Noriko Sakano

Oxidative stress biomarkers and lifestyles in Japanese healthy people

The urinary concentrations of 8-isoprostane and 8-hydroxy-2’-deoxyguanosine (8-OHdG), which are biomarkers of oxidative stress, were measured in 677 Japanese people without any diseases, and their correlations with lifestyle facotrs, lifestyle-related blood biochemical parameters, and dietary intake of antioxidative vitamins were investigated. The mean urinary concentration of 8-isoprostane and 8-OHdG was 0.58 ng/mg creatinine and 8.43 ng/mg creatinine, respectively. Mean urinary 8-isoprostane was significantly different in terms of age, gender, smoking and alcohol consumption but not different in terms of body mass index (BMI) and exercise. By multiple regression analysis, urinary 8-isoprostane was significantly influenced by smoking and age. On the other hand, mean urinary 8-OHdG showed differences only by age group. Multiple regression analysis revealed that urinary 8-OHdG was significantly influenced by age, smoking, body weight, levels of high-sensitivity C-reactive protein (Hs-CRP) and low density lipoprotein-cholesterol in females, although it was significantly influenced by body weight in males. The present study shows that urinary 8-isoprostane is associated with lipid peroxidation related-lifestyles such as smoking, and urinary 8-OHdG is associated with arteriosclerosis related-factors such as Hs-CRP. Our findings suggest that 8-isoprostane and 8-OHdG appear to be prospective biomarkers for early prediction of lifestyle related-disease risk at the population level.

A longitudinal study of environmental risk factors for subjective symptoms associated with sick building syndrome in new dwellings.

This study was performed to explore possible environmental risk factors, including indoor chemicals, mold, and dust mite allergens, which could cause sick building syndrome (SBS)-type symptoms in new houses. The study was conducted in 2004 and 2005 and the final study population consisted of 86 men and 84 women residing in Okayama, Japan. The indoor concentrations of indoor aldehydes, volatile organic compounds, airborne fungi, and dust mite allergens in their living rooms were measured and the longitudinal changes in two consecutive years were calculated. A standardized questionnaire was used concomitantly to gather information on frequency of SBS-type symptoms and lifestyle habits. About 10% of the subjects suffered from SBS in the both years. Crude analyses indicated tendencies for aldehyde levels to increase frequently and markedly in the newly diseased and ongoing SBS groups. Among the chemical factors and molds examined, increases in benzene and in Aspergillus contributed to the occurrence of SBS in the logistic regression model. Indoor chemicals were the main contributors to subjective symptoms associated with SBS. A preventive strategy designed to lower exposure to indoor chemicals may be able to counter the occurrence of SBS.

Plasma 3-nitrotyrosine, urinary 8-isoprostane and 8-OHdG among healthy Japanese people

To examine the relation between lifestyle factors and oxidative stress biomarkers, this study analysed plasma 3-nitrotyrosine (3-NT), urinary 8-isoprostane and 8-hydroxy-2’- deoxyguanosine (8-OHdG) of 323 healthy Japanese without any disease. Plasma 3-NT was significantly increased by excessive exercise (p=0.010), but it was not significantly different in terms of sex, age (< 40, ≧40), BMI (<18.5, 18.5–24.9, ≧25.0), smoking (non-smokers, smokers) and alcohol drinking per week (non-drinkers, <10 units, ≧10 units). Urinary 8-isoprostane was significantly associated with alcohol drinking (p <0.01) and sex (p <0.01), although it had no significant relevance to age and exercise. Moreover, urinary 8-OHdG was positively associated with age (p <0.05) and negatively associated with BMI (p <0.05) and fasting insulin (p <0.001). However, it was not related with sex, smoking, alcohol drinking and exercise. In conclusion, the present results suggest that 3-NT, 8-isoprostane and 8-OHdG seem to be useful biomarkers for early prediction of lifestyle-related disease risk at the population level.

C-reactive protein is associated with cigarette smoking-induced hyperfiltration and proteinuria in an apparently healthy population

Although cigarette smoking is known to be an important risk factor for renal disease, the mechanism by which smoking induces progressive renal disease in a healthy population has not been established. We hypothesized that oxidative stress (measured as 8-iso-prostaglandin F2α, 8-iso-PGF2a), inflammation (highly sensitive C-reactive protein (CRP), hs-CRP) and nitric oxide may be associated with an alteration in the estimated glomerular filtration rate (eGFR) and proteinuria in otherwise healthy smokers. A total of 649 eligible subjects were classified according to their smoking status. Plasma NOx was measured using ozone-based chemiluminescence, urinary 8-iso-PGF2a was measured using enzyme immunoassay and serum hs-CRP was measured using a latex aggregation nephelometry method. The levels of 8-iso-PGF2a and hs-CRP increased in current smokers (P=0.001 and P=0.029, respectively), although there was not an increase in the NOx level. The prevalence of a high eGFR increased in light smokers (odds ratio (OR) 1.15 (95% confidence interval (CI), 0.61–2.17)) and heavy smokers (OR 2.33 (95% CI, 1.06–5.10)) when compared with non- and past smokers (P for trend=0.024). The multivariable-adjusted mean values of the eGFR in current smokers, reported from the lowest to the highest quintiles of hs-CRP levels, were 82.1, 85.1, 86.4 and 88.5 ml per min per 1.73 m2 (P for trend=0.027). The mean values of proteinuria were 28.6, 34.6, 37.2 and 39.5 mg g−1 creatinine (P for trend=0.003). The correlation coefficient between hs-CRP and eGFR was increased significantly (P=0.03) across non- (r=0.03), past (r=−0.17), light (r=0.13) and heavy smokers (r=0.31). In conclusion, cigarette smoking is a risk factor for renal function alteration in healthy smokers and is characterized by a high eGFR and a high urinary protein associated with an increase in the hs-CRP. This finding suggests that hs-CRP may help mediate the alteration of renal function in smokers.

Interactive Effects of Job Stress and Body Mass Index on Over-eating

Interactive Effects of Job Stress and Body Mass Index on Over‐eating: Jiro Takaki, et al. Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

Combined Effects of Working Hours, Income, and Leisure Time on Suicide in All 47 Prefectures of Japan

This study describes an ecological study that evaluated the combined effects of working hours, income, and leisure time on suicide in all 47 prefectures of Japan. In men, the age-adjusted rate of suicide (per 100,000 population) was significantly correlated with working hours (r=0.587, p<0.0001) as well as significantly and negatively correlated with income (r=−0.517, p=0.0002) and times for the leisure activities of self-education (r=−0.447, p=0.0016) and hobbies (r=−0.511, p=0.0002). In addition, a stepwise multiple regression analysis identified time for leisure social activities as a determining factor in suicide rate, even after adjusting for working hours and income. However, the impact of time for leisure social activities on suicide rate was smaller than that of working hours and income. In contrast, none of these factors affected suicide rate in women. These results suggest that increasing leisure time may be useful for preventing suicide among men in Japan.

Practicality of Veterans Specific Activity Questionnaire in Evaluation of Exercise Capacity of Community-Dwelling Japanese Elderly

ObjectiveThe aim of this study is to determine whether a questionnaire-based method using the Veterans Specific Activity Questionnaire (VSAQ) is a practical tool for the development of a safe exercise program to prevent a reduction in physical performance.MethodsOne hundred and twenty-one senior residents of Yakage, Okayama, agreed to voluntarily participate in this study. They were asked to complete a questionnaire for information on age, sex, subjective health status, exercise habits and VSAQ. We investigated the relationship between age and exercise capacity predicted by VSAQ (predicted metabolic equivalents (METs)). In addition, for 36 out of the 121 participants, we performed a 6-min walk distance test (6MD) and investigated whether its results correlate with the predicted METs. Furthermore, we prepared a modified VSAQ and examined its practicality in the evaluation of the exercise capacity of Japanese elderly (n=50).ResultsWe found that the predicted METs correlate well with age. Habitual exercise and subjective health status did not affect the predicted METs. A significant correlation was observed between the predicted METs and the results of 6MD (r=0.56, p<0.001). We also found that certain activities included in the original VSAQ are unfamiliar to Japanese elderly; thus, we made a few modifications to the original VSAQ in order to evaluate the physical fitness of Japanese elderly. The number of inadequate answers was reduced by employing the modified VSAQ.ConclusionThese findings imply that the modified VSAQ is useful in evaluating the exercise capacity of Japanese elderly adequately and is a practical scale for safe exercise.

Relationship between ceruloplasmin and oxidative biomarkers including ferritin among healthy Japanese

Serum ceruloplasmin (CP), a marker relevant to copper metabolism, is one of famous inflammation markers with a reduction in Wilson’s disease, whereas serum ferritin is a marker relevant to iron metabolism. Recently, ferritin is pointed out to be related with oxidative stress. However, there is still no population research which showed the relation of CP and ferritin. Therefore, we investigated the relationship between CP and ferritin including oxidative stress biomarkers among healthy Japanese (n = 389). We measured serum CP, ferritin, Fe, high-sensitivity C-reactive protein (hs-CRP), and urinary oxidative stress biomarkers [H2O2, 8-hydroxy-2’-deoxyguanosine (8-OHdG), 8-isoprostane] and so on. Subjects showed that age; 41.7 ± 10.0 (year), CP; 31.9 ± 6.8 (mg/dl), ferritin; 123.5 ± 121.0 (ng/ml), hs-CRP; 0.89 ± 2.53 (mg/l), 8-OHdG; 10.2 ± 4.4 [ng/mg creatinine (Cre)] and H2O2; 6.5 ± 10.9 (µM/g Cre), (All data mentioned above were expressed as mean ± SD). CP was significantly and positively correlated with hs-CRP and inversely correlated with ferritin, Fe and 8-OHdG. By a multiple logistic regression analysis, odds ratio of CP according to quartiles of hs-CRP was 4.86, and according to quartiles of 8-OHdG was 0.39 after adjusting for age and other confounding factors. In conclusion, our findings suggest that CP was an antioxidative biomarker which controls oxidative stress, whereas ferritin was a marker which may participate in the generation of oxidative stress.

Evaluation of serum arginase I as an oxidative stress biomarker in a healthy Japanese population using a newly established ELISA

OBJECTIVE We reported previously that serum arginase I increased in asthmatic patients and was associated with oxidative stress in a small healthy population. However, the exact association of arginase I with oxidative stress is not known. The present study aimed to analyze the association of arginase I with oxidative stress in a larger healthy population by a newly established ELISA. DESIGN AND METHODS The new ELISA for the measurement of human arginase I was established by generating recombinant arginase I protein in human arginase I gene-transfected Escherichia coli via an ARG1 cDNA fragment-inserted vector and -specific antibody in rabbits. Serum arginase I was evaluated in a cross-sectional study on a healthy population (n=721) by comparing a commercial ELISA kit with the new ELISA. RESULTS The mean levels of serum arginase I were 20.3 ± 0.7 ng/mL and 4.7 ± 0.2 ng/mL using the commercial ELISA kit and the new ELISA, respectively. Arginase I was correlated with WBC, RBC, hs-CRP, 8-OHdG, HDL-c, ALT, and BMI. Logistic regression analysis showed independent positive associations of arginase I with WBC, RBC, and urinary 8-OHdG and inverse independent associations with serum insulin and age. The association of arginase I with hs-CRP was not independent. CONCLUSION The independent associations of arginase I with urinary 8-OHdG and serum insulin may reflect its involvement in oxidative stress and diabetes mellitus.

The new school absentees reporting system for pandemic influenza A/H1N1 2009 infection in Japan

Objective To evaluate the new Japanese School Absentees Reporting System for Infectious Disease (SARSID) for pandemic influenza A/H1N1 2009 infection in comparison with the National epidemiological Surveillance of Infectious Disease (NESID). Methods We used data of 53,223 students (97.7%) in Takamatsu city Japan. Data regarding school absentees in SARSID was compared with that in NESID from Oct 13, 2009 to Jan 12, 2010. Results Similar trends were observed both in SARSID and NESID. However, the epidemic trend for influenza in SARSID was thought to be more sensitive than that in NESID. Conclusion The epidemic trend for influenza among school-aged children could be easily and rapidly assessed by SARSID compared to NESID. SARSID might be useful for detecting the epidemic trend of influenza.