Pharmacokinetic study of Paeoniflorin Paeonimetabolin-I and Glycyrrhetic acid in humans after oral administration of Paeony Root, Glycyrrhiza and Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang)

The pharmacokinetics of Paeoniflorin (PF) , Paeonimetabolin-I (PM-I) and Glycyrrhetic acid (GA) after oral administration of the decoction of Paeony Root (PR) and Glycyrrhiza (GR) and Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang ; SK) were studied using human subjects. Concerning the intra- and inter-individual variability of PF and PM-I after oral administration of SK, each inter-individual coefficient of variation (CV) of the pharmacokinetic parameters was larger than its intra-individual CV. There was no significant correlation between each pharmacokinetic parameter and each subject\u27s physiques. These results suggested that a large inter-individual variability were not caused by differences in the subjects\u27 physiques. Regarding a comparison of the pharmacokinetic parameters, AUC and Cmax of PF of PR were significantly higher than those of SK, and MRT and Tmax of PM-I of SK were significantly longer than those of PR. AUC of GA of SK was significantly higher than those of GR. There is the possibility that PR would be better than SK when a stronger efficacy of PR is expected in a short time, and SK would be beter than PR when a longer efficacy of PR or a stronger efficacy of GR is expected. ヒト健常人において芍薬・甘草・芍薬甘草湯経口投与時のペオニフロリン(PF),ペオニメタボリン-I(PM-I),グリチルレチン酸(GA)の葉物動態の研究を施行した。芍薬甘草湯投与後のPF,PMIの個体内・個体間変動については,各々の個体問変動係数が個体内変動係数よりも大きく,また,全ての薬物動態の各パラメータと被験者の体格との間には相関はみられなかった。芍薬・甘草と芍薬甘草湯との比較では,芍薬のPFのAUC,Cmaxが芍薬甘草湯のものに比較して有意に高値を示し,芍薬甘草湯のPM-IのMRT,Tmaxが芍薬に比較して有意に長かった。また,芍薬甘草湯のGAのAUCは甘革単独投与のものに比較して有意に高値を示した。このことから,短時間に芍薬のより強い効果を期待する際には芍薬単独で用い,芍薬成分のより長い効果や甘草成分のより強い効果を期待する際には芍薬甘草湯として投与する方がよい可能性がある

How Two Brains Make One Synchronized Mind in the Inferior Frontal Cortex: fNIRS-Based Hyperscanning During Cooperative Singing.

One form of communication that is common in all cultures is people singing together. Singing together reflects an index of cognitive synchronization and cooperation of human brains. Little is known about the neural synchronization mechanism, however. Here, we examined how two brains make one synchronized behavior using cooperated singing/humming between two people and hyperscanning, a new brain scanning technique. Hyperscanning allowed us to observe dynamic cooperation between interacting participants. We used functional near-infrared spectroscopy (fNIRS) to simultaneously record the brain activity of two people while they cooperatively sang or hummed a song in face-to-face (FtF) or face-to-wall (FtW) conditions. By calculating the inter-brain wavelet transform coherence between two interacting brains, we found a significant increase in the neural synchronization of the left inferior frontal cortex (IFC) for cooperative singing or humming regardless of FtF or FtW compared with singing or humming alone. On the other hand, the right IFC showed an increase in neural synchronization for humming only, possibly due to more dependence on musical processing

How two brains make one synchronized mind in the inferior frontal cortex: FNIRS-based hyperscanning during cooperative singing

Osaka N., Minamoto T., Yaoi K., et al. How two brains make one synchronized mind in the inferior frontal cortex: FNIRS-based hyperscanning during cooperative singing. Frontiers in Psychology 6, 1811 (2015); https://doi.org/10.3389/fpsyg.2015.01811.One form of communication that is common in all cultures is people singing together. Singing together reflects an index of cognitive synchronization and cooperation of human brains. Little is known about the neural synchronization mechanism, however. Here, we examined how two brains make one synchronized behavior using cooperated singing/humming between two people and hyperscanning, a new brain scanning technique. Hyperscanning allowed us to observe dynamic cooperation between interacting participants. We used functional near-infrared spectroscopy (fNIRS) to simultaneously record the brain activity of two people while they cooperatively sang or hummed a song in face-to-face (FtF) or face-to-wall (FtW) conditions. By calculating the inter-brain wavelet transform coherence between two interacting brains, we found a significant increase in the neural synchronization of the left inferior frontal cortex (IFC) for cooperative singing or humming regardless of FtF or FtW compared with singing or humming alone. On the other hand, the right IFC showed an increase in neural synchronization for humming only, possibly due to more dependence on musical processing

Dioxins levels in human blood after implementation of measures against dioxin exposure in Japan

Background: Over the past few decades, the Japanese Ministry of the Environment has been biomonitoring dioxins in the general Japanese population and, in response to public concerns, has taken measures to reduce dioxin exposure. The objectives of this study were to assess the current dioxin dietary intake and corresponding body burden in the Japanese and compare Japanese dioxin data from 2011 to 2016 and 2002–2010 surveys. We also examined the relationship between blood dioxins and health parameters/clinical biomarkers. Methods: From 2011 to 2016, cross-sectional dioxin surveys were conducted on 490 Japanese (242 males and 248 females, aged 49.9 ± 7.6 years) from 15 Japanese prefectures. Blood (n = 490) and food samples (n = 90) were measured for 29 dioxin congeners including polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) using gas chromatography coupled with high-resolution mass spectrometry. Using the 2006 World Health Organization toxic equivalence factors, the toxic equivalents (TEQs) were calculated. Clinical biomarkers and anthropometric parameters were also measured and information on lifestyle behaviours collected. Data imputations were applied to account for blood dioxins below the detection limit. Results: The median (95% confidence interval or CI) blood levels and dioxin dietary intake was respectively 9.4 (8.8–9.9) pg TEQ/g lipid and 0.3 (0.2–0.4) pg TEQ/kg body weight/day. The median blood dioxin level in the 2011–2016 survey was found to have decreased by 41.3% compared to the 2002–2010 surveys. Participants who were older were found to be more likely to have higher dioxin levels. Blood dioxins were also significantly associated with body mass index, triglycerides, docosahexaenoic acid, eicosapentaenoic acid, and dihomo-gamma-linoleic acid levels in blood. Furthermore, associations between blood dioxin and dietary dioxin intake were evident in the unadjusted models. However, after adjusting for confounders, blood dioxins were not found to be associated with dietary dioxin intake. Conclusions: Blood dioxin levels declined over the past decade. This study showed that the measures and actions undertaken in Japan have possibly contributed to these reductions in the body burden of dioxins in the Japanese population

Neuroprotective effects of Si-based hydrogen-producing agent on 6-hydroxydopamine-induced neurotoxicity in juvenile mouse model

Togawa S., Usui N., Doi M., et al. Neuroprotective effects of Si-based hydrogen-producing agent on 6-hydroxydopamine-induced neurotoxicity in juvenile mouse model. Behavioural Brain Research 468, 115040 (2024); https://doi.org/10.1016/j.bbr.2024.115040.Neurotoxins have been extensively investigated, particularly in the field of neuroscience. They induce toxic damage, oxidative stress, and inflammation on neurons, triggering neuronal dysfunction and neurodegenerative diseases. Here we demonstrate the neuroprotective effect of a silicon (Si)-based hydrogen-producing agent (Si-based agent) in a juvenile neurotoxic mouse model induced by 6-hydroxydopamine (6-OHDA). The Si-based agent produces hydrogen in bowels and functions as an antioxidant and anti-inflammatory agent. However, the effects of the Si-based agent on neural degeneration in areas other than the lesion and behavioral alterations caused by it are largely unknown. Moreover, the neuroprotective effects of Si-based agent in the context of lactation and use during infancy have not been explored in prior studies. In this study, we show the neuroprotective effect of the Si-based agent on 6-OHDA during lactation period and infancy using the mouse model. The Si-based agent safeguards against the degradation and neuronal cell death of dopaminergic neurons and loss of dopaminergic fibers in the striatum (STR) and ventral tegmental area (VTA) caused by 6-OHDA. Furthermore, the Si-based agent exhibits a neuroprotective effect on the length of axon initial segment (AIS) in the layer 2/3 (L2/3) neurons of the medial prefrontal cortex (mPFC). As a result, the Si-based agent mitigates hyperactive behavior in a juvenile neurotoxic mouse model induced by 6-OHDA. These results suggest that the Si-based agent serves as an effective neuroprotectant and antioxidant against neurotoxic effects in the brain, offering the possibility of the Si-based agent as a neuroprotectant for nervous system diseases

出産クラス受講前後の妊婦の自己効力感と指導者のProfessional Learning Climate との関連性

【目的】出産クラス受講前後の妊婦の自己効力感と指導者の Professional Learning Climate （以下、PLCとする）との関連性を明らかにする。 【方法】２００８年７月～９月に北陸の産科施設で開催された３１の出産クラスに参加した妊婦 ２４４名とクラス指導者３９名を対象に自記式質問紙調査を行った。妊婦には出産に対する自 己効力感と指導者に対して感じたPLCについて、クラス指導者にはクラスの指導経験年数 など属性項目を調査した。また、クラスの参加観察によりクラス内容や雰囲気、参加者や 指導者の交流タイプなどを調査した。 【結果】対象全体では、自己効力感と PLCに有意な関連は認めなかった。しかし、出産経験 別の検討では、初産婦にのみ自己効力感と PLCに有意な正相関を認めた。 PLCの要素別で は「リラックスできる空間の創造」、「ユーモアとウィット」の２要素と自己効力感との間 に有意な正相関を認めた。一方、経産婦においては自己効力感と PLCに関連性は認めな かった。さらに、クラス後の自己効力感の高さには、 PLCとクラス前の自己効力感が影響 していた。 　以上より、 PLCは出産クラスを運営する際に、指導者にとって身につけることが望まし い必要な要素であることが示唆された。 : The purpose of this study was to clarify the relationship between the professional learning climate (PLC) of educators and the self-efficacy of pregnant women before and after they took a childbirth class. : A self-completed questionnaire survey was conducted on 244 pregnant women who had participated in 31 childbirth classes held in a maternity hospital in the Hokuriku district, and 39 class educators. It investigated the pregnant women s feelings of self-efficacy to cope with childbirth and PLC with the educator, and such educator attributes as the number of years of experience in teaching childbirth classes. Class content and atmosphere, and the types of interaction between participants and educators, were investigated through participant observation of the classes. The survey was conducted from July to September 2008. : No significant relationship was observed between self-efficacy and PLC in all subjects. However, among women with parity, a significant positive correlation was observed between self-efficacy and PLC in nullipara. Among individual elements of PLC, significant positive correlations were observed between self-efficacy and “creation of a relaxing space” and “humor and wit.” Among multipara, no relationship was observed between self-efficacy and PLC. In addition, the level of self-efficacy after the class was affected by PLC and self-efficacy before the class. 　The present findings suggest that skill in creating PLC is an element which educators should acquire in order to conduct childbirth classes.[原著

Potential application of measuring serum infliximab levels in rheumatoid arthritis management: A retrospective study based on KURAMA cohort data

Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or the efficacy of the treatment diminishes over time. Although previous studies have reported a relationship between serum IFX levels and therapeutic efficacy, the potential applications of IFX therapeutic drug monitoring (TDM) in clinical practice remain unclear. The purpose of this study was to investigate the potential applications of IFX TDM by analyzing a Japanese cohort database. Data were collected retrospectively from the Kyoto University Rheumatoid Arthritis Management Alliance cohort between January 1, 2011, and December 31, 2018. Serum IFX levels were measured using a liquid chromatography-tandem mass spectrometer. Out of the 311 RA patients that used IFX, 41 were eligible for the analysis. Serum IFX levels were significantly higher in responders than in non-responders. An optimal cut-off value was determined to be 0.32 μg/mL based on a receiver operating characteristic curve. At the IFX measurement point, a better therapeutic response was observed in the high IFX group (n = 32) than in the low IFX group (n = 9). Conversely, at the maximum effect point, when DAS28-ESR was the lowest between IFX introduction and measurement points, there were no differences in responder proportions between the low and high IFX groups. IFX primary ineffectiveness could be avoided with appropriate dose escalation without blood concentration measurement in clinical practice. In conclusion, IFX TDM could facilitate the identification of secondary non-responders and in turn, proper IFX use

Enhanced AKT Phosphorylation of Circulating B Cells in Patients With Activated PI3Kδ Syndrome

Activated PI3Kδ syndrome (APDS) is a primary immunodeficiency characterized by recurrent respiratory tract infections, lymphoproliferation, and defective IgG production. Heterozygous mutations in PIK3CD, PIK3R1, or PTEN, which are related to the hyperactive phosphoinositide 3-kinase (PI3K) signaling, were recently presented to cause APDS1 or APDS2 (APDSs), or APDS-like (APDS-L) disorder. In this study, we examined the AKT phosphorylation of peripheral blood lymphocytes and monocytes in patients with APDSs and APDS-L by using flow cytometry. CD19+ B cells of peripheral blood in APDS2 patients showed the enhanced phosphorylation of AKT at Ser473 (pAKT) without any specific stimulation. The enhanced pAKT in CD19+ B cells was normalized by the addition of a p110δ inhibitor. In contrast, CD3+ T cells and CD14+ monocytes did not show the enhanced pAKT in the absence of stimulation. These findings were similarly observed in patients with APDS1 and APDS-L. Among CD19+ B cells, enhanced pAKT was prominently detected in CD10+ immature B cells compared with CD10− mature B cells. Enhanced pAKT was not observed in B cells of healthy controls, patients with common variable immunodeficiency, and hyper IgM syndrome due to CD40L deficiency. These results suggest that the enhanced pAKT in circulating B cells may be useful for the discrimination of APDS1, APDS2, and APDS-L from other antibody deficiencies.The Supplementary Material for this article can be found online at https://www.frontiersin.org/articles/10.3389/fimmu.2018.00568/full#supplementary-material.This study was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (16H05355 and 16K15528 to SO, 17H04233 to SN), the Ministry of Health, Labour and Welfare, Japan (17933299 to SN), and Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development, AMED

A県産業看護職の就労実態と業務及び研修に関する調査研究

A県産業看護職の就労実態、業務および研修状況の把握を目的に、県内産業看護部会員に調査を依頼し、43名の回答を得た。産業看護職の8割は保健師で、企業等に約6割、健診機関等に約4割が勤務していた。企業等では健康管理を中心とした総合的な保健活動が実施され、健診機関等では、健康相談・保健指導・健康教育を主としており、職務内容に違いがあった。職務の違いがあるものの、職場の健康課題や受けたい研修は両者ともメンタルヘルスであった。今後、A産業看護部会では事業所の課題や研修の希望を部会活動に反映させていくことが必要である