Early Stages Of Duchenne Muscular Dystrophy Research Articles

Transport of Ca2+ and Ca2+-dependent permeability transition in heart mitochondria in the early stages of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a progressive skeletal muscle disease that is associated with severe cardiac complications in the late stages. Significant mitochondrial dysfunction is reportedly responsible for the development of cardiomyopathy with age. At the same time, adaptive changes in mitochondrial metabolism in cardiomyocytes were identified in the early stages of DMD. In this work, we evaluate the functioning of calcium transport systems (MCU and NCLX), and MPT pore in the heart mitochondria of young dystrophin-deficient mice. As compared to wild-type animals, heart mitochondria of mdx mice have been found to be more efficient both in respect to Ca2+ uniport and Na+-dependent Ca2+ efflux. The data obtained indicate that the increased rate of Ca2+ uptake by heart mitochondria of mdx mice may be due to an increase in the ratio of MCU and MCUb subunits. In turn, an increase in the rate of Ca2+ efflux from organelles in DMD may be the result of a significant increase in the level of NCLX. Moreover, the heart mitochondria of mdx mice were more resistant to MPT pore opening, which may be due to an increase in the microviscosity of mitochondrial membranes of DMD mice. At the same time, the level of putative MPT pore proteins did not change. The paper discusses the effect of rearrangements of the mitochondrial proteome involved in the transport and accumulation of calcium on the adaptation of this organ to DMD.

Pulmonary and upper limbs function in children with early stage Duchenne muscular dystrophy compared to their healthy peers

BackgroundPulmonary and upper limbs function of children with Duchenne muscular dystrophy (DMD) are known to deteriorate throughout the disease process. However, there is a lack of information on the extent of impairments in the early stages of DMD when compared to healthy peers. ObjectiveTo investigate to what extent pulmonary and upper limbs function of children with early stage DMD are impaired. MethodsSixty-one children participated in the study: 31 with Grade 1 DMD (study group) according to the Brooke Upper and Lower Extremity Functional Classification Systems, and 30 age matched healthy peers (control group). Pulmonary function was determined with pulmonary function tests. The Performance of Upper Limb test was used to evaluate the upper limbs function. ResultsStudy and control groups were homogenous in terms of physical characteristics (p>0.05). Pulmonary and upper limbs function of children with DMD were about 85% and 93% of healthy peers, respectively. ConclusionThis study provides evidence for deterioration of pulmonary and upper limbs function in children with early stage DMD. Better knowledge of deterioration rate over time may help therapists to better plan and update their plan of care.

Inspiratory Muscle Training in Patients With Duchenne Muscular Dystrophy

The aim of this study was to assess the usefulness of a specific inspiratory muscle training in Duchenne muscular dystrophy (DMD). Fifteen patients with DMD started 6 months of training the inspiratory muscles and 15 patients served as a control group. Pulmonary and inspiratory muscle function parameters were assessed 3 months before and at the beginning of training, in the first and third month of training, at the end, and 6 months after its cessation. Maximal sniff assessed esophageal and transdiaphragmatic pressure values served as indices for global inspiratory muscle strength and diaphragmatic strength, respectively. Inspiratory muscle endurance was assessed by the length of time a certain inspiratory task could be maintained. In 10 of the 15 patients, respiratory muscle function parameters improved significantly after 1 month of training. Further improvements were to be seen after 3 and after 6 months. Even 6 months after the end of training, those effects remained to a large extent. In the other five patients, there was no such improvement after 1 month of training, which was therefore discontinued. All these five patients had vital capacity values of less than 25 percent predicted and/or PaCO2 values of more than 45 mm Hg. The 15 control patients had no significant change in their respiratory muscle function parameters. We conclude that a specific inspiratory muscle training is useful in the early stage of DMD.

Abstracts

ABSTRACT In Duchenne muscular dystrophy (DMD), morphological abnormalities in freeze fractured plasma membranes of skeletal muscle cells (decrease of intramembraneous particles and orthogonal particle arrays) led to the hypothesis that a defect of the plasmalemma is correlated with a pathological influx of calcium into non‐necrotic muscle cells in early stages of the disease. This is shown light microscopically in 40 Duchenne patients by Morin‐ and Alizarin‐red‐stains and electron microscopically by the KPA (potassium pyroantimonate)‐calcium precipitation method. KPA‐calcium precipitation is observed mainly in the mitochondria, in the nuclei, moderately between the myofibrils and subsarcolemmally (delta regions). Using atomic absorption spectrometry (Dr. Frey, Physiologisches Institut, Universität Freiburg) we were able to confirm these histopathological results. There is a highly significant increase in muscular calcium accompanied by a reciprocal decrease in magnesium: the ratio Mg++/Ca++ decreases from 12.85 (healthy control muscle) to 2.16 (DMD). In contrast to DMD muscle (mean % of Ca++‐positive fibers: 7%) cellular calcium accumulation is rare in autosomal recessive and Becker‐Kiener muscular dystrophies or other myopathies, and the plasma membrane structure in freeze fracture preparation is also significantly different from DMD. In 4 of 8 investigated male fetuses at risk for DMD, similar results could be obtained with regard to the calcium accumulation light and electron microscopically, as in affected DMD patients. In freeze fracture, a high% of plasma membranes of these positive fetuses show a decrease of intramembraneous particles.The results in early stages of DMD and in fetuses at risk for DMD support the hypothesis of a basic abnormality of the plasmalemma correlated with a pathological influx of calcium into the muscle cell together with a depletion of muscle magnesium. This might account for a mitochondrial decompensation and various metabolic disturbances, finally leading to cell necrosis. Calcium antagonists may have therapeutic value in DMD. activity in the pathognomonic nerve fibers of the lamina propria could be demonstrated in HD. The tubulin antiserum stained neuronal structures such as the cytoplasm, the axon cone and axons preferentially within the deep muscle layers of the gut wall and the submucosal plexus. Neither endocrine mucosal cells nor aberrant fibers in the lamina propria in HD and VIF showed tubulin‐IR. This property could prove the tubulin antibody to be an appropriate tool in detecting neurons of the deep plexus suitable for defining the borderline of the resection of the aganglionic segment in the surgical treatment of HD. A similar staining pattern was found in MBP‐IR, demonstrating myelinated fibers and intestinal glial cells mainly within the deep plexus, and this serum could attribute to further differentiation of neuronal intestinal dysplasia syndromes with respect to Schwann cell hyperplasia. In the case of VIF, numerous normal reacting ganglionic and glial cells could be demonstrated in the submucous and myenteric plexus, but pathologically as in HD there could be found aberrant VIPergic‐cholinergic fibers in the mucosal lamina propria.Joint Meeting of the German and Scandinavian Neuropathologists Turku, FinlandEnzymhistochemistry in normal pelvic sphinctersEffects of vitamin E deficiency on skeletal muscle in the ratMixed nemaline‐core myopathy with adult‐onsetNerve fiber lesions and the consequences interpreted by enzyme histochemistryExperimental thalidomide neuropathy: the morphological correlate of reduced conduction velocityUltrastructural and morphometric findings in sural nerves of children with autosomal recessive/sporadic hereditary motor and sensory neuropathy type IImmunocytochemical demonstration of human immunoglobulins in the peripheral nerves after systemic passive transfer to mice and monkeysImmunocytochemical demonstration of immunoglobulins in sural nerve biopsiesExperimental paramyxovirus infections in the mouse brainCoronavirus‐induced demyelinating encephalomyelitis in rats: europathological and immunological studiesValidity of clinical diagnosis in senile dementia: prospective clinicopathological studyNeuronal uptake of extravasated macromolecules of horseradish peroxidase and their transport by axons to other regions from a focal vasogenic cerebral edemaThe presence of small intensely fluorescent (SIF) cells in the leptomeningesMonoclonal antibodies to intermediate filaments in neuropathologyStructural requirements for receptor‐mediated endocytosis of glycoproteins in nerve cell cultureNeuron‐associated peptides in human colonic biopsiesComparative morphometric studies of the post‐natal development of peripheral nerves