Relation of dietary inorganic arsenic exposure and urinary inorganic arsenic metabolites excretion in Japanese subjects.

Inorganic arsenic (InAs) is a ubiquitous metalloid that has been shown to exert multiple adverse health outcomes. Urinary InAs and its metabolite concentration has been used as a biomarker of arsenic (As) exposure in some epidemiological studies, however, quantitative relationship between daily InAs exposure and urinary InAs metabolites concentration has not been well characterized. We collected a set of 24-h duplicated diet and spot urine sample of the next morning of diet sampling from 20 male and 19 female subjects in Japan from August 2011 to October 2012. Concentrations of As species in duplicated diet and urine samples were determined by using liquid chromatography-ICP mass spectrometry with a hydride generation system. Sum of the concentrations of urinary InAs and methylarsonic acid (MMA) was used as a measure of InAs exposure. Daily dietary InAs exposure was estimated to be 0.087 µg kg-1 day-1 (Geometric mean, GM), and GM of urinary InAs+MMA concentrations was 3.5 ng mL-1. Analysis of covariance did not find gender-difference in regression coefficients as significant (P > 0.05). Regression equation Log 10 [urinary InAs+MMA concentration] = 0.570× Log 10 [dietary InAs exposure level per body weight] + 1.15 was obtained for whole data set. This equation would be valuable in converting urinary InAs concentration to daily InAs exposure, which will be important information in risk assessment.

Inter- and intra-individual variation in urinary excretion of daidzein and equol in female Japanese.

OBJECTIVE: To evaluate the representativeness of single measurement of urinary soy-isoflavone concentrations for the assessment of long-term intake levels. METHODS: Five urine samples taken from 14 Japanese female subjects over 2-3 months were measured for daidzein and equol by gas chromatography-mass spectrometry (GC-MS). RESULTS: Geometric mean daidzein and equol concentrations of 14 subjects were 582 and 2.66 µg/g creatinine, respectively. Intra-class correlation coefficients for daidzein and equol were 0.355 (95% CI: 0.130-0.649) and 0.741 (0.551-0.891), respectively. CONCLUSION: Single measurement of urinary equol is effective for the assessment of long-term equol status of Japanese subject while that of daidzein is not.

Urinary excretion of parabens in pregnant Japanese women.

Urinary excretion of free and total (free plus conjugated) forms of methyl, ethyl, n-propyl and n-butyl parabens (MP, EP, PP and BP, respectively) and their metabolite p-hydroxybenzoic acid were measured for 111 pregnant Japanese women. Frequent detection of parabens and their metabolite indicated that exposure takes place daily for pregnant Japanese women. The estrogenic potency of PP was 20 times higher than those of the other 3 parabens for the present subjects when both abundance in the urine and the relative estrogenic activity of each compound was considered. Detection of free parabens suggested dermal exposure, probably from their inclusion in personal care products. No statistical association was found between the anogenital index (birth weight-adjusted AGD) of male offspring and the concentrations of any parabens in the urine of the mothers suggesting that the parabens were not apparently estrogenically active at the exposure level of the present subjects.

Endocrine disrupting chemicals in urine of Japanese male partners of subfertile couples: a pilot study on exposure and semen quality.

The concentrations of chemicals with suspected endocrine disrupting effect were measured in urine samples collected from 42 Japanese male partners of couples who had infertility consultation at a gynecology clinic in Tokyo. The urinary analytes included metabolites of 5 phthalate diesters, pyrethroid insecticide (3-phenoxybenzoic acid, 3-PBA) and soy isoflavones (daidzein and equol), and cadmium. The semen parameters (semen volume, concentration and motility) of the male subjects were examined at the clinic as a diagnostic screening. Multiple regression analysis using one of the semen parameters examined as dependent variable and urinary biomarkers with age, body mass index, abstinent period, alcohol drinking, smoking and consumption frequency of selected foods as independent variables. For sperm concentration, urinary mono-n-butyl phthalate was selected as a significant independent variable with positive beta, while urinary daidzein was with negative beta. Consumption frequency of coffee (negative) and fruits (positive) were also significant. For sperm motility, urinary 3-PBA was selected as significant with negative beta as well as detectability of equol and frequency of coffee consumption with negative beta while smoking was with positive beta. This pilot study suggested the pyrethroid exposure level and dietary habit (coffee and soy products) as a significant contributor to poorer semen quality.

[Intra- and inter-individual variation in urinary iodine concentration].

OBJECTIVES: To quantitatively assess the intra- and inter-individual variation of urinary iodine concentration in Japanese to determine whether urinary analysis is applicable to assessing habitual iodine intake in subjects on an individual basis. METHODS: Five urine samples (first void) were taken from each of the 14 healthy female subjects at 2-3 week intervals over 4-5 months. Information on diet and medication use on the previous day of urine sampling was obtained by a questionnaire during each urine sampling. The concentration of iodine in urine samples was measured by inductively coupled plasma mass spectrometry (ICP-MS). Intra- and inter-individual variation was assessed by intra class correlation coefficient (ICC). RESULTS: The median concentration of iodine in 70 urine samples was 91 µg/g-cre (range: 15-4400 µg/g-cre). The mean iodine concentration in urine samples from subjects who took iodine-rich foods/medications on the day before sampling was statistically significantly higher than that from subjects who did not take such foods/medications (p < 0.01, t-test). The ICC of urinary iodine concentration of the 14 subjects was 0.55, indicating good reproducibility; however, this was 0.28 when one subject who routinely used an iodine-containing gargle was excluded from analysis. CONCLUSIONS: Urine sampled on a single occasion is not a suitable medium for the assessment of long-term intake levels of iodine in subjects on an individual basis.

Maternal exposure to low-level heavy metals during pregnancy and birth size.

We evaluated the effect of environmental, low-level exposure to heavy metals during pregnancy, as estimated by urine analysis, on birth size of the newborns. Spot urine samples were collected from unexposed 78 pregnant women in Tokyo during 2007 and 2008. The urinary concentrations of beryllium (Be), copper (Cu), arsenic (As), zinc (Zn), selenium (Se), molybdenum (Mo), cadmium (Cd), tin (Sn), antimony (Sb), and lead (Pb) were measured by ICP-MS. The birthweight (BW), length (BL) and head circumference (HC) of the newborns delivered to the subjects were measured and relationship with urinary metal concentration was examined. The geometric mean concentration of urinary Be, Cu, As, Zn, Se, Mo, Cd, Sn, Sb, and Pb were 0.031, 12.8, 393, 76.9, 37.6, 79.0, 0.766, 0.232, < 0.21, 0.483 microg g-creatinine(-1), respectively. The mean birth size of the newborn was close to the national average value in Japan. Stepwise multiple regression analysis using birth size as a dependent variable and urinary metal concentrations and covariates as independent variables extracted urinary Cd with a significant negative standardized partial regression coefficient (beta) for BW along with gestational age and maternal BMI. For HC, Sn was selected with a negative beta. The present study suggested that even a low-level Cd body burden of general population has slight but significant negative effect on BW.

Prenatal exposure to phthalate esters and PAHs and birth outcomes.

The purpose of this study was to investigate the relationship between the levels of prenatal exposure to phthalate ester and PAHs and birth outcomes among 149 Japanese pregnant women. Urinary concentrations of 9 phthalate ester metabolites, mono methyl phthalate (MMP), mono ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-iso-nonyl phthalate (MINP) and mono-n-octyl phthalate (MnOP) and PAHs metabolite (1-hydroxypyrene, 1-OHP) were analyzed in spot urine samples collected from pregnant women. Correlation analysis and multiple regression analysis were conducted between the concentrations of maternal urinary metabolites and birth outcomes such as birth weight, birth length, head circumference and gestational age. Creatinine-corrected concentration (geometric mean; microg/g cre) was 9.14 (MMP), 9.76 (MEP), 51.6 (MnBP), 5.62 (MBzP), 5.45 (MEHP), 10.6 (MEHHP), 11.3 (MEOHP), 0.031 (MINP), 0.025 (MnOP) and 0.121 (1-OHP). These concentrations are comparable with literature value. The relationships between prenatal exposure to phthalate esters and birth outcomes were not significant. Statistically significant negative correlation was observed between 1-OHP and birth weight, birth length and head circumstances although the correlation was insignificant when only non-smokers were included in multiple regression analysis. In conclusion, we found that prenatal exposure to phthalate esters or PAHs did not affect birth outcomes at the exposure level of the present subjects.

Exposure assessment of phthalate esters in Japanese pregnant women by using urinary metabolite analysis.

OBJECTIVES: Our objectives were (1) to evaluate whether single spot urine is suitable media for longer-term phthalate esters exposure assessment, and (2) to estimate intake level of phthalate esters of Japanese pregnant women using urinary metabolites as an indicator of prenatal exposure level in their offspring. METHODS: We analyzed nine metabolites (MMP, MEP, MnBP, MBzP, MEHP, MEOHP, MEHHP, MINP, MnOP) of seven phthalate esters in spot urine samples from 50 pregnant women by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Using four urine samples collected from each of 12 subjects from 50 pregnant women within 5-12 weeks, we compared intra- and interindividual variation in urinary metabolites by calculation of intraclass correlation coefficient (ICC). We estimated daily intakes of 50 pregnant women from their urinary metabolite concentrations. RESULTS: ICCs for seven phthalate metabolite concentrations in single spot urine samples were: MMP (0.57), MEP (0.47), MnBP (0.69), MBzP (0.28), MEHP (0.51), MEHHP (0.43), and MEOHP (0.41) in 12 pregnant women. Phthalate ester metabolites had high detection rates in 50 subjects. The mean daily intake ranged from 0.01 to 2 mug/kg per day. The daily intake levels in all subjects were lower than corresponding tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA), though maximum value for DnBP of 6.91 mug/kg per day accounted for 70% of TDI value. CONCLUSIONS: Higher ICCs indicated that phthalate metabolite levels in single spot urine could reflect longer-term exposure to the corresponding diesters of subjects. Although the current exposure level was less than TDIs, further studies and exposure monitoring are needed to reveal the toxicity of phthalate esters to sensitive subpopulation.

Secondary hemophagocytic syndrome in a patient with methicillin-sensitive Staphylococcus Aureus bacteremia due to severe decubitus ulcer.

A 51-year-old man with poliomyelitis was admitted to emergency because of a severe decubitus ulcer on his right hip that was associated with infection. His general condition deteriorated and he was malnourished and dehydrated. Despite adequate hyperalimentation and antibiotic administration, laboratory data indicated pancytopenia 4 days later. He was diagnosed as having secondary hemophagocytosis (HPS) associated with methicillin-sensitive Staphylococcus aureus sepsis due to decubitus inflammation based on bone marrow aspiration and a blood culture. Although granulocyte colony stimulating factor, packed red blood cell transfusions, platelet transfusions, and antibiotics gradually improved the pancytopenia, the patient died of massive gastrointestinal tract bleeding.

Postlingual collapse of language and its recovery after cochlear implantation.

A 6-year-old boy lost his normally-developed language ability within 2 months after bilateral sudden peripheral deafness. The boy became non-communicative with others, restless with frequent meaningless bursts of shouts (communication skills equivalent to 9-11 months of language development: a rapid breakdown of language). Since conservative methods were ineffective, cochlear implantation was performed. A surprising success was observed: he regained the language retracing the normal developmental stages and caught up with his contemporaries in 2 years. Behavioral improvement paralleled his language development. This case (1) provides insights into the brain function with respect to language acquisition, in relation to the plasticity during the 'critical period' of language learning, (2) reveals the close relationship between language development and behavior, and (3) suggests the predominance of auditory stimulation in learning language.