Project description:Exercise therapy and lower extremity revascularization both improve walking performance in symptomatic patients with peripheral artery disease. The combination of therapies provides greater benefit than either alone and may reduce the need for subsequent revascularization procedures, but further trials with longer follow-up are needed for the outcome of subsequent revascularization.
Project description:The purpose of this study was to determine the effect of an exercise intervention (EX) on muscular strength, cardiorespiratory fitness (CRF), and oxidative stress in cancer survivors compared with a nonexercising cancer control group (CON).Fifteen cancer patients and seven age-matched individuals with no history of cancer (NC) participated in this study. A blood draw and assessments of muscular strength and CRF were administered to cancer survivors within 6 wk of completing radiation or chemotherapy, and again 10 wk later. Eight cancer patients completed a 10-wk supervised exercise intervention, whereas seven continued standard care. Baseline oxidative stress was compared between cancer patients and the NC group. Changes in plasma protein carbonyls, 8-OHdG, and Trolox equivalent antioxidant capacity were compared between groups using repeated-measures ANOVA, and correlations between fitness and oxidative stress changes were evaluated.Baseline antioxidant capacity was significantly lower, and plasma protein carbonyls were significantly higher in cancer patients compared with NC (P = 0.001). EX had a significant increase in antioxidant capacity (P < 0.001) and decrease in protein carbonyls (P = 0.023), whereas CON did not. Improvements in composite arm (41%, P = 0.002) and leg strength (34%, P = 0.008), isometric handgrip strength (11%, P = 0.015), and V˙O2peak (16%, P = 0.018) were significant in EX but not in CON. 8-OHdG changes were significantly correlated with changes in V˙O2peak (r = -0.89, P < 0.001), arm strength (r = -0.67, P = 0.004), and leg strength (r = -0.56, P = 0.019).A whole-body exercise intervention for cancer survivors may be an effective method of concurrently increasing muscular strength, CRF, and antioxidant capacity while decreasing markers of oxidative stress.
Project description:Peripheral arterial disease (PAD) is a common vascular disease that reduces blood flow capacity to the legs of patients. PAD leads to exercise intolerance that can progress in severity to greatly limit mobility, and in advanced cases leads to frank ischemia with pain at rest. It is estimated that 12 to 15 million people in the United States are diagnosed with PAD, with a much larger population that is undiagnosed. The presence of PAD predicts a 50% to 1500% increase in morbidity and mortality, depending on severity. Treatment of patients with PAD is limited to modification of cardiovascular disease risk factors, pharmacological intervention, surgery, and exercise therapy. Extended exercise programs that involve walking approximately five times per week, at a significant intensity that requires frequent rest periods, are most significant. Preclinical studies and virtually all clinical trials demonstrate the benefits of exercise therapy, including improved walking tolerance, modified inflammatory/hemostatic markers, enhanced vasoresponsiveness, adaptations within the limb (angiogenesis, arteriogenesis, and mitochondrial synthesis) that enhance oxygen delivery and metabolic responses, potentially delayed progression of the disease, enhanced quality of life indices, and extended longevity. A synthesis is provided as to how these adaptations can develop in the context of our current state of knowledge and events known to be orchestrated by exercise. The benefits are so compelling that exercise prescription should be an essential option presented to patients with PAD in the absence of contraindications. Obviously, selecting for a lifestyle pattern that includes enhanced physical activity prior to the advance of PAD limitations is the most desirable and beneficial.
Project description:Maternal separation (MS) in mice results in behavioral deficits and gut microbiota dysbiosis that all persist into adulthood. Limosilactobacillus reuteri DSM 17938 modulates gut microbiota, alters systemic metabolites, and facilitates immune regulation. To assess the effect of DSM 17938 on biochemical and behavioural stress-associated changes, newborn mice were exposed to unpredictable MS (MSU) daily from day 7 to day 20 of life, with intragastric administration of DSM 17938 or PBS as control. Body weight, brain levels of cholecystokinin (CCK), glial fibrillary acidic protein (GFAP), corticosterone, and stool microbiota were assessed at day 21. Behaviour tests including Y-maze (YMT), Tail Suspension (TST), and Open Field (OFT) were evaluated in adult mice. MSU resulted in a decrease in early postnatal growth, which improved with DSM 17938. Reduced CCK and increased corticosterone brain levels due to MSU were reversed by DSM 17938. GFAP levels increased with MSU, indicating that the decreased brain CCK was likely secondary to neuronal damage. DSM 17938 treated offspring demonstrated better cognitive function and less anxious behaviour in adult behaviour tests. DSM 17398 corrected stress related gut microbial dysbiosis. In conclusion, early life modulation of gut microbiota by DSM 17938 had beneficial effects on stress-associated physical and biochemical changes caused by MS in neonates and on subsequent adult behaviour.
Project description:We tested the hypothesis that exercise training would attenuate metabolic impairment in a model of severe cancer cachexia and we explored the mechanisms underlying these effects.
Project description:PurposeOur aim was to determine whether pharmacologic vasodilation is an alternative to exercise stress during limb perfusion imaging for peripheral artery disease (PAD).MethodsQuantitative contrast-enhanced ultrasound (CEU) perfusion imaging of the bilateral anterior thigh and calf was performed in nine control subjects and nine patients with moderate to severe PAD at rest and during vasodilator stress with dipyridamole. For those who were able, CEU of the calf was then performed during modest plantar flexion exercise (20 watts). CEU time-intensity data were analyzed to quantify microvascular blood flow (MBF) and its parametric components of microvascular blood volume and flux rate.ResultsThigh and calf skeletal muscle MBF at rest was similar between control and PAD patients. During dipyridamole, MBF increased minimally (<twofold) for all groups and there were only nonsignificant trends for a reduction in calf MBF in those with PAD (13.5±6.9, 10.0±4.7, and 8.2±6.1 IU/s, for controls, moderate, and severe PAD, respectively; P=.11). In contrast, MBF during modest planar flexion exercise increased markedly in controls but not PAD patients (87.9±79.9 vs 15.2±12.9 IU/s, P<.05). In three moderate PAD patients restudied after undergoing surgical revascularization, MBF during dipyridamole did not change, whereas exercise MBF increased by an average of sevenfold.ConclusionsResting limb skeletal muscle MBF in patients with moderate to severe PAD is similar to that in normal subjects. However, differences in hyperemic flow during contractile exercise but not during dipyridamole allow evaluation of the degree of flow impairment from PAD and the degree of improvement with revascularization.
Project description:ObjectiveWe tested the hypothesis that exercise training would attenuate metabolic impairment in a model of severe cancer cachexia.MethodsWe used multiple in vivo and in vitro methods to explore the mechanisms underlying the beneficial effects induced by exercise training in tumor-bearing rats.ResultsExercise training improved running capacity, prolonged lifespan, reduced oxidative stress, and normalized muscle mass and contractile function in tumor-bearing rats. An unbiased proteomic screening revealed COP9 signalosome complex subunit 2 (COPS2) as one of the most downregulated proteins in skeletal muscle at the early stage of cancer cachexia. Exercise training normalized muscle COPS2 protein expression in tumor-bearing rats and mice. Lung cancer patients with low endurance capacity had low muscle COPS2 protein expression as compared to age-matched control subjects. To test whether decrease in COPS2 protein levels could aggravate or be an intrinsic compensatory mechanism to protect myotubes from cancer effects, we performed experiments in vitro using primary myotubes. COPS2 knockdown in human myotubes affected multiple cellular pathways, including regulation of actin cytoskeleton. Incubation of cancer-conditioned media in mouse myotubes decreased F-actin expression, which was partially restored by COPS2 knockdown. Direct repeat 4 (DR4) response elements have been shown to positively regulate gene expression. COPS2 overexpression decreased the DR4 activity in mouse myoblasts, and COPS2 knockdown inhibited the effects of cancer-conditioned media on DR4 activity.ConclusionsThese studies demonstrated that exercise training may be an important adjuvant therapy to counteract cancer cachexia and uncovered novel mechanisms involving COPS2 to regulate myotube homeostasis in cancer cachexia.
Project description:Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn.320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1.usual prenatal care (PC) and placebo (maltodextrine). 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 ?g), vitamin A (400 ?g), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg). 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions.Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population.NCT00872365.
Project description:We employed near-infrared optical techniques, diffuse correlation spectroscopy (DCS), and frequency-domain near-infrared spectroscopy (FD-NIRS) to test the hypothesis that supervised exercise training increases skeletal muscle microvascular blood flow and oxygen extraction in patients with peripheral artery disease (PAD) who experience claudication. PAD patients ( n = 64) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 mo of supervised exercise training. Calf muscle blood flow and oxygen extraction were optically monitored before, during, and after performance of a graded treadmill protocol at baseline and at 3 mo in both groups. Additionally, measurements of the ankle-brachial index (ABI) and peak walking time (PWT) to maximal claudication were made during each patient visit. Supervised exercise training was found to increase the maximal calf muscle blood flow and oxygen extraction levels during treadmill exercise by 29% (13%, 50%) and 8% (1%, 12%), respectively [ P < 0.001; median (25th percentile, 75th percentile)]. These improvements across the exercise group population were significantly higher than corresponding changes in the control group ( P < 0.004). Exercise training also increased PWT by 49% (18%, 101%) ( P = 0.01). However, within statistical error, the ABI, resting calf muscle blood flow and oxygen extraction, and the recovery half-time for hemoglobin\myoglobin desaturation following cessation of maximal exercise were not altered by exercise training. The concurrent monitoring of both blood flow and oxygen extraction with the hybrid DCS/FD-NIRS instrument revealed enhanced muscle oxidative metabolism during physical activity from exercise training, which could be an underlying mechanism for the observed improvement in PWT. NEW & NOTEWORTHY We report on noninvasive optical measurements of skeletal muscle blood flow and oxygen extraction dynamics before/during/after treadmill exercise in peripheral artery disease patients who experience claudication. The measurements tracked the effects of a 3-mo supervised exercise training protocol and revealed that supervised exercise training improved patient ability to increase microvascular calf muscle blood flow and oxygen extraction during physical activity.