Size-classified aerosol-bound heavy metals and their effects on human health risks in industrial and remote areas in Japan.

Airborne aerosols were collected in six size classes (PM<0.1, PM0.1-0.5, PM0.5-1, PM1-2.5, PM2.5-10 and PM>10) to investigate aerosol health risks in remote and industrial areas in Japan. We focused on heavy metals and their water-dispersed fractions. The average concentration of heavy metals was 18 ± 25-86 ± 48 ngm-3 for PM<0.1, 46 ± 19-154 ± 80 for PM0.5-1 ngm-3, 98 ± 49-422 ± 186 ngm-3 for PM1-2.5, 321 ± 305-1288 ± 727 ngm-3 for PM2.5-10 and 65 ± 52-914 ± 339 ngm-3 or PM>10, and these concentrations were higher in industrial areas. Heavy metals emitted from domestic anthropogenic sources were added to the long-range transport component of the aerosols. The water-dispersed fraction of heavy metals contained 3.3-40.1% of the total heavy metals in each size class. The relative contribution of Zn and other species (As, Cd, Cr, Ni, Pb, Mn, V and Cu) increased in the water-dispersed fraction. Smaller particles contained greater proportions of the water-dispersed heavy metal fraction. Carcinogenic risk (CR) and the hazard index (HI) were estimated for each size class. The CR of carcinogens was at acceptable levels (<1 ×10-6) for five particle size fractions. The HI values for carcinogens and noncarcinogens were also below acceptable levels (<1) for the same five size fractions. The estimated CR and HI values were dominated by contributions from the inhalation process.

Pulmonary vasodilators can lead to various complications in pulmonary "arterial" hypertension associated with congenital heart disease.

Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) is one of the major complications in patients with CHD. A timely closure of the left-to-right shunt will generally result in the normalization of the pulmonary hemodynamics, but a few patients have severe prognosis in their early childhood. We hypothesized that wide-ranging pathological mechanism in PAH could elucidate the clinical state of severe CHD-PAH. Using electronic medical records, we retrospectively analyzed six infants with severe CHD-PAH who had treatment-resistant PH. All patients were born with congenital malformation syndrome. After starting on a pulmonary vasodilator, five of the six patients developed complications including pulmonary edema and interstitial lung disease (ILD), and four patients had alveolar hemorrhage. After steroid therapy, the clinical condition improved in four patients, but two patients died. The autopsy findings in one of the deceased patients indicated the presence of recurrent alveolar hemorrhage, pulmonary venous hypertension, ILD, and PAH. Based on the clinical course of these CHD-PAH in patients and the literature, CHD-PAH can occur with pulmonary vascular obstructive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH), ILD, and/or alveolar hemorrhage. The severity of CHD-PAH may depend on a genetic disorder, respiratory infection, and upper airway stenosis. Additionally, pulmonary vasodilators may be involved in the development of PVOD/PCH and ILD. When patients with CHD-PAH show unexpected deterioration, clinicians should consider complications associated with PVOD/PCH and/or pulmonary disease. In addition, the choice of upfront combination therapy for pediatric patients with CHD-PAH should be selected carefully.

5-Aminolevulinic acid fermentation using engineered Saccharomyces cerevisiae.

BACKGROUND: 5'-Aminolevulinic acid (ALA) is widely used in the pharmaceutical industry, healthcare, and food production, and is a substrate for the biosynthesis of heme, which is required for respiration and photosynthesis. Enhancement of ALA biosynthesis has never been developed in Saccharomyces cerevisiae, which is a well-known model microorganism used for bioproduction of many value-added compounds. RESULTS: We demonstrated that metabolic engineering significantly improved ALA production in S. cerevisiae. First, we found that overexpression of HEM1, which encodes ALA synthetase, increased ALA production. Furthermore, addition of an optimal amount of glycine, a substrate for ALA biosynthesis, or levulinic acid, an inhibitor of ALA dehydrogenase, effectively increased ALA production. Next, we developed an assay for multiple metabolites including ALA and found that aconitase, encoded by ACO1 and ACO2, is the rate-limiting enzyme of ALA biosynthesis when sufficient glycine is supplied. Overexpression of ACO2 further enhanced ALA production in S. cerevisiae overexpressing HEM1. CONCLUSIONS: In this study, ALA production in S. cerevisiae was enhanced by metabolic engineering. This study also shows a strategy to identify the rate-limiting step of a target synthetic pathway by assay for multiple metabolites alongside the target product. This strategy can be applied to improve production of other valuable products in the well-studied and well-industrialized microorganism S. cerevisiae.

Contamination of the Shinano River water with mutagenic substances after the Niigata Chuetsu Earthquake.

While normally monitoring the Shinano River water quality, including examinations for mutagenicity, the Niigata Chuetsu Earthquake suddenly occurred on October 23, 2004. However, the influence of this earthquake on the mutagenicity of river water has not yet been well studied. To clarify the regional and seasonal changes in mutagenicity of the Shinano River water, blue rayon was suspended for 24 hrs at 4 sampling sites, once a month from September 2004 through August 2005. Mutagenicity was evaluated by the Ames test using Salmonella typhimurium TA98 (TA98) and TA100 with or without metabolic activation by S9 mixture. To detect and identify poly-aromatic hydrocarbons that may be responsible for the mutagenicity of the river water, we analyzed benzo[a]pyrene, benzophenone, 4-nitrotoluene, or other compounds using gas chromatography-mass spectrometry and total ion chromatogram spectra. Positive manifestations of TA98 with S9 mixture were observed at the 4 sampling sites throughout the 12-month test, showing a tendency to be higher at the downstream site and in winter. However, the highest mutagenicity was observed in the sample collected at the most upstream sampling site in December 2004, and fluoranthene or pyrene consisting mainly in coal tar was detected only in the samples collected in December 2004. Although benzo[a]pyrene, benzophenone, and 4-nitrotoluene were below the detection limits, non-mutagens such as aliphatic hydrocarbons or esters were frequently detected. Our findings indicate that either fluoranthene or pyrene was mainly responsible for the mutagenicity of the river water in December 2004, suggesting the possibility of oil contamination caused by the Niigata Chuetsu Earthquake.

Antibacterial effects of chitosan solution against Legionella pneumophila, Escherichia coli, and Staphylococcus aureus.

Chitosan has been shown to have antibacterial activities on the growth of a wide variety of bacteria. Chitosan solution has been sold commercially for use as an antibacterial agent. Chitosan solution contains not only chitosan but also organic acids as solvents and desalted Japan Sea Proper Water (dJSPW). We aimed to clarify whether chitosan solution has antibacterial activity against bacteria invading bath water, and then to explore the causative factor among these ingredients. The antibacterial activity of full-strength chitosan solution and of 10(2)- and 10(4)-fold chitosan solution diluted with purified water was studied against Legionella pneumophila serogroups 1 (L. pneumophila SG1) and 6 (L. pneumophila SG6), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus) for 7 days at 37 degrees C. To clarify the causative factor in the antibacterial activity against E. coli, the antibacterial activities of the full-strength and diluted chitosan solutions for 24 h were examined. L. pneumophila SG1 and SG6, and E. coli could not survive in the chitosan solution or in the 10(2)-fold dilute solution for over a day at 37 degrees C. The cells of S. aureus were found to have decreased more than 2.46 log cfu/ml after 1 day of incubation, not only in the chitosan solutions, but also in phosphate buffer solution as a control. No inhibitory effect of dJSPW on the growth of the bacteria was observed. The antibacterial activity of the chitosan solution was lower compared with those of the organic acids solutions, and it increased with decreasing pH value. We observed the antibacterial activity of chitosan solution against L. pneumophila SG1 and SG6, and E. coli, suggesting it may be due to the decreased pH value derived from organic acids rather than from chitosan itself or dJSPW.

Effects of Japan Sea Proper Water on the growth ofLegionella pneumophila, Escherichia coli, andStaphylococcus aureus.

OBJECTIVE: To assess whetherLegionella pneumophila serogroup 1 and serogroup 6,Escherichia coli, andStaphylococcus aureus can survive in Japan Sea Proper Water (JSPW). METHODS: The inhibitory effects of JSPW, surface seawater (SSW), phosphate buffer solution with 3.5% NaCl of pH 7.0 (3.5% NaCIPBS), and the 10(2)- and 10(4)-fold dilute solutions with purified water or phosphate buffer solution of pH 7.0, and purified water were investigated. Survival cells were counted immediately after the water and the bacteria were mixed, and at 1,3,5, and 7 days after incubation at 37°C. If the number of surviving cells was decreased more than 2 log units compared with the starting value, we judged the medium to have had an inhibitory effect on the growth of the bacteria. RESULTS: The survival cells of the bacteria in JSPW had decreased more than 2 log units compared with the starting value at 1 day after incubation. After 1 day of incubation, the cells ofLegionella pneumophila serogroup 6 andStaphylococcus aureus were found to have decreased more than 2 log units in purified water (PW) used as a control. Furthermore,Legionella pneumophila serogroup 1 in the 10(2)-fold dilute solution of JSPW was only 1.04 log units lower than the starting value at 7 days after incubation. In the 10(2)- and 10(4)-fold dilute solutions of JSPW,Escherichia coli survived for 7 days after incubation. These results were almost similar to the results in SSW and 3.5% NaCIPBS. CONCLUSIONS: The present findings demonstrate thatLegionella pneumophila serogroup 1 andEscherichia coli cannot survive in undiluted JSPW for over a day at 37°C, suggesting the inhibitory effects may be due to the sodium chloride contained in JSPW.

Effects of desalted deep seawater on hematologic and blood chemical values in mice.

Various processed foods and beverages have been manufactured using deep seawater (DSW), desalted DSW (dDSW), and concentrated DSW in Japan. To confirm the safety of dDSW, we investigated hematologic and blood chemical effects of dDSW in mice. The dDSW and desalted surface seawater (dSSW) were diluted to 6.7%, 10%, and 20% with purified water. BALB/c mice were housed for 12 weeks, and administered the diluted dDSW, dSSW, or purified water as a control during the period. The results for dDSW were compared with those for dSSW and purified water. None of the groups of mice showed any clear abnormal growth or behavior; neither did any show signs of illness nor a single case of death during the 12 weeks study. We found no significant differences between the dDSW and control groups in terms of red blood cell count, hemoglobin, hematocrit, white blood cell count, and neutrophil counts, whereas white blood cell and lymphocyte counts were significantly higher in the 10% dSSW group at the end of 4 and 12 weeks than those in the control group. A significantly higher triglyceride level was detected only in the 6.7% dSSW group. Our results show no evidence of acute or subacute effects of diluted dDSW. Effects of diluted dDSW on hematologic and blood chemical values in mice are thought to be similar to those of purified water. This finding suggests that dDSW is as safe as purified water for drinking water.