Oxidised Albumin Levels in Plasma and Skeletal Muscle as Biomarkers of Disease Progression and Treatment Efficacy in Dystrophic Mice.

Redox modifications to the plasma protein albumin have the potential to be used as biomarkers of disease progression and treatment efficacy in pathologies associated with inflammation and oxidative stress. One such pathology is Duchenne muscular dystrophy (DMD), a fatal childhood disease characterised by severe muscle wasting. We have previously shown in the mouse model of DMD that plasma albumin thiol oxidation is increased; therefore, the first aim of this paper was to establish that albumin thiol oxidation in plasma reflects levels within muscle tissue.

Antenatal creatine supplementation reduces persistent fetal lung inflammation and oxidative stress in an ovine model of chorioamnionitis.

Chorioamnionitis is a common antecedent of preterm birth and induces inflammation and oxidative stress in the fetal lungs. Reducing inflammation and oxidative stress in the fetal lungs may improve respiratory outcomes in preterm infants. Creatine is an organic acid with known anti-inflammatory and antioxidant properties.

Dimethyl fumarate modulates the dystrophic disease program following short-term treatment.

New medicines are urgently required to treat the fatal neuromuscular disease Duchenne muscular dystrophy (DMD). Dimethyl fumarate (DMF) is a potent immunomodulatory small molecule nuclear erythroid 2-related factor 2 activator with current clinical utility in the treatment of multiple sclerosis and psoriasis that could be effective for DMD and rapidly translatable. Here, we tested 2 weeks of daily 100 mg/kg DMF versus 5 mg/kg standard-care prednisone (PRED) treatment in juvenile mdx mice with early symptomatic DMD.

Evaluating Glyph Design for Showing Large-Magnitude-Range Quantum Spins.

We present experimental results to explore a form of bivariate glyphs for representing large-magnitude-range vectors. The glyphs meet two conditions: (1) two visual dimensions are separable; and (2) one of the two visual dimensions uses a categorical representation (e.g.

Muscle Pathology in Dystrophic Rats and Zebrafish Is Unresponsive to Taurine Treatment, Compared to the Mouse Model for Duchenne Muscular Dystrophy.

Inflammation and oxidative stress are strongly implicated in the pathology of Duchenne muscular dystrophy (DMD), and the sulphur-containing amino acid taurine ameliorates both and decreases dystropathology in the mouse model for DMD. We therefore further tested taurine as a therapy using dystrophic DMD rats and zebrafish models for DMD that have a more severe dystropathology. However, taurine treatment had little effect on the indices of dystropathology in both these models.

The location of protein oxidation in dystrophic skeletal muscle from the mdx mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe childhood disease characterised by progressive muscle wasting caused by widespread myofibre necrosis. Implicated in the pathology of DMD is oxidative stress, caused by excessive generation of reactive oxygen and nitrogen species (RONS). One consequence of RONS exposure is post-translational oxidative modifications to proteins, which can cause loss of protein function.

A Blood Biomarker for Duchenne Muscular Dystrophy Shows That Oxidation State of Albumin Correlates with Protein Oxidation and Damage in Mdx Muscle.

Duchenne muscular dystrophy (DMD) is a severe X-linked muscle wasting disease with no cure. While the precise mechanisms of progressive dystropathology remain unclear, oxidative stress caused by excessive generation of oxidants is strongly implicated. Blood biomarkers that could track oxidant levels in tissues would be valuable to measure the effectiveness of clinical treatments for DMD; our research has focused on developing such biomarkers.

Oxidative damage to urinary proteins from the GRMD dog and mdx mouse as biomarkers of dystropathology in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal, X-chromosome linked muscle-wasting disease affecting about 1 in 3500-6000 boys worldwide. Myofibre necrosis and subsequent loss of muscle mass are due to several molecular sequelae, such as inflammation and oxidative stress. We have recently shown increased neutrophils, highly reactive oxidant hypochlorous acid (HOCl) generation by myeloperoxidase (MPO), and associated oxidative stress in muscle from the GRMD dog and mdx mouse models for DMD.

Investigation of the effect of taurine supplementation on muscle taurine content in the mdx mouse model of Duchenne muscular dystrophy using chemically specific synchrotron imaging.

Duchenne muscular dystrophy (DMD) is a lethal genetic muscle wasting disorder, which currently has no cure. Supplementation with the drug taurine has been shown to offer therapeutic benefit in the mdx model for DMD, however the mechanism by which taurine protects dystrophic muscle is not fully understood. Mdx muscle is deficient in taurine, however it is not known if this deficiency occurs in the extracellular space, in other cells present in the tissue (such as immune cells) or in the myofibre itself.

Biomarkers for Duchenne muscular dystrophy: myonecrosis, inflammation and oxidative stress.

Duchenne muscular dystrophy (DMD) is a lethal, X-linked disease that causes severe loss of muscle mass and function in young children. Promising therapies for DMD are being developed, but the long lead times required when using clinical outcome measures are hindering progress. This progress would be facilitated by robust molecular biomarkers in biofluids, such as blood and urine, which could be used to monitor disease progression and severity, as well as to determine optimal drug dosing before a full clinical trial.

A Critical Comparison of 3D Experiments and Simulations of Tricalcium Silicate Hydration.

Advances in nano-computed X-ray tomography (nCT), nano X-ray fluorescence spectrometry (nXRF), and high-performance computing have enabled the first direct comparison between observations of three-dimensional nanoscale microstructure evolution during cement hydration and computer simulations of the same microstructure using HydratiCA. nCT observations of a collection of triclinic tricalcium silicate (CaSiO) particles reacting in a calcium hydroxide solution are reported and compared to simulations that duplicate, as nearly as possible, the thermal and chemical conditions of those experiments. Particular points of comparison are the time dependence of the solid phase volume fractions, spatial distributions, and morphologies.

Expression patterns of regulatory RNAs, including lncRNAs and tRNAs, during postnatal growth of normal and dystrophic (mdx) mouse muscles, and their response to taurine treatment.

Post-natal skeletal muscle growth in mice is very rapid and involves complex changes in many cells types over the first 6 weeks of life. The acute onset of dystropathology also occurs around 3 weeks of age in the mdx mouse model of the human disease Duchenne Muscular Dystrophy (DMD). This study investigated (i) alterations in expression patterns of regulatory non-coding RNAs (ncRNAs) in vivo, including miRNAs, lncRNAs and tRNAs, during early growth of skeletal muscles in normal control C57Bl/10Scsn (C57) compared with dystrophic mdx mice from 2 to 6 weeks of postnatal age, and revealed inherent differences in vivo for levels of 3 ncRNAs between C57 and mdx muscles before the onset of dystropathology.

Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.

Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disease manifested in young boys, for which there is no current cure. We have shown that the amino acid taurine is safe and effective at preventing dystropathology in the mdx mouse model for DMD. This study aimed to establish if treating growing mdx mice with a higher dose of taurine was more effective at improving strength and reducing inflammation and oxidative stress.

Pre-clinical evaluation of N-acetylcysteine reveals side effects in the mdx mouse model of Duchenne muscular dystrophy.

Key Points: Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation and oxidative stress. The antioxidant N-acetylcysteine (NAC) has been proposed as a therapeutic intervention for DMD boys, but potential adverse effects of NAC have not been widely investigated. We used young (6 weeks old) growing mdx mice to investigate the capacity of NAC supplementation (2% in drinking water for 6 weeks) to improve dystrophic muscle function and to explore broader systemic effects of NAC treatment.

Resistance wheel exercise from mid-life has minimal effect on sciatic nerves from old mice in which sarcopenia was prevented.

The ability of resistance exercise, initiated from mid-life, to prevent age-related changes in old sciatic nerves, was investigated in male and female C57BL/6J mice. Aging is associated with cellular changes in old sciatic nerves and also loss of skeletal muscle mass and function (sarcopenia). Mature adult mice aged 15 months (M) were subjected to increasing voluntary resistance wheel exercise (RWE) over a period of 8 M until 23 M of age.

Validation of SplitVectors Encoding for Quantitative Visualization of Large-Magnitude-Range Vector Fields.

We designed and evaluated SplitVectors, a new vector field display approach to help scientists perform new discrimination tasks on large-magnitude-range scientific data shown in three-dimensional (3D) visualization environments. SplitVectors uses scientific notation to display vector magnitude, thus improving legibility. We present an empirical study comparing the SplitVectors approach with three other approaches - direct linear representation, logarithmic, and text display commonly used in scientific visualizations.

Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice.

Background: There is much interest in the capacity of resistance exercise to prevent the age-related loss of skeletal muscle mass and function, known as sarcopenia. This study investigates the molecular basis underlying the benefits of resistance exercise in aging C57BL/6J mice of both sexes.

Results: This study is the first to demonstrate that long-term (34 weeks) voluntary resistance wheel exercise (RWE) initiated at middle age, from 15 months, prevents sarcopenia in selected hindlimb muscles and causes hypertrophy in soleus, by 23 months of age in both male and female C57BL/6J mice.

Levels of inflammation and oxidative stress, and a role for taurine in dystropathology of the Golden Retriever Muscular Dystrophy dog model for Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is a fatal skeletal muscle wasting disease presenting with excessive myofibre necrosis and increased inflammation and oxidative stress. In the mdx mouse model of DMD, homeostasis of the amino acid taurine is altered, and taurine administration drastically decreases muscle necrosis, dystropathology, inflammation and protein thiol oxidation. Since the severe pathology of the Golden Retriever Muscular Dystrophy (GRMD) dog model more closely resembles the human DMD condition, we aimed to assess the generation of oxidants by inflammatory cells and taurine metabolism in this species.

Increased taurine in pre-weaned juvenile mdx mice greatly reduces the acute onset of myofibre necrosis and dystropathology and prevents inflammation.

Background: The mdx mouse model for the fatal muscle wasting disease Duchenne Muscular Dystrophy (DMD) shows a very mild pathology once growth has ceased, with low levels of myofibre necrosis in adults. However, from about 3 weeks of post-natal age, muscles of juvenile mdx mice undergo an acute bout of severe necrosis and inflammation: this subsequently decreases and stabilises to lower adult levels by about 6 weeks of age. Prior to the onset of this severe dystropathology, we have shown that mdx mice are deficient in the amino acid taurine (potentially due to weaning), and we propose that this exacerbates myofibre necrosis and inflammation in juvenile mdx mice.

Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy.

Key Points: Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis. Cysteine precursor antioxidants such as N-acetyl cysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine. We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress.

Taurine deficiency, synthesis and transport in the mdx mouse model for Duchenne Muscular Dystrophy.

The amino acid taurine is essential for the function of skeletal muscle and administration is proposed as a treatment for Duchenne Muscular Dystrophy (DMD). Taurine homeostasis is dependent on multiple processes including absorption of taurine from food, endogenous synthesis from cysteine and reabsorption in the kidney. This study investigates the cause of reported taurine deficiency in the dystrophic mdx mouse model of DMD.

Three-dimensional optical coherence micro-elastography of skeletal muscle tissue.

In many muscle pathologies, impairment of skeletal muscle function is closely linked to changes in the mechanical properties of the muscle constituents. Optical coherence micro-elastography (OCME) uses optical coherence tomography (OCT) imaging of tissue under a quasi-static, compressive mechanical load to map variations in tissue mechanical properties on the micro-scale. We present the first study of OCME on skeletal muscle tissue.

Lipid accumulation in dysferlin-deficient muscles.

Dysferlin is a membrane associated protein involved in vesicle trafficking and fusion. Defects in dysferlin result in limb-girdle muscular dystrophy type 2B and Miyoshi myopathy in humans and myopathy in A/J(dys-/-) and BLAJ mice, but the pathomechanism of the myopathy is not understood. Oil Red O staining showed many lipid droplets within the psoas and quadriceps muscles of dysferlin-deficient A/J(dys-/-) mice aged 8 and 12 months, and lipid droplets were also conspicuous within human myofibers from patients with dysferlinopathy (but not other myopathies).