[Show abstract][Hide abstract] ABSTRACT: Autonomic imbalance is one of the important pathways through which psychological stress contributes to cardiovascular diseases/sudden death. Although previous studies have focused mainly on stress at work (work stress), the association between autonomic function and stress at home (home stress) is still poorly understood. The purpose was to clarify the effect of work/home stress on autonomic function in 1,809 Japanese male workers. We measured corrected QT (QTc) interval and QT index on the electrocardiogram along with blood pressure and heart rate. Participants provided self-reported information about the presence/absence of work/home stress and the possible confounders affecting QT indicators. Home stress was related positively to QT index (p=0.040) after adjusting for the possible confounders, though work stress did not show a significant relation to QTc interval or QT index. The odds ratio of home stress to elevated QT index (≥105) was 2.677 (95% CI, 1.050 to 6.822). Work/home stress showed no significant relation to blood pressure or heart rate. These findings suggest that autonomic imbalance, readily assessed by QT indicators, can be induced by home stress in Japanese workers. Additional research is needed to identify different types of home stress that are strongly associated with autonomic imbalance.
[Show abstract][Hide abstract] ABSTRACT: Elevated alanine aminotransferase (ALT) in serum, relevant to nonalcoholic fatty liver disease, has been often reported from Asian countries and the U.S., and it may be associated with lifestyle behavior. To clarify whether specific dietary behavior is associated with hepatocellular injury, we explored liver markers and dietary lifestyles (e.g., breakfast-skipping, eating for lunch, and snacking) in 1,809 male employees, aged 19-59 years, belonging to a health insurance union of automobile dealerships in Japan. ALT, γ-glutamyltransferase, and asparate aminotransferase (AST) were positively correlated with age and body mass index (BMI) (P < 0.0001). Odds ratios (ORs) of instant noodle ingestion for lunch to ALT elevation (> 30 IU/L), after adjusting for possible confounders including age, BMI, and drinking, were 1.33 (95% confidence interval, 1.01-1.75) at 1-2 times/week and 1.47 (1.07-2.01) at ≥ 3 times/week, compared to those who seldom ate instant noodles. Likewise, the OR of the ingestion at ≥ 3 times/week to γ-glutamyltransferase elevation (> 50 IU/L) was 1.42 (1.02-1.99), but the OR to elevated AST (> 30 IU/L) was not statistically significant. Habitual ethanol intake was significantly associated with hepatocellular injury, though the threshold of daily ethanol intake differed among liver markers. Despite the low OR, habitual instant noodle ingestion for lunch is associated with ALT elevation. Since the average content of saturated fatty acids in instant noodles is considerably high among cereal foods in Japan, workers with this habit should be advised to avoid having unbalanced diets.
No preview · Article · Dec 2013 · The Tohoku Journal of Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: A rapid and sensitive analytical method using gas chromatography-mass spectrometry (GC-MS) was developed for the measurement of neonicotinoid (NEO) metabolites 6-chloronicotinic acid (6CN), 2-chloro-1,3-thiazole-5-carboxylic acid (2CTCA) and 3-furoic acid (3FA) from human urine. After acid hydrolysis, the metabolites were extracted using solid phase extraction (SPE) column (Bond Elute Plexa PCX) and eluted with methanol. N,O-bis (trimethylsilyl) trifluoroacetamide with 1% trimethylchlorosilane (BSTFA-TMCS, 99:1) was used for the derivatization of metabolites and analyzed by GC-MS with the electron ionization mode. The elution solvent, derivatization reagent and its conditions were mainly optimized for improved detection and quantitation of the metabolites based on signal-to-noise ratio, recoveries and reproducibility. Our present method offered a sufficiently low limit of detection (0.1μg/L for each metabolite) with satisfactory within-run and between-day accuracy and precision (variability less than 12.3%, R.S.D). This method is simple, sensitive and precise, and has been successfully applied to quantify low concentrations of urinary 6CN, 2CTCA and 3FA for the occupational NEO exposures survey.
No preview · Article · Oct 2013 · Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
[Show abstract][Hide abstract] ABSTRACT: Performance of two new air sampling bags [the transparent bag (TP bag) and the semi-transparent bag (ST bag)] was examined as possible surrogates for the traditional PVF bag (the Ref bag). Solvent vapor mixture of butyl acetate, chloroform, ethyl acetate, isopropyl alcohol and toluene at administrative control levels were introduced to each bag (n=5 for each of the three types), and the decay in the concentrations (by %) was followed by use of a gas auto-sampler - FID-GC system. A trend of time-dependent decay was noted for all types including the Ref bag. When the performance was compared, the TP bag was equal to or even better than the Ref bag. In contrast, the performance of the ST bag was comparable to that of the other two types of bags with regard to toluene and chloroform when the storage time was short, but poorer than others for the other three solvents throughout the test period. The TP bag may be a bag of choice when the storage time is extended (e.g., up to 48 h) although this bag is physically less robust and requires careful handling. The ST bag may be used when analysis will be completed within 24 h.
No preview · Article · Feb 2013 · Industrial Health
[Show abstract][Hide abstract] ABSTRACT: To clarify the links between ECG QT-related parameters and heart rate variability (HRV) and the covariates possibly distorting them, the averaged RR and QT intervals in a single lead ECG were measured for 64 male and 86 female subjects aged 18-26. The QT index, defined by Rautaharju et al., in the young adults was not significantly related to any HRV parameters nor heart rate, but the Bazett's corrected QT (QTc) interval was associated negatively with the parasympathetic activity and positively with heart rate. No significant differences in the QTc interval, QT index or heart rate were seen between the men and women, but they significantly differed between both sexes after adjustment for possible covariates such as age and body mass index (BMI). Significant sex differences in parasympathetic parameters of the HRV were unchanged before and after the adjustment, but significant differences observed in the unadjusted sympathetic parameters disappeared after adjusting for covariates. Age, BMI and body fat percentage also were significant covariates affecting these ECG parameters. Consequently, QT index, unaffected by heart rate and HRV parameters, appears to be a more useful indicator than the QTc interval. Instead, the QT index and HRV parameters are recommended to be simultaneously measured in epidemiological research because they are probably complementary in assessing autonomic nervous function. Also, these parameters should be analyzed in men and women separately.
[Show abstract][Hide abstract] ABSTRACT: A recent development in analytical chemistry has enabled us to monitor systemic organophosphorus insecticide (OP) exposure at individual levels. At present, however, limited data are currently available on urinary OP metabolite levels worldwide. The purpose of this study was to assess urinary dialkylphosphate (DAP) concentrations in Japanese workers. Urine samples were collected in both summer and winter from 339 Japanese adults who worked as food distributors (FDs, n=164), apple farmers (AFs, n=147) and pest control operators (PCOs, n=28). DAPs were measured by gas chromatography-mass spectrometry after derivatization with pentafluorobenzylbromide. Dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP) were detected in the urine of over 87% of the studied populations in both seasons. The geometric mean values of total DAPs (nmol g(-1) creatinine), DMP, DMTP, DEP and DETP (μg g(-1) creatinine) in summer and winter were 106.7 and 98.3, 7.0 and 3.8, 3.4 and 4.5, 0.8 and 1.5, and 0.3 and 0.2 for the FDs, 440.8 and 197.7, 33.1 and 10.8, 10.1 and 5.8, 4.2 and 4.7 and 1.6 and 0.8 for the AFs, and 473.4 and 284.6, 28.9 and 22.2, 17.6 and 4.6, 3.5 and 4.4, and 0.5 and 0.6 for the PCOs, respectively, thereby revealing significantly higher concentrations in AFs and PCOs groups than in the FDs in both seasons except for winter DMTP. These DAP concentrations were approximately the same or at lower levels compared with those reported in the previous literature. This is one of the first studies to demonstrate urinary DAP concentrations in Japanese adults.
[Show abstract][Hide abstract] ABSTRACT: More than fifty years have passed since the outbreak of Minamata disease, and large-scale methylmercury poisoning due to industrial effluents or methylmercury-containing fungicide intoxication has scarcely happened in developed countries. On the other hand, widespread environmental mercury contamination has occurred in gold and mercury mining areas of developing countries. In this article, we provided an overview of recent studies addressing human health effects of methylmercury, which we searched using the PubMed of the US National Library of Medicine. The following suggestions were obtained for low-level methylmercury exposure: (1) In recent years, the proportion of human studies addressing methylmercury has tended to decrease. (2) Prenatal exposure to methylmercury through fish intake, even at low levels, adversely affects child development after adjusting for polychlorinated biphenyls and maternal fish intake during pregnancy, whereas maternal seafood intake has some benefits. (3) Long-term methylmercury exposure through consumption of fish such as bigeye tuna and swordfish may pose a potential risk of cardiac events involving sympathovagal imbalance. (4) In measuring methylmercury levels in preserved umbilical cord collected from inhabitants born in Minamata areas between 1945 and 1989, the elevated concentrations (≥1 mg/g) were observed mainly in inhabitants born between 1947 and 1968, and the peak coincided with the peak of acetaldehyde production in Minamata. (5) Since some developing countries appear to be in similar situations to Japan in the past, attention should be directed toward early recognition of a risky agent and precautions should be taken against it.
No preview · Article · Sep 2011 · Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene)
[Show abstract][Hide abstract] ABSTRACT: By publishing the scientific opinion entitled "Use of the benchmark dose (BMD) approach in risk assessment: Guidance of the Scientific Committee," the European Food Safety Authority (EFSA) recommended that the BMD approach, as an alternative to the traditionally used no-observed-adverse-effect level approach, be used as the method of choice for the determination of the reference point for deriving health-based guidance values and margins of exposure, and described the BMD approach as being extensively applicable to all chemicals, even to dose-effect assessment of epidemiological data. When the BMD approach was first proposed, the approach was expected to estimate the dose causing a low but measurable target organ effect. We examined whether the BMD approach can be applied to epidemiological endpoints with clinical standards.
Comparisons between the BMD approach recommended by the EFSA and classical BMD approach (hybrid method) were conducted using epidemiological data with clinical standards.
The 95% lower confidence limit of the EFSA-based BMD tended to be considerably lower than that of the hybrid method. The former approach is easily applicable to dose-response data in published papers, though it is difficult to adjust for possible confounders. The cutoff values, calculated by the hybrid method, of epidemiological endpoints are nearly concordant with the clinical standards.
By using the BMD approach recommended by the EFSA, human health safety may be better guaranteed because of the lower reference points for hazardous substances. However, its application to epidemiological data does not always reflect toxicological implications in light of the clinical standard.
No preview · Article · Apr 2011 · Sangyo eiseigaku zasshi Journal of occupational health
[Show abstract][Hide abstract] ABSTRACT: The Scientific Committee on Neurotoxicology and Psychophysiology and the Scientific Committee on the Toxicology of Metals of the International Commission on Occupational Health in 2006 recommended that the standard for blood lead (BPb) levels be reduced to 30 microg/dl for industrial workers and 5 microg/dl for children. To examine whether the critical level of lead producing adverse effects truly differs between workers and children, we provided an overview of studies addressing the critical level of lead in workers, together with a perspective on lead toxicity in children.
In 25 reports published in English with keywords of "benchmark dose (BMD)," "lead" and "humans," only five studies proved to be relevant to lead toxicity. Four more studies with figures illustrating significant relationships between lead and neurotoxic outcomes were selected.
Based on data from previous reports using a BMD approach, the critical organ of lead in workers was thought to be the nervous system and the critical BPb level (number-weighted mean) was between 10.7 and 17.5 microg/dl. The neurotoxic effects of lead exposure at such levels seemed reversible. The BPb level at which lead-associated intellectual deficits occurred in children was as low as the critical level of BPb (below 5 microg/dl) for inhibited heme synthesis in workers.
The neurotoxic effects of lead in workers appear to be initiated at BPb levels below 18 microg/dl, which are somewhat higher than the critical level of lead neurotoxicity in children. Each national institute for risk management should take evidence-based preventive action against subclinical lead poisoning in workers, as well as in children.
Preview · Article · Dec 2008 · Journal of Occupational Health
[Show abstract][Hide abstract] ABSTRACT: To scrutinize the neuromotor effects of acute alcohol ingestion, postural sway, hand tremor, and reaction time were measured before and after alcohol or juice ingestion in 13 healthy volunteers at 20-22 years (mean 20.7) of age. The dose of ethanol consumed by the subjects (mean+/-S.D.) was 0.59+/-0.07 g/kg body weight, and the blood ethanol concentrations were estimated to be 0.86+/-0.23 g/l at 30 min after ethanol ingestion; 0.88+/-0.19 g/l at 70 min; 0.74+/-0.27 g/l at 130 min. The 1-h and 2-h changes in sway area, total transversal sway (Dx), and Dx at 0-1 Hz with eyes closed were significantly larger after alcohol ingestion than after juice ingestion. Similarly, the 2-h changes in sway area, total Dx, and Dx at 0-1 Hz with eyes open were significantly larger after alcohol ingestion than after juice ingestion. No significant differences were seen between alcohol and juice ingestion regarding changes in hand tremor or reaction time. These data suggest that the static balance due to acute alcohol ingestion is characterized mainly by transversal sway of low frequency (0-1 Hz) with eyes closed, which seems to differ from the characteristics of postural sway in alcoholics.
[Show abstract][Hide abstract] ABSTRACT: The objective was to clarify the effect of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) genotypes on the diabetic risk in Japanese workers.
At the time of mandatory health checkup, the ADH2 and ALDH2 genotypes, as well as fasting plasma glucose (FPG) levels, body mass index (BMI), smoking habit, and weekly alcohol intake, were examined in 492 men and 183 women working at motor vehicle dealerships.
In using two-way analysis of variance to manipulate ADH2 and ALDH2 genotypes and alcohol intake (>70 g/week for men and >35 g/week for women), the FPG level after the adjustment for age, BMI, smoking habit, and another genotype was significantly higher in the men with ADH2*1/1 genotype than in those with the other genotypes, but there was no significant difference in the FPG level between the men with and without ALDH2*1/1 genotype. In contrast, the women with ALDH2*1/1 genotype had significantly lower FPG levels than those with the other genotypes, but there was no significant difference in the FPG level between the women with and without ADH2*1/1 genotype. Also, a significant interaction between ethanol intake and ALDH2 genotypes was seen only in the women.
These findings suggest that genotypes of ADH2 and ALDH2 can modify the diabetic risk, irrespective of amounts of alcohol consumed. Also, there may be sex differences in the effect of these enzyme genotypes on glucose metabolism.
Preview · Article · Jan 2008 · Alcohol and Alcoholism
[Show abstract][Hide abstract] ABSTRACT: An association between ambient air pollution and reduced cardiac autonomic function assessed by heart rate variability (HRV) mainly in elderly persons has been suggested by a number of epidemiological studies, but the link between the HRV and pulmonary function in humans remains unknown although such air pollution should primarily affect pulmonary function. To clarify this link, pulmonary ventilation parameters such as oxygen uptake (V(O(2))) and carbon dioxide output (V(CO(2))), as well as the HRV with spectral analysis (high- and low-frequency components of HRV, i.e., CCV(HF) and CCV(LF), reflecting cardiac parasympathetic and sympathetic activities, respectively), were measured in 66 healthy women aged 19-20 years after an overnight fast of 12 h. Significant correlations were found between the CCV(HF) of HRV and both the end-tidal carbon dioxide concentration (FET(CO(2))) and gas exchange ratio (V(CO(2))/V(O(2))) in the subjects (partial correlation coefficients r = 0.354 and 0.320, respectively), whereas there was no significant connection between the FET(CO(2)) and the V(CO(2))/V(O(2)). Similarly, the CCV(LF) correlated significantly with the resting tidal volume of lung (r = 0.364). These findings suggest that resting pulmonary ventilation function interacts with cardiac autonomic function assessed by the HRV, at least in healthy young adults, which may be useful for explaining the pathophysiology concerning the short-term effect of air pollution such as fine particulate matter on cardiovascular function.
Preview · Article · Sep 2007 · Biomedical Research
[Show abstract][Hide abstract] ABSTRACT: A cross-sectional study was carried out to clarify the physiological features of spontaneous awakening from nocturnal sleep (i.e., whether a child can spontaneously wake up on weekday mornings). The study population comprised 116 children at ages 5 and 6 years. Heart rate variability reflecting cardiac sympathetic and parasympathetic activities was measured. Children's typical bedtimes and wake times for weekdays and the presence/absence of spontaneous awakening from nocturnal sleep were reported by parents, and information about obligatory naptimes was provided by preschool teachers. The mean total sleep duration in the children was 625+/-56 (standard deviation) min. Total and nocturnal sleep durations were significantly shorter in 52 children without spontaneous awakening than in 64 children with it. Similarly, the parasympathetic activity was significantly lower in the children without spontaneous awakening, even in using analysis of covariance. Heart rate was significantly increased in the children without spontaneous awakening, but neither total nor nocturnal sleep durations were significant covariates in the analysis of covariance. In conclusion, the absence of spontaneous awakening from nocturnal sleep in preschool children is suggested to be characterized by short sleep duration, parasympathetic hypoactivity, and elevated heart rate.
No preview · Article · Jun 2007 · Autonomic Neuroscience
[Show abstract][Hide abstract] ABSTRACT: Current risk assessment of elemental mercury vapor is based on the tremor toxicity. To clarify the neuromotor effects of occupational exposure to mercury vapor, hand tremor and postural sway were measured in 27 miners and smelters (i.e., exposed workers) and 52 unexposed subjects.
Urine samples were collected and total mercury and creatinine concentrations were determined. Data of the tremor and postural sway were analyzed using the fast Fourier transformation.
The geometric means of the urinary mercury level (UHg) were 228 (range 22.6-4,577) microg/g creatinine for the exposed workers and 2.6 (1.0-17.4) microg/g creatinine for the unexposed subjects. Total tremor intensity and frequency-specific tremor intensities at 1-6 and 10-14 Hz were significantly larger in the exposed workers than in the unexposed subjects (P < 0.05), but they were not significantly related to the UHg among the exposed workers (P > 0.05). In contrast, there were no significant differences in any postural sway parameters between the above two groups (P > 0.05), but the transversal sway with eyes open was positively related to the UHg among the exposed workers in using multiple regression analysis (P < 0.05).
These findings suggest that postural sway, as well as hand tremor, may be affected by elemental mercury vapor exposure, but the former test seems to be less sensitive to mercury than the latter one.
Full-text · Article · Apr 2007 · International Archives of Occupational and Environmental Health
[Show abstract][Hide abstract] ABSTRACT: To investigate the relations among total mercury levels in hair, toenail, and urine, together with potential effects of methylmercury intake on renal tubular function, we determined their levels, and urinary N-acetyl-beta-D-glucosaminidase activity (NAG) and alpha1-microglobulin (AMG) in 59 women free from occupational exposures, and estimated daily mercury intakes from fish and other seafood using a food frequency questionnaire. Mercury levels (mean+/-SD) in the women were 1.51+/-0.91 microg/g in hair, 0.59+/-0.32 microg/g in toenail, and 0.86+/-0.66 microg/g creatinine in urine; and, there were positive correlations among them (P<0.001). The daily mercury intake of 9.15+/-7.84 microg/day was significantly correlated with total mercury levels in hair, toenail, and urine (r=0.551, 0.537, and 0.604, P<0.001). Among the women, the NAG and AMG were positively correlated with both the daily mercury intake and mercury levels in hair, toenail, and urine (P<0.01); and, these relations were almost similar when using multiple regression analysis to adjust for possible confounders such as urinary cadmium (0.47+/-0.28 microg/g creatinine) and smoking status. In conclusion, mercury resulting from fish consumption can explain total mercury levels in hair, toenail, and urine to some degree (about 30%), partly through the degradation into the inorganic form, and it may confound the renal tubular effect of other nephrotoxic agents. Also, the following equation may be applicable to the population neither with dental amalgam fillings nor with occupational exposures: [hair mercury (microg/g)]=2.44x[toenail mercury (microg/g)].
No preview · Article · Feb 2007 · Environmental Research
[Show abstract][Hide abstract] ABSTRACT: The subclinical effects of prenatal exposure to methylmercury from fish consumption on the cardiac autonomic function were assessed in 136 Japanese 7-year-old children recruited for this study.
Samples of child's hair and dry umbilical cord preserved were collected, and hair mercury and cord tissue methylmercury concentrations were determined as current and prenatal exposure biomarkers, respectively. Cardiac autonomic indicators of parasympathetic and sympathetic activities were calculated from the electrocardiographic RR intervals measured.
In the children, the cord tissue methylmercury (0.017-0.367, median 0.089 microg/g) was not significantly correlated with the hair mercury (0.43-6.32, median 1.66 microg/g). The cord tissue methylmercury was related negatively to parasympathetic components of cardiac autonomic indicators (P < 0.05) and positively to sympathovagal indices (P < 0.05), even after correction for possible confounders such as age and sex, although the hair mercury was not significantly correlated with any cardiac autonomic indicators.
Despite the potential limitations involved in the retrospective study, these findings suggest that prenatal methylmercury exposure (median of estimated maternal hair mercury at parturition, 2.24 microg/g) may be associated with reduced parasympathetic activity and/or sympathovagal shift.
No preview · Article · Jun 2006 · International Archives of Occupational and Environmental Health
[Show abstract][Hide abstract] ABSTRACT: The benchmark dose (BMD) is defined as the dose that corresponds to a specific change in an adverse response compared to the response in unexposed subjects, and the lower 95% confidence limit is termed the benchmark dose level (BMDL). In this study, the threshold of daily ethanol intake affecting blood pressure was calculated by both the BMD approach and multiple logistic regression analysis to clarify the relation between the BMDL and no-observed-adverse-effect level (NOAEL). Systolic and diastolic blood pressures (SBP and DBP) and daily ethanol intake were explored in 1,100 Japanese salesmen. The SBP and DBP were positively related to daily ethanol intake (p < 0.001) when adjusting for possible confounders such as age, body mass index, and smoking status. The adjusted risk for hypertension (SBP >or= 140 mmHg or DBP >or= 90 mmHg) increased significantly when daily ethanol intake exceeded 60 g/day, and the categorical dose of interest was 60.1-90 g/day. The BMDL and BMD of ethanol intake for increased SBP and DBP were estimated to be approximately 60 and 75 g/day, respectively. These findings suggest that the BMDL and BMD correspond to the NOAEL and lowest-observed-adverse-effect level, respectively, if the sample number of clinical data is large enough to confirm the dose-response association.