra de los segundos que afectan en forma reducida los procesos de intercambio entre las dos naciones por la interiorización de los costos como externalidades de los procesos económicos en territorio colombiano.

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Los tratados bilaterales sobre promoción y protección recíproca de inversiones (TBIs) tienen dos grandes objetivos: uno concreto e inmediato, el otro vago y mediato. Primero, estos acuerdos brindan garantías al inversor extranjero respecto del tratamiento que el Estado receptor otorgará a sus proyectos. Segundo, la firma de estos tratados pretende atraer más inversión extranjera a los países signatarios. El esquema de los TBIs, por lo tanto, se sustenta en la creencia de que los flujos de capitales extranjeros son afectados por la incapacidad institucional de los potenciales estados receptores. Estos tratados servirían para remediar esta falencia. Desde una perspectiva de política económica, no obstante, los beneficios para los países receptores son motivo de grandes discusiones. El presente trabajo busca ampliar este debate, analizando en qué medida los TBIs ayudan a los estados receptores a desarrollar las instituciones adecuadas para sus democracias y sus economías de mercado.

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Uno de los libros más leídos por los hispanoamericanos desde mediados del siglo XIX, es el Manuel de urbanidad, de Manuel Antonio Carreño. Hasta hace pocas décadas, fue texto de lectura obligatoria en la mayoría de las escuelas hispanohablantes de Latinoamérica. La familiaridad con el libro y con su autor, alimentó la creencia de que Carreño era nativo de la patria de origen de cada uno de esos receptores. El impacto que produjeron los consejos para orientar el desempeño de sus receptores en el espacio público, marcó la oferta de este letrado decimonónico desde el instante que apareció la obra. Sin lugar a dudas, el manual está señalado como un fenómeno editorial del continente, imposible de ignorar en nuestros días.

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A partir del año 2009, la cooperación energética, en particular, ha ubicado al Ecuador entre los cuatro principales receptores de financiamiento e inversión de China en América Latina. La relación en términos políticos y económicos ha sido presentada por los gobiernos de ambos países como una relación de cooperación y “mutuos beneficios”, basada en principios de igualdad, no interferencia, y complementariedad energética. Sin embargo, mucho se ha cuestionado el actuar de China en Ecuador y los reales beneficios o desafíos que están detrás de estas relaciones de “cooperación”. Encausado en la misión de diversificar la matriz energética, el Ecuador se ha vuelto hacia China para obtener financiación a través del Eximbank de China y el Banco de Desarrollo de China. De entre los muchos proyectos emblemáticos financiados y construidos por China, en este estudio se analizarán a profundidad los tres más importantes hasta la fecha tanto por su magnitud como por la inversión requerida: Coca Codo Sinclair (1500MW), Sopladora (487 MW), y Minas San Francisco (270MW). La investigación girará en torno a los procesos de negociación y financiación, así como a la construcción de las centrales y las discusiones medioambientales, tecnológicas y laborales que se han presentado.

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In the last decade, the presence of China in Latin America has been characterized by a model of economic cooperation based on pragmatic principles of complementarity and mutual benefits. Latin America is presented as a “paradise” of natural resources and expanding markets, while China stands as the main financier and investor in the region. In this scenario, particularly since 2009, Ecuador has become one of the top recipients of Chinese funding and investment, mainly in strategic sectors such as energy and infrastructure. The presence of China in the country has been the subject of extensive discussions about the true benefits and costs behind its model of economic cooperation.

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Reduced synaptic inhibition due to dysfunction of ionotropic GABAA receptors has been proposed as one factor in cerebral ischaemia-induced excitotoxic cell death. However, the participation of the inhibitory metabotropic GABAB receptors in these pathological processes has not been extensively investigated. We used oxygen–glucose deprivation (OGD) and NMDA-induced excitotoxicity as models to investigate whether ischaemia-like challenges alter the protein levels of GABAB1 and GABAB2 receptor subunits in rat organotypic hippocampal slice cultures. Twenty-four hours after the insult both OGD and NMDA produced a marked decrease in the total levels of GABAB2 (75%), while there was no significant change in the levels of GABAB1 after OGD, but an increase after NMDA treatment (100%). The GABAB receptor agonist baclofen (100 μM) was neuroprotective following OGD or NMDA treatment if added before or during the insult. GABAB receptors comprise heterodimers of GABAB1 and GABAB2 subunits and our results suggest that the separate subunits are independently regulated in response to extreme neuronal stress. However, because GABAB2 is required for functional surface expression, down-regulation of this subunit removes an important inhibitory feedback mechanism under pathological conditions.

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The Forkhead transcription factor, FoxO3a induces genomic death responses in neurones following translocation from the cytosol to the nucleus. Nuclear translocation of FoxO3a is triggered by trophic factor withdrawal, oxidative stress and the stimulation of extrasynaptic NMDA receptors. Receptor activation of phosphatidylinositol 3-kinase (PI3K) – Akt signalling pathways retains FoxO3a in the cytoplasm thereby inhibiting the transcriptional activation of death promoting genes. We hypothesised that phenolic antioxidants such as tert-Butylhydroquinone (tBHQ), which is known to stimulate PI3K-Akt signalling, would inhibit FoxO3a translocation and activity. Treatment of cultured cortical neurones with NMDA increased the nuclear localisation of FoxO3a, reduced the phosphorylation of FoxO3a, increased caspase activity and upregulated Fas ligand expression. In contrast the phenolic antioxidant tBHQ caused retention of FoxO3a in the cytosol coincident with enhanced PI3K- dependent phosphorylation of FoxO3a. tBHQ-induced nuclear exclusion of FoxO3a was associated with reduced FoxO-mediated transcriptional activity. Exposure of neurones to tBHQ inhibited NMDA-induced nuclear translocation of FoxO3a prevented NMDA-induced upregulation of FoxO-mediated transcriptional activity, blocked caspase activation and protected neurones from NMDA-induced excitotoxic death. Collectively, these data suggest that phenolic antioxidants such as tBHQ oppose stress-induced activation of FoxO3a and therefore have potential neuroprotective utility in neurodegeneration.

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Neuronal gap junctions are receiving increasing attention as a physiological means of intercellular communication, yet our understanding of them is poorly developed when compared to synaptic communication. Using microfluorimetry, we demonstrate that differentiation of SN56 cells (hybridoma cells derived from murine septal neurones) leads to the spontaneous generation of Ca(2+) waves. These waves were unaffected by tetrodotoxin (1microM), but blocked by removal of extracellular Ca(2+), or addition of non-specific Ca(2+) channel inhibitors (Cd(2+) (0.1mM) or Ni(2+) (1mM)). Combined application of antagonists of NMDA receptors (AP5; 100microM), AMPA/kainate receptors (NBQX; 20microM), nicotinic AChR receptors (hexamethonium; 100microM) or inotropic purinoceptors (brilliant blue; 100nM) was also without effect. However, Ca(2+) waves were fully prevented by carbenoxolone (200microM), halothane (3mM) or niflumic acid (100microM), three structurally diverse inhibitors of gap junctions, and mRNA for connexin 36 was detected by PCR. Whole-cell patch-clamp recordings revealed spontaneous inward currents in voltage-clamped cells which we inhibited by Cd(2+), Ni(2+) or niflumic acid. Our data suggest that differentiated SN56 cells generated spontaneous Ca(2+) waves which are propagated by intercellular gap junctions. We propose that this system can be exploited conveniently for the development of neuronal gap junction modulators.

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Ketamine and propofol are two well-known, powerful anesthetic agents, yet at first sight this appears to be their only commonality. Ketamine is a dissociative anesthetic agent, whose main mechanism of action is considered to be N-methyl-D-aspartate (NMDA) antagonism; whereas propofol is a general anesthetic agent, which is assumed to primarily potentiate currents gated by γ-aminobutyric acid type A (GABAA) receptors. However, several experimental observations suggest a closer relationship. First, the effect of ketamine on the electroencephalogram (EEG) is markedly changed in the presence of propofol: on its own ketamine increases θ (4–8 Hz) and decreases α (8–13 Hz) oscillations, whereas ketamine induces a significant shift to beta band frequencies (13–30 Hz) in the presence of propofol. Second, both ketamine and propofol cause inhibition of the inward pacemaker current Ih, by binding to the corresponding hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1) subunit. The resulting effect is a hyperpolarization of the neuron’s resting membrane potential. Third, the ability of both ketamine and propofol to induce hypnosis is reduced in HCN1-knockout mice. Here we show that one can theoretically understand the observed spectral changes of the EEG based on HCN1-mediated hyperpolarizations alone, without involving the supposed main mechanisms of action of these drugs through NMDA and GABAA, respectively. On the basis of our successful EEG model we conclude that ketamine and propofol should be antagonistic to each other in their interaction at HCN1 subunits. Such a prediction is in accord with the results of clinical experiment in which it is found that ketamine and propofol interact in an infra-additive manner with respect to the endpoints of hypnosis and immobility.

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Background: Chronic, intermittent exposure to psychostimulant drugs results in striatal neuroadaptations leading to an increase in an array of behavioral responses on subsequent challenge days. A brain-specific striatal-enriched tyrosine phosphatase (STEP) regulates synaptic strengthening by dephosphorylating and inactivating several key synaptic proteins. This study tests the hypothesis that a substrate-trapping form of STEP will prevent the development of amphetamine-induced stereotypies. Methods: A substrate-trapping STEP protein, TAT-STEP (C-S), was infused into the ventrolateral striatum on each of 5 consecutive exposure days and I hour before amphetamine injection. Animals were challenged to see whether sensitization to the stereotypy-producing effects of amphetamine developed. The same TAT-STEP (C-S) protein was used on acute striatal slices to determine the impact on long-term potentiation and depression. Results: Infusion of TAT-STEP (C-S) blocks the increase of amphetamine-induced stereotypies when given during the 5-day period of sensitization. The TAT-STEP (C-S) has no effect if only infused on the challenge day. Treatment of acute striatal slices with TAT-STEP (C-S) blocks the induction of long-term potentiation and potentates long-term depression. Conclusions: A substrate trapping form of STEP blocks the induction of amphetamine-induced neuroplasticity within the ventrolateral striatum and supports the hypothesis that STEP functions as a tonic break on synaptic strengthening.

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In the present work, we sought to mimic the internal state changes in response to a predator threat by pharmacologically stimulating the brain circuit involved in mediating predator fear responses, and explored whether this stimulation would be a valuable unconditioned stimulus (US) in an olfactory fear conditioning paradigm (OFC). The dorsal premammillary nucleus (PMd) is a key brain structure in the neural processing of anti-predatory defensive behavior and has also been shown to mediate the acquisition and expression of anti-predatory contextual conditioning fear responses. Rats were conditioned by pairing the US, which was an intra-PMd microinjection of isoproterenol (ISO; beta-adrenoceptor agonist), with amyl acetate odor-the conditioned stimulus (CS). ISO (10 and 40 nmol) induced the acquisition of the OFC and the second-order association by activation of beta-1 receptors in the PMd. Furthermore, similar to what had been found for contextual conditioning to a predator threat, atenolol (beta-1 receptor antagonist) in the PMd also impaired the acquisition and expression of OFC promoted by ISO. Considering the strong glutamatergic projections from the PMd to the dorsal periaqueductal gray (dPAG), we tested how the glutamatergic blockade of the dPAG would interfere with the OFC induced by ISO. Accordingly, microinjections of NMDA receptor antagonist (AP5, 6 nmol) into the dPAG were able to block both the acquisition, and partially, the expression of the OFC. In conclusion, we have found that PMd beta-1 adrenergic stimulation is a good model to mimic predatory threat-induced internal state changes, and works as a US able to mobilize the same systems involved in the acquisition and expression of predator-related contextual conditioning. Neuropsychopharmacology (2011) 36, 926-939; doi:10.1038/npp.2010.231; published online 5 January 2011

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The dorsal premammillary nucleus (PMd) has a critical role on the expression of defensive responses to predator odor. Anatomical evidence suggests that the PMd should also modulate memory processing through a projecting branch to the anterior thalamus. By using a pharmacological blockade of the PMd with the NMDA-receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5), we were able to confirm its role in the expression of unconditioned defensive responses, and further revealed that the nucleus is also involved in influencing associative mechanisms linking predatory threats to the related context. We have also tested whether olfactory fear conditioning, using coffee odor as CS, would be useful to model predator odor. Similar to cat odor, shock-paired coffee odor produced robust defensive behavior during exposure to the odor and to the associated context. Shock-paired coffee odor also up-regulated Fos expression in the PMd, and, as with cat odor, we showed that this nucleus is involved in the conditioned defensive responses to the shock-paired coffee odor and the contextual responses to the associated environment. (C) 2008 Elsevier Ltd. All rights reserved.

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Chicken (Gallus gallus) brains were used to investigate the typology and the immunolabel pattern for the subunits composing the AMPA-type glutamate receptors (GluR) of hindbrain neurons of the dorsal (dND) and ventral nuclei (vND) of the Deiter`s vestibular complex (CD), which is the avian correspondent of the lateral vestibular nucleus (LVN) of mammals. Our results revealed that neurons of both divisions were poor in GluR1. The vND, the GluR2/3+ and GluR4+ label presented no area or neuronal size preference, although most neurons were around 75%. The dND neurons expressing GluR2/3 are primarily around 85%, medium to large-sized 85%, and predominantly 60% located in the medial portion of the rostral pole and in the lateral portion of the caudal pole. The majority of dND neurons containing GluR4 are also around 75%, larger (70% are large and giant), exhibiting a distribution that seems to be complementary to that of GluR2/3+ neurons. This distinct arrangement indicates functional differences into and between the DC nuclei, also signaling that such variation could be attributed to the diverse nature of the subunit composition of the GluRs. Discussion addresses the morphological and functional correlation of the avian DC with the LVN of mammals in addition to the high morphological correspondence, To include these data into the modern comparative approach we propose to adopt a similar nomenclature for the avian divisions dND and vND that could be referred as dLVN and vLVN. (C) 2008 Elsevier B.V. All rights reserved.