Browsing by Author "Fortuna, Rafael"

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    Acute and Chronic Effects of Botulinum Toxin Type-A on the structure and Function of the Quadriceps Femoris Muscles of New Zealand White Rabbits
    (2015-10-01) Fortuna, Rafael; Herzog, Walter
    Botulinum toxin type-A (BTX-A) injections have become a common treatment modality for a variety of neuromuscular disorders with the primary aim to relax spastic muscles, for example, in children with cerebral palsy, or following a stroke. Once injected, BTX-A prevents acetylcholine release at the motor nerve endings, thereby producing a dose-dependent muscle paralysis. Despite an exponential growth of patients receiving BTX-A treatment, there has been no systematic evaluation of the effects of the toxin on target and non-target muscles. Therefore, the general purpose of this PhD project was to evaluate muscle mass, strength, and contractile material in injected and contralateral non-injected quadriceps muscles of New Zealand White (NZW) rabbits following single and repeated BTX-A injections. Muscle mass was assessed as the wet weight of muscles following sacrifice, strength was assessed by stimulating the knee extensor muscles via femoral nerve stimulation and quantifying the knee extensor force, the amount of contractile material was quantified histologically. We found that six-monthly BTX-A injections into the quadriceps caused substantial muscle weakness, atrophy, and contractile material loss in the injected and the contralateral non-injected muscles. Adding direct electrical muscle stimulation during the BTX-A injection help to alleviate muscle mass, strength and contractile material loss and the injected and contralateralnon injected muscles, and finally, BTX-A injections had long lasting effects that were not fully recovered at six months following the end of the injection protocol. We concluded from the results of this series of studies that BTX-A treatment resulted in adverse effects on the injected and contralateral non-injected musculature up to six months following the iii injection protocol. Future studies should be aimed at identifying strategies that minimize/prevent adverse effects of BTX-A injections on target and non-target muscles.
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    A clinically relevant BTX-A injection protocol leads to persistent weakness, contractile material loss, and an altered mRNA expression phenotype in rabbit quadriceps muscles
    (Journal of Biomechanics, 2015-07-16) Fortuna, Rafael; Sawatsky, Andrew; Herzog, Walter; Vaz, Marco Aurélio; Hart, David A.
    Botulinum toxin type-A (BTX-A) injections have become a common treatment modality for patients suffering from muscle spasticity. Despite its benefits, BTX-A treatments have been associated with adverse effects on target muscles. Currently, application of BTX-A is largely based on clinical experience, and research quantifying muscle structure following BTX-A treatment has not been performed systematically. The purpose of this study was to evaluate strength, muscle mass, and contractile material six months following a single or repeated (2 and 3) BTX-A injections into the quadriceps femoris of New Zealand white rabbits. Twenty three skeletally mature rabbits were divided into four groups: experimental group rabbits received 1, 2, or 3 injections at intervals of 3 months (1-BTX-A, 2-BTX-A, 3-BTX-A, respectively) while control group rabbits received volume-matched saline injections. Knee extensor strength, quadriceps muscle mass, and quadriceps contractile material of the experimental group rabbits were expressed as a percentage change relative to the control group rabbits. One-way ANOVA was used to determine group differences in outcome measures (α=0.05). Muscle strength and contractile material were significantly reduced in experimental compared to control group rabbits but did not differ between experimental groups. Muscle mass was the same in experimental BTX-A and control group rabbits. We concluded from these results that muscle strength and contractile material do not fully recover within six months of BTX-A treatment.
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    Effect of a prebiotic supplement on knee joint function, gut microbiota, and inflammation in adults with co-morbid obesity and knee osteoarthritis: study protocol for a randomized controlled trial
    (2021-04-07) Fortuna, Rafael; Hart, David A; Sharkey, Keith A; Schachar, Rachel A; Johnston, Kelly; Reimer, Raylene A
    Abstract Background Osteoarthritis (OA) is a chronic and painful condition where the articular cartilage surfaces progressively degenerate, resulting in loss of function and progressive disability. Obesity is a primary risk factor for the development and progression of knee OA, defined as the “metabolic OA” phenotype. Metabolic OA is associated with increased fat deposits that release inflammatory cytokines/adipokines, thereby resulting in systemic inflammation which can contribute to cartilage degeneration. There is currently no cure for OA. Prebiotics are a type of dietary fiber that can positively influence gut microbiota thereby reducing systemic inflammation and offering protection of joint integrity in rodents. However, no human clinical trials have tested the effects of prebiotics in adults with obesity suffering from knee OA. Therefore, the purpose of this double-blind, placebo-controlled, randomized trial is to determine if prebiotic supplementation can, through positive changes in the gut microbiota, improve knee function and physical performance in adults with obesity and knee OA. Methods Adults (n = 60) with co-morbid obesity (BMI > 30 kg/m2) and knee OA (Kellgren-Lawrence grade II–III) will be recruited from the Alberta Hip and Knee Clinic and the Rocky Mountain Health Clinic and surrounding community of Calgary, Canada, and randomized (stratified by sex, BMI, and age) to prebiotic (oligofructose-enriched inulin; 16 g/day) or a calorie-matched placebo (maltodextrin) for 6 months. Anthropometrics, performance-based tests, knee pain, serum inflammatory markers and metabolomics, quality of life, and gut microbiota will be assessed at baseline, 3 months, 6 months (end of prebiotic supplementation), and 3 months following the end of the prebiotic supplementation. Clinical significance There is growing pressure on health care systems for aggressive OA treatment such as total joint replacement. Less aggressive, yet effective, conservative treatment options have the potential to address the growing prevalence of co-morbid obesity and knee OA by delaying the need for joint replacement or ideally preventing its need altogether. The results of this clinical trial will provide the first evidence regarding the efficacy of prebiotic supplementation on knee joint function and pain in adults with obesity and knee OA. If successful, the results may provide a simple, safe, and easy to adhere to intervention to reduce knee joint pain and improve the quality of life of adults with co-morbid knee OA and obesity. Trial registration Clinical Trials.gov NCT04172688 . Registered on 21 November 2019.
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    In vivo Sarcomere Lengths and Sarcomere Elongations Are Not Uniform across an Intact Muscle
    (Frontiers in Physiology, 2016-05) Herzog, Walter; Moo, Eng Kuan; Fortuna, Rafael; Sibole, Scott C.; Abusara, Ziad
    Sarcomere lengths have been a crucial outcome measure for understanding and explaining basic muscle properties and muscle function. Sarcomere lengths for a given muscle are typically measured at a single spot, often in the mid-belly of the muscle, and at a given muscle length. It is then assumed implicitly that the sarcomere length measured at this single spot represents the sarcomere lengths at other locations within the muscle, and force-length, force-velocity, and power-velocity properties of muscles are often implied based on these single sarcomere length measurements. Although, intuitively appealing, this assumption is yet to be supported by systematic evidence. The objective of this study was to measure sarcomere lengths at defined locations along and across an intact muscle, at different muscle lengths. Using second harmonic generation (SHG) imaging technique, sarcomere patterns in passive mouse tibialis anterior (TA) were imaged in a non-contact manner at five selected locations (“proximal,” “distal,” “middle,” “medial,” and “lateral” TA sites) and at three different lengths encompassing the anatomical range of motion of the TA. We showed that sarcomere lengths varied substantially within small regions of the muscle and also for different sites across the entire TA. Also, sarcomere elongations with muscle lengthening were non-uniform across the muscle, with the highest sarcomere stretches occurring near the myotendinous junction. We conclude that muscle mechanics derived from sarcomere length measured from a small region of a muscle may not well-represent the sarcomere length and associated functional properties of the entire muscle.