井上 孝

Background: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelium nitric oxide synthase (NOS). ADMA binds to a substrate-binding site of NOS and then inhibits nitric oxide production from vascular endothelial cells. Elevated ADMA levels are a risk factor for cardiovascular disease. Recently, it was reported that plasma ADMA levels were negatively correlated with vegetable and fruit consumption. The purpose of this study was to examine the association between serum levels of carotenoids and serum ADMA levels in Japanese subjects. Methods: We conducted a cross-sectional study of 470 subjects (203 men and 267 women) who attended a health examination in August 2011. Serum levels of several carotenoids were separately measured by high-performance liquid chromatography. Serum ADMA levels were determined by using an enzyme-linked immunosorbent assay kit. Results: In women, the multivariate-adjusted odds ratios (ORs) of elevated serum ADMA levels were significantly decreased in the highest tertile for beta-cryptoxanthin (OR 0.47, 95% CI 0.23-0.95), alpha-carotene (OR 0.39, 95% CI 0.18-0.79), and beta-carotene (OR 0.36, 95% CI 0.17-0.73) compared to the lowest tertile. In men, significantly decreased ORs were observed in the highest tertiles of serum zeaxanthin/lutein (OR 0.23, 95% CI 0.06-0.69) and acarotene (OR 0.26, 95% CI 0.07-0.82), and in the middle and the highest tertiles of serum beta-carotene (OR 0.27, 95% CI 0.09-0.74 and OR 0.20, 95% CI 0.03-0.88, respectively) when the tertile cutoff points of women were extrapolated to men. Conclusions: Higher serum levels of carotenoids, such as alpha-carotene and beta- carotene, may help to prevent elevated serum ADMA levels in Japanese subjects.

Background: In many industrialized countries, non-alcoholic fatty liver disease (NAFLD) is recognized as an important disease that increases the risk of cardiovascular disease, type-2 diabetes, and metabolic syndrome. Most people with NAFLD are asymptomatic, and the disease is discovered incidentally during clinical laboratory tests. Present screening methods for NAFLD use ultrasound, and CT scans that are time-consuming, and a simple screening method for NAFLD is needed. In this study, we investigated whether serum miRNAs are associated with NAFLD and assessed the potential of serum miRNAs as a biomarker for NAFLD. Methods: We assessed intrahepatic fat by ultrasound scan, and the serum levels of five miRNAs (miR-21, miR-34a, miR-122, miR-145, and miR-451), which help regulate cholesterol and fatty acid homeostasis in liver tissue, by real-time PCR in a cross-sectional sample of 403 participants who attended health examinations. Results: Serum levels of miRNAs, miR-21, miR-34a, miR-122, and miR-451 were higher in participants with NAFLD. The serum level of miR-122 was correlated with the severity of liver steatosis. Conclusion: Serum levels of miRNAs, particularly miR-122, may be a useful biomarker for NAFLD. © 2013 Elsevier B.V.

Background: Albuminuria is a risk factor for not only nephropathy progression but also cardiovascular disease. Oxidative stress may have a role in the positive association between albuminuria and cardiovascular disease. Methods: This cross-sectional study investigated the associations of serum levels of carotenoids, which are dietary antioxidants, with albuminuria among 501 Japanese adults (198 men, mean age ± SD: 66.4 ± 10.0 years 303 women, mean age ± SD: 65.4 ± 9.8 years) who attended a health examination. Serum levels of carotenoids were determined by high-performance liquid chromatography. Logistic regression analysis was used to estimate odds ratios (ORs) with 95% CIs for albuminuria after adjustment for age, body mass index, smoking habits, drinking habits, hypertension, diabetes mellitus, and dyslipidemia. Results: Prevalence of albuminuria was 15.4% among men and 18.1% among women. Among women with albuminuria, geometric mean serum levels of canthaxanthin, lycopene, ß-carotene, total carotenes, and provitamin A were significantly lower than those of normoalbuminuric women. Adjusted ORs for albuminuria among women in the highest tertiles of serum ß-carotene (OR, 0.45 95% CI, 0.20-0.98) and provitamin A (OR, 0.45 95% CI, 0.20-0.97) were significantly lower as compared with those for women in the lowest tertile. There were no associations between serum carotenoids and albuminuria in men. Conclusions: An increased level of serum provitamin A, especially serum ß-carotene, was independently associated with lower risk of albuminuria among Japanese women. © 2013 Koji Suzuki et al.

Background: Several epidemiologic studies have reported an inverse association between serum levels of carotenoids and cardiovascular disease risk. However, no studies have reported an association between serum carotenoids and N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in the general population. Methods: In this cross-sectional study,we investigated whether serum carotenoids were associated with serum NTproBNP in 1056 Japanese subjects (390 men, 666 women) who attended a health examination. Serum levels of carotenoids were separately determined by high-performance liquid chromatography. Serum NT-proBNP level was measured by electrochemiluminescence immunoassay. Results: Serum NT-proBNP was elevated (≥55 pg/ml) in 31.8% of men and 48.2% of women. Multivariate logistic regression analyses adjusted for confounding factors showed a significant association between the highest quartile of serum a-carotene and elevated NT-proBNP in men (odds ratio [OR]= 0.40, 95% CI = 0.19-0.82, P for trend = 0.005) and women (OR = 0.62, 95% CI = 0.39-0.99, P for trend = 0.047). In women, moreover, elevated serum NTproBNP was significantly associated with serum canthaxanthin (OR = 0.57, 95% CI = 0.36-0.90 for highest quartile, P for trend = 0.026) and ß-cryptoxanthin (OR = 0.53, 95% CI = 0.32-0.85 for highest quartile, P for trend = 0.026), after adjusting for potential confounders. Conclusions: Higher levels of serum carotenoids were associated with lower risk of elevated serum NT-proBNP levels after adjusting for possible confounders, which suggests that a diet rich in carotenoids could help prevent cardiac overload in the Japanese population. © 2013 Japan Epidemiological Association.

Assessment of plaque formation in the common carotid artery (CCA) is important for stratification of the risk of subsequent stroke. The stiffness parameter beta, which can be assessed using an ultrasonic phase-locked echo-tracking system, was developed to evaluate arterial stiffness. The purpose this study was to examine the relationship of the stiffness parameter beta to intima-media thickness (IMT) and plaque formation. The stiffness parameter beta and mean IMT were measured using an ultrasonic phase-locked echo-tracking system and an automatic IMT measurement system, respectively, and the presence of plaque was assessed by ultrasonography in 347 subjects who took part in a health check-up program for community-dwelling people in Hokkaido. Values of the stiffness parameter beta were significantly higher in subjects with plaque formation than in those without plaque (10.60 +/- A 0.45 vs. 8.88 +/- A 0.23, P < 0.005) in whom IMT was not thickened; however, it was not different in subjects with increased IMT (> 1.0 mm). The percentage of plaque formation was significantly correlated with the value of the stiffness parameter beta. Furthermore, the stiffness parameter beta was significantly correlated with plaque formation after adjustment for several clinical variables (odds ratio 1.113-1.178, P < 0.001). The stiffness parameter beta is associated with plaque formation in the CCA, especially in subjects with a normal IMT. This could potentially be used as a predictor for plaque formation.

Background & aims: Several epidemiological studies have shown that circulating antioxidant levels are inversely associated with metabolic syndrome status. The purpose of this study was to examine the association of serum carotenoid levels, which have potent antioxidant effects, with metabolic syndrome and metabolic syndrome components in Japanese subjects. Methods: We conducted a cross-sectional study of 931 subjects (318 men and 613 women), aged 39-70 years, who attended a health examination. Metabolic syndrome was defined according to the diagnostic definition from the Japanese Examination Committee of Criteria for Metabolic Syndrome, which was released in 2005. Serum carotenoids were measured by high-performance liquid chromatography. Results: A significantly lower odds ratio (OR) for metabolic syndrome was observed in the highest tertile of serum beta-cryptoxanthin (OR:0.45; 95% CI:0.22-0.93 in men and 0.41; 0.17-0.93 in women) and beta-carotene (OR:0.45; 95% CI:0.21-0.95 in men and 0.37; 0.15-0.83 in women) compared to the lowest tertiles, in both sexes, but no significant association was found in male smokers. In women, moreover, OR for metabolic syndrome in the highest tertile of serum zeaxanthin/lutein (OR:0.37; 95% CI:0.16-0.84) was significantly lower than in the lowest tertile. Serum levels of beta-cryptoxanthin, alpha-carotene, and beta-carotene were significantly decreased with an increasing number of metabolic syndrome components in both sexes. Conclusions: These findings indicate that carotenoids may be important factors in the prevention of metabolic syndrome in nonsmokers, but further studies are required in smokers. (C) 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Background: Several studies have reported that serum concentrations of carotenoids and adiponectin are inversely associated with the risk for cardiovascular disease (CVD). However, no studies have investigated the association between serum concentrations of adiponectin and carotenoids in the general population. Methods: We investigated cross-sectionally whether serum carotenoids are associated with serum high molecular weight (HMW) adiponectin and some inflammatory markers in 437 Japanese subjects (116 men and 321 women) who attended a health examination. Results: In multiple linear regression analysis adjusted for confounding factors, serum beta-carotene concentrations were significantly associated with serum HMW adiponectin concentrations in both sexes (standardized beta coefficient = 0.197, p = 0.036 for men; standardized beta coefficient = 0.146, p = 0.012 for women). Serum alpha-carotene and beta-carotene concentrations were significantly associated with serum C-reactive protein (CRP) concentrations in men. In women, there were significant negative associations between serum carotenoids concentrations and serum interleukin-6 (IL-6) concentrations. Additional adjustment for serum concentrations of IL-6 or CRP did not significantly affect the association between carotenoids and HMW adiponectin in non-smoking men as well as in women. Conclusion: Serum beta-carotene concentrations were positively associated with serum HMW adiponectin concentrations even after adjustment for possible confounding factors including inflammatory markers. (C) 2010 Elsevier B.V. All rights reserved.

農漁業がおもな産業である北海道南部の八雲町の住民健診受診者を対象に, 自記式質問紙にて森林散策頻度の実態調査を行った。解析対象者は578人 (男性215人, 女性363人: 平均年齢 (標準偏差) 64.4 (10.2) 歳, 年齢範囲39∼89歳) であった。月1回以上, 森林散策をしている人は83人 (14.4%), 年1回以上の人は180人 (31.1%) であった。70歳代でも9.8%, 80歳代でも14.3%の人が, 週1回以上, 森林散策をしていた。都市部である静岡県中西部地区と比較した結果, 年齢, 性別, 職業, 森林散策の好き嫌いの分布を調整した後でも, 八雲町の方が森林散策頻度は有意に低く, 地域差が認められた。一方で, 森林散策と関連がある要因は静岡県中西部地区の結果と同様であり, 年齢が高く, 男性で, 森林散策が好きな人が森林散策の頻度が高い傾向が認められた。

Objectives The purpose of this study is to determine the levels of urinary 3-phenoxybenzoic acid (3-PBA) among general populations in rural and suburban areas and employees of pest control firms to evaluate the differences in the level of environmental or occupational pyrethroid (PYR) pesticides to which those populations are exposed. Methods Spot urine specimens were collected from male residents in a rural area (n = 143) and male residents in a suburban area (n = 66) in August of 2005 and 2007, respectively. Male employees of pest control firms, who also provided their urine specimens at the time of a health-checkup in August 2007, were classified either as sprayers (n = 14) or as non-sprayers ( n = 16) according to the presence of spraying during the pre-checkup week. Urinary concentrations of 3-PBA were determined using gas chromatography-mass spectrometry and corrected for the urinary creatinine concentrations. An analysis of covariance was used to examine the statistical difference in 3-PBA concentrations between these four groups after adjustment for age, body mass index, and current smoking/drinking habits. Results Multiple comparisons indicated no differences in adjusted 3-PBA concentrations between the groups of general residents from the rural areas (0.33 mu g/g cre in geometric mean) and suburban area (0.51 mu g/g cre). The group of sprayers showed a much higher level of 3-PBA concentrations (25.0 mu g/g cre) than the other three groups. A statistically significant difference, though to a lesser extent, was also exhibited in 3-PBA concentrations between the group of non-sprayers (5.6 mu g/g cre) and that of general residents. Conclusions The results indicated that the levels of background low-dose exposure to PYRs are not likely to differ evidently among general populations according to the area of residence. Moreover, employees of pest control firms, who have been away from PYR spraying operations for a week or more, still retain much higher urinary 3-PBA concentrations than general populations.

Background: Recent studies have revealed a close relationship between obesity and polymorphism in the inflammation gene. However, the association between interleukin-1beta (IL-1 beta) and obesity remains controversial. We therefore investigated the association between IL-1B C-31T polymorphism and obesity in Japanese. Methods: The participants were 802 inhabitants (281 men and 521 women) of Japan, aged 39 to 88 years, who attended a health examination in 2003. Body height, weight, waist and hip circumferences, and body fat percentage were measured. The IL-1B C-31T polymorphism was genotyped by polymerase chain reaction with confronting 2-pair primers. The association between IL-1B C-31T genotypes and various indices of obesity was then investigated. The confounding factor-adjusted odds ratios (OR) and 95% confidence intervals (CI) for obesity were calculated for each IL-1B C-31T genotype by using unconditional logistic regression analysis. Results: Among male carriers of the CT and TT genotypes, the ORs for high body fat percentage were 2.58 (95% CI, 1.17-6.34) and 2.81 (1.17-7.33), respectively, as compared to carriers of the CC genotype (P for trend = 0.037). Among women, carriers of the TT genotype had significantly higher ORs for high BMI (OR, 2.13; 95% CI, 1.25-3.67) and large waist circumference (2.49; 1.37-4.66), as compared to women with the CC genotype (P for trend = 0.005 and 0.004, respectively). Conclusions: The IL-1B C-31T polymorphism is associated with obesity in Japanese. Men and women with the TT genotype of IL-1B C-31T had a higher risk for obesity than those with the CC genotype.

Objectives The ingestion of pesticides in the daily diet is assumed to be the main modality of pesticide exposure for most people. A widely used class of pesticides in agricultural or residential settings is pyrethroid. We have examined the relationship between the intake frequency of selected items of vegetables and fruits and urinary metabolites of pyrethroid pesticides in a healthy general population. Methods A total of 535 residents (184 men and 351 women) who attended a healthcare checkup program conducted in a rural area of Hokkaido, Japan, in August 2005 provided informed consent for their spot urine samples to be used for the determination of 3-phenoxybenzoic acid (3-PBA) levels. They also completed a self-administered questionnaire regarding the intake frequency of 12 food items. The concentrations of creatinine-corrected 3-PBA were predicted by the intake frequency of each item, using analysis-of-covariance models to adjust for age, sex, body mass index, and drinking and smoking status. Results Both a significant association between the 3-PBA concentration and the frequency of tomato consumption and a significant positive linear trend was found in female subjects. In contrast, no such association was found in the male subjects. Conclusions The frequency of tomato consumption was confirmed to strongly predict the urinary pyrethroid metabolite levels in the general population\\-presumably because tomatoes are most often consumed raw and unpeeled (more so than all other vegetables and fruits analyzed in the current study). However, it should be noted that the 3-PBA levels, even among those subjects with the highest consumption of tomatoes, were far below the levels of toxicological significance, although the health consequences from long-term low-level exposure to pyrethroid requires further exploration. © 2009 The Japanese Society for Hygiene.

Background & aims: Recent studies have indicated a close relationship between hypertension and inflammation. Antioxidant substances, including beta-carotene, are known to be preventive factors for hypertension. We investigated the effect of serum P-carotene levels on the association between the interleukin-1 beta (IL-1B) C-31T polymorphism and hypertension. Methods: Subjects were 625 inhabitants (200 males and 425 females) of Japan, aged 39-70 years, who attended a health check-up examination in 2003. The IL-1B C-31T polymorphism was genotyped by polymerase chain reaction with confronting two-pair primers. Serum beta-carotene levels were measured using high-performance liquid chromatography. Results: The TT genotype of IL-1B C-31T was associated with an increased risk of hypertension in all subjects (Odds Ratio [OR] = 1.82, 95% Confidence Interval [95% CI] = 1.09-3.06, compared with CC genotype). Among male CC carriers, those with high serum P-carotene levels had a significantly lower OR (OR = 0.25, 95% CI = 0.06-0.95) for hypertension relative to those with low serum beta-carotene levels. The TT carriers had a significantly higher OR compared with the CC carriers among males with high serum beta-carotene levels (OR = 5.03, 95% CI = 1.34-21.58) and among females with low serum beta-carotene levels (OR = 2.47, 95% CI = 1.04-6.00). Conclusion: This study suggests that the IL-1B C-31T polymorphism is associated with hypertension, and that this association is modulated by serum beta-carotene levels. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Limited data are available on the background levels of exposure to synthetic pyrethroid (PYR) in Japan, despite their frequent application for agriculture and indoor extermination and possible effects of chronic and/or low-dose PYR exposure on human health. This study was conducted to describe the level and distribution of one of the major PYR metabolites, 3-phenoxybenzoic acid (3-PBA), in urine samples collected from a general population in Japan. The subjects were 535 individuals (184 men and 351 women; 61.5 +/- 9.8 years of age. mean +/- S.D.) residing in a town in Hokkaido, a dairy and agricultural area. Urinary 3-PBA was found detectable in 98% of samples above the limit of detection of 0.02 mu g/l. The geometric mean values of urinary 3-PBA in occupationally exposed farmers (n = 87) and the remaining general group without occupational exposure (n = 448) were 0.38 and 0.29 mu g/l, respectively, ranging from <LOD to 17.09 mu g/l. No significant differences in urinary 3-PBA concentrations were shown between these two groups. Moreover, 3-PBA concentrations were found comparable to those reported in some countries. The present study is, to our knowledge, the first report of a biological monitoring study of urinary 3-PBA, which elucidated the background environmental exposure level of PYR in the Japanese general population without occupational exposure. Further nationwide studies covering different seasons and age distribution are needed to monitor the urinary 3-PBA levels in Japan. (C) 2008 Elsevier Inc. All rights reserved.

Background Et aims: Few epidemiological studies have investigated the relationship between abdominal adiposity and serum levels of carotenoids. This study investigated the relationship between total and abdominal obesity and serum Levels of carotenoids. Methods: Study population consisted of healthy Japanese males (n = 192) and females (n = 398) who attended a health examination screening (age: 49-86 years). Serum carotenoids were measured by high-performance liquid chromatography. Multiple logistic regression analysis was used to provide the muttivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) of obesity indices for low levels of serum carotenoids. Results: In females, High waist circumference was associated with tow levels of serum canthaxanthin (OR = 2.00, 95% CI = 1.26-3.19) and beta-carotene (BC) (OR = 2.01, 95% CI = 1.23-3.28). High waist hip ratio was also associated with low levels of serum alpha-carotene and BC (OR = 2.44, 95% CI = 1.49-4.03, and OR = 1.97, 95% CI = 1.20-3.28, respectively). Similar results were obtained when body mass index was added to confounding factors. In mates, however, there were no significant associations between obesity indices and serum levels of carotenoids. Conclusions: Our results suggest that abdominal fat accumulation is associated with oxidative stress as determined by low levels of serum carotenoids in females. In mates, further study excluding the effect of strong confounding factors, including smoking, is needed. (c) 2006 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Chronic inflammation contributes to the process of carcinogenesis, but few epidemiologic studies have examined associations with risk of lung cancer. Relationships between lung cancer risk and serum levels of both heat shock protein 70 (Hsp70) and high-sensitivity C-reactive protein (hsCRP) were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 240 deaths from lung cancer were identified through 1999, and 569 controls were matched for sex, age, and study area. Serum levels were measured in 189 cases and 377 controls for Hsp70 and in 209 cases and 425 controls for hsCRP. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, including smoking habits, were 0.83 (0.44-1.58), 1.41 (0.77-2.60), and 1.84 (0.92-3.71) for Hsp70 (P-trend = 0.042) and 1.13 (0.67-1.91), 0.66 (0.38-1.16), and 1.19 (0.70-2.02) for hsCRP (P-trend = 0.941). In males, odds ratios (95% confidence intervals) across quartiles were 1.30 (0.59-2.84), 1.74 (0.83-3.67), and 2.49 (1.06-5.85) for Hsp70 (P-trend = 0.029). High levels of serum Hsp70 might thus be associated with increased risk of lung cancer among Japanese males, although further studies are needed to clarify associations between chronic inflammation and lung cancer.