京都府舞鶴湾の鉛を中心とした重金属汚染実態調査4ー2009年度調査結果と総括ー

Lead concentrations were determined in sediment, blue mussel (Mytilus galloprovincialis), seafood, selttling particles, atmospheric deposition, collected from Maizuru Bay, a semi-enclosed marine inlet of the Japan Sea in 2009, in order to elucidate lead contamination levels and distribution. Higher lead concentrations in sediment (824-4, 592ug/g dry) were detected in samples at 200m far from the pollution source. The highest lead concentration in settling particles (1,347ug/g dry) was detected in samples at 60m far from the pollution source. Lead concentrations in blue mussels transplanted from mon-polluted area to polluted area were increased definitely in 2 weeks,lead was not detected in the edible parts of 18 fishes and 2 shellfishes collected in Maizuru Bay. Extremely high lead pollution was kept in about 100m area from the pollution source. Reserch results from 2007-2009 on the lead pollution in Maizuru Bay were summarized

Surface Functionalization of Polypropylene Nonwoven Fabric for Introducing Repeatable Controlled Drug Release Property

We developed polypropylene nonwoven fabrics (PP NWFs) with controlled drug release property via surface modification using the photo-activated chlorine dioxide radical (ClO2•) oxidation method, followed by β-cyclodextrin (CD) loading. PP materials are challenging to functionalize for allowing the immobilization of drugs, owing to their low reactivity and surface energy. Our β-CD/PP NWFs composite showed sustained drug release behavior over 12 h in phosphate buffer, indicating that β-CDs supported on PP fibers functioned successfully. Our functionalization method is desirable for drug delivery in medicinal chemistry

Immobilization of β-cyclodextrin onto polypropylene nonwoven fabric based on photooxidative surface modification

Yamamoto, K., Asahara, H., Moriguchi, M. et al. Immobilization of β-cyclodextrin onto polypropylene nonwoven fabric based on photooxidative surface modification. Polym J (2023). https://doi.org/10.1038/s41428-022-00751-8We developed β-cyclodextrin (CD)/polypropylene (PP) composite nonwoven fabrics (NWFs) via surface modification of PP using the photoactivated chlorine dioxide radical (ClO2•) oxidation method. The hydrophilicity and dyeability of the PP NWFs were improved owing to the immobilization of β-CD. In addition, the prepared β-CD/PP composite NWFs showed sustained drug release for over 12 h in phosphate buffer, indicating that the β-CD supported on PP fibers functioned successfully

Visible-Light-Induced Phosgenation Reaction of Amines by Oxygenation of Chloroform Using Chlorine Dioxide

Carbamoyl chloride supports modern society as a building block for pharmaceuticals, agrochemicals, and polymers. Although carbamoyl chlorides are generally synthesized via the reaction of amines with phosgene (COCl2), these applications of COCl2 have recently been avoided because of its high toxicity. Herein, we report the visible-light-induced in-situ preparation of COCl2 through the oxygenation of chloroform in the presence of chlorine dioxide, which leads to the safe constructions of carbamoyl chlorides with good-to-high yields and wide substrate scopes. In addition, this method can also be applied to the synthesis of various carbonates that are the starting materials for resins such as polycarbonates and polyurethanes

Mild Organic Base-Catalyzed Primary Alcohol-Selective Aroylation Reaction Using N-Aroylcarbazoles for Underexplored Prodrugs

We report a highly primary alcohol-selective aroylation reaction using N-aroylcarbazoles (NAroCs). The aroylationproceeded smoothly in the presence of DBU, which most likely works as a general base catalyst in the reaction system. The synthetic utility was displayed in the primary alcohol-selective aroylation of complex drug molecules and natural products to their prodrugs. Stoichiometrically generated carbazole, the starting material of NAroCs could be easily recovered. We also established safer multigram and multidecagram scale preparation methods of NAroCs, which are easy-to-handle bench-stable reagents.</div

A human PET study of [11C]HMS011, a potential radioligand for AMPA receptors

Abstract Background α-Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor is a primary mediator of fast glutamatergic excitatory signaling in the brain and has been implicated in diverse neuropsychiatric diseases. We recently developed a novel positron emission tomography (PET) ligand, 2-(1-(3-([11C]methylamino)phenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl) benzonitrile ([11C]HMS011). This compound is a radiolabelled derivative of perampanel, an antiepileptic drug acting on AMPA receptors, and was demonstrated to have promising in vivo properties in the rat and monkey brains. In the current study, we performed a human PET study using [11C]HMS011 to evaluate its safety and kinetics. Four healthy male subjects underwent a 120-min PET scan after injection of [11C]HMS011. Arterial blood sampling and metabolite analysis were performed to obtain parent input functions for three of the subjects using high-performance liquid chromatography. Regional distribution volumes (V Ts) were calculated based on kinetic models with and without considering radiometabolite in the brain. The binding was also quantified using a reference tissue model with white matter as reference. Results Brain uptake of [11C]HMS011 was observed quickly after the injection, followed by a rapid clearance. Three hydrophilic and one lipophilic radiometabolites appeared in the plasma, with notable individual variability. The kinetics in the brain with apparent radioactivity retention suggested that the lipophilic radiometabolite could enter the brain. A dual-input graphical model, an analytical model designed in consideration of a radiometabolite entering the brain, well described the kinetics of [11C]HMS011. A reference tissue model showed small radioligand binding potential (BP*ND) values in the cortical regions (BP*ND = 0–0.15). These data suggested specific binding component of [11C]HMS011 in the brain. Conclusions Kinetic analyses support some specific binding of [11C]HMS011 in the human cortex. However, this ligand may not be suitable for practical AMPA receptor PET imaging due to the small dynamic range and metabolite in the brain

A human PET study of [¹¹C]HMS011, a potential radioligand for AMPA receptors

Background: α-Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor is a primary mediator of fastglutamatergic excitatory signaling in the brain and has been implicated in diverse neuropsychiatric diseases. Werecently developed a novel positron emission tomography (PET) ligand, 2-(1-(3-([11C]methylamino)phenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl) benzonitrile ([11C]HMS011). This compound is a radiolabelled derivative ofperampanel, an antiepileptic drug acting on AMPA receptors, and was demonstrated to have promising in vivoproperties in the rat and monkey brains. In the current study, we performed a human PET study using [11C]HMS011to evaluate its safety and kinetics.Four healthy male subjects underwent a 120-min PET scan after injection of [11C]HMS011. Arterial blood samplingand metabolite analysis were performed to obtain parent input functions for three of the subjects using highperformanceliquid chromatography. Regional distribution volumes (VTs) were calculated based on kinetic modelswith and without considering radiometabolite in the brain. The binding was also quantified using a reference tissuemodel with white matter as reference.Results: Brain uptake of [11C]HMS011 was observed quickly after the injection, followed by a rapid clearance. Threehydrophilic and one lipophilic radiometabolites appeared in the plasma, with notable individual variability. The kineticsin the brain with apparent radioactivity retention suggested that the lipophilic radiometabolite could enter the brain. Adual-input graphical model, an analytical model designed in consideration of a radiometabolite entering the brain, welldescribed the kinetics of [11C]HMS011. A reference tissue model showed small radioligand binding potential (BP*ND)values in the cortical regions (BP*ND = 0–0.15). These data suggested specific binding component of [11C]HMS011 inthe brain.Conclusions: Kinetic analyses support some specific binding of [11C]HMS011 in the human cortex. However, this ligandmay not be suitable for practical AMPA receptor PET imaging due to the small dynamic range and metabolite in the brain.Keywords: PET, Perampanel, AMPA, [11C]HMS011, Interspecies difference