The importance of mdx mouse in the pathophysiology of Duchenne's muscular distrophy. O camundongo mdx desenvolve distrofia muscular recessiva ligada ao cromossoma X locus Xp Palavras-chave: distrofia muscular, distrofina, mdx, modelo animal. The mdx mouse develop an X-linked recessive muscular dystrophy locus Xp

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USA - os autores estudaram a nifedipina em camundongos com distrofia muscular. A droga foi usada no tratamento de 38 meninos com DMD em doses variadas por 28 dias.

Clinical Rehabilitation, Effects of respiratory muscle training on pulmonary functions in patients with slowly progressive neuromuscular disease: a randomized controlled trial. Abstract Objective: To investigate the effects of inspiratory and expiratory muscle training on pulmonary functions in patients with slowly progressive neuromuscular disease. Design: Prospective randomized controlled double-blinded study.

Setting: Chest diseases clinic of university hospital. Subjects: Twenty-six patients with slowly progressive neuromuscular disease followed for respiratory problems were included in the study.

Methods: Spirometry, peak cough flow, maximal inspiratory pressure, maximal expiratory pressure, and sniff nasal inspiratory pressure were measured before the eighth week of study, and subsequently at end of it. Respiratory muscle training was performed by inspiratory Threshold Inspiratory Muscle Trainer and expiratory Threshold Positive Expiratory Pressure threshold loading methods. Training intensities were increased according to maximal inspiratory and expiratory pressures in the experimental group, while the lowest loads were used for training in the sham group.

Training intensity was adjusted in the training group once a week. Conclusions: As a conclusion of our study, we found that respiratory muscle strength improved by inspiratory and expiratory muscle training in patients with slowly progressive neuromuscular disease.

USA - neste importante encontro de pesquisadores eu consegui selecionar quatro pesquisas relacionadas com o tratamento da distrofia muscular, sendo 3 brasileiras. Mauricio, H. Santo Neto, M. At later stages of the disease, fibrosis deposition, mainly in respiratory muscles such as the diaphragm, is responsible for the loss of muscle function with consequent respiratory failure seen in DMD patients. Previously, we demonstrated that omega-3 protected dystrophic skeletal muscles against myonecrosis at early stages of disease, in the young mdx.

In the present study we investigated whether omega-3 therapy would benefit dystrophy at later stages of the disease, in old 13 months of age mdx. Control mdx received nujol in an equivalent dosage to the animals treated with fish oil. Omega-3 therapy started at 8 months of age, for 5 months.

Functional analysis grip strength showed that omega-3 therapy improved forelimb muscle strength over the time period studied. The serum levels of creatine kinase CK , an indicative of muscle degeneration, were 7.

At this later stage of the disease, the diaphragm showed extensive area of fibrosis In conclusion, we demonstrated that omega-3 therapy is able to benefit dystrophy at later stages of the disease, by reducing myonecrosis and fibrosis in the diaphragm muscle of old mdx mice. Moraes , F. Dos Santos , A. Macedo , T. Hermes , E.

The present study investigates the effects of the combination of antioxidant N-acetylcysteine NAC with the iron chelator Deferoxamine DFX on dystrophic diaphragm muscle. Grip strength measurement was used for functional evaluation.

Creatine kinase CK levels were determined for biochemical evaluation of muscle fiber degeneration. The results suggest that NAC plus DFX play a protective role in dystrophic muscle and support further investigations as a potential therapy for dystrophinopathies. Shiozuka, A. Nishida, Y.

Takeshima, M. Yagi , T. Lee , M. Matsuo A. Wagatsuma , M. Yoshida, M. Date , Y. Nonomura , R. Matsuda- Japan. Translational readthrough of a premature termination codon is a promising therapeutic method in more than 2, distinctly inherited human diseases caused by respective single genes.

In order to investigate potent readthrough inducer with fewer toxicity than known readthrough-inducing drug such as gentamicin, we screened from kanamycin-related antibiotics using the novel transgenic mouse strain for detection of readthrough activity, named READ Readthrough Evaluation and Assessment by Dual reporter. In consequence, we discovered that the arbekacin induced the in vivo nonsense suppression dose-dependently in READ mice.

We found that arbekacin promoted the accumulation of dystrophin, the reduction of serum creatine kinase activity and the improvement of contractile function in mdx mice which carried nonsense mutation in dystrophin gene. Moreover, arbekacin exhibited the restoration of dystrophin expression on human muscle cells obtained by biopsies from Duchenne muscular dystrophy DMD patients with nonsense mutation of dystrophin gene.

These results demonstrate the feasibility of these investigational drugs to DMD and suggest that arbekacin represents an important chemical entity for the potential treatment of genetic disorders caused by nonsense mutations. Now, we are preparing "investigator-initiated clinical trial" supported by the Japan Medical Association Center of Clinical Trials. It is our hope that arbekacin will contribute towards the teatment for DMD.

Moreira, H. Duchenne muscular dystrophy DMD is a progressive muscle-wasting disease that causes respiratory failure that results in death at about 30 years of age.

The lack of dystrophin in mdx mice, the experimental model of DMD, causes sarcolemma breakdown and increased calcium influx followed by necrosis and fibrosis. At later stages of disease, cardiac muscle is also affected and the dystrophic cardiomyopathy is characterized by cardiomyocyte hypertrophy, necrosis, myocardial fibrosis and ECG abnormalities.

Previously, we demonstrated that suramin, an antifibrotic agent and purinergic P2 receptor antagonist, decreased fibrosis and improved cardiac function in mdx mice.

Blood was obtained to determine cardiac creatine-kinase CK-cardiac. Western blot analysis showed that suramin decreased the levels of the transient receptor potencial canonical channel 1 3. Overall, we demonstrate that suramin decreases cardiomyocyte necrosis, possibly by its ability to affect cardiac muscle total calcium and a calcium channel-related protein.

Furthermore, suramin may have potential benefits in maintaining the strucutre of dystrophin-protein complex. Acting via the Mas receptor, Angiotensin Ang- is part of the renin—angiotensin system, with the opposite effect to that of angiotensin II. Infusion or oral administration of Ang- in mdx mice normalized skeletal muscle architecture, decreased local fibrosis and improved muscle function in vitro and in vivo.

These results suggest that this novel compound Ang- might be used to improve quality of life and delay death in individuals with DMD and this drug should be investigated in further pre-clinical trials. Of the numerous clinical trials for Duchenne muscular dystrophy, only the corticosteroid prednisolone has shown potential for temporal improvement in motor ability. In this study, the effects of prednisolone on intellectual ability are examined in 29 cases of Duchenne muscular dystrophy because little information has been reported.

And also, motor functions and cardiac functions were evaluated. The treated group was administered prednisolone 0. Gene mutations were investigated. Intelligence quotient scores of the treated increased to 6. Intelligence quotient scores of the patients with nonsense point mutations improved significantly Our results demonstrate the effectiveness of prednisolone in improving intellectual impairment as well as in preserving motor function and brain natriuretic peptide levels.

We presume that prednisolone has a read-through effect on the stop codons in the central nervous systems of Duchenne muscular dystrophy because intelligence quotient of point mutation case was improved significantly. Traditional measures of respiratory function in children with Duchenne muscular dystrophy DMD are based on maximal inspiratory pressure P Imax and vital capacity VC. Sniff nasal inspiratory pressure SNIP measurements are easily performed by young children with neuromuscular disorders.

The clinical value of SNIP in the longitudinal assessment of respiratory weakness remains to be assessed. SNIP was an earlier marker of decline in respiratory muscle strength at SNIP longitudinal assessment is useful in the detection of inspiratory strength decline in young DMD patients when VC values remain within normal values and as an outcome measure in clinical trials for emerging therapeutics in young DMD patients from the age of 5 years.

Merosin-deficient congenital muscular dystrophy type 1A is a severe and fatal muscle wasting disease with no cure. Aumento da gordura corporal se relacionou a hipovitaminose. Metade 6 de 12 dos meninos que foram tratados com deflazacorte teve atraso puberal.

The routine use of glucocorticoids has increased the longevity of patients with Duchenne muscular dystrophy. Long-term steroid therapy may have adverse effects on endocrine function and could influence the onset of puberty. METHODS: We assessed the pubertal development of our patients who were 14 years of age or older and had been treated with deflazacort as their only glucocorticoid. There was no difference in the age of onset, dose, or duration of deflazacort therapy between those who did and did not have delayed puberty.

Eles sugerem que estudos com inibidores do crescimento devam ser testados na distrofia muscular de Duchenne. Geurts, and Imelda J. Physical training might delay the functional deterioration caused by disuse in boys with Duchenne muscular dystrophy DMD.

Ambulatory and recently wheelchair-dependent boys with DMD were allocated to the intervention or control group. The intervention group received assisted bicycle training of the legs and arms during 24 weeks. The control group received the same training after a waiting period of 24 weeks. Group differences were examined by an analysis of covariance. Thirty boys mean age All boys in the intervention group except one completed the training.

No significant group differences were found for the A6MCT. No serious adverse events were observed. Our results suggest that assisted bicycle training of the legs and arms is feasible and safe for both ambulant and wheelchair-dependent children and may decline the deterioration due to disuse.

Progressive deterioration, however, may compromise the design of trials for DMD. Terrill, Amber Boyatzis, Miranda D. Grounds, Peter G.


[Advances in the Treatment of Duchenne Muscular Dystrophy]

Duchenne muscular dystrophy is a genetically determined disease, linked to the X chromosome, c haracterized clinically by producing progressive muscle weakness, with an incidence of 1 per males born. It is caused by the mutation of the DMD gene, which encodes dystrophin, a sub-sarcolemmal protein essential for structural muscle stability. At present there is no curative treatment, the only drug that has been shown to modify the natural history of the disease independently of the genetic mutation are corticosteroids, currently indicated in early stages of the disease. In relation to clinical trials, in the last ten years, has experienced great advances in the field of therapeutic options, divided into two major therapeutic targets: 1 the area of gene therapies and 2 trying to reverse or block the pathophysiological processes of the disease, such as inflammation, fibrosis, muscle regeneration, etc. It is likely that an effective treatment for Duchenne muscular dystrophy requires combinations of therapies that address both the primary defect and its secondary pathophysiological consequences. Keywords: Duchenne muscular dystrophy; gene therap; therapeutic advances.


Campinas - suramin inibe a citocina TGF-beta1, relacionada com a fibrose muscular na distrofia. Nesta pesquisa foram utilizados camundongos deficientes de delta-sarcoglican um modelo experimental de distrofia tipo cinturas. Sarcoglycan mutations cause muscular dystrophy and dilated cardiomyopathy. Blood pressure BP , heart rate HR , activity telemetry , baroreflex sensitivity BRS, sequence technique , cardiac vagal and sympathetic tone HR responses to atropine, propranolol , LV function echocardiography , and AT1R expression immunofluorescence and fibrosis Masson stain in skeletal muscle were measured. Comparisons were made between treated and untreated mice.

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