L'hypoxie intermittente (HI), induite par les apnées du sommeil, conduit à des altérations de la sensibilité à l'insuline et de l'homéostasie glucidique mais les mécanismes impliqués restent mal connus. L'objectif de ce travail était d'étudier les effets et les mécanismes sous jacents d'une exposition chronique à l'HI sur l'homéostasie glucidique. L'HI induit une résistance à l'insuline à la fois systémique et tissulaire, ainsi qu'une amélioration de la tolérance au glucose associée à une activation de l'AMPK musculaire. L'HI cause également des altérations du foie et du tissu adipeux associées à un changement du pattern d'expression des gènes dans ces tissus et à un risque accru de développement de pathologies vasculaires comme l'athérosclérose. Enfin, la délétion de PHD1, une des protéines régulatrices de HIF-1, entraîne une résistance à l'insuline associée une stéatose hépatique, faisant de HIF-1 une cible potentielle impliquée dans les altérations metaboliques induites par l'HI. / Intermittent hypoxia (IH), induced by sleep apnea, leads to alterations in insulin sensitivity and glucose homeostasis but the mechanisms involved remains poorly understood. The objective of this work was to study the effects and the underlying mechanisms of chronic exposure to IH on glucose homeostasis. IH induces both systemic and tissue-specific insulin resistance , as well as improved glucose tolerance associated with an activation of muscle AMPK. IH also causes a change in the pattern of gene expression in liver and adipose tissue and an increased risk of vascular pathologies such as atherosclerosis development. Finally, the deletion of PHD1, a regulatory protein of HIF-1, leads to insulin resistance associated with hepatic steatosis, making HIF-1 a possible target involved in the metabolic changes induced by IH.

The parameterization of radiative transfer is a part of numerical weather prediction and general circulation models that is both essential and computationally very expensive, and is therefore subject to never­ending compromises between accuracy and computational cost. The present thesis offers an improvement to the existing broadband radiation scheme by revising its critical components - gaseous transmissions, cloud optical properties, and calculation of internal longwave exchanges. The accuracy of the full­spectrum broadband approach is thus raised to the level required for the short range numerical weather forecast. The intermittent update of broadband gaseous transmissions is introduced as a new component, reducing computational cost while preserving the full cloud­radiation interaction. The scalability of longwave computations is ensured by adopting the net exchanged rate decomposition with bracketing, improved by an intermittently applied self­learning algorithm determining the interpolation weights. It has been demonstrated that under conditions of operational weather forecasting, this developed scheme is fully competitive with the mainstream approach, due to the improved error balance between the...

A l'éveil comme au cours du sommeil, en plaine comme en haute altitude, le maintien d'une oxygénation artérielle stable et élevée est un marqueur essentiel d'une bonne réponse physiologique de l'organisme. L'intolérance à l'altitude regroupe des pathologies graves voire fatales dont le développement est en lien direct avec le taux d'oxygénation artériel des sujets. D'autre part, en plaine, la prévalence élevée du syndrome d'apnées obstructives du sommeil (SAOS) incite les chercheurs au développement de modèles d'études spécifiques, permettant d'investiguer les conséquences du principal stimulus du SAOS : l'hypoxie intermittente. La chémosensibilité pourrait avoir un impact important dans ces deux pathologies, ayant pour rôle le maintien des gaz du sang à des valeurs normales, en adaptant la ventilation aux conditions externes ou internes à l'organisme.Les objectifs de ce travail étaient de comprendre l'impact de la chémosensibilité (avec d'autres mécanismes décrits dans la littérature) sur l'oxygénation et la tolérance à l'altitude, d'étudier les effets de la résistance expiratoire sur l'amélioration de l'oxygénation, ainsi que les conséquences de l'hypoxie intermittente chronique sur la plasticité du chémoréflexe.Il en ressort que la chémosensibilité périphérique à l'hypoxie a un impact majeur sur le développement de l'intolérance à l'altitude. Cela semble en outre être un facteur prédictif de la survenue de ces pathologies. En hypoxie, une amélioration efficace de l'oxygénation a été obtenue par l'utilisation d'une résistance expiratoire calibrée à 10 cm H2O permettant l'amélioration de la diffusion alvéolo-capillaire. L'exposition à l'hypoxie intermittente chronique nocturne a provoqué une fragmentation du sommeil ainsi qu'une intensification de la chémosensibilité à l'hypoxie et à l'hypercapnie.Ainsi, une altération de la réponse des corps carotidiens à l'hypoxémie participerait au développement du mal aigu des montagnes et de ses complications, tout en facilitant sa prédiction avant ascension. L'utilisation d'une résistance expiratoire pourrait permettre de combler la désaturation exagérée retrouvée chez les sujets sensibles à l'altitude lors d'un séjour en haute montagne. Il apparaît également que la chémosensiblité périphérique et centrale (CO2 et O2) fasse preuve d'une plasticité importante en réponse à l'hypoxie intermittente nocturne chez des sujets sains. / At awakening and during sleep, at sea level or in high altitude, maintaining a high level in arterial blood oxygenation is a marker for an adaptated physiological response external and internal factors.High altitude illness encompasses pathologies, that sometimes could be fatal, and which seems to be correlated with the level of arterial oxygenation in hypoxia.Secondly, at sea level and in general population, the high prevalence of obstructive sleep apnea syndrome (OSAS) encourage scientists to develop new models for studying consequences of the main OSAS' stimulus: intermittent hypoxia.Chemosensitivity could play an important role in those two different diseases, with regulation of blood gases and homeostasis by controlling ventilation.Our objectives was to investigate (1) impact of chemosensitivity on blood oxygenation and tolerance to high altitude, comparatively to other physiological factors commonly involved, (2) effects of using positive expiratory pressure in order to improve oxygenation in hypoxia, and (3) consequences of chronic exposure to nocturnal intermittent hypoxia on chemoreflexe plasticity.We found that peripheral chemoresponse to hypoxia play a crucial role in high altitude illness development. Moreover, this variable seems to be a predictive factor for those diseases. In hypoxic conditions, using a positive expiratory pressure (10 cmH2O) lead to a significant improve in arterial oxygenation, by increasing pulmonary diffusion. Finally, nocturnal intermittent hypoxia induced significant sleep disturbances and major changes in chemoresponse to hypoxia and hypercapnia.

Chez l'homme, l'hypoxie correspond à une inadéquation entre les besoins tissulaires et les apports en oxygène. Cet état est une caractéristique commune à l'exposition à l'altitude et au syndrome d'apnées obstructives du sommeil (SAOS), bien que celle-ci soit continue dans le premier cas et intermittente et nocturne dans le second.L'hypoxie d'altitude entraine une altération des performances cognitives et motrices. La réduction de la performance à l'exercice en altitude a longtemps été attribuée à une altération du métabolisme musculaire du fait d'une réduction de l'apport en oxygène. Les perturbations cérébrales induites par l'hypoxie pourraient également avoir un rôle majeur dans cette limitation.Le SAOS, véritable enjeu de santé publique, est associé à des troubles cognitifs pouvant ainsi influencer le fonctionnement quotidien des patients souffrant de ce syndrome et résulter en une somnolence diurne excessive, une baisse de la qualité de vie ou encore une réduction de la productivité au travail et des performances scolaires. Le fait que ces altérations cérébrales puissent influencer les capacités motrices et à l'effort des patients atteints d’apnées obstructives du sommeil reste en revanche à investiguer.Au cours de ce travail de thèse, nous nous sommes intéressés à deux modèles d’exposition hypoxique et à leurs conséquences cérébrales et neuromusculaires. Nous avons tout d’abord étudié l'effet d'une exposition à l'hypoxie d'altitude aigue (quelques heures) et prolongée (plusieurs jours) sur la fonction neuromusculaire et ses répercussions à l'exercice chez le sujet sain. Nous avons ensuite étudié l'influence du modèle d'hypoxie intermittente associé au SAOS sur la fonction neuromusculaire et la tolérance à l'exercice de ces patients. Nous avons ainsi cherché à caractériser les altérations cérébrales à l'exercice en lien avec ce syndrome et leur réversibilité suite à un traitement en ventilation par pression positive continue.Chez le sujet sain, nous avons démontré que la performance à l'exercice impliquant une masse musculaire réduite (fléchisseurs du coude) n'était pas limitée par une fatigue centrale accrue après 1 et 5 jours d'exposition à une altitude de 4350 m. Nous avons mis en évidence que la dysfonction musculaire (force et endurance réduites) observée chez le patient SAOS est associée à un déficit d'activation supraspinal et une augmentation de l'inhibition intracorticale. De plus, nos résultats suggèrent qu'une altération de la réponse cérébrovasculaire à l'exercice puissent impacter négativement la tolérance à l'exercice des patients souffrant d'un SAOS sévère. Ces altérations neuromusculaires et cérébrovasculaires n'étaient pas corrigées après un traitement de huit semaines par ventilation nocturne en pression positive continue soulignant la nature persistante de ces altérations cérébrales. / In humans, hypoxia is defined as the mismatch between tissue requirement and oxygen delivery. This condition is a common feature between high-altitude exposure and obstructive sleep apnea syndrome (OSA), although it is continuous in the first instance and intermittent and nocturnal in the second one.High-altitude exposure causes an impairment in cognitive and motor performance. The reduction in exercise performance observed under hypoxic condition has been mainly attributed to altered muscle metabolism due to impaired oxygen delivery. However, hypoxia-induced cerebral perturbations may also play a major role in exercise limitation.OSA, a major public health concern, is associated with cognitive impairment that can alter patients' daytime functioning and result in excessive daytime sleepiness, reduced quality of life and lowered work productivity and school performance. The fact that these cerebral alterations can influence motor and exercise performance in patients with obstructive sleep apnea remains to be investigated.In this thesis, we investigated two different models of hypoxic exposure and their cerebral and neuromuscular consequences. First, we assessed the effect of acute (several hours) and prolonged (several days) high-altitude exposure on the neuromuscular function and its repercussions during exercise in healthy subject. Then, we then investigated the model of intermittent hypoxia associated with OSA and its influence on the neuromuscular function and exercise tolerance in these patients. We seeked to characterize cerebral alterations during exercise associated with this syndrome and their reversibility following continuous positive airway pressure treatment.In healthy subject, we showed that exercise performance involving a small muscle mass (elbow flexors) was not limited by an exacerbated amount of central fatigue after 1 and 5 days of high-altitude exposure (4,350 m). We highlighted that muscle dysfunction (reduced strength and endurance) was associated with a supraspinal activation deficit and an increase in intracortical inhibition. Moreover, our results suggest that an alteration in cerebrovascular response during exercise may contribute to reduced exercise tolerance observed in patients with severe OSA syndrome. The neuromuscular and cerebrovascular abnormalities were not reversed following an eight-week continuous positive airway pressure treatment, highlighting the persistent nature of the cerebral alterations.

Submitted by Emanuel Varela Cardoso (emanuel.varela@ufcg.edu.br) on 2018-08-21T20:37:01Z No. of bitstreams: 1 ISRAEL BURITI GALVÃO – DISSERTAÇÃO (PPGEP) 2017.pdf: 6049302 bytes, checksum: ac315d43e0d0a7dbefdb3e01f65ae674 (MD5) / Made available in DSpace on 2018-08-21T20:37:01Z (GMT). No. of bitstreams: 1 ISRAEL BURITI GALVÃO – DISSERTAÇÃO (PPGEP) 2017.pdf: 6049302 bytes, checksum: ac315d43e0d0a7dbefdb3e01f65ae674 (MD5) Previous issue date: 2017-10-20 / O presente trabalho teve como objetivo realizar um estudo da secagem cont ínua e intermitente de pedaços de maçã fresca e pré-tratada osmoticamente, cortados na forma de paralelepípedo, utilizando modelos empíricos e difusivos na descrição da cinética desses processos. Para o modelo de difusão, foram pressupostos parâmetros termosfísicos e dimensões variáveis. Foi realizada uma revisão bibliográfica sobre o tema, detalhamento dos materiais e métodos utilizados, a validação e testes do solver em FORTRAN tridimensional desenvolvido através do método dos volumes finitos, com uma formulação totalmente implícita. Foram feitos experimentos utilizando uma incubadora refrigerada com agitação para a realização da desidratação osmótica a fim de preparar as amostras para as secagens subseqüentes. As secagens foram realizadas em uma estufa com circulação de ar nas temperaturas de 50 e 70 °C, para secagens contínuas e intermitentes das maçãs (com razão de intermitência de 2/3 e períodos de têmpera de 30 min; 60 min; e 120 min com os frutos frescos, e têmperas de 20 min e 30 min para os frutos pré-tratados osmoticamente). Os resultados das cinéticas das secagens, estimativas de parâmetros relativos às frutas estudadas, mostraram-se compatíveis com a literatura. A temperaturas e os perí odos de têmpera utilizados influenciaram significativamente as cinéticas de teor de umidade, assim como os valores dos parâmetros de processo, determinados por otimização para todas as configurações experimentadas. Este trabalho também trata sobre o impacto da secagem intermitente sobre a economia de energia. / The present work had as objective to make a study of the continuous and intermittent drying of fresh and osmotically pre-treated of apple pieces cut in form of parallelepiped, using both empirical and diffusive models to description of the kinetics of the processes. For the diffusion model, thermo-physical parameters and variable dimensions were assumed. A bibliographic review was done on the subject, details of the materials and methods used, the validation and testing of the in three-dimensional FORTRAN solver developed using the finite volume method, with a fully implicit formulation. Experiments were done using a freezer shaker incubator for the osmotic dehydration in order to prepare the samples for subsequent drying. The drying was realized in an oven with air circulation at temperatures of 50 and 70 ° C, for continuous and intermittent drying of the apples (with intermittent ratio of 2/3 and tempering periods of 30 min, 60 min and 120 min for the fresh fruits, and tempers of 20 min and 30 min for osmotically pretreated fruits). The results of drying kinetics, estimates of parameters related to the fruits studied, were compatible with the literature. At the temperatures and the tempering periods used, they significantly influenced the kinetics of the moisture content, as well as the values of the process parameters determined by optimization for all configurations. Here also is shown the impact of intermittent drying on the energy saving and how the intermittent drying change for the better the product quallity is shown.

A presente pesquisa avaliou duas alternativas para a remoção de fósforo em esgoto sanitário: uso de filtros percoladores com adição de material com potencial de ligação de fósforo e uso de banhados construídos com macrófitas com potencial assimilação de fósforo. Estas tecnologias são apropriadas para pequenas comunidades ou residências unifamiliares e também podem ser utilizadas como etapa no tratamento dos esgotos. Estes sistemas apresentam remoção satisfatória de matéria orgânica e nitrogênio amoniacal, contudo apresentam diminuta eficiência de remoção de fósforo e nitrato. Na presente pesquisa foram estudadas duas técnicas para aumentar a remoção de fósforo: utilização de materiais com potencial de remoção de fósforo nos filtros percoladores, e plantas com alta capacidade de assimilação de fósforo nos banhados construídos. Os materiais adicionados aos leitos percoladores com potencial de remoção de fósforo foram: Cavaco de Usinagem e Escória de Aciaria Elétrica. As frações de materiais adicionados foram: 10%, 20% e 40% em peso em relação ao material suporte. As plantas utilizadas foram a Luziola peruviana, a qual apresenta em sua constituição alta concentração de fósforo e a Typha latifolia, já amplamente utilizada em banhados construídos. Os materiais utilizados como meios suportes foram brita e areia. A adição de materiais com potencial remoção de fósforo auxiliou na remoção do nutriente, a qual foi mais significativa nos leitos contendo Cavaco de Usinagem. Não foi observada diferença de remoção de fósforo para as diferentes frações dos materiais testados para o período de estudo. A utilização da planta Luziola peruviana contribuiu no máximo com 2,11% da remoção de fósforo total, contudo foi observada importante função do sistema radicular no tempo de percolação, contribuindo para maior tempo de contato do efluente com material suporte, especialmente para o caso da brita. O uso de areia de granulometria grossa possibilitou eficiência de remoção de fósforo superior a 85%, entretanto, a massa de fósforo retida por unidade de área no sistema utilizando brita 0 apresentou valores duas vezes superiores aos obtidos para os leitos preenchidos com areia. / This research evaluated two alternatives to phosphorus removal from domestic wastewater: use of intermittent sand filters with materials addition with potential phosphorus binding and use of constructed wetlands with macrophytes potential phosphorus assimilation. These present themselves as technologies suitable for small communities or single family houses and can be used as a intermediate or final stage of wastewater treatment. The systems based on intermittent feed get satisfactory removal of organic matter and ammonia-N, but they have reduced efficiency of phosphorus and nitrate removal. The aim of present study was to evaluate two techniques for phosphorus removal: use of materials with potential removal of phosphorus, in the intermittent sand filters, and plants with capacity for assimilation of phosphorus metabolism, in the vertical flow constructed wetlands. The materials added to the sand filters with the potential removal of phosphorus were the Machine Bit and Electric Arc Furnace Slag. The fractions of materials added were: 10%, 20% and 40% related to material support weight. The plants tested were Luziola peruviana, which has in its constitution a high concentration of phosphorus and Typha latifolia, widely used in constructed wetlands. The support materials tested were gravel and sand. The use of materials with potential removal of phosphorus aid in the removal of phosphorus, which is more significant in the beds with Machine Bit. Difference of phosphorus removal was not observed for the different fractions of the materials tested for the study period. The use of the plant Luziola peruviana contributed at the most with 2,11% of removal of total phosphorus, however important role of the root system was observed in the percolation time, contributing to larger time of contact of wastewater with support materials, especially for use of coarse material, as it the coarse gravel. The use of coarse sand allowed removal efficiency of phosphorus higher than 85%, however, the mass of phosphorus retained per unit area in the system using gravel present values twice higher than obtained to the beds filled with sand.

Made available in DSpace on 2016-12-23T13:56:00Z (GMT). No. of bitstreams: 1 Bermudes.pdf: 1280638 bytes, checksum: cf675a18fbda30bc9b61e74a1921a53e (MD5) Previous issue date: 2007-07-06 / Intermittent fasting is frequent in medical practice and this condition has been studied as a therapeutic intervention for some diseases. Increased life span and resistance to stress is observed in rodents submitted to intermittent fasting. However there is not much information on the evolution of infections in animals submitted to these diet manipulations. To study the evolution of fecal peritonitis in mice after 72 h fasting or after different time of intermittent fasting. After 72 h of fasting mice were submitted to cecal ligature and puncture or to an intraperitoneal injection of feces (1:6 or 1:9, weight/volume dilutions). Mice submitted to intermittent fasting, three days for two weeks or the day after the other day, during four months, received intraperitoneal injection of feces with the same dilutions. Mortality was evaluated up to 14 days, when the animals were killed to quantify the intraperitonel abscesses. The abscesses were classified with the values one, two or three according they were respectively up two, between two and five or higher than five millimeters in diameter. For each animal a score was obtained by the sum of values originated from the product of the number attributed to the abscesses versus the number of each abscess type. Control mice, paired by gender and age, were submitted to the same procedures. In mice submitted to 72 h fasting or intermittent fasting the signs of septic shock appeared earlier and were more severe, with higher mortality up to 24 h, although the global mortality evaluated by Kaplan-Meyer method was not significant after two weeks. Among the survivors the score of abscesses were significantly lower in mice submitted to fasting, mainly in groups treated with feces 1:9 dilution, in which occurred less mortality. Results demonstrate that acute or intermittent fasting increases the susceptibility to endotoxic shock and induces increased resistance to bacteria, demonstrated by reduction in number and volume of abscesses. / Jejum prolongado não é infrequente na prática médica e períodos intermitentes de jejum vêm sendo estudados como intervenção terapêutica para algumas doenças. Períodos intermitentes de jejum induzem aumento da longevidade e da resistência ao estresse em roedores. No entanto, pouco se conhece sobre o efeito dessas manipulações de dieta na evolução de infecções. Estudar a evolução de peritonite fecal em camundongos após jejum de 72 horas ou após períodos de jejuns intermitentes. Camundongos foram submetidos a jejum de 72 h e em seguida à ligadura e punção do ceco ou à injeção intra-peritoneal de fezes (diluídas a 1:6 ou a 1:9). Camundongos submetidos a jejum intermitente de três dias a cada duas semanas ou em dias alternados, durante quatro meses, foram submetidos a peritonite por injeção intra-peritoneal de fezes com as mesmas diluições. Foi avaliada a mortalidade até duas semanas, quando os animais foram sacrificados para contagem e mensuração dos abscessos intraperitoneais. Os abscessos recebiam os valores 1, 2 ou 3 conforme tivessem até 2, de 2 a 5 ou acima de 5 mm de diâmetro, respectivamente. Um escore para cada animal foi calculado pela soma dos valores obtidos da multiplicação do número de abscessos pelo valor atribuído ao seu tamanho. Animais controle, mantidos em dieta ad libitum , pareados por idade e sexo, foram submetidos aos mesmos procedimentos. Nos animais submetidos ao jejum agudo ou intermitente, as manifestações do choque séptico foram sempre mais precoces e mais graves, com maior mortalidade nas primeiras 48 h, embora nem sempre a diferença na sobrevivência (Kaplan-Meyer) tenha sido significativa. Nos sobreviventes, o escore dos abscessos era significativamente menor nos grupos submetidos a jejum, especialmente quando a peritonite fecal era induzida por injeção mais diluída de fezes (1:9), com menor mortalidade. Os resultados mostram que o jejum agudo ou o jejum intermitente aumentam a susceptibilidade ao choque endotóxico, mas aumenta resistência às bactérias, demonstrada pela menor extensão dos abscessos peritoneais formados.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work investigated the effect of intermittent hypoxic training (IHT) sessions under bodyweight, food intake and biochemical parameters in Wistar rats fed normo fat (NF) and high fat (HF) diets. Forty rats were divided in two groups, which were fed a NF or a HF diet. Afterwards the rats were subdivided in four groups and submitted to intermittent hypoxia (IH) or normoxia (N) sessions for 30 days. Groups formed: NF/N, NF/IH, HF/N and HF/IH. The groups submitted to IHT followed this protocol: 15 minutes hypoxia, 10-15% inspired O2 and 5 minutes for reoxigenation). Sham group was exposed to the same conditions but with normal O2 concentrations (21%). Bodyweight and food intake were measured every two days. The rats were anesthetized on day 31 and the blood was sampled by cardiac punction for analyses. The biochemical parameters analyzed were: total cholesterol (TC), triglycerides (TG), high density cholesterol (HDL), glucose, lactate dehidrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and muscle and hepatic glycogen. In regard to diets, the HF group promoted the biggest weight gain just in normoxia groups.The food intake decrease significantly in HF/IH subgroup compared to HF/N. Although the average of the corporal weight did not decrease significantly, the differences in percentages had shown a reduction in HF/IH subgroup. In the profile biochemist, the IHT only modified the LDH, increasing it in NF subgroup and the AST, diminishing it in HF subgroup. Our findings allow to suggest that the IHT can have a promising role in the prevention of the obesity and more studies are needed to evaluate its effect in the prevention/treatment of other diseases. / Este trabalho investigou o efeito de sessões de treinamento hipóxico intermitente (THI) sobre o peso corporal, consumo calórico e variáveis bioquímicas em ratos Wistar alimentados com dieta padrão (DP) ou dieta hipercalórica (DH). Quarenta ratos foram divididos em dois grupos e alimentados com DP ou DH. Na seqüência foram subdivididos em quatro grupos e submetidos às sessões de hipóxia intermitente (HI) ou normóxia (N) por 30 dias. Os grupos formados foram: DP/N, DP/HI, DH/N e DH/IH. Os grupos submetidos ao THI seguiram o seguinte protocolo: 15 minutos de hipóxia com a concentração de O2 inspirado variando entre 10 a 15% e 5 minutos para reoxigenação. Os grupos normóxia foram expostos às mesmas condições, porém com concentrações normais de O2 (21%). O peso corporal e o consumo de ração foram avaliados a cada dois dias. No dia 31, os animais foram anestesiados e o sangue foi coletado por punção cardíaca. As variáveis bioquímicas analisadas foram: colesterol total (CT), triglicerídeos (TG), lipoproteína de alta densidade (HDL), glicose, lactato desidrogenase (LDH), alanina aminotransferase (ALT), aspartato aminotransferase (AST), glicogênio muscular e hepático. Com relação às dietas, a DH promoveu maior ganho de peso somente nos grupos em normoxia. A ingesta calórica diminuiu significativamente no subgrupo DH/HI. Embora a média do peso corporal não tenha diminuído significativamente, as diferenças em percentagens mostraram uma redução no subgrupo DH/HI. No perfil bioquímico, o THI alterou somente a LDH, aumentando-a no subgrupo DP e a AST, diminuindo-a no subgrupo DH. Nossos achados permitem sugerir que o THI pode ter um papel promissor na prevenção da obesidade e mais estudos são necessários para avaliar seus efeitos na prevenção/tratamento de outras patologias.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The experiment was carried out to evaluate the ingestive behavior and forage intake by lambs on ryegrass pasture under different forage allowance (FA): 6, 9 and 12% of body weight (BW). The grazing method was intermittent and the experimental animals were Suffolk lambs. The experimental design was completely randomized with a split-plot structure, being the forage allowance the main plots and the phenological stages the subplots, and the methods for the determination of intake were the sub-subplots. The intake, in the vegetative stage of ryegrass, is independent of forage allowance. The lower allowances limit the forage intake from pre-flowering, while in the reproductive stage of ryegrass the intake is lower, intermediate and higher in FA 6, 9 and 12% of BW, respectively. The grazing time and bite mass were similar between forage allowances. Lambs remained more time ruminating and less time doing other activities in FA 9 and 12% of BW. The number of stations visited per minute and the time at each station were related to the forage allowance in the vegetative 2 and flowering stages. The bite rate was higher in FA 6 and 9% of the BW and is associated with the canopy height. The number of meals was higher, intermediate and lower in FA 12, 9 and 6% of BW, respectively, and similar at all phenological stages and is associated with the leaf blades participation in the canopy. The duration of the meals was higher in FA 6, intermediate in 9 and lower in 12% and is associated with changes in lambs' bite rate, the leaf blades allowance and leaf blade: stem ratio. In the phenological stages of ryegrass the bite rate is adjusted to compensate for changes in bite mass. The grazing time at the phenological stages of ryegrass is associated with the forage mass and the leaf blades allowance. The duration of the interval between meals is similar between forage allowances and in different phenological stages of ryegrass it is correlated with the activities of rumination and other activities. The estimate of herbage intake on ryegrass pasture is similar when using chromium oxide and fecal nitrogen as markers. The forage intake on the basis of forage allowance is dependent on the canopy structure and is limited in the pre-flowering and flowering, due to the high mass of stems. The phenological stages of ryegrass were more important in changes in pasture structure and ingestive behavior of lambs than the forage allowances used. The bite mass is unchanged by forage allowances ranging from 6 to 12% of BW and any of them can be used in ryegrass pasture. / O trabalho foi conduzido com o objetivo de avaliar o comportamento ingestivo e consumo de forragem por cordeiras em pastagem de azevém sob diferentes ofertas de forragem (OF): 6, 9 e 12% do peso corporal (PC). O método de pastejo foi intermitente e os animais experimentais foram cordeiras da raça Suffolk. O delineamento experimental foi inteiramente casualizado, com estrutura de parcelas sub-subdivididas, sendo as ofertas de forragem as parcelas principais, os estádios fenológicos as subparcelas, e os métodos de determinação do consumo as sub-subparcelas. O consumo, no estádio vegetativo do azevém, independe da oferta de forragem. As menores ofertas limitam o consumo de forragem a partir do pré-florescimento enquanto no estádio reprodutivo do azevém o consumo é menor, intermediário e maior nas OF 6, 9 e 12% do PC, respectivamente. O tempo de pastejo e a massa de bocado foram semelhantes entre as ofertas de forragem. As cordeiras permaneceram mais tempo ruminando e menor tempo realizando outras atividades nas OF 9 e 12% do PC. O número de estações visitadas por minuto e o tempo em cada estação variou em função das ofertas de forragem nos estádios vegetativo 2 e florescimento. O número de bocados foi maior nas OF 6 e 9% do PC. O número de refeições foi maior, intermediário e menor nas OF 12, 9 e 6% PC, respectivamente e similar em todos os estádios. A duração das refeições foi maior na OF 6, intermediária na 9 e menor na 12%. A estimativa de consumo de matéria orgânica por cordeiras em pastagem de azevém é similar quando são utilizados o óxido de cromo e o nitrogênio fecal como marcadores. O consumo de forragem em função das ofertas de forragem é dependente da estrutura do dossel e é limitado no pré-florescimento e florescimento, em função da elevada massa de colmos. A taxa de bocado é dependente da altura do dossel e varia nos estádios fenológicos do azevém para compensar alterações na massa de bocado. O tempo de pastejo é similar com ofertas de forragem variando de 6 a 12% do PC, mas durante os estádios fenológicos do azevém é dependente da massa de forragem e da oferta de lâminas foliares. A duração da refeição varia com alterações na taxa de bocado de cordeiras, oferta de lâminas foliares e relação lâmina: colmo. O número de refeições não se altera com o avanço no ciclo do azevém, mas é influenciado pela participação de lâminas foliares no dossel. A duração do intervalo entre refeições é similar entre as ofertas de forragem e nos diferentes estádios fenológicos do azevém está correlacionada com as atividades de ruminação e outras atividades. A estimativa de consumo de matéria orgânica por cordeiras em pastagem de azevém é similar quando são utilizados o óxido de cromo e o nitrogênio fecal como marcadores. O consumo de forragem em função das ofertas de forragem é dependente da estrutura do dossel e é limitado no final do ciclo do pasto em função da elevada massa de colmos. Os estádios fenológicos do azevém tiveram maior importância nas mudanças ocorridas na estrutura do pasto e no comportamento ingestivo de cordeiras do que as ofertas de forragem utilizadas. A massa de bocado é inalterada por ofertas de forragem que variam entre 6 a 12 % do PC e qualquer uma delas pode ser utilizada em pastagem de azevém.

Le Syndrome d'Apnées Obstructives du Sommeil (SAOS) est défini par la survenue durant le sommeil d'épisodes fréquents d'obstruction complète ou partielle des voies aériennes supérieures, responsables d'apnées/hypopnées. L'hypoxie intermittente (HI) qui en résulte est responsable, à long terme, d'une augmentation de la morbi-mortalité cardiovasculaire (CV) dans un contexte de forte prévalence de syndrome métabolique, d'obésité et d'insulinorésistance. Certains patients SAOS obèses présentent une hypoventilation/hypercapnie, caractérisant le syndrome d'obésité hypoventilation (SOH) dont la morbi-mortalité CV est encore plus sévère que le SAOS seul. Le stress oxydant, l'inflammation de bas grade et la dérégulation du métabolisme glucido-lipidique et hormonal sont parmi les mécanismes clés responsables de la dysfonction endothéliale et in fine de l'augmentation du risque CV chez ces patients. Cependant, si ces mécanismes délétères sont démontrés par de nombreuses études fondamentales, leur mise en évidence en clinique est moins évidente, notamment du fait des multiples facteurs de co-morbidité. La première partie clinico-biologique de ce travail a été consacrée à la mise en évidence, chez des patients porteurs d'un SAOS ou d'un SOH, des déséquilibres métaboliques et hormonaux impliquant le stress oxydant, en lien avec la sévérité de ces syndromes et leurs conséquences CV. Nous avons ainsi montré chez des patients SOH les plus sévères une altération de la fonction somatotrope proportionnelle à la dysfonction respiratoire et à l'hypertriglycéridémie. Nous avons ensuite mis en évidence, chez des patients SAOS non obèses, l'implication du stress oxydant lipidique dans l'athérosclérose précoce associée à la sévérité du SAOS. Enfin, nous nous sommes intéressés à l'homocystéinémie, facteur de risque cardio-vasculaire connu, chez des patients porteurs d'un syndrome métabolique présentant ou non un SAOS. Nous avons observé une majoration de l'homocystéinémie chez les patients souffrant d'un SAOS par rapport aux patients SMet non SAOS, en lien avec la sévérité des apnées/hypopnées, avec l'athérosclérose précoce, ainsi qu'avec un déséquilibre de la balance pro/antioxydante. Dans une seconde partie fondamentale, nous avons étudié les effets de l'endothéline-1 (ET-1), peptide vasoconstricteur d'origine endothéliale dont la sécrétion est majorée par l'HI, sur le métabolisme d'adipocytes en culture. Nous avons montré que ce peptide majore la lipolyse adipocytaire via les récepteur ET-1 de type A, tend à diminuer l'incorporation du glucose, et ce de manière opposée et additionnelle aux effets de l'insuline. Chez le rat Wistar exposé 14 jours à l'HI, nous avons observé une activation du système endothéline associée à un remodelage du tissu adipeux avec diminution de taille adipocytaire. Au-delà de ses effets vasoconstricteurs, ET-1 déséquilibre donc le métabolisme glucido-lipidique adipocytaire, et pourrait ainsi participer activement à l'insulinorésistance des patients SAOS obèses. Le rôle du système endothéline au niveau du métabolisme énergétique et son impact sur le tissu adipeux constituent donc des pistes sérieuses à explorer dans ce contexte. Mots-clés : Syndrome d'apnées obstructives du sommeil, syndrome d'obésité hypoventilation, stress oxydant, hypoxie intermittente, endothéline-1, insulinorésistance, lipolyse, adipocyte et tissu adipeux. / Obstructive Sleep Apnea Syndrome (OSAS) is defined by recurrent complete (apnea) or partial (hypopnea) upper airway obstructions during sleep. The resulting intermittent hypoxia (IH) is responsible for a long-term increase in cardiovascular (CV) morbi-mortality in a context of strong prevalence of metabolic syndrome, obesity and insulin resistance. Some obese OSAS patients present with Obesity Hypoventilation Syndrome (OHS) characterized by hypoventilation/hypercapnia and an even higher risk of cardiovascular morbi-mortality. Oxidative stress, low-grade inflammation, gluco-lipidic and hormonal alterations are among the key mechanisms leading to endothelial dysfunction and in fine to increased CV risk in OSAS. However, these various mechanisms have been identified by fundamental studies and their relevance in clinical research is less evident, in particular because of the presence of multiple comorbidity factors. The clinicobiological part of this work was devoted to the exploration of the oxidative stress-related metabolic and hormonal changes in OSAS and OHS patients, in relation with the severity of these diseases and their associated CV consequences. In the most severe OHS patients, we showed an impairment of the somatotropic axis linked to respiratory dysfunction and increase in triglycerides. We then highlighted, in non-obese OSAS patients, the involvement of lipid oxidative stress in early atherosclerosis and its association with OSAS severity. Finally, we investigated homocysteine, a well-known CV risk factor, in patients suffering from metabolic syndrome (MS) with or without OSAS. We observed an increase in homocysteinemia in OSAS+MS patients compared to non-OSAS+MS patients, linked to the severity of sleep apnea, to early atherosclerosis, as well as to pro/antioxidative imbalance. In the experimental part, we investigated the effects of the hypoxia-released vasoconstrictor peptide endothelin-1 (ET-1) on the metabolism of 3T3-L1 adipocytes in vitro. We showed that through its type-A receptor, ET-1 increases adipocyte lipolysis, tends to decrease glucose uptake and significantly inhibits the effects of insulin. Moreover, ET-1 stimulates its own expression, and expression of its ET-A receptor in 3T3-L1 cells. In parallel, in Wistar rats exposed to 14 days of IH, we observed an activation of the endothelin system associated with a remodelling of adipose tissue characterized by a decrease in adipocyte size. In conclusion, beyond its vasoconstrictor effects, ET-1 can modify glucose and lipid metabolism of adipocytes, and could thus actively participate in the insulin resistance and dyslipidemia observed in OSAS obese patient. The role of the endothelin system in energetic metabolism and its impact on adipose tissue thus represent promising avenues to be investigated in OSAS. Keywords: obstructive sleep apnea syndrome, obesity hypoventilation syndrome, oxidative stress, intermittent hypoxia, endothelin-1, insulin resistance, lipolysis, adipocyte and adipose tissue.