Effects of exercise on muscle activation and metabolism in multiple sclerosis

We investigated the role of metabolism in muscle fatigue during voluntary exercise in persons with mild multiple sclerosis (MS). Six MS and 8 healthy control subjects performed intermittent, progressive, isometric contractions of the ankle dorsiflexors, during which we measured maximum voluntary force (MVC), inorganic phosphate (Pi), phosphocreatine (PCr), and pH. During exercise. MVC fell sooner in MS, but by the end of exercise the relative decrease in MVC was similar in both groups. In contrast, at the end of exercise Pi/PCr increased to 1.86 ± 0.22 in controls but to only 0.66 ± 0.04 in MS (P < 0.01); likewise, pH was 6.75±0.04 in controls and unchanged (7.06 ± 0.04) in MS (P <0.01). The smaller metabolic change at the same relative exercise intensity suggests a failure of muscle activation that is present even in mild MS. Neurophsyiologic measures of activation indicated some central activation failure and no neuromuscular junction impairment in MS, and suggested that activation failure beyond the muscle membrane(excitation–contraction coupling) may be important in MS. We conclude that metabolic factors do not play a significant role in the development of muscle fatigue during voluntary exercise in mild MS. © 1994 John Wiley & Sons, Inc.     

P-31 MR spectroscopy of skeletal and cardiac muscle metabolism in patients with systemic sclerosis: A multiple case study

Three-dimensionally localized proton-decoupled phosphorus-31 magnetic resonance (MR) spectroscopy of skeletal and cardiac muscle was performed in six patients with systemic sclerosis. Cardiac (n = 9) and skeletal (n = 6) spectra were also obtained in healthy volunteers. Metabolite ratios and intracellular pH were determined from the spectra of skeletal and cardiac muscle. The phosphocreatine-to-adenosine triphosphate ratio was normal for both skeletal and cardiac muscle in patients with systemic sclerosis. The pH values of skeletal muscle were similar in patients and control subjects (7.13 ± 0.02 vs 7.12 ± 0.01, respectively). In skeletal muscle, the inorganic phosphate-to-phosphocreatine ratio in patients was increased relative to that of control subjects (0.106 ± 0.014 vs 0.086 ± 0.006, respectively; P =.02). P-31 MR spectroscopy showed no abnormalities in the myocardium of patients with systemic sclerosis. Assessment of the inorganic phosphate-to-phosphocreatine ratio in peripheral skeletal muscle may be helpful for assessing disease activity.     

Applications of magnetic resonance spectroscopy to diagnosis and monitoring of mitochondrial disease

Magnetic resonance spectroscopy (MRS) can now be performed on routine high-field clinical magnetic resonance imaging systems. Over the last decade it has provided several useful insights into the pathophysiology of mitochondrial disorders. More recently, the feasibility of applications to clinical diagnosis and monitoring have been demonstrated. Exciting new work suggests that carefully supervised physical conditioning in conjunction with sodium dichloroacetate administration can markedly enhance both biochemical measures of aerobic metabolism and functional performance of patients with mitochondrial myopathies.

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Sommario La risonanza magnetica spettroscopica (MRS) può oggi essere effettuata di routine in apparecchi clinici di risonanza magnetica. Nell'ultima decade essa ha fornito importanti informazioni nella patofisiologia dei disordini mitocondriali. Più recentemente sono state dimostrate le sue possibilità di applicazione nella diagnosi clinica e nel monitoraggio di pazienti neurologici. Nuovi ed interessanti studi suggeriscono che un allenamento attentamente supervisionato in congiunzione con trattamento con dicloroacetato è capace di migliorare i parametri biochimici e la performance di pazienti con miopatie mitocondriali.

     

Metabolite changes with age measured by proton magnetic resonance spectroscopy in normal subjects

Abstract  To determine whether there are metabolite changes in the left medial temporal and frontal lobes with aging, we performed proton magnetic resonance spectroscopy in 36 normal subjects. The N-acetylaspartate/creatine-phosphocreatine ratio in the medial temporal lobe tended to be decreased in subjects over 60 years of age. The ratio decrease in the frontal lobe related to aging was lower than that in the medial temporal lobe. There were no significant differences in the metabolite ratios between males and females. These findings suggest that structures in the medial temporal lobe may be more susceptible to neuronal dysfunction associated with aging than those in the frontal lobe.     

不同状态胆囊组织的傅立叶变换红外光谱研究

目的 探索不同生理病理状态的胆囊组织各自特异的傅立叶变换红外光谱(Fourier transform infrared spectroscopy，FT-IR)表现。方法 应用FT-IR对8例正常胆囊组织、10例炎性胆囊组织和10例胆囊癌组织进行检测，结合常规病理结果总结不同组织的光谱特征。结果 胆囊正常、炎性和癌组织具有不同的FT-IR光谱表现，1550cm^-1处的酰胺Ⅱ带在癌组织中显得较弱，峰形低平，而在正常组织中则较强，峰形高尖。1080cm^-1处核酸的吸收谱带在癌组织中较强，I1080／I1550的比值在正常组织中为0．62，癌组织中为0．87。正常组织中1450cm^-1处的峰多强于1400cm^-1处，而在癌组织中则相反。结论 胆囊正常、炎性和癌组织的FT-UR谱图不同，主要表现为组织中蛋白质、核酸和磷脂等含量与结构的改变，FT-IR有望成为胆道疾病临床诊断的一种新手段。     

Cardiac metabolism: A technical spectrum of modalities including positron emission tomography,single-photon emission computed tomography,and magnetic resonance spectroscopy

Noninvasive techniques for the assessment of cardiac metabolism are important for the detection of potentially salvageable tissue in jeopardized areas of the myocardium. The correct identification of hibernating and stunned myocardium in patients with severely depressed cardiac function can have vital therapeutic consequences for the patient. Changes in myocardial fatty acid and glucose metabolism during acute and prolonged ischemia can be traced by positron-emitting or gamma-emitting radiopharmaceuticals. Alternatively,³¹P-labeled magnetic resonance spectroscopy can be used for the assessment of high-energy phosphate metabolism. It is not yet clear which modality will emerge as the most useful in the clinical setting. Positron emission tomography (PET) that uses combinations of flow tracers and metabolic tracers offers unique opportunities for quantification and high-resolution static and rapid dynamic studies. Currently, assessment of glucose metabolism with¹⁸F-fluorodeoxyglucose is regarded as the gold standard for myocardial viability and prediction of improvement of impaired contractile function after revascularization. However, preserved oxidative metabolism may be required for potential functional improvement, and therefore assessment of residual oxidative metabolism by¹¹C-labeled acetate PET may prove to be more accurate than¹⁸F-fluorodeoxyglucose PET, which reflects both anaerobic and oxidative metabolism. Moreover, because fatty acids are metabolized only aerobically, they are excellent candidates for the clinical assessment of myocardial viability and prediction of functional improvement after revascularization. Especially derivatives of fatty acids that are not metabolized but accumulate in the myocyte are attractive for myocardial imaging. Examples are¹²³I-beta-methyl-p-iodophenyl pentadecanoic acid and 15-(o-¹²³I-phenyl)-pentadecanoic acid. These tracers can be detected by planar scintigraphy and single-photon emission computed tomography, which are more economical and widely available than PET. In addition, 511 keV collimators have been developed recently, making the detection of positron emitters by planar scintigraphy and single-photon emission computed tomography feasible. The experience with³¹P-labeled magnetic resonance spectroscopy in humans is still limited. With current magnetic resonance spectroscopic techniques, insufficient spatial resolution is achieved for clinical purposes, but the possibility of serial measurements to monitor rapid changes of phosphate-containing molecules in time makes magnetic resonance spectroscopy very valuable for the research of myocardial metabolism.     

大鼠中枢和外周神经损伤后胞体分布区神经组织的红外光谱分析

目的：观察外周和中枢神经损伤后胞体分布区神经组织总蛋白和核酸的变化规律。方法：应用傅里叶红外光谱(FTIR)检测方法，分析大鼠脊髓和坐骨神经损伤后相应的神经元胞体分布区神经组织中归属为核酸和蛋白质的谱带吸收强度的变化。结果：伤后早期，外周和中枢神经损伤后其相应胞体部位神经组织RNA，DNA和蛋白质的含量均增加；1周后，外周和中枢神经元胞体分布区RNA，DNA和蛋白质含量均变化规律不同：外周神经元胞体RNA和DNA的含量仍较高，而中枢神经伤侧和对照侧胞体RNA和DNA的含量接近，中枢和外周神经元胞体蛋白含量变化相反。结论：外周和中枢神经损伤后再生过程中其胞体反应性不同，这一差异可能与外周和中枢神经损伤后再生差异有关。     

Identification of N2 as a metabolite of acetylhydrazine in the rat

 In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [¹⁴C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [¹⁵N]-nitrogen and ¹⁴CO₂ exhalation, after the administration of [¹⁵N₂]-[¹⁴C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of ¹⁵N and ¹⁴N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB + cobalt(II) chloride (CoCl₂) (n=3 in each group). Time-dependent ¹⁵N₂ exhalation differed significantly between treatment groups (p<0.001). At 240 min, cumulative exhalation of ¹⁵N was 1.92±0.43% (mean±SE) of the dose in the control group, 2.53±0.23% in the PB group, and 1.00±0.15% in the PB+CoCl₂ group (p<0.05 compared to controls, p<0.01 compared to PB). Cumulative exhalation of ¹⁴CO₂ in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N₂ is a metabolite of AcHz. N₂ formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N₂-liberating process in vivo. Received: 14 March 1995/Accepted: 15 August 1995     

Synergistic renal protection by combining alkaline-diuresis with lipid peroxidation inhibitors in rhabdomyolysis: possible interaction between oxidant and non-oxidant mechanisms

BACKGROUND AND PURPOSE.: Heme-proteins, besides causing renal tubular obstruction, maycontribute to rhabdomyolysis-induced renal injury through aheme-iron-mediated lipid peroxidation process. In the presentstudy, we compared the combined therapy of a lipid peroxidationinhibitor, 21-aminosteroid (21-AS) and fluid-alkaline-mannitol(FAM) diuresis with either of them alone to determine the efficacyof the combination therapy and to delineate the roles of lipidperoxidation and cast formation. METHODS AND RESULTS.: Employing Raman spectroscopy, we confirmed in vitro the abilityof 21-AS to inhibit iron-induced fatty acid peroxidation. 21-ASwas then administered to rats developing renal failure fromglycerol-induced rhabdomyolysis. Although 21-AS inhibited rhabdomyolysis-inducedplasma and renal lipid peroxidation, renal protection was incomplete.Administration of FAM to inhibit cast formation afforded a betterrenal protection. However, when these therapies were combinedto inhibit both lipid peroxidation and cast formation, therewas a synergistic renal functional protection. This was accompaniedby a maximum inhibition of renal and plasma lipid peroxidation,as well as, renal tubular necrosis and cast formation. Comparedto combination therapy, FAM therapy alone, despite identicalvolume, was accompanied by a higher tubular necrosis and castformation. CONCLUSIONS.: That combining a lipid peroxidation inhibitor with fluid-alkalinediuresis in rhabdomyolysis further lowers renal lipid peroxidation,tubular necrosis and cast formation and synergistically limitsrenal dysfunction (i) supports a role for lipid peroxidationin the pathophysiology of rhabdomyolysis ARF, (ii) underscoresthe role of intratubular heme retention, a cause for tubularobstruction as well a source for prodigious amount of iron,likely involved in the lipid peroxidation, and (iii) raisesthe possibility of interactions between non-oxidant and oxidantmechanisms.     

The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: A 31P, 23Na and 87Rb NMR spectroscopic study

An increase in intracellular Na⁺ during ischaemia has been associated with myocardial injury. In this study, we determined whether inhibition of Na⁺/K⁺ ATPase activity contributes to this increase and whether Na⁺/K⁺ ATPase activity can be maintained by provision of glucose to perfused rat hearts during low flow, 0.5 ml/min, ischemia. We used ³¹P NMR spectroscopy to determine changes in myocardial energetics and intracellular and extracellular volumes. ²³Na NMR spectroscopy, with DyTTHA^3- present as a shift reagent, was used to measure changes in intracellular Na⁺ and ⁸⁷Rb NMR spectroscopy was used to estimate Na⁺/K⁺ ATPase activity from Rb⁺ influx rates, Rb⁺ being an NMR-sensitive congener of K⁺. In hearts provided with 11 mM glucose throughout ischemia, glycolysis continued and ATP was twofold higher than in hearts without glucose. In the glucose-hearts, Rb⁺ influx rate was threefold higher, intracellular Na⁺ was fivefold lower at the end of ischemia and functional recovery during reperfusion was twofold higher. We propose that continuation of glycolysis throughout low flow ischemia allowed maintenance of sufficient Na⁺/K⁺ ATPase activity to prevent the increase in intracellular Na⁺ that would otherwise have led to myocardial injury.