Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

31P-NMR spectra were obtained from the quadriceps femoris muscle (at rest and after aerobic exercise) of the 7 cases of mitochondrial myopathies (2 cases of mitochondrial encephalomyopathy and lactic acidosis(MELA), 1 case of myoclonus epilepsy with regged red fiber, 1 case of Kearns-Sayre syndrome, 3 cases of progressive external ophthalmoplegia), using superconducting whole body MR (Magnetom, Siemens). One case showed abnormally low Pcr/Pi ratio in the resting state. An aerobic exercise using ergometer was performed on the other 6 patients. Three of them demonstrated significant reduction and delayed recovery of the Pcr/Pi ratio after exercise. This reduction was not detected in the control subjects. Histological studies of biopsied muscles revealed ragged red fibers in all the cases, the number varies, however, from 0.5 to 15.3 per cent of the total fibers. Abnormalities in the Pcr/Pi ratio of phosphorus spectra, in resting state or after exercise, tend to be observed in patients showing abundant ragged red fibers. Focal cytochrome c oxidase deficiency with relatively small amount of ragged red fibers (less than 10 per cent of the total fibers) was histologically noted in five of our patients, excluding 2 MELA patients. Biochemical assay of mitochondria enzyme was normal. It has been assumed that these patients have no primary defect in energy metabolism and the occasionally observed cytochrome c oxidase deficient fibers are non-specific findings probably caused by some devastating process occurring in these fibers. However, our present studies revealed abnormal reduction and delayed restoration of the Pcr/Pi ratio in 2 out of 5 focal cytochrome c oxidase deficiency cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[31P-NMR spectroscopy of mitochondrial myopathies: the relation between abnormal energy metabolism and muscle biopsy findings]. 254 6

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.
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PMID:Examination of a myopathy by phosphorus nuclear magnetic resonance. 611 4

A woman affected by chronic progressive external ophthalmoplegia and muscle mitochondrial DNA deletion was studied by phosphorus magnetic resonance spectroscopy (31P-MRS) prior to and after 1 and 7 months of treatment with oral lipoic acid. Before treatment a decreased phosphocreatine (PCr) content was found in the occipital lobes, accompanied by normal inorganic phosphate (Pi) level and cytosolic pH. Based on these findings, we found a high cytosolic adenosine diphosphate concentration [ADP] and high relative rate of energy metabolism together with a low phosphorylation potential. Muscle MRS showed an abnormal work-energy cost transfer function and a low rate of PCr recovery during the post-exercise period. All of these findings indicated a deficit of mitochondrial function in both brain and muscle. Treatment with 600 mg lipoic acid daily for 1 month resulted in a 55% increase of brain [PCr], 72% increase of phosphorylation potential, and a decrease of calculated [ADP] and rate of energy metabolism. After 7 months of treatment MRS data and mitochondrial function had improved further. Treatment with lipoate also led to a 64% increase in the initial slope of the work-energy cost transfer function in the working calf muscle and worsened the rate of PCr resynthesis during recovery. The patient reported subjective improvement of general conditions and muscle performance after therapy. Our results indicate that treatment with lipoate caused a relevant increase in levels of energy available in brain and skeletal muscle during exercise.
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PMID:Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo 31P-MRS in a patient with mitochondrial cytopathy. 759 80

The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS), clinical and laboratory tests. (31)P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in (31)P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included.
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PMID:Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study. 1580 48

Phosphorus magnetic resonance spectroscopic studies in bipolar disorder revealed altered brain energy metabolism resembling that of chronic progressive external ophthalmoplegia (CPEO). Mood disorder is one characteristic symptom in several families of CPEO caused by mutations of three genes, ANT1, Twinkle, and POLG. Molecular genetic analysis revealed association of bipolar disorder with mitochondrial DNA (mtDNA) 10398A polymorphism, 3644C mutation, and FDUFV2. In the postmortem brains, increased levels of mtDNA 4977bp deletion and 3243G mutation, and altered expression of mitochondria-related genes were reported. Mitochondria play an important role in neuroplasticity and apoptotic signaling via regulating intracellular calcium homeostasis. Thus, mitochondrial dysfunction may cause altered calcium homeostasis and neuroplasticity, resulting in bipolar disorder. Most molecular genetic findings in bipolar disorder regarding mitochondria and endoplasmic reticulum stress signaling are common to Parkinson's disease and diabetes mellitus. Thus, it is possible that bipolar disorder is also a disease caused by the progressive loss of some neuronal cells.
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PMID:[Mitochondrial dysfunction in bipolar disorder]. 1622 Jun 55