Insulin resistance in mice lacking neuronal nitric oxide synthase is related to an alpha-adrenergic mechanism

Rapport de synthèse : Le monoxyde d'azote (NO) joue un rôle important dans la régulation de l'homéostasie du système cardiovasculaire et du glucose. Les souris déficientes pour le gène codant l'isoforme neuronale de la synthase de monoxyde d'azote (nNOS) sont résistantes à l'insuline, mais les mécanismes sous-jacents sont inconnus. Le manque de NO produit par la nNOS pourrait être à l'origine d'une diminution de la perfusion du muscle squelettique et ainsi d'une diminution de l'apport de substrat. Alternativement, le déficit de nNOS normalement hautement exprimé dans le tissu musculaire squelettique pourrait directement y perturber la consommation de glucose. Finalement l'absence de l'action sympatholytique du NO neuronal pourrait diminuer la sensibilité à l'insuline. Afin de tester ces hypothèses nous avons étudié, chez des souris déficientes en nNOS et des souris-contrôle, la consommation corporelle totale de glucose et le flux musculaire squelettique pendant des clamps hyperinsulinémiques euglycémiques in vivo, ainsi que la consommation de glucose dans le muscle squelettique in vitro. De plus nous avons analysé les effets d'une inhibition alpha-adrénergique sur la consommation de glucose pendant les clamps hyperinsulinémiques euglycémiques in vivo. Le taux de perfusion de glucose pendant les clamps était grossièrement 15 pourcent plus bas (P<0.001) chez les souris déficientes en nNOS que chez les souris-contrôle. Cette résistance à l'insuline chez les souris déficientes en nNOS n'était due ni à une stimulation déficiente du flux sanguin musculaire par l'insuline ni à un défaut intrinsèque de la consommation de glucose du muscle (qui étaient comparables dans les deux groupes), mais à un mécanisme alpha-adrénergique, car l'administration de phentolamine rétablissait la sensibilité à l'insuline chez les souris déficientes en nNOS. Ces résultats suggèrent qu'une hyperactivité sympathique, potentiellement due à la perte de l'inhibition neuronale centrale du flux sympathique par le NO provenant de nNOS, contribue à la résistance à l'insuline des souris déficientes en nNOS. Par ailleurs ces résultats tendent à prouver qu'un défaut de production de NO provoquerait une résistance à l'insuline par des mécanismes différents selon l'isoforme de NO synthase déficiente (par exemple chez les souris déficientes pour la forme endothéliale de NO synthase, il a été montré que la résistance à l'insuline est due à un défaut de stimulation de la perfusion musculaire par l'insuline et à un défaut du signalling de l'insuline dans la cellule musculaire squelettique). Chez l'être humain il est établi que les états de résistance à l'insuline sont associés à une synthèse défectueuse et/ou une mauvaise biodisponibilité du NO, ainsi qu'à une hyperactivité sympathique. Nous spéculons que la perte d'inhibition centrale du flux sympathique représente un mécanisme contribuant à la résistance à l'insuline et ses complications cardiovasculaires chez l'être humain.

Nitric oxide and the release of lipoprotein lipase from white adipose tissue

Background/Aim: Lipoprotein lipase (LPL) is the main enzyme responsible for the distribution of circulating triacylglycerides in tissues. Its regulation via release from active sites in the vascular endothelium is poorly understood. In a previous study we reported that in response to acute immobilization (IMMO), LPL activity rapidly increases in plasma and decreases in white adipose tissue (WAT) in rats. In other stress situations IMMO triggers a generalized increase in nitric oxide (NO) production. Methods/Results: Here we demonstrate that in rats: 1) in vivo acute IMMO rapidly increases NO concentrations in plasma 2) during acute IMMO the WAT probably produces NO via the endothelial isoform of nitric oxide synthase (eNOS) from vessels, and 3) epididymal WAT perfused in situ with an NO donor rapidly releases LPL from the endothelium. Conclusion: We propose the following chain of events: stress stimulus / rapid increase of NO production in WAT (by eNOS) / release of LPL from the endothelium in WAT vessels. This chain of events could be a new mechanism that promotes the rapid decrease of WAT LPL activity in response to a physiological stimulus.

Avalanche-like vortex penetration driven by pulsed microwave fields in an epitaxial LaSrCuO thin film

Different vortex penetration regimes have been registered in the output voltage signal of a magnetometer when single microwave pulses are applied to an epitaxial overdoped La2− x Sr x CuO4 thin film in a perpendicular dc magnetic field. The onset of a significant variation in the sample magnetization which exists below threshold values of temperature, dc magnetic field, and pulse duration is interpreted as an avalanche-type flux penetration. The microwave contribution to the background electric field suggests that the nucleation of this fast vortex motion is of electric origin, which also guarantees the occurrence of vortex instabilities under adiabatic conditions via the enhancement of the flux flow resistivity. Flux creep phenomena and heat transfer effects act as stabilizing factors against the microwave-pulse-induced fast flux diffusion.

Differential stress reaction of human colon cells to oleic-acid-stabilized and unstabilized ultrasmall iron oxide nanoparticles.

Therapeutic engineered nanoparticles (NPs), including ultrasmall superparamagnetic iron oxide (USPIO) NPs, may accumulate in the lower digestive tract following ingestion or injection. In order to evaluate the reaction of human colon cells to USPIO NPs, the effects of non-stabilized USPIO NPs (NS-USPIO NPs), oleic-acid-stabilized USPIO NPs (OA-USPIO NPs), and free oleic acid (OA) were compared in human HT29 and CaCo2 colon epithelial cancer cells. First the biophysical characteristics of NS-USPIO NPs and OA-USPIO NPs in water, in cell culture medium supplemented with fetal calf serum, and in cell culture medium preconditioned by HT29 and CaCo₂ cells were determined. Then, stress responses of the cells were evaluated following exposure to NS-USPIO NPs, OA-USPIO NPs, and free OA. No modification of the cytoskeletal actin network was observed. Cell response to stress, including markers of apoptosis and DNA repair, oxidative stress and degradative/autophagic stress, induction of heat shock protein, or lipid metabolism was determined in cells exposed to the two NPs. Induction of an autophagic response was observed in the two cell lines for both NPs but not free OA, while the other stress responses were cell- and NP-specific. The formation of lipid vacuoles/droplets was demonstrated in HT29 and CaCo₂ cells exposed to OA-USPIO NPs but not to NS-USPIO NPs, and to a much lower level in cells exposed to equimolar concentrations of free OA. Therefore, the induction of lipid vacuoles in colon cells exposed to OA utilized as a stabilizer for USPIO NPs is higly amplified compared to free OA, and is not observed in the absence of this lipid in NS-USPIO NPs.

A comparison of the imaging characteristics of the new Kodak Hyper Speed G film with the current T-MAT G/RA film and the CR 9000 system.

Three standard radiation qualities (RQA 3, RQA 5 and RQA 9) and two screens, Kodak Lanex Regular and Insight Skeletal, were used to compare the imaging performance and dose requirements of the new Kodak Hyper Speed G and the current Kodak T-MAT G/RA medical x-ray films. The noise equivalent quanta (NEQ) and detective quantum efficiencies (DQE) of the four screen-film combinations were measured at three gross optical densities and compared with the characteristics for the Kodak CR 9000 system with GP (general purpose) and HR (high resolution) phosphor plates. The new Hyper Speed G film has double the intrinsic sensitivity of the T-MAT G/RA film and a higher contrast in the high optical density range for comparable exposure latitude. By providing both high sensitivity and high spatial resolution, the new film significantly improves the compromise between dose and image quality. As expected, the new film has a higher noise level and a lower signal-to-noise ratio than the standard film, although in the high frequency range this is compensated for by a better resolution, giving better DQE results--especially at high optical density. Both screen-film systems outperform the phosphor plates in terms of MTF and DQE for standard imaging conditions (Regular screen at RQA 5 and RQA 9 beam qualities). At low energy (RQA 3), the CR system has a comparable low-frequency DQE to screen-film systems when used with a fine screen at low and middle optical densities, and a superior low-frequency DQE at high optical density.

Biochar and soil nitrous oxide emissions

The objective of this work was to evaluate the effect of biochar application on soil nitrous oxide emissions. The experiment was carried out in pots under greenhouse conditions. Four levels of ground commercial charcoal of 2 mm (biochar) were evaluated in a sandy Albaqualf (90% of sand): 0, 3, 6, and 9 Mg ha-1. All treatments received 100 kg ha-1 of N as urea. A cubic effect of biochar levels was observed on the N2O emissions. Biochar doses above 5 Mg ha-1 started to mitigate the emissions in the evaluated soil. However, lower doses promote the emissions.

Temperature dependence of the magnetization processes in Co/Al oxide/Permalloy trilayers

The magnetization process of Co/Al oxide/Py trilayers and its evolution with the temperature have been analyzed. The particular behavior of the Co layers, including the shift of the hysteresis loops and a coercivity increase with the decrease of temperature, is related with the apparition of a CoO layer at the Co/Al-oxide interface.

Ventilation, Oxidative Stress, and Nitric Oxide in Hypobaric versus Normobaric Hypoxia.

PURPOSE: Slight differences in physiological responses and nitric oxide (NO) have been reported at rest between hypobaric hypoxia (HH) and normobaric hypoxia (NH) during short exposure.Our study reports NO and oxidative stress at rest and physiological responses during moderate exercise in HH versus NH. METHODS: Ten subjects were randomly exposed for 24 h to HH (3000 m; FIO2, 20.9%; BP, 530 ± 6 mm Hg) or to NH (FIO2, 14.7%; BP, 720 ± 1 mm Hg). Before and every 8 h during the hypoxic exposures, pulse oxygen saturation (SpO2), HR, and gas exchanges were measured during a 6-min submaximal cycling exercise. At rest, the partial pressure of exhaled NO, blood nitrate and nitrite (NOx), plasma levels of oxidative stress, and pH levels were additionally measured. RESULTS: During exercise, minute ventilation was lower in HH compared with NH (-13% after 8 h, P < 0.05). End-tidal CO2 pressure was lower (P < 0.01) than PRE both in HH and NH but decreased less in HH than that in NH (-25% vs -37%, P < 0.05).At rest, exhaled NO and NOx decreased in HH (-46% and -36% after 24 h, respectively, P < 0.05) whereas stable in NH. By contrast, oxidative stress was higher in HH than that in NH after 24 h (P < 0.05). The plasma pH level was stable in HH but increased in NH (P < 0.01). When compared with prenormoxic values, SpO2, HR, oxygen consumption, breathing frequency, and end-tidal O2 pressure showed similar changes in HH and NH. CONCLUSION: Lower ventilatory responses to a similar hypoxic stimulus during rest and exercise in HH versus NH were sustained for 24 h and associated with lower plasma pH level, exaggerated oxidative stress, and impaired NO bioavailability.

How Spanish in an American film is rendered in translation: dubbing Butch Cassidy and the Sundance Kid in Spain

This is a case study of the Spanish dubbed version of Butch Cassidy and the Sundance Kid (George Roy Hill 1969) to illustrate and further develop the concept of L3 as a language that appears in source texts and their translations. L3 is distinguishable from the main language(s), L1 for the source text and L2 for the translation, based on a model proposed by Corrius and Zabalbeascoa 2011, and Corrius 2008. The study reveals various possible ways of rendering L3 in translation, in particular when L3 happens to coincide with L2. It also looks into the effect that certain translation solutions may have on intratextual translation and metatranslation.

Language variation in source texts and their translations: the case of L3 in film translation

In addition to the two languages essentially involved in translation, that of the source text (L1) and that of the target text (L2), we propose a third language (L3) to refer to any other language(s) found in the text. L3 may appear in the source text (ST) or the target text (TT), actually appearing more frequently inSTs in our case studies. We present a range of combinations for the convergence and divergence of L1, L2 and L3, for the case of feature films and their translations using examples from dubbed and subtitled versions of films, but we are hopeful that our tentative conclusions may be relevant to other modalities of translation, audiovisual and otherwise. When L3 appears in an audiovisual ST,we find a variety of solutions whereby L3 is deleted from or adapted to the TT.In the latter case, L3 might be rendered in a number of ways, depending on factors such as the audience’s familiarity with L3, and the possibility that L3 inthe ST is an invented language.

SELETIVIDADE DE CHLORFENAPYR E FENBUTATIN-OXIDE SOBRE DUAS ESPÉCIES DE ÁCAROS PREDADORES (ACARI: PHYTOSEIIDAE) EM CITROS

Com o uso de bioensaios, verificaram-se os efeitos residual de contato, ovicida e de persistência dos produtos chlorfenapyr e fenbutatin-oxide sobre duas espécies de ácaros predadores, Iphiseiodes zuluagai Denmark & Muma e Euseius alatus DeLeon (Acari: Phytoseiidae), associados ao ácaro da leprose-dos-citros Brevipalpus phoenicis (Geijskes) (Acari: Tenuipalpidae). O efeito total sobre os adultos foi estudado por meio do método residual de contato com pulverização em superfície de vidro, conforme metodologia da IOBC. O efeito ovicida foi avaliado por meio de pulverização direta sobre os ovos dos ácaros predadores, também em superfície de vidro. A persistência dos produtos foi avaliada em laboratório, em arenas confeccionadas com folhas de laranjeira pulverizadas no campo, aos 0; 5; 15 e 30 dias após a aplicação. Os resultados obtidos mostraram que chlorfenapyr foi nocivo ao I. zuluagai e E. alatus e o fenbutatin-oxide foi levemente nocivo a E. alatus e inócuo a I. zuluagai. Nenhum dos produtos apresentou efeito ovicida. Fenbutatin-oxide apresentou baixa persistência para ambas as espécies de ácaros predadores, e chlorfenapyr, na dosagem de 31,3 ml, foi de baixa persistência, enquanto, na dosagem de 62,5 ml, foi moderadamente persistente. O fenbutatin-oxide apresentou-se inócuo e levemente nocivo aos ácaros predadores I. zuluagai e E. alatus, respectivamente, e de baixa persistência para ambas as espécies

Defective nitric oxide synthesis: a link between metabolic insulin resistance, sympathetic overactivity and cardiovascular morbidity.

Epidemiological studies demonstrate an association between insulin resistance, hypertension and cardiovascular morbidity. In addition to its metabolic effects, insulin also has important cardiovascular actions. The sympathetic nervous system and the nitric oxide-l-arginine pathway have emerged as central players in the mediation of these actions. Over the past decade, the underlying mechanisms and the factors that may govern the interaction between insulin and these two major cardiovascular regulatory systems have been studied extensively in healthy people and insulin-resistant individuals. Here we summarize the current understanding and gaps in knowledge on these interactions. We propose that a genetic and/or acquired defect of nitric oxide synthesis could represent a central defect triggering many of the metabolic, vascular and sympathetic abnormalities characteristic of insulin-resistant states, all of which may predispose to cardiovascular disease.