Shujitsu University

Methotrexate (MTX) is the anchor first-line drug for the treatment of rheumatoid arthritis (RA) in the RA guidelines of the ACR, JCR and EULAR. In the guidelines, MTX is primarily administered orally as low-dose pulse therapy. However, oral MTX therapy has a large interindividual variation of drug efficacy/adverse drug reactions due to bioavailability (BA) differences and it is often associated with gastrointestinal disturbances, making some patients unable to continue oral MTX therapy. MTX subcutaneous (SC) administration involves pain at the injection site and there are regulatory issues in disposal related to medical waste. The pyro-drive jet injector (PJI) is an innovative, needle-free drug delivery system that enables targeted delivery of drugs. This study investigated the pharmacokinetics (PK) and BA of MTX via the PJI in rats. PJI-injected India ink indicated penetration into the subcutis. The AUC0–∞ after oral (PO) administration was significantly less than that after intravenous (IV), SC, and PJI administration. Absolute BA values with PO, SC, and PJI administration were 30.6%, 99.1%, and 100.8%, respectively. The relative BA of the PJI compared with the SC group was 101.7%. The administration of MTX using the PJI may be useful in clinical practice, but further studies, such as BA or bioequivalence tests, are necessary in animal species with skin similar to human skin or in humans.

Human social behavior spans a continuum from self-serving actions to other-oriented sacrifices. Underlying these behaviors are reputational concerns, specifically rejection avoidance and praise seeking. However, it is unclear how reputational concerns relate to pathological altruism, which involves excessive, irrational self-sacrifice, and healthy selfishness, which prioritizes one’s own fulfillment with consideration of potential negative effects on others. This study examined whether rejection avoidance and praise seeking are associated with pathological altruism and healthy selfishness. Data were collected from 787 participants between the ages of 15 and 59. The results indicated that both rejection avoidance and praise seeking were positively correlated with pathological altruism and healthy selfishness, even after controlling for empathy. Most associations were stable across all ages, although the association between praise seeking and healthy selfishness was moderated by age. These findings provide initial empirical evidence that reputational concerns may drive individuals toward both pathological altruism and healthy selfishness. This result enhances the understanding of the motivational role of social evaluation in complex human social functioning.

This study aims to evaluate the association between serum concentrations of hydroxychloroquine (HCQ) and its derivatives and clinical efficacy in Japanese patients with rheumatoid arthritis (RA). Patients with active RA despite conventional synthetic disease-modifying antirheumatic drugs were recruited, and HCQ was administered for 24 weeks in addition to the prior treatment. Serum concentrations of HCQ, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BCQ) were measured at weeks 0, 4, 8, 12, 24, and 32. The association between each serum concentration and achievement of American College of Rheumatology (ACR) 20/50/70 was analysed. Forty-nine patients whose sera were available were included in the analysis. The serum concentrations of HCQ, DHCQ, DCQ, and BCQ reached a plateau at Week 4 and remained at the stable levels during the 24 weeks. The concentrations of HCQ, DHCQ, DCQ, and BCQ at Week 24 were higher in patients who achieved ACR20 than in those who did not. Furthermore, higher serum concentrations of DHCQ and BCQ were also associated with the achievement of ACR50 and ACR70, while those of HCQ and DCQ were not. Serum concentrations of HCQ and its derivatives are associated with the clinical effectiveness of HCQ in Japanese patients with RA.

3,3-Dialkoxy-2-oxindoles are prevalent in natural products and exhibit unique biological activities. Among them, acyclic alkoxy analogues show instability in acidic conditions, making access to acyclic isatin ketals highly challenging. Conventional methods for the synthesis of 3,3-dialkoxy-2-oxindoles usually require strongly acidic and harsh reaction conditions, resulting in a low overall efficiency. Herein, we report on an acid- and metal-free protocol for the synthesis of 3,3-dialkoxy-2-oxindoles from isatins through an iodine-catalyzed ketalization. This photochemical protocol does not require the use of any specific reagents such as metal catalysts. Furthermore, the total synthesis of an unprecedented 2-oxindole alkaloid bearing 3,3-dimethoxy moiety is achieved.

In light of the growing challenge posed by drug resistance, the focus of our research has been on the development of novel antibacterial substances. The approach involves the attachment of antibacterial functional groups to oligosaccharide, known as cyclodextrin, utilising antimicrobial peptides possessing hydrophobic groups and cationic groups as a model system. The cyclodextrin derivative, which contains seven pairs of indole rings and guanidino groups, was synthesised and exhibited potent antibacterial properties that were selective for Enterococcus faecalis. Conversely, a compound comprising a single set of functional groups was selectively antibacterial against Staphylococcus aureus. These were unique phenomena in that they were completely different from the peptides containing indole and guanidino groups and the previously reported antibacterial cyclodextrins modified with alkylamino groups that showed a broad antibacterial spectrum. The results will lead to the discovery of new chemical compounds (or functional groups) those will demonstrate specific antibacterial properties for pathogens and may be useful in the fields of cyclodextrin chemistry and development of antibacterial drugs and materials, particularly in the fight against multidrug-resistant pathogens.

Abstract BackgroundThe 25-Question Geriatric Locomotive Function Scale (GLFS-25) is one of the tests used to assess the risk of locomotive syndrome (LS). It is a comprehensive tool to measure LS improvement after total hip arthroplasty (THA) and provides beneficial information for rehabilitation after THA. This study aims to investigate the effectiveness of LS improvement three months after THA in patients who underwent THA for hip osteoarthritis (OA) by using the total clinical decision limits (CDL) 3-stage scale to identify specific trends in LS improvement based on the GLFS-25.MethodsThe participants of this study were 273 patients who underwent primary THA for hip OA. LS was evaluated using the stand-up test, two-step test, and GLFS-25 before receiving THA and three months after THA.ResultsThe total CDL was improved by THA in 132 patients (improvement rate: 48.4%). There were 15 questions out of 25 in the GLFS-25 showed improvements in more than 60% of the patients. The question Q13, “To what extent has it been difficult to walk briskly?” revealed the highest improvement rate, followed by Q12, “To what extent has it been difficult to go up and down stairs?”, and Q3, “Did you have any pain (including numbness) in your lower limbs?”.ConclusionsAt three months after THA, approximately half of the patients showed improvement in LS. Furthermore, improvement in locomotion movements was identified as the most significant area of progress among motor functions.

BackgroundUnderstanding the roles and competencies of professions outside of one’s specialty is essential for providing efficient healthcare. However, it is difficult for medical professionals to understand the roles and competencies of other related professions while performing their duties. This study examined the impact of clinical practice-based interprofessional education (IPE) on pharmacy students, who are future medical professionals.MethodsSixty-eight pharmaceutical students undergoing clinical practice were divided into non-IPE or IPE groups, with the IPE group attending an educational program with medical students conducted by doctors, pharmacists, and teachers during the clinical practice period. The effect was evaluated through a group survey using self-administered questionnaires focusing on contributing to multidisciplinary team medicine based on the Readiness for Interprofessional Learning Scale. The survey included specific behavioral objectives (SBOs), the Readiness for Interpersonal Learning Scale (RIPLS), and Kikuchi’s Scale of Social Skills (KiSS-18).ResultsRegardless of group, SBOs [non-IPE: 3.2, 95% CI (2.6–3.8), p < 0.001; IPE: 3.7, 95% CI (2.5–4.9), p < 0.001] and social skills [non-IPE: 4.0, 95% CI (2.5–6.1), p < 0.001; IPE: 6.7 95% CI (3.0–10.4), p < 0.001] showed improvement after the clinical practice. In RIPLS Factor 3, pharmacy students with IPE awareness scored significantly higher by 1.5 points [95% CI (0.2–2.8), p = 0.025] post-practice than those without IPE awareness.ConclusionsThis study suggests that IPE for students during clinical practice could enhance their expertise in multidisciplinary medicine and facilitate the development of seamless team care in the future.Trial registrationThis study was retrospectively registered and conducted in compliance with the “Ethical Guidelines for Medical Research Involving Human Subjects” and was approved by The Ethics Committee of Tokushima University Hospital (approval number: 3544).

Passive smoking from environmental tobacco smoke not only increases the risk of lung cancer and cardiovascular disease but may also be a stressor triggering neuropsychiatric and other disorders. To prevent these diseases, understanding the relationship between passive smoking and stress is vital. In this study, we developed a simple and sensitive method to simultaneously measure nicotine (Nic) and cotinine (Cot) as tobacco smoke exposure biomarkers, and cortisol (CRT), serotonin (5-HT), melatonin (MEL), dopamine (DA), and oxytocin (OXT) as stress-related biomarkers. These were extracted and concentrated from saliva by in-tube solid-phase microextraction (IT-SPME) using a Supel-Q PLOT capillary as the extraction device, then separated and detected within 6 min by liquid chromatography–tandem mass spectrometry (LC−MS/MS) using a Kinetex Biphenyl column (Phenomenex Inc., Torrance, CA, USA). Limits of detection (S/N = 3) for Nic, Cot, CRT, 5-HT, MEL, DA, and OXT were 0.22, 0.12, 0.78, 0.39, 0.45, 1.4, and 3.7 pg mL−1, respectively, with linearity of calibration curves in the range of 0.01–25 ng mL−1 using stable isotope-labeled internal standards. Intra- and inter-day reproducibilities were under 7.9% and 14.6% (n = 5) relative standard deviations, and compound recoveries in spiked saliva samples ranged from 82.1 to 106.6%. In thirty nonsmokers, Nic contents positively correlated with CRT contents (R2 = 0.5264, n = 30), while no significant correlation was found with other biomarkers. The standard deviation of intervals between normal beats as the standard measure of heart rate variability analysis negatively correlated with CRT contents (R2 = 0.5041, n = 30). After passive smoke exposure, Nic levels transiently increased, Cot and CRT levels rose over time, and 5-HT, DA, and OXT levels decreased. These results indicate tobacco smoke exposure acts as a stressor in nonsmokers.