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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Friedreich's ataxia is almost always associated with a cardiomyopathy. The cardiomyopathy and its attendant cardiopulmonary sequelae is the usual cause of death in this disease. The author reviews the known pharmacology of the heart, particularly as it applies to hypertrophic cardiomyopathy. The important role played by calcium and the possible role of taurine is stressed. Therapeutic possibilities are mentioned.
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PMID:Cardiac pharmacology and cardiomyopathy in Friedreich's ataxia. 2 6

A single case of typical Friedreich's ataxia was analyzed for cardiac changes and compared to the findings from the literature. Macroscopically, there was a cardiomegaly with some degree of ventricular hypertrophy and probable mild dilatation of the auricles. The more important and constant histologic changes were myocardial fibrosis and degeneration of the cardiac muscle cells. Granular deposits of calcium salts and iron were found in the muscle cells. A cardiomyopathy hypertrophic in type and occasionally obstructive appears to be an integral part of Friedreich's ataxia.
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PMID:Pathology of the heart in Friedreich's ataxia: review of the literature and report of one case. 18 9

In light of the available information on the cardiomyopathy of Friedreich's ataxia, the cardiomyopathic Syrian hamster may be an appropriate laboratory model. Cardiomyopathy in these animals is a result of calcium accumulation. We analyzed the atria and right and left ventricles from cardiomyopathic (CM) and random bred (RB) animals for calcium, magnesium, and iron concentrations at 30-40 and 60-70 days of age (age of maximum lesioning). There are no significant differences in the concentration of iron or magnesium among age-matched groups. The concentration of calcium in the left ventricles of the CM animals at 60 days old is 14 fold higher than that of RB animals. Although there is a significant difference in the concentration of calcium in the left ventricles of younger animals, it is not as pronounced as the difference in older animals. Analysis of the taurine concentration in 30-40 day old animals revealed that the CM animals show slightly higher taurine concentrations than RB in the whole heart. In 60 day old CM hamsters in the beta-adrenergic receptor density of the ventricles is unchanged. This indicates that calcium overload is not due to adrenergic supersensitivity.
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PMID:The Syrian golden hamster: a model for the cardiomyopathy of Friedreich's ataxia. 22 57

The regulation of cytoplasmic calcium is a key process in nerve tissue. Using a smooth muscle model we have shown that prostaglandin (PG) E2 probably regulates entry from extracellular fluid, whereas the release from intracellular stores depends on the interplay between thromboxane (TX) A2, PGEI and prostacyclin. Hormones and other agents interact with this system in the following ways: vasopressin, angiotensin and inositol mobilize arachidonic acid from membrane phospholipids and increase synthesis of PGE2 and TXA2, cortisol blocks this action. Prolactin and zinc mobilize dihomo-gamma-linolenic acid and increase synthesis of PGEI. These effects can be blocked by cortisol, lithium and taurine, three agents which on their own have no effect on basal PG production. Epileptogenic agents like penicillin and picrotoxin also stimulate PG synthesis, while diphenylhydantoin is a PG antagonist and diazepam is a TXA2 antagonist. The effects of all these agents occur at concentrations which are physiological in the case of the natural ones, and readily attained in human plasma in the case of the drgus. In view of recent evidence that calcium may be important in demyelination and considering the established role it plays in nerve conduction and synaptic transmission, we suggest that these observations may be of significance in understanding Friedreich's ataxia.
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PMID:Regulation of cytoplasmic calcium: interactions between prostaglandins, prostacyclin, thromboxane A2, zinc, copper and taurine. 34 85

Glutamic and aspartic acid uptake was measured in skin fibroblasts from patients with Friedreich's Ataxia, dicarboxylic aminoaciduria, and normal individuals. The results showed no difference in uptake kinetics of either dicarboxylic amino acids between Friedreich's Ataxia and normal cells, but reduced uptake velocities in dicarboxylic aminoaciduria fibroblasts. Friedreich's Ataxia fibroblasts were, however, less calcium-dependent and more magnesium and phosphate-dependent than controls in glucose-free incubation mixture. This difference might be related to some degree of glucose intolerance by Friedreich's Ataxia fibroblasts in culture.
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PMID:Dicarboxylic amino acid uptake in normal, Friedreich's ataxia, and dicarboxylic aminoaciduria fibroblasts. 48 20

This overview summarizes the investigations carried out during the second part of Phase Two of the Quebec Cooperative Study of Friedreich's Ataxia. These investigations outline in more details the fundamental role played by an abnormality in the fatty acid composition (deficient linoleic acid, 18:2) of the cholesterol esters of high density lipoproteins (HDL) in the phenotypic expression of the disease. They postulate a defective incorporation of linoleic acid to surface phosphatidylcholine of chylomicrons and consequent relative and absolute decreases in lipoprotein protein components because of overpacking with defective cholesteryl esters. Secondarily to these changes, the postulated lack of activation of the lipoamide dehydrogenase (LAD) of the pyruvate dehydrogenase (PDH) complex could result in slow pyruvate oxidation, glucose intolerance, deficient synthesis of acetylcholine, and depletion of glutamic and aspartic acid pools. In parallel, abnormal phosphatidyl-choline molecules could be incorporated to membranes, resulting in specific defects in some functions of these membranes, including transport of calcium and/or taurine and myelinization. The framework of an understanding of Friedreich's ataxia is now available, but much fundamental and clinical work remains to be done to fill in and prove each one of these postulated steps.
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PMID:Friedreich's ataxia 1979: an overview. 48 23

We report the presence of crystalline deposits of calcium hydroxyapatite in the mitochondria of 2 children with sporadic spinocerebellar degeneration. The deposits, identified by electron microscopy, were found in the mitochondria of neurons and smooth muscle cells in one patient and in only smooth muscle cells in the second child, but not in other cell types. The calcific nature of the deposits was confirmed by laser microprobe mass analysis. The calcium overload may interfere with mitochondrial function, as has been shown in the cardiomyopathic strain of the Syrian hamster, a model of the cardiomyopathy of Friedreich's ataxia.
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PMID:Mitochondrial hydroxyapatite deposits in spinocerebellar degeneration. 282 75

Platelets of a patient with Friedreich's ataxia have been investigated because of a codiagnosis of thrombasthenia. No aggregation occurred in response to adenosine diphosphate, platelet activating factor-acether, a stimulatory antiplatelet monoclonal antibody, or phorbol myristate acetate, although platelet aggregation could be induced with thrombin, the calcium ionophore A23187, or high concentrations of collagen. Shape change, adenosine triphosphate secretion, and the responses of the platelets' protein phosphorylation systems to all agonists were normal. Immunologic analysis of the patient's radiolabeled platelet surface proteins revealed normal levels of glycoproteins IIB and IIIa. However, no iodine 125-fibrinogen binding occurred after stimulation of the patient's platelets with adenosine diphosphate. In contrast, pretreatment of the patient's platelets with the proteolytic enzyme alpha-chymotrypsin resulted in the exposure of active 125I-fibrinogen binding sites. The patient's platelets exhibited normal aggregation to fibrinogen after their pretreatment with chymotrypsin and with elastases derived either from porcine pancreas or from human granulocytes. A murine monoclonal antibody directed against the human platelet membrane glycoproteins IIb and IIIa calcium-dependent epitope and rabbit polyclonal anti-human platelet membrane and human anti-P1A1 antibodies immunoprecipitated glycoproteins IIb and IIIa and a 66 kd cleavage product of glycoprotein IIIa from sodium dodecyl sulfate-Triton X-100 extracts of the patient's proteolytically treated platelets. The patient appears to exhibit a unique type of thrombopathy involving a defect in the exposure of fibrinogen receptors. The association between the neurologic disorder and the platelet defect is still unclear.
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PMID:Identification of a unique type of thrombopathy of human platelets: defect in the exposure of active fibrinogen receptors in a patient with Friedreich's ataxia. 283 36

Cardiac involvement in Friedreich's disease is classically a hypertrophic myocardiopathy, concentric or assymmetrical with or without dilatation. It has nothing specific in comparison to other myocardiopathies. Nevertheless, forms with a dilated myocardiopathy are also possible, but much more unfrequent. A propos of three cases, we have studied the different aspects of myocardiopathies in Friedreich's ataxia. The problem raised by the case of an hypertrophic myocardiopathy evolving toward a dilated form, unusual element of this pathology, is presented. The therapeutic potential of hypertrophic myocardiopathies is classically represented either by beta-blockers or by the more recent slow calcium inhibitors.
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PMID:[Myocardiopathies of Friedreich's disease]. 295 Aug 21

Nine patients with hypertrophic cardiomyopathy associated with Friedreich's ataxia were treated with the calcium antagonist verapamil, which is known to reduce myocardial hypertrophy and improve diastolic function in patients with idiopathic hypertrophic cardiomyopathy. Daily oral doses of 7 mg/kg were given for a mean (SD) of 24 (8) months. M mode echocardiography performed at the start of the study and at the end of follow up showed no significant difference between the treated group and an untreated control group of nine patients. Verapamil produced no changes in left ventricular wall thickness, mass index, left ventricular internal diameter, fractional shortening, peak normalised lengthening rate, peak rate of septal and posterior wall thinning, and time from minimum ventricular cavity dimension to mitral valve opening. Myocardial calcium overload has been suggested as a cause of cardiac disease in Friedreich's ataxia; however, verapamil had no beneficial effect on these patients with established myocardial hypertrophy.
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PMID:Echocardiographic evaluation of verapamil in Friedreich's ataxia. 396 8


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