Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease

Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

Combining rimonabant and fentanyl in a single entity: preparation and pharmacological results

Based on numerous pharmacological studies that have revealed an interaction between cannabinoid and opioid systems at the molecular, neurochemical, and behavioral levels, a new series of hybrid molecules has been prepared by coupling the molecular features of two well-known drugs, ie, rimonabant and fentanyl. The new compounds have been tested for their affinity and functionality regarding CB1 and CB2 cannabinoid and mu opioid receptors. In [S-35]-GTP.S (guanosine 5'-O-[gamma-thio] triphosphate) binding assays from the post-mortem human frontal cortex, they proved to be CB1 cannabinoid antagonists and mu opioid antagonists. Interestingly, in vivo, the new compounds exhibited a significant dual antagonist action on the endocannabinoid and opioid systems.

Adenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cells

Bordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. Though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. However the precise mechanism used by B. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. Here we find that adenylate cyclase toxin (ACT), one of the important toxins of B. pertussis, is sufficient to promote bacterial internalisation into non-phagocytic cells. After characterization of the entry route we show that uptake of "toxin-coated bacteria" proceeds via a clathrin-independent, caveolae-dependent entry pathway, allowing the internalised bacteria to survive within the cells. Intracellular bacteria were found inside non-acidic endosomes with high sphingomyelin and cholesterol content, or "free" in the cytosol of the invaded cells, suggesting that the ACT-induced bacterial uptake may not proceed through formation of late endolysosomes. Activation of Tyr kinases and toxin-induced Ca2+-influx are essential for the entry process. We hypothesize that B. pertussis might use ACT to activate the endocytic machinery of non-phagocytic cells and gain entry into these cells, in this way evading the host immune system.

Effects of Small-Sided Games vs. Interval Training in Aerobic Fitness and Physical Enjoyment in Young Elite Soccer Players

The purpose of this study was to compare the effects of Small-Sided Games (SSG) vs. Interval Training (IT) in soccer training on aerobic fitness and physical enjoyment in youth elite soccer players during the last 8 weeks of the season. Seventeen U-16 male soccer players (age = 15.5 +/- 0.6 years, and 8.5 years of experience) of a Spanish First Division club academy were randomized to 2 different groups for 6 weeks: SSG group (n = 9) and IT group (n = 8). In addition to the usual technical and tactical sessions and competitive games, the SSG group performed 11 sessions with different SSGs, whereas the IT group performed the same number of sessions of IT. Players were tested before and after the 6-week training intervention with a continuous maximal multistage running field test and the counter movement jump test (CMJ). At the end of the study, players answered the physical activity enjoyment scale (PACES). During the study, heart rate (HR) and session perceived effort (sRPE) were assessed. SSGs were as effective as IT in maintaining the aerobic fitness in elite young soccer players during the last weeks of the season. Players in the SSG group declared a greater physical enjoyment than IT (P = 0.006; ES = 1.86 +/- 1.07). Coaches could use SSG training during the last weeks of the season as an option without fear of losing aerobic fitness while promoting high physical enjoyment.

Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation

Sphingolipids are major constituents of biological membranes of eukaryotic cells. Many studies have shown that sphingomyelin (SM) is a major phospholipid in cell bilayers and is mainly localized to the plasma membrane of cells, where it serves both as a building block for cell architecture and as a precursor of bioactive sphingolipids. In particular, upregulation of (C-type) sphingomyelinases will produce ceramide, which regulates many physiological functions including apoptosis, senescence, or cell differentiation. Interestingly, the venom of some arthropodes including spiders of the genus Loxosceles, or the toxins of some bacteria such as Corynebacterium tuberculosis, or Vibrio damsela possess high levels of D-type sphingomyelinase (SMase D). This enzyme catalyzes the hydrolysis of SM to yield ceramide 1-phosphate (C1P), which promotes cell growth and survival and is a potent pro-inflammatory agent in different cell types. In particular, C1P stimulates cytosolic phospholipase A2 leading to arachidonic acid release and the subsequent formation of eicosanoids, actions that are all associated to the promotion of inflammation. In addition, C1P potently stimulates macrophage migration, which has also been associated to inflammatory responses. Interestingly, this action required the interaction of C1P with a specific plasma membrane receptor, whereas accumulation of intracellular C1P failed to stimulate chemotaxis. The C1P receptor is coupled to Gi proteins and activates of the PI3K/Akt and MEK/ERK1-2 pathways upon ligation with C1P. The proposed review will address novel aspects on the control of inflammatory responses by C1P and will highlight the molecular mechanisms whereby C1P exerts these actions.

Atención integral a víctimas de delitos. Las oficinas de asistencia a víctimas de delitos (OAVD)

[ES]Este proyecto trata de revisar las diferentes Oficinas de Asistencia a las Víctimas de Delitos (OAVD) de algunas Comunidades Autónomas, desde la situación en la que se encuentran las personas víctimas de delitos que acuden a estos centros, hasta la manera de proceder de los mismos en relación a su labor (asistencia, orientación, protección, ayuda, etc. a éstas); así como de delimitar las funciones que realizan con el fin de subrayar la necesidad de un modelo de atención integral a víctimas de delitos, entendido en un sentido amplio, complejo y diverso

Diseño y caracterización de sistemas nanoestructurados a partir de copolímeros SBM

215 p.

Biochemical biomarkers in samples processed by different methods in Environmental Specimen Banks

In the last decades the creation of new Environmental Specimen Banks (ESB) is increasing due to the necessity of knowing the effects of pollutants in both the environment and human populations. ESBs analyze and store samples in order to understand the effects of chemicals, emerging substances and the environmental changes in biota. For a correct analysis of the effect induced by these variables, there is a need to add biological endpoints, such as biomarkers, to the endpoints based on chemical approaches which have being used until now. It is essential to adapt ESB´s sampling strategies in order to enable scientists to apply new biological methods. The present study was performed to obtain biochemical endpoints from samples stored in the BBEBB (Biscay Bay Environmental Biospecimen Bank) of the Marine Station of Plentzia (PIE - UPV/EHU). The main objective of the present work was to study the variability caused in biochemical biomarkers by different processing methods in mussels (Mytilus galloprovincialis) from two localities (Plentzia and Arriluze) with different pollution history. It can be concluded that the selected biomarkers (glutathione S-transferase and acetylcholinesterase) can be accurately measured in samples stored for years in the ESBs. The results also allowed the discrimination of both sampling sites. However, in a further step, the threshold levels and baseline values should be characterized for a correct interpretation of the results in relation to the assessment of the ecosystem health status.

Hediste diversicolor itsas poliketoaren azterketa biokimiko eta histologikoa

[EUS] Hediste diversicolor poliketo espeziearekin burututako eta dietarekin lotutako azterketa esperimental bat azaltzen da. Baita poliketoaren populazio basati batean eta haztegiko populazioan egindako azterketa biokimiko eta histologikoak eta hauen arteko desberdintasunak.

Identification of treatments targeting PMLexpressing breast cancers

The main aim of this project is to find a suitable ATO concentration to combine with already approved chemotherapeutic agents to find that synergistic effect in triple negative breast cancer MDA-MB 231 cell line, as a new strategy to treat the disease.

Implicación de los microRNAs en la toxicidad del metotrexato en Leucemia Linfoblástica Aguda infantil

Analisis de la implicacion de los Polimorfismos de LLA en la respuesta al Metotrexato

Implicación de rs924607 del gen CEP72 en la neurotoxicidad asociada a la vincristina en pacientes con leucemia linfoblastica aguda (LLA)

Este trabajo se trata de un estudio estadístico de asociación entre el genotipo del SNP rs924607 presente en la región promotora del gen CEP72, y la neurotoxicidad asociada a la vincristina, en pacientes pediátricos de Leucemia Linfoblástica Aguda. El objetivo es determinar si el alelo presente en dicho SNP puede ser empleado como biomarcador para predecir la neurotoxicidad asociada a la vincristina.

Silenciamiento de PTPRK, un gen candidato de la enfermedad celíaca

La enfermedad celíaca, también conocida como enteropatía sensible al gluten, es un trastorno autoinmune crónico causada por la intolerancia a la ingesta de gluten y desarrollada por personas genéticamente predispuestas cuyo único tratamiento consiste en una dieta estricta libre de gluten. El desarrollo de dicha enfermedad está relacionada con una gran variedad de genes entre los que se encuentra PTPRK. Este trabajo desarrolla un estudio de la expresión de dicho gen así como un protocolo de silenciamiento del mismo.

Variantes genéticas en ANRIL y longevidad

[ES] En este trabajo se ha analizado el efecto de 4 tag-SNPs localizados en la región promotora del ARN no codificante ANRIL en la población longeva. Se cree que la desregulación de ANRIL podría estar asociada a la longevidad, considerando que esta desregulación podría ser debida a variantes genéticas en la región promotora del mismo. Idioma: Español.

Zonas de Brillouin de los grupos de capa

La base de datos de las zonas de Brillouin de los grupos de capa del Bilbao Crystallographic Server incluye tablas de vectores de onda y figuras que forman la base para la clasificación de las representaciones de los grupos de capa. Las propiedades de simetría de los vectores de onda se determinan por los llamados grupos del espacio recíproco y esta clasificación se compara con la que recoge el libro “Character Tables and Compatibility Relations of The Eighty Layer Groups and Seventeen Plane Groups” de Litvin & Wike.