Resveratrol Improved Flow-Mediated Outward Arterial Remodeling in Ovariectomized Rats with Hypertrophic Effect at High Dose

OBJECTIVES: Chronic increases in blood flow in resistance arteries induce outward remodeling associated with increased wall thickness and endothelium-mediated dilatation. This remodeling is essential for collateral arteries growth following occlusion of a large artery. As estrogens have a major role in this remodeling, we hypothesized that resveratrol, described as possessing phytoestrogen properties, could improve remodeling in ovariectomized rats. METHODS: Blood flow was increased in vivo in mesenteric arteries after ligation of adjacent arteries in 3-month old ovariectomized rats treated with resveratrol (5 or 37.5 mg/kg per day: RESV5 or RESV37.5) or vehicle. After 2 weeks arterial structure and function were measured in vitro in high flow (HF) and normal flow (NF) arteries isolated from each rat. RESULTS: Arterial diameter was greater in HF than in NF arteries in ovariectomized rats treated with RESV5 or RESV37.5, not in vehicle-treated rats. In mice lacking estrogen receptor alpha diameter was equivalent in HF and NF arteries whereas in mice treated with RESV5 diameter was greater in HF than in NF vessels. A compensatory increase in wall thickness and a greater phenylephrine-mediated contraction were observed in HF arteries. This was more pronounced in HF arteries from RESV37.5-treated rats. ERK1/2 phosphorylation, involved in hypertrophy and contraction, were higher in RESV37.5-treated rats than in RESV5- and vehicle-treated rats. Endothelium-dependent relaxation was greater in HF than in NF arteries in RESV5-treated rats only. In HF arteries from RESV37.5-treated rats relaxation was increased by superoxide reduction and markers of oxidative stress (p67phox, GP91phox) were higher than in the 2 other groups. CONCLUSION: Resveratrol improved flow-mediated outward remodeling in ovariectomized rats thus providing a potential therapeutic tool in menopause-associated ischemic disorders. This effect seems independent of the estrogen receptor alpha. Nevertheless, caution should be taken with high doses inducing excessive contractility and hypertrophy in association with oxidative stress in HF arteries

Evaluación de técnicas de defensa y de la densidad en el cultivo de una nueva hortaliza : Cucúrbita pepo var. vegetable spaghetti

El zapallo Spaghetti, cultivo vigoroso de clima templado, constituye una alternativa productiva interesante y novedosa para nuestro país. El objetivo de este estudio fue evaluar el efecto del mulching y de la densidad sobre el rendimiento total, el peso medio y el calibre de los frutos. El estudio se llevó a cabo en Azul sobre un suelo Argiudol típico en camellones de 0,80 m de ancho con diferentes densidades de siembra. Se realizó una fertilización profunda en bandas de 0,80 m con fosfato diamónico, controlando las malezas en forma química, manual y mecánicamente, y las plagas haciendo aplicaciones preventivas de insecticidas y fungicidas. La siembra manual se efectuó el 2 de noviembre y los tratamientos fueron: densidades de siembra de 20, 15, 10 y 5 mil pl/ha (D1, D2, D3 y D4), con y sin mulching. Se trabajó con 32 parcelas y cada una tenía tres surcos de seis metros de longitud separados entre si por 2m. Se realizaron cuatro cosechas al llegar a la madurez completa (15/2, 29/2, 7/3 y 3/4). Los calibres evaluados fueron: (1) 2,2 kg, (2) 1,7 kg; (3) 1,3 kg y (4) 0,8 kg / fruto. Para el análisis de los datos se utilizó un modelo de bloques completamente aleatorizados con parcelas sub-divididas. En la parcela principal se evaluó el efecto del mulching, en la subparcela la densidad y la interacción de mulching por densidad, y en la subsubparcelas las diferentes cosechas. La cosecha total mostró diferencias significativas para el efecto del mulching, obteniéndose 71,90 t/ha (a) (con mulching) y 62,02 t/ha (b) (sin mulching); para cada densidad se detectaron diferencias significativas para el efecto mulching: D1: 84,45 t/ha (a), D2: 76,47 t/ha (ab); D3: 65,14 t/ha (b) y D4: 61,55 t/ha (b). Se observaron diferencias significativas en el número de frutos cosechados: con mulching (51.667 frutos/ha) y sin mulching (44.167 frutos/ha), y para las diferentes densidades: D1: 54.167 (a); D2: 50.000 (ab); D3: 47.700 (ab) y D4: 40.833 (b) t/ha. La composición de calibres de frutos cosechados fue el mismo para todos los tratamientos y cosechas.Spaghetti Squash is a vigorous crop that grows in temperate climates and is an interesting novelty for our country. The objective of this study was to evaluate the effect of mulching and density over total yield, fruit average weight and caliber. The experimental work study was carried out in Azul on a typical Argiudol soil, on 0.80 m wide ridge with different sowing densities. Deep fertilization, on 0.80 m bands with diammonium phosphate, was made. Weed control was done chemically, manually and mechanically. Preventive applications of insecticides and fungicides were performed. Hand sowing was done on November 2nd and the treatments were: sowing densities of 20, 15, 10 and 5 thousand pl/ha (D1, D2, D3 and D4), with and without mulching. The trial was held on 32 plots and each one had three six-meter long furrows 2 m apart from each other. Four harvests at complete ripeness took place (15/2, 29/2, 7/3 and 3/4). The evaluated calibers were: (1) 2.2 kg, (2) 1.7 kg; (3) 1.3 kg and (4) 0.8 kg / fruit. A model of completely aleaterized blocks with subdivided plots was used. On the main plot the effect of muching was evaluated, on the sub-plot density and the interaction of mulching by density was considered and on the sub-sub-plots the effect of different crops. Total harvest showed significant differences with mulching, up to 71.90 t/ha and without mulching: 62.02 t/ha (b); for each density, there were significant differences with mulching: D1: 84.45 t/ha (a), D2: 76.47 t/ha (ab); D3: 65.14 t/ha (b) and D4: 61.55 t/ha (b). There were significant differences in the number of harvested fruits with mulching (51,667 fruits/ha) and without mulching (44,167 fruits/ha), and for the different densities: D1: 54,167 (a); D2: 50,000 (ab); D3: 47,700 (ab) and D4: 40,833 (b) t/ha. Harvested squash caliber percentage composition was the same for all treatments and crops

Evaluación de la eficacia de la técnica de floating system para la producción de radicchio rosso var. di Verona en condiciones controladas

La técnica de producción en Floating system constituye una alternativa económica y veloz de producción en hidroponia. Este sistema permite obtener hojas de vegetales de pequeño tamaño “Baby leaf” listas para consumir (IV Gama), cuyo consumo a nivel mundial muestra una tendencia creciente. Dicha técnica no se encuentra aún muy difundida para la producción de radicchio rosso. El objetivo de este trabajo fue evaluar el efecto del tamaño de celda, del substrato y de la técnica de floating system sobre la producción de radicchio. Los ensayos se realizaron en cámara a 25 ºC con un fotoperíodo de 16 hs de luz y 8 de oscuridad y con una intensidad de luz de 10 000 Lux. Se utilizó un diseño experimental factorial totalmente aleatorizado, con 5 repeticiones y 3 factores, cuyos niveles fueron: 1) Tamaño de celda, (T), con 3 niveles: grande, mediano y pequeño, 2) Técnica de producción, (F), con 2 niveles: floating system y sistema convencional, 3) Sustrato, (S), con 2 niveles: vermiculita y mezcla. Se analizaron las siguientes variables: 1) peso fresco, 2) peso seco, 3) largo de planta, 4) número de hojas y 5) área foliar. Los resultados obtenidos resultan alentadores respecto del empleo de la técnica de floating system. Para la obtención de plántulas con calidad de IV Gama resulta más conveniente el empleo de celdas de 80 cm3 y sustrato mezcla.Floating system is a cheap and fast alternative of hydroponic production. This system allows the obtention of ready to eat baby leaf (IV Gama) vegetables whose consumption shows a growing trend worldwide. Unfortunately this technique is poorly divulged for the production of radicchio rosso. The aim of this study was to evaluate the effect of cell size, substratum and floating system on the production of radicchio rosso. The trial was carried out in a chamber at 25ºC with a photoperiod of 16 hours of light and 8 of darkness and a light intensity of 10000 Lux. A totally 3 randomized factorial experimental design was used with five repetitions and 3 factors whose levels were:1) cell size (T) with three levels: big, medium and small; 2) production technique (F) with two levels: floating system and conventional system; 3) substratum (S) with two levels: vermiculla and mixed. The following variables were analyzed: 1) fresh weight, 2) dry weight, 3) plant length, 4) number of leaves, 5) leaf area. The results obtained are encouraging concerning the use of the floating system technique. In order to obtain seedlings with IV Gama quality, it is more appropriate to use cells of 80cm3 and mixed substratum

Autoxidation Kinetics of Tetrahydrobiopterin—Giving Quinonoid Dihydrobiopterin the Consideration It Deserves

In humans, tetrahydrobiopterin (H4Bip) is the cofactor of several essential hydroxylation reactions which dysfunction cause very serious diseases at any age. Hence, the determination of pterins in biological media is of outmost importance in the diagnosis and monitoring of H4Bip deficiency. More than half a century after the discovery of the physiological role of H4Bip and the recent advent of gene therapy for dopamine and serotonin disorders linked to H4Bip deficiency, the quantification of quinonoid dihydrobiopterin (qH2Bip), the transient intermediate of H4Bip, has not been considered yet. This is mainly due to its short half-life, which goes from 0.9 to 5 min according to previous studies. Based on our recent disclosure of the specific MS/MS transition of qH2Bip, here, we developed an efficient HPLC-MS/MS method to achieve the separation of qH2Bip from H4Bip and other oxidation products in less than 3.5 min. The application of this method to the investigation of H4Bip autoxidation kinetics clearly shows that qH2Bip’s half-life is much longer than previously reported, and mostly longer than that of H4Bip, irrespective of the considered experimental conditions. These findings definitely confirm that an accurate method of H4Bip analysis should include the quantification of qH2Bip

Resveratrol metabolism in a non-human primate, the grey mouse lemur (Microcebus murinus), using ultra-high-performance liquid chromatography-quadrupole time of flight.

The grey mouse lemur (Microcebus murinus) is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 mg.kg-1 of oral resveratrol) by ultra-high performance liquid chromatography (UHPLC), coupled to a quadrupole-time-of-flight (Q-TOF) mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives) and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives). The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism

Réseau Hydrologique Littoral Normand - RHLN - Année 2012

Le Réseau Hydrologique Littoral Normand (RHLN) a été approuvé en 2007 par ses partenaires, avec le triple objectif (1) de maintenir le suivi de la qualité des masses d’eau et d’évaluer leur niveau d’eutrophisation en réponse aux réglementations (Directive Nitrate, OSPAR, DCE), (2) de poursuivre la réflexion sur la définition des indicateurs DCE, puis (3) de développer les connaissances et de fournir des données à la modélisation. Ce rapport réalise la synthèse des résultats obtenus en 2012, onzième année depuis le début du suivi en Normandie. Le climat de cette année 2012 a été caractérisé par des températures saisonnières proches des normales malgré des écarts de température parfois importants d’un mois sur l’autre (notamment en hiver). Par rapport aux moyennes saisonnières, les précipitations ont été faibles en hiver et excédentaires le reste de l’année, surtout en automne. Par voie de conséquence, les débits et donc l’approvisionnement du milieu en nutriments ont été supérieurs à ceux des autres années. Ces apports ont favorisé la production chlorophyllienne qui, avec une moyenne (tous points confondus) de 2,6 µg.L-1, a été globalement identique à celle de 2010, mais supérieure à celle de 2011 pour près de 76 % des points. Le pic de biomasse le plus fort (24,4 µg.L-1) a été observé au point « Antifer Ponton Pétrolier » (HC16). Le nombre de blooms phytoplanctoniques (59 dépassements du seuil de 100 000 cellules par litre dont 8 dépassements du seuil de 1 000 000 cellules par litre) a été supérieur à celui de 2011 ainsi qu’à celui de 2010. Les taxons Pseudo-Nitzschia sp., Chaetoceros sp., Phaeocystis, Rhizosolenia sp. et Skeletonema costatum, ont dominé le peuplement phytoplanctonique en 2012, Chaetoceros sp. s’imposant depuis le début du RHLN comme le principal taxon responsable de ces dépassements de seuils. Les synthèses interannuelles montrent qu’à la fois le nombre de blooms phytoplanctoniques et la proportion de taxons nuisibles dans ces blooms tendraient à diminuer au cours du temps. Comme les années précédentes, le fond de la colonne d’eau est resté correctement oxygéné en 2012 (aucun risque de suboxie). Les stocks hivernaux de nutriments ont été les plus forts au niveau des masses d’eau estuariennes, avec des gradients décroissants du Sud vers le Nord de la Côte Ouest, et croissants vers l’Est de la Baie de Seine. En été, des carences potentielles en azote ont été observées sur la majorité des points sauf à proximité des estuaires de l’Orne et de la Seine, où l’azote est resté excédentaire même en été. L’évaluation du niveau d’eutrophisation des masses d’eau normandes au moyen des Indicateurs Abondance et Biomasse du phytoplancton retenus dans le cadre de la DCE et fixés par l’arrêté du 25 janvier 2010, a permis de conclure que sur les 21 masses d’eau évaluées sur la période 2007-2012, 15 sont classées en Très Bon état, 5 sont classées en Bon état, et 1 masse d’eau est classée en Etat moyen. Pour la majorité des masses d’eau, cet élément de qualité « Phytoplancton » tend à s’améliorer ou à rester stable au cours du temps. Vis-à-vis de l’élément de qualité « Oxygène dissous », l’ensemble des masses d’eau a présenté un Très bon état sur la période 2007-2012 comme les années précédentes. Une présentation des Eléments de Qualité utilisés dans les synthèses nationales a été réalisée en dernière partie de ce rapport, et accompagnée d’une discussion sur l’état actuel du développement des différents indicateurs. Malgré quelques améliorations de méthodologie possibles à l’avenir, cette synthèse nationale pour l’Elément de Qualité « Phytoplancton » et pour l’Indice « Oxygène dissous » a montré une bonne cohérence avec les synthèses RHLN 2007-2012

Fasting upregulates the monocarboxylate transporter MCT1 at the rat blood-brain barrier through PPAR δ activation

International audienceBackground: The blood-brain barrier (BBB) is pivotal for the maintenance of brain homeostasis and it strictly regulates the cerebral transport of a wide range of endogenous compounds and drugs. While fasting is increasingly recognized as a potential therapeutic intervention in neurology and psychiatry, its impact upon the BBB has not been studied. This study was designed to assess the global impact of fasting upon the repertoire of BBB transporters.Methods: We used a combination of in vivo and in vitro experiments to assess the response of the brain endothelium in male rats that were fed ad libitum or fasted for one to three days. Brain endothelial cells were acutely purified and transcriptionaly profiled using RNA-Seq. Isolated brain microvessels were used to assess the protein expression of selected BBB transporters through western blot. The molecular mechanisms involved in the adaptation to fasting were investigated in primary cultured rat brain endothelial cells. MCT1 activity was probed by in situ brain perfusion. Results: Fasting did not change the expression of the main drug efflux ATP-binding cassette transporters or P-glycoprotein activity at the BBB but modulated a restrictive set of solute carrier transporters. These included the ketone bodies transporter MCT1, which is pivotal for the brain adaptation to fasting. Our findings in vivo suggested that PPAR δ, a major lipid sensor, was selectively activated in brain endothelial cells in response to fasting. This was confirmed in vitro where pharmacological agonists and free fatty acids selectively activated PPAR δ, resulting in the upregulation of MCT1 expression. Moreover, dosing rats with a specific PPAR δ antagonist blocked the upregulation of MCT1 expression and activity induced by fasting.Conclusions: Altogether, our study shows that fasting affects a selected set of BBB transporters which does not include the main drug efflux transporters. Moreover, we describe a previously unknown selective adaptive response of the brain vasculature to fasting which involves PPAR δ and is responsible for the up-regulation of MCT1 expression and activity. Our study opens new perspectives for the metabolic manipulation of the BBB in the healthy or diseased brain

Phenylephrine-mediated contraction in mesenteric arteries submitted to high blood flow.

<p>Phenylephrine-mediated contraction was measured in mesenteric arteries submitted to a chronic increase in blood flow (high flow: HF, right panel) and in control arteries submitted to normal flow (NF, left panel). Arteries were isolated from ovariectomized rats treated with resveratrol 5.0 (R5.0 or Resv. 5.0, n = 9 rats) or 37.5mg/kg (R37.5 or Resv. 37.5, n = 9 rats) or with the vehicle (n = 10 rats). Mean ± sem is represented. *P<0.05, HF versus NF arteries. ^#P<0.05, R37.5 versus vehicle.</p