Publications by authors named "Momoko Chiba"

31 Publications

Hospital-based screening to detect patients with cadmium nephropathy in cadmium-polluted areas in Japan.

Environ Health Prev Med 2019 Jan 26;24(1). Epub 2019 Jan 26.

Department of Internal Medicine, Akita Rosai Hospital, Japan Organization of Occupational Health and Safe, Akita, 018-5604, Japan.

Background: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan.

Methods: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß-microglobulin and blood and urinary cadmium levels were measured.

Results: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß-microglobulin level higher than 10,000 μg/g cr. and a blood cadmium level higher than 6 μg/L or urinary cadmium level higher than 10 μg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy.

Conclusions: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants.

Registration Number: No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).
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http://dx.doi.org/10.1186/s12199-019-0762-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347770PMC
January 2019

Changes in thallium distribution in the scalp hair after an intoxication incident.

Forensic Sci Int 2018 Oct 5;291:230-233. Epub 2018 Sep 5.

Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address:

In cases of criminal thallium poisoning, forensic investigation is required to identify the amount and time of thallium exposure. Usually, blood and urine thallium levels are respectively used as biomarkers. Additionally, hair has the unique potential to reveal retrospective information. Although several studies have attempted to clarify how thallium is distributed in hair after thallium poisoning, none have evaluated the time course of changing thallium distribution. We investigated changes in the distribution of thallium in hair at different time points after exposure in five criminal thallotoxicosis patients. Scalp hair samples were collected twice, at 2.6 and 4.2-4.5months after an exposure incident by police. Results of our segmented analysis, a considerable amount of thallium was detected in almost all hair sample segments. The thallium exposure date estimated from both hair sample collections matched the actual exposure date. We found that determination of thallium amounts in hair samples divided into consecutive segments provides valuable information about exposure period even if a considerable time passes after exposure. Moreover, when estimating the amount of thallium exposure from a scalp hair sample, it is necessary to pay sufficient attention to individual differences in its decrease from hair.
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http://dx.doi.org/10.1016/j.forsciint.2018.08.019DOI Listing
October 2018

Sex differences in shotgun proteome analyses for chronic oral intake of cadmium in mice.

PLoS One 2015 20;10(3):e0121819. Epub 2015 Mar 20.

Isotope Research Center, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.

Environmental diseases related to cadmium exposure primarily develop owing to industrial wastewater pollution and/or contaminated food. In regions with high cadmium exposure in Japan, cadmium accumulation occurs primarily in the kidneys of individuals who are exposed to the metal. In contrast, in the itai-itai disease outbreak that occurred in the Jinzu River basin in Toyama Prefecture in Japan, cadmium primarily accumulated in the liver. On the other hand, high concentration of cadmium caused renal tubular disorder and osteomalacia (multiple bone fracture), probably resulting from the renal tubular dysfunction and additional pathology. In this study, we aimed to establish a mouse model of chronic cadmium intake. We administered cadmium-containing drinking water (32 mg/l) to female and male mice ad libitum for 11 weeks. Metal analysis using inductively coupled plasma mass spectrometry revealed that cadmium accumulated in the kidneys (927 x 10 + 185 ng/g in females and 661 x 10 + 101 ng/g in males), liver (397 x 10 + 199 ng/g in females and 238 x 10 + 652 ng/g in males), and thyroid gland (293 + 93.7 ng/g in females and 129 + 72.7 ng/g in males) of mice. Female mice showed higher cadmium accumulation in the kidney, liver, and thyroid gland than males did (p = 0.00345, p = 0.00213, and p = 0.0331, respectively). Shotgun proteome analyses after chronic oral administration of cadmium revealed that protein levels of glutathione S-transferase Mu2, Mu4, and Mu7 decreased in the liver, and those of A1 and A2 decreased in the kidneys in both female and male mice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0121819PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368563PMC
February 2016

Long-term oral lithium treatment attenuates motor disturbance in tauopathy model mice: implications of autophagy promotion.

Neurobiol Dis 2012 Apr 10;46(1):101-8. Epub 2012 Jan 10.

Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.

Lithium, a drug used to treat bipolar disorders, has a variety of neuroprotective mechanisms including inhibition of glycogen synthase kinase-3 (GSK-3), a major tau kinase. Recently, it has been shown that, in various neurodegenerative proteinopathies, lithium could induce autophagy. To analyze how lithium is therapeutically beneficial in tauopathies, transgenic mice overexpressing human mutant tau (P301L) were treated with oral lithium chloride (LiCl) for 4 months starting at the age of 5 months. At first, we examined the effects of treatment on behavior (using a battery of behavioral tests), tau phosphorylation (by biochemical assays), and number of neurofibrillary tangles (NFTs) (by immunohistopathology). In comparison with control mice, LiCl-treated mice showed a significantly better score in the sensory motor tasks, as well as decreases in tau phosphorylation, soluble tau level, and number of NFTs. Next, we examined lithium effects on autophagy using an antibody against microtubule-associated protein 1 light chain 3 (LC3) as an autophagosome marker. The number of LC3-positive autophagosome-like puncta was increased in neurons of LiCl-treated mice. Neurons containing NFTs were completely LC3-negative, whereas LC3-positive autophagosome-like puncta contained phosphorylated-tau (p-tau). The protein level of p62 was decreased in LiCl-treated mice. These data suggested that oral long-term lithium treatment could attenuate p-tau-induced motor disturbance not only by inhibiting GSK-3 but also by enhancing autophagy in tauopathy model mice.
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http://dx.doi.org/10.1016/j.nbd.2011.12.050DOI Listing
April 2012

Long-term oral intake of aluminium or zinc does not accelerate Alzheimer pathology in AβPP and AβPP/tau transgenic mice.

Neuropathology 2012 Aug 28;32(4):390-7. Epub 2011 Nov 28.

Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Whether or not the oral intake of metals such as aluminium (Al) and zinc (Zn) is a risk for Alzheimer's disease (AD) has been a matter of controversy. Lack of AD pathology in patients with Al encephalopathy indicates Al does not cause AD. On the other hand, some epidemiological studies have suggested high Al increases the occurrence of AD. Our purpose is to test if high Al in drinking water is a risk factor for AD. We administered Al and Zn in drinking water to Tg2576, a transgenic mouse model for amyloid β-protein (Aβ) deposition with the Aβ precursor protein (AβPP) mutations (K670N/M671L), and Tg2576/tau(P301L), a model for Aβ and tau deposition. Deionized water was given to the control Tg2576 and Tg2576/tau. After administration for 4-10 months of approximately 100 mg/kg body weight Al or Zn per day, we were not able to find by quantitative immunohistochemical analyses differences in the deposition of Aβ and tau between the treated and untreated groups. Nor did the Al or Zn treatment affect the amount of soluble Aβ and Aβ*56, an Aβ oligomer, measured by ELISA or immunoblot. The oral intake of excess Al or Zn does not accelerate AD pathology in the transgenic mouse models for Aβ and tau accumulation. Such results do not seem to support the notion that excessive oral intake of Al or Zn is a risk factor for AD.
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http://dx.doi.org/10.1111/j.1440-1789.2011.01274.xDOI Listing
August 2012

Simultaneous determination of selenomethionine enantiomers in biological fluids by stable isotope dilution gas chromatography-mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2011 Nov 7;879(29):3253-8. Epub 2011 Apr 7.

Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan.

A method for the stereoselective determination of D- and L-enantiomers of selenomethionine in mouse plasma was developed using gas chromatography-mass spectrometry with selected-ion monitoring (GC-MS-SIM). DL-[(2)H(3,)(82)Se]selenomethionine was used as analytical internal standard to account for losses associated with the extraction, derivatization and chromatography. Selenomethionine enantiomers in mouse plasma were purified by cation-exchange chromatography using BondElut SCX cartridge and derivatized with HCl in methanol to form methyl ester followed by subsequent N-acylation with optically active (+)-α-methoxy-α-trifluoromethylphenylacetyl chloride to form diastereomeric amide. Quantification was performed by SIM of the molecular-related ions of the diastereomers on the chemical ionization mode. The intra- and inter-day precision for D- and L-selenomethionine spiked to mouse plasma gave good reproducibility with relative standard deviation of 3% and 3% for D-selenomethionine and 6% and 3% for L-selenomethionine, respectively. The estimated amounts were in good agreement with the actual amounts spiked, the intra- and inter-day relative error being 5% and 2% for D-selenomethionine and 2% and 1% for L-selenomethionine, respectively. The present method is sensitive enough to determine pharmacokinetics of selenomethionine enantiomers.
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http://dx.doi.org/10.1016/j.jchromb.2011.03.057DOI Listing
November 2011

Chronic magnesium deficiency decreases tolerance to hypoxia/reoxygenation injury in mouse heart.

Life Sci 2011 Apr 18;88(15-16):658-63. Epub 2011 Feb 18.

Department of Physiology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

Aims: Magnesium (Mg) deficiency has been reported to be associated with the development of the metabolic syndrome, cardiovascular diseases, and sudden death. We examined the influence of chronic Mg deficiency on cardiac tolerance to hypoxia/reoxygenation injury.

Main Methods: Mice were fed an Mg-deficient diet for 4 weeks, and then their hearts were excised for Langendorff perfusion experiments. The levels of total Mg in the blood and heart were quantified by atomic absorption spectrometry.

Key Findings: In Mg-deficient mice, the Mg concentration in whole blood was markedly decreased; however, that in the heart remained unchanged. When the hearts of control mice were exposed to hypoxia/reoxygenation, removal of extracellular Mg from a normal Krebs solution containing 1.2 mM Mg resulted in a significant decrease in the recovery of the tension-rate product (TRP) upon reoxygenation. In Mg-deficient mice, the recovery of TRP in the heart was reduced significantly in the absence of extracellular Mg compared to that in controls. The addition of Mg to the perfusate did not improve TRP recovery. During hypoxia/reoxygenation, cardiac damage evaluated by myocardial aspartate amino transferase (AST) release was greater in hearts of Mg-deficient mice than in that of control mice.

Significance: These results indicate that chronic Mg deficiency causes severe hypomagnesemia and a decrease in cardiac tolerance to hypoxia, without changing the intracellular Mg content. The decreased tolerance to hypoxia was not affected by the presence or absence of extracellular Mg, suggesting that some intracellular metabolic abnormalities develop in the cardiac myocytes of Mg-deficient mice.
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http://dx.doi.org/10.1016/j.lfs.2011.01.027DOI Listing
April 2011

Synthesis of D- and L-selenomethionine double-labeled with deuterium and selenium-82.

Chem Pharm Bull (Tokyo) 2010 Dec;58(12):1658-60

Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.

The synthesis of D- and L-selenomethionine labeled with ⁸²Se and three deuteriums at Se-methyl group (D- and L-[²H₃, ⁸²Se]selenomethionine) was described. D- And L-[²H₃, ⁸²Se]selenomethionine were prepared by condensation of (R)- and (S)-2-amino-4-bromobutylic acid with lithium [²H₃, ⁸²Se]methaneselenolate, which was prepared from metal (82)Se and [²H₃]methyl iodide. The optical purities of D- and L-[²H₃, ⁸²Se]selenomethionine were determined by HPLC with a chiral stationary phase column and were found more than 99% ee. The chemical ionization mass spectra showed that the molecular related ion for N-isobutyloxycarbonyl ethyl ester derivatives of [²H₃, ⁸²Se]selenomethionine did not overlap with the m/z values known from that of non-labeled selenomethionine.
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http://dx.doi.org/10.1248/cpb.58.1658DOI Listing
December 2010

Blood lead at currently acceptable levels may cause preterm labour.

Occup Environ Med 2011 Mar 26;68(3):231-4. Epub 2010 Aug 26.

National Institute of Occupational Safety and Health, 6-21-6 Nagao, Tama-ku, Kawasaki 214-8585, Japan.

Objectives: Although occupational and environmental exposures to lead have been dramatically reduced in recent decades, adverse pregnancy outcomes have been observed at 'acceptable' levels of blood lead concentrations (≤ 10 μg/dl).

Methodology: Blood samples were collected from 348 singleton pregnant women, aged 16-35 years, during the first trimester of pregnancy (8-12 weeks) for lead measurement by inductively coupled plasma-mass spectrometry. Subjects were followed up and divided into two groups (preterm and full-term deliveries) according to duration of gestation.

Results: The average (range) and geometric means of blood lead levels were 3.8 (1.0-20.5) and 3.5 μg/dl, respectively. Blood lead level was significantly (p<0.05) higher in mothers who delivered preterm babies than in those who delivered full-term babies (mean±SD: 4.46±1.86 and 3.43±1.22 μg/dl, respectively). Logistic regression analysis demonstrated that a 1 unit increase in blood lead levels led to an increased risk of preterm birth (OR 1.41, 95% CI 1.08 to 1.84).

Conclusion: Adverse pregnancy outcomes may occur at blood lead concentrations below the current acceptable level.
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http://dx.doi.org/10.1136/oem.2009.050419DOI Listing
March 2011

Genotoxicity studies of heavy metals: lead, bismuth, indium, silver and antimony.

J Occup Health 2009 23;51(6):498-512. Epub 2009 Oct 23.

Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo 160-8582, Japan.

Objectives: Many kinds of heavy metals are used in industry; thus, it is important for us to clarify their toxicity. For example, lead, which is a component of solder, is notorious for its neurotoxicity, and substitute materials have been sought for many years. Therefore, we examined the genotoxicity of lead and also those of metallic bismuth, indium, silver and antimony which are possible substitutes for lead in solder.

Methods: Bacterial reverse mutation tests and chromosomal aberration tests in cultured mammalian cells were performed according to standard procedures.

Results: Antimony showed genotoxicity in both tests, and bismuth also showed positive results in the chromosomal aberration test. In contrast, lead, indium, and silver were considered to be inactive by the criteria of the present study.

Conclusions: Although further studies are needed because of the difficulty of genotoxicity evaluation using an in vitro system, sufficient precautions should be made when antimony and bismuth are used.
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http://dx.doi.org/10.1539/joh.l9080DOI Listing
January 2010

Isotopic analysis of calcium in blood plasma and bone from mouse samples by multiple collector-ICP-mass spectrometry.

Anal Sci 2008 ;24(11):1501-7

Laboratory for Planetary Sciences, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro, Tokyo 152-8551, Japan.

The biological processing of Ca produces significant stable isotope fractionation. The level of isotopic fractionation can provide key information about the variation in dietary consumption or Ca metabolism. To investigate this, we measured the 43Ca/42Ca and 44Ca/42Ca ratios for bone and blood plasma samples collected from mice of various ages using multiple collector-ICP-mass spectrometry (MC-ICP-MS). The 44Ca/42Ca ratio in bones was significantly (0.44-0.84 per thousand) lower than the corresponding ratios in the diet, suggesting that Ca was isotopically fractionated during Ca metabolism for bone formation. The resulting 44Ca/42Ca ratios for blood plasma showed almost identical, or slightly higher, values (0.03-0.2 per thousand) than found in a corresponding diet. This indicates that a significant amount of Ca in the blood plasma was from dietary sources. Unlike that discovered for Fe, there were no significant differences in the measured 44Ca/42Ca ratios between female and male specimens (for either bone or blood plasma samples). Similarity, the 44Ca/42Ca ratios suggests that there were no significant differences in Ca dietary consumption or Ca metabolism between female and male specimens. In contrast, the 44Ca/42Ca ratios of blood plasma from mother mice during the lactation period were significantly higher than those for all other adult specimens. This suggests that Ca supplied to infants through lactation was isotopically lighter, and the preferential supply of isotopically lighter Ca resulted in isotopically heavier Ca in blood plasma of mother mice during the lactation period. The data obtained here clearly demonstrate that the Ca isotopic ratio has a potential to become a new tool for evaluating changes in dietary consumption, or Ca metabolism of animals.
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http://dx.doi.org/10.2116/analsci.24.1501DOI Listing
December 2008

Oral toxicity of indium in rats: single and 28-day repeated administration studies.

J Occup Health 2008 16;50(6):471-9. Epub 2008 Oct 16.

Department of Preventive Medicine and Public Health, Keio University School of Medicine, Japan.

Indium is widely used in the electronics industry to make semiconductors, liquid-crystal panels, and plasma display panels, and its production is increasing. However, it is necessary to handle it more cautiously than before, because the pulmonary toxicity of inhaled indium has been identified. The present study aimed to characterize the potential toxic effects of indium through oral administration and observation for fourteen days following a single dose of 0 or 2,000 mg/kg (acute oral toxicity study), and repeated oral administration for 28 days at dose levels of 0, 40, 200, or 1,000 mg/kg daily (28-day repeated oral dose toxicity study) to male and female Crj:CD (SD) IGS rats (SPF). No deaths and no abnormalities in clinical signs, body weights, and necropsy findings were observed for any of the animals in the acute oral toxicity study. Furthermore, no changes related to indium were also observed in the dose groups up to 1,000 mg/kg of the 28-day repeated oral dose toxicity study. From the results described above, the lethal dose 50% (LD(50)) of indium is greater than 2,000 mg/kg under these study conditions, and the no-observed-adverse-effect-level (NOAEL) is considered to be 1,000 mg/kg for males and females under these conditions.
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http://dx.doi.org/10.1539/joh.l8070DOI Listing
February 2009

Trace and major elements status in bronchoalveolar lavage fluid in dogs with or without bronchopneumonia.

Biol Trace Elem Res 2008 Jul 3;124(1):92-6. Epub 2008 Jun 3.

Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-8510, Japan.

The aim of this study was to investigate the relationships between the bronchopneumonia and mean concentrations of those trace elements in bronchoalveolar lavage fluid (BALF). Twenty-nine dogs were included this study (17 healthy dogs and 12 dogs with respiratory disease). Each BALF sample had been obtained during bronchoscope examination by use of a standardized method. The concentrations of Al, Br, Ca, Cu, Fe, K, Ni, P, Si, Sr and Zn in BALF were measured by the particle-induced X-ray emission method. We found no relationship between the bronchopneumonia and the levels of elements in the BALF, except Ca, P and Zn. The dogs with respiratory disease were found to have a large amount of Ca and Zn, and a high Ca/P and Zn/Cu ratios in BALF compared to those without respiratory disease.
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http://dx.doi.org/10.1007/s12011-008-8149-0DOI Listing
July 2008

Selenium-enriched Japanese radish sprouts influence glutathione peroxidase and glutathione S-transferase in an organ-specific manner in rats.

J Occup Health 2008 ;50(2):147-54

Department of Preventive Medicine, Shinshu University School of Medicine, Japan.

Selenium-enriched Japanese radish sprouts (Se-enriched JRS), in which Se-methylselenocysteine accounted for 80% of Se compounds, inhibited mammary tumorigenesis induced by 7,12-dimethylbenz[a]anthracene in rats. The effects of Se-enriched JRS on the oxidative stress-scavenging enzymes were investigated in rats. F344 female rats were fed test diets, in which Se-enriched JRS was added at 0, 2.4, 5.0, 8.8 or 12.5 ppm Se to commercial rodent chow for 3 wk. Glutathione peroxidase (GPx) and glutathione S-transferase (GST) in rat livers, kidneys and lungs were measured. Tissue Se concentrations at the highest Se dose (12.5 ppm) were high in order as follows: kidney > liver > lung. The diet at 12.5 ppm Se reduced the increase in body weight and, conversely, increased the liver weight. The Se test diets decreased hepatic and renal GPx activity at more than 2.4 ppm and 5.0 ppm, respectively. In contrast, the test diets increased pulmonary GPx activity at more than 2.4 ppm Se. The diets increased hepatic GST activity at more than 2.4 ppm Se dose dependently, whereas they reduced pulmonary GST activity at more than 2.4 ppm. The diet of 12.5 ppm Se induced GST Yp in all 3 organs and GST Yb1 in the liver. Thus, Se-enriched JRS influenced GPx and GST activity in a symmetrical manner in the livers and lungs of rats, with hepatic GST possibly affected, in part, by the induction of GST Yb1.
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http://dx.doi.org/10.1539/joh.l7130DOI Listing
June 2008

Relationship between hair elements and severity of atrioventricular block in horses.

Biol Trace Elem Res 2007 Mar;115(3):255-64

Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-8510, Japan.

The aim of this study was to investigate the relationships between the mean concentrations of trace elements and the severity of the second-degree atrioventricular (AV) block in the mane hair of horses. Electrocardiographs of horses were continually recorded for 6 h using a holter cardiac monitor to determine dropped ventricular beats (DVBs) which can be used as an indicator of the severity of the AV block. Mane hair Ca, Cu, Mg, and Zn concentrations were measured by the particle-induced X-ray emission method. The Zn/Cu ratio and Ca concentration in mane hair were significantly and positively correlated with the hourly DVBs in horse with a second-degree AV block (p<0.01, r2=0.485; p<0.05, r2=0.351, respectively). Proposed diagnostic cutoff points for hair Ca concentration and Zn/Cu ratio based on receiver operating characteristics curves analysis in detecting second-degree AV block were set at 1536 microg/g and 26.0, respectively. Those results with horse hair suggest that the evaluation of the Ca, Cu, Mg, and Zn status in mane hair by this method is strongly related to the severity of second-degree AV block and might predict the susceptibility of an individual much before the development of the symptom.
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http://dx.doi.org/10.1007/BF02686000DOI Listing
March 2007

Chemopreventive effect of selenium-enriched Japanese radish sprout against breast cancer induced by 7,12-dimethylbenz[a]anthracene in rats.

Tohoku J Exp Med 2007 Jun;212(2):191-8

Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.

Breast cancer is one of the major cancers in women, and dietary intake must be controlled to prevent it. Selenium (Se), especially Se compound in vegetables, is thought to be a promising chemopreventive dietary ingredient for preventing breast cancer. In this study, we developed Se-enriched Japanese radish sprout using a special Se-additional fertilizer, and identified the Se chemical forms. The newly developed Se-enriched sprout is produced within a week by the tank forming method, and the major chemical form was identified as Se-methylselenocysteine (MeSeCys) (80%). Then, the chemopreventive effects of the Se-enriched sprout were investigated using Sprague-Dawley female rats with mammary cancer, induced by a single oral dose of 10 mg or 14 mg of 7, 12-dimethylbenz[a]anthracene (DMBA). Mammary tumors were found in 11, 16 and 2 rats treated with DMBA and thereafter fed the basal (n = 34), sprout-added basal (n = 30) and Se-enriched sprout-added test diets (n = 30), respectively. The incidence of mammary tumors was significantly lower in the Se-enriched sprout-added test diet group (7%) than in the basal diet group (32%) or sprout-added basal diet group (53%). In contrast, no significant difference was detected in the numbers and incidence of the tumor between the basal diet group and Se-enriched sprout-added test diet group before DMBA-dosing. These results suggest that the diet supplement of Se-enriched sprout after DMBA-dosing provides a significant chemoprevention against chemical-induced mammary cancer. Thus, Se-enriched sprout may be a useful dietary ingredient for preventing breast cancer.
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http://dx.doi.org/10.1620/tjem.212.191DOI Listing
June 2007

Relationship between trace elements status in mane hair and atrial fibrillation in horse.

J Vet Med Sci 2006 Jul;68(7):769-71

Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fukisawa, Kanagawa, Japan.

To investigate the relationships between trace elements concentrations in hair and atrial fibrillation (AF) in horses, concentrations of nineteen trace elements were detected in hair using the particle induced X-ray emission (PIXE) method. The horses were assigned to either control (n=22, no abnormalities) or AF groups (n=5) based on electrocardiograph findings. The mean concentrations of Ca and Zn in the hair of the AF group were significantly higher than those in the control group. The Zn/Cu ratio of the hair in the AF group (29.8 +/- 5.5) was significantly higher than that in the control group (23.4 +/- 2.2, P<0.05). The results of the present study suggest that there is a relationship between elevated concentrations of Ca and Zn in hair and AF.
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http://dx.doi.org/10.1292/jvms.68.769DOI Listing
July 2006

[Trace elements and sperm parameters in semen of male partners of infertile couples].

Nihon Eiseigaku Zasshi 2005 Nov;60(4):418-25

Department of Epidemiology and Environmental Health, Junte University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113 8421, Japan.

Objective: The relationships between element concentrations and sperm parameters in semen samples were investigated.

Methods: Semen samples (n = 113) were donated voluntarily by male partners of infertile couples. The concentrations of fourteen elements (Na, K, P, Ca, Zn, Mg, Fe, Cu, Se, Mn, Sn, Co, Ni, and Cd) in semen were determined by atomic absorption spectrometry, fluorometry, or colorimetry. Element concentrations in seminal plasma and in sperm were also measured.

Results: Element concentrations in semen were in the order Na > P, K > Ca > Zn > Mg > > Fe> Cu, Se > Mn > Sn, Ni, Co, Cd. When the samples were divided into two groups in terms of sperm concentration and number, the Se concentration in semen with normal parameter values (sperm concentration > or = 20 x 10(6) and sperm number > or = 40 x 10(6)), 99.4 +/- 37.4 ng/ml, was higher than that in semen with abnormal parameter values (sperm concentration < or = 20 x 10(6) and/or sperm number < or = 40 x 10(6)), 72.1 +/- 33.9 ng/ml (p < 0.001). A clearer positive correlation between the Se concentration and the sperm concentration was observed in the sperm portion (r = 0.853, p < 0.001) than in semen (r = 0.512, p < 0.001) and seminal plasma (r = 0.292, p = 0.003). Statistically significant correlations were also observed between the concentration of Se, P, Zn, Cu, Fe, or Mn in semen, the sperm portion or seminal plasma and the sperm concentration, semen volume or abnormal morphology, although correlation coefficients were small.

Conclusion: Among biologically essential elements in semen of infertile males, Se was a good indicator of sperm concentration; however, other trace elements did not indicate clear relationships between their concentrations and sperm parameters.
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http://dx.doi.org/10.1265/jjh.60.418DOI Listing
November 2005

Correlation between 25 element contents in mane hair in riding horses and atrioventricular block.

Biol Trace Elem Res 2005 ;108(1-3):127-36

Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-8510, Japan.

The influence of atrioventricular block (AV-block) on the trace elemental status in a horse hair was studied. The particle-induced X-ray emission (PIXE) method has provided a reliable, rapid, easy, and relatively inexpensive diagnostic method. Twenty-five elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Hg, K, Mg, Mn, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, Y, and Zn) in mane hair and serum were measured by the PIXE method. A horse hair with first- and second-degree AV-block contained significantly greater amounts of Br, Ca, Sr, and Zn than those of horses without electrocardiographic abnormalities, whereas there was no significant differences in the elemental contents of the serum of the both groups. Those results in contents of a horse hair suggest that the evaluation of the degree of ionic imbalance by this method might be used to predict the susceptibility of a horse to heart disease much before symptoms appear.
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http://dx.doi.org/10.1385/BTER:108:1-3:127DOI Listing
March 2006

Anaemia, iron deficiency and vitamin A status among school-aged children in rural Kazakhstan.

Public Health Nutr 2005 Sep;8(6):564-71

Department of International Community Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Objectives: To investigate the prevalence of anaemia and iron deficiency and vitamin A status among school-aged children in rural Kazakhstan and identify factors associated with anaemia in this population.

Design: A cross-sectional design.

Setting: School-aged children in rural Kazakhstan.

Subjects: Socio-economic and anthropometric information was collected from 159 school-aged children living in the Kzyl-Orda region of Kazakhstan. Blood samples were collected and the concentrations of haemoglobin (Hb), serum iron, serum ferritin (SF), erythrocyte protoporphyrin (EP), serum retinol and beta-carotene, total iron binding capacity (TIBC), transferrin saturation (TS) and other haematological indices were measured.

Results: Among the 159 children, the prevalence of anaemia and iron deficiency defined by the multiple criteria model (SF, TS and EP) was 27% and 13%, respectively. Nine per cent had iron-deficiency anaemia and 21% had serum retinol value < 1.05 micromol l(-1). Mean SF and serum iron concentrations and TS were significantly lower in anaemic children than in their non-anaemic peers, while TIBC and EP were significantly higher in children with anaemia. Hb was significantly correlated with serum iron and retinol concentrations. Serum retinol and SF concentrations and mean corpuscular volume were significantly correlated with Hb by multiple regression analysis.

Conclusions: Anaemia among school-aged children in rural Kazakhstan appears to be related to iron indices and vitamin A status.
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http://dx.doi.org/10.1079/phn2004717DOI Listing
September 2005

Twenty-eight element concentrations in mane hair samples of adult riding horses determined by particle-induced X-ray emission.

Biol Trace Elem Res 2005 Nov;107(2):135-40

Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-8510, Japan.

The concentrations of 28 elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Ga, Hg, K, Mg, Mn, Mo, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, V, Y, and Zn) were measured in mane hair by the particle-induced X-ray emission method. Except for Br, Cl, K, S, and P, the trace element concentrations in mane hair of horses are similar to literature values for human hair. The values obtained are not dependent on the horse's age, breed, and sex and could be used as reference values in the assessment of diseases and nutritional status in equines.
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http://dx.doi.org/10.1385/BTER:107:2:135DOI Listing
November 2005

Oral toxicity of bismuth in rat: single and 28-day repeated administration studies.

J Occup Health 2005 Jul;47(4):293-8

Department of Preventative Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan.

The consumption and production of bismuth are increasing, however there is very little information about the direct toxic effect of bismuth. The present study aimed to characterize the potential toxic effects of bismuth through oral administration and observation for fourteen days following single dose of 0 and 2,000 mg/kg (acute oral toxicity study), and repeated oral administration for twenty-eight days at dose levels of 0, 40, 200, and 1,000 mg/kg daily (28-d repeated oral dose toxicity study) to male and female Crj:CD (SD) IGS rats (SPF). We found no deaths and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute oral toxicity study and no changes attributable to bismuth in either males or females in the dose group up to 1,000 mg/kg of the 28-d repeated-dose toxicity study. Therefore, we determined that the lethal dose with a 50% mortality rate (LD50) is greater than 2,000 mg/kg and the no-observed-adverse-effect level (NOAEL) of bismuth is 1,000 mg/kg in both sexes. We conclude that the adverse toxic effects of bismuth as a simple metal substance are low compared to lead toxicity under the conditions tested in our studies.
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http://dx.doi.org/10.1539/joh.47.293DOI Listing
July 2005

A 13-week toxicity study of bismuth in rats by intratracheal intermittent administration.

J Occup Health 2005 May;47(3):242-8

Department of Preventative Medicine and Public Health, School of Medicine, Keio University, Japan.

Although bismuth is widely used as a lead substitute in the industrial field, the toxicity of bismuth by inhalation is little known. We performed a 13-wk intratracheal intermittent bismuth dose toxicity study. Bismuth was administered at dose levels of 0, 0.8, 4, 20 mg/kg to male Crj:CD(SD)IGS rats (SPF) by intratracheal intermittent administration once a week for thirteen weeks to investigate its potential toxic effects; especially for specific adverse effects and changes related to pre-neoplastic lesions. Our results showed foreign body inflammation in the lungs, which was caused by intratracheal administration of bismuth, and physical changes related to pulmonary lesions; however, there were no serious changes in other organs. We concluded that dose-dependent, but not specific adverse effects, were attributable to bismuth inhalation in the rat.
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http://dx.doi.org/10.1539/joh.47.242DOI Listing
May 2005

Precise Zn isotopic ratio measurements of human red blood cell and hair samples by multiple collector-ICP-mass spectrometry.

Anal Sci 2005 Apr;21(4):425-8

Laboratory for Planetary Sciences, Department of Earth and Planetary Sciences, Graduate School of Science and Technology, Tokyo Institute of Technology, Ohokayama 2-12-1, Meguro, Tokyo 152-8551, Japan.

Precise 66Zn/64Zn and 68Zn/64Zn isotopic ratios of biochemical samples have been measured using multiple collector-ICP-mass spectrometry (MC-ICPMS). In order to eliminate the mass spectrometric interferences on Zn isotopes (e.g., 64Ni+ and 136Ba2+), we chemically purified the analyte using an ion chromatographic technique. The resulting precisions of the 66Zn/64Zn and 68Zn/64Zn ratio measurements were 0.05/1000 and 0.10/1000 (2SD), respectively, which were enough to detect the isotopic variation of Zn in nature. Red blood cell (RBC) samples were collected from five volunteers (four males and one female), including a series of 12 RBC samples from one person through monthly-based sampling over a year. These were analyzed to test possible seasonal changes and variations in 66Zn/64Zn and 68Zn/64Zn ratios among the individuals. The 66Zn/64Zn and 68Zn/64Zn ratios for a series of 12 RBC samples collected over a year were 0.43/1000 and 0.83/1000 higher than the values of highly purified Zn metal (JMC Zn), and no seasonal change could be found. The 66Zn/64Zn and 68Zn/64Zn ratios for RBC samples collected from five volunteers did not vary significantly. In order to investigate Zn isotopic heterogeneity in a human body, Zn isotopic ratios of a hair sample collected from one of the volunteers was also analyzed. The 66Zn/64Zn and 68Zn/64Zn ratios for the hair sample were 0.59/1000 and 1.14/1000 lower than the mean value of RBC samples. This result demonstrates that detectable isotopic fractionation occurs in the human body. The data obtained here suggest that the isotopic ratios of trace metals could provide new information about transportation of metal elements in vivo.
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http://dx.doi.org/10.2116/analsci.21.425DOI Listing
April 2005

Influence of the coat color on the trace elemental status measured by particle-induced X-ray emission in horse hair.

Biol Trace Elem Res 2005 Feb;103(2):169-76

Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-8510, Japan.

The influence of hair color on the trace elemental status in horse's hair has been studied. A current analytical technique such as particle-induced X-ray emission (PIXE) used in this study has provided reliable, rapid, easy, and relatively inexpensive diagnostic methods. Twenty-eight elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Ga, Hg, K, Mg, Mn, Mo, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, V, Y, and Zn) in mane hair were detected by the PIXE method. The gray hair contains significantly greater amounts of Cu, Ti, and Zn, and lower amounts of Br, Ca, Se, and Sr than those in other colored horse hairs (p<0.05). Those results measured in the horse's hair were similar to those found in human and dog hair. When interpreting a result, it should be kept in mind that hair color, especially gray hair, influences the concentrations of some elements in horse hair.
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http://dx.doi.org/10.1385/BTER:103:2:169DOI Listing
February 2005

Respiratory symptoms and pulmonary function among school-age children in the Aral Sea region.

Arch Environ Health 2003 Nov;58(11):676-82

Research Center for Tropical Infectious Diseases, Nagasaki University Institute of Tropical Medicine, Nagasaki, Japan.

The saline Aral Sea in central Asia was once the 4th largest inland lake in the world. Desiccation of the Aral Sea as a result of diversion of inflow for irrigation has resulted in significant adverse health effects among residents of surrounding areas. This study was conducted to examine respiratory symptoms and function among children who lived in "the heavily affected disaster zone" (i.e., within 200 km of the Aral Sea), by comparing them with children who lived in "the slightly affected disaster zone" (i.e., located approximately 500 km from the Aral Sea). A questionnaire-based interview was conducted among 383 students 6-15 yr of age who lived in the study area and 432 students who lived in the reference area. Pulmonary function tests were completed by 337 children in the study area and 417 children in the reference area. Prevalence of current cough and current wheezing was higher among the study group participants. Percentage of predicted forced vital capacity (FVC% predicted) was lower in the study group (median = 96.6%) than in the reference group (median = 100.5%), and prevalence of restrictive pulmonary dysfunction was higher in the study group (10.6%) than in the reference group (2.6%). Multivariate analysis indicated that FVC% predicted was lower among females and in the study area, but was not associated with socioeconomic factors.
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http://dx.doi.org/10.3200/AEOH.58.11.676-682DOI Listing
November 2003

Intracellular targeting of sodium mercaptoundecahydrododecaborate (BSH) to solid tumors by transferrin-PEG liposomes, for boron neutron-capture therapy (BNCT).

J Control Release 2004 Aug;98(2):195-207

Department of Pharmaceutics, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan.

The successful treatment of cancer by boron neutron-capture therapy (BNCT) requires the selective delivery of relatively high concentration of 10B compounds to malignant tumor tissue. This study focuses on a new tumor-targeting drug delivery system for BNCT that uses small (less than 200 nm in diameter), unilamellar mercaptoundecahydrododecaborate (BSH)-encapsulating, transferrin (TF)-conjugated polyethyleneglycol liposomes (TF-PEG liposomes). When TF-PEG liposomes were injected at a dose of 35 mg 10B/kg, we observed a prolonged residence time in the circulation and low uptake by the reticuloendothelial system (RES) in Colon 26 tumor-bearing mice, resulting in enhanced accumulation of 10B into the solid tumor tissue (e.g., 35.5 microg/g). TF-PEG liposomes maintained a high 10B level in the tumor, with concentrations over 30 microg/g for at least 72 h after injection. This high retention of 10B in tumor tissue indicates that binding and concomitant cellular uptake of the extravasated TF-PEG liposomes occurs by TF receptor and receptor-mediated endocytosis, respectively. On the other hand, the plasma level of 10B decreased, resulting in a tumor/plasma ratio of 6.0 at 72 h after injection. Therefore, 72 h after injection of TF-PEG liposomes was selected as the time point of BNCT treatment. Administration of BSH encapsulated in TF-PEG liposomes at a dose of 5 or 20 mg 10B/kg and irradiation with 2 x 10(12) neutrons/cm2 for 37 min produced tumor growth suppression and improved long-term survival compared with PEG liposomes, bare liposomes and free BSH. Thus, intravenous injection of TF-PEG liposomes can increase the tumor retention of 10B atoms, which were introduced by receptor-mediated endocytosis of liposomes after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. These results suggest that BSH-encapsulating TF-PEG liposomes may be useful as a new intracellular targeting carrier in BNCT therapy for cancer.
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http://dx.doi.org/10.1016/j.jconrel.2004.04.018DOI Listing
August 2004

Isotopic analysis of Fe in human red blood cells by multiple collector-ICP-mass spectrometry.

Anal Sci 2004 Apr;20(4):617-21

Department of Earth and Planetary Sciences, Graduate School of Science and Technology, Tokyo Institute of Technology, 2-12-1 Ohokayama, Meguro, Tokyo 152-8551, Japan.

Precise 56Fe/54Fe and 57Fe/54Fe isotopic ratios on human red blood cell (RBC) samples have been measured using multiple collector-ICP-mass spectrometry (MC-ICPMS). The mass spectrometric interferences on Fe isotopes (e.g., 56ArO+ and 57ArOH+) were successfully minimized by a dry plasma condition achieved by a desolvating nebulizer sample-introduction technique. In order to eliminate possible variations in the measured isotopic ratios due to non-mass spectrometric interferences, Fe was separated from remaining organic compounds and major co-existing elements using an ion chromatographic technique. The resulting precisions of the 56Fe/54Fe and 57Fe/54Fe ratio measurements were 0.12 per thousand and 0.20 per thousand, respectively, which were high enough to detect the isotopic variation of Fe in nature. For an interlaboratory comparison, all of the Fe isotopic ratio data were normalized by the ratios for the IRMM-014 international isotopic standard. A series of 12 RBC samples were collected from one person through monthly-based sampling over a period of one year. These were analyzed to test possible seasonal changes in the 56Fe/54Fe and 57Fe/54Fe ratios. Moreover, in order to test possible variations in the 56Fe/54Fe and 57Fe/54Fe ratios among different people, RBC samples were collected from five volunteers (four males and one female). The 56Fe/54Fe and 57Fe/54Fe ratios for a series of 12 RBC samples collected over a one-year period show 3.06 per thousand and 4.51 per thousand lower than the values of IRMM-014, and no significant seasonal change could be found in the ratios. The lack in seasonal changes in the Fe isotopic ratios could be explained by a small contribution of the daily net-intake of Fe (1 - 2 mg/day) onto the total amount of Fe in the human body (2 - 4 g). The 56Fe/54Fe and 57Fe/54Fe ratios for RBC samples collected from four male samples did not vary measurably, whereas the Fe isotopic ratios for a female RBC were 0.3 per thousand/amu heavier than the mean value of four male samples. This difference in Fe isotopes among the individuals can be the result of a difference in uptake efficiency of the Fe through a dietary process from the digestive tract. The data obtained here demonstrate that the isotopic ratios of trace metals can provide new information about metabolic efficiencies of the metallic elements.
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http://dx.doi.org/10.2116/analsci.20.617DOI Listing
April 2004

Another factor influencing the urinary calcium excretion.

Pediatr Nephrol 2003 Aug 16;18(8):843-4; author reply 845. Epub 2003 May 16.

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http://dx.doi.org/10.1007/s00467-003-1188-zDOI Listing
August 2003

Seasonal variation of trace element loss to sweat during exercise in males.

Environ Health Prev Med 2002 May;7(2):60-3

Department of Health and Physical Education, Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, 102-8159, Tokyo, Japan,

Objective: To clarify the seasonal differences of the trace element excretion in sweat, the trace element concentration in sweat and their loss during exercise were compared between summer and winter.

Methods: Sweat samples were collected from ten healthy adult males. Bicycle ergometer exercise was conducted by each subject at a heart rate of 140 beats/min for 1 hour, in summer and in winter. Sweat was collected by the arm bag method.

Results: Concentrations of major (Na, K, Ca, and Mg) and trace elements (Zn, Cu, Fe, Ni, Mn, and Cr) in sweat tended to be lower in summer than in winter, and significantly lower concentrations of Mg (p<0.01), Na, Cu, and Mn (p<0.05) were found in summer. The sweat volume in summer (0.90 L) was 1.7-fold larger than that in winter (0.52 L) (p<0.01). The amount of loss of each element to sweat calculated from the concentrations in sweat and sweat volume showed no significant difference between summer and winter.

Conclusions: It is suggested that there was no significant difference in the amount of loss of trace elements in sweat due to exercise between summer and winter.
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http://dx.doi.org/10.1007/BF02897331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723400PMC
May 2002
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