RESUMO
To characterize the white matter structural changes at the tract level and tract group level, comprehensive analysis with 4 metrics derived from diffusion tensor imaging (DTI), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD), was conducted. Tract groups, namely limbic, commissural, association, and projection tracts, include white matter tracts of similar functions. Diffusion tensor imaging data were acquired from 61 subjects (26 Alzheimer's disease [AD], 11 subjects with amnestic mild cognitive impairment [aMCI], and 24 age-matched controls). An atlas-based approach was used to survey 30 major cerebral white matter tracts with the measurements of FA, MD, AxD, and RD. Regional cortical atrophy and cognitive functions of AD patients were also measured to correlate with the structural changes of white matter. Synchronized structural changes of cingulum bundle and fornix, both of which are part of limbic tract group, were revealed. Widespread yet distinctive structural changes were found in limbic, commissural, association, and projection tract groups between control and AD subjects. Specifically, FA, MD, and RD of limbic tracts, FA, MD, AxD, and RD of commissural tracts, MD, AxD, and RD of association tracts, and MD and AxD of projection tracts are significantly different between AD patients and control subjects. In contrast, the comparison between aMCI and control subjects shows disruption only in the limbic and commissural tract groups of aMCI subjects. MD values of all tract groups of AD patients are significantly correlated to cognitive functions. Difference between AD and control and that between aMCI and control indicates a progression pattern of white matter disruption from limbic and commissural tract group to other tract groups. High correlation between FA, MD, and RD measurements from limbic tracts and cortical atrophy suggests the disruption of the limbic tract group is caused by the neuronal damage.
Assuntos
Doença de Alzheimer/patologia , Mapeamento Encefálico , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética , Fibras Nervosas Mielinizadas/patologia , Idoso , Anisotropia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estatística como AssuntoRESUMO
BACKGROUND: Individuals with nonalcoholic fatty liver disease (NAFLD) have excess intrahepatic triglycerides. This is due, in part, to increased hepatic synthesis of fat from carbohydrates via lipogenesis. Although weight loss is currently recommended to treat NAFLD, little attention has been given to dietary carbohydrate restriction. OBJECTIVE: The aim of this study was to determine the effectiveness of 2 wk of dietary carbohydrate and calorie restriction at reducing hepatic triglycerides in subjects with NAFLD. DESIGN: Eighteen NAFLD subjects (n = 5 men and 13 women) with a mean (±SD) age of 45 ± 12 y and a body mass index (in kg/m(2)) of 35 ± 7 consumed a carbohydrate-restricted (<20 g/d) or calorie-restricted (1200-1500 kcal/d) diet for 2 wk. Hepatic triglycerides were measured before and after intervention by magnetic resonance spectroscopy. RESULTS: Mean (±SD) weight loss was similar between the groups (-4.0 ± 1.5 kg in the calorie-restricted group and -4.6 ± 1.5 kg in the carbohydrate-restricted group; P = 0.363). Liver triglycerides decreased significantly with weight loss (P < 0.001) but decreased significantly more (P = 0.008) in carbohydrate-restricted subjects (-55 ± 14%) than in calorie-restricted subjects (-28 ± 23%). Dietary fat (r = 0.643, P = 0.004), carbohydrate (r = -0.606, P = 0.008), posttreatment plasma ketones (r = 0.755, P = 0.006), and respiratory quotient (r = -0.797, P < 0.001) were related to a reduction in liver triglycerides. Plasma aspartate, but not alanine, aminotransferase decreased significantly with weight loss (P < 0.001). CONCLUSIONS: Two weeks of dietary intervention (≈4.3% weight loss) reduced hepatic triglycerides by ≈42% in subjects with NAFLD; however, reductions were significantly greater with dietary carbohydrate restriction than with calorie restriction. This may have been due, in part, to enhanced hepatic and whole-body oxidation. This trial was registered at clinicaltrials.gov as NCT01262326.
Assuntos
Dieta com Restrição de Carboidratos , Dieta Redutora , Fígado Gorduroso/dietoterapia , Fígado/metabolismo , Triglicerídeos/metabolismo , Redução de Peso , Adulto , Índice de Massa Corporal , Fígado Gorduroso/sangue , Feminino , Humanos , Cetonas/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Consumo de OxigênioRESUMO
A single voxel proton NMR double quantum filter (DQF) for measurement of glutathione (GSH) in human brain at 3T is reported. Yield enhancement for the CH(2) resonances of the cysteine moiety at 2.95ppm has been achieved by means of dual encoding. After the preparation of double quantum and zero quantum coherences (DQC and ZQC) at equal magnitude, the first DQC encoding was followed by interchange of DQC and ZQC, and another DQC encoding. The multi-quantum coherences were fully utilized to generate a GSH target signal at approximately 2.95ppm. The optimal echo time and the editing efficiency were obtained with numerical analysis of the filtering performance and phantom measurements. The dual-DQC encoding method provided GSH yield greater by a factor of 2.1 than single-DQC encoding for identical slice-selective RF pulses in phantom tests. Using the phantom relaxation times and the ratio of edited GSH to N-acetylaspartate (NAA) 2.0-ppm peak areas, the concentration of GSH in the medial parietal cortex of the healthy human brain in vivo was estimated to be 1.0+/-0.3mM (mean+/-SD, n=7), with reference to NAA at 10mM.
Assuntos
Química Encefálica , Glutationa/análise , Espectroscopia de Ressonância Magnética/métodos , Adulto , Algoritmos , Aminoácidos/química , Cisteína/química , Interpretação Estatística de Dados , Feminino , Glutationa/química , Humanos , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Masculino , Lobo Parietal/química , Imagens de Fantasmas , Valores de Referência , Água/química , Adulto JovemRESUMO
UNLABELLED: Carbohydrate restriction is a common weight-loss approach that modifies hepatic metabolism by increasing gluconeogenesis (GNG) and ketosis. Because little is known about the effect of carbohydrate restriction on the origin of gluconeogenic precursors (GNG from glycerol [GNG(glycerol)] and GNG from lactate/amino acids [GNG(phosphoenolpyruvate (PEP))]) or its consequence to hepatic energy homeostasis, we studied these parameters in a group of overweight/obese subjects undergoing weight-loss via dietary restriction. We used (2)H and (13)C tracers and nuclear magnetic resonance spectroscopy to measure the sources of hepatic glucose and tricarboxylic acid (TCA) cycle flux in weight-stable subjects (n = 7) and subjects following carbohydrate restriction (n = 7) or calorie restriction (n = 7). The majority of hepatic glucose production in carbohydrate restricted subjects came from GNG(PEP). The contribution of glycerol to GNG was similar in all groups despite evidence of increased fat oxidation in carbohydrate restricted subjects. A strong correlation between TCA cycle flux and GNG(PEP) was found, though the reliance on TCA cycle energy production for GNG was attenuated in subjects undergoing carbohydrate restriction. Together, these data imply that the TCA cycle is the energetic patron of GNG. However, the relationship between these two pathways is modified by carbohydrate restriction, suggesting an increased reliance of the hepatocyte on energy generated outside of the TCA cycle when GNG(PEP) is maximal. CONCLUSION: Carbohydrate restriction modifies hepatic GNG by increasing reliance on substrates like lactate or amino acids but not glycerol. This modification is associated with a reorganization of hepatic energy metabolism suggestive of enhanced hepatic beta-oxidation.