glycogen and Myositis

The metabolic myopathies are a heterogeneous group of diseases, including glycogenoses, disorders of lipid metabolism, and mitochondrial myopathies, that result primarily from inborn errors of metabolism. Most of these metabolic defects cause medical conditions that manifest early in life. Nevertheless, clinical presentations during the teenage years and adulthood are increasingly being recognized. Many of the clinical manifestations of these diseases are difficult to differentiate from those observed in the idiopathic inflammatory myopathies, especially polymyositis. A directed evaluation using the clinical, laboratory, and genetic approaches summarized in this article, however, should allow for the differentiation of most metabolic myopathies from polymyositis and other forms of idiopathic inflammatory myopathy. The diagnosis of a metabolic myopathy should be considered in patients who appear to have polymyositis but lack the characteristic changes of inflammation found on EMG, MRI, or muscle histology, or in such patients who are refractory to immunosuppressive therapy. The forearm ischemic exercise test is especially useful to screen for some inborn errors of glycogen metabolism or glycolysis and for myoadenylate deaminase deficiency. Thorough analysis of muscle tissue, including histology, histochemistry, biochemistry, and occasionally electron microscopy, is often necessary to make the diagnosis of a metabolic myopathy. Advances in molecular biology methods and knowledge of the precise genetic defects associated with these metabolic defects are dramatically increasing our capacity to diagnose patients with a widening range of myopathies. It is expected that, with further understanding of the mechanisms of the metabolic and idiopathic inflammatory myopathies, the differentiation of these disorders into their pathogenetic components, and the capacity to diagnose them will continue to improve. These are essential factors in improving genetic counseling and eventually the therapy of these serious, and currently incurable, disorders.

Topics: Diagnosis, Differential; Exercise Test; Glycogen; Humans; Lipid Metabolism; Metabolic Diseases; Mitochondrial Myopathies; Muscle, Skeletal; Myositis

While thioridazine (Tio) inhibits the antioxidant defenses of Trypanosoma cruzi, the gold standard antitrypanosomal drug benznidazole (Bz) has potent anti-inflammatory and pro-oxidant properties. The combination of these drugs has never been tested to determine the effect on T. cruzi infection. Thus, we compared the impact of Tio and Bz, administered alone and in combination, on the development of skeletal myositis and liver inflammation in T. cruzi-infected mice. Swiss mice were randomized into six groups: uninfected untreated, infected untreated, treated with Tio (80 mg/kg) alone, Bz (50 or 100 mg/kg) alone, or a combination of Tio and Bz. Infected animals were inoculated with a virulent T. cruzi strain (Y) and treated by gavage for 20 days. Mice untreated or treated with Tio alone developed the most intense parasitemia, highest parasitic load, elevated IL-10, IL-17, IFN-γ, and TNF-α plasma levels, increased N-acetylglucosaminidase and myeloperoxidase activity in the liver and skeletal muscle, as well as severe myositis and liver inflammation (P < 0.05). All parameters were markedly attenuated in animals receiving Bz alone (P < 0.05). However, the co-administration of Tio impaired the response to Bz chemotherapy, causing a decrease in parasitological control (parasitemia and parasite load), skeletal muscle and liver inflammation, and increased microstructural damage, when compared to the group receiving Bz alone (P < 0.05). Altogether, our findings indicated that Tio aggravates systemic inflammation, skeletal myositis and hepatic inflammatory damage in T. cruzi-infected mice. By antagonizing the antiparasitic potential of Bz, Tio limits the anti-inflammatory, myoprotectant and hepatoprotective effects of the reference chemotherapy, aggravating the pathological remodeling of both organs. As the interaction of T. cruzi infection, Bz and Tio is potentially toxic to the liver, inducing inflammation and microvesicular steatosis; this drug combination represents a worrying pharmacological risk factor in Chagas disease.

Topics: Acetylglucosaminidase; Animals; Chagas Disease; Cytokines; Disease Models, Animal; Drug Combinations; Female; Glycogen; Hepatitis; Mice; Muscle, Skeletal; Myositis; NADH, NADPH Oxidoreductases; Nitroimidazoles; Parasite Load; Parasitemia; Peroxidase; Thioridazine; Transaminases; Trypanocidal Agents; Trypanosoma cruzi

Muscle biopsies of 20 alcoholic patients (15 males and 5 females), most of whom had liver disease and with no clinical or analytical evidence of neuromyopathy, were studied. 10 abstemious patients with no neuromuscular disease were selected as controls. Conventional histology failed to show significant skeletal muscle changes. A characteristic histochemical picture of tubular aggregates was found in one patient. An enlargement of the intermyofibrillar space with increase in glycogen deposition and fat droplets were detected ultrastructurally while 2 of the patients showed tubular aggregates. The mitochondriae of the alcoholic patients had a smaller perimeter and area than those of the control group (P less than 0.004 and P less than 0.008, respectively). These results suggest that the prolonged ingestion of alcohol can cause a mitochondrial alteration only evidenced by morphometry, with poor clinical, biochemical, electrophysiological and histological expression of myopathy. These findings can represent an early stage of alcoholic skeletal muscle injury.

Topics: Adenosine Triphosphatases; Adult; Alcoholism; Biopsy; Female; Glycogen; Humans; Lipid Metabolism; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Mitochondria, Muscle; Muscles; Myofibrils; Myositis

We studied picornavirus-like inclusions in muscle of a 66-year-old man with chronic polymyositis. Inoculation of a muscle homogenate to suckling mice and VeRo cells failed to detect any virus. After treatment of ultrathin sections with 2% amylase, individual particles that constituted inclusions were digested, as were free glycogen particles in the same section. Particles of the inclusions were stained with periodic acid-thiocarbohydrazide-silver proteinate and alkaline-bismuth, as were glycogen particles. The picornavirus-like inclusions seemed to consist of glycogen particles than form a crystalline arrangement in degenerated muscle fibers.

Topics: Aged; Chronic Disease; Crystallization; Glycogen; Histocytochemistry; Humans; Male; Muscles; Myositis; Picornaviridae

Two adult brothers became ill within 48 hours of each other, and both had severe myoglobinuria. One brother died of oliguric renal failure. The other did not have renal failure and survived. Acute influenza A infection was documented serologically and from throat washings in the surviving brother, and by isolation of the influenza A virus from throat cultures and lung tissue of the brother who died. It is not certain whether a genetic myopathy made these brothers susceptible to viral-induced myoglobinuria, but a normal response of venous lactate to ischemic work excluded lack of phosphorylase or phosphofructokinase as a cause of the myoglobinuria in the surviving brother. Neither brother had a history of recurrent episodes of myoglobinuria precipitated by exercise, cold, or fasting, thus making carnitine palmityl transferase deficiency unlikely.

Topics: Acute Kidney Injury; Adult; Age Factors; Glycogen; Humans; Influenza, Human; Male; Muscles; Myoglobinuria; Myositis; Necrosis

Topics: Biopsy; Electroencephalography; Electromyography; Electrophoresis; Female; Glycogen; Herpes Zoster; Humans; Inclusion Bodies, Viral; Male; Microscopy, Electron; Middle Aged; Mitochondria; Muscles; Muscular Atrophy; Myofibrils; Myositis

Topics: Glycogen; Humans; Hypokalemia; Muscle Spindles; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Myofibrils; Myositis; Paralysis; Polymyalgia Rheumatica

Topics: Adult; Cytoplasmic Granules; Glycogen; Histocytochemistry; Humans; Male; Microscopy, Electron; Muscles; Myositis

Topics: Adolescent; Adult; Aged; Child; Dermatomyositis; Glycogen; Glycolysis; Hexosephosphates; Humans; Lactates; Middle Aged; Motor Neurons; Muscles; Muscular Diseases; Muscular Dystrophies; Myasthenia Gravis; Myositis; Oculomotor Muscles; Phosphotransferases; Polyarteritis Nodosa

Topics: Amyloidosis; Carbohydrate Metabolism; Congenital Abnormalities; Endocrinology; Glycogen; Humans; Mitochondria; Muscular Diseases; Muscular Dystrophies; Myositis; Neurology; Neuromuscular Diseases; Paralyses, Familial Periodic