RESUMO
OBJECTIVE: Magnetic resonance spectroscopy (MRS) (specifically, (1)H-MRS) has been used to show changes in the brain following peripheral nerve injury in subjects without diabetes. This study used (1)H-MRS to examine the brain in subjects with or without painful diabetic neuropathy. RESEARCH DESIGN AND METHODS: Twenty-six diabetic subjects (12 with and 14 without chronic neuropathic pain) were compared, with 18 subjects without diabetes and pain. The left thalamus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC) were assessed using (1)H-MRS. RESULTS: In the DLPFC, diabetic subjects had a decrease in N-acetyl aspartate (NAA) and creatine relative to the control group. In the thalamus, there was a reduction of NAA in the diabetic group with pain compared with that in patients with diabetes and no pain. CONCLUSION: Subjects with diabetes have metabolite differences in the brain compared with control subjects. Subjects with painful neuropathy showed reduced NAA in the thalamus, which may explain the genesis of pain in some cases.
Assuntos
Mapeamento Encefálico , Encéfalo/patologia , Neuropatias Diabéticas/fisiopatologia , Dor/fisiopatologia , Adulto , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Colina/metabolismo , Creatina/metabolismo , Neuropatias Diabéticas/patologia , Feminino , Lobo Frontal/patologia , Giro do Cíngulo/patologia , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dor/patologia , Valores de Referência , Limiar Sensorial , Tálamo/patologiaRESUMO
Patients with mitochondrial myopathy (MM) have a reduced capacity to perform exercise due to a reduced oxidative capacity. We undertook this study to determine whether skeletal muscle metabolism could be improved with oxygen therapy in patients with MM. Six patients with MM and six controls, matched for age, gender and physical activity, underwent (31)P-magnetic resonance spectroscopy ((31)P-MRS) examination. (31)P-MR spectra were collected at rest and in series during exercise and recovery whilst breathing normoxic (0.21 O(2)) or hyperoxic (1.0 O(2)) air. At rest, MM showed an elevated [ADP] (18 +/- 3 micromol/l) and pH (7.03 +/- 0.01) in comparison to the control group (12 +/- 1 micromol/l, 7.01 +/- 0.01) (P < 0.05) consistent with mitochondrial dysfunction. Oxygen supplementation did not change resting metabolites in either MM or the control group (P > 0.05). Inferred maximal ATP synthesis rate improved by 33% with oxygen in MM (21 +/- 3 vs. 28 +/- 5 mmol/(l min), P < 0.05) but only improved by 5% in controls (40 +/- 3 vs. 42 +/- 3 mmol/(l min), P > 0.05). We conclude that oxygen therapy is associated with significant improvements in muscle metabolism in patients with MM. These data suggest that patients with MM could benefit from therapies which improve the provision of oxygen.
Assuntos
Mitocôndrias Musculares/metabolismo , Miopatias Mitocondriais/terapia , Músculo Esquelético/metabolismo , Oxigenoterapia , Oxigênio/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Adulto , Exercício Físico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Miopatias Mitocondriais/metabolismo , Miopatias Mitocondriais/fisiopatologia , Contração Muscular , Músculo Esquelético/fisiopatologia , Fósforo , Recuperação de Função Fisiológica , Resultado do TratamentoRESUMO
Exercise therapy improves mitochondrial function in patients with mitochondrial myopathy (MM). We undertook this study to determine the metabolic abnormalities that are improved by exercise therapy. This study identified metabolic pathology using (31)P-magnetic resonance spectroscopy and magnetic resonance imaging (MRI) in a group of patients with MM compared to a control group matched for age, gender, and physical activity. We also observed the effect of exercise therapy for 12 weeks on muscle metabolism and physical function in the MM group. During muscle activity, there was impaired responsiveness of the mitochondria to changes in cytosolic adenosine diphosphate concentration, increased dependence on anaerobic energy pathways, and an adaptive increase in proton efflux in patients with MM. Following exercise therapy, mitochondrial function and muscle mass improved without any change in proton efflux rate. These metabolic findings were accompanied by improvements in functional ability. We conclude that there are significant metabolic differences between patients with MM and a control population, independent of age, gender, and physical activity. Exercise therapy can assist in improving mitochondrial function in MM patients.
Assuntos
Exercício Físico/fisiologia , Miopatias Mitocondriais/metabolismo , Músculo Esquelético/metabolismo , Adulto , Algoritmos , Teste de Esforço , Terapia por Exercício , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/metabolismo , Miopatias Mitocondriais/patologia , Músculo Esquelético/patologia , Tamanho do Órgão , Fósforo/metabolismo , PrótonsRESUMO
BACKGROUND: Phosphate supplementation has been used in an effort to enhance athletic performance by increasing erythrocyte 2,3-bisphosphoglycerate levels ([2,3-BPG]) and hence improve oxygen offloading from haemoglobin. Claimed effects of phosphate loading upon both exercise performance and erythrocyte [2,3-BPG] are inconsistent, and the basis of any change in [2,3-BPG] is unknown. METHODS: We analysed plasma inorganic phosphate concentration ([P(i)]) and erythrocyte [P(i)] and [2,3-BPG] in venous blood samples from 12 healthy subjects. We re-examined a subset of five of these subjects after 7 days of phosphate loading. RESULTS: There were significant positive correlations between plasma [P(i)] and erythrocyte [P(i)] (r(2)=0.51, p=0.009) and between erythrocyte [P(i)] and [2,3-BPG] (r(2)=0.68, p<0.001). Following phosphate loading, there was a 30% increase in plasma [P(i)] (1.02+/-0.22 to 1.29+/-0.15 mmol/l (mean+/-S.D.), p=0.03) and a 25% increase in erythrocyte [2,3-BPG] (6.77+/-1.12 to 9.11+/-1.87 mmol/l cells, p=0.03). There is no relation between [2,3-BPG] and plasma [P(i)]. CONCLUSIONS: Phosphate loading increases both plasma and erythrocyte phosphate pools and the rise in [2,3-BPG] is probably a consequence of the rise in cell [P(i)].