N. Tim Cable

Lifestyle factors and colorectal cancer risk (2): a systematic review and meta-analysis of associations with leisure-time physical activity

Objective Increased physical activity may decrease the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we performed a systematic review and meta‐analysis of prospective observational studies to quantify gender‐specific risk associated with increased leisure‐time physical activity (LT‐PA).

Lifestyle factors and colorectal cancer risk (1): systematic review and meta‐analysis of associations with body mass index

Objective  Excess body weight, defined by body mass index (BMI), may increase the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we undertook a systematic review and meta‐analysis of prospective observational studies to quantify colorectal cancer risk associated with increased BMI and explore for differences by gender, sub‐site and study characteristics.

Acute β-Adrenergic Overload Produces Myocyte Damage through Calcium Leakage from the Ryanodine Receptor 2 but Spares Cardiac Stem Cells

A hyperadrenergic state is a seminal aspect of chronic heart failure. Also, “Takotsubo stress cardiomyopathy,” is associated with increased plasma catecholamine levels. The mechanisms of myocyte damage secondary to excess catecholamine exposure as well as the consequence of this neurohumoral burst on cardiac stem cells (CSCs) are unknown. Cardiomyocytes and CSCs were exposed to high doses of isoproterenol (ISO), in vivo and in vitro. Male Wistar rats received a single injection of ISO (5 mg kg-1) and were sacrificed 1, 3, and 6 days later. In comparison with controls, LV function was impaired in rats 1 day after ISO and started to improve at 3 days. The fraction of dead myocytes peaked 1 day after ISO and decreased thereafter. ISO administration resulted in significant ryanodine receptor 2 (RyR2) hyperphosphorylation and RyR2-calstabin dissociation. JTV519, a RyR2 stabilizer, prevented the ISO-induced death of adult myocytes in vitro. In contrast, CSCs were resistant to the acute neurohumoral overload. Indeed, CSCs expressed a decreased and inverted complement of β1/β2-adrenoreceptors and absence of RyR2, which may explain their survival to ISO insult. Thus, a single injection of ISO causes diffuse myocyte death through Ca2+ leakage secondary to the acutely dysfunctional RyR2. CSCs are resistant to the noxious effects of an acute hyperadrenergic state and through their activation participate in the response to the ISO-induced myocardial injury. The latter could contribute to the ability of the myocardium to rapidly recover from acute hyperadrenergic damage.

Physical activity before and after diagnosis of colorectal cancer: disease risk, clinical outcomes, response pathways and biomarkers.

Physical inactivity may be responsible for 13–14% of colon cancer, an attributable risk greater than family history. Epidemiological evidence shows an association between occupational and recreational physical activity and colon cancer, but has not established whether physical activity is protective against low-risk or more advanced adenomas. The evidence is inconclusive as to whether physical activity protects against rectal cancer and is conflicting with respect to whether physical activity has equal effects on male and female risk of colorectal cancer. The effect of exercise ‘interventions’ on the risk of colorectal cancer is currently not known. Also, although inferences can be made from epidemiological studies, no optimal exercise regimen can be confidently prescribed for protection against colorectal cancer. There is little available evidence for the benefits of physical activity before diagnosis of colorectal cancer for disease-specific survival and prognosis, and the clinical effects of an exercise intervention after diagnosis have not been investigated. There is some evidence that improvements in cardiorespiratory fitness reduce adverse effects from cancer treatment when physical activity is undertaken following diagnosis of colorectal cancer. Markers/mechanisms by which physical activity may protect against colorectal cancer and/or improve disease prognosis include gastrointestinal transit-time, chronic inflammation, immune function, insulin levels, insulin-like growth factors, genetics and obesity. Research evidence is, however, limited as to whether these markers are beneficially affected by physical activity, either before or after diagnosis of colorectal cancer.

Basic science behind the cardiovascular benefits of exercise

Cardiorespiratory fitness is a strong predictor of cardiovascular (CV) disease and all-cause mortality, with increases in cardiorespiratory fitness associated with corresponding decreases in CV disease risk. The effects of exercise upon the myocardium and vascular system are dependent upon the frequency, intensity and duration of the exercise itself. Following a prolonged period (≥6 months) of regular intensive exercise in previously untrained individuals, resting and submaximal exercising heart rates are typically 5–20 beats lower, with an increase in stroke volume of ∼20% and enhanced myocardial contractility. Structurally, all four heart chambers increase in volume with mild increases in wall thickness, resulting in greater cardiac mass due to increased myocardial cell size. With this in mind, the present paper aims to review the basic science behind the CV benefits of exercise. Attention will be paid to understanding (1) the relationship between exercise and cardiac remodelling; (2) the cardiac cellular and molecular adaptations in response to exercise, including the examination of molecular mechanisms of physiological cardiac growth and applying these mechanisms to identify new therapeutic targets to prevent or reverse pathological remodelling and heart failure; and (3) vascular adaptations in response to exercise. Finally, this review will briefly examine how to optimise the CV benefits of exercise by considering how much and how intense exercise should be.

The prolactin responses to active and passive heating in man.

The aim of this study was to compare the prolactin and blood pressure responses at identical core temperatures during active and passive heat stresses, using prolactin as an indirect marker of central fatigue. Twelve male subjects cycled to exhaustion at 60% maximal oxygen uptake ( ) in a room maintained at 33°C (active). In a second trial they were passively heated (passive) in a water bath (41.56 ± 1.65°C) until core temperature was equal to the core temperature observed at exhaustion during the active trial. Blood samples were taken from an indwelling venous cannula for the determination of serum prolactin during active heating and at corresponding core temperatures during passive heating. Core temperature was not significantly different between the two methods of heating and averaged 38.81 ± 0.53 and 38.82 ± 0.70°C (data expressed as means ±s.d.) at exhaustion during active heating and at the end of passive heating, respectively (P > 0.05). Mean arterial blood pressure was significantly lower throughout passive heating (active, 73 ± 9 mmHg; passive, 62 ± 12 mmHg; P < 0.01). Despite the significantly reduced blood pressure responses during passive heating, during both forms of heating the prolactin response was the same (active, 14.9 ± 12.6 ng ml−1; passive, 13.3 ± 9.6 ng ml−1; n.s.). These results suggest that thermoregulatory, i.e. core temperature, and not cardiovascular afferents provide the key stimulus for the release of prolactin, an indirect marker of central fatigue, during exercise in the heat.

Endurance exercise training enhances cutaneous microvascular reactivity in post-menopausal women

OBJECTIVE To compare cutaneous microvascular reactivity between untrained young and post-menopausal women, and assess the effects of 48 weeks of endurance exercise training on cutaneous microvascular reactivity in post-menopausal women. METHODS Twenty post-menopausal and 12 young women completed this study. Using laser-Doppler flowmetry, an index of skin blood flow was measured on the forearm at rest, during post-occlusive reactive hyperaemia (PORH), and during localised heating to 42°C. Cutaneous vascular conductance (CVC) was calculated as the ratio of laser-Doppler flow to mean arterial pressure (in AU mm Hg(-1)). For the post-menopausal women, this assessment was also performed after 6, 12, 24, 36, and 48 weeks of endurance exercise training. RESULTS PORH and maximum CVC responses were depressed in untrained post-menopausal women compared with young controls (P ≤ 0.011 for all methods of data expression). PORH was increased (P<0.05) in the post-menopausal women after 24 weeks of exercise training (0.51 ± 0.16 vs. 0.65 ± 0.23 AU mm Hg(-1)), with further increases after 36 and 48 weeks (0.76 ± 0.27 and 0.88 ± 0.32 AU mm Hg(-1), respectively). Similarly, maximum CVC was increased (P<0.05) after 24 weeks (2.20 ± 0.31 vs. 2.66 ± 0.27 AU mm Hg(-1)), and at the 36-week assessment (2.90 ± 0.30 AU mm Hg(-1)). Cardiopulmonary fitness (V˙O(2)max) increased after 12 weeks (23.5 ± 4.4 vs. 25.4 ± 5.1 mL kg(-1)min(-1); P<0.05), and improved further throughout the intervention (31.6 ± 5.9 mL kg(-1)min(-1) at week 48). There was a moderate positive relationship between the change in PORH (in AU mm Hg(-1)) between weeks 0 and 48 and the concomitant change in V˙O(2)max (r=0.65, P=0.002). After 24-36 weeks of exercise training, the PORH and maximum CVC responses of the post-menopausal women did not differ to those of the young untrained women (P>0.05). CONCLUSION Cutaneous microvascular reactivity is reduced in post-menopausal women compared to young controls and increased to similar levels after 24-36 weeks of mild-to-moderate endurance exercise.

Seasonal Reduction in Physical Activity and Flow-Mediated Dilation in Children

PURPOSE cardiovascular disease is a process that has its origins in childhood. Endothelial dysfunction is the earliest detectable manifestation of cardiovascular disease. This study aimed to assess the impact of seasonal changes in physical activity (PA) and body composition on conduit artery endothelial function in children. METHOD we studied 116 children (70 girls aged 10.7 ± 0.3 yr and 46 boys aged 10.7 ± 0.3 yr) on two occasions; in the northern summer (June) and late autumn (November). We assessed flow-mediated dilation (FMD) using high-resolution Doppler ultrasound. Body composition was measured by dual-energy x-ray absorptiometry. PA was assessed using accelerometry. RESULTS FMD (10.0% ± 4.3% to 7.9% ± 3.9%, P < 0.001) and PA (94.1 ± 34.8 to 77.8 ± 33.7 min·d, P < 0.01) decreased, while percentage body fat increased (27.6% ± 6.8% to 28.0% ± 6.6%, P < 0.001) between summer and autumn. Decreases in FMD correlated with decreases in high-intensity PA (r = 0.23, P = 0.04), and change in high-intensity PA was the only predictor of change in FMD. No relationships were evident between changes in body composition and FMD. CONCLUSIONS vascular function decreased between summer and autumn in this cohort. There were no relationships between change in FMD and changes in body composition or low/moderate-intensity PA. The associations between FMD and high-intensity PA suggests that future interventions should encourage this form of behavior, particularly at the times of year associated with lower PA.

Arterial Compression during Overhead Throwing: A Risk for Arterial Injury?

Case studies reporting aneurysm formation in the axillary artery have been described in overhead throwing athletes, possibly due to repetitive arterial compression by the humeral head that has been transiently observed during sonographic diagnostic arm manoeuvres. Whether compression negatively alters arterial health has not been investigated and was the focus of this study. The throwing arm of elite overhead athletes was screened for inducible axillary artery compression. Compressors (COMP, n = 11, mean age: 20 (SD: 2) year, 7 male, 4 female) were age and sex matched with noncompressing (NONCOMP) athlete controls. Four indices of arterial health (flow mediated dilation [FMD], conduit artery vasodilatory capacity [CADC], glyceryl-trinitrate [GTN]-induced vasodilation and intima-media thickness [IMT]) were assessed with high-resolution ultrasound at the brachial and the axillary, artery. No significant between-group differences were observed at the brachial, or axillary, artery for FMD (brachial: COMP: mean (SD) 6.2 (3.1)%, NONCOMP: 6.1 (3.5)%, p = 0.967, axillary: COMP: 8.0 (5.5)%, NONCOMP: 9.0 (3.6)%, p = 0.602), CADC (brachial: COMP: 10.4 (3.4)%, NONCOMP: 10.4 (5.4)%, p = 0.999, axillary: COMP: 9.6 (4.2)%, NONCOMP: 8.5 (3.2)%, p = 0.492), GTN-induced vasodilation (brachial: COMP: 17.9 (5.1)%, NONCOMP:14.1 (7.2)%, p = 0.173, axillary: COMP: 9.5 (4.3)%, NONCOMP: 7.7 (3.1)%, p = 0.302) or IMT (brachial: p = 0.084, axillary: p = 0.581). These results suggest that transient arterial compression, observed during diagnostic arm manoeuvres in overhead throwing athletes, is not associated with abnormal indices of artery function or structure and that other mechanisms must be responsible for the published cases of aneurysm formation in elite athletes performing overhead throwing actions.