Preliminary studies on the effect of moderate physical activity on blood levels of glutathione

Molecular epidemiological approaches are being used to study how physical activity may protect against cancer. Prior epidemiological data suggest that physical activity protects against lung cancer; however, interpretation of these data is complicated by potential confounding by smoking. Glutathione (GSH) detoxifies cigarette smoke carcinogens and the paper tests whether physical activity levels are associated with blood GSH levels. Study subjects were enrolled in a chemoprevention trial testing whether antioxidant micronutrient supplementation reduces genetic damage from cigarette smoking. Physical activity data were collected by questionnaire from 178 subjects at 12 months of follow-up in the trial. Total GSH (tGSH), which is the sum of free and protein-bound GSH and glutathione disulfide levels, was measured using the 5,5'-dithiobis-(2-nitrobenzenoic acid) colormetric assay with red blood cell samples collected at the 12-month time point. In multivariate linear regression analyses that controlled for gender and cigarettes smoked per day, tGSH was positively associated with hours per week of moderate intensity activity (β=0.005, p=0.02). Hours per week of vigorous intensity activity were unassociated with tGSH and the effect of moderate activity remained after control for vigorous activity. The results are consistent with prior research showing differential effects of moderate and vigorous activity and suggest a mechanism through which physical activity may influence lung cancer risk.     

Ethnic Differences in Physical Activity and Inactivity Patterns and Overweight Status

Objective: To examine the relationship between physical activity and inactivity patterns and overweight in U.S. adolescents using baseline and 1-year change in activity and inactivity data. Research Methods and Procedures: Nationally representative data from 12,759 participants (6997 non-Hispanic whites, 2676 non-Hispanic blacks, 2185 Hispanics, and 901 Asians) in the National Longitudinal Study of Adolescent Health (1995 and 1996). Data on moderate to vigorous and low-intensity physical activity, TV/video viewing, and video game/computer use were obtained from questionnaires. Multivariate models assessed the association of overweight (body mass index ≥ 95th percentile Centers for Disease Control and Prevention/National Center for Health Statistics 2000 curves) with initial (and 1-year change) activity and inactivity levels, controlling for age, ethnicity, socioeconomic status, urban residence, cigarette smoking, and region of residence. Results: Overweight prevalence was positively associated with high level TV/video viewing among white boys (odds ratio [OR] = 1.52; 95% confidence interval [1.08 to 2.14]) and girls (OR = 2.45 [1.51 to 3.97]). The odds of overweight decreased with high levels of moderate to vigorous physical activity among white boys (OR = 0.81 [0.76 to 0.87]), non-Hispanic black boys (OR = 0.86 [0.76 to 0.98]) and girls (OR = 0.88 [0.78 to 0.99]), and Hispanic boys (OR = 0.90 [0.83 to 0.97]) and girls (OR = 0.91 [0.84 to 0.99]). Discussion: Predicted probabilities generated from the logistic regression models, which examined the experimental effects of altering hours of TV/video viewing and bouts of moderate to vigorous physical activity, show lower overweight among adolescents who watched less TV per week combined with frequent moderate to vigorous physical activity than those who watched more TV per week combined with fewer bouts of weekly moderate to vigorous physical activity. Predicted probabilities suggest important sex and ethnic differences in these associations.     

Associations between Multiple Accelerometry-Assessed Physical Activity Parameters and Selected Health Outcomes in Elderly People – Results from the KORA-Age Study

Introduction

Accelerometry is an important method for extending our knowledge about intensity, duration, frequency and patterns of physical activity needed to promote health. This study has used accelerometry to detect associations between intensity levels and related activity patterns with multimorbidity and disability. Moreover, the proportion of people meeting the physical activity recommendations for older people was assessed.

Methods

Physical activity was measured in 168 subjects (78 males; 65–89 years of age), using triaxial GT3X accelerometers for ten consecutive days. The associations between physical activity parameters and multimorbidity or disability was examined using multiple logistic regression models, which were adjusted for gender, age, education, smoking, alcohol consumption, lung function, nutrition and multimorbidity or disability.

Results

35.7% of the participants met the physical activity recommendations of at least 150 minutes of moderate to vigorous activity per week. Only 11.9% reached these 150 minutes, when only bouts of at least 10 minutes were counted. Differences in moderate to vigorous activity between people with and without multimorbidity or disability were more obvious when shorter bouts instead of only longer bouts were included. Univariate analyses showed an inverse relationship between physical activity and multimorbidity or disability for light and moderate to vigorous physical activity. A higher proportion of long activity bouts spent sedentarily was associated with higher risk for multimorbidity, whereas a high proportion of long bouts in light activity seemed to prevent disability. After adjustment for covariates, there were no significant associations, anymore.

Conclusions

The accumulated time in moderate to vigorous physical activity seems to have a stronger relationship with health and functioning when shorter activity bouts and not only longer bouts were counted. We could not detect an association of the intensity levels or activity patterns with multimorbidity or disability in elderly people after adjustment for covariates.     

Physical activity and lung cancer among non-smokers: a pilot molecular epidemiological study within EPIC

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by ³²P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35–0.90), higher GSH levels (+1.87 μmol GSH g^?1 haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38–2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84–1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.     

A prospective cohort study of physical activity in relation to lung cancer incidence among Black women

BackgroundBlack women have higher lung cancer incidence and mortality rates despite a lower smoking prevalence than White women. Physical activity may reduce lung cancer risk through several pathways, including the immune and inflammatory systems, as well as those with effects on sex hormones and metabolism.MethodsWe examined vigorous physical activity, walking for exercise, sitting watching television, and metabolic equivalents (METs) in relation to lung cancer risk among 38,432 participants in a prospective cohort of Black women. We used Cox proportional hazards models adjusted for covariates to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsIn 1995–2017, 475 incident lung cancer cases accrued. Participants who engaged in ≥ 1 h/week of vigorous physical activity or expended the highest tertile of METs experienced a decreased risk of lung cancer (HR: 0.85, 95% CI: 0.65–1.10; 0.89, 0.68–1.18; respectively). An increased risk was observed for sitting watching television (≥1 h/week: 1.27, 0.72–2.21). In stratified models, an inverse association between walking for exercise and lung cancer risk was only present among former smokers (≥1 h/week: 0.71, 0.52–0.98), while inverse associations between vigorous physical activity (≥1 h/week: 0.45, 0.28–0.73) and METs (tertile 3: 0.54, 0.34–0.85) and lung cancer risk were present among smokers with ≥ 20 pack-years.ConclusionPhysical activity may play a role in reducing lung cancer risk among Black women, particularly among smokers. Future studies should explore biologic mechanisms whereby physical activity may influence carcinogenesis and investigate the role of exercise interventions in reducing lung cancer risk among smokers.     

Recommended Levels of Physical Activity Are Associated with Reduced Risk of the Metabolic Syndrome in Mexican-Americans

PurposeTo measure the association between physical activity and the metabolic syndrome risk in Mexican-Americans.MethodsParticipants were drawn from the Cameron County Hispanic Cohort (n = 3,414), a randomly selected Mexican-American cohort in Texas on the US-Mexico border. Moderate and vigorous physical activity was assessed using reliable and validated instruments. The metabolic syndrome was defined as having 3 or more metabolic abnormalities.ResultsOne thousand five hundred and twenty-four participants of the cohort (45.02%) were found to have the metabolic syndrome. Compared to participants who did not meet US physical activity guidelines, participants who met physical activity guidelines of 150 moderate and vigorous minutes per week (≥ 600 MET adjusted minutes) had 36% lower risk for the metabolic syndrome (OR = 0.64; 95% CI: 0.42–0.98), and participants with total minutes per week of moderate and vigorous/strenuous activity greater than 743 MET adjusted minutes had 37% lower risk for the metabolic syndrome (OR = 0.63; 95% CI: 0.42–0.94) compared with their counterparts, after adjusting for age, gender, annual household income, body mass index, smoking and alcohol drinking status, total portions of fruit and vegetable intake, census tracts and blocks, and survey version for physical activity.ConclusionsMeeting or exceeding physical activity guidelines significantly was inversely associated with the risk for the metabolic syndrome in Mexican-Americans. Improving levels of physical activity appears to be an effective target for the metabolic syndrome prevention and control among Mexican-Americans independent of other factors.     

Physical activity compliance: differences between overweight/obese and normal-weight adults

Objectives: Comparisons of physical activity measured by accelerometers in overweight/obese adults and their normal‐weight counterparts are limited. Compliance with the 2002 Institute of Medicine (IOM) exercise recommendations for 60 minutes of moderate‐intensity exercise daily has not been reported. The purpose of this study was to compare physical activity, as measured by accelerometers, in overweight/obese adults vs. normal‐weight controls and to assess compliance with recommendations for physical activity by the IOM in 2002 and by the Centers for Disease Control and Prevention and American College of Sports Medicine in 1995 for 30 minutes of moderate‐intensity activity, preferably all days of the week. Research Methods and Procedures: Sixty‐two overweight/obese subjects, BMI ≥ 25, included 31 adults, 12 men and 19 women, 25 to 69 years old, and their normal‐weight controls, BMI 18.5 to 24.9, matched for gender, age, and height. Body composition was assessed using DXA. Physical activity was measured with Actigraph accelerometers (MTI, Fort Walton Beach, FL) worn by each participant for 7 consecutive days. Results: Accelerometry data indicated that overweight/obese adults recorded ～60 counts per minute less per day and spent 21 minutes less engaged in moderate or greater intensity activity than their normal‐weight counterparts. Although 71% to 94% of those studied met 1995 recommendations, only 13% of overweight/obese subjects and 26% of normal‐weight participants met 2002 exercise recommendations. Discussion: These results suggest that daily minutes spent in moderate‐intensity activity or greater are associated with weight status and that the 2002 IOM recommendations may be difficult to meet even for normal‐weight individuals.     

Mortality in relation to tar yield of cigarettes: a prospective study of four cohorts.

OBJECTIVE--To investigate relation between tar yield of manufactured cigarettes and mortality from smoking related diseases. DESIGN--Prospective epidemiological study of four cohorts of men studied between 1967 and 1982. SETTING--Combined data from British United Provident Association (BUPA) study (London), Whitehall study (London), Paisley-Renfrew study (Scotland), and United Kingdom heart disease prevention project (England and Wales). SUBJECTS--Of the 56,255 men aged over 35 who were included in the studies, 2742 deaths occurred among 12,400 smokers. Average follow up was 13 years. MAIN OUTCOME MEASURES--Relative mortality from smoking related diseases according to tar yields of cigarettes smoked. RESULTS--Age adjusted mortality from smoking related diseases in smokers of filter cigarettes was 9% lower (95% confidence interval 1% to 17%) than in smokers related diseases consistently decreased with decreasing tar yield. Relative mortality in cigarette smokers for a 15 mg decrease in tar yield per cigarette was 0.75 (0.52 to 1.09) for lung cancer, 0.77 (0.61 to 0.97) for coronary heart disease, 0.86 (0.50 to 1.50) for stroke, 0.78 (0.40 to 1.48) for chronic obstructive lung diseases, 0.78 (0.65 to 0.93) for these smoking related diseases combined, and 0.77 (0.65 to 0.90) for all smoking related diseases. CONCLUSION--About a quarter of deaths from lung cancer, coronary heart disease, and possibly other smoking related diseases would have been avoided by lowering tar yield from 30 mg per cigarette to 15 mg. Reducing cigarette tar yields in Britain has had a modest effect in reducing smoking related mortality.     

Carcinogen mmetabolism and DNA adducts in human lung tissues as affected by tobacco smoking or metabolic phenotype: a case-control study on lung cancer patients

Individual variations in activity of pulmonary enzymes that metabolize tobacco-derived carcinogens may affect an individual's cancer risk from cigarette smoking. To investigate whether some of these enzymes (e.g., cytochrome P450IA-related) can serve as markers for carcinogen-induced DNA damage accumulating in the lungs of smokers, non-tumorous lung tissue specimens were taken during surgery from middle-aged men with either lung cancer (n = 54) or non-neoplastic lung disease (n = 20). Phase I (AHH, ECDE) and phase II (EH, UDPGT, GST) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were analyzed for DNA adducts, using ³²P-postlabeling.

Data analysis of subsets or the whole group of patients yielded the following results. (1) Phase I and II drug-metabolizing enzyme (AHH, EH, UDPGT, GST) activities in histologically normal surgical specimens of lung parenchyma were correlated with the respective enzyme activities in bronchial tissues of the same subject. (2) In lung parenchyma, enzyme (AHH, ECDE, EH, UDPGT) activities were significantly and positively related to each other, implying a similar regulatory control of their expression. (3) Mean activities of pulmonary enzymes (AHH, ECDE) were significantly (2- and 7-fold, respectively) higher in lung cancer patients who had smoked within 30 days before surgery (except GST, which was depressed) than in cancer-free subjects with a similar smoking history. (4) In the cancer patients, the time required for AHH, EH and UDPGT activities to return to the level found in non-smoking subjects was several weeks. (5) Bronchial tree and peripheral lung parenchyma preparations exhibited a poor efficiency in activating promutagens to bacterial mutagens in Salmonella. However, they decreased the mutagenicity of several direct-acting mutagens, an effect which was more pronounced in tissue from recent smokers. GSH concentration and GST activity were positively correlated with mutagen inactivation in the same sample. (6) In recent smokers, AHH activity in lung parenchyma was positively correlated with the level of tobacco smoke-derived DNA adducts. (7) Pulmonary AHH and EH activity had prognostic value in tobacco-related lung cancer patients. (8) An enhanced level of pro-oxidant state in the lungs was associated with recent cigarette smoking. Malondialdehyde level in lung parenchyma was associated with the degree of small airway obstruction, suggesting a common free radical-mediated pathway for both lung cancer induction and small airway obstruction.

These results demonstrate the pronounced effect of recent cigarette smoke exposure on pulmonary xenobiotic metabolism and lipid peroxidation and lend further support to the hypothesis that the inducibility of pulmonary AHH activity (cytochrome P450IA1 levels) in tobacco smokers is associated with lung cancer risk. Results on DNA adducts in smokers' lung tissue may help to explain why a certain metabolic phenotype accumulates more DNA damage in lung cells.     

Smoking Habits of Men Employed in Industry,and Mortality

A study of the relation between smoking habits and lung cancer in male industrial workers over a period of three years has confirmed the earlier findings in doctors that the death-rate from lung cancer correlates closely with the number of cigarettes smoked. Of 54,460 men studied 68.7% were current cigarette smokers. The annual mortality rate from lung cancer was 0.33 per thousand in non-smokers and ex-smokers, and 1.2 per thousand for all cigarette smokers, and higher in heavy smokers.Heavy cigarette smokers who retained the cigarette in the mouth between puffs (“drooping” cigarette habit) had an annual mortality rate of 4.1 per thousand.The mortality from coronary thrombosis in smokers was nearly three times that in non-smokers. A mortality gradient with rising consumption of cigarettes was observed.Some correlation between smoking and cancer of other sites and from non-neoplastic lung disease was observed in older men, but no correlation was found with other cardiovascular diseases and cerebrovascular diseases.     

Effects of acclimation and incubation temperature on the glutathione antioxidant system in killifish and RTH-149 cells

Glutathione (GSH) is an important antioxidant that is involved in a multitude of cellular processes. However, in fish, GSH levels, turnover, and activity of associated enzymes are low when compared to those of mammals. To determine whether temperature influences the GSH antioxidant system in fish, and can explain the differences in GSH between fish and mammals, we examined the effects of acclimation temperature on total GSH (tGSH) levels and apparent half-life (as an estimate of turnover) in a rainbow trout hepatoma cell line (RTH-149), and GSH levels, and glutathione peroxidase (GPx) and reductase (GR) activity in the eurythermal killifish. Increasing incubation temperature decreased half-life and transiently increased levels of tGSH in RTH-149 cells. In killifish, increased acclimation temperature increased tGSH levels in the liver, brain and muscle, and increased hepatic GPx and GR activities. When the relationships between temperature and GSH half-life, levels and enzyme activity were extrapolated to 37 degrees C, temperature could only partially accounted for differences in the GSH antioxidant system in fish compared to mammals. The differences in the GSH antioxidant system between fish and mammals may not be solely due to temperature effects, but also to the increased metabolic cost of endothermy in mammals.     

Sedentary Behaviors,Physical Activity,and Metabolic Syndrome in Middle‐aged French Subjects

Objective: To study the relationships of time spent in sedentary occupations with the National Cholesterol Education Program—defined metabolic syndrome (MS), taking into account the habitual level of physical activity (PA). Research Methods and Procedures: This was a cross‐sectional analysis in 1902 men and 1932 women 50 to 69 years of age participating in the French Supplementation with Antioxidant Vitamins and Minerals study. We assessed past‐year PA, television watching or computer use, and reading during leisure with the Modifiable Activity Questionnaire. Subjects who performed at least 150 min/wk of moderate‐intensity PA (3 to 6 metabolic equivalent tasks) or 60 min/wk of vigorous PA (>6 metabolic equivalent tasks) were considered as meeting recommended levels. Results: The frequency of most MS components increased with time spent in front of a screen and decreased with increasing PA levels. The likelihood to have MS, adjusted for age, education, and smoking, was decreased by one‐third in subjects meeting moderate PA guidelines and by two‐thirds in subjects meeting vigorous PA recommendations [odds ratio (95% CI), 0.34 (0.17 to 0.66) in women, 0.44 (0.28 to 0.68) in men] compared with those with insufficient PA. Independently of PA levels, time spent in front of a screen was positively associated with the likelihood to have the MS in women [odds ratio (95% CI), 3.30 (2.04 to 5.34)], whereas in both sexes, no association was found with time spent reading. Discussion: The relationship of the MS with a sedentary lifestyle differs according to sex and type of sedentary occupation. These results suggest the need to assess selected indicators of sedentary behavior in preventive programs.     

Lung glutathione adaptive responses to cigarette smoke exposure

Background

Smoking tobacco is a leading cause of chronic obstructive pulmonary disease (COPD), but although the majority of COPD cases can be directly related to smoking, only a quarter of smokers actually develop the disease. A potential reason for the disparity between smoking and COPD may involve an individual''s ability to mount a protective adaptive response to cigarette smoke (CS). Glutathione (GSH) is highly concentrated in the lung epithelial lining fluid (ELF) and protects against many inhaled oxidants. The changes in GSH that occur with CS are not well investigated; therefore the GSH adaptive response that occurs with a commonly utilized CS exposure was examined in mice.

Methods

Mice were exposed to CS for 5 h after which they were rested in filtered air for up to 16 h. GSH levels were measured in the ELF, bronchoalveolar lavage cells, plasma, and tissues. GSH synthesis was assessed by measuring γ-glutamylcysteine ligase (GCL) activity in lung and liver tissue.

Results

GSH levels in the ELF, plasma, and liver were decreased by as much as 50% during the 5 h CS exposure period whereas the lung GSH levels were unchanged. Next, the time course of rebound in GSH levels after the CS exposure was examined. CS exposure initially decreased ELF GSH levels by 50% but within 2 h GSH levels rebound to about 3 times basal levels and peaked at 16 h with a 6-fold increase and over repeat exposures were maintained at a 3-fold elevation for up to 2 months. Similar changes were observed in tissue GCL activity which is the rate limiting step in GSH synthesis. Furthermore, elevation in ELF GSH levels was not arbitrary since the CS induced GSH adaptive response after a 3d exposure period prevented GSH levels from dropping below basal levels.

Conclusions

CS exposures evoke a powerful GSH adaptive response in the lung and systemically. These data suggests there may be a sensor that sets the ELF GSH adaptive response to prevent GSH levels from dipping below basal levels. Factors that disrupt GSH adaptive responses may contribute to the pathophysiology of COPD.     

Comparison of antioxidant enzymes in saliva of elderly smokers and non-smokers

Objectives: This study was designed to compare the levels of copper/zinc superoxide dismutase (Cu/Zn SOD), peroxidase (POx) and glutathione peroxidase (GSH‐Px) in saliva of smokers and those in saliva of non‐smokers. Methods: Unstimulated saliva samples were collected from 88 elderly males (65 years old or over) who visited a private dental clinic. Forty‐four subjects were current smokers (more than 20 cigarettes daily for at least 30 years) and 44 were non‐smokers. The levels of salivary thiocyanate, Cu/Zn SOD, GSH‐Px, and POx activity were measured using standard procedures. Results: The mean levels of salivary thiocyanate (SCN^?) and SOD were significantly higher (p < 0.01) in the smoking group than in the non‐smoking group, whereas the specific activity levels of POx and GSH‐Px were significantly higher (p < 0.05) in the non‐smoking group than in the smoking group. Significant correlation coefficients were found between the levels of SCN^? and SOD (r = 0.37, p < 0.001). In the non‐smoking group, a significant positive association was found between specific activity of POx and age (r = 0.33, p < 0.05). Conclusion: Measurement of SCN^? and Cu/Zn SOD in human saliva might be useful for estimating the level of oxidative stress caused by cigarette smoke. Despite increased H₂O₂ level as a defense system induced by SOD, detoxification of H₂O₂ might be deteriorated in the oral cavity of elderly smokers.     

Physical Activity and Sedentary Behavior of Cancer Survivors and Non-Cancer Individuals: Results from a National Survey

Increasing physical activity and decreasing sedentary behavior are associated with a higher quality of life and lower mortality rates for cancer survivors, a growing population group. Studies detailing the behavior of cancer survivors are limited. Therefore, we investigated physical activity and sedentary behavior of cancer survivors using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Participants were those who provided physical activity and sedentary behavior data. Those who were pregnant, <20 years old, or <3 years from their cancer diagnosis were excluded. A cancer case was a self-reported diagnosis by a physician. We identified 741 cancer survivors and 10,472 non-cancer participants. After adjustment for age, race, gender, education status, body mass index, and smoking status, cancer survivors (n = 10,472) reported significantly longer duration of sedentary behavior (OR = 1.42, 95% CI (1.12, 1.80) for 8 or more hours, p-value for trend = 0.09), compared to non-cancer participants (n = 741). They also reported non-significant increases in maximum intensity, duration, frequency, and energy expenditure, whereas they reported significant increases in moderate intensity (OR = 1.26, 95% CI (1.01, 1.57)), moderate frequency (1–4 times/week) (OR = 1.32, 95% CI (1.00, 1.74)), and moderate energy expenditure (4018.5–7623.5 kcal) (OR = 1.30, 95% CI (1.00, 1.71)) of physical activity, compared to non-cancer participants. These patterns are similar for breast and prostate cancer survivors, with prostate cancer survivors more likely to engage in physical activity for more than one hour per day (OR = 1.98, 95% CI (1.05, 3.71)). Our findings suggest that cancer survivors tend to have more physical activity, but they are also more likely to engage in sedentary behavior.     

Cigarette smoke suppresses the ubiquitin-dependent degradation of OLC1

The newly identified gene, overexpressed in lung cancer 1 (OLC1), is highly expressed as OLC1 protein in the tumor tissues of lung cancer patients with histories of cigarette smoking. However, the underlying mechanisms of how the gene is affected by cigarette smoke have been poorly characterized. In this study, we investigated how OLC1 is regulated in lung cancer cells by cigarette smoke condensate (CSC).Compared to the controls, CSC treatment increased OLC1 protein levels in a dose- and time-dependent manner without affecting OLC1 mRNA levels in lung cancer cells. Ubiquitination of OLC1 protein was blocked upon CSC treatment. Biochemical analysis revealed that the ubiquitin E3 ligase anaphase promoting complex (APC) and its activators cell-division cycle protein 20 (CDC20) and cadherin-1 (CDH1) are responsible for the degradation of OLC1. However, upon introducing CSC the binding of OLC1 to the proteins CDC20, CDH1, and APC2 was impaired. These results demonstrate that CSC regulates OLC1 expression in lung cancer cells by compromising its ubiquitination and subsequent degradation through the ubiquitin E3 ligase APC.     

Exhalation of H2O2 and thiobarbituric acid reactive substances (TBARs) by healthy subjects

Enhanced exhalation of H2O2 and TBARs have been reported in various inflammatory lung diseases. This may reflect activated phagocytes influx and free radical generation in the airways. However, to apply these compounds as markers of oxidative stress it is necessary to understand factors influencing their exhalation in healthy subjects. We investigated the concentration of H2O2 and TBARs in expired breath condensate (EBC) of 58 healthy volunteers. EBC was collected seven times every 4 h during 24 h and three times every 7 d during 2 consecutive weeks. The H2O2 exhalation revealed diurnal variation with two-peak values 0.45 +/- 0.29 microM and 0.43 +/- 0.22 microM at 12:00 and 24:00 h. The lowest concentrations, 0.26 +/- 0.13 microM and 0.25 +/- 0.26 microM, were found at 20:00 and 8:00 h. Cigarette smokers exhaled about 2.4 times more H(2)O(2) than never smoked subjects. Moreover, in contrast to nonsmokers, cigarette smokers' H2O2 exhalation was stable over 2 week observation. The mean H2O2 concentration estimated over the whole 2 week period was higher in subjects above 40 years regardless of smoking habit, and it positively correlated with age in never smoked subjects (p <.004). Smoking of one cigarette caused 1.8-fold rise in H2O2 exhalation (p <.01). The baseline H2O2 levels correlated with cumulative cigarette consumption (p <.05) and MEF 25% of predicted (p <.05). Neither moderate exercise nor one puff of salbutamol nor ipratropium influenced significantly the concentration of H2O2 and TBARs in EBC. Only 4 of 120 EBC specimens from never smoked subjects revealed detectable levels of TBARs. Cigarette smokers exhaled more TBARs (p <.05) than never smoked volunteers. Our results indicate that healthy never smoked subjects exhale H2O2 with diurnal variation and significant changes over 2 week observation. Cigarette smoking enhanced H2O2 generation in the airways. These results could be useful for planning studies with exhaled H2O2 as a marker of airway inflammation. Occasional detection of TBARs in EBC of never smoked persons may be a result of sufficient antioxidant activity in the airways that protects tissues from peroxidative damage.     

Physical activity patterns using accelerometry in the National Weight Control Registry

The National Weight Control Registry (NWCR) was established in 1993 to examine characteristics of successful weight‐loss maintainers. This group consistently self‐reports high levels of physical activity. The aims of this study were to obtain objective assessments of physical activity in NWCR subjects and compare this to physical activity in both normal‐weight and overweight controls. Individuals from the NWCR (n = 26) were compared to a never obese normal‐weight control group matched to the NWCR group's current BMI (n = 30), and an overweight control group matched to the NWCR group's self‐reported pre‐weight‐loss BMI (n = 34). Objective assessment of physical activity was obtained for a 1‐week period using a triaxial accelerometer. Bouts of moderate‐to‐vigorous physical activity (MVPA) ≥10 min in duration, as well as nonbout MVPA (bouts of MVPA 1–9 min in duration) were summed and characterized. NWCR subjects spent significantly (P = 0.004) more time per day in sustained bouts of MVPA than overweight controls (41.5 ± 35.1 min/day vs. 19.2 ± 18.6 min/day) and marginally (P = 0.080) more than normal controls (25.8 ± 23.4). There were no significant differences between the three groups in the amount of nonbout MVPA. These results provide further evidence that physical activity is important for long‐term maintenance of weight loss and suggest that sustained volitional activity (i.e., ≥10 min in duration) may play an important role. Interventions targeting increases in structured exercise may be needed to improve long‐term weight‐loss maintenance.     

Sedentary Behaviour and Physical Activity in South Asian Women: Time to Review Current Recommendations?

Objective

Our aims were to describe activity and sedentary behaviours in urban Asian women, with dysglycaemia (diagnosed at recruitment), and without dysglycaemia and examine the relative contribution of these parameters to their glycaemic status.

Methods

2800 urban women (30–45 years) were selected by random cluster sampling and screened for dysglycaemia for a final sample of 272 newly diagnosed, drug naive dysglycaemic and 345 normoglycaemic women. Physical activity and sedentary behaviours were assessed by the International Physical Activity Questionnaire (IPAQ). Demographic data, diet and anthropometry were recorded. Logistic regression analysis assessed contribution of all parameters to dysglycaemia and exposure attributable fractions were calculated.

Results

The mean energy expenditure on walking (2648.5±1023.7 MET-min/week) and on moderate and vigorous physical activity (4342.3±1768.1 MET-min/week) for normoglycemic women and dysglycaemic women (walking;1046.4±728.4 MET-min/week, moderate and vigorous physical activity; 1086.7±1184.4 MET-min/week) was above the recommended amount of physical activity per week. 94.3% of women spent >1000 MET-minutes/week on activity. Mean sitting and TV time for normoglycaemic and dysglycaemic women were 154.3±62.8, 38.4±31.9, 312.6±116.7 and 140.2±56.5 minutes per day respectively. Physical activity and sedentary behaviour contributed to dysglycaemia after adjustment for family history, diet, systolic blood pressure and Body Mass Index. Exposure attributable fractions for dysglycaemia were; lower physical activity: 78%, higher waist circumference: 94%, and TV viewing time: 85%.

Conclusions

Urban South Asian women are at risk of dysglycaemia at lower levels of sedentary behaviour and greater physical activity than western populations, indicating the need for re-visiting current physical activity guidelines for South Asians.     

Systematic review of the epidemiological evidence comparing lung cancer risk in smokers of mentholated and unmentholated cigarettes

Background

US mentholated cigarette sales have increased considerably over 50 years. Preference for mentholated cigarettes is markedly higher in Black people. While menthol itself is not genotoxic or carcinogenic, its acute respiratory effects might affect inhalation of cigarette smoke. This possibility seems consistent with the higher lung cancer risk in Black men, despite Black people smoking less and starting smoking later than White people. Despite experimental data suggesting similar carcinogenicity of mentholated and non-mentholated cigarettes, the lack of convincing evidence that mentholation increases puffing, inhalation or smoke uptake, and the similarity of lung cancer rates in Black and White females, a review of cigarette mentholation and lung cancer is timely given current regulatory interest in the topic.

Methods

Epidemiological studies comparing lung cancer risk in mentholated and non-mentholated cigarette smokers were identified from MedLine and other sources. Study details were extracted and strengths and weaknesses assessed. Relative risk estimates were extracted, or derived, for ever mentholated use and for long-term use, overall and by gender, race, and current/ever smoking, and meta-analyses conducted.

Results

Eight generally good quality studies were identified, with valid cases and controls, and appropriate adjustment for age, gender, race and smoking. The studies afforded good power to detect possible effects. However, only one study presented results by histological type, none adjusted for occupation or diet, and some provided no results by length of mentholated cigarette use. The data do not suggest any effect of mentholation on lung cancer risk. Adjusted relative risk estimates for ever use vary from 0.81 to 1.12, giving a combined estimate of 0.93 (95% confidence interval 0.84-1.02, n = 8), with no increase in males (1.01, 0.84-1.22, n = 5), females (0.80, 0.67-0.95, n = 5), White people (0.87, 0.75-1.03, n = 4) or Black people (0.90, 0.73-1.10, n = 4). Estimates for current and ever smokers are similar. The combined estimate for long-term use (0.95, 0.80-1.13, n = 4) again suggests no effect of mentholation.

Conclusion

Higher lung cancer rates in Black males cannot be due to their greater preference for mentholated cigarettes. While some study weaknesses exist, the epidemiological evidence is consistent with mentholation having no effect on the lung carcinogenicity of cigarettes.