Myoglobinuria in boys with Duchenne muscular dystrophy on corticosteroid therapy

Garrood, Pva; Eagle, M.; Jardine, P.; Bushby, K.; Straub, Volker

doi:10.1016/j.nmd.2007.07.006

Cited by 24 publications

(15 citation statements)

References 8 publications

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“…However, known musclespecific differences in the susceptibility to exercise-related damage (quadriceps more than other limb muscles) (10) anticipate differential permeability related to the severity of the dystrophic phenotype and changes in membrane strain during contraction of muscle that vary in architecture (18, 79). As well, increased animal activity after prednisone treatment (5,7,61) would itself increase exercise-induced fiber damage, similar to the myoglobinuria reported in DMD despite steroid treatment (32,41). Altered calcium homeostasis with membrane dysfunction (1) would also raise permeability after prednisone.…”

Section: Discussionmentioning

confidence: 75%

Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm

Mizunoya¹,

Upadhaya²,

Burczynski

et al. 2011

American Journal of Physiology-Cell Physiology

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Mizunoya W, Upadhaya R, Burczynski FJ, Wang G, Anderson JE. Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm. Am J Physiol Cell Physiol 300: C1065-C1077, 2011. First published January 26, 2011 doi:10.1152/ajpcell.00482.2010.-In Duchenne muscular dystrophy (DMD), palliative glucocorticoid therapy can produce myopathy or calcification. Since increased nitric oxide synthase activity in dystrophic mice promotes regeneration, the outcome of two nitric oxide (NO) donor drugs, MyoNovin (M) and isosorbide dinitrate (I), on the effectiveness of the anti-inflammatory drug prednisone (P) in alleviating progression of dystrophy was tested. Dystrophic mdx mice were treated (18 days) as controls or with an NO donor Ϯ P. Fiber permeability and DNA synthesis were labeled by Evans blue dye (EBD) and bromodeoxyuridine uptake, respectively. P decreased body weight gain, M increased quadriceps mass, and I increased heart mass. P increased fiber permeability (%EBDϩ fibers) and calcification in diaphragm. Treatment with NO donors ϩ P (MϩP, IϩP) reduced %EBDϩ fibers and calcification vs. P alone. %EBDϩ fibers in MϩP diaphragm did not differ from control. NO donor treatment reduced proliferation and the population of c-metϩ cells and accelerated fiber regeneration. Concurrent with P, NO donor treatment suppressed two important detrimental effects of P in mice, possibly by accelerating regeneration, rebalancing satellite cell quiescence and activation in dystrophy, and/or increasing perfusion. Results suggest that NO donors could improve current therapy for DMD.Duchenne muscular dystrophy; skeletal muscle; satellite cells; glucocorticoid MUSCULAR DYSTROPHIES are lethal genetic muscle diseases, and the most common form, Duchenne muscular dystrophy (DMD), is caused by mutation in the dystrophin gene (37). Absence of dystrophin from the cytoskeleton in DMD fibers leads to disruption of the sarcolemma by mechanical stress or exercise and progressive muscle weakness and wasting (20,27,56,69). Investigations of possible therapeutic interventions using the mdx mouse model of DMD have examined gene therapy by viral delivery of full-length dystrophin (28) or microdystrophin (97), stem (satellite) cell transplantation (40), and read-through (91) or exon-skipping approaches (2, 55, 93) to restore dystrophin expression. As these investigations are ongoing, pharmacological treatment with glucocorticoids remains the current "gold standard" therapy in DMD.Treatment with prednisone promotes a palliative reduction in inflammation and delays disease progression (57, 58) in DMD. In DMD patients and mdx mice, prednisone and deflazacort reduce the secondary inflammation that extends muscle fiber necrosis outside the region of primary damage that is caused by exercise-induced membrane breaks or eccentric contraction (25, 63). In addition, deflazacort also upregulates the calcineurin/nuclear factor of activated T cells (NFAT) pathway activity, which counteracts the muscle-specific activation of JNK1 that damages...

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Section: Discussionmentioning

confidence: 75%

Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm

Mizunoya¹,

Upadhaya²,

Burczynski

et al. 2011

American Journal of Physiology-Cell Physiology

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“…However, two studies showed that running or step exercise damaged the tibialis anterior muscle and caused myoglobinuria immediately after training in patients aged 6–10 years [93, 94]. Theoretically, damage induced by short-term exercise does not prevent long-term improvement in muscle status.…”

Section: Experimental Procedures For Exercise In Patients With Dmdmentioning

confidence: 99%

Comparison of Experimental Protocols of Physical Exercise for mdx Mice and Duchenne Muscular Dystrophy Patients

Hyzewicz

Rüegg

Takeda

2015

Journal of Neuromuscular Diseases

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Duchenne Muscular Dystrophy (DMD) is caused by mutations in the gene coding for dystrophin and leads to muscle degeneration, wheelchair dependence and death by cardiac or respiratory failure. Physical exercise has been proposed as a palliative therapy for DMD to maintain muscle strength and prevent contractures for as long as possible. However, its practice remains controversial because the benefits of training may be counteracted by muscle overuse and damage.The effects of physical exercise have been investigated in muscles of dystrophin-deficient mdx mice and in patients with DMD. However, a lack of uniformity among protocols limits comparability between studies and translatability of results from animals to humans. In the present review, we summarize and discuss published protocols used to investigate the effects of physical exercise on mdx mice and DMD patients, with the objectives of improving comparability between studies and identifying future research directions.

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“…Whether this outcome is volitionally or pathophysiologically imposed, work is performed at the subject's discretion. We pose the question: Do DMD patients develop an awareness and memory of a given workload/physical activity if significant muscle pain or myoglobinuria follows the activity53? If so, does this affect their choices regarding participation in physical activities?…”

Section: Mechanical Weakening Of the Sarcolemmamentioning

confidence: 99%

Exercise and duchenne muscular dystrophy: Toward evidence‐based exercise prescription

et al. 2011

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To develop a rational framework for answering questions about the role of exercise in Duchenne muscular dystrophy (DMD), we focused on five pathophysiological mechanisms and offer brief hypotheses regarding how exercise may beneficially modulate pertinent cellular and molecular pathways. We aimed to provide an integrative overview of mechanisms of DMD pathology that may improve or worsen as a result of exercise. We also sought to stimulate discussion of what outcomes/dependent variables most appropriately measure these mechanisms, with the purpose of defining criteria for well-designed, controlled studies of exercise in DMD. The five mechanisms include pathways that are both intrinsic and extrinsic to the diseased muscle cells.

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Myoglobinuria in boys with Duchenne muscular dystrophy on corticosteroid therapy

Cited by 24 publications

References 8 publications

Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm

Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm

Comparison of Experimental Protocols of Physical Exercise for mdx Mice and Duchenne Muscular Dystrophy Patients

Exercise and duchenne muscular dystrophy: Toward evidence‐based exercise prescription

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