Authorship：Lead author,　Corresponding author   Language：English  

DOI： https://doi.org/10.1016/j.forsciint.2022.111475

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Glyphosate (GLYP) and glufosinate (GLUF) are phosphorus-containing amino acid type herbicides that are used worldwide. With their rising consumptions, fatal intoxication cases due to these herbicides, whether accidental or intentional, cannot be ignored. Both compounds are difficult to detect, and their pretreatment for instrumental analysis are complicated and time-consuming. Our aim was to develop a simple and rapid quantification method for the two herbicides and their metabolites with liquid chromatography/tandem mass spectrometry (LC/MS/MS). We also compared 2-amino-4-phosphonobutyric acid and DL-2-amino-5-phosphonopentanoic acid as alternative internal standards (IS) to GLYP13C2 15N. Herbicide-containing specimens were highly diluted, evaporated to dryness, and derivatized with acetate/acetic anhydride and trimethyl orthoacetate for 30 min. at 120°C. Our optimized LC conditions successfully separated the target analytes, with acceptable linearities (R 2>0.98) and matrix effects (65%-140%). Accuracy and precision ranged from 80.2 % to 111 %, and from 1.3 % to 13 % at the higher concentration, respectively.The concentration of the herbicides and their metabolites were investigated in a postmortem case of suspected herbicide poisoning cases, in which we detected GLYP and its metabolites. Using one of the three ISs, the GLYP concentrations ranged from 3.1 to 3.5 mg/mL, and 3.3 to 4.5 mg/mL in plasma and urine, respectively; GLYP metabolite concentrations in plasma and urine were 18 to 20 μg/mL and 44 to 54 μg/mL. We thus succeeded in developing a rapid method without extraction for measuring GLYP and GLUF along with their metabolites, and demonstrated its practical applicability.

DOI： 10.18999/nagjms.83.3.567

Web of Science

Scopus

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

A sialidase NEU1 that removes sialic acids from glycoconjugates has been implicated in diverse cellular functions. Aberrant NEU1 activity is associated with various pathologies including lysosomal storage disorder sialidosis, autoimmune diseases and the malignancy and metastasis of cancer cells. We recently reported that NEU1 activity increases during 3T3-L1 adipogenesis and that it is higher in the epididymal fat of obese and diabetic mice. However, the precise functions of NEU1 in adipocytes have not been elucidated. Knockdown of NEU1 using siRNA transfection in 3T3-L1 adipocytes significantly decreased the mRNA expression and protein secretion of IL-6 and MCP-1 induced by LPS. The promoter activities of both IL-6 and MCP-1 as well as nuclear factor-kappa B (NF-κB) nuclear translocation were reduced in adipocytes transfected with an siRNA sequence that targets NEU1(siNEU1). NEU1 suppression using siNEU1 affected TLR4 sialylation. These findings suggest that NEU1 is involved in the production of IL-6 and MCP-1 in adipocytes possibly through TLR4/NF-κB signalling.

DOI： 10.1093/jb/mvx006

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Fatty acids are stored within adipocytes in lipid droplets (LDs) as triacylglycerol (TG), which is converted to free fatty acid (FFA) and glycerol via lipolysis. Increased plasma FFA levels in obesity are associated with several clinical conditions. We previously found that Neu1 activity is aberrant in the epididymal fat and liver of obese and diabetic mice. Here, we examined involvement of Neu1 in lipolysis in 3T3-L1 adipocytes. Small interfering RNA against Neu1 was introduced into adipocytes, and glycerol concentrations were measured in the culture medium. We then assessed the effects of Neu1 knockdown on lipolytic protein expression and phosphorylation, as well as interactions between perilipin 1 (Plin1) and hormone-sensitive lipase (HSL) after isoproterenol (IS) stimulation. Interactions between Neu1 and Plin1 were analyzed by immunoprecipitation and immunofluorescent imaging using adipocytes transfected with pCMV6-mNeu1-myc-DYKDDDDK (mNeu1DDK). Neu1 knockdown increased glycerol concentrations in culture media and Plin1 phosphorylation in whole lysates of IS-stimulated cells. Neu1 knockdown increased interaction between Plin1 and HSL after IS stimulation whereas that between Neu1 and Plin1 on LD observed under basal conditions was lost. These results suggest that Neu1 inhibits lipolysis induced by β-adrenergic stimulation in adipocytes via interactions with Plin1 on LD.

DOI： 10.1111/gtc.12490

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Mammalian sialidases (NEU1, NEU2, NEU3 and NEU4) that remove sialic acids from glycoconjugates have been implicated in diverse cellular functions. Human sialidases are involved in the development of various disease states such as cancer, diabetes and arteriosclerosis. Unregulated acidic sialidase NEU1 activity is associated with the pathogenesis of lysosomal storage disorder (LSD) sialidosis, abnormal immune responses and cancer progression. Obesity is closely related to several chronic diseases such as diabetes, cardiovascular diseases, hyperlipidemia or hypertension that are associated with metabolic syndrome. We examined fluctuations in mRNA levels and sialidase activities of NEU1 in two strains of obese and diabetic mice to assess the involvement of NEU1 in obesity. The activity of NEU1 was preferentially higher in epididymal fat and lower in the livers of two strains of obese and diabetic mice. Fluctuations in NEU1 activity might be associated with the pathological status of these tissues in obesity.

DOI： 10.1248/bpb.b12-00995

PubMed

Total pages：4784   Language：Japanese

ASIN

Language：Japanese

Psychopharmaceuticals contain various drugs of which chemical structures and pharmacological effects are different. Each substance varies in usefulness for medication purposes as well as risk of abuse. Various substance abuse countermeasures have thus been implemented internationally and within each country. In this chapter, the three main International Conventions for controlling and regulating narcotics and psychotropics are outlined: the Single Convention on Narcotic Drugs of 1961, the Convention on Psychotropic Drugs of 1971, and the Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances of 1988. The history on the abuse of narcotics and psychotropics in Japan is explained, and their countermeasures including the four main domestic laws are then presented: the Stimulants Control Act, the Narcotics and Psychotropic Drugs Control Act, the Cannabis Control Act, and the Opium Control Act. Finally, specific topics including the issues on benzodiazepines including etizolam and on synthetic cannabinoids in Japan are described.

DOI： 10.1007/978-3-030-62059-2_386

Scopus

Authorship：Lead author,　Corresponding author   Language：English  

Aconitum contains highly toxic alkaloids such as aconitine, hypaconitine, jesaconitine, and mesaconitine. Since Aconitum ingestion causes fatal intoxication, it is important to analyze aconitines and their metabolites in the blood. In forensic toxicology, postmortem drug redistribution is known as one factor that would hamper accurate evaluation of concentrations. Therefore, it is recommended to collect multiple blood samples from various sites and compare the results to avoid miss identification of causative compounds for intoxication. In this study, we evaluated aconitines and their metabolites in postmortem blood specimens from ten sites by QuEChERS extraction and liquid chromatography-tandem mass spectrometry (LC/MS/MS). The recovery rates and matrix effects of analytes were approximately 74-80% and 94-100%, respectively. The correlation coefficients were over 0.99. The validation studies revealed that accuracies and precisions were around 97-2% (intraday) and 100-4% (interday), respectively. Finally, the concentrations of aconitine and jesaconitine were from 2.72 to 7.20 ng/mL and from 14.9 to 26.3 ng/mL, respectively. The concentrations of mesaconitine were from 0.32 to 0.88 ng/mL in four samples and detected in two. The concentrations were highest in the right atrium and lowest in the femoral vein. Our results suggest that aconitine and jesaconitne are accumulated in right atrium blood after death, and that right atrium specimen is suitable for measuring aconitine compounds in fatal intoxication cases.

DOI： 10.1016/j.forsciint.2022.111475

Web of Science

Scopus

PubMed

Authorship：Lead author  

J-GLOBAL

Authorship：Lead author  

J-GLOBAL