Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating

Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves; assessing 1) the age-related decline and, 2) the effect of aerobic fitness. We measured skin blood flow (SkBF)(laser-Doppler flowmetry) in young (24±1 yr) and older (64±1 yr) endurance-trained and sedentary men (n=7 per group) at baseline and during 35 min of local skin heating to 42 °C at three forearm sites: 1) untreated; 2) bretylium tosylate (BT), preventing neurotransmitter release from noradrenergic sympathetic nerves; and 3) yohimbine and propranolol (YP), antagonising α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC) (SkBF/mean arterial pressure) and normalized to maximal CVC (%CVCmax) achieved by skin heating to 44 °C. Pharmacological agents were administered using microdialysis. In the young trained, the rapid vasodilator response was reduced at the BT and YP sites (P0.05) but treatment with BT did (P>0.05). Neither BT nor YP treatments affected the rapid vasodilator response in the older sedentary group (P>0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men, and non-adrenergic sympathetic cotransmitters (e.g., neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system

Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design: Sixty patients with stable angina will be recruited and randomised 1: 1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion: This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training

Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Article: Bourke, L., Tew, G.A., Milo, M. et Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. S T U D Y P R O T O C O L Open Access Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina Abstract Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity

High-level production of animal-free recombinant transferrin from saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Animal-free recombinant proteins provide a safe and effective alternative to tissue or serum-derived products for both therapeutic and biomanufacturing applications. While recombinant insulin and albumin already exist to replace their human counterparts in cell culture media, until recently there has been no equivalent for serum transferrin.</p> <p>Results</p> <p>The first microbial system for the high-level secretion of a recombinant transferrin (rTf) has been developed from <it>Saccharomyces cerevisiae </it>strains originally engineered for the commercial production of recombinant human albumin (Novozymes' Recombumin^®USP-NF) and albumin fusion proteins (Novozymes' albufuse^®). A full-length non-N-linked glycosylated rTf was secreted at levels around ten-fold higher than from commonly used laboratory strains. Modification of the yeast 2 μm-based expression vector to allow overexpression of the ER chaperone, protein disulphide isomerase, further increased the secretion of rTf approximately twelve-fold in high cell density fermentation. The rTf produced was functionally equivalent to plasma-derived transferrin.</p> <p>Conclusions</p> <p>A <it>Saccharomyces cerevisiae </it>expression system has enabled the cGMP manufacture of an animal-free rTf for industrial cell culture application without the risk of prion and viral contamination, and provides a high-quality platform for the development of transferrin-based therapeutics.</p

Body image, body dissatisfaction and weight status in south asian children: a cross-sectional study

Background Childhood obesity is a continuing problem in the UK and South Asian children represent a group that are particularly vulnerable to its health consequences. The relationship between body dissatisfaction and obesity is well documented in older children and adults, but is less clear in young children, particularly South Asians. A better understanding of this relationship in young South Asian children will inform the design and delivery of obesity intervention programmes. The aim of this study is to describe body image size perception and dissatisfaction, and their relationship to weight status in primary school aged UK South Asian children. Methods Objective measures of height and weight were undertaken on 574 predominantly South Asian children aged 5-7 (296 boys and 278 girls). BMI z-scores, and weight status (underweight, healthy weight, overweight or obese) were calculated based on the UK 1990 BMI reference charts. Figure rating scales were used to assess perceived body image size (asking children to identify their perceived body size) and dissatisfaction (difference between perceived current and ideal body size). The relationship between these and weight status were examined using multivariate analyses. Results Perceived body image size was positively associated with weight status (partial regression coefficient for overweight/obese vs. non-overweight/obese was 0.63 (95% CI 0.26-0.99) and for BMI z-score was 0.21 (95% CI 0.10-0.31), adjusted for sex, age and ethnicity). Body dissatisfaction was also associated with weight status, with overweight and obese children more likely to select thinner ideal body size than healthy weight children (adjusted partial regression coefficient for overweight/obese vs. non-overweight/obese was 1.47 (95% CI 0.99-1.96) and for BMI z-score was 0.54 (95% CI 0.40-0.67)). Conclusions Awareness of body image size and increasing body dissatisfaction with higher weight status is established at a young age in this population. This needs to be considered when designing interventions to reduce obesity in young children, in terms of both benefits and harms

Search for time-dependent B0s - B0s-bar oscillations using a vertex charge dipole technique

We report a search for B0s - B0s-bar oscillations using a sample of 400,000 hadronic Z0 decays collected by the SLD experiment. The analysis takes advantage of the electron beam polarization as well as information from the hemisphere opposite that of the reconstructed B decay to tag the B production flavor. The excellent resolution provided by the pixel CCD vertex detector is exploited to cleanly reconstruct both B and cascade D decay vertices, and tag the B decay flavor from the charge difference between them. We exclude the following values of the B0s - B0s-bar oscillation frequency: Delta m_s < 4.9 ps-1 and 7.9 < Delta m_s < 10.3 ps-1 at the 95% confidence level.Comment: 18 pages, 3 figures, replaced by version accepted for publication in Phys.Rev.D; results differ slightly from first versio

Interventions to improve exercise behaviour in sedentary people living with and beyond cancer: a systematic review

Background: To systematically review the effects of interventions to improve exercise behaviour in sedentary people living with and beyond cancer. Methods: Only randomised controlled trials (RCTs) that compared an exercise intervention to a usual care comparison in sedentary people with a homogeneous primary cancer diagnosis, over the age of 18 years were eligible. The following electronic databases were searched: Cochrane Central Register of Controlled Trials MEDLINE; EMBASE; AMED; CINAHL; PsycINFO; SportDiscus; PEDro from inception to August 2012. Results: Fourteen trials were included in this review, involving a total of 648 participants. Just six trials incorporated prescriptions that would meet current recommendations for aerobic exercise. However, none of the trials included in this review reported intervention adherence of 75% or more for a set prescription that would meet current aerobic exercise guidelines. Despite uncertainty around adherence in many of the included trials, the interventions caused improvements in aerobic exercise tolerance at 8–12 weeks (SMD=0.73, 95% CI=0.51–0.95) in intervention participants compared with controls. At 6 months, aerobic exercise tolerance is also improved (SMD=0.70, 95% CI=0.45–0.94), although four of the five trials had a high risk of bias; hence, caution is warranted in its interpretation. Conclusion: Expecting the majority of sedentary survivors to achieve the current exercise guidelines is likely to be unrealistic. As with all well-designed exercise programmes, prescriptions should be designed around individual capabilities and frequency, duration and intensity or sets, repetitions, intensity of resistance training should be generated on this basis

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives