Implicación de la molécula de adhesión ALCAM en el daño cerebral. Modelo de daño neuronal mediante la administración de MDMA/éxtasis en rata / Implication of the adhesion molecule ALCAM in the experimental rat model of brain damage caused by MDMA/ecstasy

Objetivo: Caracterizar la expresión de ALCAM en vasos de corteza cerebral de ratas tratadas con MDMA. 2) Estudiar el efecto que sobre su expresión y sobre la neurotoxicidad producida por MDMA tiene ibuprofeno. Materiales y métodos: Se administró una dosis neurotóxica de MDMA a ratas Dark Agouti e buprofeno a diferentes tiempos. Se midió la temperatura de los animales durante los tratamientos y se estudió la expresión de ALCAM en los vasos de corteza. El daño cerebral se estudió midiendo los niveles de ácido 5-indolacético, serotonina y la densidad de su transportador. Resultados: MDMA produce un aumento de ALCAM a las 24 horas (p<0.01). El co-tratamiento con ibuprofeno lo disminuye (p<0.01) y atenúa el daño cerebral disminuyendo los efectos neurotóxicos de MDMA sobre los niveles de serotonina cortical (p<0.0001) y la densidad del transportador (p<0.0001). Ibuprofeno disminuye ligeramente la hipertermia producida por MDMA. Conclusiones: MDMA aumenta la expresión de ALCAM. Los datos sugieren la posibilidad de utilizar compuestos anti-inflamatorios como ibuprofeno que reducen este efecto sobre ALCAM y que disminuyen parcialmente el daño cerebral, si bien es necesario analizar la participación de la disminución de la temperatura en dicha protección (AU)

Objective: 1) Characterization of ALCAM adhesion molecule expression in cortical vessels of MDMA-treated rats. 2) Study of the effect of the anti-inflammatory compound ibuprofen on ALCAM expression and on the neurotoxicity produced by MDMA. Material and methods: Male Dark Agouti rats were given a neurotoxic dose of MDMA. Ibuprofen was given before and at various times after MDMA. Rectal temperature was monitored during the treatment and ALCAM expression in vessels from cerebral cortex was determined at 24 h. In neurotoxicity studies, cortical 5-HT tissue levels and 5-HT transporter density were measured. Results: ALCAM expression was increased 24 h after MDMA treatment (p<0.01). Co-treatment with ibuprofen attenuated the increase in ALCAM levels (p<0.01) and partially prevented cerebral injury, reducing MDMA-induced 5-HT (p<0.0001) and 5-HT transporter (p<0.0001) loss. Ibuprofen produced a minor modification in the MDMA-induced hyperthermia. Conclusions: Our study demonstrates an effect of MDMA on ALCAM expression. Thus, anti-inflammatory compounds such as ibuprofen may result useful in brain protection by inhibiting the effects of ALCAM and reducing brain damage although the potential contribution of the attenuation of MDMA-induced hyperthermia must also be considered (AU)

Seasonal trends and spatial relations between environmental/meteorological factors and leishmaniosis sand fly vector abundances in Central Spain.

This paper reports on an entomological survey performed over the period 2006-2008 in Central Spain (mainly in the Madrid province) where canine leishmaniosis (CanL) is endemic. The study area was selected on the grounds of its wide altitude range, which determines both broad climate and vegetation ranges that could affect sand fly distributions. This area was surveyed from NE to SW across its mountain range (Sistema Central) and plateau area using sticky traps mainly on embankments. In 2006 and 2007, 123 sites were sampled (9557 sand flies captured) to establish possible relations between environmental or meteorological factors and vector densities (Phlebotomus perniciosus and Phlebotomus ariasi). The factors correlated with higher vector densities were: a sample site between villages or at the edge of a village, the lack of a paved road, a rural habitat, an east or south-facing wall or wall sheltered from the wind, the presence of livestock or birds, a holm-oak wood vegetation, a lower summer mean temperature and lower annual mean precipitation. This study was followed by a seasonal survey conducted at 16 selected sites (14,353 sand flies) sampled them monthly from May to November 2008. P. perniciosus showed a diphasic seasonal trend with two abundance peaks in July and September whereas P. ariasi showed a monophasic trend with one peak in August. Comparing with data from studies performed in 1991 in the same area, vector densities are significantly higher. A possible explanation for this is that the vectors (mainly P. ariasi) are moving towards higher altitudes perhaps because of global change. This increasing trend could have an impact on CanL and its geographical distribution.

Emerging trends in the seroprevalence of canine leishmaniasis in the Madrid region (central Spain).

This report describes a cross-sectional serological survey of the epidemiology of canine leishmaniasis (CanL) performed in 2006 and 2007 in the Madrid region (central Spain) where the disease is endemic. The work presented here is one of the several studies conducted in different Spanish regions under the Integrated Project of the European Commission entitled Emerging Diseases in a changing European eNvironment (EDEN). The aim of this project is to identify and catalogue European ecosystems and environmental conditions that determine the spatial and temporal distributions and dynamics of several pathogenic agents including Leishmania infantum (EDEN-LEI). The study area (Madrid Autonomous Region) was selected on the grounds of its wide altitude range. This area was surveyed from NE to SW across its mountain range (Sistema Central) and plateau area. One thousand and seventy-six dogs from 32 villages were examined for clinical signs of CanL, and serum samples were obtained to determine several haematological and biochemical variables. Leishmaniasis-specific antibodies were identified using an indirect immunofluorescence antibody test (IFAT). 87 of the 1076 dogs were seropositive for the protozoan (IFAT: cut-off>or=1/80) indicating a seroprevalence of 8.1% (0-16.1% depending on the village). On the basis of a physical examination and the biochemical/haematological status of each dog, 32 of the 87 infected dogs were described as clinically healthy (37%). Seroprevalence showed a peak in young dogs (1-2 years) and a second larger peak among the older dogs (7-8 years). Factors correlated with a higher infection risk were age (OR=1.15 [95% CI: 1.07-1.22]), weight (OR=1.10 [95% CI: 1.04-1.16]), and living outdoors as opposed to in a home (OR=3.38 [95% CI: 1.42-8.05]). According to data from studies performed in 1992 in the same area, the seroprevalence of CanL has increased 1.54-fold [95% CI: 1.04-2.29]. Given that this increasing trend cannot be attributed to differences in the sociodemographic characteristics of the dog populations, it is proposed that environmental changes could have had an impact on vector and reservoir densities and their geographical distributions. Further studies designed to explain this trend should attempt to correlate sand fly densities and CanL seroprevalences with climate, land use and human changes.

Theoretical studies of d(A:T)-based parallel-stranded DNA duplexes.

Poly d(A:T) parallel-stranded DNA duplexes based on the Hoogsteen and reverse Watson-Crick hydrogen bond pairing are studied by means of extensive molecular dynamics (MD) simulations and molecular mechanics coupled to Poisson-Boltzmann (MM-PB/SA) calculations. The structural, flexibility, and reactivity characteristics of Hoogsteen and reverse Watson-Crick parallel duplexes are described from the analysis of the trajectories. Theoretical calculations show that the two parallel duplexes are less stable than the antiparallel Watson-Crick duplex. The difference in stability between antiparallel and parallel duplexes increases steadily as the length of the duplex increases. The reverse Watson-Crick arrangement is slightly more stable than the Hoogsteen duplex, the difference being also increased linearly with the length of the duplex. A subtle balance of intramolecular and solvation terms is responsible for the preference of a given helical structure.

Parallel-stranded hairpins containing 8-aminopurines. Novel efficient probes for triple-helix formation.

We describe novel oligomers with a greater propensity to form triplexes than oligomers containing only natural bases. They consist of a polypyrimidine sequence linked head-to-head with a polypurine sequence carrying one or several 8-aminoadenine or 8-aminoguanines. The presence of 8-aminopurines also stabilised the parallel-stranded duplex structure.

The effect of amino groups on the stability of DNA duplexes and triplexes based on purines derived from inosine.

The effect of amino groups attached at positions 2 and 8 of the hypoxanthine moiety in the structure, reactivity and stability of DNA duplexes and triplexes is studied by means of quantum mechanical calculations, as well as extended molecular dynamics (MD) and thermodynamic integration (MD/TI) simulations. Theoretical estimates of the change in stability related to 2'-deoxyguanosine (G) --> 2'-deoxyinosine (I) --> 8-amino-2'-deoxyinosine (8AI) mutations have been experimentally verified, after synthesis of the corresponding compounds. An amino group placed at position 2 stabilizes the duplex, as expected, and surprisingly also the triplex. The presence of an amino group at position 8 of the hypoxanthine moiety stabilizes the triplex but, surprisingly, destabilizes the duplex. The subtle electronic redistribution occurring upon the introduction of an amino group on the purine seems to be responsible for this surprising behavior. Interesting 'universal base' properties are found for 8AI.

Is polarization important in cation-pi interactions?

The importance of cation->aromatic polarization effects on cation-pi interactions has been explored. Theoretical calculations demonstrate that polarization is a large contribution to cation-aromatic interactions, and particularly to cation-pi interactions. For a series of compounds with a similar aromatic core, polarization is constant and makes small influence in the relative cation-binding energies. However, when the aromatic core changes polarization contributions might be very different. We found that the generalized molecular interaction potential with polarization is a very fast and powerful tool for the prediction of cation binding of aromatic compounds.

Antiviral effects of xanthate D609 on the human respiratory syncytial virus growth cycle.

The antiviral compound tricyclo-decan-9-yl-xanthogenate (D609) inhibits respiratory syncytial (RS) virus growth in human epithelial (Hep 2) cells. D609 treatment resulted in a decrease in the accumulation of viral proteins, in the phosphorylation of the viral phosphoprotein, and in the amount of extracellular antigens and infectious particles. The relative accumulation of viral proteins was also unbalanced, however no differences were found in the amount of viral RNA with plus or minus polarity. In addition nucleocapsids formation was not inhibited. These observations suggested that this antiviral compound affects the relative proportion of viral proteins and the phosphorylation of P protein. Both features appear to be important in RS virus morphogenesis.