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The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd on all-cause mortality in the Japanese general population. A 19-year cohort study was conducted in 1067 men and 1590 women aged 50 years or older who lived in three cadmium non-polluted areas in Japan. The subjects were divided into four quartiles based on creatinine adjusted U-Cd (µg g−1 cre). The hazard ratio (HR) and 95% confidence interval (CI) for continuous U-Cd or the quartiles of U-Cd were estimated for all-cause mortality using a proportional hazards regression.The all-cause mortality rates per 1000 person years were 31.2 and 15.1 in men and women, respectively. Continuous U-Cd (+1 µg g−1 cre) was significantly related to the all-cause mortality in men (HR 1.05, 95% CI: 1.02-1.09) and women (HR 1.04, 95% CI: 1.01-1.07). Furthermore in men, the third (1.96-3.22 µg g−1 cre) and fourth quartile (≥3.23 µg g−1 cre) of U-Cd showed a significant, positive HR (third: HR 1.35, 95% CI: 1.03-1.77, fourth: HR 1.64, 95% CI: 1.26-2.14) for all-cause mortality compared with the first quartile (<1.14 µg g−1 cre). In women, the fourth quartile of U-Cd (≥4.66 µg g−1 cre) also showed a significant HR (1.49, 95% CI 1.11-2.00) for all-cause mortality compared with the first quartile (<1.46 µg g−1 cre).In the present study, U-Cd was significantly associated with increased mortality in the Japanese general population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non-polluted areas in Japan. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this study was to estimate the reference level of cadmium in rice as the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for various renal effects by applying an updated hybrid approach. The participants were 1120 men and 1274 women aged 50 years or older who lived in the environmentally exposed Kakehashi river basin for at least 30 years. As indicators of renal dysfunction, glucose, protein, aminonitrogen, metallothionein and β2-microgrobulin in urine were measured. Cadmium concentration was determined for rice samples stored in warehouses of the farmers in all of the polluted hamlets. The BMD and BMDL that corresponded to an additional risk of 5% were calculated with background risk at a zero exposure set at 5%. The obtained BMDLs were 0.39 (aminonitrogen), 0.26 (metallothionein), 0.25 (β2-microgrobulin) mg kg-1 in men and 0.44 (glucose), 0.32 (protein), 0.33 (aminonitrogen), 0.28 (metallothionein) and 0.24 (β2-microgrobulin) mg kg-1 in women. The lowest BMDL was 0.25 and 0.24 mg kg-1 (β2-microgrobulin) in men and women respectively. These values were lower than the maximum level (0.4 mg kg-1) determined by the Codex Alimentarius Commission, indicating that these BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies have reported that maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces socioemotional and cognitive disturbances in rat offspring. In the present study, the effects of maternal TCDD exposure on putative inhibitory interneurons were investigated in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), hippocampus (HP), and superior colliculus (SC) in rat offspring. Dams were given TCDD (1.0μg/kg) on gestational day 15. When offspring rats reached adulthood (14 weeks old), parvalbumin (PV)- and calbindin (Calb)-immunoreactive neurons were immunohistochemically investigated. The histological investigations indicated that the mean area of the mPFC had increased, whereas the mean area of the SC decreased in the exposed male rats. In the exposed female rats, the mean SC area increased. Furthermore, the number and area of PV-immunoreactive neurons increased in the mPFC of the female exposed rats. In contrast, the number of PV-immunoreactive neurons in the BLA, HP, and SC decreased in the male and female exposed rats. The number of Calb-immunoreactive neurons decreased in the HP of the male and female exposed rats and the SC of the female exposed rats. Because PV- and Calb-immunoreactive neurons, which are putatively GABAergic, have been implicated in various higher brain functions, the effects of TCDD on socioemotional and cognitive functions might be mediated partly through these alterations in PV- and Calb-immunoreactive neurons in these areas. [Copyright &y& Elsevier]

Objective: Nearly 40 years after Agent Orange was last sprayed, we conducted a cross-sectional study to evaluate the impact of dioxin exposure on salivary hormones in Vietnamese primiparae. Our previous studies found higher levels of salivary cortisol and cortisone in one of the most highly dioxin-contaminated areas, known as a 'hot-spot', than in a non-exposed area. As a result, we suggested that further research with a larger number of participants would be needed to confirm whether dioxin affects steroid hormone levels in Vietnamese primiparae. Methods: The concentration of steroid hormones in saliva was determined by liquid chromatography (electrospray ionization tandem mass spectrometry), whereas the concentrations of polychlorinated dibenzo- p-dioxins (PCDDs) and dibenzofurans (PCDFs) in breast milk were determined by gas chromatography-high resolution mass spectrometry, for a sample of the population from a 'hot-spot' ( n = 16) and a non-exposed area ( n = 10). All subjects were aged between 20 and 30 years and had children aged between 4 and 16 weeks. Results: The mean toxic equivalence of PCDDs, PCDFs and PCDDs + PCDFs in breast milk in the hot-spot area was found to be significantly higher than in the non-exposed area ( p < 0.001). Likewise, salivary cortisol, cortisone and dehydroepiandrosterone (DHEA) levels were significantly higher in the hotspot area than in the non-exposed area ( p < 0.05). As a result, herein we report, for the first time, that salivary DHEA levels in primiparae are higher in a hot-spot than in a non-exposed area, and that this may be the result of dioxin exposure. Conclusions: Our findings highlight the long-term effects of Agent Orange/dioxin on steroid hormones in Vietnamese primiparae in the post-war period. [ABSTRACT FROM AUTHOR]

Objectives: Japan has a relatively high prevalence of smoking in men. Despite the importance of behavioral patterns on successful smoking cessation, only limited information is available in Japan. The present study collected data from former smokers in a rural community in Japan in order to identify health status at the time of cessation, predominant motivating factors, and the role of smoking cessation aids in individuals who successfully stopped smoking. Methods: This cross-sectional study collected data using a self-reported questionnaire from 149 randomly-selected former smokers (119 men and 30 women, aged 20-79 years) who were residents of Nanao, Ishikawa Prefecture, Japan. Results: Of the male participants, 14.3% quit due to serious personal health problems, including cardiovascular disease, cancer, or respiratory tract disease, while 20.8% of former smokers experienced mild personal health problems or were pregnant at the time of cessation. An approximately equal number stopped smoking due to fear of illness in the absence of immediate health concerns. Compared to personal health motivations, a smaller number of male smokers quit due to anti-smoking social pressure or expense. We also observed a marked increase in former smokers who quit for these reasons in recent years. Smoking lost its appeal in 19.3% of male and 10.0% of female smokers. Approximately, 95% of quitters did not utilize health professional counseling or pharmacological therapy. Conclusions: Personal health concerns in former smokers in Nanao, Japan were the predominant motivation for quitting smoking, with the vast majority of former smokers achieving successful smoking cessation by themselves. [ABSTRACT FROM AUTHOR]

Abstract: This study evaluated residual congener patterns of dioxin/furan (=PCDD/DF) related to tactical herbicides aerially sprayed over the regions of southern Vietnam through Operation Ranch Hand. The study focused on Cam Chinh (CC) commune, Quang Tri province (an area sprayed with tactical herbicides), and the Cam Phuc (CP) commune, Ha Tinh province (a non-sprayed area). Breast milk samples for analysis were collected in September 2002 and July 2003 from lactating primiparous and multiparous mothers born after the war (<31years old). We found the levels of each congener in the CC commune were higher than in the CP commune, and determined specificity in the PCDD/DF congener pattern in CC commune samples by cluster analysis. The congener pattern is characterized by higher (the hexa-, the hepta-, and the octa-) chlorinated PCDD/DFs; this appears to be the same profile as that presented by pentachlorophenol (PCP), rather than 2,4,5-trichlorophenoxy acid (2,4,5-T) contaminated with 2,3,7,8-TCDD. A GC/MS study in the 1970s detected the chlorophenols 2,4-di and 2,4,6-trichlorophenol in some Agent Orange samples, which contained, like PCP, a wide variety of PCDD/DF congeners. In this context, it may be expected that certain tactical herbicides contaminated with various chlorophenol impurities, have a unique congener pattern when compared with pure 2,4,5-T formulations. [Copyright &y& Elsevier]

Some residents of the Mae Sot district in Thailand have suffered long-term exposure to elevated dietary levels of cadmium. To test the hypothesis that chronic dietary cadmium exposure can cause imbalance in calcium dynamics and accelerate bone resorption, a group of these residents (156 men and 256 women aged ≥ 50) were selected on the basis of previous records of elevated urinary cadmium and tested for urinary and blood cadmium, bone formation and resorption markers, and the renal tubular dysfunction markers. Both genders had high levels of blood and urinary cadmium and high urinary levels of the markers for renal dysfunction and bone resorption in a dose–response relationship to urinary cadmium. The excretion of bone resorption markers was positively correlated to the ratio of excreted calcium and urinary cadmium. The results of a multivariate regression analysis indicated that bone resorption was accelerated by impaired calcium reabsorption in renal tubules. [ABSTRACT FROM AUTHOR]

The article focuses on a survey on the link between dioxin concentrations in breast milk and food group intake in Vietnamese herbicide-sprayed and nonsprayed areas. A questionnaire obtained information on personal characteristics and usual dietary intake. It concluded that bioxin exposure was less affected by dietary intake in the sprayed area compared with the nonsprsayed area.

The article presents a study on the correlativity of dioxin concentration in soil, sediment and breast milk in Vietnamese region sprayed with herbicide using a geographic information system (GIS). Soil, sediment and breast milk samples were analyzed using the geostatistical log-normal Kriging algorithm. The study showed that mean dioxin levels in herbicide-sprayed area were significantly higher than non-sprayed area.

Dioxins are known to affect infant growth and neurodevelopment in both humans and animals. In this study, we examined the relationship between neonatal head circumference, which is related to fetal brain development, and the concentration of dioxins in breast milk as an indicator of maternal exposure. A total of 42 milk samples were obtained on the fifth to eighth postpartum day from mothers in Japan exposed to dioxins in the environment. The levels of seven dioxins and 10 furan isomers were measured in each milk sample using an HR-GC/MS system. The relationships between the concentration of each dioxin isomer and newborn size, including head circumference, were then investigated after adjustment for confounding factors. The concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin isomer, negatively correlated with newborn head circumference, even after adjustment for gestational age, infant sex, parity and other confounding factors. However, there were no significant relationships between the concentration of other dioxin and furan isomers in maternal breast milk and infant height, weight and chest circumference at birth. These facts suggested that fetal brain development might be influenced by maternal exposure to TCDD in the environment.Journal of Exposure Science and Environmental Epidemiology (2008) 18, 246–251; doi:10.1038/sj.jes.7500589; published online 6 June 2007 [ABSTRACT FROM AUTHOR]

We examined the interrelationships between phenotype of hepatic cytochrome P450 2A6 (CYP2A6), nephropathy, and exposure to cadmium and lead in a group of 118 healthy Thai men and women who had never smoked. Their urinary Cd excretion ranged from 0.05 to 2.36 μg/g creatinine, whereas their urinary Pb excretion ranged from 0.1 to 12 μg/g creatinine. Average age and Cd burden of women and men did not differ. Women, however, on average showed a 46% higher urinary Pb excretion (p < 0.001) and lower zinc status, suggested by lower average serum Zn and urinary Zn excretion compared with those in men. Cd-linked nephropathy was detected in both men and women. However, Pb-linked nephropathy was seen only in women, possibly because of higher Pb burden coupled with lower protective factors, notably of Zn (p < 0.001), in women compared with men. In men, Pb burden showed a negative association with CYP2A6 activity (adjusted β = -0.29, p = 0.003), whereas Cd burden showed a positive association with CYP2A6 activity (adjusted β = 0.38, p = 0.001), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. The weaker correlation between Cd burden CYP2A6 activity in women despite similarity in Cd burden between men and women is consistent with opposing effects of Pb and Cd on hepatic CYP2A6 phenotypic expression. A positive correlation between Cd-linked nephropathy (urinary N-acetyl-β-D-glucosaminidase excretion) and CYP2A6 activity in men (r = 0.39, p = 0.002) and women (r = 0.37, p = 0.001) suggests that Cd induction of hepatic CYP2A6 expression and Cd-linked nephropathy occurred simultaneously. [ABSTRACT FROM AUTHOR]

Relationships between cadmium (Cd) body burden, kidney function and coumarin metabolism were investigated using two groups of 197 and 200 healthy Thais with men and women in nearly equal numbers. A mean age of one group was 30.5 years and it was 39.3 years for the other group. Of 397, 20 subjects (5%) excreted urine Cd between 1.4 μg/g and 3.8 μg/g creatinine and these subjects faced 10–15% increase in the probability of having abnormal urinary excretion of N-acetyl-β-d-glucosaminidase (NAG-uria). The prevalence of NAG-uria varied with Cd body burden in a dose-dependent manner (χ2=22, P<0.008). Also NAG-nuria was one of the three kidney effect markers tested that showed the greatest strength of correlation with urine Cd in both men and women (r=0.48, P<0.001). In addition, urine Cd excretion of men and women showed a positive correlation (r=0.46 to 0.54, P<0.001) with urine 7-hydroxycoumarin (7-OHC) excretion which was used as a marker of liver cytochrome P450 2A6 (CYP2A6) enzyme activity. Urinary Cd excretion accounted for 25% of the total variation in urine 7-OHC excretion (P<0.001). These data suggest that Cd may increase the expression of CYP2A6 in liver, resulting in enhanced coumarin metabolism in subjects with high Cd body burden. [Copyright &y& Elsevier]

A study to clarify the food composition and nutritional factors that contribute to the levels of blood and urinary cadmium (Cd) was conducted on 50 pregnant Japanese women with mean age of 29 years. The mean iron (Fe) intake of subjects was 9.2 mg, which is much lower than the recommended level of 20 mg for pregnant women. Cd in urine samples collected at 30–32 weeks of gestation were correlated (r=0.354), but urinary Cd was related to age more than blood Cd. Urinary Cd and blood Cd levels were inversely related to total energy (rpartial=−0.325, and −0.334, respectively) and fat intake (rpartial=−0.419,and −0.379, respectively), even after adjustment for age. Blood Cd was also correlated to protein and iron intake (rpartial=−0.299, and −0.353, respectively). These results indicate that Cd exposure levels of pregnant women with low energy intake, especially less fat intake, were higher than those of women with more energy and fat intake. In particular, blood Cd may be affected by protein and iron intake in pregnant women with increased these nutrients demand. [Copyright &y& Elsevier]

To clarify the influence of dioxin exposure on brain morphometry, the present study investigated associations between dioxin exposure at high levels and brain structural irregularities in 32 Vietnamese men. Two exposure markers were used: blood dioxin levels, as a marker of exposure in adulthood, and perinatal dioxin exposure, estimated by maternal residency in a dioxin-contaminated area during pregnancy. All subjects underwent brain magnetic resonance imaging (MRI) scans. We analyzed correlations between regional gray matter volumes and blood dioxin levels, and compared regional volumes between men with and without perinatal dioxin exposure using the voxel-based morphometry (VBM) tool from Statistical Parametric Mapping 12 (SPM12). Blood 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with low volume of the medial temporal pole and fusiform gyrus. Toxic equivalency (TEQ)-PCDDs were correlated with low medial temporal pole volume. However, 1,2,3,4,7,8-HxCDD was associated with high middle frontal gyrus and cerebellum volume. In men with perinatal dioxin exposure, the left inferior frontal gyrus pars orbitalis volume was significantly lower than in those without perinatal exposure. These results suggest that dioxin exposure during the perinatal period and in adulthood may alter regional brain volume, which might lead to cognitive deficits and unusual social emotional behavior in Vietnamese men living in dioxin-contaminated areas. [ABSTRACT FROM AUTHOR]

For 8 years, we have followed up a birth cohort comprising 241 mother-and-infant pairs living around the Da Nang airbase, a hot spot of dioxin contamination in Vietnam, and have reported the impacts of perinatal dioxin exposure on the neurodevelopment of children at various ages. In the present study, 9 years after birth, we investigated the effects of perinatal dioxin exposure on mu and theta rhythms by analyzing EEG power during the execution and observation of hand movements, which indicate mirror neuron system activity. One hundred fifty-five 9-year-old children (86 boys and 69 girls) from the Da Nang birth cohort participated in the EEG examination with free viewing of hand movements. The dioxin levels in their mothers' breast milk, measured 1 month after birth, were used as perinatal dioxin exposure markers. A log transform of the ratio of EEG power during execution or observation of the hand movements relative to the power during observation of a bouncing ball for theta and mu rhythms was used to evaluate mirror neuron activity. In both brain hemispheres, the log power ratio in the theta band was significantly higher (i.e., less reduction of power) during observation of hand movements in girls exposed to high levels of TCDD. In boys, however, dioxin congeners other than TCDD, including HxCDDs and several PCDF congeners, contributed to increased log power ratios in the theta band. Particularly for PCDF congeners, the log power ratios in the lowest group among 4 exposure groups were lowest and significantly increased (i.e., decreasing reduction of power) with increasing dose. Perinatal TCDD exposure may influence the mirror neuron system of the brain, which plays an important role for social-emotional behavior in children, particularly in girls living in a hot spot of dioxin contamination in Vietnam. [Display omitted] • Perinatal TCDD exposure decreased mirror neuron activity in 9-year-old girls. • Increasing some PCDF congeners significantly decreased mirror neuron activity in boys. • Mirror neuron impairment may be involved in developmental deficits due to dioxin exposure. [ABSTRACT FROM AUTHOR]

We used ultrasound (US) transmission to evaluate the speed of sound (SOS) and broadband ultrasonic attenuation (BUA) in the calcaneus in 17 male and 18 female inhabitants of a Cd-polluted area and 23 men and 45 women living in a nonpolluted area. Significant decreases in SOS and stiffness (Stiff), which was an index empirically derived from SOS and BUA, were found in Cd-exposed women. To evaluate the usefulness of the US measurements for detecting bone abnormality in Cd-exposed people, we examined the associations with the bone measurements of metacarpus by the previously used microdensitometry (MD) method and the grade of renal tubular damage due to Cd exposure. Bone density estimated by MD, SigmaGS/D, was significantly correlated with BUA, SOS, and Stiff in the Cd-exposed men and with BUA and Stiff in the Cd-exposed women. Further, in the Cd-exposed women, the decreases in BUA and Stiff correlated significantly with the increases in urinary theta2-microglobulin, while SigmaGS/D by the MD method did not. These results suggest that the m easurem ent of the calcaneus using US is not only radiation free but also can be used as a tool for population surveys aim ing to evaluate bone damage in people, especially women, showing renal tubular damage due to environmental Cd exposure. [ABSTRACT FROM AUTHOR]