A great number of synthetic chemicals are released into the environment, many of which are known or thought to interfere with normal thyroid hormone (TH) function. THs play important roles in regulating growth and development and maintaining metabolic homeostasis. For example, amphibian tadpole metamorphosis is a TH-triggered and controlled developmental process, and has proven to be useful as a screening tool for environmental pollutants suspected of disrupting TH functions. TH disruption is thought to be caused through a variety of mechanisms, including increased thyroxine (T₄) metabolism by uridine diphosphate glucuronyl transferases (UDPGTs), blocking TH signaling through TH receptors (TRs), and induction of mitochondrial membrane permeability transition (MPT). As our knowledge concerning the specific effects of these chemicals is very limited, further research is needed to obtain accurate information to be used in establishing guidelines for the protection of health in humans and wildlife.

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Aluminium (Al) in the blood is bound to transferrin (Tf), a glycoprotein of about 80 kDa that is characterized by its need for a synergistic anion. The binding affinity of both Al and iron (Fe) for Tf is surveyed in the context of our recent studies by on-line high-performance liquid chromatography/high-resolution inductively coupled plasma mass spectrometry (HPLC/HR-ICP-MS). First, Al in human serum without any in vitro Al-spikes was present in a form bound to the N-lobe site of human serum Tf (hTf). Next, the effects of sialic acid in the carbohydrate chain of hTf on the binding affinity of Al (or Fe) for hTf were studied by using asialo-hTf obtained by treating hTf with sialidase. The binding affinity of Fe for asialo-hTf and native-hTf was similar, but the binding affinity of Al for asialo-hTf was greater than that for native-hTf. These findings are discussed in relation to diseases in which the serum concentrations of carbohydrate-deficient Tf and oxalate are increased.

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In this study, we investigated the effect of amine- and hydroxyl-terminated Generation 2 and 3 (G2 and G3) poly(amidoamine) (PAMAM) dendrimers on the viability and induction of apoptosis in human MCF-7 and MDA-MB-231 breast cancer cells. It was shown that amino-terminated PAMAM dendrimers were cytotoxic, with IC₅₀ value after 24 hr of incubation in MCF-7 and MDA-MB-231 breast cancer cells 153±3 μM and 140±2 μM for G2 PAMAM and 120±3 μM and 99±2 μM for G3 PAMAM, respectively. Experiments made with annexin V-fluorescein isothiocyanate (V-FITC) and detection of apoptosis by a fluorescent microscopy assay revealed that G2 and G3 PAMAM-NH₂ dendrimers inhibited the proliferation of MCF-7 and MDA-MB-231 malignant cells by increasing the number of apoptotic and necrotic cells. The cytotoxic and apoptotic effect of G2 and G3 PAMAM-OH dendrimers was significantly weaker.

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The present study was designed to determine the effects of benzylglucosinolate on endurance capacity in mice. Mice were orally administered either vehicle or benzylglucosinolate (0.015 or 0.03 mg/kg) via stomach intubation for a 6-week period. Benzylglucosinolate-treated mice showed a significantly increased endurance exercise capacity. Benzylglucosinolate significantly decreased blood lactate concentrations and significantly elevated plasma non-esterified fatty acid (NEFA) during exercise. Lastly, benzylglucosinolate treatment significantly decreased fat accumulation. These data suggest that benzylglucosinolate enhanced swimming endurance due to increased fatty acid utilization as an energy source.

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An analytical method using liquid chromatography tandem mass spectrometry equipped with electrospray ionization (ESI) was demonstrated for the determination of medicinal ingredients, such as fenfluramine (FF), N-nitrosofenfluramine (NFF), sibutramine (SIB), sildenafil (SDF), vardenafil (VDF), tadalafil (TDF) and xanthoanthrafil (XAF), in so-called health-promoting food. These analytes were clearly separated with acetonitrile-water (40:60) containing 4 mM formic acid and 8 mM ammonium formate used in the mobile phase on a pentafluorophenyl (PFP) column under isocratic conditions. The retention times of FF, SIB, SDF and VDF on the PFP column were longer than those on the C18 column under the same mobile phase conditions. Within wide ranges, all peaks were proportional and the coefficient of determination (r²) showed more than 0.9950 in a linear regression analysis. The limit of quantification (LOQ) of the developed method was 0.8-42.2 μg/l (S/N=10). The recoveries of analytes admixed with commercially available health-promoting food ranged from 80.2 to 113.3% and were acceptable for quantitative analysis. Analytes of more than 2 μg in a health-promoting food sample (0.5 g) were able to be identified by the European Communities (EC) criteria.

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The present study was undertaken to investigate the amounts of artificial radionuclides ingested through the daily diet by inhabitants of Kanagawa Prefecture, Japan. To this end, the level of cesium-137 (¹³⁷Cs) contained in the daily diets of females (combined samples from 5 females) aged 40-69 living in urban and suburban districts of Kanagawa Prefecture was measured. Furthermore, 11 elements (Ca, Cl, Cr, Cs, Fe, K, Mn, Na, Rb, Sc, and Zn) in the diets were quantified by instrumental neutron activation analysis. The study revealed that the intake of ¹³⁷Cs increased markedly in 1986, the year the Chernobyl accident occurred, and it tended to decrease gradually thereafter. In recent years, the reduction in the dietary intake of ¹³⁷Cs has been slowing down. When the intake of nutrients ingested by inhabitants of the two survey areas was compared with the Dietary Reference Intakes for Japanese (2005), the amount ingested in each of the two survey areas approximately satisfied or was slightly lower than the reference levels. Among others, the amount of Ca and Fe ingested in the urban district was particularly low (52 and 64% of the national reference, respectively). For many elements, the amount ingested was greater in the suburban than in the urban district. When the ingredients of the subjects' meals were classified into food groups, the meals prepared by suburban inhabitants were found to be composed of more diverse ingredients, covering all food groups, compared to those prepared by urban inhabitants. The daily food intake was also greater in the suburban district. When the daily dietary samples from individual subjects were analyzed separately, without being combined, both the level of ¹³⁷Cs and the amount of stable elements contained in the separate samples showed greater variations from day to day than those in the combined samples. There was no correlation between the dietary intake of ¹³⁷Cs and that of Cs.

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The study was undertaken to evaluate the antihyperglycemic potential of mangiferin purified from methanolic root extract of Salacia chinensis (S. chinensis) in control and streptozotocin (STZ)-induced diabetic rats. The mangiferin was administered orally at a dose of 40 mg/kg weight per day (30 days) to STZ-induced diabetic rats. The mangiferin treated diabetic rats significantly decreased the level of blood glucose, glycosylated hemoglobin as well as increased level of insulin and hemoglobin. The activities of hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glycogen synthase, and glycogen content level were increased to near normal in mangiferin treated diabetic rats. The activities of lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-diphosphatase and glycogen phosphorylase were significantly decreased in liver tissue of diabetic treated rats. These findings demonstrated that mangiferin possess antidiabetic activity against STZ-induced diabetic rats. The antidiabetic effect of mangiferin was compared with standard antidiabetic drug glibenclamide.

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Donepezil (acetyl cholinesterase inhibitor) is a mainstay of clinical intervention to contain memory deficits of Alzheimer's disease. However, its beneficial role in endothelial dysfunction-associated dementia i.e. vascular dementia still needs to be explored. The present study was designed to investigate the effect of donepezil on vascular endothelial dysfunction, and associatedmemory deficits in rats. Atorvastatin (3-hydroxy-4-methyl-glutaryl (HMG)-CoA inhibitor) was taken as the standard. Rats were administered L-methionine (1.7 g/kg per day, p.o., 4 weeks and 4 days i.e. chronic treatment) to produce endothelial dysfunction and dementia. Serum nitrite level was estimated as a marker of endothelial function. Morris water maze (MWM) test was employed for assessment of memory. Brain tissue thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were estimated to assess oxidative stress. Brain acetylcholine esterase (AChE) activity and serum total cholesterol level were also estimated. L-methionine produced endothelial dysfunction as reflected by significant decrease of serum nitrite concentration. L-methionine-treated rats performed poorly on MWM indicating impairment of memory as well. These rats also showed a significant rise in brain oxidative stress, AChE activity and serum total cholesterol levels. Donepezil (0.1 mg/kg p.o.) and atorvastatin (10 mg/kg p.o.) attenuated L-methionine-induced endothelial dysfunction. This intervention reversed L-methionine-induced rise of brain oxidative stress and AChE activity. Furthermore, atorvastatin produced a reduction of L-methionine-induced rise in serum cholesterol. The beneficial effects of donepezil may be attributed to its multiple effects and this study highlights the potential of donepezil in vascular dementia.

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The B-type natriuretic peptide receptor (NPR-B) is a specific receptor for the C-type natriuretic peptide (CNP) and the binding of the peptide to NPR-B stimulates the bone formation by osteoblasts. However, the mechanism behind the regulation of NPR-B expression in osteoblasts remains unknown. In this study, we examined the role of prostaglandin E₂ (PGE₂) through the PGE₂ receptor subtypes, EP1, EP2, EP3 and EP4, in the regulation of NPR-B expression using calvarial osteoblasts from rats of various ages. Reverse Transcription-PCR (RT-PCR) and Western blotting analyses revealed that PGE₂ or 17-phenyl-ω-trinor PGE₂, an EP1 agonist, increased the expression of NPR-B of calvarial osteoblasts from 25-week-old rats in a time- and dose-dependent manner. The PGE₂- and EP1 agonist-induced increase in NPR-B expression was blocked by treating with SC19220, an EP1 antagonist. By contrast, agonists for EP2, EP3, and EP4 failed to affect the NPR-B expression. The basal mRNA level of NPR-B and EP1 continuously decreased with the age of cell donors between 10 to 60 weeks and remained constant over 60 weeks. The degree of EP1 agonist-induced increase in NPR-B mRNA level gradually decreased with age of cell donors between 10 to 60 weeks, and no significant effect of EP1 agonist on the NPR-B mRNA level was observed over 60 weeks. From these results, we concluded that PGE₂ acts as a regulator of NPR-B expression through the EP1 receptor in osteoblasts and age-related decrease in EP1 expression causes a decrease in NPR-B expression.

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Smoking is a risk factor for various disorders. Strategies have been established in various countries. To support smoking cessation, the nicotine patch was developed, and various clinical studies have been conducted to evaluate its effects. However, its long-term effects remain to be clarified. We conducted a meta-analysis based on the results of randomized, comparative studies, with high-level scientific reliability, to investigate the long-term efficacy of the nicotine patch. We reviewed the 1-year results of nicotine-patch use in 18 studies using a fixed effect model via the PubMed and Cochrane Library. The combined odds and risk ratios were 1.753 [95% confidence interval (CI): 1.520-2.021] and 1.594 (95% CI: 1.406-1.806), respectively. In the nicotine-patch group, the success rate for smoking cessation was significantly higher than that in the nicotine-patch-free group. Furthermore, the combined risk difference was 5.33% (95% CI: 3.99-6.66%); nicotine-patch prescription increased the rate at which smoking cessation was successfully achieved, by approximately 5%. The number of persons requiring treatment after 1 year was 19. Based on the results of RCTs, we calculated the combined odds ratio, combined risk ratio, combined risk difference, and number needed to treat (NNT). The nicotine patch significantly increased the success rate for smoking cessation after 1 year. The possibility of publication bias cannot deny completely because the funnel plots were not symmetrical.

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The conversion of quinolinic acid (QA) into a fluorescent compound by the catalytic activity of horseradish peroxidase (HRP) was investigated in the presence of hydrogen peroxide without exposure to light. Nonfluorescent quinolinic acid was converted into a fluorescent compound with maximum excitation and emission wavelengths at 328 and 377 nm, respectively. This fluorescent derivatization reaction with HRP in the presence of hydrogen peroxide was adopted for the determination of trace amounts of QA. The calibration curve obtained was linear from 0.1 to 5.0 nmol of QA in a 1.0 ml sample solution. The detection limit was 0.04 nmol/ml. The relative standard deviation at 3.0 nmol of QA was 3.58% (n=8). This method was applied to the determination of QA spiked in control serum I and II. The recovery rates of QA were greater than 98%, and satisfactory results were obtained for both control serum I and II.

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The present study demonstrates the occurrence of pharmaceuticals and personal care products (PPCPs) in surface water from the Mankyung River, South Korea. Samples collected at 5 Sites along theMankyung River were assayed using a liquid chromatograph coupled with a tandem mass spectrometer (LC/MS/MS) for 13 PPCPs. Overall, 11 out of the 13 selected PPCPs, which span a range of therapeutic classes and one personal care product, were detected in surface water samples collected from the Mankyung River. The most prevalent contaminants were ibuprofen, with average concentrations ranging from not detected (ND) to 414 ng/l, followed by carbamazepine (ND-595 ng/l), atenolol (ND-690 ng/l), clarithromycin (ND-443 ng/l), mefenamic acid (ND-326 ng/l), erythromycin (ND-137 ng/l), fluconazole (ND-111 ng/l), levofloxacin (ND-87.4 ng/l), indomethacin (ND-33.5 ng/l), propranolol (ND-40.1 ng/l), ifenprodil (ND-35.4 ng/l), disopyramide (ND) and triclosan (ND). PPCP concentrations were highest in surface water samples collected downstream from a sewage treatment plant (STP), implying possibly insufficient removal efficiency of the PPCPs in the STP. Contamination by PPCPs such as ibuprofen, carbamazepine, atenolol, mefenamic acid and clarithromycin was high in the Mankyung River compared to concentrations in other countries.

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Cigarette smoking is one of the avoidable causes for diseases such as lung cancers, but biomarkers for health condition by cigarette cessation are expected. Biochemical data in plasma from 3053 Japanese in Tokyo were investigated who underwent an annual health check-up from 2003 to 2007 with amount and duration of cigarette smoking. Dose-dependent effects of cigarette smoking as indicated by Brinkman index (daily number of cigarettes × years) were observed on increased circulating white blood cell counts in men and women, red blood cell in women, and plasma triglycerides concentrations in men. Higher levels of hemoglobin and hematocrit in females were seen with ≤ 400 of Brinkman index, but these increases were observed in the male group with ≤ 800 of index. Decreased high-density lipoprotein cholesterol levels in blood were seen in men (> 800 of index). Decreased low-density lipoprotein cholesterol levels and enhanced glucose levels were only seen in a pooled heavy smoker group. Since increased ratios for the white blood cell counts in men and women by cigarette smoking were high among the markers tested in this study, the recovery of these parameters by cigarette cessation was investigated. The white blood cell counts were recovered time-dependently after quitting smoking for 1-3 years as evident with 38 other former smokers. These results suggest white blood cell counts would be sensitive biomarkers for smoking exposures and time-dependent recovery in hearty volunteers in monitoring and educating cigarette smoking and cessation.

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Electrolytes and minerals are involved in most cellular activities and assume a major role in metabolism. The present study is aimed to understand the influence of electrolyte alterations on serum lipid profile and enzymes in chronic cigarette smokers. Thirty human male volunteers in each group, aged between 27 and 35 taking local diet and smoking for 7-10 years at least 8-12 cigarettes per day were chosen as experimental subjects. All the subjects were using cigarettes without a filter. Controls (age, sex and diet matched) who did not smoke were selected for the study. Blood samples drawn from human volunteers by venipuncture and were used immediately for analysis. There was no significant change observed in serum sodium, chloride levels, where as significant (p<0.05) increase was observed in potassium, iron, calcium and phosphate in chronic cigarette smokers when compared to controls. Further, enhanced activities of the serum enzymes viz., transaminases (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and with no change in γ-glutamyl transferase (γGT) were observed. The concentration of calcium was positively correlated with serum total cholesterol and low-density lipoprotein (LDL) cholesterol (r=0.252, r=0.347) respectively and negatively (r=-0.164) correlated with high-density lipoprotein (HDL) cholesterol, further, potassium was positively correlated with LDH, ALP and ALT (r=0.419, r=0.174, 0.248) respectively in chronic cigarette smokers. Chronic cigarette smoking might have induced alterations in membrane permeability properties of tissues and organs, which might have resulted in changes in signal transduction and electrolyte imbalance.

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The objective of this study was to investigate the effect of various selenium (Se) status on glucose intolerance and pancreatic oxidative stress or the defense systems in Nagoya-Shibata-Yasuda (NSY) mice as the animal model for type 2 diabetes mellitus. To let the mice become Se-insufficient to Se-sufficient conditions, the NSY mice were given normal or Se-deficient diet with 0-7.0 mg/l Na₂SeO₃-containing drinking water for 6, 8 or 12 weeks. In NSY mice ingested normal diet, levels of blood glucose and plasma insulin after intraperitoneal glucose tolerance test (IPGTT) were not significantly affected by Na₂SeO₃-supplementation. In Se-deficient diet-treatment groups, however, the supplementation resulted in the decrease of blood glucose and the increase of plasma insulin after IPGTT. Although glutathione peroxidase (GPX) 1 activity in pancreas of the NSY mice ingested Se-deficient diet was augmented by Na₂SeO₃-supplementation, pancreatic glutathione was depressed by the supplementation, accompanying by the increase of 2-thiobarbituric acid-reactive substances. These results indicated that although the supplemented Na₂SeO₃ may not protect against oxidative stress in the pancreas of NSY mice under Se-insufficient condition, the Se compound improved glucose intolerance of the mice.

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The leaching of acetyl tributyl citrate (ATBC) from plastic kitchen wrap into water, aqueous acetic acid solution, and aqueous skim milk solution heated to 60°C was investigated. A new extraction method was developed to determine the leaching rate. It was found that ATBC is prone to migrate into protein liquids, such as aqueous skim milk solution.

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A formulation of Ocimum sanctum, Phyllanthus emblica, and Glycyrrhiza glabra in a defined ratio termed CIM-Candy was prepared based on Ayurvedic methodology. To study the humoral immune response, rabbit red blood corpuscles (rRBCs) were used as an antigen. Mice were immunized on day 7 and 14 days the start of the experiment using an intraperitoneal injection of 200 μl of rRBCs (2×10⁸ cells/ml). Humoral immune response, body weight variation, and hematology parameters were studied. CIM-Candy at doses of 10 and 100 mg/kg body weight enhanced the immune function by significantly increasing (p<0.05) the hemagglutination antibody titer response against the rRBCs. Significant changes were not observed in body weight and hematology parameters when comparing the normal vehicle control and treatment groups. As the biological activity of the plant-derived formulation was not assigned to a single chemical, high performance thin layer chromatography (HPTLC) fingerprinting was also performed to confirm the chemical characteristic of the formulation. The results of this study suggest that the standardized formulation CIM-Candy exhibited significant humoral immune response in Swiss albino mice.

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This study determined the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (dioxin-like PCBs) in five selected plant materials [dokudami (from houttuynia herb), rose hip (from rosa fruit), ebisugusa (from cassia seed), rooibos, and tochu (from eucommia leaf)] used as health teas in Japan. The toxic equivalent (TEQ) levels for dioxins in the samples ranged from <0.001 to 0.27 pg-TEQ/g weight, when undetectable and trace amounts were taken as zero. The mean of total TEQ level in commercial tea materials was estimated as 0.08 pg-TEQ/g (n=5). The total TEQ in these samples was mainly dominated by the levels of PCDD/Fs (representing ca. 80% of the total TEQ).

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The aim of the present study was to examine the effects of cigarette smoking (CS) on fasting blood insulin, homeostasis model assessment index (HOMA-R index), glucose and lipids in Japanese collegiate women. Twenty-six smokers were individually matched for physical activity scores, age, and body mass index with 26 nonsmokers. Information on smoking, physical activity habits, and diet record were collected. Blood samples were taken and analyzed to evaluate their associations with CS. The results showed significantly higher mean serum insulin, HOMA-R index, and glucose while lower mean high-density lipoprotein two cholesterol (HDL₂-C) in smokers as compared with nonsmokers. The mean nutrient intakes showed no significant differences between smokers and nonsmokers. In conclusion, it appears that CS is associated with insulin resistance, impaired fasting glucose and lower HDL₂-C in young Japanese female smokers. This may partly explain the deleterious effects of smoking on coronary heart disease risk.

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Cow's milk is an important foodstuff and beneficial to human health. In the present study, commercial milks from China and Japan and raw milk from Inner Mongolia of China were collected. The contents of 18 elements were determined using inductively coupled plasma-optical emission spectrometry (ICP-OES), atomic absorption spectrometry (AAS) and atomic fluorescence spectrometry (AFS). Our analysis showed both Chinese and Japanese milks are rich in macroelements, such as calcium, potassium. However, the milk contents of chromium, manganese and zinc, which belong to microelements, were higher in Chinese commercial milks than in Japanese commercial milks. Heavy metals in food pose potential healthy risk. Although lead and cadmium contents in Chinese milk did not exceed the tolerance limits of Chinese National Standards, they were higher than those in Japanese commercial milks. Based on the high contents of some microelements and heavy metals in Chinese milk, we should innovate the technology and improve quality control for milk process and decrease environmental pollution.

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Irrigation of crops with treated wastewater has been employed in many regions of the world. It mitigates the pressure of water demand, however, it also introduces effluent-derived organic contaminants into surface waters via agricultural runoff. In this study, a potato field located in southern California was selected as the research site. Runoff samples were collected during irrigation events, and a variety of compounds were identified both in irrigation water and runoff samples. Treatments on the field included polyacrylamide (PAM) application, deep plow, previous-grown Sudan grass, and control (without above treatments). The compounds included pharmaceuticals (e.g., clofibric acid, ibuprofen, naproxen, ketoprofen, diclofenac), personal care product (e.g., triclosan), endocrine disrupting compounds (e.g., bisphenol A, 4-n-nonylphenol, 4-t-octylphenol), and estrogenic compounds (e.g., estrone, 17β-estradiol, 17α-ethynylestradiol). Themonitoring results showed the presence of these compounds in runoff samples. They were at concentrations from below limits of quantification (LOQ) to sub μg/l levels. Although their levels were low, their potential to elicit adverse effects in aquatic organisms cannot be overlooked.

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We established stable HeLa transformants with reporter genes containing nuclear factor (NF)-κB response elements to measure NF-κB inhibition. Tumor necrosis factor (TNF)-α treatment induced a 6-fold activation of NF-κB in HeLa_NF-κB-3 cells. Three chloro-derivatives of fourteen dibenzoylmethane derivatives inhibited NF-κB activity.

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We examined the effect of δ-tocotrienol on melanin content in mouse melanoma B16 cells. Melanin content was significantly reduced in cells treated with 50 and 100 μM δ-tocotrienol, but not 10 μM δ-tocotrienol. The activity and amount of tyrosinase also significantly decreased in cells treated with 10, 50, and 100 μM δ-tocotrienol. Furthermore, the mRNA level of tyrosinase as measured using realtime PCR was significantly decreased compared to controls in cells treated with 100 μM δ-tocotrienol, but not 10 or 50 μM δ-tocotrienol. These results indicated that at first δ-tocotrienol caused tyrosinase degradation, and then caused a further decrease in the tyrosinase protein level via both tyrosinase degradation and a decrease in the mRNA level of tyrosinase. We conclude that the decrease of melanin content in the cells by δ-tocotrienol was the result of the decrease of the protein level of tyrosinase (tyrosinase degradation is more important than the decrease of mRNA).

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Oxidative DNA damages involve reduction-oxidation reactions between certain metals and compounds, and result in genetic abnormalities leading to diseases including cancer and neurodegenerative disorders. Here, we report that DNA damages mediated by combination of a neurotransmitter dopamine and copper accompany a unique DNA conformational change. Copper(II) [Cu(II)] was shown as bound to consecutive guanines (G-G) of DNA, by demonstrating the G-G selective inhibition of restriction enzymes. When dopamine was added to calf thymus DNA in the presence of Cu(II), DNA guanines were oxidized. UV and ¹H NMR analyses suggested that dopamine was oxidized to the quinone form in the presence of Cu(II). The circular dichroism experiments showed DNA spectral changes under the conditions of oxidative DNA damage, indicating a conformational change of the DNA strand by dopamine and copper. The DNA conformational change was suppressed by adding a Cu(I)-specific chelator bathocuproine. Therefore, the conformational change can be explained by a rearrangement of the copper-coordination geometry in DNA through Cu(II) reduction to Cu(I). Thus, changes in DNA conformation could be involved in metal-mediated genotoxicity as well as oxidative damage but via different mechanism.

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