FTY720 attenuates excitotoxicity and neuroinflammation

Background: FTY720 (fingolimod, Gilenya(TM)), a structural analog of sphingosine-1-phosphate (S1P), is the first oral drug approved for treatment the relapsing-remitting form of multiple sclerosis (MS), and its efficacy has been related to induced lymphopenia and consequent immunosuppression via modulation of S1P(1) receptors (S1P(1)R). However, due to its lipophilic nature, FTY720 crosses the blood brain barrier (BBB) and could act directly on neural cells. In this study, we investigated the effectiveness of FTY720 as a neuroprotective agent using in vitro and in vivo models of excitotoxic neuronal death and examined if FTY720 exerts a direct action on neurons, or/and an indirect modulation of inflammation-mediated neurodegeneration as a possible mechanism of neuroprotection. Methods: Primary neuronal and organotypic cortical cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excitotoxic cell death (measured by lactate dehydrogenase (LDH) assay or propidium iodide uptake, respectively). The effects of FTY720 treatment (10, 100 and 1,000 nM) on neuronal survival were examined. As an in vivo model of neuronal death and inflammation, we used intracerebroventricular (icv) administration of kainic acid (KA; 0.5 mu g/2 mu l) in Sprague-Dawley rats. FTY720 was applied icv (1 mu g/2 mu l), together with KA, plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 3 days after icv. Rats were evaluated for neurological score, neuronal loss in CA3 hippocampal region and activation of microglia at the lesion site. In addition, we tested FTY720 as a modulator of microglia responses using microglial cell cultures activated with lipopolysaccharide (LPS) and its effects in stress signalling pathways using western blotting for p38 and JNK1/2 mitogen-activated protein kinases (MAPKs). Results: FTY720 was able to reduce excitotoxic neuronal death in vitro. Moreover, in vivo repeated FTY720 administration attenuated KA-induced neurodegeneration and microgliosis at the CA3 lesion site. Furthermore, FTY720 negatively modulates p38 MAPK in LPS-activated microglia, whereas it had no effect on JNK1/2 activation. Conclusions: These data support a role for FTY720 as a neuroprotective agent against excitotoxin-induced neuronal death and as a negative modulator of neuroinflammation by targeting the p38 MAPK stress signalling pathway in microglia.

Contribución al estudio de las estructuras tumulares en arqueología: entre la similitud morfológica y la disparidad de funciones

[ES] El artículo trata el tema de las estructuras tumulares, su variabilidad formal y funcional (funeraria, lugar de habitación, etc.), así como su distinta cronología. Se describe los casos concretos de Txoritegi (Zerain —Gipuzkoa—) y Galardi (Txoritegi —Gipuzkoa—), unas estructuras tumulares tipo mota utilizadas, posiblemente, a modo de atalaya de vigía en el contexto del período de conflictividad bajomedieval. Es un elemento novedoso en el territorio para cuya interpretación se ha efectuado un análisis de las cuencas visuales mediante SIG.

Establecimientos de habitación al aire libre. Los fondos de cabaña de morfología tumular: características, proceso de formación y cronología

[ES] En este artículo se describen una serie de estructuras de tipo tumular, que si aparentemente pudieran recordar a las estructuras funerarias clásicas se alejan de éstas por su morfología, composición, funcionalidad y cronología. Los trabajos de prospección realizados durante los últimos años en la Sierra de Aralar (Gipuzkoa) han permitido localizar medio centenar de estas estructuras tumulares, así como abrir nuevos campos de investigación en torno a la vivienda temporal de los grupos pastoriles en las zonas de montaña.

Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

Background: Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods: A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results: Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: p(M-H) = 0.0005; ORM-H (95% CI) = 1.27 (1.11-1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [p(M-H) = 0.0003, ORM-H (95% CI) = 1.32 (1.14-1.53)]. Conclusion: Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.

Do Nutritional Supplements Have a Role in Age Macular Degeneration Prevention?

Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids (omega-3) supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and omega-3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain). Results. High dietary intakes of omega-3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and omega-3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.

"Leioar" antroponimoaren lekuko toponimiko gehiago

[EN] The Basque anthroponym "Leioar" was analyzed by Alfonso Irigoien, which explained the origin of the name and the derived place names. In this paper we present new names derived, nine in total, the names are explained, also the appeared differences.

Podemos y el Populismo

En este trabajo nos planteamos la cuestión en torno a la etiqueta «populista» que se le suele asignar a Podemos y que han usado sobre todo sus críticos, entendida como algo negativo, engañoso. ¿Es cierto que se puede tildar a Podemos como un fenómeno populista? ¿Cuáles son las claves de discurso que Podemos y sus líderes han utilizado para llegar a una base social heterogénea y en un plazo de tiempo tan corto? Más aún, ¿qué es el populismo?, ¿cómo se manifiesta?

Characteristics of the sportsmanship and unsportsmanlike conduct evaluation tools in youth sport

World Conference on Psychology and Sociology 2012

Ethnography as a linking method between psychology and sociology: research design

World Conference on Psychology and Sociology 2012

Socioeconomic status, parental support, motivation and self-confidence in youth competitive sport

World Conference on Psychology and Sociology 2012

Sportsmanship rating scale in tennis competition with young players

World Conference on Psychology and Sociology 2012

Evaluación de la violencia y deportividad en el deporte: un análisis bibliométrico

Nº monográfico: Análisis de datos en estudios observacionales de Ciencias del Deporte (2). Aportaciones desde Mixed Methods.

Magnetoimpedancia en sistemas homogéneos y heterogéneos

La magnetoimpedancia (MI) se define como el gran cambio en la impedancia eléctrica que sufren los materiales ferromagnéticos cuando son expuestos a un campo magnético externo. Este fenómeno es causado por la dependencia de la permeabilidad del material con el campo magnético, la cual causa variaciones en la profundidad de penetración (δ) de las corrientes que fluyen por la muestra. Esto se conoce como efecto pelicular o skin effect. Los materiales ferromagnéticos blandos tienen alta permeabilidad y baja coercitividad, y por tanto estrechos ciclos de histéresis. Entre ellos se encuentra el permalloy (Py), una aleación de hierro y níquel (Fe_20 Ni_80). Siendo este el principal material de investigación del presente trabajo, se tratará de dar primero un estudio analítico del fenómeno de la MI para muestras en forma de hilo, así como películas delgadas (monocapas y tricapas). Las herramientas utilizadas de cómputo son MATLAB y FEMM para el apartado que a simulaciones se refiere. El trabajo incluye una segunda parte experimental. Mediante LabVIEW, con los instrumentos y técnicas adecuadas, el efecto de la MI puede ser debidamente cuantificado, y es precisamente el objetivo final de este análisis la comparación de los resultados experimentales con las simulaciones.