Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids.

The possible modulatory effect of the functional LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids, on the catecholaminergic and cholinergic neurotransmission, affecting cognition decline during aging has been studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or control diets. The enzymes involved in catecholaminergic and cholinergic metabolism were determined by both immunohistological and western blot analyses. Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis. Theobromine, present in cocoa, the main LMN diet component, was analysed in parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both cholinergic and catecholaminergic transmissions was observed on 20 day fed mice. Similar effect was observed with theobromine, besides its antioxidant capacity inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and theobromine on the levels of acetylcholine-related enzymes, dopamine and specially noradrenalin confirms the beneficial role of this diet on the "cognitive reserve" and hence a possible reducing effect on cognitive decline underlying aging and Alzheimer's disease.

Cribado combinado de síndrome de Down en primer trimestre: comparación de resultados de 4 años de aplicación con los 4 años precedentes / First-trimester combined screening for Down syndrome: comparison of the 4-year results with the previous 4 years

Objetivo. Analizar los resultados de 4 años de aplicación del programa de cribado combinado del primer trimestre y su impacto sobre las tasas de detección de síndrome de Down, cobertura poblacional y procedimientos invasivos. Sujetos y métodos. Estudio retrospectivo poblacional de 8 años consecutivos (17.564 gestaciones que contienen 51 síndromes de Down), en 2 periodos: 31 de enero de 2002 a 30 de enero de 2006, sin cribado (8.182 gestaciones y 24 síndromes de Down) y 31 de enero de 2006 a 30 de enero de 2010, con cribado (8.382 gestaciones y 27 síndromes de Down). El cribado se aplicó en 2 fases: bioquímica a la 10 semana y ecografía a la 12 semana. Se comparan los resultados del cribado con los del periodo precedente basado en la edad materna y la medida de la translucencia nucal. Resultados. La cobertura poblacional fue de 93%. La tasa de detección de síndrome de Down por aplicación del cribado combinado ha sido del 89% (91% para feto único) para un 3,5% de falsos positivos y se realizaron 824 procedimientos invasivos (34,3 para 1 diagnóstico). En los 4 años previos a la aplicación del cribado, la tasa de detección era del 71% y se realizaron 1.406 procedimientos invasivos (87,8 para un diagnóstico). Conclusión. El cribado combinado ha mejorado las tasas de detección para síndrome de Down en un 18%, al tiempo que ha permitido reducir en un 41% los procedimientos invasivos (AU)

Objective. To analyze the 4-year results of first-trimester combined screening and its impact on rates of Down syndrome detection, population coverage and invasive procedures. Subjects and methods. We performed a retrospective population-based study over 8 consecutive years (17,564 gestations with 51 cases of Down syndrome) divided in two periods: from January 31, 2002 to January 30, 2006 without combined screening (8,182 gestations and 24 cases of Down syndrome) and from January 31, 2006 to January 30, 2010 with combined screening (8,382 gestations and 27 cases of Down syndrome). Combined screening was applied in two phases: biochemical analysis was performed in the 10th week of pregnancy and ultrasound examination in the 12th week. We compared the results of screening with the previous period based on maternal age and fetal nuchal translucency measurement. Results. Population coverage was 93%. The rate of Down syndrome detection due to the application of combined screening was 89% (91% for a single fetus) with a false-positive rate of 3.5%. There were 824 invasive procedures (34.1 to diagnose one episode). During the 4 years prior to the application of combined screening, the detection rate was 71% with 1,406 invasive procedures (87.8 to diagnose one episode). Conclusion. Combined screening has improved the Down syndrome detection rate by 18% and has reduced the use of invasive procedures by 41% (AU)

LMN diet, rich in polyphenols and polyunsaturated fatty acids, improves mouse cognitive decline associated with aging and Alzheimer's disease.

We examined whether LMN diet, reported to induce neurogenesis in adult mice, was able to antagonize the age-related behavioural impairment and neuropathology in wild type (WT) mice and Tg2576 mice, a mouse model of Alzheimer's disease (AD). Thirteen-month-old mice (once the amyloid (Aß) plaques were formed) were fed with the LMN diet for 5 months, and in the last 2 months of the regimen they received a battery of behavioural tests. In general, both aging and (to a higher extent) Tg2576 genotype deteriorated sensorimotor reflexes, exploratory behaviour in the hole board, activity (but not anxiety) in the elevated plus-maze, ambulation in the home cage during the dark phase, and spatial learning in the Morris water maze. LMN diet did not affect the detrimental effects observed in sensorimotor reflexes, but clearly reversed the effects of both aging and Tg2576 genotype. This behavioural amelioration was correlated with a 70% increase in cellular proliferation in subventricular zone (SVZ) of the brain, but did not correlate with a decrease of amyloid plaques. In contrast, administration of LMN diet to 10 months old mice (before the plaques are formed) strongly suggested a putative delay in the formation of plaques, as indicated by a decreasing tendency of soluble and fibrillar Aß levels in hippocampus which correlated with a decrease in Aß (1-40, 1-42) plasma content. Herein we describe for the first time that LMN diet rich in polyphenols, dry fruits and cocoa, was able to decrease behavioural deterioration caused by aging and Tg2576 genotype and to delay the Aß plaque formation. These results corroborate the increasing importance of polyphenols as human dietary supplements in amelioration of the cognitive impairment during aging and neurological disorders such as AD.

Growth arrest-specific gene 6 (GAS6). An outline of its role in haemostasis and inflammation.

GAS6 (growth arrest-specific 6) belongs structurally to the family of plasma vitamin K-dependent proteins. GAS6 has a high structural homology with the natural anticoagulant protein S, sharing the same modular composition and having 40% sequence identity. Despite this, the low concentration of GAS6 in plasma and the pattern of tissue expression of GAS6 suggest a distinct function among vitamin-K dependent proteins. Indeed, GAS6 has growth factor-like properties through its interaction with receptor tyrosine kinases of the TAM family; Tyro3, Axl and MerTK. GAS6 employs a unique mechanism of action, interacting through its vitamin K-dependent GLA (gamma-carboxyglutamic acid) module with phosphatidylserine-containing membranes and through its carboxy-terminal LamG domains with the TAM membrane receptors. During the last years there has been a considerable expansion of our knowledge of the biology of TAM receptors that has lead to a clear picture of their importance in inflammation, haemostasis and cancer, making this system an interesting target in biomedicine. The innate immune response and the coagulation cascade have been shown to be interconnected. Mediators of inflammation are essential in the initiation and propagation of the coagulation cascade, while natural anticoagulants have important anti-inflammatory functions. GAS6 represents a new player in this context, while protein S seems to have new functions beyond its anticoagulant role through its interaction with TAM receptors.

Oxido nítrico: fisiopatología

El Oxido Nítrico es una molécula gaseosa que está involucrada en los cambios hemodinámicos que se ven en el Síndrome de Respuesta Inflamatoria Sistémica (SRIS) y que van desde la Insuficiencia cardíaca pasando por el shock séptico, hasta los cambios que se observan durante el Síndrome de Enfermedad Respiratoria Aguda (ARDS), lo mismo que en el hígado o riñones durante el Síndrome de Enfermedad de Organos Múltiples (MODS), desempeñando además funciones fisiológicas que son imprescindibles para el mantenimiento de la economía(AU)