Glucuronidation of tizoxanide, an active metabolite of nitazoxanide, in liver and small intestine: Species differences in humans, monkeys, dogs, rats, and mice and responsible UDP-glucuronosyltransferase isoforms in humans.

Tizoxanide (TZX) is an active metabolite of nitazoxanide (NTZ) originally developed as an antiparasitic agent, and is predominantly metabolized into TZX glucuronide. In the present study, TZX glucuronidation by the liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice, and recombinant human UDP-glucuronosyltransferase (UGT) were examined. The kinetics of TZX glucuronidation by the liver and intestinal microsomes followed the Michaelis-Menten or biphasic model, with species-specific variations in the intrinsic clearance (CL).

Hepatic glucuronidation of tetrabromobisphenol A and tetrachlorobisphenol A: interspecies differences in humans and laboratory animals and responsible UDP-glucuronosyltransferase isoforms in humans.

Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA), bisphenol A (BPA) analogs, are endocrine-disrupting chemicals predominantly metabolized into glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in humans and rats. In the present study, TBBPA and TCBPA glucuronidation by the liver microsomes of humans and laboratory animals (monkeys, dogs, minipigs, rats, mice, and hamsters) and recombinant human hepatic UGTs (10 isoforms) were examined. TBBPA glucuronidation by the liver microsomes followed the Michaelis-Menten model kinetics in humans, rats, and hamsters and the biphasic model in monkeys, dogs, minipigs, and mice.

A modified high-resolution melting-based assay (HRM) to identify the SARS-CoV-2 N501Y variant.

High-resolution melting (HRM) analysis is a PCR-based method that can be used as a screening assay to identify SARS-CoV-2 variants. However, conventional HRM assays hardly detect slight melting temperature differences at the A-T to T-A transversion. As the N501Y substitution results from A-T to T-A transversion in A23063, few or no studies have shown that a conventional HRM assay can identify N501Y variants.

Hydrolysis of dibutyl phthalate and di(2-ethylhexyl) phthalate in human liver, small intestine, kidney, and lung: An in vitro analysis using organ subcellular fractions and recombinant carboxylesterases.

Phthalates are widely used plasticizers that are primarily and rapidly metabolized to monoester phthalates in mammals. In the present study, the hydrolysis of dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) in the human liver, small intestine, kidney, and lung was examined by the catalytic, kinetic, and inhibition analyses using organ microsomal and cytosolic fractions and recombinant carboxylesterases (CESs). The V (y-intercept) values based on the Eadie-Hofstee plots of DBP hydrolysis were liver > small intestine > kidney > lung in microsomes, and liver > small intestine > lung > kidney in cytosol, respectively.

A Rapid Screening Assay for Clarithromycin-Resistant Mycobacterium avium Complex Using Melting Curve Analysis with Nonfluorescent Labeled Probes.

Mycobacterium avium complex (MAC) thrives in various environments and mainly causes lung disease in humans. Because macrolide antibiotics such as clarithromycin or azithromycin are key drugs for MAC lung disease, the emergence of macrolide-resistant strains prevents the treatment of MAC. More than 95% of macrolide-resistant MAC strains are reported to have a point mutation in 23S rRNA domain V.

Species differences in activation of TRPA1 by resin additive-related chemicals relevant to indoor air quality.

Transient Receptor Potential Ankyrin 1 (TRPA1), which is expressed in the airways, has causative and exacerbating roles in respiratory diseases. TRPA1 is known as a target of sick building syndrome-related air pollutants, such as formaldehyde. Thus, an in vitro TRPA1 activation assay would be useful for predicting the potential risk of air pollution.

Rapid Identification of SARS-CoV-2 Omicron BA.5 Spike Mutation F486V in Clinical Specimens Using a High-Resolution Melting-Based Assay.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.5 emerged as of February 2022 and replaced the earlier Omicron subvariants BA.1 and BA.

Isoform-Specific Quantification of Human Bitter Taste Receptor Transcripts Using Real-Time PCR Analysis.

Bitter taste receptors (TAS2Rs) are expressed by oral cavity cells in mammals and classically function as sensors for bitter compounds. There are 25 functional isoforms of human TAS2Rs, with individual bitter ligands. Each human TAS2R isoform is distributed in several tissues, such as the airway epithelia and gastrointestinal tract, and plays an important role in physiological functions.

Discrimination of SARS-CoV-2 Omicron Sublineages BA.1 and BA.2 Using a High-Resolution Melting-Based Assay: a Pilot Study.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. As of March 2022, Omicron variant BA.2 is rapidly replacing variant BA.

Global DNA Methylation in Cord Blood as a Biomarker for Prenatal Lead and Antimony Exposures.

DNA methylation is an epigenetic mechanism for gene expression modulation and can be used as a predictor of future disease risks. A prospective birth cohort study was performed to clarify the effects of neurotoxicants on child development, namely, the Tohoku Study of Child Development, in Japan. This study aimed to evaluate the association of prenatal exposure to five toxic metals-arsenic, cadmium, mercury, lead (Pb), antimony (Sb), and polychlorinated biphenyls (PCBs, N = 166)-with global DNA methylation in umbilical cord blood DNA.

Simultaneous Screening of SARS-CoV-2 Omicron and Delta Variants Using High-Resolution Melting Analysis.

A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain, the Omicron variant (Pango lineage B.1.1.

[Analysis of Cyanide Compounds in Foods by the Purge Method Using a Midget Impinger].

Cyanogenic glycosides in loquat (Eriobotrya japonica) seeds, which are used in so-called health foods, pose a public concern in Japan due to their potential health risks. Several pretreatment methods, such as the steam distillation and Conway microdiffusion methods, have been established for the determination of cyanogenic glycoside concentrations in foods. However, these methods are time-consuming and have extremely low throughput.

A rapid screening assay for L452R and T478K spike mutations in SARS-CoV-2 Delta variant using high-resolution melting analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been reported worldwide and novel SARS-CoV-2 variants continue to emerge. A novel SARS-CoV-2 strain, the Delta variant (B.1.

Less Carcinogenic Chlorinated Estrogens Applicable to Hormone Replacement Therapy.

Human estrogens prescribed for hormone replacement therapy (HRT) are known to be potent carcinogens. To find safer estrogens, several chlorinated estrogens were synthesized and their carcinogenic potential were determined. A pellet containing either 2-chloro-17β-estradiol (2-ClE) or 4-chloro-17β-estradiol (4-ClE) was implanted subcutaneously for 52 weeks into August Copenhagen Irish (ACI) rats, a preferred animal model for human breast cancer.

Development of a genotyping platform for SARS-CoV-2 variants using high-resolution melting analysis.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus causing coronavirus disease 2019 (COVID-19), has been expanding globally since late 2019. SARS-CoV-2, an RNA virus, has a genome sequence that can easily undergo mutation. Several mutated SARS-CoV-2 strains, including those with higher infectivity than others, have been reported.

Favipiravir biotransformation in liver cytosol: Species and sex differences in humans, monkeys, rats, and mice.

Favipiravir is an antiviral agent effective against several RNA viruses that is converted into an inactive oxidative metabolite (M1), mainly by aldehyde oxidase, in humans. In the present study, the biotransformation of favipiravir into M1 in male and female humans, monkeys, rats, and mice was examined in an in vitro system using liver cytosolic fractions. The kinetics for M1 formation followed the Michaelis-Menten model in all species.

Evaluation of the sensitization potential of volatile and semi-volatile organic compounds using the direct peptide reactivity assay.

The purpose of this study was to evaluate the sensitization potential of 82 compounds classified as volatile and/or semi-volatile organic compounds using the direct peptide reactivity assay (DPRA), given that these chemical compounds have been detected frequently and at high concentrations in a national survey of Japanese indoor air pollution and other studies. The skin sensitization potential of 81 of these compounds was evaluable in our study; one compound co-eluted with cysteine peptide and was therefore not evaluable. Twenty-five of the evaluated compounds were classified as positive.

Catecholamine oxidation-mediated transcriptional inhibition in Mn neurotoxicity.

Manganese (Mn) poisoning may result in a neurological disorder called manganism. Although the neurotoxic mechanism of Mn is unclear, oxidative stress may be involved based on the interactions between neurotransmitter catecholamines and metals such as iron. Here, we propose a novel mechanism in which Mn oxidizes catecholamines and inhibits cellular transcription.

Skin transferability of phthalic acid ester plasticizers and other plasticizers using model polyvinyl chloride sheets.

The transferability of phthalic acid esters (PAEs) and other plasticizers, from model polyvinyl chloride (PVC) sheets to the skin of 11 subjects was assessed by measuring the amount of substance transferred using PVC sheets containing PAEs and alternative plasticizers of different types and contents. For all subjects, the transferred amount, from sheets containing 28 wt% PAE or from mixed sheets containing 14 wt% each of di (2-ethylhexyl) phthalate (DEHP) and other PAE, was greater than that from sheets containing 15 wt% each of PAE or alternative plasticizer only. A comparison of the transferability of five types of PAE showed that transfer tended to occur more readily as the -octanol-water partition coefficient increased, suggesting that PAE hydrophobicity affected its transferability.

Risk assessment concepts and approaches for indoor air chemicals in Japan.

Individuals living in general indoor environments are exposed to a greater variety of chemical pollutants, albeit at lower concentrations, compared with industrial workers in occupational environments. These pollutants can result in a variety of adverse health effects, including those affecting the respiratory, neurological, reproductive, dermatologic, and cardiovascular systems. In Japan, indoor air quality guidelines have been established for 13 chemicals since 1997, and these developments have continued on the basis of scientific discussions in the Committee on Indoor Air Pollution (CIAP) that was set up by the Ministry of Health, Labour and Welfare.

Carcinogenic potential of fluorinated estrogens in mammary tumorigenesis.

Fluorination preventing metabolic hydroxylation of 17β-estradiol (E) was applied to investigate the mechanisms underlying estrogen-induced carcinogenesis. Either 2-fluoro-17β-estradiol (2-FE) or 4-fluoro-17β-estradiol (4-FE) was administered subcutaneously for 52 weeks to August Copenhagen Irish (ACI) rats, the preferred animal model for human breast cancer. 4-FE induced frequent mammary tumors whereas 2-FE did not.