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jtitle_s:("Acta mol")
1.  Markers of degeneration and regeneration in Duchenne muscular dystrophy 
Acta Myologica  2009;28(3):94-100.
Summary
Dystrophin deficiency associated with Duchenne muscular dystrophy (DMD) results in chronic inflammation and severe skeletal muscle degeneration, where the extent of muscle fibrosis contributes to disease severity. The microenvironment of dystrophic muscles is associated with variation in levels of markers of degeneration and regeneration. Since in dystrophic muscle apoptosis precedes necrosis, markers of apoptosis can be used as indicators of degeneration, while regeneration can be measured in terms of cytokines and growth factor expression”; and then throughout the text use “markers of apoptosis/degeneration. The present study is an attempt to evaluate the extent of degeneration and regeneration in DMD patient blood. Subjects were 24 boys with DMD diagnosed at the molecular level versus 20 age and socioeconomic matching healthy boys. In their blood, levels of Fas and FasL and Bax/Bcl-2 and plasma DNA fragmentation were measured as markers of apoptosis. The cytokine tumor necrosis factor alfa (TNF-α), and the growth factors: basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were measured as markers of regeneration. Plasma DNA fragmentation (0.38% ± 0.12 vs. 0.2% ± . 0.1.5) and Fas (9.9 ± 2.8 vs. 2 ± 0.1, p < 0.001) together with FasL mRNA expression in circulating lymphocytes (0.47 ± .09 vs. 0.24 ± .04, p < 0.001) were significantly increased in DMD patients compared to controls. There was a significant increase in Bax (0.19 ± 0.7 vs. 0.05 ± 0.1, p < 0.00001) expression and a significant decrease in Bcl-2 protein (6.4 ± 1.6 vs10 ± 2.8, p < 0.00001) as compared to controls. Among markers of regeneration, TNF- α (30.2 ± 9.5 vs. 3.6 ± 0.9) and bFGF (21.7 ± 10.3 vs. 4.75 ± 2.2) were significant increased while VEGF was significantly decreased (190 ± 115 vs. 210 ± 142.) in blood of DMD patients compared to controls. Our results indicate that Fas/FasL and Bax/Bcl-2 are involved in muscle atrophy and degeneration in DMD patients, while regeneration process does not cope with the degeneration.
PMCID: PMC2858946  PMID: 20476668
Apoptosis; basic fibroblast growth factor; Duchenne muscular dystrophy
3.  Markers of oxidative stress and aging in Duchene muscular dystrophy patients and the possible ameliorating effect of He:Ne laser 
Acta Myologica  2007;26(1):14-21.
Summary
Replicative aging and oxidative stress are two plausible theories explaining the etiology of muscular dystrophy. The first theory indicates that replicative aging of myogenic cells (satellite cells), owing to enhanced myofiber turnover, is a plausible explanation of the progression of Duchenne muscular dystrophy (DMD). The oxidative stress theory indicates that failure of muscle regeneration to keep up with the ongoing apoptosis and necrosis following oxidative stress, that normally associates muscular exercise, leads to muscle atrophy in DMD.
To test for these two theories, markers of replicative aging and oxidative stress were assessed in the blood of 30 DMD patients vs. 20 normal healthy age matching controls. Markers of replicative aging showed significantly lower telomerase activity, significantly increased expression of receptors for advanced glycation end products (RAGEs) mRNA and Bax mRNA (an apoptotic gene) in DMD compared to controls. There was a significant increase in markers of oxidative stress among DMD patients compared to controls, measured in terms of increased apoptotic percentage in circulating mononuclear cells, increased lipid peroxidation measured in terms of plasma malondialdehyde (MDA) and increased protein carbonyls. Levels of plasma nitric oxide (NO), which neutralizes oxygen radicals, and expression of inducible nitric oxide synthase (iNOS) mRNA in neutrophils was significantly lower among DMD compared to controls.
Biostimulation of WBC by helium neon (He:Ne) laser irradiation induced a significant increase in the expression of iNOS mRNA and plasma NO levels, but still at a lower level compared to controls. He:Ne laser irradiation induced a marked decrease in markers of oxidative stress among DMD patients compared to their level before irradiation, measured in terms of decreased plasma protein carbonyls, decreased plasma MDA, and decreased apoptosis percentage.
Conclusion: This study points to that oxidative stress is the prime cause for muscle degeneration in DMD and points out to the possible ameliorative effect of He:Ne laser on this stress.
PMCID: PMC2949317  PMID: 17915565
Apoptosis; Bax mRNA; He:Ne laser; lipid peroxidation; nitric oxide; nitric oxide synthase; receptors for advanced glycation end products (RAGEs); telomerase reverse transcriptase

Results 1-3 (3)