ascorbic-acid and Muscular-Diseases

Topics: Adult; Ascorbic Acid; Female; Humans; Male; Middle Aged; Muscular Diseases; Pain; Succinylcholine

This study was designed to examine the potential involvement of reactive oxygen species in skeletal muscle dysfunction linked with stretching in a mouse model and to explore the effects of combined antioxidant intake on peripheral leukocyte apoptosis following eccentrically-biased downhill runs in human subjects. In the mouse model, diaphragmatic muscle was stretched by 30% of its optimal length, followed by 5-min contraction. Muscle function and extracellular reactive oxygen species release was measured ex vivo. In human models, participants performed two trials of downhill running either with or without antioxidant supplementation, followed by apoptotic assay of inflammatory cells in the blood. The results showed that stretch led to decreased muscle function and prominent ROS increase during muscle contraction. In human models, we observed an elevation in circulating leukocyte apoptosis 24-48 hours following acute downhill runs. However, there is an attenuated leukocyte apoptosis following the second bout of downhill run. Interestingly, the combination of ascorbic acid (vitamin C) and α-tocopherol (vitamin E) supplementation attenuated the decrease in B-cell lymphoma 2 (Bcl-2) at 24 hours following acute downhill running. These data collectively suggest that significant ROS formation can be induced by muscle-lengthening associated with eccentric exercise, which is accompanied by compromised muscle function. The combination of antioxidants supplementation appears to have a protective role via the attenuation of decrease in anti-apoptotic protein.

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Leukocytes; Male; Mice; Muscle, Skeletal; Muscular Diseases; Oxidation-Reduction; Physical Conditioning, Animal; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Vitamin E

Endoplasmic reticulum (ER) and oxidative stress are two related phenomena that have important metabolic consequences. As many skeletal muscle diseases are triggered by oxidative stress, we explored the chain of events linking a hyperoxidized ER (which causes ER and oxidative stress) with skeletal muscle dysfunction. An unbiased exon expression array showed that the combined genetic modulation of the two master ER redox proteins, selenoprotein N (SEPN1) and endoplasmic oxidoreductin 1 (ERO1), led to an SEPN1-related myopathic phenotype due to excessive signalling of transforming growth factor (TGF)-beta. The increased TGF-beta activity in the genetic mutants was caused by accelerated turnover of the ER localized (anti-oxidant) ascorbic acid that affected collagen deposition in the extracellular matrix. In a mouse mutant of SEPN1, which is dependent on exogenous ascorbic acid, a limited intake of ascorbic acid revealed a myopathic phenotype as a consequence of an altered TGF-beta signalling. Indeed, systemic antagonism of TGF-beta re-established skeletal muscle function in SEPN1 mutant mice. In conclusion, this study sheds new light on the molecular mechanism of SEPN1-related myopathies and indicates that the TGF-beta/ERO1/ascorbic acid axis offers potential for their treatment.

Topics: Animals; Antioxidants; Ascorbic Acid; Endoplasmic Reticulum; Gene Expression Profiling; Glycoproteins; Histocytochemistry; Mice; Mice, Transgenic; Microarray Analysis; Microscopy, Electron; Muscle Proteins; Muscle, Skeletal; Muscular Diseases; Mutant Proteins; Oxidative Stress; Oxidoreductases; Selenoproteins; Signal Transduction; Transforming Growth Factor beta

Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare mitochondrial fatty acid β-oxidation disorder. We aimed to explore the clinical, biochemical, and genetic findings, treatments and outcomes in eight Chinese VLCADD patients.. Eight patients from six unrelated Chinese families with symptomatic VLCADD were diagnosed in the past 4 years. The clinical features and ACADVL gene mutations were analyzed.. One patient underwent newborn screening and has been treated timely, she hardly had any symptoms. The remaining seven patients were found because of edema, diarrhea, coma, liver damage and psychomotor retardation. Seven patients had fatty liver. Five had myopathy. All patients had elevated blood tetradecanoylcarnitine. Nine heterozygous mutations of the ACADVL gene were found. Three (c.1102C > T, c.1795G > A and IVS10, +6T > A) were novel. Seven patients completely recovered after treatment. One patient died before diagnosis due to cardiomyopathy. His mother underwent amniocentesis for prenatal diagnosis. The fetus had the same gene mutation of the proband and markedly elevated tetradecanoylcarnitine in amniotic fluid. The boy has been treated after birth and he is healthy now.. Dietary treatment usually leads to good outcomes to VLCADD patients. Amniocytes ACADVL mutations and amniotic fluid tetradecanoylcarnitine analysis are useful for the prenatal diagnosis.

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Acyl-CoA Dehydrogenases; Amniotic Fluid; Ascorbic Acid; Asian People; Bezafibrate; Carnitine; Case-Control Studies; China; Chromatography, Liquid; Congenital Bone Marrow Failure Syndromes; DNA, Complementary; Exons; Female; Genetic Testing; Heterozygote; Humans; Infant; Infant Formula; Infant, Newborn; Lipid Metabolism, Inborn Errors; Male; Mitochondrial Diseases; Muscular Diseases; Mutation, Missense; Neonatal Screening; Prenatal Diagnosis; Sequence Alignment; Sequence Analysis, DNA; Tandem Mass Spectrometry; Treatment Outcome; Triglycerides; Vitamin B Complex

We hypothesized that zebrafish (Danio rerio) undergoing long-term vitamin E deficiency with marginal vitamin C status would develop myopathy resulting in impaired swimming. Zebrafish were fed for 1 y a defined diet without (E-) and with (E+) vitamin E (500 mg α-tocopherol/kg diet). For the last 150 days, dietary ascorbic acid concentrations were decreased from 3500 to 50 mg/kg diet and the fish sampled periodically to assess ascorbic acid concentrations. The ascorbic acid depletion curves were faster in the E- compared with E+ fish (P < 0.0001); the estimated half-life of depletion in the E- fish was 34 days, while in it was 55 days in the E+ fish. To assess swimming behavior, zebrafish were monitored individually following a "startle-response" stimulus, using computer and video technology. Muscle histopathology was assessed using hematoxylin and eosin staining on paramedian sections of fixed zebrafish. At study end, E- fish contained 300-fold less α-tocopherol (p < 0.0001), half the ascorbic acid (p = 0.0001) and 3-fold more malondialdehyde (p = 0.0005) than did E+ fish. During the first minute following a tap stimulus (p < 0.05), E+ fish swam twice as far as did E- fish. In the E- fish, the sluggish behavior was associated with a multifocal, polyphasic, degenerative myopathy of the skeletal muscle. The myopathy severity ranged from scattered acute necrosis to widespread fibrosis and was accompanied by increased anti-hydroxynonenal staining. Thus, vitamin E deficiency in zebrafish causes increased oxidative stress and a secondary depletion of ascorbic acid, resulting in severe damage to muscle tissue and impaired muscle function.

Topics: alpha-Tocopherol; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Behavior, Animal; Fibrosis; Half-Life; Malondialdehyde; Muscle, Skeletal; Muscular Diseases; Necrosis; Oxidative Stress; Severity of Illness Index; Swimming; Vitamin E Deficiency; Zebrafish

Some authors have suggested a possible loss of antioxidant factors in alcoholic skeletal myopathy. To assess the relationship between ethanol consumption and serum and muscle levels of alpha-tocopherol, ascorbic acid, and retinol in chronic alcoholics with and without skeletal myopathy, a prospective cross-sectional study was performed in the Alcohol Unit of a 1000-bed university hospital. Twenty-five chronic male alcoholic patients (10 with skeletal myopathy) and 15 male controls of similar age were included. Evaluation of daily and lifetime ethanol consumption, assessment of anthropometric and protein nutritional parameters, and open biopsy of the left deltoid muscle were performed, as well as determinations of serum and muscle levels of retinol, alpha-tocopherol, and ascorbic acid by HPLC analysis. Ten of the 25 chronic alcoholic patients presented histological criteria of skeletal myopathy. Four alcoholics presented caloric malnutrition and three protein malnutrition. All of the muscle biopsies of the control group were entirely normal, as were their nutritional studies. The serum and muscular levels of alpha-tocopherol, ascorbic acid, and retinol were normal and were similar in both alcoholics and controls. Except for serum retinol, these values were also similar in alcoholic patients with or without skeletal myopathy. In the univariate analysis, we identified the total lifetime dose of ethanol (p < 0.003), the muscle arm area (p < 0.05), and serum levels of prealbumin (p < 0.03) and retinol-binding protein (p < 0.05) as factors influencing the development of alcoholic myopathy. However, in multivariate analysis, the total lifetime dose of ethanol was the only independent factor in relation to alcoholic myopathy (p < 0.003). Serum and muscle levels of the antioxidants alpha-tocopherol, ascorbic acid, and retinol do not influence the presence of skeletal myopathy in chronic alcoholic patients.

Topics: Adult; Aged; Alcoholism; Ascorbic Acid; Biopsy; Cross-Sectional Studies; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases; Prealbumin; Prospective Studies; Protein-Energy Malnutrition; Retinol-Binding Proteins; Risk Factors; Vitamin A; Vitamin E

Neurolathyrism is a neurological condition seen among people who eat the seeds of Lathyrus sativus (LS) as a principal source of food energy for 2 months or more. It is characterized by severe muscular rigidity and paralysis of the lower limbs. beta-N-Oxalyl-L-alpha,beta-diaminopropionic acid is the principal toxin found in the seed. No experimental animal model for neurolathyrism could be produced by feeding either the seeds or the toxin, although the condition has been known for centuries. We discovered that experimental neurolathyrism could be produced in guinea pigs and primates that needed an external supply of ascorbic acid by making them subclinically deficient in ascorbic acid and feeding them the seeds of LS or extracts thereof. Autoclaving the seeds of LS with lime removes the toxin.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Fabaceae; Food Contamination; Guinea Pigs; Haplorhini; Lathyrism; Male; Muscular Diseases; Plants, Medicinal

Topics: Acidosis, Lactic; Adolescent; Ascorbic Acid; Electron Transport; Energy Metabolism; Female; Humans; Mitochondria, Muscle; Muscular Diseases; Physical Exertion; Vitamin K

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

Topics: Adolescent; Adult; Ascorbic Acid; Back Pain; Bone Diseases; Child; Fractures, Bone; Humans; Muscular Diseases; Neoplasms; Osteogenesis Imperfecta; Pain

Rats fed a vitamin E-deficient diet containing 10% "stripped" corn oil had reduced growth rate and elevated platelet count by 12 weeks of age, and a normocytic anemia with elevated reticulocytes by 16 weeks of age. After 5 months, rats became emaciated and developed kyphoscoliosis. Some rats developed skin ulcers and tremors, and mortality was high. Neuromuscular lesions included a chronic necrotizing myopathy and localized axonal dystrophy. There was also a selective activation of lysosomes in the central nervous system microcirculation. Liver ascorbic acid of deficient rats was the same as in those receiving vitamin E. Urinary excretion of p-hydroxyphenylpyruvate after a tyrosine load was also the same in deficient and control rats. It was concluded that neither vitamin C synthesis or utilization was affected the E-deficient rats.

Topics: Age Factors; Anemia; Animals; Ascorbic Acid; Female; Kyphosis; Male; Muscular Diseases; Necrosis; Nervous System Diseases; Rats; Scoliosis; Skin Ulcer; Thrombocytosis; Vitamin E Deficiency

We determined the respiration, respiratory control, and Pi:O ratios with different substrates in mitochondria isolated from five cases of human neuromuscular disorders (two cases of central core disease, two cases of neuropathy of Dejerine-Sottas, and one case of Kugelberg-Welander's disease) and compared them with normal human muscle. In all the myopathies studied, a severe derangement of the respiratory control with variable derangement of oxidative phosphorylation was found. This supports the idea that a group of neuromyopathies shares the same biochemical lesion as the so-called mitochondrial myopathies, forming with them a group of myopathies which may be related through a similar biochemical lesion of varying degree. Alternatively, disturbance of mitochondrial functions in a number of myopathies could be considered as a non-specific finding.

Topics: Adenosine Diphosphate; Adolescent; Adult; Ascorbic Acid; Child; Female; Glutamates; Humans; Hypertrophy; Infant; Malates; Male; Middle Aged; Mitochondria, Muscle; Motor Neurons; Muscular Atrophy; Muscular Diseases; Myotonic Dystrophy; Neuromuscular Diseases; Oxidative Phosphorylation; Oxidative Phosphorylation Coupling Factors; Oxygen Consumption; Phosphates; Spinal Cord Diseases; Succinates

Topics: Adult; Antigens; Ascorbic Acid; Blood Glucose; Blood Protein Disorders; Body Weight; Carbon Isotopes; Cholesterol; Diet Therapy; Epinephrine; Epithelium; Fatigue; Gingival Diseases; Hemorrhage; Humans; Immunization; Insulin; Joint Diseases; Keratosis; Lipids; Male; Middle Aged; Muscular Diseases; Nutritional Requirements; Pain; Plasma; Scurvy; Time Factors; Typhoid Fever; Water

Topics: Adult; Aged; Arthritis, Rheumatoid; Ascorbic Acid; Drug Synergism; Female; Humans; Male; Middle Aged; Muscular Diseases; Neuralgia; Pain; Salicylamides; Spinal Diseases; Surveys and Questionnaires; Triamcinolone

Topics: Animals; Ascorbic Acid; Creatine Kinase; Diaphragm; Glutathione; Glycerolphosphate Dehydrogenase; Glycolysis; Injections, Intraperitoneal; Muscular Diseases; Myocardium; Quinolines; Rats; Sulfhydryl Compounds; Vitamin E

Topics: Aminopyrine; Antirheumatic Agents; Ascorbic Acid; Caffeine; Carbamates; Humans; Methocarbamol; Muscle Relaxants, Central; Muscular Diseases; Osteochondritis; Prednisolone; Thoracic Outlet Syndrome

Topics: Aminopyrine; Ascorbic Acid; Bone Diseases; Caffeine; Disease; Joint Diseases; Muscle Relaxants, Central; Muscle Relaxation; Muscles; Muscular Diseases; Vitamins

Topics: Aminopyrine; Ascorbic Acid; Connective Tissue Diseases; Hip; Humans; Joint Diseases; Muscle Relaxants, Central; Muscular Diseases; Osteoarthritis, Hip; Prednisolone; Spinal Diseases