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本研究の目的は，日本的自己観から要介護高齢者の主体性を把握することにより，入所施設の入居者における主体性発揮への支援についての示唆を得ることである。社会福祉分野における主体性は，他者に依存することなく，個人の意思や選択に基づいた判断や決定，行動等，個のありようが重視されていた。一方，日本的自己観に基づいて主体性を把握した場合，日本人の主体性は，他者との関係や，周囲の状況により導かれるものであった。ゆえに，他者からの支援に頼らなければ生活することが困難な入所施設の要介護高齢者の主体性発揮への支援においては，その生活の場における他者との関係や周囲の状況を視野に入れた支援が重要であることが示唆された。, The purpose of this study was to get suggestions on how to support for expressing the resident's initiative in care Homes for the Elderly, by understanding the initiative of the elderly requiring long-term care from the Japanese self-view. Iinitiative in the field of social welfare were emphasized individual behavior such as judgments, decisions, and actions based on individual intentions and choices, without depending on others. On the other hand, when the initiative was grasped based on the Japanese self-view, the initiative of the Japanese was derived from the relation with others and the surrounding situation. Therefore, in support for the initiative of the elderly requiring long-term care in the care Homes, where they cannot live without relying on the support of others, it was shown that there is a need for support that considered the relation with the others and surrounding situation., 論文(Article)

本研究の目的は，要介護高齢者の「生活の場」としての入所施設における，生活支援を通した，利用者の社会関係への支援の意義を明らかにし，生活支援としてのケアワークが，利用者の生活空間や人間関係等の社会関係の拡がりにつながる支援へと発展する可能性を提示することである。現在，入所施設において広く展開されているユニットケアは，利用者を取り巻く社会関係が限定され，また利用者の重度化により，多様な他者とのかかわりや関係が保障される「生活の場」としての課題がある。入所施設の生活支援においては，ケアワークを通して，他利用者や職員との関係やつながりづくりを創出する社会関係への支援の視点が必要である。, The purpose of this study is to clarify the significance of support for social relations of users in living support at the care homes for elderly as a "A place to live a life" for the elderly requiring long-term care, and to show the possibility that care work as living support will develop into support that will lead to the expansion of social relations such as the living space and human relations of users. Currently, unit care, which is widely deployed in care homes for elderly, has limited social relations surrounding users, and the nursing care level is increasing of users.Therefore, there is a issue as a "A place to live a life" that guarantees relations with others. In the living support of the care homes for elderly, it is necessary to have a viewpoint of support for social relations that create relations and connections with other users and care worker through care work., 論文(Article)

Transdermal fentanyl is widely used in the treatment of severe pain because of convenience, safety, and stable blood concentrations. Nevertheless, patients often develop tolerance to fentanyl, necessitating the use of other opioids; transdermal buprenorphine patch is widely used as an analgesic agent, though available formulation does not provide comparable analgesic effect as transdermal fentanyl patch. Opioids bind to the opioid receptor (OR) to activate both G protein-mediated and β-arrestin-mediated pathways. We synthesized morphine-related compounds with high transdermal absorbability (N1 and N2) and evaluated their OR activities pharmacologically in comparison with fentanyl and morphine.In cells stably expressing μ-opioid receptor (MOR), δ-opioid receptor (DOR), and κ-opioid receptor (KOR), G protein-mediated pathways were assessed using the CellKey and an intracellular cyclic adenosine monophosphate (cAMP) assay, while β-arrestin-mediated pathways were analyzed with β-arrestin recruitment and receptor internalization assays. Furthermore, analgesic effects were evaluated using a tail-flick test in mice, and the analgesic effect on fentanyl-tolerant mice was evaluated.In the CellKey and cAMP assays, both N1 and N2 showed the highest affinity for MOR and acted as full agonists as well as partial agonists for DOR and KOR. In the β-arrestin and internalization assays, only fentanyl acted as a full agonist; N1 and N2 acted as partial agonists of MOR. In the mouse tail-flick test, N1 and N2 showed analgesic effects equivalent to those of fentanyl and morphine. In fentanyl-tolerant mice, fentanyl showed a diminished analgesic effect, whereas N1 and N2 as well as morphine retained their analgesic effects.While N1 and N2 have higher transdermal absorbability than fentanyl, they also have analgesic effects comparable to those of morphine, suggesting that they may be attractive compounds for the development of novel opioid patches for transitioning from fentanyl patches.

Activated opioid receptors transmit internal signals through two major pathways: the G-protein-mediated pathway, which exerts analgesia, and the β-arrestin-mediated pathway, which leads to unfavorable side effects. Hence, G-protein-biased opioid agonists are preferable as opioid analgesics. Rubiscolins, the spinach-derived naturally occurring opioid peptides, are selective δ opioid receptor agonists, and their p.o. administration exhibits antinociceptive effects. Although the potency and effect of rubiscolins as G-protein-biased molecules are partially confirmed, their in vitro profiles remain unclear. We, therefore, evaluated the properties of rubiscolins, in detail, through several analyses, including the CellKeyTM assay, cADDis® cAMP assay, and PathHunter® β-arrestin recruitment assay, using cells stably expressing µ, δ, κ, or µ/δ heteromer opioid receptors. In the CellKeyTM assay, rubiscolins showed selective agonistic effects for δ opioid receptor and little agonistic or antagonistic effects for µ and κ opioid receptors. Furthermore, rubiscolins were found to be G-protein-biased δ opioid receptor agonists based on the results obtained in cADDis® cAMP and PathHunter® β-arrestin recruitment assays. Finally, we found, for the first time, that they are also partially agonistic for the µ/δ dimers. In conclusion, rubiscolins could serve as attractive seeds, as δ opioid receptor-specific agonists, for the development of novel opioid analgesics with reduced side effects.

Background The misuse of opioids has led to an epidemic in recent times. The endothelin A receptor (ETAR) has recently attracted attention as a novel therapeutic target to enhance opioid analgesia. We hypothesized that endothelin A receptors may affect pain mechanisms by heterodimerization with μ opioid receptors. We examined the mechanisms of ETAR-mediated pain and the potential therapeutic effects of an ETAR antagonist, Compound-E, as an agent for analgesia. Methods Real-time in vitro effect of Compound-E on morphine response was assessed in HEK293 cells expressing both endothelin A and μ opioid receptors through CellKey™ and cADDis cAMP assays. Endothelin A/μ opioid receptor dimerization was assessed by immunoprecipitation and live cell imaging. The in vivo effect of Compound-E was evaluated using a morphine analgesia mouse model that observed escape response behavior, body temperature, and locomotor activity. Results In CellKey™ and cAMP assays, pretreatment of cells with endothelin-1 attenuated morphine-induced responses. These responses were improved by Compound-E, but not by BQ-123 nor by bosentan, an ETAR and endothelin B receptor antagonist. Dimerization of ETARs and μ opioid receptors was confirmed by Western blot and total internal reflection fluorescence microscopy in live cells. In vivo, Compound-E potentiated and prolonged the analgesic effects of morphine, enhanced hypothermia, and increased locomotor activity compared to morphine alone. Conclusion The results suggest that attenuation by endothelin-1 of morphine analgesia may be caused by dimerization of Endothelin A/μ opioid receptors. The novel ETAR antagonist Compound-E could be an effective adjunct to reduce opioid use.

Opioid agonists elicit their analgesic action mainly via μ opioid receptors; however, their use is limited because of adverse events including constipation and respiratory depression. It has been shown that analgesic action is transduced by the G protein-mediated pathway whereas adverse events are by the β-arrestin-mediated pathway through μ opioid receptor signaling. The first new-generation opioid TRV130, which preferentially activates G protein- but not β-arrestin-mediated signal, was constructed and developed to reduce adverse events. TRV130 and other G protein-biased compounds tend to elicit desirable analgesic action with less adverse effects. In clinical trials, the intravenous TRV130 (oliceridine) was evaluated in Phase I, II and III clinical studies. Here we review the discovery and synthesis of TRV130, its main action as a novel analgesic having less adverse events, its up-to-date status in clinical trials, and additional concerns about TRV130 as demonstrated in the literature.

生活型福祉施設のなかで，ケアワークを通してどのように生活支援が営まれているかを整理し，その上で，生活型福祉施設におけるケアワークの意義や役割の再構築を試みた。生活は，社会関係のうえに成り立つ。ゆえに，生活支援とは，無限の拡がりを持つ社会的関係も支援する必要がある。身体的側面への支援だけでなく，社会的関係の中でケアワークを捉え直すことにより，場に支えられるケアワーク実践の可能性について示唆した。, 論文(Article)