8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases.

We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) and monoamine oxidases (hMAO-A/B) for the therapy of neurodegenerative diseases. We identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition of hBChE (IC50 = 1.06 ± 0.31 nmol/L) and hMAO-B (IC50 = 4.46 ± 0.18 µmol/L). The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding, which was further studied by enzyme kinetics. Compound 19 acted as a free radical scavenger and biometal chelator, crossed the blood-brain barrier, was not cytotoxic, and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease. In addition, in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination. Importantly, chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice, underscoring the disease-modifying effect of QN 19.

Relació entre les aportacions enterals de vitamina D I els nivells plasmàtics en nadons prematurs / Relación entre las aportaciones enterales de vitamina D y los niveles plasmáticos en recién nacidos prematuros / Relationship between the enteral intake of vitaminD and plasma levels in premature newborns

FONAMENT: En els prematurs, uns nivells inadequats de vitamina D poden comportar més comorbiditat, però hi ha controvèrsia en les recomanacions de suplementació. OBJECTIU: Intentar correlacionar aportacions (dieta I suplementació) de vitamina D amb nivells inadequats d'aquesta vitamina. MÉTODE: Estudi descriptiu retrospectiu dels prematurs als quals se'ls determina calcifediol (25(OH)D3) entre els mesos de gener I desembre del 2016 al nostre centre. RESULTATS: Incloem 36 determinacions de 25(OH)D3 de 17 nadons (58,8% de sexe masculí) amb mediana d'edat gestacional de 29,8 setmanes (rang: 24,85-35,14) I mediana de pes de 980 g (rang: 420-2.220 g). La mediana d'edat en dies en el moment de l'extracció és 58,5 (rang: 6-188); la mediana de 25(OH)D3 és 53,92ng/ml (rang: 17,1-150). Segons el càlcul de les aportacions de vitamina D, s'obté una mediana de 885 U/dia (rang: 2-1416). Hi ha una correlació estadísticament significativa entre 25(OH)D3 plasmàtica I aportacions. El 75% que rep aportacions de <400 U tenen nivells insuficients; el 62,5% que rep >1.200 U tenen nivells tòxics. Dels que reben 400-1.200 U, el 84% tenen nivells òptims; hi ha diferència entre els que reben 400-800 U, amb un 60% amb nivells suficients, I els que reben 800-1.200 U, amb un 92% amb nivells adequats. Hi ha diferència en el percentatge de mostres amb nivells insuficients segons la classificació de 2009 respecte de l'actual. CONCLUSIONS: Les aportacions de vitamina D d'entre 800 I 1.200 U/dia s'associen a nivells òptims en un percentatge elevat de nadons. Les aportacions inferiors a 400 U o superiors a 1.200 U s'associen a nivells inadequats. L'alimentació per si sola no garanteix els requeriments necessaris de vitamina D, però és una dada essencial que s'ha de tenir en compte. Cal individualitzar la dosi segons els nivells plasmàtics

FUNDAMENTO: En los prematuros, unos niveles inadecuados de vitamina D pueden comportar mayor comorbilidad, pero existe controversia en las recomendaciones de suplementación. OBJETIVO: Intentar correlacionar aportaciones (dieta y suplementación) de vitamina D con niveles inadecuados de esta vitamina. MÉTODO: Estudio descriptivo retrospectivo de los prematuros a los que se les realiza determinación de calcifediol (25(OH)D3) entre enero y diciembre de 2016 en nuestro centro. RESULTADOS: Incluimos 36 determinaciones de 25(OH)D3 de 17 pacientes (58,8% de sexo masculino) con mediana de edad gestacional de 29,8 semanas (rango: 24,85-35,17) y mediana de peso de 980 g (rango: 420-2.220 g). La mediana de edad en días en el momento de la extracción es 58,5 (rango: 6-188); la mediana de 25(OH)D3 es 53,92 ng/ml (rango: 17,1-150). Según el cálculo de los aportes de vitamina D, se obtiene una mediana de 885 U/día (rango: 2-1.416). Existe una correlación estadísticamente significativa entre niveles de 25(OH)D3 y aportes. El 75% que recibe aportes de <400 U tienen niveles insuficientes; el 62,5% que recibe >1.200 U tienen niveles tóxicos. De los que reciben 400-1200 U, el 84% tienen niveles óptimos; existe diferencia entre aquellos que reciben 400-800 U, con un 60% con niveles suficientes, y los que reciben 800-1.200 U, con un 92% con niveles adecuados. Existe diferencia en el porcentaje de muestras con niveles insuficientes según la clasificación de 2009 versus la actual. CONCLUSIONES: Los aportes de vitamina D entre 800 y 1.200 U/día se asocian a niveles óptimos en un porcentaje elevado de prematuros. Las aportaciones inferiores a 400 U o superiores a 1.200 U se asocian a niveles inadecuados. La alimentación por sí sola no garantiza los requerimientos necesarios de vitamina D, pero es un dato esencial a tener en cuenta. Es necesario individualizar la dosis en función de los niveles plasmáticos

BACKGROUND: Inadequate levels of vitamin D in premature newborns may lead to additional comorbidities; however, controversy exists regarding recommendations for supplementation. OBJECTIVE: To analyze correlations between vitamin D intake (diet and supplementation) with inadequate calcifediol (25(OH)D3) levels. METHOD: Descriptive, retrospective study of premature babies, whose 25(OH)D3 levels were determined between January and December 2016, in our medical centre. RESULTS: Thirty-six plasma level determinations of 25(OH)D3 in 17 patients (58.8% male) with median gestational age of 29.8 weeks (range: 24.85-35.14) and median weight of 980g (range 420-2220). The median age in days was 58,5 (range: 6-188) at the moment of determination, and the median plasma level of 25(OH)D3 was 53,92ng/ml (range:17.1-150). The median vitamin D intake was 885U/day (range: 2-1416). There was a significant correlation between 25(OH)D3 levels and vitamin D intake. Seventy-five percent of patients who received <400U intake had insufficient levels; and 62,5% who received >1200 had toxic levels. Eighty-four percent of those who received between 400 and 1200U had adequate levels; 60% of premature newborns who received 400-800U had sufficient levels versus 92% of babies who received 800 to 1200U. There were differences in percentage of samples with insufficient levels according to 2009 classification versus the current one. CONCLUSIONS: In a high percentage of premature babies, 800-1200U vitamin D intake result in adequate levels. Vitamin D in-take of <400U or >1200U correlate with inadequate levels. It is important to consider that nutrition by itself doesn't guarantee the required vitamin D intake. Individualized doses are needed according to blood plasma levels

Training of panellists for the sensory control of bottled natural mineral water in connection with water chemical properties.

As bottled mineral water market is increasing in the world (especially in emergent and developed countries), the development of a simple protocol to train a panel to evaluate sensory properties would be a useful tool for natural drinking water industry. A sensory protocol was developed to evaluate bottled natural mineral water (17 still and 10 carbonated trademarks). The tasting questionnaire included 13 attributes for still water plus overall impression and they were sorted by: colour hues, transparency and brightness, odour/aroma and taste/flavour/texture and 2 more for carbonated waters (bubbles and effervescence). The training lasted two months with, at least, 10 sessions, was adequate to evaluate bottled natural mineral water. To confirm the efficiency of the sensory training procedure two sensory groups formed the whole panel. One trained panel (6 persons) and one professional panel (6 sommeliers) and both participated simultaneously in the water tasting evaluation of 3 sample lots. Similar average scores obtained from trained and professional judges, with the same water trademarks, confirmed the usefulness of the training protocol. The differences obtained for trained panel in the first lot confirm the necessity to train always before a sensory procedure. A sensory water wheel is proposed to guide the training in bottled mineral water used for drinking, in connection with their chemical mineral content.