Department of Physical Therapy Articles

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Browsing Department of Physical Therapy Articles by Author "Allen, Matthew R."

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    Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease
    (Plos, 2016-08-03) Avin, Keith G.; Chen, Neal X.; Organ, Jason M.; Zarse, Chad; O'Neil, Kalisha; Conway, Richard G.; Konrad, Robert J.; Bacallao, Robert L.; Allen, Matthew R.; Moe, Sharon M.; Department of Physical Therapy, School of Health and Rehabilitation Sciences
    Skeletal muscle atrophy and impaired muscle function are associated with lower health-related quality of life, and greater disability and mortality risk in those with chronic kidney disease (CKD). However, the pathogenesis of skeletal dysfunction in CKD is unknown. We used a slow progressing, naturally occurring, CKD rat model (Cy/+ rat) with hormonal abnormalities consistent with clinical presentations of CKD to study skeletal muscle signaling. The CKD rats demonstrated augmented skeletal muscle regeneration with higher activation and differentiation signals in muscle cells (i.e. lower Pax-7; higher MyoD and myogenin RNA expression). However, there was also higher expression of proteolytic markers (Atrogin-1 and MuRF-1) in CKD muscle relative to normal. CKD animals had higher indices of oxidative stress compared to normal, evident by elevated plasma levels of an oxidative stress marker, 8-hydroxy-2' -deoxyguanosine (8-OHdG), increased muscle expression of succinate dehydrogenase (SDH) and Nox4 and altered mitochondria morphology. Furthermore, we show significantly higher serum levels of myostatin and expression of myostatin in skeletal muscle of CKD animals compared to normal. Taken together, these data show aberrant regeneration and proteolytic signaling that is associated with oxidative stress and high levels of myostatin in the setting of CKD. These changes likely play a role in the compromised skeletal muscle function that exists in CKD.
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    Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD)
    (American Society of Nephrology, 2019-10-01) Avin, Keith G.; Allen, Matthew R.; Chen, Neal X.; Srinivasan, Shruthi; O’Neill, Kalisha D.; Troutman, Ashley D.; Mast, Garrison; Swallow, Elizabeth A.; Brown, Mary Beth; Wallace, Joseph M.; Zimmers, Teresa A.; Warden, Stuart J.; Moe, Sharon M.; Physical Therapy, School of Health and Human Sciences
    Background Reduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality. Methods We tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy/+ IU) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2–3 of CKD. We then measured the effects of wheel running on serum biochemistry, tissue weight, voluntary grip strength, maximal aerobic capacity (VO2max), body composition and bone micro-CT and mechanics. Results Wheel running improved serum biochemistry with decreased creatinine, phosphorous, and parathyroid hormone in the rats with CKD. It improved muscle strength, increased time-to-fatigue (for VO2max), reduced cortical porosity and improved bone microarchitecture. The CKD rats with voluntary wheel access also had reduced kidney cystic weight and reduced left ventricular mass index. Conclusions Voluntary wheel running resulted in multiple beneficial systemic effects in rats with CKD and improved their physical function. Studies examining exercise interventions in patients with CKD are warranted.