The purpose of this study is to compare therapeutic effects of furosemide, a short-acting loop diuretic, and azosemide, a long-acting one, in patients with heart failure, and to test our hypothesis that long-acting diuretics are superior to short-acting types in heart failure.

开始日期2006-06-01

申办/合作机构

Hyogo University of

100 项与阿佐赛米相关的临床结果

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100 项与阿佐赛米相关的转化医学

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100 项与阿佐赛米相关的专利（医药）

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145

项与阿佐赛米相关的文献（医药）

2024-12-01·GLIA

Endothelin‐1 increases Na⁺‐K⁺‐2Cl⁻ cotransporter‐1 expression in cultured astrocytes and in traumatic brain injury model: An involvement of HIF1α activation

Article

作者: Koyama, Yutaka ; Izumi, Yasuhiko ; Fukui, Yura ; Hosogi, Nami ; Fujimoto, Rina ; Hishinuma, Shigeru ; Michinaga, Shotaro ; Hamada, Yasuhiro ; Takahashi, Kenta ; Ogawa, Yasuhiro

Abstract:

Na+‐K+‐2Cl− cotransporter‐1 (NKCC1) is present in brain cells, including astrocytes. The expression of astrocytic NKCC1 increases in the acute phase of traumatic brain injury (TBI), which induces brain edema. Endothelin‐1 (ET‐1) is a factor that induces brain edema and regulates the expression of several pathology‐related genes in astrocytes. In the present study, we investigated the effect of ET‐1 on NKCC1 expression in astrocytes. ET‐1 (100 nM)‐treated cultured astrocytes showed increased NKCC1 mRNA and protein levels. The effect of ET‐1 on NKCC1 expression in cultured astrocytes was reduced by BQ788 (1 μM), an ETB antagonist, but not by FR139317 (1 μM), an ETA antagonist. The involvement of ET‐1 in NKCC1 expression in TBI was examined using a fluid percussion injury (FPI) mouse model that replicates the pathology of TBI with high reproducibility. Administration of BQ788 (15 nmol/day) decreased FPI‐induced expressions of NKCC1 mRNA and protein, accompanied with a reduction of astrocytic activation. FPI‐induced brain edema was attenuated by BQ788 and NKCC1 inhibitors (azosemide and bumetanide). ET‐1‐treated cultured astrocytes showed increased mRNA and protein expression of hypoxia‐inducible factor‐1α (HIF1α). Immunohistochemical observations of mouse cerebrum after FPI showed co‐localization of HIF1α with GFAP‐positive astrocytes. Increased HIF1α expression in the TBI model was reversed by BQ788. FM19G11 (an HIF inhibitor, 1 μM) and HIF1α siRNA suppressed ET‐induced increase in NKCC1 expression in cultured astrocytes. These results indicate that ET‐1 increases NKCC1 expression in astrocytes through the activation of HIF1α.

2024-05-01·Environmental pollution (Barking, Essex : 1987)

Leaching of unexpected cyazofamid degradation products into groundwater demonstrates gaps in current pesticide risk assessment

Article

作者: Bollmann, Ulla E ; Haarder, Eline B ; Albers, Christian N ; Badawi, Nora ; Karan, Sachin ; Kørup, Kirsten

To investigate the formation and leaching potential of degradation products N,N-dimethylsulfamide (DMS) and dimethylsulfamic acid (DMSA) from cyazofamid under real-world agricultural conditions, the fungicide cyazofamid was applied in a potato crop as part of the Danish Pesticide Leaching Assessment Programme (PLAP). Leaching of DMS, DMSA, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile (CCIM), and 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carboxylicacid (CTCA) was monitored in water from the variably saturated zone (suction cups) and groundwater for more than two years following the applications. In total, 424 samples were analyzed for the content of the four degradation products. An additional laboratory study was executed in parallel with the field monitoring study. Here, cyazofamid was applied to soil columns and leaching of the four degradation products was studied under controlled conditions. In the EFSA conclusion on cyazofamid, CCIM and CTCA are mentioned as major relevant metabolites; DMS is not mentioned in the risk assessment and DMSA is only included in acute oral toxicity studies and an in vitro bacterial mutation assay. In contrast to the EFSA conclusion on cyazofamid, our studies showed no leaching of the two major metabolites, CTCA and CCIM, but instead, major leaching of DMS and DMSA in both the field and laboratory studies was observed. That is, both DMS and DMSA leached to the groundwater in concentrations >0.1 μg/L for more than half a year. Based on this, we suggest improvements to the current pesticide risk assessment.

2023-08-15·Bioorganic & medicinal chemistry letters

Synthesis and biological evaluation of 2-(Tetrazol-5-yl)sulfonylacetamides as inhibitors of Mycobacterium tuberculosis and Mycobacterium marinum.

Article

作者: Gao, Yamin ; Ozga, Théo ; Tu, Zhengchao ; Henches, Robin ; Zhang, Tianyu ; Francis, Craig L

A series of 2-(tetrazol-5-yl)sulfonylacetamide derivatives were synthesized and evaluated for their in vitro inhibitory activity against Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm). The most active compounds exhibited in vitro MIC₉₀ values of 1.25 μg/mL against Mtb, but they were less effective against Mm (MIC₉₀ ≥ 10 μg/mL). Despite the most active compounds having favourable physicochemical properties and one of them having a half-life of ∼3 h when incubated with mouse liver microsomes, two representative highly active compounds showed strong chemical reactivity to cysteine derivatives, as surrogate in vivo sulfur-centred nucleophiles, indicating excessive electrophilicity, and therefore, likely indiscriminate chemical reactivity in vivo, representing an unacceptably high risk of general toxicity, and low likelihood of being therapeutically effective.

100 项与阿佐赛米相关的药物交易

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