Discriminant ability of phenolic compounds and short chain organic acids profiles in the determination of quality parameters of Brandy de Jerez.

Brandy de Jerez is the most produced spirit in Spain. The rules of its Regulatory Council require the spirit to age in American oak casks that have previously contained any kind of sherry wine. This use, called seasoning, releases wine compounds into the spirit. Because of the differences among sherries, the organoleptic features of a brandy will be significantly different from any other depending on the seasoning. In addition, its specific features make it different from any other spirit. The chromatographic profiles of Brandy de Jerez are reported to be different depending on the seasonings through their ageing process. Different types of Brandy de Jerez have been characterised, regarding their seasoning, using chromatographic techniques. Applying statistical analysis, correlations between the chromatographic profiles and the seasonings have risen up. In addition, the profiles have demonstrated to possess a high degree of correlation with the ageing time of the samples.

Fast Determination of Phenolic Compounds in Rice Grains by Ultraperformance Liquid Chromatography Coupled to Photodiode Array Detection: Method Development and Validation.

There are several phenolic compounds in rice grains providing benefits for human health. The concentration of phenolic compounds in rice is strongly affected by the polishing steps during rice production. A new sensitive ultraperformance liquid chromatography-ultraviolet-visible spectroscopy method with a photodiode array detection protocol has been developed and validated for the quantitation of phenolic compounds in rice grains. Several working variables and two different columns were evaluated. Finally, a less than 3 min analysis time was developed to achieve enough resolution for the simultaneous determination of the 20 most common phenolic compounds in rice. The analytical properties for the separation method produced an adequate sensitivity for all phenolic compounds in the regular range for phenolics in rice, 0.5-100 mg L-1 ( R2 > 0.997), with high precisions for both repeatability and intermediate precisions (coefficients of variation less than 0.4 and 2.5% for the retention time and area of the peaks, respectively).

Study of a laboratory-scaled new method for the accelerated continuous ageing of wine spirits by applying ultrasound energy.

During the ageing of brandies, many physicochemical processes take place involving the distilled spirit and the wood of the casks. Because of these reactions, the polyphenolic content of brandies and their content of organic acids increase with the ageing. These reactions are slow, and the ageing of high-quality brandies takes several years. In this paper, the development of a system that uses the circulation of the wine distillate through encapsulated American oak chips and the application of ultrasound energy with the aim of producing aged wine spirits has been carried out, and the influences of the operation variables over the characteristics of the produced drink have been measured. With that proposal, the influence of different powers of ultrasound, and also the influence of the movement of the liquor through oak chips, was determined first. This way, the results show that higher powers of ultrasound, of nearly 40W/L, in addition with the movement of the spirit, improve the extraction of phenolic compounds in a 33.94%, after seven days of ageing. Then, applying Youden and Steiner's experimental design, eight experiments of ageing were performed, and the samples obtained by this new method were analysed to obtain information related to their physicochemical and oenological characterisation in order to determine the experimental conditions that produce the best ageing results. This way, the best spirit produced by this new method of ageing is obtained with a high alcoholic strength of the distilled wine and a high quantity of oak chips, and with room temperature and high flow rate. In addition, the presence of oxygen in the sample and the absence of light increase the quality of the produced spirit. Finally, the application of ultrasound energy in large pulses is related with the improvement of two important ageing markers: the intensity of the colour and the TPI. As a last experiment, we applied this ageing method to five varietal spirits. The sensorial analysis of aged samples showed the aged spirits had better ratings than the initial distilled wine.

Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease.

BACKGROUND: Given the implication of histone acetylation in memory processes, histone deacetylase inhibitors (HDACIs) have been postulated as potential modulators of cognitive impairment in Alzheimer's disease (AD). However, dose-dependent side effects have been described in patients with the currently available broad-spectrum HDACIs, explaining why their therapeutic potential has not been realized for chronic diseases. Here, by simultaneously targeting two independent enzyme activities, histone deacetylase (HDAC) and phosphodiesterase-5 (PDE5), we propose a novel mode of inhibitory action that might increase the therapeutic specificity of HDACIs. RESULTS: The combination of vorinostat, a pan-HDACI, and tadalafil, a PDE5 inhibitor, rescued the long-term potentiation impaired in slices from APP/PS1 mice. When administered in vivo, the combination of these drugs alleviated the cognitive deficits in AD mice, as well as the amyloid and tau pathology, and it reversed the reduced dendritic spine density on hippocampal neurons. Significantly, the combination of vorinostat and tadalafil was more effective than each drug alone, both against the symptoms and in terms of disease modification, and importantly, these effects persisted after a 4-week washout period. CONCLUSIONS: The results highlight the pharmacological potential of a combination of molecules that inhibit HDAC and PDE5 as a therapeutic approach for AD treatment.

Sildenafil restores cognitive function without affecting ß-amyloid burden in a mouse model of Alzheimer's disease.

BACKGROUND AND PURPOSE: Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory-related behaviour were investigated. EXPERIMENTAL APPROACH: Sildenafil was administered to the Tg2576 transgenic mouse model of Alzheimer's disease and to age-matched negative littermates (controls). Memory function was analysed using the Morris water maze test and fear conditioning tasks. Biochemical analyses were performed in brain lysates from animals treated with saline or with sildenafil. KEY RESULTS: Treatment of aged Tg2576 animals with sildenafil completely reversed their cognitive impairment. Such changes were accompanied in the hippocampus by a reduction of tau hyperphosphorylation and a decrease in the activity of glycogen synthase kinase 3ß (GSK3ß) and of cyclin-dependent kinase 5 (CDK5) (p25/p35 ratio). Moreover, sildenafil also increased levels of brain-derived neurotrophic factor (BDNF) and the activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus without any detectable modification of brain amyloid burden. CONCLUSIONS AND IMPLICATIONS: Sildenafil improved cognitive functions in Tg2576 mice and the effect was not related to changes in the amyloid burden. These data further strengthen the potential of sildenafil as a therapeutic agent for Alzheimer's disease.

[Hormonal profile and participation of nitric oxide in salt-sensitive and salt-resistant essential arterial hypertension]. / Perfil hormonal y participación del óxido nítrico en la hipertensión arterial esencial "sal sensible" y "sal resistente".

Recent studies have shown that cardiovascular events and end-organ damage occur more frequently in patients with salt-sensitive essential hypertension (SH) than in salt-resistant essential hypertension (RH). Nitric oxide (NO) plays an important role in regulating the pressure-natriuresis relationship. Therefore impaired NO synthesis may produce or aggravate salt-sensitive hypertension. This study was conducted to determine the hormonal levels and nitric oxide metabolites in hypertensive patients. 25 patients underwent salt sensitivity testing. 24 h ambulatory blood pressure was recorded after a 5-day period on low salt diet (20 mEq/d) and after a 5-day period on a high salt diet (200 mEq/d). Subjects showing > or = 10 mmHg increase in mean BP when changing from low to high dietary salt intake were classified as salt sensitive and as salt resistant when the BP changes were < 10 mmHg. Based on BP recordings 13 patients were characterised as white coat hypertension (WC), 13 patients as salt resistant (SR) and 12 as salt sensitive (SS). A significative relationship was seen between plasma glucose-insulin concentration and body mass index. The ventricular mass index was similar in SS and SR patients. The plasma uric acid, triglicerides and PAI-I were elevated in SS compared with SR, and control group (C). During low sodium intake, plasma renin and aldosterone were decreased in SS compared with SR, and C. No differences in plasma catecholamines or their changes with intake sodium modifications were seen among the patients. During high sodium intake urinary NO excretion increased in SR (38 +/- 9 vs 18 +/- 2 mg/g creat), and C (24 +/- 2 vs 16 +/- 3 mg/g creat) (p < 0.01) but not in SS patients (21 +/- 3 vs 26 +/- 4 mg/g creat). The NO excretion changes showed negative correlation with BP changes (r = 0.49, p < 0.01). During low sodium intake, SR and SS patients showed a normal nocturnal decrease of BP (dippers). During high sodium intake SS patients became non-dippers. Our results showed that patients with salt sensitive hypertension displayed a suppressed renin-aldosterone system, an attenuated nocturnal decline in blood pressure on high-salt diet and an impairment of endothelial function. The relationship between urinary nitrate excretion and arterial pressure suggest that the salt sensitivity of arterial pressure may be related bo blunted generation of endogenous nitric oxide.

Perfil hormonal y participación del óxido nítrico en la hipertensión arterial esencial 'sal sensible' y 'sal resistente' / Hormonal profile and role of nitric oxide in salt-sensitive and salt-resistant essential hypertension

Se desconoce la causa de la sensibilidad a la sal en la hipertensión arterial esencial (HTA). Dada la importancia del óxido nítrico (ON) en el manejo renal de Na+, es posible que existan diferencias en la generación de ON entre enfermos con HTA sensible a la sal (SS) e HTA resistente a la sal (SR). En el presente trabajo estudiamos el perfil hormonal y la participación del ON en 25 enfermos con HTA esencial que fueron clasificados como SS o SR por los cambios de la presión arterial media (PAM) de 24 horas, registrada por Spacelabs, en una dieta de 20 mEq/d de Na+ durante 5 días (fase hiposódica) y una dieta de 200 mEq/d de Na+ (fase hipersódica).En 13 enfermos la variación de la PAM fue _ 10 mmHg (SS). En todos los grupos hubo gran adherencia a la dieta demostrada por la natriuresis e ingesta proteica. No existieron diferencias en el filtrado glomerular (FG) entre los grupos con HTA. Los niveles de uricemia, triglicéridos e inhibidor del activador del plasminógeno (PAI-I) fueron mayores en el grupo SS que en SR y en controles sanos (C). Los niveles de actividad renina y aldosterona en la fase hiposódica fueron significativamente inferiores en los enfermos SS que en SR y en C. La variación porcentual de estas hormonas a la ingesta de sal fue inferior en los enfermos con HTA SS. No se observaron diferencias significativas en los valores de catecolaminas ni en las variaciones de éstas a los cambios de la ingesta de sal entre los diferentes grupos. Todos los enfermos presentaron, en la fase hiposódica, un descenso normal de la PAM nocturna. En la fase hipersódica, sin embargo, el descenso fue significativamente inferior en el grupo SS. Tras la sobrecarga de sodio se observó un aumento significativo de la excreción urinaria de metabolitos de ON, nitratos y nitritos (NOx), en C (24 ñ 2 vs 16 ñ 3), y en SR (38 ñ 9 vs 18 ñ 2 mglg creat.). Los NOx no se modificaron en los enfermos SS. Se objetivó una correlación inversa entre ANOx y APAM (r: -0,50, p < 0,01). El análisis de regresión logística reveló que la falta de incremento de la excreción de NOx era un factor de riesgo para la sensibilidad a la sal. Nuestros resultados demuestran que en los enfermos con HTA SS, comparados con los SR, hay una mayor supresión del sistema resina-aldosterona que es menos modificable con los cambios de ingesta de sal, y una pérdida del ritmo circadiano de la PA inducida por alta ingesta de NA+. Las alteraciones encontradas en el comportamiento de los metabolitos del ON y sus relaciones con la PA suscitan la importancia de aquel en la génesis de la sensibilidad a la sal (AU)

[L-arginine-nitric oxide pathway in hemodialysis]. / Vía de L-arginina-óxido nítrico en la hemodiálisis.

Nitric oxide (NO) is derived from the metabolism of the amino acid L-arginine by NO synthase (NOS). One of the forms of NOS (i-NOS) can be induced by cytokines, bradykinin and endotoxin. During hemodialysis (HD), blood-dialysis membrane interaction can induce production of these mediators. HD can also induce changes of asymmetrical dimethylarginine (ADA), a potent inhibitor of NOS. The aim of this study was to investigate the effect of HD, using cuprophane (C, polyacrilonytrile (PAN) and special polyacrylonitrile (SPAN) membranes, on cellular NOS activity, and changes of plasma tumor necrosis factor (TNF-alpha), bradykinin, ADA and nitrate concentration. Before HD, cellular i-NOS activity was similar with the three membranes. Cuprophane HD induced a significant increase in i-NOS activity from 31 +/- 10 to 48 +/- 12 fmol-1 10(6) cells (p < 0.05). No changes were found in PAN and SPAN HD. The TNF-alpha values increased significantly during HD with C (56 +/- 6 vs 47 +/- 5 pg/ml, p < 0.05). No changes of bradykinin concentration were found during HD. A significant decrease of ADA and nitrate levels was observed during HD with three membranes. No significant correlation was found between percentage increase in i-NOS activity and the changes in other parameters. These findings suggest that HD with bioincompatible membranes can induce activation of cellular i-NOS.

Vía de L-arginina-óxido nítrico en la hemodiálisis / L-arginine-no pathway in hemodialysis

El óxido nítrico (ON) deriva de la acción de la óxido nítrico sintasa (ONS). Una de las isoformas de esta enzima, la ONS tipo II puede ser inducida (ONS-i) por diversos estímulos como citoquinas, endotoxinas y bradiquinina entre otros. Durante la Hemodiálisis (HD) pueden generarse, dependiendo de las características de la membrana, estos mediadores. La HD puede también inducir cambios en la concentración de sustancias con capacidad de inhibir la ONS como dimetil-L-arginina asimétrica (DAA).En el presente trabajo se analizan los efectos de la HD con membranas de diferente biocompatibilidad cuprofán (C), poliacrilonitrilo (PAN) y poliacrilonitrilo especial (SPAN) en la actividad celular de la ONS-i, en los niveles de activadores de la ONS como factor de necrosis tumoral (TNF-a) y bradiquinina, y de inhibidores de la ONS como la DAA, y los cambios de nitratos, marcadores de la generación de ON. La actividad de la ONS-i celular pre-HD fue similar en todas las membranas. Tras la HD se evidenció un aumento significativo de la actividad ONS-i en la membrana de C (31 ñ 10 frente a 48 ñ 23 fmol -1.106 células, p < 0,05) mientras que no se modificó en las membranas de PAN y SPAN (31 ñ 9 frente a 31 ñ 6 y 44 ñ 14 frente a 34 ñ 11 fmol-1.106 células, respectivamente). En la HD con C se observó un aumento significativo de TNFa. Esta monoquina descendió tras la HD con PAN y no se modificó en la HD con SPAN. Con ninguna de las membranas se observaron modificaciones significativas de la bradiquinina. Con los tres procedimientos se observó un descenso significativo de los niveles de DAA y nitratos en el transcurso de la HD. No se observó correlación significativa entre las modificaciones de la actividad de la ONS-i celular y las variaciones de TNFalfa, bradiquinina, DAA, nitratos ni los valores de la presión arterial. Estos resultados evidencian que durante l a HD puede producirse un aumento de la actividad de la ONS-i celular por mecanismos relacionados con la biocompatibilidad de la membrana de diálisis. Por otra parte, la determinación de nitratos no es útil como marcador de la generación de ON durante la HD debido a sus pérdidas transdialíticas (AU)

A study of behavioural groupings of polyphenolic species in "fino" sherry wine. Evolution during vinification and mechanical treatment of the grape.

The different groups and/or classes among phenolic acids and aldehydes identified during the elaboration process of "fino" sherry wine have been studied. The study was carried out using different processes during the elaboration of the wine and we have attempted to establish whether the different treatments of the grape affect these groupings. The study was undertaken by means of cluster and multifactorial analysis on the data obtained by the quantitative determination of phenolic acids and aldehydes during vinification and in experiments carried out on the grape under different mechanical treatments. The analysis of phenolic acids and aldehydes was done with HPLC, using a C-18 mu-Bondapak and a stepwise composite gradient. The samples were previously extracted with ethylic ether.