Age-related TFEB downregulation in proximal tubules causes systemic metabolic disorders and occasional apolipoprotein A4-related amyloidosis.

With the aging of society, the incidence of chronic kidney disease (CKD), a common cause of death, has been increasing. Transcription factor EB (TFEB), the master transcriptional regulator of the autophagy-lysosomal pathway, is regarded as a promising candidate for preventing various age-related diseases. However, whether TFEB in the proximal tubules plays a significant role in elderly CKD patients remains unknown.

Development of a simple estimation method of serum caffeine concentration using a point-of-care test kit for urinary caffeine.

Purpose: Serum caffeine concentration is an indicator of caffeine intoxication; however, it is difficult to measure it in most emergency departments. We developed a simple estimation method using a point-of-care test kit for urinary caffeine.

Methods: Caffeine-spiked human serum (100, 50, 25, and 10 µg/mL) was diluted 10-, 20-, 50-, and 100-fold with phosphate-buffered saline and applied to the kit.

Effects of natural environments on drug contents in nails: comparison of drug residual rates between nails and hair to determine the drug-use history of corpses in unnatural death cases using micro-segmental analysis.

Purpose: We previously developed evaluation methods using micro-segmental analysis (MSA) to examine the effects of external environments on drug content in hair and nails. In this study, the effects of the natural environmental factors (water, temperature, humidity, light, and soil) on drug contents in nails were examined and compared with our previous experimental data on hair.

Methods: Four hay-fever medicines were used as model drugs (fexofenadine, epinastine, cetirizine, and desloratadine) to evaluate drug stability in the nails.

Synthesis and analytical characterization of 1-(2-thienoyl)-6-allyl-nor-d-lysergic acid diethylamide (1T-AL-LAD).

Lysergic acid diethylamide (LSD) analogs have emerged as new psychoactive substances (NPS) since the mid-2010s, and new compounds continue to emerge for recreational use. Since the end of 2023, "1D-AL-LAD" appeared on X (formerly Twitter) and other websites. As for the compound "1D-LSD" (which also has "1D" in the name), several studies show that the ingredient of seized blotter paper printed "1D-LSD" was actually 1-(2-thienoyl)-LSD (1T-LSD).

Effects of temperature, humidity, light, and soil on drug stability in hair: a preliminary study for estimating personal profiles using micro-segmental analysis of corpse hair.

Purpose: Micro-segmental hair analysis (MSA), which enables detailed measurement of the distribution of drugs in a single hair strand, is useful for examining the day of death and drug use history of a person. However, corpses are often found in severe environments, such as soil and freezers, which affect the drug contents in hair. Therefore, we examined the effects of temperature, humidity, light, and soil on drug stability in hair as a preliminary study to estimate personal profiles using MSA of corpse hair.

Identifying a suspect powder as a cannabis concentrate through chemical analysis and DNA testing.

Purpose: Cannabis is regulated in many countries, and cannabis products are diversifying, which can hinder identification. Here, we report the seizure of a powder sample with a cannabis-like odor in a spice bottle labeled "nutmeg" and identification of the sample by chemical testing and cannabis DNA testing.

Methods: The sample was observed under a microscope, extracted with methanol, and analyzed by gas chromatography-mass spectrometry (GC-MS).

Preparation of glucuronides using liver microsomes and their characterization by 1D/2D NMR spectroscopy and mass spectrometry: Application to fentanyl metabolites.

A simple, low-cost method for preparing glucuronic acid-conjugated metabolites was developed using fentanyl, a potent synthetic opioid, as a model drug. Five glucuronic acid-conjugated metabolites of fentanyl were measured in the culture medium of fresh human hepatocytes incubated with fentanyl. These glucuronides were also formed by incubation of their corresponding substrates (e.

Changes in methamphetamine impurity profiles induced by tert-butoxycarbonylation.

Analysis of impurities in methamphetamine (MA) can be used to characterize MA seizures, investigate the relationship among MA seizures, and provide information on their synthetic routes. Recently, chemically derivatized MA, such as tert-butoxycarbonyl (t-Boc) MA, has been seized and attracted attention because routine forensic analysis methods may fail to correctly identify them. Chemical derivatization is a simple method for protection and deprotection of a compound, and protection of MA using t-Boc can be used to mask the MA.

Identification of 1-(thiophene-2-carbonyl)-LSD from blotter paper falsely labeled "1D-LSD".

Purpose: Since the mid-2010s, lysergic acid diethylamide (LSD) analogs made for substance abuse have periodically emerged. In this case, three pieces of blotter paper labeled "1D-LSD" and presumably impregnated with this LSD analog, were seized. Several websites indicate that 1D-LSD is 1-(1,2-dimethylcyclobutane-1-carbonyl)-LSD.

Rapid enantiomeric analysis of zopiclone in serum by supercritical fluid chromatography-tandem mass spectrometry.

Zopiclone (ZOP) is a hypnotic drug prescribed to treat insomnia. Due to the chiral nature of ZOP, the psychologically active S-form and inactive R-form need to be determined enantiomerically in a forensic drug analysis. In the present study, a supercritical fluid chromatography (SFC) method was designed with a faster analysis ability than that of previously reported techniques.

Evaluation of applicability of micro-segmental analysis to hair treated with heat and haircare products.

Purpose: Micro-segmental analysis (MSA), which enables the measurement of detailed drug distributions in hair by segmenting a single hair strand at 0.4 mm intervals, is indispensable for estimating the day of drug ingestion. However, haircare with dryers and various products can influence drug concentrations in hair.

Evaluation of decarboxylation efficiency of Δ-tetrahydrocannabinolic acid and cannabidiolic acid by UNODC method.

Purpose: Decarboxylation of Δ-tetrahydrocannabinolic acid (Δ-THCA) to Δ-tetrahydrocannabinol (Δ-THC) by heating is a common method for determining total Δ-THC. In the manual for cannabis identification and analysis, the United Nations Office on Drugs and Crime (UNODC) proposed decarboxylation conditions. Although the manual's primary analytical target is Δ-THC, some reports also quantified cannabidiol (CBD).

Agonistic activity of fentanyl analogs and their metabolites on opioid receptors.

Purpose: This study aims to expose the toxicity of fentanyl analogs and their metabolites by measuring the agonistic activity of these compounds on opioid receptors.

Methods: The agonistic activity of fentanyl, four analogs of fentanyl (acetylfentanyl, butyrylfentanyl, tetrahydrofuranylfentanyl, and furanylfentanyl), and their metabolites were evaluated using a cell-based assay system, which measured the cellular cAMP level after the reaction of a test compound with cells expressing opioid receptor.

Results: Fentanyl and its four analogs showed agonistic activity on μ-opioid receptor at < 10 nM, whereas these compounds were inactive at δ- and κ-opioid receptors even at 100 nM.

Distribution profiles of diphenhydramine and lidocaine in scalp, axillary, and pubic hairs measured by micro-segmental hair analysis: good indicator for discrimination between administration and external contamination of the drugs.

Purpose: Drug distribution in scalp hair can provide historical information about drug use, such as the date and frequency of drug ingestion. We previously developed micro-segmental hair analysis, which visualizes drug distribution at 0.4-mm intervals in individual hairs.

Thin-layer chromatography on silver nitrate-impregnated silica gel for analysis of homemade tetrahydrocannabinol mixtures.

Purpose: Various forms of cannabidiol (CBD)-containing products are sold in Japan. CBD is easily converted to mixtures of ∆-tetrahydrocannabinol (∆-THC) and its isomer, ∆-THC, using household chemicals like diluted hydrochloric acid. This ease of production increases concerns regarding production of homemade THC mixtures.

Micro-segmental hair analysis: detailed procedures and applications in forensic toxicology.

Purpose: Since the 1980s, the detection sensitivity of mass spectrometers has increased by improving the analysis of drugs in hair. Accordingly, the number of hair strands required for the analysis has decreased. The length of the hair segment used in the analysis has also shortened.

Analysis of highly potent synthetic opioid nitazene analogs and their positional isomers.

Four nitazenes (metonitazene, etonitazene, protonitazene, and isotonitazene), highly potent benzimidazole synthetic opioids, and their four nitro group positional isomers (isonitazenes) were synthesized and analyzed using infrared (IR) spectroscopy, gas chromatography/mass spectrometry (GC/MS), and liquid chromatography/mass spectrometry (LC/MS). In addition, the agonistic activity of all compounds at the human μ-opioid receptor was measured using a cell-based assay system. In the IR spectra, characteristic peaks for nitazenes and isonitazenes were observed.

Possibility of drug-distribution measurement in the hair of drowned bodies: evaluation of drug stability in water-soaked hair using micro-segmental analysis.

In postmortem examinations, the drug analysis of hair is effective for revealing drug-use history. Additionally, a method to estimate the day of death using hair was previously developed by analyzing a single hair strand segmented at 0.4-mm intervals (micro-segmental hair analysis).

Post-translational control of beige fat biogenesis by PRDM16 stabilization.

Compelling evidence shows that brown and beige adipose tissue are protective against metabolic diseases. PR domain-containing 16 (PRDM16) is a dominant activator of the biogenesis of beige adipocytes by forming a complex with transcriptional and epigenetic factors and is therefore an attractive target for improving metabolic health. However, a lack of knowledge surrounding the regulation of PRDM16 protein expression hampered us from selectively targeting this transcriptional pathway.