The Knowledge and Awareness for Radiocesium Food Monitoring after the Fukushima Daiichi Nuclear Accident in Nihonmatsu City, Fukushima Prefecture.

On 11 March 2011, Japan experienced a massive earthquake and tsunami that triggered the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, resulting in the release of large amounts of cesium-134 and -137 into the atmosphere. In addition to the food radioactivity control in the markets throughout the country, radiocesium concentrations in locally grown foods were voluntarily inspected and the results were shown to the residents by the local government to raise their awareness of the internal radiation contamination risk from low knowledge in Nihonmatsu City, Fukushima Prefecture. In this longitudinal study, local food products for in-home consumption were evaluated by seven different food radioactivity measuring devices in Nihonmatsu City from 2011⁻2017. Radiocesium was detected in local foods in Nihonmatsu City even six years after the FDNPP accident. The highest number of products tested was in 2012, with the number steadily decreasing thereafter. Most foods had contamination levels that were within the provisional regulation limits. As edible wild plants and mushrooms continue to possess high radiocesium concentrations, new trends in radioactivity in foods like seeds were discovered. This study highlights that the increased risk of radiation exposure could possibly be due to declining radiation awareness among citizens and food distributors. We recommend the continuation of food monitoring procedures at various points in the food processing line under the responsibility of the government to raise awareness for the reduction of future risks of internal exposure.

Mucosal-Associated Invariant T Cells in Regenerative Medicine.

Although antibiotics to inhibit bacterial growth and small compounds to interfere with the productive life cycle of human immunodeficiency virus (HIV) have successfully been used to control HIV infection, the recent emergence of the drug-resistant bacteria and viruses poses a serious concern for worldwide public health. Despite intensive scrutiny in developing novel antibiotics and drugs to overcome these problems, there is a dilemma such that once novel antibiotics are launched in markets, sooner or later antibiotic-resistant strains emerge. Thus, it is imperative to develop novel methods to avoid this vicious circle. Here, we discuss the possibility of using induced pluripotent stem cell (iPSC)-derived, innate-like T cells to control infection and potential application of these cells for cancer treatment. Mucosal-associated invariant T (MAIT) cells belong to an emerging family of innate-like T cells that link innate immunity to adaptive immunity. MAIT cells exert effector functions without priming and clonal expansion like innate immune cells and relay the immune response to adaptive immune cells through production of relevant cytokines. With these characteristics, MAIT cells are implicated in a wide range of human diseases such as autoimmune, infectious, and metabolic diseases, and cancer. Circulating MAIT cells are often depleted by these diseases and often remain depleted even after appropriate remedy because MAIT cells are susceptible to activation-induced cell death and poor at proliferation in vivo, which threatens the integrity of the immune system. Because MAIT cells have a pivotal role in human immunity, supplementation of MAIT cells into immunocompromised patients suffering from severe depletion of these cells may help recapitulate or recover immunocompetence. The generation of MAIT cells from human iPSCs has made it possible to procure MAIT cells lost from disease. Such technology creates new avenues for cell therapy and regenerative medicine for difficult-to-cure infectious diseases and cancer and contributes to improvement of our welfare.

Roles of children and their parents in the reduction of radiation risk after the 2011 Fukushima Daiichi Nuclear Power Plant accident.

INTRODUCTION: On March 11, 2011, Japan experienced its largest recorded earthquake with a magnitude of 9.0. The resulting tsunami caused massive damage to the Fukushima Daiichi Nuclear Power Plant reactors, and the surrounding environment was contaminated with radioactive materials. During this period, some residents were exposed to high levels of radiation (up to 5 millisieverts [mSv]), but since then, many residents have been exposed to low levels of radiation (<1 mSv). This study was conducted to assess the effects of lifestyle and attitude factors on external radiation exposure among Fukushima residents. METHODS: This community-based, cross-sectional study was conducted in Nihonmatsu City of the Fukushima Prefecture from May to July 2014. The population survey targeted 6,884 children between the ages of 0-15 years, and a personal radiation badge and questionnaire were administered to each of the residences. Multiple linear regression analysis was used to assess the impact of lifestyle and attitude factors on external radiation dose. RESULTS: The study participants (population size [n] = 4,571) had an additional mean radiation dose of 0.65 mSv/year, which is small as compared to the mean radiation dose 6 months after the disaster (1.5 mSv/year), in 2012 (1.5 mSv/year), and in 2013 (1.0 mSv/year). External radiation doses statistically varied by socio-demographic and lifestyle factors. Participants living in wooden residences (p-value<0.001) and within 100 meters of a forest (p = 0.001) had higher radiation exposure. Conversely, participants with a cautious attitude towards radiation had lower radiation exposure (beta [b] = -0.124, p = 0.003). CONCLUSION: Having a cautious attitude towards radiation and being aware of exposure risks proved to be significant in the reduction of external radiation dose. Therefore, in the event of future radiation disasters, attitudes towards and awareness of radiation should be considered in the reduction of exposure risk and implementation of radiation protection.

Clinical Outcome After Permanent Pacemaker Implantation in Patients With a High Percentage of Ventricular Pacing.

Previous reports have suggested that right ventricular apical pacing may lead to cardiac dysfunction. Septal pacing is thought to be superior to apical pacing in the prevention of cardiac dyssynchrony, however, there have been no reports on the contribution of septal pacing to improving clinical outcome.We retrospectively evaluated factors associated with cardiac events in patients with right ventricular pacing.The study population consisted of 256 consecutive patients newly implanted with permanent pacemakers and followed-up for 29 ± 18 months. Cardiac events, consisting of cardiac death or heart failure requiring hospitalization, occurred in 22 patients. Kaplan-Meier curves revealed that patients with a high percentage of ventricular pacing (> 90%, n = 101, group H) had a higher incidence of cardiac events than patients with a low percentage of ventricular pacing (< 10%, n = 83, group L) (P = 0.002). In group H, multivariate analysis showed that age (HR: 1.174, 95%CI: 1.066-1.291, P = 0.001), ejection fraction (EF) (HR: 0.898, 95%CI: 0.836-0.964, P = 0.003), QRS duration during cardiac pacing (HR: 1.059, 95%CI: 1.017-1.103, P = 0.006), and existing basal cardiac diseases (HR: 13.080, 95%CI: 2.463-69.479, P = 0.003) were significant predictors of cardiac events, although pacing site had no significant association with prognosis (P = 0.56).Higher age, lower EF, longer QRS duration during cardiac pacing, and existing basal cardiac diseases are associated with poor prognosis in patients with a high percentage of ventricular pacing.

2D-DIGE-based proteome expression changes in leaves of rice seedlings exposed to low-level gamma radiation at Iitate village, Fukushima.

The present study continues our previous research on investigating the biological effects of low-level gamma radiation in rice at the heavily contaminated Iitate village in Fukushima, by extending the experiments to unraveling the leaf proteome. 14-days-old plants of Japonica rice (Oryza sativa L. cv. Nipponbare) were subjected to gamma radiation level of upto 4 µSv/h, for 72 h. Following exposure, leaf samples were taken from the around 190 µSv/3 d exposed seedling and total proteins were extracted. The gamma irradiated leaf and control leaf (harvested at the start of the experiment) protein lysates were used in a 2-D differential gel electrophoresis (2D-DIGE) experiment using CyDye labeling in order to asses which spots were differentially represented, a novelty of the study. 2D-DIGE analysis revealed 91 spots with significantly different expression between samples (60 positive, 31 negative). MALDI-TOF and TOF/TOF mass spectrometry analyses revealed those as comprising of 59 different proteins (50 up-accumulated, 9 down-accumulated). The identified proteins were subdivided into 10 categories, according to their biological function, which indicated that the majority of the differentially expressed proteins consisted of the general (non-energy) metabolism and stress response categories. Proteome-wide data point to some effects of low-level gamma radiation exposure on the metabolism of rice leaves.

A Study of Thyroid 131I Activity of Five Human Subjects Exposed to a Radioactive Plume at Tamura City in Fukushima.

Thyroid 131I activities were determined for five human subjects from a disaster medical assistance team of Fukui Prefectural Hospital. The team was dispatched to the Tamura City Sports Park, 40 km from the Fukushima Daiichi nuclear power plant. They were exposed to a radioactive plume on 15 March 2011. In vivo measurements at Fukui Prefectural Hospital were conducted around 17 h after the team left the park. A thyroid counter equipped with a 51-mm-diameter × 51-mm-thick NaI(Tl) detector with a 20-mm-thick lead collimator was used. Mock iodine (133Ba and 137Cs) with a thyroid uptake neck phantom was used for calibration. On 16 March 2011, at 11:30, thyroid activity of a member of the team age 53 y, who was never administered stable iodine, was 268 ± 38 Bq. The remaining four men, aged 49, 35, 34, and 27 y, ingested two stable iodine pills (a total of 100 mg of potassium iodide) approximately 36 h before being exposed to the plume. Their thyroid activity values were 249 ± 86 Bq, 676 ± 107 Bq, 569 ± 96 Bq, and 1,082 ± 119 Bq, respectively. An inverse relationship between age and thyroid activity was observed among those who ingested potassium iodide before exposure, indicating that stable iodine administration may have a protective effect. Thyroid 131I activity was reduced by approximately 70% in the oldest person. This can be explained by the iodine metabolism in the thyroid of younger individuals being significantly faster than that of older individuals.

Unraveling low-level gamma radiation--responsive changes in expression of early and late genes in leaves of rice seedlings at Iitate Village, Fukushima.

In the summer of 2012, 1 year after the nuclear accident in March 2011 at the Fukushima Daiichi nuclear power plant, we examined the effects of gamma radiation on rice at a highly contaminated field of Iitate village in Fukushima, Japan. We investigated the morphological and molecular changes on healthy rice seedlings exposed to continuous low-dose gamma radiation up to 4 µSv h(-1), about 80 times higher than natural background level. After exposure to gamma rays, expression profiles of selected genes involved in DNA replication/repair, oxidative stress, photosynthesis, and defense/stress functions were examined by RT-PCR, which revealed their differential expression in leaves in a time-dependent manner over 3 days (6, 12, 24, 48, and 72 h). For example, OsPCNA mRNA rapidly increased at 6, 12, and 24 h, suggesting that rice cells responded to radiation stress by activating a gene involved in DNA repair mechanisms. At 72 h, genes related to the phenylpropanoid pathway (OsPAL2) and cell death (OsPR1oa) were strongly induced, indicating activation of defense/stress responses. We next profiled the transcriptome using a customized rice whole-genome 4×44K DNA microarray at early (6h) and late (72 h) time periods. Low-level gamma radiation differentially regulated rice leaf gene expression (induced 4481 and suppressed 3740 at 6 h and induced 2291 and suppressed 1474 genes at 72 h) by at least 2-fold. Using the highly upregulated and downregulated gene list, MapMan bioinformatics tool generated diagrams of early and late pathways operating in cells responding to gamma ray exposure. An inventory of a large number of gamma radiation-responsive genes provides new information on novel regulatory processes in rice.

Effects of valsartan on cardiovascular morbidity and mortality in high-risk hypertensive patients with new-onset diabetes mellitus.

BACKGROUND: The KYOTO HEART Study demonstrated that Valsartan Add-on treatment was effective to reduce new-onset diabetes in high-risk hypertensive patients. The purpose of the present study was to examine the effects of Valsartan Add-on treatment on cardiovascular (CV) events in patients with or without diabetes. METHODS AND RESULTS: A total of 3,031 patients were divided at baseline: Baseline Diabetes (n=807) and Baseline Non-Diabetes (n=2,224). Among the Non-Diabetes patients, 144 developed diabetes (New-Onset Diabetes) and the remaining patients did not throughout the study (Final Non-Diabetes, n=2,080). Baseline Diabetes showed significantly higher CV event rates than Baseline Non-Diabetes (10.3% vs. 7.0%, P=0.00400). Valsartan Add-on treatment significantly reduced CV event rates than Non-angiotensin receptor blocker (ARB) treatment both in Baseline Diabetes (6.7% vs. 13.8%, P=0.00274) and in Baseline Non-Diabetes (5.0% vs. 8.9%, P=0.00036), respectively. New-Onset Diabetes showed a similar CV event rate (12.5%) to Baseline Diabetes (10.3%) but the event rate was significantly higher than that of Final Non-Diabetes (6.6%, P=0.0065). In the New-Onset Diabetes, Valsartan add-on treatment significantly reduced CV event rate than Non-ARB treatment (5.2% vs. 17.4%, P=0.04601). CONCLUSIONS: CV event risk in New-Onset Diabetes was relatively equivalent to Baseline Diabetes. Valsartan Add-on treatment was effective for the reduction of CV events not only in Baseline Diabetes but also in New-Onset Diabetes.

Triphenyltin impairs insulin secretion by decreasing glucose-induced NADP(H) and ATP production in hamster pancreatic ß-cells.

Oral administration of triphenyltin chloride (TPT) (6 mg/100g body weight) inhibits insulin secretion by decreasing glucose-induced cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in pancreatic ß-cells of the hamster. To test the possibility that the abnormal level of the [Ca(2+)](i) induced by TPT administration could be due to a defect in the metabolic signal of glucose in the ß-cells, we tested the effects of TPT administration on the glucose-induced NAD(P)H and ATP production, and on the changes of membrane potential and [Ca(2+)](i) by glucose and high K(+) in the ß-cells. The [Ca(2+)](i) was measured in islet cells loaded with fura-2. TPT administration significantly reduced the NAD(P)H and ATP production, the depolarization of plasma membrane, and insulin secretion by 15 mM glucose in islet cells. TPT administration also reduced the insulin secretion by 10mM dihydroxyacetone and glyceraldehyde. However, TPT administration did not affect the increase of [Ca(2+)](i) and the insulin secretion by 30 mMK(+) or 100 µM tolbutamide, and the membrane potential by 30 mMK(+), and the insulin secretion by 10mM α-ketoisocaproic acid and 0.5mM formycin A, an analog of ATP in the presence of 15 mM glucose. These results suggested that the pathogenesis of TPT-induced hyperglycemia in hamster involves the reduction of [Ca(2+)](i) and insulin secretion in response to K(ATP) channel-dependent depolarization, which is related to the decrease of NAD(P)H and ATP production in pancreatic islet cells after glucose metabolism.

Combination effect of calcium channel blocker and valsartan on cardiovascular event prevention in patients with high-risk hypertension: ancillary results of the KYOTO HEART Study.

The ancillary analysis of the KYOTO HEART Study (n = 3031) was designed to assess the combined treatment with calcium channel blocker (CCB) plus valsartan for high-risk hypertension. With-CCB (n = 1807) showed less primary events than without-CCB (n = 1224) (P = .037), in which acute myocardial infarction was significantly reduced. With-CCB plus valsartan (n = 773) showed lower incidence than with-CCB plus non-angiotensin receptor blocker (ARB) (n = 1034) (P = .0002), in which angina pectoris and heart failure were significantly reduced. Without-CCB plus valsartan (n = 744) was superior to without-CCB plus non-ARB (n = 480) (P = .0013), in which stroke was reduced. CCB-based therapy was useful, and CCB plus valsartan combination provided a more efficient prevention for high-risk hypertensive patients.

Enhanced cardiovascular protective effects of valsartan in high-risk hypertensive patients with left ventricular hypertrophy--sub-analysis of the KYOTO HEART study.

BACKGROUND: The objective of the present study was to examine whether baseline electrocardiographically diagnosed left ventricular hypertrophy (ECG-LVH) influenced the angiotensin II receptor blocker (ARB) valsartan add-on effects on the cardio-cerebrovascular morbidity and mortality in the high-risk hypertensive patients who participated in the KYOTO HEART Study. METHODS AND RESULTS: The primary endpoint was the same as in the main study: a composite of defined cardiovascular and cerebrovascular events. The median follow-up period was 3.27 years. The study group was divided into 2 groups according to the presence of ECG-LVH: with LVH, n=803; without LVH, n=2,228. The primary endpoint events occurred more frequently in patients with LVH than in patients without LVH (9.3% vs. 7.3%; hazard ratio [HR], 1.33; 95% confidence interval [CI]: 1.01-1.75). Valsartan add-on significantly decreased the occurrence of primary endpoint events in both LVH-positive patients (5.8% vs. 12.9%; HR, 0.45; 95%CI: 0.28-0.72) and LVH-negative patients (5.5% vs. 9.2%; HR, 0.59; 95%CI: 0.44-0.81) compared with non-ARB treatment. The reduction in combined cardiovascular events (composite of acute myocardial infarction, angina pectoris, and heart failure) due to valsartan treatment in patients with LVH was significantly larger than that in patients without LVH (P<0.0001). Changes in blood pressure during the follow-up period did not differ significantly among the study subgroups. CONCLUSIONS: High-risk hypertensive patients with ECG-LVH might gain more cardiovascular benefits from valsartan add-on treatment, compared with patients without ECG-LVH.

A nation-wide survey on indoor radon from 2007 to 2010 in Japan.

In two previous nation-wide surveys in the late 1980s and early 1990s, Japanese indoor radon concentrations increased in homes built after the mid 1970s. In order to ascertain whether this trend continued, a nation-wide survey was conducted from 2007 to 2010. In total 3,900 houses were allocated to 47 prefectures by the Neyman allocation method and 3,461 radon measurements were performed (88.7% success). The fraction of reinforced concrete / concrete block buildings was 32.4%, similar to the value from national statistics. Arithmetic mean (standard deviation, SD) and geometric mean (geometric SD) of radon concentration after adjusting for seasonal fluctuation were 14.3 (14.7) and 10.8 (2.1) Bq/m(3). The corresponding population-weighted values were 13.7 (12.3) and 10.4 (2.0) Bq/m(3), respectively. It was estimated that only 0.1% of dwellings exceed 100 Bq/m(3), a new WHO reference level for indoor radon. Radon concentrations were highest in houses constructed in the mid 1980s and decreased thereafter. In conclusion, arithmetic mean indoor radon in the present survey was slightly lower than in previous surveys and significant reductions in indoor radon concentrations in both wooden and concrete houses can be attributed to alterations in Japanese housing styles in recent decades.

Measurement of microdosimetric spectra produced from a 290 MeV/n Spread Out Bragg Peak carbon beam.

This study describes measurements on secondary particles produced by a 290 MeV/n Spread Out Bragg Peak (SOBP) carbon beam. Microdosimetric distributions of secondary fragments from the SOBP carbon beam have been measured by using a new tissue equivalent proportional counter (TEPC) system at the Heavy Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences. The new TEPC system consists of a TEPC, two solid-state detectors (SSD) and a scintillation counter (FSC: forward scintillation counter). The SSDs and FSC can separately identify charged fragments and secondary neutrons produced by the incident carbon ions. Microdosimetric distributions were measured for secondary particles including neutrons produced by a body-simulated phantom consisting of various PMMA plates (thickness: 0, 34.81, 55.2, 60.95, 64.83, 95.03, 114.79, 124.69, 135.2 and 144.98 mm, respectively) to cover the SOBP (at 60-125 mm depth). The new system can separately determine produced fragments from the incident SOBP carbon beam in a body-simulated phantom.

Ultra low-dose radiation: stress responses and impacts using rice as a grass model.

We report molecular changes in leaves of rice plants (Oryza sativa L. - reference crop plant and grass model) exposed to ultra low-dose ionizing radiation, first using contaminated soil from the exclusion zone around Chernobyl reactor site. Results revealed induction of stress-related marker genes (Northern blot) and secondary metabolites (LC-MS/MS) in irradiated leaf segments over appropriate control. Second, employing the same in vitro model system, we replicated results of the first experiment using in-house fabricated sources of ultra low-dose gamma (gamma) rays and selected marker genes by RT-PCR. Results suggest the usefulness of the rice model in studying ultra low-dose radiation response/s.

Integrated transcriptomics, proteomics, and metabolomics analyses to survey ozone responses in the leaves of rice seedling.

Ozone (O(3)), a serious air pollutant, is known to significantly reduce photosynthesis, growth, and yield and to cause foliar injury and senescence. Here, integrated transcriptomics, proteomics, and metabolomics approaches were applied to investigate the molecular responses of O(3) in the leaves of 2-week-old rice (cv. Nipponbare) seedlings exposed to 0.2 ppm O(3) for a period of 24 h. On the basis of the morphological alteration of O(3)-exposed rice leaves, transcript profiling of rice genes was performed in leaves exposed for 1, 12, and 24 h using rice DNA microarray chip. A total of 1535 nonredundant genes showed altered expression of more than 5-fold over the control, representing 8 main functional categories. Genes involved in information storage and processing (10%) and cellular processing and signaling categories (24%) were highly represented within 1 h of O(3) treatment; transcriptional factor and signal transduction, respectively, were the main subcategories. Genes categorized into information storage and processing (17, 23%), cellular processing and signaling (20, 16%) and metabolism (18, 19%) were mainly regulated at 12 and 24 h; their main subcategories were ribosomal protein, post-translational modification, and signal transduction and secondary metabolites biosynthesis, respectively. Two-dimensional gel electrophoresis-based proteomics analyses in combination with tandem mass spectrometer identified 23 differentially expressed protein spots (21 nonredundant proteins) in leaves exposed to O(3) for 24 h compared to respective control. Identified proteins were found to be involved in cellular processing and signaling (32%), photosynthesis (19%), and defense (14%). Capillary electrophoresis-mass spectrometry-based metabolomic profiling revealed accumulation of amino acids, gamma-aminobutyric acid, and glutathione in O(3) exposed leaves until 24 h over control. This systematic survey showed that O(3) triggers a chain reaction of altered gene, protein and metabolite expressions involved in multiple cellular processes in rice.

Growth retardation and death of rice plants irradiated with carbon ion beams is preceded by very early dose- and time-dependent gene expression changes.

The carbon-ion beam (CIB) generated by the heavy-ion medical accelerator in Chiba (HIMAC) was targeted to 7-day-old rice. Physiological parameters such as growth, and gene expression profiles were examined immediately after CIB irradiation. Dose-dependent growth suppression was seen three days post-irradiation (PI), and all the irradiated plants died by 15 days PI. Microarray (Agilent rice 22K) analysis of the plants immediately after irradiation (iai) revealed effects on gene expression at 270 Gy; 353 genes were up-regulated and 87 down-regulated. Exactly the same set of genes was affected at 90 Gy. Among the highly induced genes were genes involved in information storage and processing, cellular processes and signaling, and metabolism. RT-PCR analysis confirmed the microarray data.

DNA microarray analyses reveal a post-irradiation differential time-dependent gene expression profile in yeast cells exposed to X-rays and gamma-rays.

Ionizing radiation (IR) is the most enigmatic of genotoxic stress inducers in our environment that has been around from the eons of time. IR is generally considered harmful, and has been the subject of numerous studies, mostly looking at the DNA damaging effects in cells and the repair mechanisms therein. Moreover, few studies have focused on large-scale identification of cellular responses to IR, and to this end, we describe here an initial study on the transcriptional responses of the unicellular genome model, yeast (Saccharomyces cerevisiae strain S288C), by cDNA microarray. The effect of two different IR, X-rays, and gamma (gamma)-rays, was investigated by irradiating the yeast cells cultured in YPD medium with 50 Gy doses of X- and gamma-rays, followed by resuspension of the cells in YPD for time-course experiments. The samples were collected for microarray analysis at 20, 40, and 80 min after irradiation. Microarray analysis revealed a time-course transcriptional profile of changed gene expressions. Up-regulated genes belonged to the functional categories mainly related to cell cycle and DNA processing, cell rescue defense and virulence, protein and cell fate, and metabolism (X- and gamma-rays). Similarly, for X- and gamma-rays, the down-regulated genes belonged to mostly transcription and protein synthesis, cell cycle and DNA processing, control of cellular organization, cell fate, and C-compound and carbohydrate metabolism categories, respectively. This study provides for the first time a snapshot of the genome-wide mRNA expression profiles in X- and gamma-ray post-irradiated yeast cells and comparatively interprets/discusses the changed gene functional categories as effects of these two radiations vis-à-vis their energy levels.

Dose effect for Japanese due to 232Th and 238U in imported drinking water.

The consumption rate of bottled mineral water in Japan has increased due to changes in eating habits and contamination of water sources. Radioactivity levels of 238U and 232Th in imported mineral water were checked from the viewpoint of internal radiation for Japanese subjects. Concentration ranges of 238U and 232Th in imported bottled mineral water, domestic bottled mineral water, domestic tap water, and domestic soft drinks were as follows: for U, N.D to 7.48 x 10(3), 1.07 to 344, 0.66 to 104, and 3.04 to 46.2 ng dm (ppt); for Th, 0.60 to 5.12, 0.65 to 22.4, 0.64 to 22.1, and 11.0 to 48.5 ng dm, respectively. In some brands of imported bottled mineral water, U concentration was sometimes much higher than domestic bottled mineral water and domestic tap water. The annual effective dose (1.5 x 10(-3) mSv y(-1) estimated from intake of 238U was approximately 7 times higher than that through dietary intake in Japanese. However, the internal dose added by drinking the imported portable water is negligible compared with total annual internal dose. Concentrations of non-radioactive elements were also compared between imported and domestic bottled water. Geometric means of cobalt, arsenic, strontium, cesium, phosphorous, and calcium in imported bottled water were higher compared with those of domestic bottled mineral water and domestic tap water. Maximum values of 11 elements (arsenic, rubidium, strontium, cesium, barium, sodium, magnesium, potassium, calcium, and manganese) were also found in imported bottled water.

HMG CoA reductase inhibitor suppresses the expression of tissue factor and plasminogen activator inhibitor-1 induced by angiotensin II in cultured rat aortic endothelial cells.

BACKGROUND: It has been demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HRIs) reduce the incidence of acute cardiovascular events in patients with hyperlipidemia. Recent reports have shown that the protective effects of these drugs against cardiovascular events are also observed in patients without hyperlipidemia, but the mechanism of this favorable effect still remains unclear. In this study, the effects of HRIs on the endothelial regulation of thrombus formation were elucidated. METHODS AND RESULTS: The mRNA and protein expression of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by angiotensin II (Ang II) were evaluated in cultured rat aortic endothelial cells. Pretreatment with simvastatin (0.03-3 microg/ml) significantly inhibited TF and PAI-1 induction by Ang II in a dose- and time-dependent manner. These inhibitions were significantly attenuated by mevalonic acid or geranylgeranyl pyrophosphate. Both Rho inhibitor, C3 exoenzyme, and Rho kinase inhibitor, Y-27632, mimicked the inhibitory effects of simvastatin against TF and PAI-1 induced by Ang II. This result suggested that the Rho/Rho kinase pathway is related to the TF and PAI-1 induction by Ang II. CONCLUSION: It was indicated that simvastatin maintains endothelial cells to be antithrombotic by inhibiting TF and PAI-1 expression via the Rho/Rho kinase pathways in which AngII induces TF and PAI-1 expression. These observations explain, at least partly, the mechanism of the favorable effects of simvastatin in reducing the thrombotic events.