miRNAs as serum biomarkers for Duchenne muscular dystrophy

Dystrophin absence in Duchenne muscular dystrophy (DMD) causes severe muscle degeneration. We describe that, as consequence of fibre damage, specific muscle-miRNAs are released in to the bloodstream of DMD patients and their levels correlate with the severity of the disease. The same miRNAs are abundant also in the blood of mdx mice and recover to wild-type levels in animals ‘cured’ through exon skipping. Even though creatine kinase (CK) blood levels have been utilized as diagnostic markers of several neuromuscular diseases, including DMD, we demonstrate that they correlate less well with the disease severity. Although the analysis of a larger number of patients should allow to obtain more refined correlations with the different stages of disease progression, we propose that miR-1, miR-133, and miR-206 are new and valuable biomarkers for the diagnosis of DMD and possibly also for monitoring the outcomes of therapeutic interventions in humans. Despite many different DMD therapeutic approaches are now entering clinical trials, a unifying method for assessing the benefit of different treatments is still lacking

Identification of Muscle-Specific MicroRNAs in Serum of Muscular Dystrophy Animal Models: Promising Novel Blood-Based Markers for Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin. Creatine kinase (CK) is generally used as a blood-based biomarker for muscular disease including DMD, but it is not always reliable since it is easily affected by stress to the body, such as exercise. Therefore, more reliable biomarkers of muscular dystrophy have long been desired. MicroRNAs (miRNAs) are small, ∼22 nucleotide, noncoding RNAs which play important roles in the regulation of gene expression at the post-transcriptional level. Recently, it has been reported that miRNAs exist in blood. In this study, we hypothesized that the expression levels of specific serum circulating miRNAs may be useful to monitor the pathological progression of muscular diseases, and therefore explored the possibility of these miRNAs as new biomarkers for muscular diseases. To confirm this hypothesis, we quantified the expression levels of miRNAs in serum of the dystrophin-deficient muscular dystrophy mouse model, mdx, and the canine X-linked muscular dystrophy in Japan dog model (CXMDJ), by real-time PCR. We found that the serum levels of several muscle-specific miRNAs (miR-1, miR-133a and miR-206) are increased in both mdx and CXMDJ. Interestingly, unlike CK levels, expression levels of these miRNAs in mdx serum are little influenced by exercise using treadmill. These results suggest that serum miRNAs are useful and reliable biomarkers for muscular dystrophy

A model of open-loop control of equilibrium position and stiffness of the human elbow joint

According to the equilibrium point theory, the control of posture and movement involves the setting of equilibrium joint positions (EP) and the independent modulation of stiffness. One model of EP control, the α-model, posits that stable EPs and stiffness are set open-loop, i.e. without the aid of feedback. The purpose of the present study was to explore for the elbow joint the range over which stable EPs can be set open-loop and to investigate the effect of co-contraction on intrinsic low-frequency elbow joint stiffness (

Actions of Calcium on Smooth Muscle a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72185/1/j.1749-6632.1988.tb33358.x.pd

Cardiac biomarkers of acute coronary syndrome: from history to high-sensitivity cardiac troponin

The role of cardiac troponins as diagnostic biomarkers of myocardial injury in the context of acute coronary syndrome (ACS) is well established. Since the initial 1st-generation assays, 5th-generation high-sensitivity cardiac troponin (hs-cTn) assays have been developed, and are now widely used. However, its clinical adoption preceded guidelines and even best practice evidence. This review summarizes the history of cardiac biomarkers with particular emphasis on hs-cTn. We aim to provide insights into using hs-cTn as a quantitative marker of cardiomyocyte injury to help in the differential diagnosis of coronary versus non-coronary cardiac diseases. We also review the recent evidence and guidelines of using hs-cTn in suspected ACS

Effects of fatigue of plantarflexors on control and performance in vertical jumping

INTRODUCTION: We investigated the effects of a mismatch between control and musculoskeletal properties on performance in vertical jumping. METHODS: Six subjects performed maximum-effort vertical squat jumps before (REF) and after the plantarflexors of the right leg had been fatigued (FAT) while kinematic data, ground reaction forces, and EMG of leg muscles were collected. Inverse dynamics was used to calculate the net work at joints, and EMG was rectified and smoothed to obtain the smoothed rectified EMG (SREMG). The jumps of the subjects were also simulated with a musculoskeletal model comprising seven body segments and 12 Hill-type muscles, and having as only input muscle stimulation. RESULTS: Jump height was approximately 6 cm less in FAT jumps than in REF jumps. In FAT jumps, peak SREMG level was reduced by more than 35% in the right plantarflexors and by approximately 20% in the right hamstrings but not in any other muscles. In FAT jumps, the net joint work was reduced not only at the right ankle (by 70%) but also at the right hip (by 40%). Because the right hip was not spanned by fatigued muscles and the reduction in SREMG of the right hamstrings was relatively small, this indicated that the reduction in performance was partly due to a mismatch between control and musculoskeletal properties. The differences between REF and FAT jumps of the subjects were confirmed and explained by the simulation model. Reoptimization of control for the FAT model caused performance to be partly restored by approximately 2.5 cm. CONCLUSION: The reduction in performance in FAT jumps was partly due to a mismatch between control and musculoskeletal properties. © 2011 The American College of Sports Medicine

Effects of hypoxia on the distribution of calcium in arterial smooth muscle cells of rats and swine

Exposure to hypoxia caused an increase in the hematocrit and right heart weight of experimental rats, but did not affect calcium-45 uptake by pulmonary arterial smooth muscle cells. However, autoradiographic studies showed that hypoxia apparently caused a shift of 45-Ca from primarily extracellular sites in arteries of control rats to intracellular sites in tissues of hypertensive rats. Cytochemical studies of calcium distributions in pulmonary arterial smooth muscle cells support the autoradiographic data and show that in both rats and swine the majority of pyroantimonate granules occur extracellularly in control tissues. In contrast, hypoxic tissues displayed a greatly reduced number of granules in extracellular sites and an increase in the amount of precipitate in intracellular sites. In pulmonary arterial smooth muscle cells from hypoxic rats most of the precipitate was associated with the caveolae intracellulares, while in corresponding cells from hypoxic swine the majority of the pyroantimonate granules were localized to the sarcoplasmic reticulum. Hypoxia may produce pulmonary hypertension by interfering with the ability of the arterial smooth muscle cells to maintain transmembrane ionic gradients, thus producing an effective increase in cytoplasmic calcium levels. The increased calcium may then activate the contractile apparatus to produce a sustained vasoconstriction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47664/1/441_2004_Article_BF00223235.pd