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Description
This study examines the effect of exercise therapy on a stationary bike on cognitive function, specifically inhibition and set-switching, in adolescents with Down syndrome. 44 participants were randomly divided between the voluntary cycling therapy group (VCT) (i.e., self-selected cadence), assisted cycling therapy group (ACT) (i.e., 30% faster than self-selected cadence accomplished by a motor), and a control group (NC) in which the participants did not undergo any exercise therapy. Both cycling groups rode a stationary bicycle, for 30 minutes, three times a week, for eight-weeks. At the beginning (i.e., pretest) and end (i.e., posttest) of the eight-week session the participants completed tasks to evaluate their cognitive function. They completed three trials of the card sort test (i.e., set-switching) and three trials of the knock-tap test (i.e, inhibition) before and after eight-weeks of cycling therapy. The scores of these tests were analyzed using one-way ANOVA between groups and paired samples t-tests. The results showed that after eight-weeks of cycling therapy the participants in the VCT group performed worse in the knock-tap test, but improved in two trials of the card sort test. The results also showed that the participants in the ACT group performed worse after eight-weeks of exercise therapy in one trial of the card sort test. No significant changes were seen for the control group. Due to the fact that on average the participants in the VCT group cycled with a higher heart rate, our results suggest exercise that significantly elevates heart rate can improve cognitive function, specifically set-switching, in adolescents with Down syndrome.
ContributorsBenson, Alicia Meigh (Author) / Ringenbach, Shannon (Thesis director) / Amazeen, Eric (Committee member) / Maraj, Brian (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Doxorubicin (DOX) is a cardiotoxic, anthracycline-based, anti-neoplastic agent that causes pathological cardiac remodeling due to altered protein expression associated with cardiotoxicity. DOX cardiotoxicity causes increased Akt phosphorylation, blunted AMPK phosphorylation and upregulated mTOR phosphorylation. Akt is activated by cellular stress and damage. AMPK is activated by increases in AMP and ADP concentrations and decreased ATP concentration. mTOR is active in cellular growth and remodeling. These proteins are cellular kinases with cascades that are influenced by one another. Exercise preconditioning may diminish the cardiotoxic effects on these proteins. Female, Ovariectomized Sprague-Dawley rats (N=33) were randomized to: Exercise+DOX (EX+DOX, n=9); Exercise+Vehicle (EX+VEH, n=8); Sedentary+DOX (SED+DOX, n=8); and Sedentary+Vehicle (SED+VEH, n=8) groups. DOX (4mg/kg) or VEH (saline) intraperitoneal injections were administered bi-weekly (cumulative dose of 12mg/kg). VEH animals received body weight matched volumes of saline based on dosing in animals receiving DOX. Exercise (EX) animals underwent high intensity (85-95% VO2 peak) interval training (HIIT) (4x4 min bouts) separated by low intensity (50-60% VO2max) intervals (2 min bouts) 5 days per week. Exercise began 1 week prior to the first injection and was continued throughout the study. Rats were euthanized 5 days after the last injection. Left ventricular tissue was isolated, processed into lysate and used for western blot analyses [2x2 ANOVA; (α=0.05)]. DOX induced significant phosphorylation of Akt and mTOR (p=0.035; p=0.032) only in SED+DOX rats, but unchanged in EX+DOX rats. No significant differences (p=0.374) in AMPK phosphorylation were observed between groups. Exercise Preconditioning prevents some DOX-induced changes in the cardiac mTOR signaling pathway implicated in pathological remodeling.
ContributorsPanknin, Timothy M (Author) / Angadi, Siddhartha (Thesis director) / Sweazea, Karen (Committee member) / Dickinson, Jared (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.
ContributorsO'Neill, Liam Martin (Author) / Sweazea, Karen (Thesis director) / Angadi, Siddhartha (Committee member) / Dickinson, Jared (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Estimates indicate that in the United States 1 in 8 women will develop breast cancer in their lifetime. Improved cancer screenings, early detection, and targeted treatments have increased breast cancer survival rates. However, breast cancer patients treated with chemotherapy are at an increased risk for cardiovascular disease, functional impairments, and loss of cardiorespiratory fitness. These negative outcomes have implications for early morbidity and mortality. The purpose of this thesis was to test the hypothesis that high-intensity exercise preconditioning (exercise commenced prior to initiating chemotherapy and continued throughout treatment cycles) preserves health-related outcomes in breast cancer patients treated with anthracycline-containing chemotherapy. Here, we present a subset of preliminary data from an ongoing trial (NCT02842658) that is focused on VO2peak and skeletal muscle outcomes from the first 10 participants that have enrolled in the trial. Breast cancer patients (N=10; 50 ± 11 y; 168 ± 4 cm; 92 ± 37 kg; 32.3 ± 12.3 kg/m2) scheduled to receive anthracycline-containing chemotherapy were randomly assigned to one of two interventions: 1) exercise preconditioning, (3 days per week of supervised exercise throughout treatment) or 2) standard of care (attention-control). Pre-testing occurred 1-2 week prior to chemotherapy. The interventions were initiated 1 week prior to chemotherapy and continued throughout anthracycline treatment. Post-testing occurred 3-7 days following the last anthracycline treatment. VO2peak (L/min) was reduced by 16% in the control group (P < 0.05), whereas VO2peak was preserved in the exercise preconditioning group. Trends for greater preservation and/or improvement in the exercise preconditioning group were also observed for lean body mass and peak heart rate. Hand grip strength was not changed in either group (P > 0.05). Both groups demonstrated an increase in ultrasound-derived echogenicity measures of the vastus lateralis (P < 0.05), indicating changes in the composition of the skeletal muscle during treatment. These preliminary data highlight that exercise preconditioning may serve as a strategy to preserve cardiorespiratory fitness and perhaps lean mass during anthracycline treatment of breast cancer. There remains a need for larger, definitive clinical trials to identify strategies to prevent the array of chemotherapy-induced toxicities that are observed in breast cancer patients treated with anthracyclines.
ContributorsCasey, Kathleen (Author) / Angadi, Siddhartha (Thesis director) / Gaesser, Glenn (Committee member) / Dickinson, Jared (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05