ラット膵腫瘍モデルにおけるSN-38含有ミセル型ナノ粒子を用いた動注療法

Purpose To evaluate advantages of micellar nanoparticles encapsulating SN-38, a biologically active metabolite of irinotecan, in intraarterial therapy for pancreatic cancer. Materials and Methods Rat pancreatic cancer cells (DSL-6A/C1) were implanted in Lewis rats under laparotomy. This study consists of two parts. Firstly, after confirming tumor formation by ultrasonography, celiac arteriography was performed, and tumor blood supply was visually evaluated by dye injection and CT during arteriography. Secondly, 18 rats were divided into two groups; the Micellar Nanoparticles group and the Irinotecan Infusion group. Micellar nanoparticles or irinotecan was injected via the celiac artery, and SN-38 and irinotecan concentrations in the tumor, duodenum and pancreatic parenchyma, were measured at 5 min, 6 h and 24 h. Results The maximum concentration (Cmax) of SN-38 were shown at 6 h in the Micellar Nanoparticles group, while Cmax of irinotecan was shown at 5 min in the Irinotecan Infusion group. Tumor concentration in the Micellar Nanoparticles group maintained elevated for 24 h without significant decrease (P = 0.068). Conversely, a significant decrease was observed in the regular pancreas parenchyma (P = 0.006) and duodenum (P = 0.028). In the Irinotecan Infusion group, tumor irinotecan concentration significantly decreased at 24 h (P = 0.016). Conclusion Micellar nanoparticles may improve arterial infusion chemotherapy for pancreatic cancer. These nanoparticles have the potential to reduce SN-38 accumulation in duodenum, while increasing it in the tumor. Further research is warranted to validate and expand upon these findings.権利情報：© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 202

トホグリフロジンは肝硬変ラットにおける類洞毛細血管化を抑制することで門脈圧亢進症を抑制する

Background: Liver cirrhosis leads to portal hypertension (PH) with capillarization of liver sinusoidal endothelial cells (LSECs), although drug treatment options for PH are currently limited. Sodium glucose transporter 2 inhibitors, which are antidiabetic agents, have been shown to improve endothelial dysfunction. We aimed to elucidate the effect of tofogliflozin on PH and liver fibrosis in a rat cirrhosis model. Methods: Male-F344/NSlc rats repeatedly received carbon tetrachloride (CCl4 ) intraperitoneally to induce PH and liver cirrhosis alongside tofogliflozin (10 or 20 mg/kg). Portal hemodynamics and hepatic phenotypes were assessed after 14 weeks. An in vitro study investigated the effects of tofogliflozin on the crosstalk between LSEC and activated hepatic stellate cells (Ac-HSC), which are relevant to PH development. Results: Tofogliflozin prevented PH with attenuated intrahepatic vasoconstriction, sinusoidal capillarization, and remodeling independent of glycemic status in CCl4-treated rats. Hepatic macrophage infiltration, proinflammatory response, and fibrogenesis were suppressed by treatment with tofogliflozin. In vitro assays showed that tofogliflozin suppressed Ac-HSC-stimulated capillarization and vasoconstriction in LSECs by enhancing the antioxidant capacity, as well as inhibited the capilliarized LSEC-stimulated contractive, profibrogenic, and proliferative activities of Ac-HSCs. Conclusions: Our study provides strong support for tofogliflozin in the prevention of liver cirrhosis-related PH.権利情報：© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)

卵巣癌の予後予測マーカーとしての組織経路インヒビター2 の有用性についての検討

Abstract. Tissue factor pathway inhibitor‑2 (TFPI2) is a tumor marker for diagnosing ovarian cancer and ovarian clear cell carcinoma (OCCC); however, its effectiveness as a prognostic marker remains unclear. The present study aimed to investigate the utility of TFPI2 as a prognostic marker for ovarian cancer. A total of 256 cases of ovarian cancer was collected at Nara Medical University (Kashihara, Japan) from January 2008 to January 2022. The majority of cases were serous carcinoma (109, 42.6%), followed by OCCC (66, 25.8%), mucinous carcinoma (40, 15.6%), endometrial carcinoma (15, 5.9%), and other (26, 10.2%). The median preoperative serum TFPI2 for ovarian cancer was 219.0 (82.5‑5,824.2) pg/ml. Overall survival (OS) of patients with non‑OCCC and OCCC was calculated using the cut‑off value determined obtained through receiver operating characteristic curve analysis. Cut‑off values of TFPI2 for OS were 201 for non‑OCCC and 255 pg/ml for OCCC. In univariate analysis, OS was significantly elevated in patients with non‑OCCC and OCCC who had TFPI2 levels ≥201 pg/ml (P<0.001) and ≥255 pg/ml (P=0.036), respectively. Progression‑free survival (PFS) was significantly elevated in patients with non‑OCCC and OCCC who had TFPI2 levels ≥201 and ≥255 pg/ml (both P<0.001), respectively. Multivariate analysis revealed that OS was significantly higher in patients with non‑OCCC who had TFPI2 levels ≥201 pg/ml (P=0.021), while PFS was significantly higher in patients with OCCC who had TFPI2 levels ≥255 pg/ml (P=0.020). These findings suggest that TFPI2 is a potential prognostic marker for ovarian carcinoma.権利情報：© Maehana et al. This is an open access article distributed under the terms of Creative Commons Attribution License

加齢がマウスの耳石器の形態と機能に与える影響について

Background: Increased fall risk caused by vestibular system impairment is a significant problem associated with aging. A vestibule is composed of linear acceleration-sensing otoliths and rotation-sensing semicircular canals. Otoliths, composed of utricle and saccule, detect linear accelerations. Otolithic organs partially play a role in falls due to aging. Aging possibly changes the morphology and functions of otoliths. However, the specific associations between aging and otolith changes remain unknown. Therefore, this study aimed to clarify these associations in mice. Methods: Young C56BL/6 N (8 week old) and old (108–117 weeks old) mice were used in a micro-computed tomography (μCT) experiment for morphological analysis and a linear acceleration experiment for functional analysis. Young C56BL/6 N (8 week old) and middle-aged (50 week old) mice were used in electron microscopy experiments for morphological analysis. Results: μCT revealed no significant differences in the otolith volume (p = 0.11) but significant differences in the otolith density (p = 0.001) between young and old mice. μCT and electron microscopy revealed significant differences in the structure of striola at the center of the otolith (μCT; p = 0.029, electron microscopy; p = 0.017). Significant differences were also observed in the amplitude of the eye movement during the vestibulo-ocular reflex induced by linear acceleration (maximum amplitude of stimulation = 1.3G [p = 0.014]; maximum amplitude of stimulation = 0.7G [p = 0.015]), indicating that the otolith function was worse in old mice than in young mice. Discussion: This study demonstrated the decline in otolith function with age caused by age-related morphological changes. Specifically, when otolith density decreased, inertial force acting on the hair cells decreased, and when the structure of striola collapsed, the function of cross-striolar inhibition decreased, thereby causing a decline in the overall otolith function.権利情報：© 2024 Ueda, Imai, Ito, Okayasu, Harada, Kamakura, Ono, Katsuno, Tanaka, Tatsumi, Hibino, Wanaka and Kitahara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

MgO添加β-TCPはin vitroおよびin vivoのラットモデルにおいて骨形成を促進する

Allogeneic bone grafts are used to treat bone defects in orthopedic surgery, but the osteogenic potential of artificial bones remains a challenge. In this study, we developed a β-tricalcium phosphate (β-TCP) formulation containing MgO, ZnO, SrO, and SiO2 and compared its bone-forming ability with that of β-TCP without biological　elements. We prepared β-TCP discs with 60% porosity　containing 1.0 wt% of these biological elements. β-TCP scaffolds were loaded with bone marrow-derived mesenchymal stem cells (BMSC) from 7-week-old male rats and cultured for 2 weeks. ALP activity and mRNA expression of osteogenic markers were evaluated. In addition, scaffolds were implanted subcutaneously in rats and analyzed after 7 weeks. In vitro, the MgO group showed lower Ca concentrations and higher osteogenic marker expression compared to controls. In vivo, the MgO group showed higher ALP activity compared to controls, and RT-qPCR analysis showed significant expression of BMP2 and VEGF. Histopathology, fluorescent immunostaining, and micro-CT also showed relatively better bone formation in the MgO group. β-TCP with MgO may enhance bone morphology in vitro and in vivo and improve the prognosis of patients with substantial and refractory bone defects.権利情報：© The Author(s) 2024. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/

β-ヒドロキシ酪酸はラットにおける血液暴露に起因する関節障害の病理学的変化を抑制する

Arthropathy is a common complication in haemophilia and decreases quality of life. It has been known that concentrations of β-hydroxybutyrate (BHB) in blood are increased by a ketogenic diet, and elevated levels of circulating BHB restricts the progression of inflammation-mediated joint pathological changes. We hypothesized that elevation of blood BHB concentrations could be effective for reducing the progression of bleeding-induced arthropathy by moderating the inflammatory responses of macrophages. In this study, we investigated whether BHB alleviates the arthropathy caused by repeated intra-articular blood injection in rats. To increase blood BHB levels, rats were fed with ketogenic diet. Repeated intra-articular blood injection induced significant joint swelling, whereas ketogenic diet intake significantly increased blood BHB concentrations and ameliorated the joint swelling. The periarticular tissue-fibrosis observed in the control diet intake group appeared to be significantly alleviated in the ketogenic diet intake group. In addition, the IL-1β, which is involved in the progression of arthropathy, levels in the supernatants of blood-exposed macrophages derived from THP-1 cell line were significantly suppressed by BHB supplementation. In summary, BHB moderated the pathological joint changes caused by intra-articular blood exposure.権利情報：© The Author(s) 2024. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

The Progress and Future Directions in Support for Persons with Mental Disorder

精神に障害がある人への支援の動向として、精神医療政策の転換により、地域生活支 援が重視され、看護師の役割は病院内のケアから訪問看護やデイケアなど地域支援へと拡 大した。支援の中心となる概念のリカバリー志向が日本でも活用されるようになり、患者 の自己決定や社会的役割の再構築が目指されている。また、多職種連携による包括的支援 が進んできた。COVID-19の影響により患者の治療やケアにおいてテクノロジーが進展 し、新たな治療やケア手法が導入されている。一方、精神に障害がある人への支援者の人 材確保や精神看護教育では人材育成の課題が指摘される。国際的には、地域ケアやデジタ ル技術を活用した支援が進展しているが、日本では患者の長期入院の問題や支援者の倫理 的問題の課題が指摘されている。今後日本において、地域ケアやテクノロジー活用がさら に進み、精神看護の実践は新たなステージに入ると予測される。その中で看護師は、柔軟 な思考と高い専門性を発揮し続ける必要がある

頚髄圧迫を診断する身体所見の正診度と信頼性についての横断的研究

Introduction: Cervical myelopathy diagnosis is based on specific symptoms, physical signs, and imaging findings. However, information on the accuracy and reliability of physical signs, particularly the Wartenberg reflex and the finger escape sign (FES), is lacking. Therefore, this study aimed to assess the validity and reliability of the Hoffmann and Trömner signs, FES, Wartenberg reflex, and combination of any one positive of these four physical signs. Methods: We reviewed the Hoffmann and Trömner signs, FES, and Wartenberg reflex from the medical records of patients with cervical cord compression who underwent surgery. We included those who underwent lumbar spine surgery as controls, except those with upper extremity symptoms or a history of cerebrospinal disease. Subsequently, we calculated the sensitivity and specificity of cervical cord compression. The primary and secondary observers performed two and one trial, respectively, to measure the intra- and interobserver reliabilities. Results: This study included 46 cases and 42 controls. The diagnostic sensitivities for the Hoffmann sign, Trömner sign, Wartenberg reflex, FES, and combination of any one positive were 46%, 72%, 63%, 22%, and 83%, respectively; the diagnostic specificities were 98%, 79%, 95%, 98%, and 79%, respectively; the intraobserver kappa value (κ) was 0.80, 0.82, 0.86, 0.66, and 0.95, respectively; and the interobserver κ was 0.84, 0.51, 0.51, −0.02, and 0.60, respectively. Notably, all κ values, except the interobserver κ for the FES, were obtained with P<0.01. Conclusions: Each physical sign had high specificity but low sensitivity in predicting cervical cord compression. Therefore, they may be useful for definitive diagnosis but not for screening tests. The combination of the four physical signs exhibited improved sensitivity and may be useful for screening tests. However, the results of these physical signs should be carefully interpreted owing to the low level of interobserver reliability.権利情報：© 2025 The Japanese Society for Spine Surgery and Related Research. SSRR is an Open Access journal distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Anyone may download, reuse, copy, reprint, or distribute articles published in the journal for not-for-profit purposes if they cite the original authors and source properly. If you remix, transform, or build upon the material, you may not distribute the modified material. https://creativecommons.org/licenses/by-nc-nd/4.0