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Despite the worldwide trend of introducing of zero-fuel-based vehicles to the market, the emissions of air pollutants and greenhouse gases from passenger vehicles are likely to remain a concern for the coming 20 to 30 years. In this study, exhaust emissions of gasoline engines running after varying parking durations were measured using a chassis dynamometer. The experimental results showed that exhaust emissions of hydrocarbons, nitrogen oxides, and carbon monoxide from most vehicles increased dramatically following 60 to 120 min of parking, and were higher than cold-start (1040 + min parking) emissions, indicating the impact of parking duration on atmospheric pollutant emissions. The after-treatment capacity of the three-way catalytic converter was evaluated by chemical kinetic modeling of the chemical reactions on the catalyst coupled with a time-dependent energy conservation equation. The results of the model calculation indicated that both the initial temperature of the three-way catalytic converter and the inlet engine gas temperature are critical factors impacting exhaust pollutants after parking; therefore, proper management to reduce the emissions after middle-term parking durations should be developed to mitigate air pollution.

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The second largest epidemic of hand, foot, and mouth disease since 1982 occurred in 2017, which involved 6,173 cases in Osaka City, Japan. The main causative agent was coxsackievirus A6 (CV-A6). Phylogenetic analysis revealed that the detected CV-A6 strains belonged to genetic groups A3 and A4 in clade A.

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An efficient enantioselective synthesis of 3,3-disubstituted phthalides possessing a chiral quaternary carbon center was achieved via catalytic asymmetric bromolactonization that utilized BINOL-derived bifunctional sulfide catalysts. Transformations of the bromo group in optically active phthalide products were also performed to demonstrate the utility of this novel synthetic protocol.

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In this study, we conducted seven-day diurnal breathing loss (DBL) tests on gasoline vehicles. We propose a model based on the theory of thermodynamics that can represent the experimental results of the current and previous studies. The experiments were performed using 14 physical parameters to determine the dependence of total emissions on temperature, fuel tank fill, and fuel vapor pressure. In most cases, total emissions after an apparent breakthrough were proportional to the difference between minimum and maximum environmental temperatures during the day, fuel tank empty space, and fuel vapor pressure. Volatile organic compounds (VOCs) were measured using a Gas Chromatography Mass Spectrometer and Flame Ionization Detector (GC-MS/FID) to determine the Ozone Formation Potential (OFP) of after-breakthrough gas emitted to the atmosphere. Using the experimental results, we constructed a thermodynamic model for estimating the amount of evaporative emissions after a fully saturated canister breakthrough occurred, and a comparison between the thermodynamic model and previous models was made. Finally, the total annual evaporative emissions and OFP in Japan were determined and compared by each model.

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Various effective strategies have recently been described in the treatment of breast cancer, including endocrine therapy, chemotherapy, and molecular-targeted therapy, providing long-term survival benefits even after cancer recurrence. However, terminal-stage patients experience side effects and worse quality of life (QOL), in addition to deterioration of their general condition caused by the progression of the disease itself. When providing the best supportive care, use of anti-cancer drugs is not taboo and can represent a good option as long as physical, social, psychological, and spiritual supports are provided to both the patients and their families. Medroxyprogesterone acetate (MPA) is an endocrine therapeutic drug. In Japan, MPA is used only as a late-line endocrine therapy for breast cancer recurrence because many other endocrine therapy drugs are much more effective and MPA increases the risk of thrombosis and obesity. Here, we report 2 patients with breast cancer who reached terminal stage more than 10 years after the first diagnosis. MPA was administered as the final-line treatment. During that time, their appetite and QOL improved and the patients became more active than when they had been undergoing aggressive anticancer treatment. Both patients spent quality time with their families until their death. MPA may be a good option as part of palliative care of breast cancer patients in terminal stage.

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A photocatalytic synthesis of homoallyl ketones was achieved via a one-pot procedure starting from a Norrish Type I reaction of cyclopentanones, followed by a decatungstate-catalyzed hydroacylation of electron-deficient olefins by the resulting 4-pentenals. The site-selective formyl H-abstraction in the second step can be explained by radical polar effects in the transition state.

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ß- or γ-Site-selective C-H alkylation of aliphatic nitriles has been achieved using a decatungstate salt as the photocatalyst. The observed site selectivity was justified by a radical polar effect in transition states for hydrogen abstraction.

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Elevated amyloid-ß peptide (Aß) in brain contributes to Alzheimer's disease (AD) pathogenesis. We demonstrated the presence of exosome-associated Aß in the cerebrospinal fluid (CSF) of cynomolgus monkeys and APP transgenic mice. The levels of exosome-associated Aß notably decreased in the CSF of aging animals. We also determined that neuronal exosomes, but not glial exosomes, had abundant glycosphingolipids and could capture Aß. Infusion of neuronal exosomes into brains of APP transgenic mice decreased Aß and amyloid depositions, similarly to what reported previously on neuroblastoma-derived exosomes. These findings highlight the role of neuronal exosomes in Aß clearance, and suggest that their downregulation might relate to Aß accumulation and, ultimately, the development of AD pathology.

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BACKGROUND: We investigated the change in the urine albumin-to-creatinine ratio (ACR) to examine the effect of sitagliptin on diabetic nephropathy. METHODS: Sitagliptin at a dose of 50 mg was administered to 247 outpatients with type 2 diabetes. Data were collected on the patients' laboratory results (including the ACR), blood pressure, and body weight. Clinical data were compared before and after 3 months' administration of sitagliptin. RESULTS: The ACR changed from 150.0 ± 538.6 mg/gCre to 148.3 ± 764.6 mg/gCre over 3 months. In the patients with micro- and macro-albuminuria, the ACR after 3 months significantly decreased compared with the baseline (P = 0.04 and P = 0.02, respectively). The subjects whose ACR decreased experienced significantly larger decreases over the 3-month period in blood pressure and estimated glomerular filtration rate (eGFR) than the other subjects. There was no significant correlation between change in ACR (ΔACR) and change in hemoglobin A1c (ΔHbA1c) during 3 months (r = 0.04, P = 0.59), but there was a significant correlation between change in ΔACR and change in systolic blood pressure (r = 0.16, P = 0.03). Multiple regression analysis revealed that the significant predictors for ΔACR were change in systolic blood pressure (ß = 0.21, P = 0.016) and change in eGFR (ß = 0.20, P = 0.024) over 3 months (r = 0.35, P = 0.04). CONCLUSIONS: Sitagliptin reduces the ACR through decreasing both blood pressure and eGFR, with no correlation with a decrease in HbA1c over a 3-month period. These results may reflect the direct action of sitagliptin on the kidneys.

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Elevated levels of amyloid-ß peptide (Aß) in the human brain are linked to the pathogenesis of Alzheimer disease. Recent in vitro studies have demonstrated that extracellular Aß can bind to exosomes, which are cell-secreted nanovesicles with lipid membranes that are known to transport their cargos intercellularly. Such findings suggest that the exosomes are involved in Aß metabolism in brain. Here, we found that neuroblastoma-derived exosomes exogenously injected into mouse brains trapped Aß and with the associated Aß were internalized into brain-resident phagocyte microglia. Accordingly, continuous intracerebral administration of the exosomes into amyloid-ß precursor protein transgenic mice resulted in marked reductions in Aß levels, amyloid depositions, and Aß-mediated synaptotoxicity in the hippocampus. In addition, we determined that glycosphingolipids (GSLs), a group of membrane glycolipids, are highly abundant in the exosomes, and the enriched glycans of the GSLs are essential for Aß binding and assembly on the exosomes both in vitro and in vivo. Our data demonstrate that intracerebrally administered exosomes can act as potent scavengers for Aß by carrying it on the exosome surface GSLs and suggest a role of exosomes in Aß clearance in the central nervous system. Improving Aß clearance by exosome administration would provide a novel therapeutic intervention for Alzheimer disease.

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PURPOSE: The aim of this study is to assess whether the risk or types of suicide change in Fukushima in the aftermath of a series of disaster, including earthquake, tsunami and nuclear accident in March 2011. METHOD: The clinical records of all patients visited to the medical centre near the nuclear plant from 1 year before to 1 year after the disaster were reviewed (n = 981). Patients with non-fatal suicide attempt were divided into two categories depending on their method of suicide attempt. Standardised mortality ratios were calculated to adjust for changes in demographic profiles. RESULTS: The risk of non-fatal suicide attempts using high-mortality methods was significantly higher for 4 months, by three to four times after the series of disasters, and then decreased. There was no significant increase of non-fatal suicide attempts using low-mortality methods after the disaster. CONCLUSIONS: After such a disaster, immediate psychiatric support may be required because of the increased risk of non-fatal suicide attempts in the immediate aftermath.

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Peripheral neuropathy is a common side effect of the chemotherapeutic agent oxaliplatin (Oxp), and is associated with hypersensitivity to cold sensation in the acute stage. Recently, gosha-jinki-gan (GJG), a Japanese herbal medicine, was reported to improve Oxp-induced cold hypersensitivity. However, the mechanism for this effect was not elucidated. We hypothesized that the effect of GJG on Oxp-induced cold hypersensitivity may be associated with the expression of the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) channels, which are cold-gated ion channels. To assess this hypothesis, we examined alteration of the withdrawal response to cold stimulation following coadministration of GJG and Oxp in rats, and the relationship between this altered withdrawal response and the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG). Assessment of cold hypersensitivity was performed at 4 and 10°C using a cold plate. Compared with Oxp administration alone, coadministration of GJG (oral dose: 1 g/kg/day for 12 days) and Oxp (intraperitoneal dose: 4 mg/kg twice a week) significantly reduced the withdrawal response to cold stimulation. On the 12th day of drug administration, the L4-L6 DRG were removed and the expression of TRPM8 and TRPA1 mRNA was determined using RT-PCR. The expression of TRPM8 and TRPA1 in the DRG of rats that were coadministered GJG and Oxp decreased significantly compared with that in the rats administered Oxp alone. These results suggest that coadministration of GJG may improve Oxp-induced cold hypersensitivity by suppressing the overexpression of TRPM8 and TRPA1 mRNA.

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BACKGROUND: The genus Chromobacterium consists of 7 recognized species. Among those, only C. violaceum, commonly found in the soil and water of tropical and subtropical regions, has been shown to cause human infection. Although human infection is rare, C. violaceum can cause life-threatening sepsis, with metastatic abscesses, most frequently infecting those who are young and healthy. CASE PRESENTATION: We recently identified a case of severe bacteremia caused by Chromobacterium haemolyticum infection in a healthy young patient following trauma and exposure to river water, in Japan. The patient developed necrotizing fasciitis that was successfully treated with a fasciotomy and intravenous ciprofloxacin and gentamicin. CONCLUSIONS: C. haemolyticum should be considered in the differential diagnosis of skin lesions that progressively worsen after trauma involving exposure to river or lake water, even in temperate regions. Second, early blood cultures for the isolation and identification of the causative organism were important for initiating proper antimicrobial therapy.

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INTRODUCTION: Many studies suggest that elevated triglyceride levels are associated with increased long-term risk of stroke, including transient ischemic attacks. In addition, elevated triglyceride levels independently contribute to plasma viscosity and decreased blood flow. However, no consensus has been reached regarding the significance of hypertriglyceridemia as an independent risk factor for ischemic stroke. CASE PRESENTATION: We report the case of a patient admitted to our hospital for sudden onset of coma. Laboratory test results revealed he had high blood glucose (28.2mmol/L), high glycated hemoglobin (11.4 percent), considerably high serum triglyceride levels (171.5mmol/L; type V hyperlipoproteinemia), and high plasma viscosity (1.90mPa/s) with normal ß-hydroxybutyric acid levels. His triglyceride levels decreased after administering intravenous fluids. Our patient's consciousness level improved gradually over three days. All serum lipid levels decreased seven days after admission. CONCLUSIONS: The findings in our patient's case are likely explained by triglyceride-mediated hyperviscosity causing a transient ischemic attack. In the present report we suggest that when several tests do not reveal the cause of stroke-like symptoms, measurement of plasma viscosity may be informative.

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HS (heparan sulfate) is synthesized by HS co-polymerases encoded by the EXT1 and EXT2 genes (exostosin 1 and 2), which are known as causative genes for hereditary multiple exostoses, a dominantly inherited genetic disorder characterized by multiple cartilaginous tumours. It has been thought that the hetero-oligomeric EXT1-EXT2 complex is the biologically relevant form of the polymerase and that targeted deletion of either EXT1 or EXT2 leads to a complete lack of HS synthesis. In the present paper we show, unexpectedly, that two distinct cell lines defective in EXT1 expression indeed produce small but significant amounts of HS chains. The HS chains produced without the aid of EXT1 were shorter than HS chains formed in concert with EXT1 and EXT2. In addition, biosynthesis of HS in EXT1-defective cells was notably blocked by knockdown of either EXT2 or EXTL2 (EXT-like), but not of EXTL3. Then, to examine the roles of EXTL2 in the biosynthesis of HS in EXT1-deficient cells, we focused on the GlcNAc (N-aetylglucosamine) transferase activity of EXTL2, which is involved in the initiation of HS chains by transferring the first GlcNAc to the linkage region. Although EXT2 alone synthesized no heparan polymers on the synthetic linkage region analogue GlcUAbeta1-3Galbeta1-O-C2H4NH-benzyloxycarbonyl, marked polymerization by EXT2 alone was demonstrated on GlcNAcalpha1-4GlcUAbeta1-3Galbeta1-O-C2H4N-benzyloxycarbonyl (where GlcUA is glucuronic acid and Gal is galactose), which was generated by transferring a GlcNAc residue using recombinant EXTL2 on to GlcUAbeta1-3Galbeta1-O-C2H4NH-benzyloxycarbonyl. These findings indicate that the transfer of the first GlcNAc residue to the linkage region by EXTL2 is critically required for the biosynthesis of HS in cells deficient in EXT1.

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We have revealed that in Caenorhabditis elegans, non-sulfated chondroitin is required for normal cell division and cytokinesis at an early developmental stage, whereas heparan sulfate is essential for embryonic morphogenesis in the later stages of development. To clarify the roles of chondroitin sulfate and heparan sulfate in early embryogenesis in mammals, we generated glucuronyltransferase-I (GlcAT-I) knock-out mice by gene targeting. GlcAT-I is an enzyme required for the synthesis of both chondroitin sulfate and heparan sulfate. Here we report that mice with a deletion of GlcAT-I showed remarkable reduction of the synthesis of chondroitin sulfate and heparan sulfate and embryonic lethality before the 8-cell stage because of failed cytokinesis. In addition, treatment of wild-type 2-cell embryos with chondroitinase ABC had marked effects on cell division, although many heparitinase-treated embryos normally developed to blastocysts. Taken together, these results suggest that chondroitin sulfate in mammals, as with non-sulfated chondroitin in C. elegans, is indispensable for embryonic cell division.

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The synthesis of phytochelatins (PCs) in a marine alga, Dunalliela tertiolecta, is strongly induced by Zn. Pretreatment of the cells with Zn enhances the tolerance toward toxic heavy metals such as Cd, Hg, Cu, Pb, and arsenate. Moreover, the pretreatment also increases the tolerance toward oxidative stress caused by hydrogen peroxide or paraquat. In vitro analysis shows that PC is a stronger scavenger of hydrogen peroxide and superoxide radical than glutathione. These results suggest that PCs inducibly synthesized by Zn treatment could play a role not only in detoxification of heavy metals but also in mitigation of oxidative stress.

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