Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical and biochemical findings in skeletal muscle in 11 patients with chronic fatigue myalgia syndromes of unknown aetiology are reported. All patients had severe asthenia for from one to 10 years with greatly limited exercise capacity and protracted exhaustion after minor exercise. Diffuse myalgia was prominent and was exacerbated for hours to days after exercise. Assay of skeletal muscle carnitine, phosphorylase, all glycolytic enzymes and the mitochondrial marker enzymes monoamine oxidase, isocitrate dehydrogenase and cytochrome oxidase were normal. These findings lend no support to the presence of a major defect in muscle intermediary energy pathways in this syndrome.
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PMID:Chronic fatigue and myalgia syndrome: mitochondrial and glycolytic studies in skeletal muscle. 303 60

Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl) and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful, sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT, ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction has an influence on the clinical application of these agents, especially at high doses and when combined. They have produced in humans a new category of acquired mitochondrial toxins that cause clinical manifestations resembling the genetic mitochondrial disorders.
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PMID:Peripheral neuropathy and antiretroviral drugs. 1129 2

The pathophysiological link between work-related exposures and neck myalgia remains a puzzle. According to the hypothesis presented here, neck myalgia is evoked when low-level contractions in the trapezius muscle are combined with sympathetic vasoconstriction due to psychological stress or prolonged head-down neck flexion at work. These ischemic contractions increase nitric oxide/oxygen concentration ratio in the muscle fibres, enhancing herewith the reversible inhibition of mitochondrial cytochrome oxidase by nitric oxide. The result is depletion of adenosine triphosphate, which elicits production/efflux of lactic acid, in turn activating and sensitising proton-sensitive nociceptive fibres in the connective tissue, causing myalgic pain and tenderness. High estrogen-level, which gives a high expression of nitric oxide synthase in the muscle, accentuates the situation. During episodes of sustained inhibition of cytochrome oxidase by nitric oxide, peroxynitrite may be produced and cause irreversible inactivation of several enzymes in the mitochondrial electron-carrier chain. With repeated episodes, an increasing part of the enzymatic capacity for cellular respiration is inactivated. Even if this process only takes place within a small portion of the muscle fibres, it may contribute to frequent exacerbations of pain. Effects of peroxinitrite may also explain the mitochondrial abnormalities found in the trapezius muscle of many neck myalgia patients. Adrenergic antagonists and nitric oxide synthase inhibitors could reduce symptoms. Ascorbic acid, alpha tocopherol, and flavonoids, which are safe and effective scavengers of peroxynitrite, could prevent chronicity. The most effective non-pharmacological measure may be to reduce exposure to prolonged head-down neck flexions and psychosocial stress at work.
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PMID:Linking work factors to neck myalgia: the nitric oxide/oxygen ratio hypothesis. 1508 96

Tubular aggregate myopathy (TAM) is a rare form of myopathy with an autosomal dominant or recessive pattern. Four rare cases of TAM are described. All patients presented with muscle aches and pains, sometimes cramps. Muscle biopsies were snap frozen and processed for routine, special, enzyme, and immunohistochemistry. Tissue was also processed for electron microscopy. Muscle biopsy revealed similar changes characterized by subsarcolemmal accumulation of granular material that stained red with modified Gomori trichrome stain, intense blue with nicotinamide adenine dinucleotide-tetrazolium reductase, but was non-reactive to succinyl dehydrogenase and cytochrome oxidase stains. Ultrastructural examination showed aggregates of hexagonal tubules in the subsarcolemmal region, which are pathognomonic of this entity. This report highlights the importance of histochemistry and electron microscopy for accurate diagnosis; otherwise TAM can be misdiagnosed on clinical grounds as a metabolic or mitochondrial myopathy.
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PMID:Tubular aggregate myopathy: a rare form of myopathy. 1882 61

In 2006, the Thailand Ministry of Public Health studied 28 patients from a village in northern Thailand. All had myalgia, edema, fever, and gastrointestinal symptoms; most had eaten wild boar. A muscle biopsy specimen from a patient showed nonencapsulated larvae with a cytochrome oxidase I gene sequence of Trichinella papuae.
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PMID:Outbreak of trichinellosis caused by Trichinella papuae, Thailand, 2006. 1904 19

A patient with a known family history of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) due to the MT-TL1 m.3243A>G mutation presented with mild myalgia and very minor upper limb proximal muscle weakness. Muscle histology revealed low levels of cytochrome oxidase-negative fibres and non-specific myositis. Using the last "hot cycle" polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), the MELAS MT-TL1 m.3243A>G mutation was only detected in urine, and not in hair, blood or skeletal muscle. This report highlights the need to screen various tissues to achieve an accurate mitochondrial genetic diagnosis and suggests the likelihood of myositis arising secondary to the MELAS MT-TL1 m.3243A>G mutation.
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PMID:Association of the MELAS m.3243A>G mutation with myositis and the superiority of urine over muscle, blood and hair for mutation detection. 1950 62