Three flame retardants, tris(1-aziridinyl) phosphine oxide (APO), tris(2,3-dibromopropyl) phosphate (TDBPP), and bis(2,3-dibromopropyl) phosphate (BDBPP), are prohibited for use in textile products under the “Act on the Control of Household Products Containing Harmful Substances” in Japan. The currently used method for analyzing these substances by the Ministry of Health, Labor and Welfare in Japan (MHLWJ), is GC, which uses carcinogenic solvents and hazardous reagents during sample processing. Furthermore, due to the global shortage of helium gas used as carrier gas for GC, the development of an alternative method is necessary. In this study, we developed a method to simultaneously analyze the three flame retardants using LC–MS/MS. In addition, this method is an improvisation of ISO 17881-2, which involves extraction with acetone under acidic conditions and replacing it with acetonitrile. This prevents the acid decomposition of APO and the thermal decomposition of BDBPP. For accurate and sensitive quantification, deuterated compounds, APO-d₁₂, TDBPP-d₁₅, and BDBPP-d₁₀, were used as surrogate standards. The calibration curve displayed linearity within the 0.005–1.0 µg/mL range for APO and the 0.01–2.0 µg/mL range for TDBPP and BDBPP. The limits of detection for APO, TDBPP, and BDBPP were 0.19, 0.87, and 1.0 µg/g, respectively. These values were 2.2, 9.2, and 10 times more sensitive than the current detection limits of 0.4, 8, and 10 µg/g, respectively. The recovery of the three flame retardants in various textile products using the developed analytical method was 83.7–120.8%, which confirms their satisfactory analyses.

To clarify the factors contributing to the interictal burden of migraine, we conducted a questionnaire survey among women with migraine. A questionnaire survey was conducted on the Internet of 400 women between the ages of 20 and 50 who tested positive on the migraine screener. The subjects were divided into a high burden group (n = 260) and a low burden group (n = 140) according to their Migraine Interictal Burden Scale-4 (MIBS-4) score. Using multivariate stepwise logistic regression analysis, we demonstrated that Headache Impact Test-6 (HIT-6) score, type of migraine, the causes of headaches (weather changes and anxiety) and Epworth sleepiness scale (ESS) score influenced to the interictal burden of migraine. Odds ratios of HIT-6 score, type of migraine, weather changes and anxiety in causes of headaches and ESS score were 3.669 (≤55 vs. ≥56; 95% CI = 1.900 – 7.090), 2.327 (migraine without aura vs. migraine with aura; 95% CI = 1.300 – 4.168), 1.810 (yes vs. no; 95% CI = 1.086 – 3.015), 1.703 (no vs. yes; 95% CI = 1.009 – 2.874) and 1.625 (≤10 vs. ≥11; 95% CI = 1.028 – 2.568), respectively. Our findings suggest that multiple factors independently contribute to the interictal burden of migraine.

Introduction: Cephalosporins are widely used antimicrobials; however, their potential to induce coagulopathy-related events, particularly hypoprothrombinemia, raises safety concerns. Methods: This study aimed to comprehensively evaluate the risk of coagulopathy-related events associated with the use of intravenous cephalosporins using the Japanese Adverse Drug Event Report (JADER) database. We analyzed 783,788 cases from the JADER database to identify coagulopathy-related events associated with the use of eleven intravenous cephalosporins between 2004 and 2024. Reporting odds ratios (ROR) with 95% confidence intervals were calculated to detect potential signals. Subsequently, odds ratios were calculated to assess the influence of age and sex on the occurrence of coagulopathy-related events. Results: Cefmetazole (CMZ), cefoperazone/sulbactam (CPZ/SBT), flomoxef (FMOX), and ceftriaxone (CTRX) showed statistically significant signals for coagulopathy-related events (ROR: 10.87, 5.20, 2.67, and 1.38, respectively). Age emerged as a significant factor, with individuals aged >70 years exhibiting higher odds of experiencing coagulopathy-related events associated with CMZ, CPZ/SBT, FMOX, and CTRX use. However, no significant association was observed with sex. Our findings suggest that certain intravenous cephalosporins (CMZ, CPZ/SBT, FMOX, and CTRX) are associated with an increase of coagulopathy-related events, particularly in patients aged >70 years. Conclusions: These findings highlight the need for vigilance and careful consideration of patient-specific factors when prescribing these antibiotics.

Various molecules have been reported to be involved in the induction of HL-60 cell differentiation by all-trans retinoic acid (ATRA). Notably, the transfection of an antisense oligonucleotide targeting proteinase 3 (PRTN3, formerly known as myeloblastin) into HL-60 cells induces differentiation, though the underlying mechanism remains unclear. Here we found that the levels of secreted PRTN3 were significantly reduced when differentiation was initiated by ATRA treatment, suggesting that secreted PRTN3 inhibits HL-60 cell differentiation. The addition of anti-PRTN3 antibody to the culture medium of HL-60 cells promoted their differentiation. Conversely, when ATRA-treated HL-60 cells were cultured in conditioned media prepared from HEK293 cells transfected with the preproPRTN3 plasmid, differentiation was significantly suppressed. Moreover, conditioned media from HEK293 cells transfected with an inactive PRTN3 mutant (S203G) also suppressed HL-60 cell differentiation. These results suggest that PRTN3 secreted from HL-60 cells has an autocrine inhibitory effect on differentiation, independent of its enzymatic activity.

Tadalafil is a potent selective phosphodiesterase 5 inhibitor used to treat pulmonary arterial hypertension. As tadalafil is a substrate of CYP3A, coadministration with a CYP inducer or inhibitor may affect the pharmacokinetics and pharmacological activity of tadalafil. Additionally, CYP expression is regulated by biological clocks and its activity fluctuates diurnally. Moreover, tadalafil's dosing time may also affect its pharmacokinetics. Therefore, this study aimed to investigate the effects of phenobarbital and tadalafil dosing time on the plasma concentration and pharmacological activity of tadalafil. Adult male ICR mice were treated with phenobarbital for 5 days, followed by oral administration of tadalafil perorally. Phenobarbital pretreatment decreased plasma tadalafil and pulmonary cGMP levels in a dose-dependent manner. In mice without phenobarbital pretreatment, the plasma tadalafil concentration tended to be higher when administered in the morning than in the evening. In contrast, plasma tadalafil concentration was higher when administered in the evening than in the morning in mice pretreated with phenobarbital. Similarly, pulmonary cGMP levels were higher when tadalafil was administered in the evening than in the morning in mice pretreated with phenobarbital. Notably, these effects on metabolism and pharmacological activity were observed at clinically relevant doses. Conclusively, these results indicate that the coadministration of phenobarbital and tadalafil may suppress the plasma levels and pharmacological activities of tadalafil. Additionally, dosing time should be carefully considered to maximize the efficacy of tadalafil.