Anandamide inhibits Theiler's virus induced VCAM-1 in brain endothelial cells and reduces leukocyte transmigration in a model of blood brain barrier by activation of CB1 receptors

<p>Abstract</p> <p>Background</p> <p>VCAM-1 represents one of the most important adhesion molecule involved in the transmigration of blood leukocytes across the blood-brain barrier (BBB) that is an essential step in the pathogenesis of MS. Several evidences have suggested the potential therapeutic value of cannabinoids (CBs) in the treatment of MS and their experimental models. However, the effects of endocannabinoids on VCAM-1 regulation are poorly understood. In the present study we investigated the effects of anandamide (AEA) in the regulation of VCAM-1 expression induced by Theiler's virus (TMEV) infection of brain endothelial cells using <it>in vitro </it>and <it>in vivo </it>approaches.</p> <p>Methods</p> <p>i) <it>in vitro</it>: VCAM-1 was measured by ELISA in supernatants of brain endothelial cells infected with TMEV and subjected to AEA and/or cannabinoid receptors antagonist treatment. To evaluate the functional effect of VCAM-1 modulation we developed a blood brain barrier model based on a system of astrocytes and brain endothelial cells co-culture. ii) <it>in vivo</it>: CB₁receptor deficient mice (Cnr1^-/-) infected with TMEV were treated with the AEA uptake inhibitor UCM-707 for three days. VCAM-1 expression and microglial reactivity were evaluated by immunohistochemistry.</p> <p>Results</p> <p>Anandamide-induced inhibition of VCAM-1 expression in brain endothelial cell cultures was mediated by activation of CB₁receptors. The study of leukocyte transmigration confirmed the functional relevance of VCAM-1 inhibition by AEA. <it>In vivo </it>approaches also showed that the inhibition of AEA uptake reduced the expression of brain VCAM-1 in response to TMEV infection. Although a decreased expression of VCAM-1 by UCM-707 was observed in both, wild type and CB₁receptor deficient mice (Cnr1^-/-), the magnitude of VCAM-1 inhibition was significantly higher in the wild type mice. Interestingly, Cnr1^-/-mice showed enhanced microglial reactivity and VCAM-1 expression following TMEV infection, indicating that the lack of CB₁receptor exacerbated neuroinflammation.</p> <p>Conclusions</p> <p>Our results suggest that CB₁receptor dependent VCAM-1 inhibition is a novel mechanism for AEA-reduced leukocyte transmigration and contribute to a better understanding of the mechanisms underlying the beneficial role of endocannabinoid system in the Theiler's virus model of MS.</p

La evaluación de resultados en el tratamiento y rehabilitación de trastornos mentales crónicos.

En este trabajo efectuamos una revisión de los criterios teóricos y técnicos exigibles para diseñar y/o elegir instrumentos adecuados de evaluación en el ámbito de los resultados valorables en las personas con trastornos mentales crónicos que participan en los programas de salud mental. Asimismo se ofrece un análisis comparativo de las características técnicas de los instrumentos más frecuentes utilizados en los protocolos de evaluación. Del análisis de los instrumentos se concluye que una evaluación de resultados adecuada debería incluir al menos los siguientes dominios: síntomas, funcionamiento, salud física, calidad de vida, bienestar y seguridad propia y del entorno, y satisfacción con los servicios

La evaluación de resultados en el tratamiento y rehabilitación de trastornos mentales crónicos.

En este trabajo efectuamos una revisión de los criterios teóricos y técnicos exigibles para diseñar y/o elegir instrumentos adecuados de evaluación en el ámbito de los resultados valorables en las personas con trastornos mentales crónicos que participan en los programas de salud mental. Asimismo se ofrece un análisis comparativo de las características técnicas de los instrumentos más frecuentes utilizados en los protocolos de evaluación. Del análisis de los instrumentos se concluye que una evaluación de resultados adecuada debería incluir al menos los siguientes dominios: síntomas, funcionamiento, salud física, calidad de vida, bienestar y seguridad propia y del entorno, y satisfacción con los servicios

La evaluación de resultados en el tratamiento y rehabilitación de trastornos mentales crónicos.

En este trabajo efectuamos una revisión de los criterios teóricos y técnicos exigibles para diseñar y/o elegir instrumentos adecuados de evaluación en el ámbito de los resultados valorables en las personas con trastornos mentales crónicos que participan en los programas de salud mental. Asimismo se ofrece un análisis comparativo de las características técnicas de los instrumentos más frecuentes utilizados en los protocolos de evaluación. Del análisis de los instrumentos se concluye que una evaluación de resultados adecuada debería incluir al menos los siguientes dominios: síntomas, funcionamiento, salud física, calidad de vida, bienestar y seguridad propia y del entorno, y satisfacción con los servicios

Multi-level approach to the optimization of unrepeatered WDM systems with distributed amplification

we present a new general, simplified, approach to the optimization of unrepeatered systems using distributed amplification. Our approach is based on the procedure first presented in for long-distance transmission systems, adapted to the particular constraints of modern unrepeatered transmission, in which full recovery of signal power at the end of the span is not a requirement, allowing for an extra degree of freedom. The method presented is equally applicable to ASK and PSK formats, as well as to any form of WDM configuration

Atomically resolved single-molecule triplet quenching

Little is known about the atomistic mechanism that nature uses to mitigate the destructive interaction of triplet-excited pigment chromophores with omnipresent oxygen. Peng et al. tackled this challenge by developing a technique based on conducting atomic force microscopy to populate and track triplets in a single pentacene molecule, a model pi-conjugated system, placed on a sodium chloride surface (see the Perspective by Li and Jiang). The authors show how the triplet-state lifetime can be quenched in controllable manner by atomic-scale manipulations with oxygen co-adsorbed in close vicinity. The presented single-molecule spectroscopy paves the way for further atomically resolved studies of triplet excited states that play an important role in many other fields, such as organic electronics, photocatalysis, and photodynamic therapy.Science, abh1155, this issue p. 452; see also abj5860, p. 392The nonequilibrium triplet state of molecules plays an important role in photocatalysis, organic photovoltaics, and photodynamic therapy. We report the direct measurement of the triplet lifetime of an individual pentacene molecule on an insulating surface with atomic resolution by introducing an electronic pump-probe method in atomic force microscopy. Strong quenching of the triplet lifetime is observed if oxygen molecules are coadsorbed in close proximity. By means of single-molecule manipulation techniques, different arrangements with oxygen molecules were created and characterized with atomic precision, allowing for the direct correlation of molecular arrangements with the lifetime of the quenched triplet. Such electrical addressing of long-lived triplets of single molecules, combined with atomic-scale manipulation, offers previously unexplored routes to control and study local spin-spin interactions