The biological, medical and environmental roles of trace elements have attracted considerable attention over the years. In spite of their relevance in nutritional, occupational and toxicological aspects, there is still a lack of consistent and reliable measurement techniques and reliable information on reference values. In this review our understandings of the urinary profilings of boron, lithium and strontium are summarized and fundamental results obtained in our laboratory are discussed.
Over the past decade we have successfully used inductively coupled plasma emission spectrometry for the determination of reference values for urinary concentrations of boron, lithium and strontium. Taking into account the short biological half-life of these elements and the fact that their major excretion route is via the kidney, urine was considered to be a suitable material for monitoring of exposure to these elements. We confirmed that urinary concentrations of boron, lithium and strontium follow a lognormal distribution. The geometric mean reference values and 95% confidence intervals were 798 μg/l (398–1599 μg/l) for boron, 23.5 μg/l (11.0–50.5 μg/l) for lithium and 143.9 μg/l (40.9–505.8 μg/l) for strontium. There were no discrepancies between our values and those previously reported. Our reference values and confidential intervals can be used as guidelines for the health screening of Japanese individuals to evaluate environmental or occupational exposure to these elements.

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Max von Pettenkofer (1818–1901) belonged to the scientific elite of the 19th century. With his stringent search for the laws of nature and his fight for scientific truth, Pettenkofer was the prototype of a modern researcher. In the field of hygiene, he sought ways and means of preserving health and preventing sickness. With his consistent application of the experimental method to the field of public health, Pettenkofer helped the discipline of hygiene to provide precise and reliable answers to sanitary questions. In his experimental work on hygiene, Pettenkofer sought an answer to every imaginable question concerning the connection between the human organism and its environment.
To proceed in this direction, Pettenkofer combined medical expertise with physics, chemistry, technique and statistics. This even today modern “crossover-thinking” made hygiene to the first interdisciplinary medical field. With his Institute of Hygiene, Pettenkofer established 1879 the first centre of competence for hygiene and environment in the world, opening a new era of environmental observation.
In the framework of hygiene, Pettenkofer turned also to questions of nutrition and the quality of foodstuff. The science of hygiene owes to Max von Pettenkofer not only its development and cartography, but also its introduction as an academic discipline. Finally he regarded hygiene also as an economic and cultural feature. His idea about a clean soil in the cities and his promotion of adequate water supply and sufficient sewage networks are linked to his theory of the cholera. Pettenkofer believed that a battle against this epidemic could be won.

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Objectives: The prevalence of thoracic kyphosis is considered to increase as the population is ageing in Japan. However, little is known about the clinical and preventive significance of kyphosis. The purpose of the study is to assess the association of kyphosis with subjective poor health and functional activity in the community-dwelling Japanese elderly. The relation of kyphosis with blood pressure, as a subclinical indicator of arteriosclerosis, is also examined.
Methods: The subjects consisted of 536 (male 241, female 295) elderly persons aged 65 years old and older. Trained examiners measured thoracic kyphosis using a flexicurve, and kyphosis index was calculated. Information on the subjects’ subjective poor health and functional activity were collected through a face-to-face interview, and blood pressure was measured by a conventional method.
Results: In females, their kyphosis index increased with age increased, whereas in males, there was no clear age-related change. An increased kyphosis index was associated with subjective poor health only among females. Compared with the lowest kyphosis index tertile, adjusted odds ratios for being in poor health were 5.4 (95% confidence interval: 1.1–27.4) in the middle tertile, and 6.4 (95% confidence interval: 1.3–32.1) in the highest tertile. Kyphosis index did not seem to be associated with functional activity score and blood pressure both in males and females even after adjustment.
Conclusions: Kyphosis is associated with subjective poor health in the community-dwelling female elderly in this study population, but not with functional activity and blood pressure both in males and females.

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Objective: There are several reports of cellular-aging-dependent alterations in the antioxidant capacity of human fibroblasts. Fibroblasts show slower the growth rate at late passages (referred to hereafter as old cells) than at early passages (referred to hereafter as young cells). Antioxidants may control cellular growth by modulating reactive oxygen species (ROS). Methanolic extracts from broad beans (MEBB) contain phenolic compounds and have ROS-scavenging activities. In this study, we investigated the effects of MEBB on cellular growth and antioxidant levels in normal human lung fibroblasts.
Methods: To determine cytosolic superoxide dismutase (SOD) activities, cytosolic glutathione peroxidase (GSH-Px) activities, catalase activities, reduced glutathione (GSH) concentrations, and growth rate, MEBB treatments were performed on young and old cells.
Results: In young and old cells treated with 120 μg/ml MEBB, the growth rates increased by 28.1 and 15.2%, respectively, compared with controls. The MEBB treatment of young cells caused a 62.5% increase in SOD activity, but the treatment of old cells caused a 39.5% decrease. The catalase activities of the young and old cells treated with MEBB were equal to those of control cells. Young and old cells treated with MEBB were equal to the control cells in terms of GSH-Px activity. The GSH concentrations in the young and old cells treated with 120 μg/ml MEBB increased by 22.1 and 45.9%, respectively.
Conclusion: These studies elucidated a new cellular growth mechanism whereby human lung fibroblasts modulate intracellular GSH levels via the action of MEBB.

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Objectives: Bisphenol A (BPA), a raw material commonly used in the manufacture of resins such as polycarbonate and epoxy, is a possible xenoestrogen that is hypothesized to disrupt the human endocrine system. Humans are widely exposed to BPA. We investigated the urinary concentration of BPA in infertile Japanese women and its possible association with endometriosis.
Materials and Methods: We recruited 166 women (aged 20–45) who had complained of infertility and visited a university hospital in Tokyo. The subjects were interviewed and their urine samples were obtained prior to a laparoscopic diagnosis of endometriosis between January 2000 and December 2001. Urinary total BPA concentration in 140 eligible urine samples was then measured using enzymatic deconjugation of glucuronide and sulfate and high-performance liquid chromatography isotope-dilution tandem mass spectrometry.
Results: Median (25th–75th percentile) unadjusted and creatinine-adjusted urinary BPA concentrations were 1.6 (0.69–2.8) μg/L and 0.80 (0.45–1.3) μg/g creatinine. No significant monotonic association of endometriosis with urinary BPA concentration was observed. Median urinary BPA concentration in women with stage 0–I endometriosis (0.74 μg/g creatinine) did not significantly differ from that in those with stage II–IV endometriosis (0.93 μg/g creatinine) (p for difference=0.24).
Conclusions: This study, based on a larger number of samples than those in previous studies in Japan and using the most reliable analytical method currently available, showed that urinary concentrations of BPA in women who consulted a physician for infertility were not higher than those in other populations. Moreover, no association between urinary BPA concentration and endometriosis was found in this cross-sectional study.

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Objectives: Only a few long-term follow-up studies with a focus on the association between lung function and mortality in the Japanese population have been undertaken. In this study, we examined the associations of lung function, smoking and the results of allergy skin tests with mortality in a longitudinal study of the Japanese population.
Methods: Baseline measurements were performed on residents of Fukui, Japan in 1972, and a follow-up survey was conducted in 2002. By employing a nested case-control design, 596 cases (deaths) and 596 age and sex-matched controls (survivals) were selected. Lung function was assessed using forced vital capacity (FVC) expressed as the normal percent predicted (FVC %pred) and the ratio of forced expiratory volume in 1 second (FEV₁) to FVC (FEV₁/FVC). Allergy skin tests were performed with extracts of house dust, candidia and mixed fungal samples (bronchomycosis). The Brinkman index was used to assess smoking intensity. The Cox proportional hazards model was used to evaluate whether lung function was associated with mortality after adjustment for other potential confounding variables.
Results: Those categorized into the first- or second-lowest quartile of FVC %pred had a higher mortality [hazard ratios (HRs) and 95% confidence intervals (CIs): 2.01 (1.26−3.19) and 1.84 (1.11−3.05)], respectively. On top of these, heavy smoking (BI≥400) was associated with a higher mortality [HR and 95%CI: 1.73 (1.18−2.53)]. There were only weak of associations between the results of allergy skin tests and mortality.
Conclusions: These results suggest that FVC %pred of lung function and smoking can serve as long-term independent predictors of mortality.

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Objective: Human diploid cells are more susceptible to oxidative stress at late passage than at early passage, presumably because of the decrease in cellular-reduced glutathione (GSH) concentration. Water-soluble protein (WSP) from broad beans scavenges free radicals. The effects of WSP on the glutathione system were examined in PDL 20 (early passage) and PDL 50 (late passage) human lung fibroblasts (TIG-1).
Methods: To determine cytosolic glutathione peroxidase (GSH-Px) activities, glutathione reductase (GR) activities, oxidized glutathione (GSSG) concentrations, and GSSG/reduced glutathione (GSH) ratios, WSP and hydrocortisone (HC) treatments of TIG-1 cells (PDL 20→50 and PDL 50→75) were performed for 40 days. We also investigated the GSSG concentrations and GR activities in PDL 20 cells that were continuously treated with WSP until PDL 39 and 55.
Results: GSSG concentrations decreased in WSP- and HC-treated PDL 50→75 cells. The GSSG/GSH ratios in PDL 50→75 cells became low after the treatments. Increases in GR activities were observed in treated PDL 50→75 cells. The decline in the GSSG concentration of PDL 50→75 cells correlated with the increase in GR activity. The GSSG levels in control cells were higher following cellular age, whereas the levels in treated cells were lower than those in the control. The studies on cellular age-related changes indicated that greater increases in GR activity were found in treated cells than in the control.
Conclusion: These results indicated that WSP influences the GSSG concentration that is associated with cellular aging, but the mechanism of GSSG reduction by WSP remains unknown. The enhancement of glutathione status following WSP treatment may be related to the delay in the cellular aging.

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