A number of study about trace elements have been actively presented and discussed in Japan Society for Biomedical Research on Trace Elements established in 1990. During this time, analytical instrument and technique have also developmented remarkably and consequently standard value changed in some biological trace elements. Hot springs have a great deal with people since ancient times and have been attracted widespread popularity as relaxing and healing place via bath or drinking, and Japanese people especially enjoy hot spring. A wide variety of trace elements included in hot spring water have an important role for healing effectiveness of hot spring. There are many studies about effects of hot spring for human body. The study about elucidation of generative mechanism of hot spring and influence of heavy metal at spring water drinking progress at rapid speed with improvement of measurement accuracy. On the other hand, effluent regulation have also been a big problem in hot-spring area. In particular some trace elements are involved in the effluent regulation. In this paper, definition of trace elements in hot spring including geochemical significance, problem of effect for human body of trace elements at spring water drinking and effluent regulation were discussed.

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A total of 37 elements including Na, Mg, Al, K, Ca, Fe, Ba, Cd, Fe, Cd, Cr, Cu, Ga, Li, Mn, Pb, Se, Sr, V, Zn, As, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu and Th in Antarctic snow were analyzed by ICP-MS in a class 1000 clean room. Chromatographic analysis for Cl^-, SO₄^2- and NO₃^- were also conducted. Antarctic snow samples were collected at Asuka Station(71°32'S, 24°08'E, 930 m a.s.l. )over a period from July to December 1991. Concentration of the most of the elements in Antarctic snow is 1-3 orders of magnitude smaller than that of Arctic snow collected in 1992. Pronounced peak concentration in most of the elements together with non sea salt sulfate was observed in late September to early October. Enrichment factor analysis suggest for Na, Mg, Ca, K and Sr of marine origine and Al, Fe, Mn, Rb, Cr, Ni, Ga, V and all the rare earth elements of crustal origine. Volcanic eruption of Mt.Pinatubo(June, 1991)and / or Mt. Hudson(August, 1991)could be the reason for the precipitations of Pb, Cd, Cu, Zn and Se together with acidic components in the drifting snow. Surface snow samples along a 2200 km route including one at Dome Fuji(77°32'S, 24°08'E; 3810 m a.s.l. )have been collected in 1991- 1993. Spacial distribution of trace elements of surface snow in Antarctica may reflect polar stratospheric precipitation or long range transport from the southern hemisphere. Rare earth element(REE)pattern in surface snow shows a distinctive pattern in the Antarctic inner most highland area. This study will help researchers to gain further investigations of deep ice cores, which will have provided a wealth of information on global climate change and atmospheric composition.

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Solid phase extraction with chelating adsorbents is useful for the preconcentration of trace metals in seawater. We have examined a number of chelating adsorbents and developed simultaneous determination methods for trace metals in seawater on the basis of preconcentration by solid phase extraction and determination by ICP-MS. Here we review the results on the determination of trace bioactive metals(Fe, Co, Ni, Cu, Zn, Cd and Pb)using fluoride-containing metal alkoxide glass immobilized 8-hydroxyquinoline(MAF-8HQ)and the determination of the second and third transition series metals(Zr, Hf, Nb, Ta, Mo and W)using vinyl polymer resin immobilized 8-hydroxyquinoline(TSK-8HQ).

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Deep sea water experience facility “THALASSOPIA” was opened in 1998 in Namerikawa City, Toyama Prefecture. There were no scientific reports on thalathotherapy using deep sea water which is rich in elemental contents and clean. In order to clarify effects of deep sea water bathing on relaxation and sleep, comparison examinations were carried out with empty bath, tap water bath and bath of surface sea water, in subjects of daytime duty persons and night duty persons using physiological and psychological index. It was indicated that there was hyperemia effect in deep sea water bathing which is easy to warm and is difficult to cool. Deep sea water bathing showed better subjective sleep latency for sleep questionnaire and significantly better vigor status for mood questionnaire among 4 kinds of bathing. Equipments which concentrated deep sea water of about 3.4% salinity using reverse osmosis membrane to about 15% salinity and to about 30% salinity by evaporation were developed. It was reported that floating bath was possible using the concentrated water as well as ”Dead Sea”. To study relaxation effects by floating bath during 15 minutes in the concentrated water of about 30% salinity, participated persons in “Namerikawa deep sea water fair 2003” were examined. By floating bath using the concentrated water, it was indicated that mental refresh effect and relaxation effect of muscles were obtained. Penetration through skin of elements of concentrated deep sea water was examined using skins of infantile pigs similar to human skin. It was found that infantile pig skin induced experimental inflammation contained much sodium, potassium and magnesium after concentrated deep sea bathing by measuring secondary ion mass spectrogram. It is wanted to study on the relation between skin penetration of elements and anti-allergy, anti-inflammatory effects.

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Effects of westernizing of food habits and lack of exercise on health status based urbanizing of daily life are focused in Japan. With these changes of life habits, protein and lipid intakes are increasing, and mineral and vitamin intakes are decreasing. So that, people with elevated serum cholesterol concentrations are increasing and are at increased risk of developing atherosclerosis and coronary artery disease. On the other hand, the role of magnesium(Mg)in prevent of these disease by improving lipid metabolism is well-known. But in Japanese also with westernizing of food habits, fishes, vegetables and algae intakes are decreasing, and Mg intake is coming lower. To prevent of atherosclerosis and coronary artery disease, the natural Mg rich drink “deep sea water” were made from deep sea water by desalting treatment. The effects of oral administration of “deep sea water” on lipid metabolism of rats were studied. The “deep sea water” were made from deep sea water to remove NaCl and prepared concentration(mg/L)(1):control: distilled water(Mg<1 ppm, Ca<1 ppm),(2)Mg200(Mg200 ppm, Ca67 ppm),(3)Mg600(Mg600 ppm, Ca200 ppm),(4)Mg1000(Mg1000 ppm, Ca333 ppm). Male Wistar rats weighing about 90 g were fed synthetic diets and for drinking water, distilled water and above three kinds “deep sea water” were provided ad libitum for 12 weeks. Eleven items of blood and twenty-four items of plasma biochemical analyses were automatic methods. The physiological behavior, food intake and water consumption in the rats did not found significant differences in each group. The pathological changes were also not found. In the plasma biochemical data, total cholesterol values in plasma of rats drank 2 kinds of high Mg concentration “deep sea water”((3)Mg600: Mg600 ppm, Ca200 ppm,(4)Mg1000: Mg1000 ppm, Ca333 ppm)resulted in significantly decrease compared to the rats drank distilled water(control group). These results suggest that magnesium rich drinking water made from “deep sea water“ without salt may be a useful natural drink to improve lipid metabolism and to prevent of atherosclerosis and coronary artery disease.

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Zinc is essential for the growth of the human and animals. Bone growth retardation is a common finding in various conditions associated with zinc deficiency, suggesting a physiologic role of zinc in the growth and mineralization of bone tissues. Bone zinc content is decreased by development with aging, skeletal unloading, and postmenopausal conditions. Zinc deficiency may play a pathophysiologic role in the deteriodation of bone metabolism. Zinc has been demonstrated to have a stimulatory effect on osteoblastic bone formation and mineralization; the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in osteoblastic cells, and it stimulates cellular protein synthesis. Zinc has been shown to stimulate gene expression of the transcription facter Runx2 that is related to differentiation into osteoblastic cells. Moreover, zinc inhibits osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear factor(NF)-κB ligand(RANKL)-induced osteoclastogenesis, indicating that the metal inhibits RANKL signaling in pre-osteoclasts. Zinc may act on the process of bone resorbing factors-induced protein kinase C activation, which is involved in Ca²⁺ signaling in osteoclastic cells. Zinc plays a role in the preservation of bone mass. β-Alanyl-L-histidinato zinc(AHZ)is a zinc compound, in which zinc is chelated to β-alanyl-L-histidine. The stimulatory effect of AHZ on bone formation was more intensive than that of zinc sulfate. Also, zinc acexamate has a potent- anabolic effect on bone metabolism. The effect of AHZ or zinc acexamate on bone formation is equal in comparison with the effect of various bone-regulating hormones and other factors. The oral administration of AHZ or zinc acexamate has a fine restorative effect on bone loss with various pathophysiologic conditions(including aging, skeletal unloading, aluminium bone toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen deficiency, diabetes, and fracture healing). Zinc compounds may be designed as new drugs in the therapy of osteoporosis.

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Dose-response relationships between dietary zinc(Zn)and physiological and biochemical parameters including total food intake, body weight gain, hemoglobin, liver and thymus weights, plasma Zn concentration, and plasma alkaline phosphatase(ALP)and angiotensin converting enzyme(ACE)activities were studied. Forty-eight 3-week-old male Sprague-Dawley rats were divided into 8 groups and fed diets containing graded levels of supplemental Zn: 0, 3, 6, 9, 12, 15, 18 and 30ppm(or mg/kg diets). The 12ppm of dietary Zn corresponds to NRC Zn requirement. The 30ppm of dietary Zn corresponds to the Zn level of AIN-93G formula. These diets were made with a modified formula of AIN-93G using spray-dried albumen in place of casein with supplemental biotin(2 mg/kg). The basal diet without supplemental Zn contained 0.3ppm Zn arising from albumen. Data were compared with 12 and 30ppm by Student's t-test, and also compared with 30ppm by Williams's test. Compared with 12 and 30ppm, total food intakes, body weight gains, plasma Zn concentrations, plasma ACE activities, plasma ALP activities, liver weights and thymus weights were significantly changed at 0 and 3ppm. Total food intakes, body weight gains, plasma Zn concentrations, plasma ACE activities and liver weights were significantly changed at 6ppm. Plasma Zn concentrations and plasma ACE activities were significantly changed at 9ppm. The apparent plateau breakpoints in these dose response relationships were placed between 15 and 18ppm.

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In recent years, lanthanum(La)compounds have been increasingly used in the optical and electronic industries. Such industrial sources of La pose potential environmental problems, and it is therefore necessary to investigate the effects of La on humans and animals. A simple technique involving staining of La at the light microscopic level with alizarin complexone has been developed. This method is based on the formation of insoluble alizarin complexone-La-F in response to NaF treatment. The reactive material is reddish-purple in color and shows on absorption maximum at 530 nm. Application of this method to paraffin-embedded liver sections from rats treated with LaCl₃ allowed for the selective staining of La at the light microscopic level. Thus, this method can be used for pathologic diagnosis in paraffin-embedded sections.

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We developed a colorimetric reagent kit for determination of zinc in serum, “ACCURAS AUTO Zn”. The reagent is applicable to all auto-analyzers widely used in hospital laboratories, without any serum pretreatment. Within-run and between-run precisions(C. V. )were 0.7-1.0% and 1.4-1.9%, respectively. The calibration curve was linear up to 500 µg/dl, and the detection limit was 5 µg/dl. Interference from iron and copper was eliminated by a masking agent. A good correlation(r = 0.996)was obtained between the results of the present method and those of atomic absorption spectrophotometry. This kit enables accurate and immediate assay of zinc with a clinical chemistry auto-analyzer, and saves time and efforts in the field of a nutrition support team(NST)work in hospitals.

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We examined the recovery mechanisms of carp(Cyprinus carpio)in response to severe lead poisoning by exposure over 28 and 114 days. Based on the findings, we developed a hypothesis to explain the main defense mechanisms employed by carp. Under conditions of acute lead poisoning using lead concentrations exceeding 1.0 mg/L, the mechanism employed to prevent the absorption of lead in solution through the gill epithelia was the formation of a mucous membrane on the surface of the gills and body, which acted as a ligand for lead. Conversely, for lead concentrations lower than those required to induce acute lead poisoning, carp may prevent lead uptake by hematopoietic organs by elevating production of 5-aminolevulinic acid dehydratase(ALA-D),which has a high affinity for lead, in the erythrocytes. Since this mechanism is thought to occur in conjunction with hemoglobin biosynthesis, the general defense mechanism employed by carp is thought to be a cumulative response using the two aforementioned physiological mechanisms.

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The nutritional availability of selenium(Se)in Se-enriched pumpkin(Se-pumpkin)was assessed by comparing with selenite and Se-enriched Kaiware radish sprouts(Se-sprouts). Male weanling ddY mice were fed a Torula yeast-based Se-deficient diet. After feeding for 3 weeks, mice were divided into 7 groups and fed the basal diet or a diet supplemented with 0.05 or 0.25µg/g of Se as either sodium selenite, Se-pumpkin or Se-sprouts for further one week. Supplementation of Se dose-dependently increased serum and liver Se concentrations and glutathione peroxidase(GPX)activities. In serum Se and GPX, the increases by Se supplementation did not significantly vary with Se source, but in the liver Se and GPX, the increases by selenite supplementation were significantly higher than those by supplementation with Se-pumpkin or Se-sprouts. A difference between the effect of Se-pumpkin and that of Se-sprouts was found in the elevation of liver Se concentration; supplementation with Se-pumpkin caused significantly higher elevation of liver Se than that with Se-sprouts. When liver Se was used, the nutritional availabilities of Se from Se-pumpkin and that Se-sprouts were estimated to be 97% and 65% to selenite Se, respectively. However, when liver GPX was used for the estimation, the availability of Se from either Se-pumpkin or Se-sprouts was less than 50% to selenite Se.

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Aluminum(Al)is the 3^rd most abundant on the earth. However, it is not essential and harmful to life beings. Al has been suspected to have a relation with various neurodegenerative diseases. The increased concentration of Al in the soil is implicated in the death of plants or fishes caused by acid rain. The toxic effects of Al are largely influenced by its chemical speciation; the concentration and the type of ligands coexist. Polynuclear hydroxy-aluminum complexes such as aluminum tridecamer(Al₁₃; [AlO₄Al₁₂(OH)₂₄(H₂O)₁₂]⁷⁺)is formed in the water under partially neutralization, and is more toxic in the growth of plant roots compared to monomeric Al³⁺ ion. In this study, we investigated the formation and the stability of Al₁₃ using ²⁷Al-NMR and developed a pulse-exposure method to apply chemically-identified Al₁₃ to primary cultured neurons of rat cerebral cortex. After 14 days of the exposure at 1 h, Al₁₃-intoxicated neurons exhibited significant decrease in cell viability. Meanwhile, monomeric Al³⁺ did not cause significant cell death. Our results will aid for the understanding the molecular mechanism of Al neurotoxicity.

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Cadmium fluoride(CdF₂)is commonly used as an insulator for super-high-speed mass telecommunications equipment, and there is a considerable risk that industrial workers will inhale CdF₂ particles. Despite the possibility that acute exposure can cause harmful systemic effects, there are no studies to date that address the health consequences of acute CdF₂ exposure. This study therefore aimed to determine the acute lethal dose of CdF₂ and its effects on various target organs, including the liver and kidney. We also determined the effect of CdF₂ on serum electrolytes and acid-base balance. The effective lethal dose was determined and dose-response study was conducted after intravenous administration of CdF₂ in rats. The 24h LD₅₀ of CdF₂ was determined to be 3.29 mg/kg. The dose-response study used doses of 1.34, 2.67, 4.01 mg/kg CdF₂. Saline or sodium fluoride solution were used for controls. Severe hepatocellular injury was induced at doses greater than 2.67 mg/kg, as demonstrated by AST and ALT activities greater than 1,500 IU/L in rats injected with a dose of 4.01 mg/kg. Acute renal failure was induced at doses greater than 2.67 mg/kg. Decreased serum Ca, increased serum K and metabolic acidosis were induced at a dose of 4.01mg/kg. It was suggested that decreased serum Ca was caused by the exposure to ionized F. CdF₂ has the strongest lethal and hepatic toxicity among all Cd containing compounds.

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Cadmium fluoride(CdF₂)have been recently used for electronics device in industrial fields. In previous study, we investigated the dose-effect relationships of acute toxicities from the standpoint of occupational health. It would be strongly influenced by metabolism of CdF₂. Therefore, this study was designed to investigate the early dynamic state of Cd and F in bile and urine after the acute exposure of CdF₂. Rats were received a single intravenous injection of saline or CdF₂(1.34, 2.67, or 4.01 mg/kg)which were the same doses of the previous study. Bile was collected at intervals of 30 min until 300 min. Urine was collected for 300 min. Volume of bile and urine were decreased in CdF₂ treated groups. Total biliary Cd was excreted in the 2.67 and 4.01 group much more than 1.34 group. The peaks of maximum excretion were 30-60 min in the 2.67 group and 60-90 min in the 4.01 group respectively. Our previous study indicated that CdF₂ caused severe liver dysfunction at a dose of 2.67 and 4.01 mg/kg and proximal tubular damage at a dose of 4.01 mg/kg. Abnormalities in Cd kinetics could be resulted from extensive hepatic damage at a toxic dose. The differences of kinetics would be caused by the saturation of the accumulation capacity of the liver. Although biliary ionized F(F)was dose-relatedly excreted, urinary F did not show dose-related excretion. Therefore, the metabolism of F was mainly disordered by renal dysfunction rather than hepatic damage. The toxicity of CdF₂ may be enhanced by kinetics abnormalities caused by liver and kidneys dysfunctions.

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