- and hence regulating transition between cell cycle phases. Several authors have shown that overexpression of CCNA1 may cause chromatin condensation, dysregulated double strand break repair and, consequently, apoptosis. Therefore, up-regulation of CCNA1 might lead to similar results in FSHD [12–16]. Moreover, cyclin A1 is normally suppressed or expressed on a low level in most somatic cells . Recently, two independent research groups have identified cell cycle dysregulation in FSHD by gene expression profiling. Both FSHD-1 and FSHD-2 cells show common and distinctive dysregulation in gene expression pattern and alterations in cell cycle control. Interestingly, FSHD-1 myoblasts (when compared to healthy control cells) showed dysregulation in cell cycle activity and proliferation processes whereas FSHD-2 myotubes are mainly linked to dysregulated RNA processing. Transcriptional profiles of several genes have been also investigated in human muscle biopsies selected according to different MRI patterns. In FSHD muscles, myopathic and inflammatory changes are characterized by increased signals of T2 - short tau inversion recovery (T2-STIR) sequences (also inmuscle not yet replaced by fat tissue). Normal healthy muscle does not present elevated T2 values. Following alterations inmuscle regeneration (derived only from musclewith elevated T2 which indicates T2-STIR hyperintensity), up-regulation of CCND1, CCND2, CCND3, CCNA1 and CDK 4 and CDK6 and down- regulation of CDKN1B were found . In this article we present evidence ofcyclin A1 overexpression at both RNA and protein level in FSHD-1, but not in other muscular dystrophies such as caveolinopathy 3 (CAV 3), dysferlinopathy (DYSF) and four and a half LIM domains protein 1 deficiency (FHL1).
The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. Objective: To report the relative frequency of common neuromuscular diagnoses in a reference center. Methods: A 17-year chart review ofpatientswith suspicion of myopathy. Results: Among 3,412 examinations, 1,603 (46.98%) yielded conirmatory results: 782 (48.78%) underwent molecular studies, and 821 (51.21%) had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%), mitochondriopathy 330 (20.59%), spinal muscular atrophy 158 (9.86%), limb girdle muscular dystrophy 157 (9.79%), Steinert myotonic dystrophy 138 (8.61%), facioscapulohumeral muscular dystrophy 99 (6.17%), and other diagnoses 261 (16.28%). Conclusion: Using the presently-available diagnostic techniques in this service, a speciic limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.
Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder that affects 1in 3.500–6.000 male births. DMD is characterized by rapid and irreversible replacement of normal muscle by connective tissue and fat. Although the disease causing gene product, dys- trophin, is present in many different tissues throughout the body, disease pathology is predomi- nantly restricted to muscle tissue. In the muscle, dystrophin is located close to the inner surface of the plasmalemma and interacts as a structural protein both with a number of membrane pro- teins that form the dystrophin-associated glycoprotein complex (DGC), and cytoskeletal proteins [1, 2]. Therefore, loss of dystrophin in DMD is associated with loss of cytoskeletal and sarcolem- mal integrity. It is believed that this structural defect gives rise to dysregulated calcium homeosta- sis through mechano-sensitive Ca ++ -channels, activation of proteases, such as calpain, and increased production of reactive oxygen species (ROS), which cause protein and membrane dam- age. One of the major sources of cellular ROS are mitochondria, implying altered mitochondrial function in DMD. However, while patientswith mitochondrial dysfunction disorders frequently display impaired muscle function , mitochondrial dysfunction as a feature of DMD is not gen- erally accepted despite numerous reports. One of the first publications that described impaired oxidative phosphorylation as a feature of DMD was reported in 1985 . Later, using 31 P mag- netic resonance spectroscopy, increased ADP and Pi levels relative to ATP and reduced phospho- creatine levels were found inmuscleof DMD patients . Sperl et al.  also reported decreased oxidation rates inmuscle biopsies from DMD patients and some indication of loose coupling of oxidative phosphorylation in mitochondria from those patients. These findings were also sup- ported by later observations of reduced rates of cellular respiration and lower activities of enzymes of the mitochondrial respiratory chain in biopsy samples of a DMD patient.
sion and flexion losses for the knee joint are seen together in AS patients, there was no statistically significant difference in Ag/An scores. The low le - vel of the work fatigue showed that the work of knee extensor is decreased in the first third and the last third period of the work thus indica ting a de- crease in endurance capacity of the muscles. The main finding of this study indicates that in AS pa- tients the tested knee muscles were significantly weaker and the muscle endurance capacity de- creases compared to apparently healthy controls. Interestingly, the results of this study show that the forces at different angles and endurance of the tes - ted muscles related to non-involvement joints inpatientswith AS are lower than those of control subjects.
3. Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigaré R, et al. An official American Thoracic Society/ European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;189(9):15-62. http://dx.doi.org/10.1164/rccm.201402-0373ST 4. Barreiro E, Bustamante V, Cejudo P, Gáldiz JB, Gea J, de
The immunohistochemmical pattern in the asymptomatic BMD carrier, with numerous defective fibers, was indistinguishable from that seen in two mani- festing carriers of DMD. It is possible that in this patient the structural dys- trophin alteration was not severe enough to allow the disruption of the fibers and consequent weakness, but was enough to be detected by the anti-dystrophin antibody we used. A similar phenomenon has recently been reported in a family 5.
Introduction: Chronic kidney disease as- sociated with hemodialysis treatment can have a variety of musculoskeletal com- plications, in addition to repercussions in pulmonary function. Objective: To evaluate the effects of inspiratory muscle training on inspiratory muscle strength, pulmonary function, and functional ca- pacity inpatientswith chronic kidney failure undergoing hemodialysis. Method: Non-controlled clinical trial, comprising 15 individuals diagnosed with chronic kidney failure and undergoing hemodi- alysis. Maximum inspiratory (PI max ) and expiratory (PE max ) pressures were assessed by use of pressure vacuum meter reading. Pulmonary function was assessed by use of spirometry. Functional capacity was as- sessed by use of walked distance and oxy- gen consumption obtained in the six-min- ute walk test (6MWT). For eight weeks, the inspiratory muscle training (IMT) protocol was applied during hemodialy- sis sessions, with load set to 40% of PI max and weekly frequency of three alternate days. Results: A significant increase in the walked distance was observed after train- ing (455.5 ± 98 versus 557.8 ± 121.0; p = 0.003). No statistically significant differ- ence was observed in the other variables when comparing their pre- and post-train- ing values. Conclusion: The study showed no statistically significant difference in respiratory muscle strength, pulmonary function, and oxygen consumption. An increase in the walked distance was ob- served in the 6MWT.
Conversely, other authors concluded that patientswith CA show a decrease of 50% in MIP, generated during the manovacuometry. This inability to generate normal pressures may be due to the effects of CA on the central nervous system, inspiratory muscle atrophy, or isotonic contractile dysfunction of the diaphragm (29, 30). These findings differ from the results of the present study, which did not identify loss of inspiratory muscle strength. An experimental study demonstrated a 14% decrease in the percentage of type I muscle fibers and a 13% increase in type II muscle fibers of the diaphragm. The animals evaluated showed a significant decrease in the strength of this muscle. The cause was related to a sarcomeric dysfunction with degradation of myosin heavy chain with a decrease of 27% without decrease in actin, troponin, and tropomyosin (31, 32).
SUMMARY: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder characterized by the progressive loss of muscular strength. Mdx mutant mice show a marked deficiency in dystrophin, which was related to muscle membrane stability. The aim of this study was to verify the possible protective anti-inflammatory effect of citrus oil on mdx muscle fibers. Thus, adult male and female mdx mice (014/06-CEEA) were divided into control and citrus-treated. After 60 days of treatment, one ml of blood was collected for creatine kinase (CK) test. Diaphragm, sternomastoideus, anterior tibial and gastrocnemius muscles were removed and processed according to histological routine methods. The observed alterations indicate a direct effect of citrus. Recent studies have improved the diagnosis of muscular diseases but with no definitions of efficient treatments. Intervention with several therapies is important to many patients presenting muscular dystrophy, which enables them to live longer and be more active, while there is no development of gene therapies.
OBJECTIVES. The ANKRD1 gene codes for the ankyrin repeat domain containing protein 1 and has an important role in myogenesis and possibly also in angiogenesis. Microvasculopathy is a cornerstone and an early pathological marker of change in dermatomyositis, leading to hypoxia and muscle perifascicular atrophy. These alterations could upregulate genes involved in myogenesis and angiogenesis such as ANKRD1. Therefore, we analyzed ANKRD1 expressioninmuscle biopsies of dermatomyositis and correlated with other hypoxia parameters and with histological changes.
LEF1 showed greater expression at 21 dpi and 40 dpi in commercial and at 21 dpi in Piau pigs, with lower expres- sion thereafter. This gene belongs to the WNT signaling pathway and is related to the biological process of embryo development. The WNT pathway is important for muscle development because it can control the expressionof myogenic regulatory factors such as MYF5 and MYOD, thereby influencing myogenic differentiation and survival (Cossu and Borello, 1999; von Maltzahn et al., 2012). LEF1 can induce cellular cycle progression, cellular differ- entiation and apoptosis through transcriptional activation of E2F1 (Zhou et al., 2008). Based on the expression pro- file observed here, LEF1 is more important in the early stages ofmuscle development, mainly at 21 dpi when so- mites are formed and proliferate. The additional peak of ex- pression seen at 40 dpi in commercial pigs indicates that LEF1 is possibly involved in the greater proliferation and fusion of myoblasts in this breed, which could account for the greater number of primary fibers in commercial pigs. Indeed, as mentioned above, LEF1 can induce cell cycle progression and cellular differentiation (Zhou et al., 2008).
Patientswith systemic sclerosis (SSc) can have muscle involvement in the form of myositis or non-infl ammatory myopathy. The muscle involvement can be associated with left ventricular dysfunction (LVD) inpatientswith SSc, resulting in worse prognosis. Eighty-seven patientsof the Hospital de Clínicas of the Universidade Federal do Paraná, diagnosed with SSc, were assessed regarding the presence of skeletal muscle manifestations and their relation with LVD. A 42.5% prevalence ofmuscle involvement was observed in the patients studied, as well as a positive correlation with the diffuse form of the disease. Excluding other causes of LVD, three of the four patientswith ejection fraction below the normal reference value had alteration of the muscle strength, atrophy and/or serum creatine phosphokinase (CPK) elevation.
A prospective quasi-experimental study was conducted among patients who underwent CABG and were recruited from the waiting list for a phase II CRP at the Outpatient Cardiology Clinic of Hospital Universitário de Santa Maria (HUSM), Santa Maria, RS, Brazil. The eligibility criteria included patients under- going CABG up to three weeks before the initiation of the study at HUSM, a clinical course without complications during hospital- ization, the absence of smoking (previous or current), and agree- ment to participate. Patientswith chronic obstructive pulmonary disease, unstable angina, acute decompensated heart failure, acute pericarditis or myocarditis, complex arrhythmias, uncontrolled hypertension, severe orthopedic or neurological disorders, uncon- trolled diabetes, and labyrinthitis were excluded.
was indicated by inability of the patient to achieve at least 80% of the predetermined inspiratory pressure during three consecutive breaths. Intercostal and limb muscle blood volume and oxygenation were continuously recorded by near-infrared spectroscopy (NIRS; Oxiplex TS, ISS, USA) using transducers having a fixed 3-cm distance between the light source and detector. The transducers were placed over the seventh left intercostal space as described by Vogiatzis et al. (9), between the anterior axillary line and the midclavicular line beyond the insertion of serratus anterior, and on the ventral surface of the left forearm. NIRS estimates local microvascular concentration of oxyhemoglobin+ +myoglobin (oxy-Hb) and deoxyhemoglo- bin+ +myoglobin by measuring light absorbency at 850 and 760 nm, respectively. Muscle blood volume was estimated by total hemoglobin/myoglobin and muscle oxygenation by
Materials and Methods: A prospective study was done inpatientswith bladder outlet obstruction undergoing transurethral prostate resection. Patients were divided into 33 with obstruction and 14 in acute urinary retention. A total of 15 males without obstruction undergoing transurethral prostate resection for bladder tumor formed the control group. Detrusor specimens were obtained during transurethral prostate resection. Detrusor muscle cell diameter was measured using light microscopy and a semiautomatic image analysis system. The connective tissue-to-smooth muscle ratio was automatically determined with computer assisted image analysis. Symptoms and urodynamic assessment were performed preoperatively and 6 months postoperatively.
The heart showed dilation of the 4 chambers and bi- ventricular cavitary thrombosis (fig. 2). The left ventricular wall was not thickened (7mm). Microscopically, narrowing of the myocardial fibers occurred as well as scarce foci of fibrosis (fig. 3) and a mononuclear inflammatory cell infiltra- tion, with no aggression to the cardiomyocytes. Despite fo- cal disarrangement of myocardial fibers, the amount was not enough to characterize hypertrophic cardiomyopathy. Thromboembolism with recent hemorrhagic infarct in the lower lobe of the left lung and in the middle and lower lobes of the right lung (fig. 4) was observed. Death resulted from
ABSTRACT - Objective: To examine auditory cognitive evoked potentials (P300 potentials) and neuropsy- chological dysfunction inpatientswith Duchenne muscular dystrophy (DMD). Method: P300 potentials and neuropsychological test results were obtained from 16 healthy control boys and 20 DMD patients. Full Intelligence Quotients (IQ) were estimated for patients and control group. Mean age was 9.5 years in the DMD patient group, and 10 years in the control group (p>0.05). Results: The mean IQ values were 64.35 in the DMD patients and 82.68 in the control group (p=0.01). Mean P300 values were 347.6 in the DMD group and 337.4 in the control group (p=0.14). There was no significant correlation between parameters in each group. Conclusion: DMD patients showed a poor performance as evaluated by P300 potential compared to the control group, although the difference was not statistically significant. Systematic alter- ations in neuropsychological test results were found, the differences paralleling those detected in IQ. KEY WORDS: P300, Duchenne muscular dystrophy, neuropsychologic dysfunction.
the distribution of nAChRs and terminal axon along the muscle fiber with immunostaining using α-bungarotoxin associated with rhodamine and anti-neurofilament, respectively. After the immunostaining, the analysis was performed using laser scanning confocal microscope and the area of nAChRs was measured using the Image J software. Our results showed an increase in the mRNA of γ subunits, α, ε, δ and β1 in the AS group and decreased expressionof γ α, β1 and δ in the ASTR group. Only the ε subunit expressionin the group ASTR was more expressed. The expressionof the MRFs, Myogenin and MyoD did not change in the groups studied. The immunostaining of nAChRs revealed that there was no difference in the morphology of the receptors that show a distribution as a continuous branches or pretzel. The area analysis revealed a modulation in the distribution of nAChRs,being high in AS(20 at 30 µm 2 ) and ASTR(31 at 40 µm 2 ) groups. Our study showed changes in the distribution and expressionof nAChRs subunits during heart failure. Aerobic training was beneficial and attenuated nAChRs subunits changes in the neuromuscular junctions. This protocol could be critical to the intervention of future therapies for life quality improvement inpatientswith heart failure.
were pig iron, steel scrap, Fe-75%Si, Fe-80%V and Fe-80%Nb and Fe-80%Mn-8%N. The metal was preheated at 1500 o C and then poured into sand mould to get normalized Y-shaped castings. Spheroidizing and inoculation process was made in gating system using Fe-Si-5%Mg alloy, and Foundrysil inoculant containing 0,5 % Ce in amounts 1,0 % and 0,8 % with relation to bath weight, respectively. One of the purpose of our research is to develop a method of nanoparticles synthesis in ferritic matrix of ductile cast iron, which are supposed to increase its strength without affecting notably its ductility.