phosphocreatine and Muscular-Diseases

The presence of abnormalities in fibromyalgia muscle using current methodological approaches is well established. The more serious abnormalities are demonstrated by histologic studies particularly on electron microscopy: disorganisation of Z bands and abnormalities in the number and shape of mitochondria. Biochemical studies and P 31 magnetic resonance spectroscopy show inconstant abnormalities of ATP and phosphocreatine levels. Mitochondrial abnormalities reduced capillary circulation and thickened capillary endothelium may result in decreased availability of oxygen and impaired oxidative phosphorylation as well as ATP synthesis. These abnormalities do not seem to be the consequences of the much-discussed deconditioning of muscles although these consequences are not well known. Further studies of energy metabolism of the muscle during exercise are needed.

Topics: Adenosine Triphosphate; Endothelium, Vascular; Energy Metabolism; Fibromyalgia; Humans; Microcirculation; Microscopy, Electron; Mitochondria, Muscle; Muscle, Skeletal; Muscular Diseases; Pain; Phosphocreatine

31P MRS and 1H MRI of skeletal muscle have become major new tools allowing a complete non invasive investigation of muscle function both in the clinical setting and in basic research. The comparative analysis of normal and diseased muscle remains a major requirement to further define metabolic events surrounding muscle contraction and the metabolic anomalies underlying pathologies. Also, standardized rest-exercise-recovery protocols for the exploration of muscle metabolism by P-31 MRS in healthy volunteers as well as in patients with intolerance to exercise have been developed. The CRMBM protocol is based on a short-term intense exercise, which is very informative and well accepted by volunteers and patients. Invariant metabolic parameters have been defined to characterize the normal metabolic response to the protocol. Deviations from normality can be directly interpreted in terms of specific pathologies in some favorable cases. This protocol has been applied to more than 4,000 patients and healthy volunteers over a period of 15 years. On the other hand, MRI investigations provide anatomical and functional information from resting and exercising muscle. From a diagnostic point of view, dedicated pulse sequences can be used in order to detect and quantify muscle inflammation, fatty replacement, muscle hyper and hypotrophy. In most cases, MR techniques provide valuable information which has to be processed in conjunction with traditional invasive biochemical, electrophysiological and histoenzymological tests. P-31 MRS has proved particularly useful in the therapeutic follow-up of palliative therapies (coenzyme Q treatment of mitochondriopathies) and in family investigations. It is now an accepted diagnostic tool in the array of tests which are used to characterize muscle disorders in clinical routine. As a research tool, it will keep bringing new information on the physiopathology of muscle diseases in animal models and in humans and should play a role in the metabolic characterization of gene and cell therapy.

Topics: Adenosine Triphosphate; Calibration; Energy Metabolism; Equipment Design; Exercise Test; Humans; Hydrogen; Magnetic Resonance Spectroscopy; Metabolism, Inborn Errors; Mitochondrial Myopathies; Muscle Contraction; Muscle, Skeletal; Muscular Diseases; Myositis; Neuromuscular Diseases; Phosphates; Phosphocreatine; Phosphorus Isotopes; Rest

In recent years, COPD has become increasingly thought of as a systemic disease affecting many tissues and organs in addition to the lungs. The skeletal muscles in particular have been the target of much research focusing on whether the universally observed exercise limitation reflects a systemic myopathic effect of COPD, or simply the consequences of extreme, long-term inactivity. In this paper, the evidence is reviewed for COPD patients without loss of muscle mass and who are not taking systemic steroids. While altered levels of antioxidant defences (lower), circulating inflammatory biomarkers (higher) and anabolic hormones (lower) have been found in COPD, cause and effect remains to be established for the link of inflammation/oxidative stress to muscle dysfunction. Other evidence used to propose a myopathic state (early lactate release, reduced power output, lower metabolic enzyme capacities, greater phosphocreatine breakdown and slower phosphocreatine restoration after exercise, and altered fibre type distribution) also occur in normal subjects who are extremely inactive. Furthermore, intense small muscle mass training can normalize small muscle function in these patients. Based on these data, it remains to be shown that the muscles in COPD patients without loss of muscle mass are myopathic. The interesting discussion about systemic effects of COPD should not get in the way of systematic muscle training, which has been shown to be an effective component of rehabilitation.

Topics: Exercise Therapy; Forced Expiratory Volume; Humans; Insulin-Like Growth Factor I; Interleukin-6; Lactates; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Oxidative Stress; Phosphocreatine; Physical Fitness; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Testosterone; Tumor Necrosis Factor-alpha

Nuclear magnetic resonance spectroscopy has progressed far since the original description of the phenomenon (30,31) and now permits noninvasive and harmless measurements to be repeatedly made of tissue biochemistry. Currently, there is a paucity of NMR data on normal human metabolism and the interpretation of spectra recorded from diseased tissues must be circumspect. This is further complicated by the inability of NMR spectroscopy to render accurate quantitative measurements and all observations must be considered to be compatible with, rather than diagnostic of, specific diseases. Nevertheless, NMR is an important addition to the clinician's armamentarium and these relatively expensive instruments should be situated in regional referral centres. Undoubtedly the most significant advances in NMR will only occur following the successful combination of the imaging and spectroscopic techniques, since that will enable anatomical and metabolic data to be obtained from a single site without the need for biopsy. Nuclear magnetic resonance spectroscopy has much to offer and the practical hazards appear to be few. In the next few years we will undoubtedly see an improvement in the quality of the data obtainable an a growing diversity of clinical applications.

Topics: Humans; Hypoxia, Brain; Magnetic Resonance Spectroscopy; Muscles; Muscular Atrophy; Muscular Diseases; Neoplasms; Phosphates; Phosphocreatine; Phosphofructokinase-1

Nuclear magnetic resonance is a new method for assaying the content of phosphate metabolites in intact tissues. Its nondestructive nature allows simultaneous and repeated determinations of these compounds with a minimum perturbation of tissue. Changes in the concentrations of the phosphates as a function of time characterize the metabolic machinery of the tissue and reveal alterations in enzymic activity that result from drug treatment or disease. The entire phosphate profile shows differences between normal and diseased muscle which should be of diagnostic value. Further, by examining phosphate profiles we detected a family of chemical compounds that were not previously known to exist as major constituents in muscle. Of these, two have been isolated and one has been identified as glycerol 3-phosphorylcholine. Finally, shifts in the positions of resonances monitor the internal environment of the living system, its hydrogen ion concentration, the complexing of alkaline earth metals with ATP, and compartmentalization within the cell.

Topics: Adenosine Triphosphate; Animals; Caffeine; Chickens; Humans; Magnetic Resonance Spectroscopy; Muscle Contraction; Muscles; Muscular Diseases; Muscular Dystrophies; Perchlorates; Phosphates; Phosphocreatine

Malignant hyperthermia (MH) is a metabolic myopathy with an abnormal release of calcium by the sarcoplasmic reticulum (SR), triggered by volatile anesthetics and succinylcholine. Similarly, caffeine enhances Ca(2+)release by the SR in vitro. In a prospective, randomized study, high-energy phosphates were studied by intramuscular 31-phosphorus magnetic resonance spectroscopy ((31)P-MRS) in 10 MH-susceptible (MHS) and 7 MH-nonsusceptible (MHN) subjects before and after injection of 0.5 ml caffeine (20 mM). Intramuscular energy balance, measured by the ratios of P(i)/PCr and P(i)/gamma-ATP, did not differ between MHS and MHN patients before and after intramuscular caffeine injection. However, within each group, P(i)/PCr and P(i)/gamma-ATP increased significantly only in the MHS group. Intramuscular caffeine injection seemed to impair the metabolic balance in MHS individuals. This may reflect a local calcium overload leading to consumption of high-energy phosphates and increase of inorganic phosphate. Intramuscular stimulation by caffeine and (31)P-MRS may provide a valuable tool to investigate MH-related metabolic disturbances.

Topics: Adult; Age Factors; Caffeine; Calcium; Calcium Signaling; Disease Susceptibility; Female; Humans; Injections, Intramuscular; Magnetic Resonance Spectroscopy; Male; Malignant Hyperthermia; Metabolic Diseases; Middle Aged; Muscle, Skeletal; Muscular Diseases; Oxidative Phosphorylation; Phosphocreatine; Phosphorus; Phosphorus Radioisotopes; Prospective Studies; Radionuclide Imaging; Sex Factors

Topics: Adenosine Triphosphate; Adult; Creatine; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Humans; Middle Aged; Muscle, Skeletal; Muscular Diseases; Phosphocreatine; Weight Lifting

Phosphocreatine (PCr) plays a vital role in neuron and myocyte energy homeostasis. Currently, there are no routine diagnostic tests to noninvasively map PCr distribution with clinically relevant spatial resolution and scan time. Here, we demonstrate that artificial neural network-based chemical exchange saturation transfer (ANNCEST) can be used to rapidly quantify PCr concentration with robust immunity to commonly seen MRI interferences. High-quality PCr mapping of human skeletal muscle, as well as the information of exchange rate, magnetic field and radio-frequency transmission inhomogeneities, can be obtained within 1.5 min on a 3 T standard MRI scanner using ANNCEST. For further validation, we apply ANNCEST to measure the PCr concentrations in exercised skeletal muscle. The ANNCEST outcomes strongly correlate with those from

Topics: Diagnostic Tests, Routine; Humans; Magnetic Resonance Imaging; Muscle, Skeletal; Muscular Diseases; Neural Networks, Computer; Phosphocreatine

Our study evaluated the effect of creatine and homoarginine in AGAT- and GAMT-deficient mice after simvastatin exposure. Balestrino and Adriano suggest that guanidinoacetate might explain the difference between AGAT- and GAMT-deficient mice in simvastatin-induced myopathy. We agree with Balestrino and Adriano that our data shows that (1) creatine possesses a protective potential to ameliorate statin-induced myopathy in humans and mice and (2) homoarginine did not reveal a beneficial effect in statin-induced myopathy. Third, we agree that guanidinoacetate can be phosphorylated and partially compensate for phosphocreatine. In our study, simvastatin-induced damage showed a trend to be less pronounced in GAMT-deficient mice compared with wildtype mice. Therefore, (phospo) guanidinoacetate cannot completely explain the milder phenotype of GAMT-deficient mice, but we agree that it might contribute to ameliorate statin-induced myopathy in GAMT-deficient mice compared with AGAT-deficient mice. Finally, we agree with Balestino and Adriano that AGAT metabolites should further be evaluated as potential treatments in statin-induced myopathy.

Topics: Amidinotransferases; Amino Acid Metabolism, Inborn Errors; Animals; Creatine; Developmental Disabilities; Glycine; Guanidinoacetate N-Methyltransferase; Homoarginine; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intellectual Disability; Mice; Muscular Diseases; Phosphocreatine; Speech Disorders

Rhabdomyolysis is common in very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and other metabolic myopathies, but its pathogenic basis is poorly understood. Here, we show that prolonged bicycling exercise against a standardized moderate workload in VLCADD patients is associated with threefold bigger changes in phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations in quadriceps muscle and twofold lower changes in plasma acetyl-carnitine levels than in healthy subjects. This result is consistent with the hypothesis that muscle ATP homeostasis during exercise is compromised in VLCADD. However, the measured rates of PCr and Pi recovery post-exercise showed that the mitochondrial capacity for ATP synthesis in VLCADD muscle was normal. Mathematical modeling of oxidative ATP metabolism in muscle composed of three different fiber types indicated that the observed altered energy balance during submaximal exercise in VLCADD patients may be explained by a slow-to-fast shift in quadriceps fiber-type composition corresponding to 30% of the slow-twitch fiber-type pool in healthy quadriceps muscle. This study demonstrates for the first time that quadriceps energy balance during exercise in VLCADD patients is altered but not because of failing mitochondrial function. Our findings provide new clues to understanding the risk of rhabdomyolysis following exercise in human VLCADD.

Topics: Acetylcarnitine; Acyl-CoA Dehydrogenase, Long-Chain; Adenosine Triphosphate; Adolescent; Adult; Case-Control Studies; Congenital Bone Marrow Failure Syndromes; Exercise; Female; Humans; Lipid Metabolism, Inborn Errors; Male; Mitochondria; Mitochondrial Diseases; Models, Statistical; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscular Diseases; Oxidative Phosphorylation; Phosphates; Phosphocreatine; Rhabdomyolysis

We used ³¹P-magnetic resonance spectroscopy to test the hypothesis that exercise-induced muscle damage (EIMD) alters the muscle metabolic response to dynamic exercise, and that this contributes to the observed reduction in exercise tolerance following EIMD in humans. Ten healthy, physically active men performed incremental knee extensor exercise inside the bore of a whole body 1.5-T superconducting magnet before (pre) and 48 h after (post) performing 100 squats with a load corresponding to 70% of body mass. There were significant changes in all markers of muscle damage [perceived muscle soreness, creatine kinase activity (434% increase at 24 h), and isokinetic peak torque (16% decrease at 24 h)] following eccentric exercise. Muscle phosphocreatine concentration ([PCr]) and pH values during incremental exercise were not different pre- and post-EIMD (P > 0.05). However, resting inorganic phosphate concentration ([P(i)]; pre: 4.7 ± 0.8; post: 6.7 ± 1.7 mM; P < 0.01) and, consequently, [P(i)]/[PCr] values (pre: 0.12 ± 0.02; post: 0.18 ± 0.05; P < 0.01) were significantly elevated following EIMD. These mean differences were maintained during incremental exercise (P < 0.05). Time to exhaustion was significantly reduced following EIMD (519 ± 56 and 459 ± 63 s, pre- and post-EIMD, respectively, P < 0.001). End-exercise pH (pre: 6.75 ± 0.04; post: 6.83 ± 0.04; P < 0.05) and [PCr] (pre: 7.2 ± 1.7; post: 14.5 ± 2.1 mM; P < 0.01) were higher, but end-exercise [P(i)] was not significantly different (pre: 19.7 ± 1.9; post: 21.1 ± 2.6 mM, P > 0.05) following EIMD. The results indicate that alterations in phosphate metabolism, specifically the elevated [P(i)] at rest and throughout exercise, may contribute to the reduced exercise tolerance observed following EIMD.

Topics: Adolescent; Adult; Analysis of Variance; Biomarkers; Biomechanical Phenomena; Creatine Kinase, MM Form; Energy Metabolism; Exercise; Exercise Tolerance; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Muscle Contraction; Muscle Fatigue; Muscle, Skeletal; Muscular Diseases; Pain; Pain Measurement; Phosphates; Phosphocreatine; Phosphorus Isotopes; Time Factors; Torque; Young Adult

The purpose of this study was to determine whether greater body fat mass (FM) relative to lean mass would result in more severe muscle damage and greater decrements in leg strength after downhill running. The relationship between the FM-to-fat-free mass ratio (FM/FFM) and the strength decline resulting from downhill running (-11% grade) was investigated in 24 male runners [age 23.4 +/- 0.7 (SE) yr]. The runners were divided into two groups on the basis of FM/FFM: low fat (FM/FFM = 0.100 +/- 0.008, body mass = 68.4 +/- 1.3 kg) and normal fat (FM/FFM = 0.233 +/- 0.020, body mass = 76.5 +/- 3.3 kg, P < 0.05). Leg strength was reduced less in the low-fat (-0.7 +/- 1.3%) than in the normal-fat individuals (-10.3 +/- 1.5%) 48 h after, compared with before, downhill running (P < 0.01). Multiple linear regression analysis revealed that the decline in strength could be predicted best by FM/FFM (r2 = 0.44, P < 0.05) and FM-to-thigh lean tissue cross-sectional area ratio (r2 = 0.53, P < 0.05), with no additional variables enhancing the prediction equation. There were no differences in muscle glycogen, creatine phosphate, ATP, or total creatine 48 h after, compared with before, downhill running; however, the change in muscle glycogen after downhill running was associated with a higher FM/FFM (r = -0.56, P < 0.05). These data suggest that FM/FFM is a major determinant of losses in muscle strength after downhill running.

Topics: Adenosine Triphosphate; Adult; Anaerobic Threshold; Body Composition; Creatine; Creatine Kinase; Glycogen; Humans; Lactic Acid; Leg; Male; Muscle, Skeletal; Muscular Diseases; Oxygen Consumption; Phosphocreatine; Physical Fitness; Regression Analysis; Running

31-P MR spectroscopy has been used to investigate metabolic events surrounding muscular contraction in a patient with an unusual myopathy characterized by clinical signs of muscle stiffness and swelling after prolonged exercise. Histological assays demonstrated a predominance of type II fibers with tubular aggregates. These structures had low calcium content although calcium-ATPase protein was present. Metabolic measurements were normal at rest except for the presence of a marked signal in the phosphodiester region which could reflect membrane abnormalities. Exercise-induced PCr consumption was in the normal range but the extent of the related intracellular acidosis was abnormally large. Kinetics of PCr and PCr/Pi ratio post-exercise recovery were delayed, but were likely to reflect the effect of the very low end-of-exercise pH rather than an aerobic deficiency. Finally, proton efflux from muscle to bloodstream, measured during the initial recovery period, was delayed, indicating altered mechanisms of proton handling. The most prominent metabolic abnormality recorded is the large glycogenolysis-induced pH decrease which might be linked to either abnormal activation of glycogenolysis and/or impaired proton and lactate handling within the muscle. The association between tubular aggregates and hyperacidosis is of interest but the exact causal relationship remains to be elucidated.

Topics: Adult; Biopsy; Exercise; Female; Humans; Magnetic Resonance Spectroscopy; Male; Microscopy, Electron; Muscle, Skeletal; Muscular Diseases; Phosphates; Phosphocreatine; Physical Exertion; Reference Values

Topics: Adenosine Triphosphate; Adult; Evaluation Studies as Topic; Fatigue; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Muscle, Skeletal; Muscular Diseases; Phosphocreatine; Phosphorus; Photopheresis; Scleroderma, Systemic

To investigate the use of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) in characterizing the metabolic and functional status of muscles in patients with amyopathic dermatomyositis (DM) and to compare the findings with those in patients with classic myopathic DM.. Nine patients with amyopathic DM, 11 patients with myopathic DM, and 11 normal individuals were studied. MRI images of thigh muscles were obtained, and T1 and T2 relaxation times were calculated. Biochemical status was quantitated with P-31 MRS, by determining concentrations of phosphate metabolites during rest and exercise.. Patients with amyopathic DM showed no muscle inflammation, and MRS data obtained during rest were normal. During exercise at 25% and 50% maximum voluntary contractile force, the MRS data revealed significant differences between amyopathic DM patients and control subjects indicating inefficient metabolism. In contrast, muscles of patients with myopathic DM showed inflammation and metabolic abnormalities even during rest.. Metabolic deficiencies in patients with amyopathic DM were unmasked by exercise, suggesting that the 2 DM syndromes may share muscle abnormalities. MRI/MRS may be useful in diagnosis and optimization of treatment.

Topics: Adult; Aged; Dermatomyositis; Exercise; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Muscular Diseases; Phosphates; Phosphocreatine; Phosphorus Isotopes; Rest; Skin Diseases; Work Capacity Evaluation

Dermatomyositis is an autoimmune disease characterized by an erythematous rash and severe muscle weakness. 31P Magnetic resonance spectroscopy (MRS) provides quantitative data for longitudinal monitoring of disease status and responses to immunosuppressive therapy. A disease variant, amyopathic dermatomyositis, presents with a typical rash but no clinical muscle weakness. However, metabolic abnormalities in the oxidative capacity of muscles of amyopathic patients during exercise were detected with 31P MRS. Because MRS provided the best quantitative data for evaluating dermatomyositis, the 31P metabolic parameters derived from the MR spectra were further processed using an artificial neural network (XERION). The neural network analyses provided additional clinical information from the weighted correlations of multiple 31P parameters, namely, inorganic phosphate, phosphocreatine, ATP, phosphodiesters, and selected ratios. This investigation analyzes the relative importance of the various metabolic parameters for accurate patient characterization and provides insights into the pathogenesis of the disease.

Topics: Adenosine Triphosphate; Adolescent; Adult; Aged; Dermatomyositis; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Muscular Diseases; Neural Networks, Computer; Phosphates; Phosphocreatine

To investigate anterior tibial muscle fatigability and metabolism in postpoliomyelitis syndrome patients and controls, we performed measurements of force and relaxation time, as well as 31P magnetic resonance spectroscopy, during intermittent, low-intensity, isometric, voluntary exercise. Both maximum voluntary contraction and tetanic force declined significantly more during exercise and subsequently recovered less in patients compared with controls, indicating greater fatigue in patients. However, intracellular pH and phosphocreatine were not different in the two groups at rest or during exercise or recovery, suggesting that the greater fatigue of the patients was not due to an excessive change of metabolites. Moreover, the pre-exercise half-relaxation time of the tetanus was significantly prolonged in patients compared with controls, and the decline in tetanic force during exercise was linearly related to the half-relaxation time of tetanus, suggesting impaired calcium kinetics. Taken together, the findings of increased fatigability, delayed recovery, and prolonged half-relaxation time, without differences in metabolites, suggest that the fatigue in postpoliomyelitis syndrome may be due to impaired activation beyond the muscle membrane.

Topics: Action Potentials; Aged; Female; Humans; Isometric Contraction; Male; Middle Aged; Muscle Contraction; Muscles; Muscular Diseases; Phosphocreatine; Physical Exertion; Postpoliomyelitis Syndrome

Topics: Adult; Coronary Disease; Forearm; Humans; Hydrogen-Ion Concentration; Middle Aged; Muscles; Muscular Diseases; Phosphocreatine; Syndrome

This study investigates the potential of in vivo 31P magnetic resonance spectroscopy (MRS) to characterize musculoskeletal tumors and to determine preoperative levels of histological necrosis, which is an important clinical indicator of patient response. Pretherapy MRS was performed on 28 patients with large musculoskeletal tumors: 13 with osteosarcoma, 3 with chondrosarcoma, 5 with malignant fibrous histiocytoma, 1 with desmoid tumor, 1 with Ewing's, 2 with hemangioendothelioma, 1 with myxoid liposarcoma, 1 with synovial cell sarcoma, and 1 with rhabdomyosarcoma. Fifteen patients had follow-up MRS examinations after commencement of chemotherapy (mean of five/patient), eight of whom have now had surgery. Elevated levels of PMEs (P < 0.01), P(i) (P < 0.01), and PDEs (P < 0.02) as well as elevated tumor pH (P < 0.05) were observed in all patients. The synovial cell sarcoma was characterized by high levels of PMEs (> 20%) and low pH (pH 6.76). This contrasted with the spectra obtained from the malignant fibrous histiocytomas which had high levels of PDEs (17 +/- 5%). Reductions in PDE levels postchemotherapy were associated with a high degree of necrosis (> 90%) at surgery, while an increase in PDE levels was associated with a low level of histological necrosis. Likewise, reductions in the ratios PDE/NTP and PDE/PCr and an increase in P(i)/PDE were also associated with a high level of necrosis.

Topics: Adult; Aged; Bone Neoplasms; Chemotherapy, Adjuvant; Ethanolamines; Female; Glycerylphosphorylcholine; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscular Diseases; Necrosis; Neoplasm Staging; Neoplasms; Osteosarcoma; Phosphatidylethanolamines; Phosphocreatine; Phosphorus; Phosphorylcholine; Preoperative Care

Topics: Calcitriol; Calcium; Humans; Kidney Failure, Chronic; Muscular Diseases; Myosins; Phosphocreatine; Renal Dialysis; Troponin; Uremia

Prompted by the report of a mitochondrial myopathy associated with chronic administration of zidovudine (AZT), an inhibitor of mitochondrial DNA synthesis, we obtained 31P magnetic resonance spectra from the calf muscles of AZT-treated patients and age-matched control subjects at rest and during an exercise protocol with a 12-second time resolution. The recovery of phosphocreatine following exercise reflects mitochondrial oxidative function and was significantly delayed in the AZT-treated patients (time constants, 43.3 +/- 12.5 seconds versus control subjects, 24.4 +/- 3.9 seconds). These findings support the hypothesis that the myopathy associated with chronic AZT results from the inhibitory effects of AZT on mitochondrial DNA synthesis and, secondarily, on the inhibition of mitochondrial oxidative metabolism.

Topics: Adult; Exercise; HIV Infections; Humans; Male; Mitochondria, Muscle; Muscular Diseases; Phosphocreatine; Zidovudine

We have investigated the sensitivity and specificity of a rapid phosphorus magnetic resonance spectroscopy (MRS) protocol for detecting metabolic abnormalities in vivo in skeletal muscle of patients with mitochondrial disease. We examined 17 patients with mitochondrial myopathies. Sixteen had only mild or minimal myopathic signs and symptoms. Phosphorus magnetic resonance spectra from the resting gastrocnemius muscles showed an abnormal intracellular energy state (marked by an increased intracellular inorganic phosphate concentration) in 14/17. In 3/17, this was associated with a decreased phosphocreatine concentration. We also studied 20 patients with other diseases of muscle (inflammatory myopathies, metabolic myopathies, muscular dystrophies, and myasthenia gravis) that can present with similar clinical features. Spectra showed increased intracellular inorganic phosphate concentrations in 6/20. All of these muscle diseases were associated with evidence of muscle fiber necrosis. Abnormalities in the muscle energy state in these cases may be due to secondary mitochondrial dysfunction. Except for cases of polymyositis and dermatomyositis, these 6 other myopathies could be readily distinguished from the mitochondrial myopathies on the basis of the clinical examination and blood tests. We conclude that phosphorus MRS of resting muscle is practical in a clinical setting and has a useful sensitivity and specificity for mitochondrial myopathies when used in conjunction with standard noninvasive tests.

Topics: Adenosine Triphosphate; Adolescent; Adult; Aged; Biopsy; Child; Child, Preschool; Esters; Humans; Infant; Magnetic Resonance Spectroscopy; Middle Aged; Mitochondria, Muscle; Muscles; Muscular Diseases; Phosphocreatine; Phosphorus; Sensitivity and Specificity

A 34-year-old man affected by exercise intolerance, mild proximal weakness and severe lactic acidosis is described. Muscle biopsy revealed mitochondrial abnormalities and an increase of cytochrome c oxidase histochemical reaction. Biochemical investigations on isolated muscle mitochondria as well as polarographic studies revealed a mitochondrial NADH-CoQ reductase (complex I) deficiency. Mitochondrial dysfunction was confirmed by 31P nuclear magnetic resonance spectroscopy. Immunological investigation showed a generalized reduction of all complex I polypeptides. Genetic analysis did not reveal mitochondrial DNA deletions. The biochemical defect was not present in the patient's muscle tissue culture. Metabolic measurements and functional evaluation showed a reduced mechanical efficiency during exercise.

Topics: Acidosis, Lactic; Adenosine Triphosphate; Adult; Cells, Cultured; DNA, Mitochondrial; Enzyme-Linked Immunosorbent Assay; Exercise; Humans; Magnetic Resonance Spectroscopy; Male; Mitochondria, Muscle; Muscles; Muscular Diseases; NAD(P)H Dehydrogenase (Quinone); Oxygen Consumption; Phosphocreatine; Quinone Reductases

P31 nuclear magnetic resonance spectroscopy (NMRS) is a new noninvasive method for the study of normal and diseased muscle. Significant differences between the spectra of normal and pathological human muscles were reported in some known myopathies and in patients with congestive heart failure. The possibility that metabolic disturbances are linked to contraction abnormalities led to the investigation of malignant hyperthermia susceptible (MHs) muscle with NMRS. At rest, no differences were found between patients and normal subjects. During exercise, and recovery, MHs exercise hyperthermic patients developed an abnormal P31 spectral configuration, indicating a defective energy metabolism. This technique is of great interest, and could be used in patients with muscle diseases of unknown origin. NMRS with P31 and, simultaneously, other nuclei (C13, H1) could refine the results already obtained.

Topics: Disease Susceptibility; Energy Metabolism; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Malignant Hyperthermia; Muscle Contraction; Muscle Relaxation; Muscles; Muscular Diseases; Phosphocreatine; Phosphorus

Chronic administration of the NADH-CoQ reductase inhibitor, diphenyleneiodonium to rats at two dose levels, 1.0 and 1.5 mg/kg per day, caused a 40% and 60% reduction, respectively, in the in vitro rate of NAD-linked respiration by skeletal muscle mitochondria. At the highest dose, muscle fatigue, lactic acidosis and an over-utilization of phosphocreatine was observed in the gastrocnemius muscle during mild stimulation of 1 Hz frequency. The resynthesis of phosphocreatine following muscle stimulation was about 2 fold slower in the treated animal group. At the low dose, no significant biochemical changes were observed during muscle stimulation at 4 Hz. The results are discussed in terms of skeletal muscle "oxidative reserve", twitch tension maintenance and the relevance to the human diseased state of mitochondrial myopathy.

Topics: Acidosis; Animals; Dose-Response Relationship, Drug; Male; Mitochondria, Muscle; Muscles; Muscular Diseases; NAD(P)H Dehydrogenase (Quinone); Onium Compounds; Phosphocreatine; Quinone Reductases; Rats; Rats, Inbred Strains; Time Factors

In rats with phosphoryl-creatine depletion (fed a standard Randoin-Causeret diet containing 1% beta-guanidine propionic acid) abnormal mitochondria were observed in slow skeletal muscles, often containing paracrystalline inclusions very like those induced by ischaemia or mitochondrial poisons and in human mitochondrial myopathy.

Topics: Animals; Body Weight; Creatine; Guanidines; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Phosphocreatine; Propionates; Rats; Rats, Inbred Strains; Time Factors

In vivo and in vitro 31P-NMR spectroscopy was used to study the high energy phosphate metabolism of VX-2 tumors implanted into rabbit liver, kidney, and hind-limb muscle. Tumors, at various stages of growth, were first examined by in vivo 31P-NMR spectroscopy, then they were excised and underwent histologic examination and biochemical analysis; both in vitro 31P-NMR and standard enzymatic techniques were used. There was good correlation among the in vivo NMR spectra, the in vitro NMR data, and the biochemical analyses. Although the tumor spectra showed characteristics similar to those reported in the other tumor models, there was a striking variability in the spectra obtained from tumors implanted in the same site and from different sites. There was poor correlation between the degree of necrosis in the tumor and the tumor pH and between the Pi:ATP ratio and necrosis. This variability has important implications for the potential value of using 31P-NMR spectroscopy to monitor tumor growth and therapy in vivo.

Topics: Adenosine Triphosphate; Animals; Carcinoma; In Vitro Techniques; Kidney Neoplasms; Liver Neoplasms; Magnetic Resonance Spectroscopy; Muscular Diseases; Neoplasms, Experimental; Phosphocreatine; Phosphorus; Rabbits

In vivo phosphorus magnetic resonance spectroscopy was used to evaluate the changes in muscle bioenergetics in a patient with a partial glycolytic block. Phosphoglycerate mutase-deficient muscle showed the following evidence: Abnormal accumulation of sugar phosphates does occur, even when 6% enzyme activity is present. The elimination of sugar phosphates was faster than in complete glycolytic blocks. Mild intracellular acidosis occurred during ischemic exercise. The energy state was slightly low at rest but not during exercise. Postexercise recovery was mildly slowed. These findings suggest that phosphorus magnetic resonance spectroscopy can detect partial defects, as well as full glycolytic blocks, in muscle metabolism.

Topics: Adenosine Triphosphate; Adult; Female; Glycolysis; Humans; Magnetic Resonance Spectroscopy; Muscles; Muscular Diseases; Organophosphates; Phosphocreatine; Phosphoglycerate Mutase; Phosphorus; Phosphotransferases; Physical Exertion

Acute administration of phospholine [diethyl-S-(2-dimethyl aminoethyl)phosphorothioate] at 0.2 mg/kg sc produces a myopathy characterized by initial focal changes in the subsynaptic area of the skeletal muscle. The onset of the myopathy is associated with fasciculations of high frequency. Agents that either prevent or reduce the fasciculations, such as d-tubocurarine, atropine sulfate, and diazepam, were effective in reducing the number of muscle lesions. These agents may reduce spontaneous muscle activity by blocking the postsynaptic receptor, by modifying the ionic-channel characteristics, by reducing presynaptic acetylcholine (ACh) release, or by a combination of any of these mechanisms. Creatine phosphate (CP) does not reduce fasciculations, but it is effective in reducing the number of necrotic fibers, probably by stimulating and sustaining the mechanism of Ca2+ uptake into the sarcoplasmic reticulum. It is postulated that an increase in the sarcoplasmic Ca2+ concentration triggers the events that lead to muscle necrosis.

Topics: Animals; Atropine; Calcium; Diaphragm; Diazepam; Injections, Subcutaneous; Male; Muscles; Muscular Diseases; Organothiophosphorus Compounds; Phosphocreatine; Rats; Rats, Inbred Strains; Tubocurarine

Phosphorus magnetic resonance spectroscopy (P MRS) affords and innovative approach to the study of the oxidative enzyme content of normal and diseased muscles. Examples of the evaluation of the enzyme content of normal muscles by an exercise protocol are provided. The protocol affords a hyperbolic work/cost profile, the Vmax of which is calculated by the reciprocal plots giving the enzyme content and the "effective Michaelis constant" with an evaluation of the resting metabolism. This steady state protocol clearly illustrates enzyme adaptation, on the one hand, and tissue atrophy particularly in the case of tissue injury, Duchenne's dystrophy, and genetic deletion of specific enzymes, on the other hand. The method is rapid, safe, and affords a quantitative evaluation of the disease process and possibilities for following appropriate therapies. So far, approx 1000 examinations of normal and diseased human limbs have been carried out in our laboratory in over the past four years.

Topics: Acidosis; Adenine Nucleotides; Age Factors; Animals; Cattle; Cytochrome b Group; Energy Metabolism; Humans; Immobilization; Kinetics; Magnetic Resonance Spectroscopy; Mitochondria, Muscle; Muscles; Muscular Diseases; Muscular Dystrophies; NAD; Phosphates; Phosphocreatine; Phosphofructokinase-1; Physical Exertion

Intact as well as neuromuscular affected skeletal muscles can be precisely analysed by MR tomography with high magnetic field strengths. The substitution of muscle by adipose tissue under atrophic conditions is seen most clearly in fat images, while the morphology of small structures is predominantly shown by water images. The aim of in-vivo spectroscopy is an identification and quantification of metabolites. A relative increase in the amount of adipose tissue within atrophic muscles was confirmed by the 1-H spectrum. As concluded from 13-C and 31-P spectra there was neither a change in adipose tissue composition nor a modification of energy metabolism.

Topics: Adenosine Triphosphate; Humans; Magnetic Resonance Spectroscopy; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Phosphates; Phosphocreatine

A patient with mitochondrial myopathy due to complex III deficiency who was treated with vitamin K3 (menadiol sodium diphosphate, 40 mg daily) and vitamin C showed clinical improvement. A 1-year study with phosphorus 31 nuclear magnetic resonance (31P-NMR) monitoring has shown that clinical and metabolic improvement was maintained by this therapy; increasing the dose of vitamin K3 to 80 mg daily improved the bioenergetic state of the patient's muscles at rest; postexercise recovery was less responsive to the increased dose; and a higher dose of vitamin K3 (80 mg/day) did not produce side effects. The differential therapeutic effects of vitamin K3 at rest and during exercise recovery are probably due to the differential kinetics of each metabolic state. Monitoring muscle bioenergetics with 31P-NMR is valuable in documenting therapeutic improvements in mitochondrial myopathies.

Topics: Adult; Ascorbic Acid; Drug Therapy, Combination; Electron Transport Complex III; Female; Follow-Up Studies; Humans; Magnetic Resonance Spectroscopy; Multienzyme Complexes; Muscles; Muscular Diseases; Phosphates; Phosphocreatine; Quinone Reductases; Vitamin K

To demonstrate the importance of creatine and phosphocreatine in skeletal muscle during periods of metabolic stress, thyrotoxicosis was induced in mice fed the creatine transport inhibitor, beta-guanidinopropionic acid (beta-GPA). Adding 2% of beta-GPA to the diet of normal mice inhibited weight gain and caused a 75% reduction of creatine and phosphocreatine concentrations in skeletal muscle. Addition of 0.25% or 2% of thyroid powder to the diet of normal mice was associated with hyperactivity, cardiomegaly, and a high mortality rate. Superimposing thyrotoxicosis on mice already depleted of creatine and phosphocreatine resulted in degeneration of muscle fibers. These results indicate that high concentrations of creatine and phosphocreatine are essential for the maintenance of muscle integrity during periods of metabolic stress.

Topics: Animals; Biological Transport; Body Weight; Creatine; Guanidines; Hyperthyroidism; Male; Mice; Muscles; Muscular Diseases; Phosphocreatine; Propionates

Nuclear magnetic resonance spectroscopy can now be used to investigate the biochemical energetics of human tissues and organs noninvasively. The method already has increased our understanding of some muscle diseases, has provided information from muscle metabolism about whole-body functions, control, and hormonal status, has helped in the elucidation of hitherto unrecognized causes of disease, and yielded new ideas about the control of bioenergetics in vivo. Studies on the biochemistry of human brain, liver, heart, and kidney are just beginning. Further investigations of well-selected patients are likely to bring biochemistry and clinical practice closer together.

Topics: Adenosine Triphosphate; Energy Metabolism; Humans; Magnetic Resonance Spectroscopy; Muscles; Muscular Diseases; Phosphocreatine; Phosphorus

Topics: Adenosine Diphosphate; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Mitochondria, Muscle; Muscular Diseases; Phosphocreatine; Physical Exertion

Abnormal mitochondria are an increasingly recognized cause of neuromuscular disease. We have used phosphorus magnetic resonance spectroscopy to monitor noninvasively the metabolism of high-energy phosphates and the intracellular pH of human skeletal muscle in vivo in 12 patients with mitochondrial myopathy. At rest, an abnormality could be demonstrated in 11 of 12 patients. Ten patients had evidence of a reduced muscle energy state with at least one of the following abnormalities: low phosphorylation potential, low phosphocreatine concentration, high adenosine diphosphate concentration, or high inorganic phosphate concentration. Two patients had abnormal resting muscle intracellular pH. In some patients phosphocreatine concentration decreased to low values during exercise despite limited work output. This was not accompanied by particularly severe intracellular acidosis. Evidence of impaired rephosphorylation of adenosine diphosphate to adenosine triphosphate during recovery from exercise was found in approximately half the patients. Phosphorus magnetic resonance spectroscopy is useful in the noninvasive diagnosis of mitochondrial myopathies and in defining the pathophysiological basis of these disorders.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adolescent; Adult; Aged; Female; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Metabolic Diseases; Middle Aged; Mitochondria, Muscle; Muscles; Muscular Diseases; Phosphocreatine; Phosphorus

Infusion of dinitrophenol intra-arterially into rat hind limb caused an irreversible failure of isometric twitch tension and the induction of a severe progressive contracture. Metabolite analysis of muscle in which the twitch response had grossly fatigued revealed low levels of ATP and phosphocreatine together with lactate accumulation. Studies using 31P-n.m.r. confirmed the decrease in ATP and creatine phosphate concentrations and indicated a fall in intracellular pH. It is concluded that dinitrophenol-induced myopathy does not represent a good model for the human mitochondrial myopathic condition as has been previously suggested.

Topics: 2,4-Dinitrophenol; Adenosine Triphosphate; Animals; Dinitrophenols; Disease Models, Animal; Electric Stimulation; Isometric Contraction; Magnetic Resonance Spectroscopy; Mitochondria, Muscle; Muscular Diseases; Phosphocreatine; Rats; Rats, Inbred Strains; Uncoupling Agents

Frogs were injected for several weeks with beta-guanidinopropionate, an isomer of creatine. Their sartorius muscles were isolated, poisoned with iodoacetate and stimulated isometrically with 75 shocks/min in nitrogen until rigor. In comparison with sartorius muscles of untreated frogs, they contained more free creatine and less phosphocreatine, but the same content in total creatine and ATP. They also contained beta-guanidinopropionate both free and phosphorylated. However, muscles in rigor contained the same concentration of the phosphorylated form as resting muscles, i.e., phospho-beta-guanidinopropionate was not split during contraction. The number of twitches performed before rigor was decreased. There was no change in the chemical energy usage (sum of phosphocreatine breakdown and twice ATP breakdown) per twitch.

Topics: Adenosine Triphosphate; Animals; Chromatography, Thin Layer; Creatine; Energy Metabolism; Guanidines; Isomerism; Muscle Contraction; Muscles; Muscular Diseases; Phosphocreatine; Propionates; Rana temporaria

A patient with familial adult-onset hypophosphataemia, whose myopathy was closely related to the plasma phosphate concentration, was investigated by phosphorus nuclear magnetic resonance spectroscopy (31P n.m.r.) in vivo of the right flexor digitorum superficialis muscle. During hypophosphataemia induced by stopping oral phosphate a significant reduction in measured muscle strength occurred, but the ratios of the intramyocellular levels of phosphocreatine (PCr), adenosine triphosphate (ATP) and inorganic phosphate (Pi) remained unchanged at rest. During exercise these levels changed, as did the intramyocellular pH, but they did not differ from the pattern previously recorded in normal subjects. In four adults with inherited infantile-onset hypophosphataemia (vitamin D-resistant rickets, VDRR) without myopathy, the n.m.r. measurements were normal at rest and during exercise. In one patient with inherited hyperphosphataemia (tumoral calcinosis) the resting PCr: Pi ratio was significantly reduced.

Topics: Adenosine Triphosphate; Adult; Female; Humans; Hypophosphatemia, Familial; Isometric Contraction; Magnetic Resonance Spectroscopy; Male; Methylhistidines; Middle Aged; Muscles; Muscular Diseases; Osteomalacia; Phosphates; Phosphocreatine

Muscle weakness and abnormal electrical activity of muscle cells have been described in magnesium-depleted patients and animals. The cellular mechanisms by which magnesium depletion causes the skeletal myopathy are not known. We review here the available clinical and experimental data on the effects of magnesium on: skeletal muscle cellular bioenergetics; excitation-contraction coupling, and biochemical and functional integrity of the cellular membrane. The data suggest that abnormalities in one or more of the above pathways may mediate the myopathy of magnesium depletion.

Topics: Adenosine Triphosphate; Animals; Cell Membrane; Electric Conductivity; Energy Metabolism; Humans; Magnesium Deficiency; Muscle Contraction; Muscles; Muscular Diseases; Phosphocreatine

Topics: Adenine Nucleotides; Animals; Cell Membrane; Creatine Kinase; Energy Metabolism; Glucosephosphates; Glycogen; Mitochondria, Muscle; Muscles; Muscular Diseases; Myofibrils; Oxygen Consumption; Phosphates; Phosphocreatine; Phosphorylation; Rats; Rats, Inbred Strains; Time Factors

To assess the role of the purine nucleotide cycle in human skeletal muscle function, we evaluated 10 patients with AMP deaminase deficiency (myoadenylate deaminase deficiency; MDD). 4 MDD and 19 non-MDD controls participated in an exercise protocol. The latter group was composed of a patient cohort (n = 8) exhibiting a constellation of symptoms similar to those of the MDD patients, i.e., postexertional aches, cramps, and pains; as well as a cohort of normal, unconditioned volunteers (n = 11). The individuals with MDD fatigued after performing only 28% as much work as their non-MDD counterparts. Muscle biopsies were obtained from the four MDD patients and the eight non-MDD patients at rest and following exercise to the point of fatigue. Creatine phosphate content fell to a comparable extent in the MDD (69%) and non-MDD (52%) patients at the onset of fatigue. Following exercise the 34% decrease in ATP content of muscle from the non-MDD subjects was significantly greater than the 6% decrease in ATP noted in muscle from the MDD patients (P = 0.048). Only one of four MDD patients had a measurable drop in ATP compared with seven of eight non-MDD patients. At end-exercise the muscle content of inosine 5'-monophosphate (IMP), a product of AMP deaminase, was 13-fold greater in the non-MDD patients than that observed in the MDD group (P = 0.008). Adenosine content of muscle from the MDD patients increased 16-fold following exercise, while there was only a twofold increase in adenosine content of muscle from the non-MDD patients (P = 0.028). Those non-MDD patients in whom the decrease in ATP content following exercise was measurable exhibited a stoichiometric increase in IMP, and total purine content of the muscle did not change significantly. The one MDD patient in whom the decrease in ATP was measurable, did not exhibit a stoichiometric increase in IMP. Although the adenosine content increased 13-fold in this patient, only 48% of the ATP catabolized could be accounted for by the combined increases of adenosine, inosine, hypoxanthine, and IMP. Studies performed in vitro with muscle samples from seven MDD and seven non-MDD subjects demonstrated that ATP catabolism was associated with a fivefold greater increase in IMP in non-MDD muscle. There were significant increases in AMP and ADP content of the muscle from MDD patients following ATP catabolism in vitro, while there was no detectable increase in AMP or ADP in non-MDD muscle. Adenosine content of MDD muscle increa

Topics: Adenosine Triphosphate; Adult; AMP Deaminase; Female; Humans; Hypoxanthine; Hypoxanthines; Inosine; Inosine Monophosphate; Male; Middle Aged; Muscles; Muscular Diseases; Nucleotide Deaminases; Phosphocreatine; Physical Exertion; Purine Nucleotides

Topics: Biopsy; Glycogen Storage Disease Type V; Humans; Hydrogen-Ion Concentration; Infant; Magnetic Resonance Spectroscopy; Muscles; Muscular Diseases; Muscular Dystrophies; Phosphocreatine; Phosphorus

Topics: Adult; Female; Humans; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Male; Mitochondria, Muscle; Muscular Diseases; NAD(P)H Dehydrogenase (Quinone); NADH, NADPH Oxidoreductases; Phosphocreatine; Physical Exertion; Quinone Reductases

A 16-year-old boy with myopathy, ophthalmoplegia, and raised basal metabolic rate was examined by the non-invasive technique of phosphorus-31 nuclear magnetic resonance (31 P NMR). The muscles of the forearm showed an abnormal 31P NMR spectrum with a high inorganic phosphate (Pi) content in relation to phosphocreatine (PCr) (PCr/Pi = 4; control = 10). This finding was compatible with the abnormality of mitochondrial function already established by biopsy and offers in addition an explanation for the raised oxygen consumption in this patient. The method of 31P NMR is suited to rapid non-invasive diagnosis in various muscle disorders.

Topics: Acidosis; Adolescent; Humans; Hydrogen-Ion Concentration; Lactates; Magnetic Resonance Spectroscopy; Male; Mitochondria, Muscle; Muscular Diseases; Oxygen Consumption; Phosphates; Phosphocreatine; Phosphorus Radioisotopes

Skeletal muscle morphology and mitochondrial oxidative phosphorylation capacity were examined in a family whose members showed very combinations of mental subnormality, cardiomyopathy and muscle weakness. Light and electron microscopic findings suggested a neuropathic process, while tests of mitochondrial function indicated a state of tight coupling of oxidative phosphorylation, a feature in marked contrast to those in biochemical studies so far reported.

Topics: Adenosine Triphosphate; Biopsy; Cardiomyopathies; Electron Transport Complex IV; Female; Humans; Male; Mitochondria, Muscle; Muscles; Muscular Diseases; NADH Dehydrogenase; Oxidative Phosphorylation; Phosphocreatine

A method is presented for the in vitro testing of the energy metabolism of human skeletal muscle. The levels of creatine phosphate, ATP, ADP and AMP, which are defined by the activity of many enzyme system, are measured after incubation of the muscle homogenate with various substrates in the presence or absence of specific inhibitors. Detection of abnormal metabolite concentrations is important for diagnosis of patients with myopathic syndromes.

Topics: Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Arsenic; Arsenites; Child; Dinucleoside Phosphates; Energy Metabolism; Humans; In Vitro Techniques; Male; Muscles; Muscular Diseases; Phosphocreatine

Topics: Adenylate Kinase; Adenylyl Cyclases; Adolescent; Adult; Aged; Aspartate Aminotransferases; Blood Glucose; Creatine Kinase; Enzyme Reactivators; Glucosephosphate Dehydrogenase; Humans; Malate Dehydrogenase; Middle Aged; Muscular Diseases; Myocardial Infarction; NADP; Phosphocreatine

High-resolution 31P NMR spectra of normal and malignant muscle tissue from mice were obtained at 100 MHz. The spectrum of normal muscle was found to resemble that obtained by Hoult et al. for normal rat skeletal muscle. But the spectrum of malignant muscle tumor (rhabdomyosarcoma) was found to comprise only the inorganic phosphate and sugar phosphate peaks, which indicates potential usefulness of this NMR method for diagnosis. Moreover, the inorganic phosphate peak was observed to be shifted downfield 70 Hz from the location seen in normal muscle. This identification of an NMR absorption frequency different in cancer tissue than in normal, singles out what may be the first of many absorption frequencies that could be utilized as target frequencies for delivery of cancer-destructive radiation.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred CBA; Muscular Diseases; Neoplasms; Phosphocreatine; Rhabdomyosarcoma

This communication presents evidence in support of a neuropathic basis for the myopathy associated with malignant hyperpyrexia (MH). Muscle from MH susceptible individuals showed a reduced calcium uptake by the sarcoplasmic reticulum. There was a reduced concentration of phosphocreatine and ATP and an increased concentration of glucose-6-phosphate in these muscle samples.

Topics: Actomyosin; Adenosine Triphosphatases; Adenosine Triphosphate; Adolescent; Calcium; Carrier State; Creatine Kinase; Female; Glucosephosphates; Halothane; Humans; Infant; Malignant Hyperthermia; Microscopy, Electron; Middle Aged; Muscles; Muscular Diseases; Myofibrils; Phosphocreatine; Phosphorylases; Sarcoplasmic Reticulum

A suspected case of xanthine oxidase deficiency has been further investigated. The patient complained of arthralgia and myalgia. Further studies included histochemical and ultramicroscopic analysis of muscle sarcoplasmic reticulum, and biochemical studies. High levels of xanthine and hypoxanthine were found, while uric acid was absent in the muscle extracts.

Topics: Adenosine Triphosphatases; Adult; Calcium; Dihydrolipoamide Dehydrogenase; Female; Glucosephosphates; Glycogen; Histocytochemistry; Humans; Hypoxanthines; Muscles; Muscular Diseases; Phosphocreatine; Sarcoplasmic Reticulum; Uric Acid; Xanthines

Topics: Adenosine Triphosphate; Biopsy; Body Temperature Regulation; Electric Stimulation; Fatigue; Humans; Lactates; Muscle Contraction; Muscles; Muscular Diseases; Phosphocreatine

Topics: Acute Kidney Injury; Adult; Aspartate Aminotransferases; Barbiturates; Chlorpromazine; Coma; Drug-Related Side Effects and Adverse Reactions; Female; Glutethimide; Heroin; Humans; Kidney Function Tests; L-Lactate Dehydrogenase; Male; Methadone; Methamphetamine; Muscular Diseases; Myoglobinuria; Phosphocreatine; Pyruvate Kinase; Quinine; Substance-Related Disorders

Topics: Adenosine Triphosphatases; Animals; Energy Transfer; Ischemia; Lactates; Muscles; Muscular Diseases; Phosphocreatine; Physical Exertion; Rabbits; Regional Blood Flow

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Child; Creatine Kinase; Female; Humans; Male; Middle Aged; Muscular Diseases; Nervous System Diseases; Phosphocreatine

Topics: Adenine Nucleotides; Child; Child, Preschool; Creatine Kinase; Fructose-Bisphosphate Aldolase; Humans; Muscles; Muscular Diseases; NAD; NADP; Phosphates; Phosphocreatine

Topics: Animals; Creatine Kinase; Diaphragm; Muscles; Muscular Diseases; Necrosis; Phosphocreatine; Quinolines; Rabbits

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Anura; Cell Membrane; Electrophysiology; Heart; In Vitro Techniques; Lactates; Muscular Diseases; Phosphates; Phosphocreatine; Stomach

Topics: Child; Creatine Kinase; Electromyography; Humans; Male; Muscular Diseases; Musculoskeletal Abnormalities; Phosphocreatine

Topics: Adenine Nucleotides; Adenosine Triphosphate; Blood Chemical Analysis; Contracture; Electromyography; Glycogen; Humans; In Vitro Techniques; Lactates; Metabolism, Inborn Errors; Muscle Contraction; Muscle Cramp; Muscle Proteins; Muscles; Muscular Diseases; Myoglobinuria; Phosphocreatine; Phosphotransferases; Physical Exertion; Spectrophotometry

Topics: Adolescent; Anemia; Anemia, Hypochromic; Coenzymes; Fructose-Bisphosphate Aldolase; Geriatrics; Humans; Muscular Diseases; Muscular Dystrophies; Neurotic Disorders; Pharmacology; Phosphocreatine; Respiratory Tract Diseases; Urology

Topics: Animals; Coenzymes; Creatine; Creatinine; Glutathione; Glycogen; Histocytochemistry; Leg; Metabolism; Mice; Muscle, Skeletal; Muscular Diseases; Pathology; Peptides; Phosphocreatine; Sarcocystosis

The iodoacetate-nitrogen-poisoned muscle offers the possibility of studying the stoichiometry of the single muscle twitch since metabolic resynthesis by glycolysis and oxidative phosphorylation are blocked, and there remains as an energy source only the creatine phosphoryltransfer system, creatine phosphate reacting with adenosinediphosphate to give the triphosphate and creatine. It is shown, preparatory to a determination of the amount of phosphocreatine split in a single twitch, that iodoacetate does not inhibit creatine phosphoryltransferase at concentrations which block glycolysis. An analysis is developed which assumes that the transferase maintains the creatine phosphoryl transfer reaction in equilibrium following contraction, and further that the creatine phosporyltransfer reaction and the myokinase reaction are isolated in muscle. On the basis of this analysis and the data obtained, an estimate of the equilibrium constant of the creatine phosphoryl reaction in muscle is obtained which agrees with values determined in vitro. Using the estimated equilibrium constant, and the concentrations of creatine, creatine phosphate, and adenosinetriphosphate found, a value for the concentration of free adenosinediphosphate is obtained which is considerably less than that found by direct chemical analysis.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Coenzymes; Creatine; Glycolysis; Iodoacetates; Muscles; Muscular Diseases; Oxidative Phosphorylation; Phosphocreatine

Topics: Adenosine; Adenosine Triphosphate; Muscles; Muscular Diseases; Musculoskeletal Physiological Phenomena; Phosphocreatine; Polyphosphates