Cholesterol enhances phospholipid-dependent activated protein C anticoagulant activity

The influence of cholesterol on activated protein C (APC) anticoagulant activity in plasma and on factor Va inactivation was investigated. Anticoagulant and procoagulant activities of phosphatidylcholine/phosphatidylserine (PC/PS) vesicles containing cholesterol were assessed in the presence and absence of APC using factor Xa-1-stage clotting and factor Va inactivation assays. Cholesterol at approximate physiological membrane levels (30%) in PC/PS (60%/10% w/w) vesicles prolonged the factor Xa-1-stage clotting time dose-dependently in the presence of APC but not in the absence of APC. APC-mediated cleavage of purified recombinant factor Va variants that were modified at specific APC cleavage sites (Q306/Q679-factor Va; Q506/Q679-factor Va) was studied to define the effects of cholesterol on APC cleavage at R506 and R306. When compared to control PC/PS vesicles, cholesterol in PC/PS vesicles enhanced factor Va inactivation and the rate of APC cleavage at both R506 and R306. Cholesterol also enhanced APC cleavage rates at R306 in the presence of the APC cofactor, protein S. In summary, APC anticoagulant activity in plasma and factor Va inactivation as a result of cleavages at R506 and R306 by APC is markedly enhanced by cholesterol in phospholipid vesicles. These results suggest that cholesterol in a membrane surface may selectively enhance APC activities. © 2005 International Society on Thrombosis and Haemostasis.

Fitness and fatness in childhood obesity : implications of physical activity

Overweight and obesity are a significant cause of poor health worldwide, particularly in conjunction with low levels of physical activity (PA). PA is health-protective and essential for the physical growth and development of children, promoting physical and psychological health while simultaneously increasing the probability of remaining active as an adult. However, many obese children and adolescents have a unique set of physiological, biomechanical, and neuromuscular barriers to PA that they must overcome. It is essential to understand the influence of these barriers on an obese child's motivation in order to exercise and tailor exercise programs to the special needs of this population. Chapter Outline • Introduction • Defining Physical Activity, Exercise, and Physical Fitness • Physical Activity, Physical Fitness, And Motor Competence In Obese Children • Physical Activity and Obesity in Children • Physical Fitness in Obese Children • Balance and Gait in Obese Children • Motor Competence in Obese Children • Physical Activity Guidelines for Obese Children • Clinical Assessment of the Obese Child • Physical Activity Characteristics: Mode • Physical Activity Characteristics: Intensity • Physical Activity Characteristics: Frequency • Physical Activity Characteristics: Duration • Conclusion

Relationship between physical activity and stiff or painful joints in mid-aged women and older women: a 3-year prospective study

This prospective study examined the association between physical activity and the incidence of self-reported stiff or painful joints (SPJ) among mid-age women and older women over a 3-year period. Data were collected from cohorts of mid-age (48–55 years at Time 1; n = 4,780) and older women (72–79 years at Time 1; n = 3,970) who completed mailed surveys 3 years apart for the Australian Longitudinal Study on Women's Health. Physical activity was measured with the Active Australia questions and categorized based on metabolic equivalent value minutes per week: none (<40 MET.min/week); very low (40 to <300 MET.min/week); low (300 to <600 MET.min/week); moderate (600 to <1,200 MET.min/week); and high (1,200+ MET.min/week). Cohort-specific logistic regression models were used to examine the association between physical activity at Time 1 and SPJ 'sometimes or often' and separately 'often' at Time 2. Respondents reporting SPJ 'sometimes or often' at Time 1 were excluded from analysis. In univariate models, the odds of reporting SPJ 'sometimes or often' were lower for mid-age respondents reporting low (odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.63–0.94), moderate (OR = 0.82, 95% CI = 0.68–0.99), and high (OR = 0.75, 95% CI = 0.62–0.90) physical activity levels and for older respondents who were moderately (OR = 0.80, 95% CI = 0.65–0.98) or highly active (OR = 0.83, 95% CI = 0.69–0.99) than for those who were sedentary. After adjustment for confounders, these associations were no longer statistically significant. The odds of reporting SPJ 'often' were lower for mid-age respondents who were moderately active (OR = 0.71, 95% CI = 0.52–0.97) than for sedentary respondents in univariate but not adjusted models. Older women in the low (OR = 0.72, 95% CI = 0.55–0.96), moderate (OR = 0.54, 95% CI = 0.39–0.76), and high (OR = 0.61, 95% CI = 0.46–0.82) physical activity categories had lower odds of reporting SPJ 'often' at Time 2 than their sedentary counterparts, even after adjustment for confounders. These results are the first to show a dose–response relationship between physical activity and arthritis symptoms in older women. They suggest that advice for older women not currently experiencing SPJ should routinely include counseling on the importance of physical activity for preventing the onset of these symptoms.