Longitudinal change in coronary heart disease risk factors in older runners

BACKGROUND: it is currently not clear how coronary heart disease (CHD) risk factors change over time in chronic exercisers. Therefore, the purpose of this study is to describe the longitudinal change in CHD risk factors in chronically endurance-trained men and women, and to determine the exercise and nutritional factors associated with those respective changes. METHODS AND RESULTS: ninety-one middle-aged runners (56 male, 35 female) were tested on two occasions approximately 10 years apart (aged 50.8 +/- 8.0 versus 60.0 +/- 7.9 years at respective visits). Body composition, VO2max, blood pressure (BP) and blood chemistries were measured, and the subjects' self-reported training and nutritional history. Data were analysed by factorial analysis of variance (ANOVA) and multivariate step-wise regression. Among the entire sample, training volume decreased (61.1 +/- 28.2 versus 44.7 +/- 24.6 km/week, P<0.05) but nutritional variables did not change. Body fat (16.9 +/- 5.3% for men versus 21.1 +/- 5.3% for women, P<0.05), blood lipids, blood glucose and systolic and diastolic BP all changed negatively over the study duration. These changes occurred similarly in both genders and irrespective of menstrual and hormone replacement status among the women. Lastly, the changes in CHD risk factors were not predicted by change in exercise or nutritional patterns. CONCLUSIONS: despite the maintenance of significant volumes of exercise and the absence of changes in diet, most CHD risk factors demonstrated unfavourable changes over 10 years in chronic men and women runners. However, the absolute values for most CHD risk factors remained better than those reported for sedentary peers of comparable age.     

Predicting erythroid response to recombinant erythropoietin plus granulocyte colony-stimulating factor therapy following a single subcutaneous bolus in patients with myelodysplasia

We randomized 21 patients with low-risk myelodysplastic syndromes (MDS) to receive a single subcutaneous bolus of recombinant erythropoietin (epoietin) +/- granulocyte-colony stimulating factor (G-CSF), or placebo and monitored erythropoietic response over 7 days. In this small study, the reticulocyte response at day 7 was highly predictive of subsequent response to a therapeutic trial of epoietin + G-CSF.     

Insulin stimulation of adipocyte membrane glucose transport. A graded biologic response insensitive to bilayer lipid disordering

Aspects of the mechanism by which insulin stimulates the membrane glucose transport system were examined by assessing the influence of the bilayer lipid structure on transport stimulation characteristics, and considering the form of the insulin dose-response curve. We tested the effects of membrane lipid perturbation on the insulin stimulation process. Benzyl alcohol, at concentrations (25 mM) that grossly fluidize lipids forming the adipocyte membrane bilayer matrix, caused 50% inhibition of intrinsic transporter activity. However, this membrane perturbation had no significant effect on either the insulin dose-response curve (conducted at 37 degrees) or the time-course of the insulin stimulation of hexose transport (conducted at 32 degrees). These data are difficult to rationalize in terms of a model in which transport stimulation involves interaction of transporters and hormone-bound receptors that is limited by lateral diffusion of these proteins in the fluid lipid bilayer. Curve-fitting experimental insulin dose-response data for stimulation of 2-deoxy-D-glucose and D-glucose uptake provided an estimate of an insulin "association constant" for transport regulation that may be compared with recent insulin receptor binding data. Similar magnitude constants were obtained whether estimated directly from plots of transport velocity versus arithmetic hormone dose, or by extrapolation from linear segments of sigmoidal velocity versus log dose plots, or from inverse (Lineweaver-Burk-type) plots of the insulin dose-response data. Insulin apparently regulates transport by associating with a binding site, having an apparent dissociation constant which is determinable through kinetic measurements of hexose uptake (KDapp approx. 17-40 pM). This is in good agreement with the dissociation constant, KD, determined from Scatchard plots of recent binding data to adipocytes, for a class of receptors representing the "high affinity" binding sites for insulin. Insulin dose-response curve simulations also indicated that the stimulation process may be classified in pharmacologic terms as a typical graded biologic response and may involve insulin association with a site that regulates transport rates in a manner kinetically analogous to allosteric modulation of a V-series enzyme by a noncompetitive ligand. From the results we suggest that a relatively close association occurs between transport and receptor proteins in the membrane, where the relative activation of transport depends on the fractional occupancy of functional high affinity receptors by insulin, and the insulin stimulation of transport involves regions of the membrane that are not influenced significantly by