O estado de Rondonia possui hoje o 8° maior rebanho bovino do pais. Essa caracteristica o torna urn estado essencialmente pecuarista, muito embora ja se perceba um avanco na atividade agricola. Em termos de impacto ambiental, a pecuaria é extremamente agressiva, pois nas praticas antigas de manejo do gado era comum a conversdo direta da floresta em pastagem e consecutivas queimas nos primeiros anos para a limpeza da biomassa remanescente da floresta. Este trabalho tem por objetivo avaliar possiveis alteracOes na biogeoquimica das aguas do rio Urupd mediante esse cenario de contraste entre areas que preservam as caracteristicas naturais e areas corn elevado grau de perturbacao. Corn este intuito, foram realizadas amostragens em seis pontos ao longo do rio Urupd, de forma a termos um gradativo cendrio de perturbacdo no use do solo. 0 primeiro ponto refere-se ao setor da nascente, e é o mais preservado da bacia, corn praticamente 100% de suas caracteristicas naturais, ao passo que o Ultimo, que abrange toda a bacia de drenagem, mantem aproximadamente 51% de floresta. Para essas unidades de drenagens foram analisadas as concentraeOes de ions maiores (Nat, Kt, Mg2+, Ca2+, HCO3\", CY e SO42), de carbono organic° dissolvido (COD), e a razao isotOpica do carbono inorganic° dissolvido (613C do CID). Em geral, os resultados mostraram que, apesar da quantidade de pastagem aumentar de uma unidade de drenagem para outra, e as concentracCies de ions dissolvidos aumentarem consideravelmente, as diferencas nas concentracOes apresentam melhor relacdo coin a distribuicao da Capacidade Efetiva de Troca de Cations, caracteristica inerente dos solos. Portanto, em termos das concentracOes de ions maiores, apesar do extenso desmatamento, ndo ha indicios de que os processos naturais tenham sido suplantados por antropogenicos como principais fatores determinantes da dinamica neste sistema. Contudo, a distribuicdo espacial e temporal das concentraceies de carbono organic° dissolvido demonstram que o aumento do percentual de pastagens relaciona-se corn concentracOes significativamente maiores desta forma de C nas aguas do canal principal. A composicao isot6pica (613C) do carbono inorganic° dissolvido demonstrou que, nos setores mais a juzante da bacia do rio Urupd, a quimica das aguas e predominantemente determinada por processos de intemperismo de rochas carbonatadas / The state of Rondonia has the 8th largest cow herd of the country. This characteristic makes it a state where cattle raising dominates the landscape, although other agricultural uses are becoming noticeable. In terms of environmental impacts cattle raising is extremely aggressive, since early practices were based on slash and burn techniques. This study intends to evaluate changes in the biogeochemistry of the Urupá river waters in such a scenario of remaining pristine areas and heavily impacted ones. In order to understand that, 6 sampling stations were established along the river, at different degrees of land use changes. The first station refers to the headwaters and is the most pristine reach, with almost 100% of its original vegetation, whereas the the last corresponds to the whole basin and has only 51% or remaining forests. The waters where analyzed for the concentrations of major ions (Na+, K+, Mg2+, Ca2+, HCO3-, Cl- e SO42-), dissolved organic carbon (DOC) and the isotopic composition (?13C) of dissolved inorganic carbon (DIC). Generally, the results show that, although the percentages of pasture and major ion concentrations increase significantly along the basin, the latter relates better with a natural characteristic of the soils, which is the effective cation exchange capacity. Consequently, in terms of the ionic concentration of these waters, even with the extensive deforestation observed in the basin, it is not possible to conclude that anthropogenic processes have overcome natural ones as main forces driving the dynamics of this system. However spatial and temporal DOC distributions show that pastures are directly related to increases of this form of C in these waters. DIC isotopic composition (?13C) shows that the chemistry of the Urupá river lower reaches is controlled by the weathering of carbonate rocks

<p>Oligosaccharides (carbohydrates) are a large class of biological molecules that are important as energy sources in the human body and have enormously varied biological functions. It is generally believed that biological activities of carbohydrates are related to their internal dynamics. The dynamic properties of some oligosaccharides in solution are studied in this thesis, by NMR relaxation. We have employed relaxation interference effects to investigate the conformational dynamics within oligosaccharides (in-tramolecular dynamics) and paramagnetic relaxation enhancement (PRE) as an experimental tool to study intermolecular dynamics. Most of the thesis concerns the dynamics of the methylene group in the two possibly mobile parts of the oligosaccharide: in the exocyclic hydroxymethyl moiety and in the glycosidic linkage position. To perform conformational dynamic studies, the more traditional auto-relaxation pa-rameters are combined with the relaxation interference terms or the cross-correlated relaxation rates (CCRRs). Some experimental schemes based on the initial-rate technique were developed for measuring CCRRs. The techniques are useful for labelled sugars as well as naturally abundant ones. Furthermore, various dynamical models ranging from the Lipari–Szabo approach to several more informative and complicated models such as the two-site jump model, restricted internal rotation and slowly relaxing local structure (SRLS), have been employed to interpret our experimental data. We have combined and com-pared different models; we have also developed a novel approach to existing models, by scaling dipolar coupling constants (DCC), to extract the dynamic behaviour and structural properties of the system. We found that the auto- and cross-correlated relaxation data analyses yield a consistent picture of the dynam-ics in all cases. Additionally, our investigations show that CCRRs are practically important for verifica-tion of certain dynamical and structural information that is difficult to be determined by other means. Moreover, the anisotropy of the carbon-13 chemical shielding tensor in the methylene group has been estimated, using the interference between dipole-dipole and chemical shift anisotropy.</p><p>This thesis also discusses using the PRE to investigate sugar dynamics relative to a paramagnetic MRI contrast agent in solution, which might be important in medicine. We have studied the intramolecu-lar dynamics of the trisaccharide raffinose in the presence of a gadolinium complex. We also investigated the effect of translational diffusion instead of rotational diffusion, which is normally more important in NMR. The paramagnetically enhanced spin–lattice relaxation rates of aqueous protons over a wide range of magnetic fields and of carbon-13 and protons of the sugar at high fields have been measured. The nuclear magnetic relaxation dispersion of water protons and the PREs of proton and carbon in the sugar are interpreted in terms of the model recently developed in our laboratory, allowing both outer- and inner-sphere PREs for water protons, but allowing only the outer sphere PRE for nuclei in the sugar. We found that the relative diffusion has a stronger effect on the PRE than the electron spin relaxation.</p>

Oligosaccharides (carbohydrates) are a large class of biological molecules that are important as energy sources in the human body and have enormously varied biological functions. It is generally believed that biological activities of carbohydrates are related to their internal dynamics. The dynamic properties of some oligosaccharides in solution are studied in this thesis, by NMR relaxation. We have employed relaxation interference effects to investigate the conformational dynamics within oligosaccharides (in-tramolecular dynamics) and paramagnetic relaxation enhancement (PRE) as an experimental tool to study intermolecular dynamics. Most of the thesis concerns the dynamics of the methylene group in the two possibly mobile parts of the oligosaccharide: in the exocyclic hydroxymethyl moiety and in the glycosidic linkage position. To perform conformational dynamic studies, the more traditional auto-relaxation pa-rameters are combined with the relaxation interference terms or the cross-correlated relaxation rates (CCRRs). Some experimental schemes based on the initial-rate technique were developed for measuring CCRRs. The techniques are useful for labelled sugars as well as naturally abundant ones. Furthermore, various dynamical models ranging from the Lipari–Szabo approach to several more informative and complicated models such as the two-site jump model, restricted internal rotation and slowly relaxing local structure (SRLS), have been employed to interpret our experimental data. We have combined and com-pared different models; we have also developed a novel approach to existing models, by scaling dipolar coupling constants (DCC), to extract the dynamic behaviour and structural properties of the system. We found that the auto- and cross-correlated relaxation data analyses yield a consistent picture of the dynam-ics in all cases. Additionally, our investigations show that CCRRs are practically important for verifica-tion of certain dynamical and structural information that is difficult to be determined by other means. Moreover, the anisotropy of the carbon-13 chemical shielding tensor in the methylene group has been estimated, using the interference between dipole-dipole and chemical shift anisotropy. This thesis also discusses using the PRE to investigate sugar dynamics relative to a paramagnetic MRI contrast agent in solution, which might be important in medicine. We have studied the intramolecu-lar dynamics of the trisaccharide raffinose in the presence of a gadolinium complex. We also investigated the effect of translational diffusion instead of rotational diffusion, which is normally more important in NMR. The paramagnetically enhanced spin–lattice relaxation rates of aqueous protons over a wide range of magnetic fields and of carbon-13 and protons of the sugar at high fields have been measured. The nuclear magnetic relaxation dispersion of water protons and the PREs of proton and carbon in the sugar are interpreted in terms of the model recently developed in our laboratory, allowing both outer- and inner-sphere PREs for water protons, but allowing only the outer sphere PRE for nuclei in the sugar. We found that the relative diffusion has a stronger effect on the PRE than the electron spin relaxation.

The study of two pharmaceutically active systems that each display polymorphism has provided a platform upon which to develop and apply solid-state NMR techniques in order to increase the understanding of the solid-state structure of small organic molecules. The multidisciplinary approach adopted has highlighted the advantages of solid-state NMR as a non-invasive probe of molecular conformation and crystallographic packing.Carbon-13 CP/MAS spectra of the two polymorphs of BRL55834 - a fluorinated benzopyran derivative - immediately suggest the presence of one and three molecules in the asymmetric unit. A lack of crystals suitable for single-crystal XRD has catalysed the application of high-power powder X-ray diffraction studies. Subsequent attempts at structure solution using Genetic Algorithm techniques are showing preliminary results that reinforce predictions made from solid-state NMR. Novel triple-channel techniques have aided assignment and resolution of die complex (^13)C CP/MAS spectra. Enrichment of the (^15)N site appears to have resulted in the formation of a new polymorph. Techniques for the analysis of detection Units have been developed using solid-state Raman spectroscopy and chemometric analysis. The aminoxanthine derivative, BRL61063, provides interesting inter-form variations in molecular disorder, solid-state packing, and hydrogen bonding. A previously basic understanding of the single-crystal XRD data has been further evaluated through the course of this Ph.D. and solid-state NMR spectral editing techniques have been developed and applied to identify these phenomena. Recrystallisation studies have produced two samples that appear to exist in an intermediate state between the rigid and mobile structural limits. Temperature variation causes interesting changes in the relaxation characteristics and natural abundance (^15)N and (^13)C CP/MAS spectra. Residual dipolar coupling effects vary in their manifestation within the (^13)C CP/MAS spectra of the polymorphic systems studied and comparison with the literature yields important information regarding molecular conformation. Nitrogen-15 enrichment and operation at higher magnetic field have been applied to reduce these second order effects. Finally, some distance has been travelled along the path towards decoupling (^14)N. Future development of this technique holds potential for resolution enhancement in the solid state spectra of most naturally occurring, nitrogen-containing molecules.

Made available in DSpace on 2014-06-11T19:32:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-11-12Bitstream added on 2014-06-13T19:03:45Z : No. of bitstreams: 1 gottmann_r_dr_botfmvz.pdf: 570514 bytes, checksum: fb0152d1a999675ba1bb7cf5964a9b5e (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / O objetivo deste trabalho foi identificar a inclusão de níveis crescentes de farinha de vísceras (FV) na alimentação de frangos de corte, usando os isótopos estáveis de carbono e nitrogênio na análise do sangue e músculo peitoral das aves coletados semanalmente. Foram utilizados 560 pintos machos (Cobb), com um dia de idade, distribuídos aleatoriamente em tratamentos: controle (dieta vegetal), os demais tratamentos tiveram a inclusão de 0,5; 1,0; 1,5; 2,0; 2,5; 3,0; 3,5; 4,0 e 8,0% de FV na dieta. A cada 7 dias foram separadas ao acaso oito aves (n = 8) por tratamento e coletados sangue e músculo peitoral para análise da razão isotópica do carbono e nitrogênio. Tanto no sangue quanto no músculo peitoral das aves aos 7 dias de idade a FV foi detectada a partir de 3,5%, valor que é mantido para o sangue aos 14 dias de idade. No músculo peitoral aos 14 dias a detecção foi a partir de 4,0%. Com 21 dias de idade no sangue a FV foi detectada a partir 2,0% e no músculo peitoral acima de 0,5% de inclusão. Aos 28, 35 e 42 dias no sangue foi detectado a partir de 4,0; 2,5 e 3,0%; respectivamente. No músculo peitoral aos 28 e 35 dias de idade foi identificada a FV em nível a partir de 2,0% e oas 42 dias a partir de 1,5%. A coleta de amostras ao longo do período de criação é necessária para acompanhar a variação do nível de inclusão de FV na alimentação de frangos de corte, devido as mudanças de dieta de acordo com as fase de criação de aves. O músculo peitoral comparado ao sangue das aves identifica a FV na alimentação de frangos de corte em menores níveis. A análise estatística linear discriminante é boa ferramenta para identificação de menores níveis de inclusão de FV na alimentação de frangos de corte comparada a análise estatística manova / The aim of this paper was to identify the increasing levels of poultry offal meal (POM) in feed for broiler chickens using stable isotopes of carbon and nitrogen in the blood analysis and breast muscle of birds at each week. They were used 560 male chicks (Cobb), one day age. They were randomly assigned to treatments: control (vegetable diet), all other treatments had the inclusion of 0.5, 1.0; 1.5; 2.0; 2.5; 3.0; 3.5; 4.0 and 8.0% of POM in the diet. For analysis of the isotope ratio carbon and nitrogen at every 7 days were separated at random eight birds (n = 8) per treatment and collected blood and breast muscle. Both in blood as in breast muscle at 7 days old POM was detected at 3.5%, which is maintained for the blood at 14 days old. In the breast muscle at 14 days the detection was from 4.0%. Within 21 days of age in the POM blood was detected from 2.0% in the breast muscle and above the 0.5% inclusion. At 28, 35 and 42 days in the blood was detected from 4.0, 2.5 and 3.0%, respectively. In the breast muscle at 28 and 35 days of age was identified in the POM level from 2.0% and 42 days from 1.5%. The collection of samples throughout the growing period is needed to monitor the level of inclusion variação POM in feed for broiler chickens, because of changes in diet according to the phase of poultry. The breast muscle compared to the blood of birds identified the POM in the supply of broilers at lower levels. Statistical analysis of linear discriminant is a good tool for identification of lower levels of inclusion of POM in feed for broiler chickens compared to Manova statistical analysis

Dissolution dynamic nuclear polarisation is an emerging clinical technique which enables the metabolism of hyperpolarised 13C-labelled molecules to be dynamically and non- invasively imaged in tissue. The first molecule to gain clinical approval is [1-13C]pyruvate, the conversion of which to [1-13C]lactate has been shown to detect early treatment re- sponse in cancers and correlate with tumour grade. As the technique has recently been translated into humans, accurate and reliable quantitative methods are required in order to detect, analyse and compare regions of altered metabolism in patients. Furthermore, there is a requirement to understand the biological processes which govern lactate pro- duction in tumours in order to draw reliable conclusions from this data. This work begins with a comprehensive analysis of the quantitative methods which have previously been applied to hyperpolarised 13C data and compares these to some novel approaches. The most appropriate kinetic model to apply to hyperpolarised data is determined and some simple, robust quantitative metrics are identified which are suitable for clinical use. A means of automatically segmenting 5D hyperpolarised imaging data using a fuzzy Markov random field approach is presented in order to reliably identify regions of abnormal metabolic activity. The utility of the algorithm is demonstrated on both in silico and animal data. To gain insight into the processes driving lactate metabolism, a mathematical model is developed which is capable of simulating tumour growth and treatment response under a range of metabolic and tissue conditions, focusing on the interaction between tumour and stroma. Finally, hyperpolarised 13C-pyruvate imaging data from the first human subjects to be imaged in Cambridge is analysed. The ability to detect and quantify lactate production in patients is demonstrated through application of the methods derived in earlier chapters. The mathematical approaches presented in this work have the potential to inform both the analysis and interpretation of clinical hyperpolarised 13C imaging data and to aid in the clinical translation of this technique.

Orientador: Antonio Celso Pezzato / Banca: Carlosw Ducatti / Banca: Valquíria Cação da Cruz / Resumo: O presente trabalho teve por objetivo avaliar a capacidade da técnica dos isótopos estáveis em rastrear a farinha de vísceras de aves (FVA), na alimentação de codornas de corte criadas por longo período, após a substituição da dieta com 8% de FVA por dieta vegetal. Foram utilizadas 320 codornas, distribuídas aleatoriamente em oito tratamentos: dieta vegetal (T1) e sete tratamentos com inclusão de 8% de FVA na dieta, um mantendo a dieta até o final do período experimental (T2), e nos demais a dieta foi substituída aos 42; 56; 70; 84; 98; 112 dias; respectivamente, por dieta vegetal. Para coleta das amostras de músculo peitoral foram sacrificadas ao acaso, quatro aves (n = 4) por tratamento, a cada 14 dias, sendo que no T1 e T2 tiveram início aos 42 dias e nos demais a partir da troca das dietas. Os resultados isotópicos obtidos foram submetidos à análise multivariada de variância (MANOVA) com auxílio do procedimento GLM do programa estatístico SAS. Os tratamentos diferiram do vegetal quando as aves foram sacrificadas duas semanas após a troca da dieta; após esse período os tratamentos experimentais tiveram comportamento semelhante ao vegetal, exceto o T3, que se mostrou semelhante ao T1 no abate 14 dias após a troca da dieta; e do T2 que em todos os períodos de comparação diferiu do T1. Conclui-se que a aplicação da técnica dos isótopos estáveis de carbono e nitrogênio na rastreabilidade da FVA, na alimentação de codornas de corte criadas por longo período é possível nas aves abatidas 14 dias após a troca de dieta, com exceção das aves sacrificadas aos 56 dias de idade. / Abstract: The present work aimed to evaluate the capability of the stable isotope technique to trace poultry visceral meal (PVM) in the diet of meat quails raised for a long period after substitution of an 8% PVM diet for a vegetable diet. Three hundred and twenty poultries (320) were randomly distributed into eight treatments: vegetable diet (T1) and seven treatments containing 8% PVM in the diet: in one treatment, the same diet was kept until the end of the experimental period (T2), and in the remaining treatments, the diet was substituted at 42, 56, 70, 84, 98, and 112 days, respectively, for a vegetable diet. To collect chest muscle samples, four poultries (n = 4) per treatment were randomly sacrificed at every 14 days, starting at 42 days in T1 and T2 and from diet substitution in the remaining treatments. The obtained isotopic results were subjected to multivariate analysis of variance (MANOVA) using the GLM procedure of SAS statistical software. Treatments differed from the vegetable diet when poultries were sacrificed at two weeks following the diet substitution; after such period, the behavior of experimental treatments was similar to that of the vegetable diet, except for T3, which was similar to T1 at slaughtering at 14 days after the diet substitution, and T2 which, in all comparison periods, differed from T1. In conclusion, the technique of stable isotopes of carbon and nitrogen can be used to trace PVM in the diet of meat quails slaughtered at 14 days after diet substitution, except for poultries sacrificed at 56 days. / Mestre

Honey Lake Basin is a large, hydrologically closed valley with two playa lakes that are separated by a low elevation sill. The Basin has a complex hydrogeologic setting, with numerous groundwater flow paths that interact with surface waters and three basic aquifers; shallow, deep, and geothermal. Thirteen flow paths; eleven cold and two thermal, are identified and the geochemical evolution of those paths are characterized by integrating solute chemistry and isotopic data. The chemical flow paths include recharge in either granitoid or volcanic terrains in the Sierra Nevada Range and the Modoc Plateau, respectively. The groundwater then flows through alluvial fan and stream sedimentary environments and eventually flows through lacustrine and playa sediments in the closed basin. This investigating characterizes geochemical evolution of groundwater flow from both mafic and granitic terrains to lacustrine sediments with evaporite minerals, in a closed basin environment. Temperature data reveal that thermal waters circulate to 1.6-3.0 km and 2.8-3.8 km along two major fault zones. Shallow groundwaters above 17°C are determined to have a component of thermal water and mixing ratios are presented. δ18O and δD data show that deep groundwater was recharged by cooler, more humid precipitation from the last ice age, whereas shallow groundwaters reflect current meteoric conditions and show extensive evaporation trends. The two thermal flow paths show exchange with silicate minerals at high temperatures (>100°C). δ13C data show interaction with carbonate minerals in basin fill lacustrine sediments. 3H concentrations and 14C ages show that deep groundwaters throughout the Basin and shallower groundwaters in the center of the basin are not greatly affected by post-1952 recharge. Mean 14C ages range from modern to 23,500 years old. NETPATH was used to model geochemical evolution along the flow paths. Groundwater on the west side of the basin (granitic terrain) is typically low TDS (~150 mg/L) calcium-bicarbonate water and evolves into higher TDS (~300 mg/L) sodium-bicarbonate groundwater as it interacts with granitic rocks and then lacustrine sediments. Groundwater on the east side of the basin (mafic terrain) is typically low TDS (~200 mg/L) sodium-bicarbonate water and evolves into high TDS (~300 mg/L) sodium-bicarbonate water groundwater as it interacts with mafic rocks and then lacustrine sediments. Dissolution of silicate minerals and calcite, and ion exchange with clays is responsible for major chemistry changes. As both of these types of groundwaters come into contact with lacustrine sediments with evaporite minerals on the playas, dissolution of halite and gypsum dominate and the groundwater becomes extremely high in TDS (~ 1100 mg/L on the Honey Lake Playa and ~ 43,000 mg/L on the Fish Spring Playa) and strongly sodium-chloride in character.

No / We examined multiple natural abundance isotope ratios of human hair to assess biological variability within and between geographic locations and, further, to determine how well these isotope values predict location of origin. Sampling locations feature differing seasonality and mobile populations as a robust test of the method. Serially-sampled hair from Cambridge, MA, USA, shows lower δ2 H and δ18 O variability over a one-year time course than model-predicted precipitation isotope ratios, but exhibits considerable differences between individuals. Along a ∼13° northsouth transect in the eastern USA (Brookline, MA, 42.3 ° N, College Park, MD, 39.0 ° N, and Gainesville, FL, 29.7 ° N) δ18 O in human hair shows relatively greater differences and tracks changes in drinking water isotope ratios more sensitively than δ2 H. Determining the domicile of humans using isotope ratios of hair can be confounded by differing variability in hair δ18 O and δ2 H between locations, differential incorporation of H and O into this protein and, in some cases, by tap water δ18 O and δ2 H that differ significantly from predicted precipitation values. With these caveats, randomly chosen people in Florida are separated from those in the two more northerly sites on the basis of the natural abundance isotopes of carbon, nitrogen, hydrogen, and oxygen. / This work was partially supported by the National Geospatial Agency under grant [HM1582-08-0024]. / Originally presented at the IAEA International Symposium on Isotope Hydrology: Revisiting Foundations and Exploring Frontiers, 11–15 May 2015, Vienna, Austria

Glucose and ketones are important energy substrates in the human body and brain. Their use is highly regulated depending on energy status which can vary according to multiple factors such as type of cell, fed or fasted state, type of diet, or health state. Use of either substrate is also subject to multiple homeostatic feedback loops. Energy substrate availability has implications in several disorders including declining cognitive function in the elderly. While glucose availability is known to decrease in elderly with cognitive deficits, it is unclear whether this also occurs in healthy elderly, either in the body or brain. Also unknown is whether, in healthy elderly, the use of ketones as energy substrates is affected, and whether ketones could be used as an alternative energy substrate in situations of a decline in glucose availability. A clearer understanding of the use of glucose and ketones in aging is necessary to determine whether declining energy substrate availability that may occur in the elderly is a contributing factor to cognitive deficits, a result of cognitive pathology, or simply a feature of the physiological aging process. Objective. The overall goal of the laboratory where this research was carried out is to ascertain whether alternate energy sources to glucose, i.e. ketones, may help alleviate the risk of declining cognitive function during aging. The specific objective of the research project presented in this thesis was to evaluate the metabolism of glucose and ketones in the healthy elderly compared to young or middle age subjects during mild, short-term ketosis induced by a ketogenic breakfast. Results. Elderly people in relatively good health have a similar capacity to produce ketones and to oxidize [superscript 13]C-glucose and [superscript 13]C-β-hydroxybutyrate as middle-aged or young adults. Discussion. The results of this project encourage further exploration of whether ketones could be used as and alternative energy substrate to glucose as, at least in healthy elderly, there is no impedance of raising plasma ketones in response to a ketogenic intervention. // Résumé : Introduction. Le glucose et les cétones sont des substrats énergétiques importants pour le corps et le cerveau humain. Leur utilisation est spécifiquement régulée selon I'état énergétique qui varie en fonction du type de cellule, de I'état nourrie ou à jeun, du type de diète, de I'état de la santé. L'utilisation est également régulée par des voies de rétrocontrôle homéostatique. La disponibilité des substrats énergétiques est impliquée dans plusieurs désordres, dont le déclin des fonctions cognitives, chez les personnes âgées où une diminution de la disponibilité du glucose est démontrée. Cependant, il n'est pas encore connu si cette diminution est présente chez les personnes âgées en bonne santé ; soit dans le corps ou le cerveau. La capacité d'utiliser les cétones comme substrats énergétiques chez les personnes âgées saines et la possibilité d'utiliser les cétones comme substrat énergétique alternatif dans le cas d'un déclin de la disponibilité de glucose sont inconnues. Une meilleure compréhension de I'utilisation du glucose et des cétones sera nécessaire pour clarifier si une diminution de la disponibilité des substrats énergétique contribue au déclin cognitif, se manifeste à la suite des pathologies cognitives, ou encore est simplement une caractéristique du processus physiologique du vieillissement. Objectif. L'objectif principal du laboratoire est de déterminer si les sources d'énergie alternatives au glucose, c'est-à-dire les cétones, pourraient ralentir le déclin cognitif chez les personnes âgées. L'objectif du projet de recherche de ce mémoire était d'évaluer le métabolisme du glucose et des cétones chez les sujets âgés, d'âge moyen, et jeune après la prise d'un déjeuner induisant une faible cétogénèse de courte durée. Résultats. Les personnes âgées en santé ont une capacité similaire au sujet d'âge moyen et jeune à produire des cétones et à oxyder le [indice supérieur 13]C-glucose et le [indice supérieur 13]C-β- hydroxybutyrate. Perspectives. Les résultats de ce projet incitent à continuer à explorer si les cétones pourraient être utilisés comme substrats énergétiques afin de contourner le problème d'un déclin de I'utilisation du glucose, car il n'y a aucun obstacle dans la production des cétones suite a une intervention cétonique chez des sujets âgées en bonne santé.