A pilot randomised controlled trial of a periodised resistance training and protein supplementation intervention in prostate cancer survivors on androgen deprivation therapy.

INTRODUCTION: Prostate cancer survivors (PCS) receiving androgen deprivation therapy (ADT) experience deleterious side effects such as unfavourable changes in cardiometabolic factors that lead to sarcopenic obesity and metabolic syndrome (MetS). While loss of lean body mass (LBM) compromises muscular strength and quality of life, MetS increases the risk of cardiovascular disease and may influence cancer recurrence. Exercise can improve LBM and strength, and may serve as an alternative to the pharmacological management of MetS in PCS on ADT. Prior exercise interventions in PCS on ADT have been effective at enhancing strength, but only marginally effective at enhancing body composition and ameliorating cardiometabolic risk factors. This pilot trial aims to improve on existing interventions by employing periodised resistance training (RT) to counter sarcopenic obesity in PCS on ADT. Secondary aims compare intervention effects on cardiometabolic, physical function, quality of life and molecular skeletal muscle changes. An exploratory aim examines if protein supplementation (PS) in combination with RT elicits greater changes in these outcomes. METHODS AND ANALYSIS: A 2×2 experimental design is used in 32 PCS on ADT across a 12-week intervention period. Participants are randomised to resistance training and protein supplementation (RTPS), RT, PS or control. RT and RTPS groups perform supervised RT three times per week for 12 weeks, while PS and RTPS groups receive 50 g whey protein per day. This pilot intervention applies a multilayered approach to ameliorate detrimental cardiometabolic effects of ADT while investigating molecular mechanisms underlying skeletal muscle changes in PCS. ETHICS AND DISSEMINATION: This trial was approved by the University of Southern California Institutional Review Board (HS-13-00315). Results from this trial will be communicated in peer-reviewed publications and scientific presentations. TRIAL REGISTRATION NUMBER: NCT01909440; Pre-results.

Reducing the Risk of Breast Cancer Recurrence: an Evaluation of the Effects and Mechanisms of Diet and Exercise.

With recent medical advances in diagnosis and treatment, the increasing numbers of long-term survivors of breast cancer is considerable and has resulted in the expansion of scientific research to include examination of lifestyle modifications as means of prevention of recurrence, new breast cancer events, and mortality. The objective of this report is to review randomized controlled trials (RCTs) including diet and/or exercise interventions on breast cancer recurrence in women with a history of breast cancer as well as pertinent recent epidemiologic evidence. Implicated biologic mechanisms are discussed to elucidate the impact of diet and exercise on disease recurrence.

Acute Response of PGC-1α and IGF-1 Isoforms to Maximal Eccentric Exercise in Skeletal Muscle of Postmenopausal Women.

PGC-1α4, a novel isoform of the transcriptional coactivator PGC-1α, was recently postulated to modulate the expression of anabolic and catabolic genes and therefore regulate skeletal muscle hypertrophy. Resting levels of PGC-1α4 messenger RNA (mRNA) expression were found to increase in healthy adults after resistance training. However, the acute effect of resistance exercise (RE) on PGC-1α4 expression in populations prone to progressive muscle loss, such as postmenopausal women, has not been evaluated. Here, we investigated alterations in mRNA expression of PGC-1α4 and PGC-1α1, a regulator of muscle oxidative changes, in postmenopausal women after high-intensity eccentric RE and analyzed these findings with respect to changes in insulin-like growth factor (IGF)-1 and catabolic gene expression. Nine postmenopausal women (age, 57.9 ± 3.2 years) performed 10 sets of 10 maximal eccentric repetitions of single-leg extension with 20-second rest periods between sets. Muscle biopsies were obtained from the vastus lateralis of the exercised leg before and 4 hours after the RE bout with mRNA expression determined by quantitative real-time polymerase chain reaction. No significant changes in the mRNA expression of either PGC-1α isoform were observed after acute eccentric RE (p > 0.05). IGF-1Ea mRNA expression significantly increased (p ≤ 0.05), whereas IGF-1Eb and mechano-growth factor (MGF) did not significantly change (p > 0.05). PGC-1α4 mRNA expression was associated with reduced mRNA expression of the catabolic gene myostatin (R = -0.88, p < 0.01), whereas MGF mRNA expression was associated with reduced mRNA expression of the catabolic gene FOXO3A (R = -0.81, p ≤ 0.05). These data demonstrate an attenuated response of PGC-1α isoforms to an acute bout of maximal eccentric exercise with short rest periods in postmenopausal women.

Effects of aerobic exercise on lipid-effector molecules of the innate immune response.

INTRODUCTION: Consistent, moderate-to-vigorous-intensity exercise has been associated with a lower risk of upper respiratory tract infection (URI). However, the molecular basis for this apparent protection has not yet been fully resolved. Host-derived lipids such as cholesteryl esters (CE) have emerged as important effector molecules of innate defense against infections. Here, we compared antimicrobial CE in nasal fluid before and after moderate-to-vigorous exercise between active and inactive subjects. METHODS: Nasal fluid was collected from 14 healthy, recreationally active subjects (32 ± 11 yr, 7 men and 7 women) and 14 healthy, inactive subjects (25 ± 3 yr, 7 men and 7 women) before and after treadmill exercise at 70% heart rate reserve. Nasal fluid was analyzed for lysozyme, cholesteryl linoleate (CL), cholesteryl arachidonate (CA), and albumin (Alb) concentrations. RESULTS: Baseline concentrations (mean ± SEM, inactive vs active) of lysozyme (117.7 ± 31.1 vs 122.9 ± 15.5 µg·mL), CL + CA (15.3 ± 1.8 vs 26.2 ± 10.05 µg·mL), and Alb (156.6 ± 54.5 vs 126.9 ± 32.8 µg·mL) were similar to previously reported levels and did not differ significantly between study groups. However, postexercise, CL + CA concentration was significantly lower in inactive compared with active subjects (7.8 ± 1.5 vs 20.1 ± 4.8 µg·mL, P = 0.036) dropping below the antimicrobial effective range. Once adjusted to Alb concentrations, the changes were no longer significant, suggesting that plasma transudation accounted for the increased CA + CL concentration postexercise in the active group relative to the inactive group. CONCLUSIONS: Moderate-to-vigorous aerobic exercise acutely decreases the antimicrobial CE response in inactive subjects but does not modify baseline levels of CE between active and inactive subjects. This suggests that compared with active individuals, inactive individuals may be at greater risk for upper respiratory tract infection immediately postexercise.

Evolving neural network optimization of cholesteryl ester separation by reversed-phase HPLC.

Cholesteryl esters have antimicrobial activity and likely contribute to the innate immunity system. Improved separation techniques are needed to characterize these compounds. In this study, optimization of the reversed-phase high-performance liquid chromatography separation of six analyte standards (four cholesteryl esters plus cholesterol and tri-palmitin) was accomplished by modeling with an artificial neural network-genetic algorithm (ANN-GA) approach. A fractional factorial design was employed to examine the significance of four experimental factors: organic component in the mobile phase (ethanol and methanol), column temperature, and flow rate. Three separation parameters were then merged into geometric means using Derringer's desirability function and used as input sources for model training and testing. The use of genetic operators proved valuable for the determination of an effective neural network structure. Implementation of the optimized method resulted in complete separation of all six analytes, including the resolution of two previously co-eluting peaks. Model validation was performed with experimental responses in good agreement with model-predicted responses. Improved separation was also realized in a complex biological fluid, human milk. Thus, the first known use of ANN-GA modeling for improving the chromatographic separation of cholesteryl esters in biological fluids is presented and will likely prove valuable for future investigators involved in studying complex biological samples.