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Exercise training improves vascular function and secondary health measures in survivors of pediatric oncology related cerebral insult.

ABSTRACT: Adolescent and young adult (AYA) survivors of pediatric oncology related cerebral insult are vulnerable to numerous treatment-induced deficits that significantly enhance cardiovascular disease risk. Regular exercise improves endothelial function, fitness, body composition and musculoskeletal function which may reduce predisposition for cardiovascular disease. Here we assessed the feasibility and effectiveness of a 24-week exercise intervention on cardiovascular, physical and metabolic outcomes in this population. Thirteen survivors (6 male, 7 female; median age 19 y (range 16-23 y) were recruited to participate in a 48-week study consisting of a 24-week control period (regular care) followed by a 24-week exercise intervention. Outcome measures were collected at entry (week 0) and following regular care (24-week) and exercise (48-week). Assessed variables included endothelial function (flow mediated dilation, FMD), blood pressure, heart rate (HR), aerobic capacity, anthropometry, body composition, muscular strength (3 repetition maximum testing), muscular endurance (repetitions/min) and physical activity levels (accelerometry). Compared to baseline, delta diameter (p = 0.008) and FMD (p = 0.029) of the brachial artery increased following exercise. Bicep-curl strength also increased following exercise compared to baseline (p = 0.019), while submaximal (6 min mark) measures of ventilation (p = 0.012), rating of perceived exertion (p = 0.012), HR (p = 0.001), absolute (p = 0.000) and relative (p = 0.000) aerobic capacity decreased. Breaks in sedentary time increased (p = 0.043) following exercise compared to regular care. Although the sample was small and heterogeneous, this study demonstrates that exercise is achievable and has positive effects on vascular function, submaximal fitness, local strength and physical activity in a population of AYA survivors of pediatric oncology related cerebral insult.

SUBMITTER: Long TM

PROVIDER: S-EPMC6084859 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Exercise training improves vascular function and secondary health measures in survivors of pediatric oncology related cerebral insult.

Long Treya M TM Rath Shoshana R SR Wallman Karen E KE Howie Erin K EK Straker Leon M LM Bullock Andrew A Walwyn Thomas S TS Gottardo Nicholas G NG Cole Catherine H CH Choong Catherine S CS Naylor Louise H LH

PloS one 20180809 8

Adolescent and young adult (AYA) survivors of pediatric oncology related cerebral insult are vulnerable to numerous treatment-induced deficits that significantly enhance cardiovascular disease risk. Regular exercise improves endothelial function, fitness, body composition and musculoskeletal function which may reduce predisposition for cardiovascular disease. Here we assessed the feasibility and effectiveness of a 24-week exercise intervention on cardiovascular, physical and metabolic outcomes i ...[more]

PMID: 30092052

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Project description:Key pointsObesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells.AbstractAlthough previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti-inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic specific genes, including VEGFR-3 and Prox1. Taken together, our findings suggest that obesity impairs lymphatic function via multiple mechanisms and that these pathological changes can be reversed, in part, with aerobic exercise, independent of weight loss. In addition, our study shows that obesity-induced lymphatic endothelial cell gene expression changes are reversible with behavioural modifications.

Project description:BackgroundPhysical activity may attenuate age-related cognitive decline by improving cerebrovascular function. The aim of this study was therefore to investigate effects of aerobic exercise training on cerebral blood flow (CBF), which is a sensitive physiological marker of cerebrovascular function, in sedentary older men.MethodsSeventeen apparently healthy men, aged 60-70 years and with a BMI between 25 and 35 kg/m2, were included in a randomized, controlled cross-over trial. Study participants were randomly allocated to a fully-supervised, progressive, aerobic exercise training or no-exercise control period for 8 weeks, separated by a 12-week wash-out period. Measurements at the end of each period included aerobic fitness evaluated using peak oxygen consumption during incremental exercise (VO2 peak), CBF measured with pseudo-continuous arterial spin labeling magnetic resonance imaging, and post-load glucose responses determined using an oral glucose tolerance test (OGTT). Furthermore, cognitive performance was assessed in the domains of executive function, memory, and psychomotor speed.ResultsVO2 peak significantly increased following aerobic exercise training compared to no-exercise control by 262 ± 236 mL (P < 0.001). CBF was increased by 27% bilaterally in the frontal lobe, particularly the subcallosal and anterior cingulate gyrus (cluster volume: 1008 mm3; P < 0.05), while CBF was reduced by 19% in the right medial temporal lobe, mainly temporal fusiform gyrus (cluster volume: 408 mm3; P < 0.05). Mean post-load glucose concentrations determined using an OGTT decreased by 0.33 ± 0.63 mmol/L (P = 0.049). Furthermore, executive function improved as the latency of response was reduced by 5% (P = 0.034), but no changes were observed in memory or psychomotor speed.ConclusionAerobic exercise training improves regional CBF in sedentary older men. These changes in CBF may underlie exercise-induced beneficial effects on executive function, which could be partly mediated by improvements in glucose metabolism. This clinical trial is registered on ClinicalTrials.gov as NCT03272061.

Project description:INTRODUCTION:Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate-intensity continuous training (MICT) on intestinal metabolism and microbiota in subjects with insulin resistance. METHODS:Twenty-six, sedentary subjects (prediabetic, n = 9; type 2 diabetes, n = 17; age, 49 [SD, 4] yr; body mass index, 30.5 [SD, 3]) were randomized into SIT or MICT. Intestinal insulin-stimulated glucose uptake (GU) and fatty acid uptake (FAU) from circulation were measured using positron emission tomography. Gut microbiota composition was analyzed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit. RESULTS:V?O2peak improved only after SIT (P = 0.01). Both training modes reduced systematic and intestinal inflammatory markers (tumor necrosis factor-?, lipopolysaccharide binding protein) (time P < 0.05). Training modified microbiota profile by increasing Bacteroidetes phylum (time P = 0.03) and decreasing Firmicutes/Bacteroidetes ratio (time P = 0.04). Moreover, there was a decrease in Clostridium genus (time P = 0.04) and Blautia (time P = 0.051). Only MICT decreased jejunal FAU (P = 0.02). Training had no significant effect on intestinal GU. Colonic GU associated positively with Bacteroidetes and inversely with Firmicutes phylum, ratio Firmicutes/Bacteroidetes and Blautia genus. CONCLUSIONS:Intestinal substrate uptake associates with gut microbiota composition and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.

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Exercise training improves vascular function and secondary health measures in survivors of pediatric oncology related cerebral insult.

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Exercise training improves vascular function and secondary health measures in survivors of pediatric oncology related cerebral insult.

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