Pinellic Acid Isolated from Quercetin-rich Onions has a Peroxisome Proliferator-Activated Receptor-Alpha/Gamma (PPAR-α/γ) Transactivation Activity.

Quercetin, a flavonol, is a functional compound that is abundant in onions and is known to have antioxidant and anti-inflammatory effects. Quercetin and its glucoside are known to function as peroxisome proliferator-activated receptor (PPAR) ligands and showed high PPAR-α transactivation activity but little PPAR-γ transactivation activity in some reports. In this study, we demonstrated that an aqueous extract of a quercetin-rich onion cultivar increased transactivation activities not only of PPAR-α but also of PPAR-γ. We isolated (9S,12S,13S)-(10E)-9,12,13-trihydroxyoctadec-10-enoic acid (pinellic acid) obtained from the aqueous extract using PPAR-γ transactivation as an index. Furthermore, it was revealed that pinellic acid could transactivate PPAR-α. Our findings are the first report mentioned showing that trihydroxyoctadec-10-enoic acids showed PPAR-α/γ transactivation activities.

Seasonal Fluctuations of Aroma Components of Essential Oils from Larix leptolepis.

Conifer resins are used as chemical raw materials for daily necessities. There have been many reports on the aroma components of turpentine oil from rosin, but there has been no reports on fluctuations in the aroma components through spring to late autumn. We speculated that the aroma components in the essential oils of deciduous coniferous larches might fluctuate during maturation of the foliage. In this study, we focused on the aroma components of larch essential oils and we clarified by multivariate analysis how the aroma components fluctuate during leaf maturation. The results of analysis showed that there was a drastic seasonal fluctuation of the chemical components in larch essential oils, especially in senescent leaves in late autumn. Cryptone and linalool were identified as the characteristic aroma components in essential oil from senescent larch leaves.

A Epidemiological Investigation of a Nosocomial Outbreak of Multidrug-Resistant Acinetobacter baumannii in a Critical Care Center in Japan, 2011-2012.

Volume 69, no. 2, p. 143-148, 2016. Page 143, Title should appear as shown below.An Epidemiological Investigation of a Nosocomial Outbreak of Multidrug-Resistant Acinetobacter baumannii in a Critical Care Center in Japan, 2011-2012.

A Epidemiological Investigation of a Nosocomial Outbreak of Multidrug-Resistant Acinetobacter baumannii in a Critical Care Center in Japan, 2011-2012.

In 2011, a multidrug-resistant Acinetobacter baumannii (MDRAB) outbreak occurred at a Japanese critical care center (CCC) in a tertiary care hospital. Multidrug-resistance in Japan is defined as resistance to the antimicrobials amikacin, carbapenem, and fluoroquinolone. We conducted a retrospective epidemiological investigation of this outbreak to identify the risk factors for MDRAB respiratory tract acquisition in this hospital. Cases were defined as hospitalized patients with MDRAB-positive cultures at least 3 days post admission to the CCC between June 1, 2011 and April 20, 2012. Fifteen MDRAB cases were identified, including 3 with infection and 12 with colonization. This case-control study demonstrated that hypoalbuminemia along with carbapenem administration were associated with MDRAB respiratory tract acquisition. Pulsed-field gel electrophoresis analysis and multilocus sequence typing using MDRAB isolates suggested a clonal dissemination of MDRAB strains with sequence type 74 occurred primarily among patients admitted to the CCC. From April 16, 2012, a decreased isolation rate of MDRAB in the hospital occurred after the implementation of the following infection control measures: closing the emergency room, discontinuing admission to the CCC, isolating patients with MDRAB colonization or infection to single room status, and conducting environmental cleaning. No MDRAB cases were detected between March 23 and April 20, 2012.

Utility of the triglyceride level for predicting incident diabetes mellitus according to the fasting status and body mass index category: the Ibaraki Prefectural Health Study.

AIM: The levels of lipids, especially triglycerides (TG), and obesity are associated with diabetes mellitus (DM). Although typically measured in fasting individuals, non-fasting lipid measurements play an important role in predicting future DM. This study compared the predictive efficacy of lipid variables according to the fasting status and body mass index (BMI) category. METHODS: Data were collected for 39,196 nondiabetic men and 87,980 nondiabetic women 40-79years of age who underwent health checkups in Ibaraki-Prefecture, Japan in 1993 and were followed through 2007. The hazard ratios (HRs) for DM in relation to sex, the fasting status and BMI were estimated using a Cox proportional hazards model. RESULTS: A total of 8,867 participants, 4,012 men and 4,855 women, developed DM during a mean follow-up of 5.5 years. TG was found to be an independent predictor of incident DM in both fasting and non-fasting men and non-fasting women. The multivariable-adjusted HR for DM according to the TG quartile (Q) 4 vs. Q1 was 1.18 (95% confidence interval (CI): 1.05, 1.34) in the non-fasting men with a normal BMI (18.5-24.9). This trend was also observed in the non-fasting women with a normal BMI. That is, the multivariable-adjusted HRs for DM for TG Q2, Q3 and Q4 compared with Q1 were 1.07 (95% CI: 0.94, 1.23), 1.17 (95%CI: 1.03, 1.34) and 1.48 (95%CI: 1.30, 1.69), respectively. CONCLUSIONS: The fasting and non-fasting TG levels in men and non-fasting TG levels in women are predictive of future DM among those with a normal BMI. Clinicians must pay attention to those individuals at high risk for DM.

Associations between metabolic syndrome and mortality from cardiovascular disease in Japanese general population, findings on overweight and non-overweight individuals. Ibaraki Prefectural Health Study.

BACKGROUND: The impact of being overweight, as a component of the metabolic syndrome (MetS), for cardiovascular disease (CVD) mortality was investigated and compared with the predictive value of MetS by 2 different definitions. METHODS AND RESULTS: A 12-year prospective study of 30,774 Japanese men and 60,383 women aged 40-79 years was conducted. The multivariate hazard ratio (HR; 95% confidence interval) of total CVD mortality for overweight subjects with >or=2 additional risk factors with reference to subjects with 0 of 4 MetS components was 1.83 (1.41-2.38) for men and 1.90 (1.45-2.49) for women, and for non-overweight subjects with >or=2 additional risk factors 1.75 (1.38-2.24) and 1.97 (1.52-2.55), respectively. The proportion of excess CVD deaths in the latter group was 1.5-fold higher than that in the former group. Multivariate HRs of coronary heart disease and total CVD mortality for MetS by the modified criteria of the American Heart Association/National Heart, Lung, and Blood Institute were 1.62 (1.31-2.00) and 1.23 (1.09-1.39), respectively, for men and 1.32 (1.05-1.65) and 1.12 (1.00-1.25), respectively, for women. The respective HRs for MetS by the International Diabetic Federation definition did not reach statistical significance, except for coronary heart disease in men. CONCLUSIONS: Non-overweight individuals with metabolic risk factors, as well as overweight individuals with such factors, should be targeted to reduce the CVD burden in the general population.

Low-density lipoprotein cholesterol concentrations and death due to intraparenchymal hemorrhage: the Ibaraki Prefectural Health Study.

BACKGROUND: Few studies have examined the association between low levels of low-density lipoprotein (LDL) cholesterol and risk of intraparenchymal hemorrhage. METHODS AND RESULTS: A total of 30 802 men and 60 417 women, 40 to 79 years of age with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance was performed through 2003, and 264 intraparenchymal hemorrhage deaths were identified. LDL cholesterol levels were calculated with the Friedewald formula. Persons with LDL cholesterol > or =140 mg/dL had half the sex- and age-adjusted risk of death due to intraparenchymal hemorrhage of those with LDL cholesterol <80 mg/dL. After adjustment for cardiovascular risk factors, the multivariable hazard ratio compared with persons with LDL cholesterol <80 mg/dL was 0.65 (95% CI 0.44 to 0.96) for those with LDL cholesterol 80 to 99 mg/dL, 0.48 (0.32 to 0.71) for 100 to 119 mg/dL, 0.50 (0.33 to 0.75) for 120 to 139 mg/dL, and 0.45 (0.30 to 0.69) for >/=140 mg/dL. These inverse associations were not altered substantially after the exclusion of persons with hypertriglyceridemia, after analysis with a Cox proportional hazard model with time-dependent covariates, or in sensitivity analysis for the potential effect of competing risks. CONCLUSIONS: Low LDL cholesterol levels are associated with elevated risk of death due to intraparenchymal hemorrhage.

Human H5N2 avian influenza infection in Japan and the factors associated with high H5N2-neutralizing antibody titer.

BACKGROUND: H5N2 avian influenza virus infection of humans has not been reported thus far. The first H5N2 avian influenza infection of poultry in Japan occurred in Ibaraki. METHODS: The subjects were workers at 35 chicken farms in Ibaraki Prefecture, where the H5N2 virus or antibody was isolated from chickens. None of the subjects exhibited influenza symptoms. The H5N2-neutralizing antibody titers of the first and second paired sera samples were compared. To investigate the possible factors for this increase, the H5N2-neutralizing antibody titer (1:40 or more) was calculated for the second samples. A logistic regression analysis was performed to examine the association of these factors with H5N2-neutralizing antibody positivity. RESULTS: We performed Wilcoxon matched-pairs signed-ranked test on data collected from 257 subjects, and determined that the H5N2 antibody titers of the second paired sera samples were significantly higher than those of the first samples (P < 0.001). The H5N2 antibody titers of paired sera of 13 subjects without a history of seasonal influenza vaccination within the previous 12 months increased 4-fold or more. The percentage of antibody positivity was 32% for subjects with a history of seasonal influenza vaccination (28% of all subjects) and 13% for those without a history of the same. The adjusted odds ratio of H5N2-neutralizing antibody positivity was 4.6 (95% confidence interval: 1.6-13.7) for those aged over 40 and 3.1 (95% confidence interval: 1.6-6.1) for those with a history of seasonal influenza vaccination within the previous 12 months. CONCLUSION: The results suggest that this may have been the first avian influenza H5N2 infection of poultry to affect humans. A history of seasonal influenza vaccination might be associated with H5N2-neutralizing antibody positivity.

Comparison between computed tomography (CT) and autopsy findings in cases of abdominal injury and disease.

We report 10 autopsy cases involving fatal pathological changes in abdominal organs, for which findings of computed tomography (CT) on admission or after death were compared with autopsy findings. Two of the cases were death due to natural causes and eight were death due to traffic accidents. From the findings at autopsy, the causes of death were considered to be rupture of an aortic aneurysm in one case, gastrointestinal bleeding due to gastric cancer in one case, retroperitoneal bleeding in two cases, laceration of the liver in three cases, and traumatic rupture of the small intestine in three cases. CT findings revealed ascites or retroperitoneal bleeding in eight cases. However, in the cases of small-intestinal rupture, CT findings on admission revealed no free air. Therefore, ascites on CT should be regarded as a useful indicator of blunt abdominal trauma. Hepatic portal venous gas, known to be a post-mortem change, was significantly evident on post-mortem CT in cases of traumatic liver or intestinal injury, and was also seen in cases where the period between the accident and CT examination was long.

Metabolism and hepatic toxicity of flutamide in cytochrome P450 1A2 knockout SV129 mice.

BACKGROUND: Flutamide, a nonsteroidal antiandrogen used for treatment of prostate cancer, causes a temporary increase in transaminase and in some cases severe liver dysfunction. It is dominantly metabolized by cytochrome P450 (CYP) 1A2 into 2-hydroxyflutamide (OH-flutamide), which has stronger antiandrogenic activity without obvious cytotoxicity to cultured hepatocytes. We hypothesized that another subsidiary metabolite might be responsible for induction of hepatotoxicity. METHODS: Flutamide was administered daily to CYP1A2 knockout mice and parental SV129 mice to compare pharmacokinetics and appearance of hepatic toxicity. RESULTS: In the CYP1A2 knockout mice, the plasma concentration of flutamide maintained at a high level and OH-flutamide stayed low; a higher amount of FLU-1, an alternative metabolite of flutamide, was detected in urine. Simple repetitive administration of 800 mg/kg of flutamide for 28 days to CYP1A2 knockout mice did not show abnormal elevation of plasma alanine aminotransferase (ALT). However, after the knockout mice were fed with an amino acid-deficient diet for 2 weeks, which reduced the glutathione (GSH) content to 27% of the initial, administration of 400 mg/kg of flutamide increased ALT to over 200 IU/l and histopathologically moderate hepatitis developed. Since FLU-1 itself did not show cytotoxicity or reduce GSH content in vitro, a further metabolized molecule must cause the hepatotoxicity. CONCLUSIONS: Blockade of CYP1A2 produced an unknown potential hepatotoxic molecule through FLU-1, and GSH might play an important role in diminishing the reactive hepatotoxic metabolite.

Diphenylarsinic acid poisoning from chemical weapons in Kamisu, Japan.

We noted a new clinical syndrome with prominent cerebellar symptoms in apartment building residents in Kamisu, Japan. The well that provided drinking water contained diphenylarsinic acid, a degradation product of diphenylcyanoarsine or diphenylchloroarsine, which were developed for use as chemical weapons, inducing severe vomiting and sneezing. Characteristics of diphenylarsinic acid poisoning include brainstem-cerebellar and cerebral symptoms. Mental retardation associated with brain atrophy in magnetic resonance images was evident in some infants. We must be vigilant to prevent or minimize the effects of further diphenylarsinic acid poisoning in Japan or elsewhere.

Hepatic portal venous gas and hyper-dense aortic wall as postmortem computed tomography finding.

Postmortem computed tomography (PMCT) is useful for diagnosis of cause of death not only by emergency physicians but also medical examiners or police surgeons conducting postmortem studies. However, postmortem biological conditions are quite different from those in the living body. Hepatic portal venous gas (HPVG) and a hyperdense aortic wall (HDAW) are often found by PMCT, although no significant autopsy findings are evident in the liver or aorta. In this study we compared the findings of PMCT with those obtained at autopsy, and discussed the cause of these PMCT features. PMCT was conducted in 12 autopsy cases, comprising eight cases of natural death and four of unnatural death. HPVG was seen in five cases and HDAW in seven. In the cases showing HPVG, visceral abdominal injury, bowel distention or acute circulatory dysfunction was found at autopsy. In the cases showing HDAW, atherosclerosis or an increase in blood viscosity due to dehydration or postmortem changes was evident. Although the precise causes of these PMCT findings are not completely clear, the changes evident at autopsy provide some clues.

Right ventricular damage due to pulmonary embolism: examination of the number of infiltrating macrophages.

To investigate the pathological changes in the heart induced by pulmonary embolism, 20 autopsy cases of pulmonary embolism and 10 control cases of acute death from traumatic injury were examined. Adding to the routine hematoxylin-eosin (HE) staining, immunostaining with CD68 pan-macrophage marker was performed on the specimens obtained from both right and left ventricular walls. The number of macrophages was counted semi-quantitatively in 100 random high-power fields (HPF). Although typical pathological findings of myocardial infarction was not observed in any of the cases, 16 of the 20 pulmonary embolism cases showed an increase in the number of macrophages, mainly in the right ventricular wall. Four cases showed massive macrophage infiltration in the entire right ventricular wall. It is speculated that ischemia due to pulmonary embolism may be connected to its pathogenesis.

Effect of algal extract on H2 production by a photosynthetic bacterium Rhodobium marinum A-501: analysis of stimulating effect using a kinetic model.

We have established a system for hydrogen (H2) production from algal starch via lactic acid using a mixed culture of a lactic acid bacterium, Lactobacillus amylovorus, and a photosynthetic bacterium, Rhodobium marinum A-501. We found that the H2 production from lactate was stimulated in the presence of algal extract, which was obtained from algal biomass homogenate used as a substrate in the system by removing settleable solids including starch. To analyze the stimulating effect of algal extract on H2 production, we developed a kinetic model for H2 production by R. marinum A-501. The model revealed that approximately 20% of lactate was consumed for cell mass production, and the remaining portion was a source of reducing power to drive hydrogen production or other cellular processes. In the presence of algal extract, the model indicated that the conversion efficiency from lactate to the reducing power increased from 0.56 to 0.80 and nitrogenase activity increased up to twofold, resulting in the increase in yield of hydrogen from lactate from 29% to 48%. These results suggest that algal extract can attenuate the limitation process in lactate catabolism by which the supplementation of reducing power to drive H2 production was suppressed.

Highly Selective Thioselenation of Vinylcyclopropanes with a (PhS)(2)-(PhSe)(2) Binary System and Its Application to Thiotelluration.

A novel, highly selective method for introducing organic sulfur, selenium, and tellurium functions into vinylic cyclopropanes has been developed on the basis of the relative reactivities of organic dichalcogenides and chalcogen-centered radicals. Upon irradiation with the light of wavelength over 300 nm, the reaction of vinylcyclopropanes with diphenyl disulfide and diphenyl diselenide proceeds smoothly to provide the corresponding gamma-(selenoethyl)allylic sulfides regioselectively in good yields. Similarly, vinylcyclopropanes undergo regioselective thiotelluration by use of a novel (PhS)(2)-(PhTe)(2) binary system, affording the corresponding ring-opened thiotelluration product in good yields. Furthermore, the scope and limitations of this (PhS)(2)-(PhTe)(2) binary system are discussed.

Highly Selective Three-Component Coupling of Ethyl Propiolate, Alkenes, and Diphenyl Diselenide under Visible-Light Irradiation.

Just the right strength of carbon-radical trapping by diphenyl diselenide facilitates its selective three-component coupling with an electron-poor alkyne and an electron-rich alkene [Eq. (1)]. In contrast, (PhS)2 is too weak and (PhTe)2 too strong a radical trap, and polymerization of the unsaturated compounds and addition of (PhTe)2 to the alkyne occur, respectively.