Oxidative Stress Response to Short Duration Bout of Submaximal Aerobic Exercise in Healthy Young Adults

The purpose of this study was to investigate the oxidative stress response to a short duration bout of submaximal exercise in a cohort of healthy young adults. 15 apparently healthy college age males and females completed a modified Bruce-protocol treadmill test to 75–80% of their heart rate reserve. Blood samples collected immediately before (pre-exercise), immediately after, 30, 60 and 120 minutes post-exercise were assayed for total antioxidant capacity (TAC), superoxide disumutase (SOD), thiobarbituric acid-reactive substances (TBARS), and protein carbonyls (PC). SOD activity was significantly increased from pre-exercise levels at 30 minutes (77%), 60 minutes (33%), and 120 minutes (37%) post-exercise. TAC levels were also significantly increased from pre-exercise levels at 60 minutes (30%) and 120 minutes (33%) post-exercise. There were no significant changes in biomarkers for reactive oxygen/nitrogen species (RONS) mediated damage (TBARS and PC) across all post-exercise time points. In a cohort of healthy young adults, a short duration bout of submaximal aerobic exercise elicited increases in antioxidant activity/concentration, but did not evoke changes in oxidative stress-induced damage. These results may suggest that: (1) short duration bouts of submaximal aerobic exercise are sufficient to induce RONS generation; and (2) the antioxidant defense system is capable of protecting against enhanced RONS production induced by a short duration, submaximal exercise bout in healthy young adults

Oxidative stress response to short duration bout of submaximal aerobic exercise in healthy young adults

The purpose of this study was to investigate the oxidative stress response to a short duration bout of submaximal exercise in a cohort of healthy young adults. 15 apparently healthy college age males and females completed a modified Bruce-protocol treadmill test to 75-80% of their heart rate reserve. Blood samples collected immediately before (pre-exercise), immediately after, 30, 60 and 120 minutes post-exercise were assayed for total antioxidant capacity (TAC), superoxide disumutase (SOD), thiobarbituric acid-reactive substances (TBARS), and protein carbonyls (PC). SOD activity was significantly increased from pre-exercise levels at 30 minutes (77%), 60 minutes (33%), and 120 minutes (37%) post-exercise. TAC levels were also significantly increased from pre-exercise levels at 60 minutes (30%) and 120 minutes (33%) post-exercise. There were no significant changes in biomarkers for reactive oxygen/nitrogen species (RONS) mediated damage (TBARS and PC) across all post-exercise time points. In a cohort of healthy young adults, a short duration bout of submaximal aerobic exercise elicited increases in antioxidant activity/concentration, but did not evoke changes in oxidative stress-induced damage. These results may suggest that: (1) short duration bouts of submaximal aerobic exercise are sufficient to induce RONS generation; and (2) the antioxidant defense system is capable of protecting against enhanced RONS production induced by a short duration, submaximal exercise bout in healthy young adults

Increased Nitric Oxide and Attenuated Diastolic Blood Pressure Variability in African Americans with Mildly Impaired Renal Function

We investigated the relationship between renal function, blood pressure variability (BPV), and nitric oxide (NO) in a group of African Americans with normal or mildly impaired renal function. 24-hour ambulatory blood pressure monitoring was performed, NO measured, and glomerular filtration rate (GFR) calculated in 38 African Americans. Participants were categorized as having normal (GFR > 90 mL/min per 1.73 m2) or mildly impaired (GFR 60–89 mL/min per 1.73 m2) renal function. Diastolic BPV was significantly lower in the mildly impaired renal function group. Regression analyses revealed a significant positive association between GFR and diastolic BPV for the entire study group. Plasma NO levels were significantly higher in the mildly impaired renal function group and negatively correlated with diastolic BPV. In conclusion, diastolic BPV was reduced in African Americans with mildly impaired renal function, which may be the result of increased NO production. These results conflict with previous findings in diseased and nonblack populations and could provide rationale for studying BPV early in the disease state when BP-buffering mechanisms are still preserved

Primitive Erythropoiesis Is Regulated by miR-126 via Nonhematopoietic Vcam-1+ Cells

SummaryPrimitive erythropoiesis defines the onset of hematopoiesis in the yolk sac of the early embryo and is initiated by the emergence of progenitors assayed as colony-forming cells (EryP-CFCs). EryP-CFCs are detected for only a narrow window during embryonic development, suggesting that both their initiation and termination are tightly controlled. Using the embryonic stem differentiation system to model primitive erythropoiesis, we found that miR-126 regulates the termination of EryP-CFC development. Analyses of miR-126 null embryos revealed that this miR also regulates EryP-CFCs in vivo. We identified vascular cell adhesion molecule-1 (Vcam-1) expressed by a mesenchymal cell population as a relevant target of miR-126. Interaction of EryP-CFCs with Vcam-1 accelerated their maturation to ßh1-globin+ and Ter119+ cells through a Src family kinase. These findings uncover a cell nonautonomous regulatory pathway for primitive erythropoiesis that may provide insight into the mechanism(s) controlling the developmental switch from primitive to definitive hematopoiesis

Clinical Activity and Quality of Life Indices Are Valid Across Ulcerative Colitis But Not Crohn’s Disease Phenotypes

Background Clinical activity and quality of life (QOL) indices assess disease activity in Crohn’s disease (CD) and ulcerative colitis (UC). However, a paucity of data exists on the validity of these indices according to disease characteristics. Aims To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics. Methods We used a prospective registry to identify CD and UC patients ≥18 years old with available information on Short Inflammatory Bowel Disease Questionnaire scores (SIBDQ), Harvey–Bradshaw Index (HBI) and simple endoscopic scores for CD (SES-CD), and Simple Clinical Colitis Activity Index (SCCAI) and Mayo endoscopic score for UC. We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics. Results Among 282 CD patients, we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics. Conversely, among 226 UC patients, clinical activity and QOL had good correlation to Mayo endoscopic score (r = 0.55 and −0.56, respectively) with better correlations observed with left-sided versus extensive colitis (r = 0.73 vs. 0.45, p = 0.005) and shorter duration of disease (r = 0.61 vs. 0.37, p = 0.04). Conclusions Our data suggest good correlation between SCCAI and endoscopic disease activity in UC, particularly in left-sided disease. Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes.American Gastroenterological Associatio

Vascular Health in American Football Players: Cardiovascular Risk Increased in Division III Players

Studies report that football players have high blood pressure (BP) and increased cardiovascular risk. There are over 70,000 NCAA football players and 450 Division III schools sponsor football programs, yet limited research exists on vascular health of athletes. This study aimed to compare vascular and cardiovascular health measures between football players and nonathlete controls. Twenty-three athletes and 19 nonathletes participated. Vascular health measures included flow-mediated dilation (FMD) and carotid artery intima-media thickness (IMT). Cardiovascular measures included clinic and 24 hr BP levels, body composition, VO2 max, and fasting glucose/cholesterol levels. Compared to controls, football players had a worse vascular and cardiovascular profile. Football players had thicker carotid artery IMT (0.49 ± 0.06 mm versus 0.46 ± 0.07 mm) and larger brachial artery diameter during FMD (4.3 ± 0.5 mm versus 3.7 ± 0.6 mm), but no difference in percent FMD. Systolic BP was significantly higher in football players at all measurements: resting (128.2 ± 6.4 mmHg versus 122.4 ± 6.8 mmHg), submaximal exercise (150.4 ± 18.8 mmHg versus 137.3 ± 9.5 mmHg), maximal exercise (211.3 ± 25.9 mmHg versus 191.4 ± 19.2 mmHg), and 24-hour BP (124.9 ± 6.3 mmHg versus 109.8 ± 3.7 mmHg). Football players also had higher fasting glucose (91.6 ± 6.5 mg/dL versus 86.6 ± 5.8 mg/dL), lower HDL (36.5±11.2 mg/dL versus 47.1±14.8 mg/dL), and higher body fat percentage (29.2±7.9% versus 23.2±7.0%). Division III collegiate football players remain an understudied population and may be at increased cardiovascular risk

Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant

White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)

Background Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk. Methods To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55–59, 60–64, 65–69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. The ratio of 5-methyl-2’ deoxycytidine [5-mdC] to 2’-deoxyguanine [dG], assuming [dG] = [5-mdC] + [2’-deoxycytidine [dC]] (%5-mdC), was determined by liquid chromatography-electrospray ionization-tandem mass spectrometry, an especially accurate method for assessing total genomic DNA methylation. Results Odds ratio (OR) estimates and 95% confidence intervals (CI) for breast cancer risk adjusted for age at entry, year of entry, and period of DNA extraction, were 1.0 (referent), 0.89 (95% CI, 0.6–1.3), 0.88 (95% CI, 0.6–1.3), and 0.84 (95% CI, 0.6–1.2) for women in the highest compared to lowest quartile levels of %5md-C (p for trend = .39). Effects did not meaningfully vary by time elapsed from WBC collection to diagnosis. Discussion These results do not support the hypothesis that global DNA hypomethylation in WBC DNA is associated with increased breast cancer risk prior to the appearance of clinical disease

Effects of Moderate Aerobic Exercise Training on Vascular Health and Blood Pressure in African Americans

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that African Americans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, the authors reported that 6 months of aerobic exercise improved inflammatory markers, flow-mediated dilation (FMD), and levels of circulating endothelial microparticles (EMPs) in African American adults. This study is a subgroup analysis of the aerobic exercise–induced changes in vascular health and blood pressure (BP) measures, including carotid artery intima-media thickness (IMT), nitroglycerin-mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2 years; 21 women and 5 men) showed improved vascular health but no change in BP. Carotid artery IMT decreased 6.4%, plasma nitric oxide levels increased 76.6%, plasma EMP levels decreased, percentage of FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P<.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in African Americans, even without improvements in BP measures or NMD (ie, smooth muscle function). To our knowledge, this is the first study to report such findings in African Americans

Effects of Moderate Aerobic Exercise Training on Vascular Health and Blood Pressure in African Americans

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that African Americans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, the authors reported that 6 months of aerobic exercise improved inflammatory markers, flow-mediated dilation (FMD), and levels of circulating endothelial microparticles (EMPs) in African American adults. This study is a subgroup analysis of the aerobic exercise–induced changes in vascular health and blood pressure (BP) measures, including carotid artery intima-media thickness (IMT), nitroglycerin-mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2 years; 21 women and 5 men) showed improved vascular health but no change in BP. Carotid artery IMT decreased 6.4%, plasma nitric oxide levels increased 76.6%, plasma EMP levels decreased, percentage of FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P<.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in African Americans, even without improvements in BP measures or NMD (ie, smooth muscle function). To our knowledge, this is the first study to report such findings in African Americans