Exhaled nitric oxide concentration upon acute exposure to moderate altitude.

The purpose of this study was to assess immediate changes in the partial pressure of nitric oxide (NO) in exhaled gas (PE NO ) in healthy trained subjects who were acutely exposed to moderate altitude. One group of nine and another group of 20 healthy subjects were exposed to an ambient pressure of 728 hPa (546 mmHg) corresponding to an altitude of 2800 m for 5 and 90 min, respectively, in an altitude chamber. PE NO was measured offline by sampling exhaled gas in tight metal foil bags at 5, 30, 60, and 90 min. A correction for increased expiratory flow rate due to gas density effects at altitude was performed (PE NO corr). PE NO was significantly decreased by 13-16%, while the fraction of NO in exhaled gas (FE NO) was increased by 16-19% compared to sea level. There was no significant change in PE NO corr after exposure to altitude for 5, 30, 60, and 90 min. We conclude that there was no change in PENO upon arrival at altitude after correcting for gas density effects on expiratory flow rate. Corrections for altitude effects must be done before comparing measurements performed at different altitudes when using measurements of FENO to monitor athletes who have asthma during training at altitude.

Calcium signalling-dependent mitochondrial dysfunction and bioenergetics regulation in respiratory chain Complex II deficiency.

Despite advanced knowledge on the genetic basis of oxidative phosphorylation-related diseases, the molecular and/or cellular determinants for tissue-specific dysfunction are not completely understood. Here, we report the cellular events associated with mitochondrial respiratory Complex II deficiency occurring before cell death. Mutation or chronic inhibition of Complex II determined a large increase of basal and agonist-evoked Ca(2+) signals in the cytosol and the mitochondria, in parallel with mitochondrial dysfunction characterized by membrane potential (Δψ(mit)) loss, [ATP] reduction and increased reactive oxygen species production. Cytosolic and mitochondrial Ca(2+) overload are linked to increased endoplasmic reticulum (ER) Ca(2+) leakage, and to SERCA2b and PMCA proteasome-dependent degradation. Increased [Ca(2+)](mit) is also contributed by decreased mitochondrial motility and increased ER-mitochondria contact sites. Interestingly, increased intracellular [Ca(2+)] activated on the one hand a compensatory Ca(2+)-dependent glycolytic ATP production and determined on the second hand mitochondrial pathology. These results revealed the primary function for Ca(2+) signalling in the control of mitochondrial dysfunction and cellular bioenergetics outcomes linked to respiratory chain Complex II deficiency.

Interventions for weight loss and weight gain prevention among youth: current issues.

The recent increase in the prevalence of paediatric obesity is one of the most pressing public health concerns today because of the immediate and long term health consequences associated with this often intractable disease. Efforts are currently being made to reduce the prevalence of paediatric obesity. Youth weight loss studies have produced significant long term results. Most of these programmes included behaviour modification, diet and exercise. Studies have suggested that lifestyle exercise programmes may produce the best long term results. Effective components of these programmes appear to be parental involvement, reduced intake of foods having high energy density and reductions in physical inactivity. Future weight loss studies need to determine the type, intensity, and duration of exercise that will produce acceptable adherence and consequent long term weight loss, and to ascertain the reinforcing factors that determine youth behaviour choice. Weight gain prevention interventions for youth are clearly in their infancy. This review describes 3 completed and 2 ongoing weight gain prevention trials. One study showed reductions in the prevalence of obesity among junior high school girls, but not among boys. Another study among elementary school students showed significant mean decreases in body mass index in boys and girls following an intervention specifically to reduce time spent viewing television. Whether these studies altered food intake or increased physical activity remains unclear. A combination of weight loss treatment and weight gain prevention strategies employed in parallel is likely to yield the greatest benefits. Development and testing of novel intervention strategies, using innovative behavioural approaches to increase the likelihood that children will adopt healthy dietary, physical activity, and sedentary behaviour patterns, holds great promise to significantly reduce the epidemic of obesity.

Field evaluation of energy expenditure from continuous and intermittent walking in women.

RATIONALE: Recent physical activity recommendations suggest that comparable amounts of prescribed physical activity, done as a single continuous bout or as a set of intermittent bouts, will produce equal amounts of energy expenditure (EE) during the prescribed activity as well as throughout the day. HYPOTHESES: In a field setting, we tested two hypotheses: (1) continuous and intermittent walking conditions will result in significantly greater total daily EE than a control condition, and (2) continuous and intermittent walking conditions will result in similar total daily METHODS: Thirty women (mean age [yr] = 43.7+/-5.8; mean body mass index [kg x m(-2)]= 24.7+/-4.0) participated in a repeated-measures design so that each woman participated in three walking conditions on successive days of the week: a single 30-min brisk walk (continuous): three 10-min brisk walks (intermittent); and no activity (control). Throughout the study protocol, women wore a TRITRAC-R3D accelerometer programmed to estimate EE in 2-min intervals. RESULTS: Mean total EE estimates (kcal) for the three walking conditions were as follows: continuous: 2181+/-308; intermittent: 2121+/-305; and control: 1948+/-270. A repeated-measures analysis of variance omnibus test indicated that EE differed significantly by experimental condition [F(2,58) = 40.2, P < 0.001). To test the first hypothesis, contrasts were examined revealing that EE in the continuous and intermittent conditions was significantly greater than EE in the control condition [F(1,29) = 58.2, P < 0.001]. To test the second hypothesis, contrasts revealed that EE in the continuous condition was significantly greater than EE in the intermittent condition [F(1,29) = 7.0, P = 0.013]. CONCLUSION: For the purposes of total EE, selecting a continuous mode of walking may offer additional benefit over an intermittent mode, given the same total prescribed duration.

Physical activity, falls, and fractures among older adults: a review of the epidemiologic evidence.

OBJECTIVES: Assess the relationship between physical activity and risk for falls and osteoporotic fractures among older adults. DESIGN: Review and synthesis of published literature. MEASUREMENTS: We searched the literature using MEDLINE, Current Contents, and the bibliographies of articles identified. We included randomized controlled trials (RCT) of the effects of physical activity on the incidence of falls and case-control and prospective cohort studies of the association of physical activity with osteoporotic fracture risk. We also summarized mechanisms whereby physical activity may influence risk for falls and fractures. RESULTS: Observational epidemiologic studies and randomized clinical trials evaluating the effectiveness of physical activity programs to prevent falls have been inconclusive. However, many studies have lacked adequate statistical power, and recent trials suggest that exercise, particularly involving balance and lower extremity strength training, may reduce risk of falling. There is consistent evidence from prospective and case-control studies that physical activity is associated with a 20-40% reduced risk of hip fracture relative to sedentary individuals. The few studies that have examined the association between physical activity and risk of other common osteoporotic fractures, such as vertebral and wrist fractures, have not found physical activity to be protective. CONCLUSIONS: Epidemiologic studies suggest that higher levels of leisure time physical activity prevent hip fractures and RCTs suggest certain exercise programs may reduce risk of falls. Future research needs to evaluate the types and quantity of physical activity needed for optimal protection from falls and identify which populations will benefit most from exercise.

Changes in physical activity patterns in the United States, by sex and cross-sectional age.

PURPOSE: To determine sex-specific, age-related changes in physical activity patterns. METHODS: We examined cross-sectional data from the National Health Interview Survey, using the 1992 Youth Risk Behavior Survey supplement for adolescents and the 1991 Health Promotion/Disease Prevention supplement for adults. Physical activity patterns were modeled after Healthy People 2000 objectives. RESULTS: Among adolescents, physical activity patterns generally eroded most from ages 15 through 18. The "regular, vigorous activity" and strengthening patterns declined consistently from ages 12 through 21. Young adulthood (18-29 yr) often marked continuing erosion of activity patterns, whereas middle adulthood (30-64 yr) often revealed relatively stable patterns. At retirement age (65 yr), there was a stabilizing, or even an improving, tendency in activity patterns, usually followed by further erosion through the final period of life. Strengthening behavior eroded dramatically with advancing age among adults, especially among men. Among adolescents, differences between female and male respondents were large for regular, vigorous activity (11.3 percentage points greater for male respondents). In comparison with female adolescents and adults, male respondents reported much higher rates of regular, sustained activity (5.5 and 5.9 percentage points, respectively), and strengthening (18.2 and 11.3 percentage points, respectively). Among adults, levels of physical inactivity among women were moderately greater (5.5 percentage points) than for men. Absolute rates of change per year were mostly large to very large (3.0-8.0 percentage points x yr(-1)) during ages 15-18 yr, but, for adults, they were small (<0.5 percentage points x yr(-1)) for 33 of 40 sex, age, and pattern groupings. CONCLUSION: These data suggest that early and continued intervention will be necessary to offset these declines in physical activity throughout adolescence and adulthood.

The sarco/endoplasmic reticulum calcium-ATPase 2b is an endoplasmic reticulum stress-inducible protein.

The sarco/endoplasmic reticulum calcium-ATPase (SERCA) translocates Ca(2+) from the cytosol to the lumen of the endoplasmic reticulum. This Ca(2+) storage is important for cellular processes such as calcium signaling and endoplasmic reticulum (ER)-associated posttranslational protein modifications. We investigated the expression of the SERCA2 and SERCA3 isozymes in PC12 cells exposed to agents interfering with different aspects of the posttranslational protein processing within the ER, thereby activating the ER stress-induced unfolded protein response (UPR). All agents increased the SERCA2b mRNA level 3-4-fold, in parallel with increasing mRNA levels for the ER stress marker proteins BiP/GRP78 and CHOP/GADD153. In contrast, SERCA3 mRNA levels did not change. SERCA2b mRNA stability was not changed, indicating that the mechanism of its up-regulation was transcriptional, in accordance with the presence of ER stress response elements in the promoter region of the SERCA2 gene. SERCA2b was also increased at the protein level upon ER stress treatments. Induction of ER stress by tunicamycin, dithiothreitol, or l-azetidine 2-carboxylic acid did not result in depletion of ER calcium, showing that such depletion was not necessary for up-regulation of SERCA2b expression or UPR activation in general. We conclude that the SERCA2b expression can be controlled by the UPR pathway independently of ER Ca(2+) depletion.

Baseline and previous physical activity in relation to mortality in elderly men: the Zutphen Elderly Study.

Understanding the effect of changes in physical activity on mortality risk may help researchers clarify intervention strategies. This study investigated associations of physical activity at baseline and 5 years previously with all-cause mortality risk in a cohort of 472 elderly Dutch men. Relative risks were estimated for relations between mortality in 1990-1995 and physical activity levels in 1990 and 1985. Adjustments were made for baseline age, chronic diseases, functional status, and lifestyle factors. In contrast to previous levels of physical activity (adjusted p-trend = 0.39), baseline total time spent in physical activity was inversely associated with mortality risk (p-trend = 0.004; for the most active tertile vs. the least active, relative risk = 0.44; 95% confidence interval: 0.25, 0.80). No consistent associations were observed after fractionating total physical activity into activities of differing intensity or into four different types of activity. Relative to maintaining a physically active lifestyle (i.e., walking or bicycling for 20 minutes at least three times per week) in both survey years, a gradient of increasing risk was observed from adopting an active lifestyle to becoming sedentary to remaining sedentary (p-trend = 0.004). Recent levels of physical activity were more important for mortality risk among elderly men than activity 5 years previously. Becoming or remaining sedentary was significantly associated with increased mortality risk in comparison with remaining physically active.

ACTA, a fluorescent analogue of thapsigargin, is a potent inhibitor and a conformational probe of skeletal muscle Ca2+-ATPase.

Thapsigargin is a highly potent and selective inhibitor of sarco-endoplasmic reticulum (SERCA) family of Ca2+-ATPases and a useful tool in research concerning the function of intracellular Ca2+ stores. We describe here a novel fluorescent derivative (8-O-(4-aminocinnamoyl)-8-O-debutanoylthapsigargin, termed ACTA) of this compound, acting as a Ca2+-ATPase inhibitor with a potency approaching that of thapsigargin. Binding of ACTA to the skeletal muscle sarcoplasmic reticulum vesicles results in a strong fluorescence enhancement, approximately 66% of which depends on ACTA association with Ca2+-ATPase. This specific component of ACTA fluorescence is sensitive to the E1-E2 conformational equilibrium of the pump. The combined properties of high potency and binding-dependent fluorescence suggest ACTA to be a useful probe for a range of studies involving the SERCA class of ATPases.

Physical activity epidemiology applied to children and adolescents.

Physical activity epidemiology is central to establishing the importance of physical activity to public health. However, epidemiologic research applied to children and adolescents is still in its infancy. For example, in the studies we reviewed, many instances could be found where samples were inadequately described or where response rates and completion rates suggest that the final sample may no longer be representative of the population of interest. Many studies also had incomplete statistical adjustment for confounding influences. The need for epidemiologic research was clearly demonstrated where initially beneficial findings were negated by such adjustment. Hence, physical activity epidemiologists can play a considerable role. Their research will be the basis for expanding policy and promotional efforts to educate children and adolescents on the benefits of physical activity and the skills needed to be active, thereby helping them to build a foundation for a lifetime of physical activity.

Physical activity and 10-year mortality from cardiovascular diseases and all causes: The Zutphen Elderly Study.

BACKGROUND: Little is known about physical activity and mortality risk in the elderly. Therefore, we describe the associations between the physical activity pattern of elderly men and the mortality from cardiovascular diseases (CVDs), particularly coronary heart disease (CHD) and stroke, and all causes. METHODS: Self-reported physical activity was assessed with a validated questionnaire for retired men in a population-based sample of 802 Dutch men, aged 64 to 84 years at baseline. Relative risks were estimated for 10-year mortality from CVD (199 deaths), CHD (90), stroke (47), and all causes (373) for tertiles of time spent on physical activity (reference, lowest tertile). Adjustments were made for baseline age, relevant major chronic diseases, cigarette smoking, and alcohol consumption. RESULTS: Mortality risks from CVD and all causes decreased with increasing physical activity (P for trend = .04) with adjusted relative risks of 0.70 (95% confidence interval, 0.48-1.01) and 0.77 (95% confidence interval, 0.59-1.00) in the highest tertile of total physical activity, respectively. Except for CHD, time spent in more intense activities (> or = 4 kcal/kg per hour) was more strongly associated with all mortality outcomes than less intense activities, but no single type of activity was particularly protective. Walking or cycling at least 3 times per week for 20 minutes (our definition of activity based on general health recommendations) was associated with reduced mortality from CVD (adjusted relative risk, 0.69; 95% confidence interval, 0.50-0.88) and all causes (relative risk, 0.71; 95% confidence interval, 0.58-0.88). Additional adjustment for biological cardiovascular risk factors did not affect the strength of any association. CONCLUSION: In a general population of elderly men, physical activity may protect against mortality from CVDs and all causes.

A tool coming of age: thapsigargin as an inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPases.

Thapsigargin is the most widely used inhibitor of the ubiquitous sarco-endoplasmic reticulum Ca(2+)-ATPases in mammalian cells. Over the past ten years, this guaianolide compound of plant origin has become a popular tool in a host of studies directed at elucidating the mechanisms of intracellular Ca2+ signalling. Its remarkable potency and selectivity have been instrumental in widening our view of the function of intracellular Ca2+ stores to include such key aspects as store-operated Ca2+ entry or the involvement of the stores in protein synthesis or cell growth. In this article Marek Treiman, Casper Caspersen and Søren Brøgger Christensen review the key pharmacological features of thapsigargin action; they also discuss some of the ways in which its unique properties have shown to be important for obtaining new insights into the biology of Ca2+ stores, and how these properties might encompass a therapeutic potential. In parallel, attention is drawn to some of the limitations and pitfalls encountered when working with thapsigargin.

Age, period, and cohort effects on physical activity among elderly men during 10 years of follow-up: the Zutphen Elderly Study.

BACKGROUND: Data regarding the nature of change in physical activity as elderly people become progressively older are scarce. The present study describes changes in the physical activity pattern of a cohort of elderly Dutch men between 1985 and 1995. METHODS: Self-reported physical activity was assessed with a reliable and valid questionnaire designed for retired men. In 1985, 863 men (aged 65-84 years) were examined, in 1990, 520 surviving men, and in 1995, 343 men. Three analytical perspectives (cross-sectional, longitudinal, and time-series) were used concurrently to untangle effects of aging, period, and birth cohort on the 10-year change in physical activity. RESULTS: Mean total time spent on physical activity decreased by 33% (28 min/day) during 10 years of follow-up. Time spent on bicycling, gardening, and total activity decreased with aging. A period effect was observed for time spent on bicycling and total activity in 1990 (increase) and gardening in 1995 (decrease). No differences in physical activity between birth cohorts were observed. Time spent on walking remained stable during follow-up, but its relative contribution to total time spent on physical activity increased with aging. The pattern of change in total activity was not affected by functional status. CONCLUSIONS: Mean total time spent on physical activity by elderly men clearly decreased during follow-up. This could not be fully explained by declining functional status, but was partly explained by aging. In contrast to other physical activity parameters, time spent on walking was not affected by aging. These results suggest an increasingly restrictive physical activity pattern with aging.

Risk factors for sudden coronary death in the United States.

We assessed risk factors for sudden coronary death among persons without a history of coronary heart disease (unexpected sudden coronary death) and persons with a history of coronary heart disease (sudden coronary heart disease death). We analyzed national data to calculate death rates and odds ratios for both types of sudden coronary death. Among modifiable factors that we examined, only cigarette smoking increased risk for unexpected sudden coronary death [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.2-2.7]. Diabetes mellitus (OR = 3.8; 95% CI = 2.5-5.8 for women), cigarette smoking (OR = 1.5; 95% CI = 1.0-2.1), and hypertension (OR = 1.4; 95% CI = 1.1-1.9) increased the risk for sudden coronary heart disease death. Etiologic factors for sudden death appear to differ depending on the presence or absence of coronary disease. With preexisting coronary disease, factors associated with chronic coronary disease may elevate sudden death risk; without coronary disease, factors that provoke ventricular arrhythmias may trigger sudden death.

Haemostatic parameters and lifestyle factors in elderly men in Italy and The Netherlands.

The association between plasma fibrinogen, factor VII, factor X, activated partial thromboplastin time, antithrombin III and the lifestyle factors cigarette smoking, alcohol use, fat intake and physical activity was assessed in 802 men aged 70-90 years in Zutphen (The Netherlands), Montegiorgio and Crevalcore (Italy). Smoking was positively associated with fibrinogen, also after adjustment for other lifestyle factors, age, use of anticoagulants and aspirin like drugs, body mass index, and history of myocardial infarction. Alcohol use was associated with increased levels of factor X and decreased levels of antithrombin III. Fat intake was positively associated with antithrombin III. Between cohorts, considerable differences were observed in levels of haemostatic parameters and the lifestyle factors. Compared to the mediterranean cohorts the Zutphen cohort showed the highest levels of fibrinogen and factor VII. Differences in lifestyle factors could, however, not explain differences between cohorts in levels of any of the haemostatic parameters, despite the observed associations between lifestyle factors and haemostatic parameters.

The shape up challenge: a community-based worksite exercise competition.

PURPOSE: To assess organizational and employee participation during three community-wide worksite exercise competitions in two communities. DESIGN: A one-group, posttest-only design was used. Lack of controls, exercise baseline, and the short-term nature of the interventions were limitations. SETTING: The Minnesota Heart Health Program conducted annual exercise campaigns between 1982 and 1989 within three intervention communities to reduce behavioral risk for cardiovascular disease. The Shape Up Challenge was a worksite exercise competition designed, in conjunction with other campaign activities, to increase levels of physical activity. SUBJECTS: A total of 119 participating companies in two Minnesota communities, and 17,626 employees within these worksites, composed the subjects in this study. INTERVENTION: Eligible worksites were invited to participate in a month-long competition during which employees recorded minutes spent daily in aerobic activities. Incentives were established to promote intragroup cooperation and intergroup competition. Companies competed for awards that were based on average minutes of exercise per employee versus per participant. MEASURES: Numbers of companies recruited and participating, campaign activities, minutes of exercise, and costs were recorded on implementation logs. Companies completed surveys describing business type, number and sex of employees, existing health promotion programs, and perceived benefits of participation. RESULTS: Of the 365 companies invited to participate, 33% participated (range 15% to 50%). Participating companies were more likely than nonparticipating companies to offer other health promotion programs and perceived greater benefits from participation. Women and smaller companies had significantly greater participation rates than men and larger companies. Average employee participation rates ranged from as high as 84% in smaller organizations to as low as 16% as organization size increased. CONCLUSIONS: Community-based worksite exercise competitions appear to be a viable strategy for promoting employee exercise, particularly in smaller companies. Group-based contingencies applied in natural work units may facilitate employee participation. Further research is needed to assess the relative efficacy of this approach, compare alternative incentives, and identify strategies to enhance exercise maintenance after the intervention has ceased.

Leisure-time physical activity among older adults. United States, 1990.

OBJECTIVE: To investigate the prevalence and selected correlates of leisure-time physical activity in a nationally representative sample of persons aged 65 years or older. METHODS: Data from 2783 older male and 5018 older female respondents to the 1990 National Health Interview Survey were used. Regular physical activity was defined as participation in leisure-time physical activities 3 times or more per week for 30 minutes or more during the previous 2 weeks. Odds ratios (ORs) were estimated from multivariate logistic regression analysis. RESULTS: Prevalence of regular physical activity was 37% among older men and 24% among older women. Correlates of regular physical activity included the perception of excellent to good health (men: OR, 1.5; 95% confidence interval [CI], 1.1-1.9; women: OR, 1.6; 95% CI, 1.3-1.9), correct exercise knowledge (men: OR, 2.4; 95% CI, 1.9-3.1; women: OR, 2.7; 95% CI, 2.2-3.4), no activity limitations (men: OR, 1.3; 95% CI, 1.0-1.6; women: OR, 1.7; 95% CI, 1.4-2.0) and not perceiving "a lot" of stress during the previous 2 weeks (men: OR, 1.7; 95% CI, 1.2-2.4; women: OR, 1.3; 95% CI, 1.0-1.6). Among those who had been told at least twice that they had high blood pressure, physician's advice to exercise was associated with regular physical activity (men: OR, 1.6; 95% CI, 1.2-2.3; women: OR, 1.5; 95% CI, 1.2-1.9). The 2 major activities among active older adults were walking (men, 69%; women, 75%) and gardening (men, 45%; women, 35%). CONCLUSIONS: Prevalence of regular physical activity is low among older Americans. Identifying the correlates of physical activity will help to formulate strategies to increase physical activity in this age group.

Physical activity and cardiovascular risk factors among elderly men in Finland, Italy, and the Netherlands.

Physical activity pattern and its relation with cardiovascular risk factors was investigated in 1,402 men aged 69-90 years who participated in the 30-year follow-up survey of the Finnish (Eastern and Western Finland), Italian (Montegiorgio and Crevalcore), and Dutch (Zutphen) cohorts of the Seven Countries Study. Physical activity was assessed with a validated self-administered questionnaire designed for retired men. Total physical activity varied largely within cohorts. Median total reported physical activity ranged from 50 minutes/day in Montegiorgio to 89 minutes/day in Crevalcore. Walking, gardening, and bicycling together contributed more than 70% of total physical activity in all cohorts. Depending on the definition of physical inactivity, the estimated prevalence of inactivity varied between 5% and 33% in Zutphen and between 18% and 68% in Montegiorgio. Total physical activity was inversely associated with resting heart rate (r= -0.11, p < 0.001) and was positively associated with high density lipoprotein (HDL) cholesterol (r = 0.08, p < 0.01) in pooled data. These associations remained statistically significant after adjustment for age, cohort, smoking, body mass index, and alcohol intake. Total activity was not associated with total cholesterol, non-HDL cholesterol, blood pressure, or body mass index. The authors conclude that physical activity may have a beneficial effect on HDL cholesterol levels in elderly men. Walking, gardening, and bicycling contribute substantially to their physical activity pattern.