榎木　裕紀 （エノキ　ユウキ）

Enoki, Yuki

写真a

所属（所属キャンパス）

薬学部 薬学科 薬効解析学講座 （芝共立）

職名

専任講師
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  • 「ニガテさん」のための薬物動態

    榎木裕紀、松元一明, じほう, 2021年07月,  ページ数： 230

    担当範囲: 第4章 患者背景によるADMEの変化に注目できる！ー高齢者の薬物動態ー,  担当ページ： 154-161

  • スペシャル・ポピュレーションの抗菌薬投与設計

    榎木裕紀、松元一明, じほう, 2020年07月,  ページ数： 226

    担当範囲: 8.四肢切断患者,  担当ページ： 212-219

  • Molecular mechanism of muscle wasting in CKD

    Watanabe H., Enoki Y., Maruyama T., Recent Advances of Sarcopenia and Frailty in CKD, 2020年01月

    　概要を見る

    Chronic kidney disease (CKD), a chronic catabolic condition, is characterized by muscle wasting and a decreased muscle endurance. Many insights have made into the molecular mechanisms of muscle atrophy in CKD. A persistent imbalance between protein synthesis and degradation causes a loss of muscle mass. A decrease in insulin/IGF-1-Akt-mTOR signaling and an increased ubiquitin-proteasome system (UPS) have emerged as inducers of muscle loss. During muscle wasting, abnormal levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in skeletal muscle. These increased ROS and inflammatory cytokine levels induce the expression of myostatin. The binding of myostatin to its receptor ActRIIB stimulates the expression of Foxo-dependent atrogenes. An impaired mitochondrial function also contributes to reduced muscle endurance. Increased glucocorticoid, angiotensin II, parathyroid hormone, and protein-bound uremic toxin levels that are observed in CKD all have a negative effect on muscle mass and endurance. The loss of skeletal muscle mass during the progression of CKD further contributes to the development of renal failure. Some potential therapeutic approaches based on the molecular mechanisms of muscle wasting in CKD are currently in the testing stages using animal models and clinical settings.

  • Uremic Solutes and Sarcopenia

    Watanabe H., Kato H., Enoki Y., Maeda H., Maruyama T., Uremic Toxins and Organ Failure, 2020年01月

    　概要を見る

    Sarcopenia in chronic kidney disease (CKD) is characterized by muscle wasting and decreased muscle endurance. Many insights have been made into the molecular mechanisms of muscle atrophy in CKD. A persistent imbalance between protein synthesis and degradation causes a loss of muscle mass. A decrease in insulin/IGF-1-Akt-mTOR signaling and an increased ubiquitin–proteasome system have emerged as inducers of muscle loss. During muscle wasting, abnormal levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in skeletal muscle. The increased ROS and inflammatory cytokine induce the expression of myostatin, a negative regulator of muscle growth. An impaired mitochondrial function also contributes to reduced muscle endurance. Uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and parathyroid hormone have a negative effect on muscle mass and endurance by affecting protein synthesis and degradation in addition to mitochondrial function in skeletal muscle. Some potential therapeutic approaches based on the molecular mechanisms of muscle wasting in CKD are currently in the testing stages.

  • 調剤と情報-高齢者の低栄養と薬-

    榎木 裕紀松元　一明, じほう, 2018年10月

    担当範囲: 高齢者が低栄養になるとどうなる？-体内動態の変化と服薬上のリスク-

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  • Predictive Value of Vancomycin AUC<inf>24</inf>/MIC Ratio for 30-day Mortality in Patients with Severe or Complicated Methicillin-Resistant Staphylococcus aureus Infections: A Multicenter Retrospective Study

    Hanai Y., Hashi H., Hanawa K., Endo A., Miyazaki T., Yamaguchi T., Harada S., Yokoo T., Uekusa S., Namiki T., Yokoyama Y., Asakawa D., Isoda R., Enoki Y., Taguchi K., Matsumoto K., Matsuo K.

    Pharmaceutical Research 41 （ 7 ） 1381 - 1389 2024年07月

    ISSN  07248741

    　概要を見る

    Background: Although vancomycin is typically employed against methicillin-resistant Staphylococcus aureus (MRSA) infections, the optimal ratio of 24-h area under the concentration–time curve to minimum inhibitory concentration (AUC24/MIC) for severe or complicated infections lacks clear guideline recommendations. This study aimed to determine the target AUC24/MIC ratio associated with treatment outcomes of infections treated with vancomycin. Methods: This retrospective multicenter cohort study included adult patients receiving ≥ 5 days of vancomycin for severe/complicated MRSA infections (e.g., osteoarticular, pulmonary, endocarditis, etc.) between January 2018 and December 2023. The primary outcome was 30-day mortality, with secondary outcomes including clinical success, microbiological eradication, and nephrotoxicity. Receiver operating characteristic (ROC) curve analysis was used to identify the AUC24/MIC cutoff for 30-day mortality. Multivariate regression analysis was used to determine association between AUC24/MIC and outcomes. Results: This study included 82 patients. ROC identified a target AUC24/MIC of ≥ 505 for 30-day mortality. The overall 30-day mortality rate (22.0%) was significantly higher for below average AUC24/MIC cutoff (34.1%) than for above AUC24/MIC cutoff group (9.8%). Multivariate analysis confirmed AUC24/MIC of < 505 as an independent predictor (adjusted odds ratio, 5.001; 95% confidence interval, 1.335–18.75). The clinical success rate differed significantly between below- and above-cutoff groups, whereas microbiological eradication tended to favor the above-cutoff group. The nephrotoxicity rates were comparable between groups. Conclusions: In treating severe/complicated MRSA infections, vancomycin AUC24/MIC ratio ≥ 505 was independently associated with favorable 30-day mortality. Given the retrospective nature of this study, further prospective studies are essential to confirm the reliability of the target AUC24/MIC ratios.

  • Relationship between nephrotoxicity and area under the concentration-time curve of vancomycin in critically ill patients: a multicenter retrospective study

    Ishigo T., Matsumoto K., Yoshida H., Tanaka H., Ibe Y., Fujii S., Fukudo M., Fujihara H., Yamaguchi F., Ebihara F., Maruyama T., Hamada Y., Samura M., Nagumoi F., Komatsu T., Tomizawa A., Takuma A., Chiba H., Nishi Y., Enoki Y., Taguchi K., Suzuki A.

    Microbiology Spectrum 12 （ 7 ） e0373923 2024年07月

    ISSN  2165-0497

    　概要を見る

    We aimed to assess the frequency of acute kidney injury (AKI) in differentareas under the concentration-time curve (AUC) values of vancomycin (VAN) using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. This multicenter retrospective observational study was conducted in eight hospitals. We retrospectively analyzed the data of patients who had received VAN in an intensive care unit (ICU) between January 2020 and December 2022. The primary outcome was the incidence of AKI. Patients were classifiedinto three groups according to the AUC24-48h at the initial therapeutic drug monitoring (TDM) as follows: <500, 500-600, and ≥600 μg h/mL. The AUC24-48h values were calculated using the Bayesian estimation software Practical AUC-guided TDM. Among 146 patients [median age (interquartile range), 67 (56-78) years; 39% women], the AUC24-48h <500 μg h/mL had an AKI rate of 6.5% (7/107), the AUC24-48h 500-600 μg h/mL had an AKI rate of 28.0% (7/25), and the AUC24-48h ≥600 μg h/mL had an AKI rate of 42.9% (6/14). In multivariate Cox proportional hazard analysis, the AUC24-48h 500-600 μg h/mL [hazard ratio 5.4, 95% confidenceinterval (CI) 1.64-17.63] and the AUC24-48h ≥600 μg h/mL (hazard ratio 7.0, 95% CI 2.31-21.18) significantlycorrelated with a higher incidence of AKI compared with the AUC24-48h <500 μg h/mL. In conclusion, we identifiedan association between AUC on day 2 and the risk of AKI in ICU patients, suggesting that not only AUCs above 600 μg h/mL but also those between 500 and 600 μg h/mL pose a risk for AKI.

  • Anti-edematous effects of epinastine, cetirizine and its enantiomers in λ-carrageenan-induced edema in rat hind paw

    Taguchi K., Chuang V.T.G., Ozawa M., Sakamoto Y., Hara R., Iketani O., Enoki Y., Kizu J., Hori S., Matsumoto K.

    Pharmazie 79 （ 6 ） 98 - 100 2024年06月

    ISSN  00317144

    　概要を見る

    Urticaria is induced by the histamine released from mast cells which develops wheals (edema) as a visual feature. In clinical practice, second-generation histamine H1-receptor blockers are routinely used as the first-line symptomatic treatment for urticaria. Nevertheless, not much research has directly examined the second-generation histamine H1-receptor blockers’ ability to reduce edema. In this study, we directly evaluated the anti-edematous activities of three second-generation histamine H1-receptor blockers available in the market (epinastine hydrochloride, cetirizine hydrochloride, and levocetirizine hydrochloride) using a λ-carrageenan-induced footpad edema model. One hour before the induction of edema with 1% λ-carrageenan injection, all second-generation histamine H1-receptor blockers (5, 10, 50 and 100 mg/kg) were subcutaneously administered to rats. At 0.5 and 3 hours after λ-carrageenan administration, the edema volume was evaluated using a Plethysmometer. Epinastine hydrochloride significantly suppressed the edema growth in a dose-dependent manner. Cetirizine hydrochloride showed a slight anti-edematous effect, while levocetirizine significantly inhibited the development of edema in a dose-dependent manner. On the other hand, dextrocetirizine did not prevent edema from growing. In summary, second-generation histamine H1-receptor blockers, at least those examined in this study, may be able to reduce the clinical symptoms of urticaria associated with edema. Levocetirizine hydrochloride is also anticipated to have stronger anti-edematous effects than cetirizine hydrochloride because levocetirizine is responsible for cetirizine’s anti-edematous activity.

  • Dual delivery of carbon monoxide and doxorubicin using haemoglobin-albumin cluster: proof of concept for well-tolerated cancer therapy

    Ito C., Taguchi K., Yamada T., Hanaya K., Enoki Y., Sugai T., Komatsu T., Matsumoto K.

    Journal of Materials Chemistry B 12 （ 23 ） 5600 - 5608 2024年05月

    ISSN  2050750X

    　概要を見る

    A serious concern of doxorubicin (DOX) therapy is that it causes severe adverse effects, particularly cardiotoxicity. Carbon monoxide (CO) possesses powerful cytoprotective effects against drug-induced organ injury and is expected to ameliorate DOX-induced cardiotoxicity. In this study, a dual carrier of DOX and CO (CO-HemoAct-DOX) was fabricated based on a haemoglobin-albumin cluster (HemoAct), which is a protein cluster with a haemoglobin core structure wrapped by serum albumin. CO-HemoAct-DOX was synthesised by binding CO to a haemoglobin core and covalently conjugating (6-maleimidocaproyl)hydrazone derivative of DOX to an albumin shell. The average DOX/cluster ratio was about 2.6. In the in vitro cytotoxicity assay against cancer cells, the anti-tumour activity of CO-HemoAct-DOX was 10-fold lower than that of DOX in a 2D-cultured model, whereas CO-HemoAct-DOX suppressed the growth of tumour spheroids to the same extent as DOX in the 3D-cultured model. In colon-26 tumour-bearing mice, CO-HemoAct-DOX achieved DOX delivery to the tumour site and alleviated tumour growth more effectively than DOX. Furthermore, CO-HemoAct attenuated DOX-induced cardiomyocyte atrophy in H9c2 cells and elevated the levels of cardiac biomarkers in mice exposed to DOX. These results suggest that the dual delivery of CO and DOX using HemoAct is a promising strategy as an anti-tumour agent to realise well-tolerated cancer therapy with minimal cardiotoxicity.

  • Direct comparison of anti-inflammatory effects of 14-, 15-, and 16-membered macrolide antibiotics in experimental inflammation model induced by carrageenan in rats

    Taguchi K., Chuang V.T.G., Ogino H., Hara R., Iketani O., Enoki Y., Kizu J., Hori S., Matsumoto K.

    Pharmazie 79 （ 3-5 ） 64 - 66 2024年05月

    ISSN  00317144

    　概要を見る

    Some macrolide antibiotics, which share a basic lactone ring structure, also exhibit anti-inflammatory actions in addition to their antibacterial activities. However, no study has directly compared anti-inflammatory effects on acute inflammation among macrolide antibiotics with the distinct size of the lactone ring. In this study, we evaluated and compared the anti-inflammatory activities of four 14-membered macrolides (erythromycin, clarithromycin, roxithromycin, oleandomycin), one 15-membered macrolide (azithromycin), and three 16-membered macrolides (midecamycin, josamycin, leucomycin) using a rat carrageenan-induced footpad edema model. All macrolide antibiotics were intraperitoneally administered to rats one hour before the induction of inflammatory edema with 1% λ-carrageenan. The anti-inflammatory effects on acute inflammation were evaluated by changing the edema volume. All 14-membered and 15-membered macrolide antibiotics significantly suppressed the development of edema. Conversely, none of the 16-membered macrolide antibiotics inhibited the growth of edema. In conclusion, compared to 16-membered macrolide antibiotics, 14-membered and 15-membered macrolide antibiotics have stronger anti-inflammatory effects. Further research should be done to determine why different lactone ring sizes should have distinct anti-inflammatory effects.

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  • <i>Clostridioides difficile</i>に対する治療薬の<i>in vitro</i>抗菌活性評価及び<i>Clostridioides difficile</i>感染症マウスモデルでの糞中濃度測定

    田代 渉, 水上 雄貴, 榎木 裕紀, 田口 和明, 松元 一明

    日本薬理学会年会要旨集 （公益社団法人 日本薬理学会）  95 （ 0 ） 1-YIA-30 2022年

    　概要を見る

    <p><b>[Background, Purpose]</b> Metronidazole (MNZ), vancomycin (VCM), and fidaxomicin (FDX) are standard therapeutic drugs against <i>Clostridioides difficile</i> infection (CDI). MNZ resulted in lower clinical cure rate compared with VCM. Detail information about antibacterial activities of the drugs and reasons for MNZ inferiority are not clear. Therefore, we evaluated the <i>in vitro</i> antibacterial activities, and measured fecal concentrations in CDI mouse models. </p><p><b>[Method] </b>Minimum inhibitory concentration (MIC) against seven strains of <i>C. difficile</i> were determined. Time-kill curves and post-antibiotic effect (PAE) were determined against <i>C. difficile</i> ATCC<sup>®</sup>43255. In addition, fecal concentrations in CDI mouse models were measured. </p><p><b>[Results] </b>MNZ, VCM, and FDX geometric mean MIC were 0.91, 1.81, and 0.34 µg/mL, respectively. MNZ exhibited concentration-dependent and rapid antibacterial activities at low concentrations ranged from 0.5 to 2.0 µg/mL. On the other hands, VCM and FDX exhibited time-dependent and slow antibacterial activities at high concentrations ranged from 0.5 to 32 µg/mL.<b> </b>MNZ showed the shortest PAE (1.9 h).<b> </b>In addition, maximal fecal concentration of MNZ (21.7 µg/g) was significantly lower than that of VCM (222.7 µg/g) at the dose of 40 mg/kg. </p><p><b>[Conclusion] </b>MNZ exhibited noteworthy antibacterial activities against <i>C. difficile</i>. However, MNZ PAE was short, and the fecal exposure was significantly small. We think the two characteristics are responsibility for the MNZ inferiority in clinical cure rate.</p>

  • フルコナゾールの血中濃度が定常状態に達するまでに時間を要した移植後患者の一例

    坂本 靖宜, 松元 一明, 磯野 ひかる, 小池 博文, 榎木 裕紀, 田口 和明, 萩原 真紀, 松本 憲二, 中島 秀明, 佐橋 幸子

    日本薬理学会年会要旨集 （公益社団法人 日本薬理学会）  93 （ 0 ） 2 - O-036 2020年

    その他, 共著

    　概要を見る

    <p>[Introduction]</p><p>Fluconazole is anti-fungal agent widely used to prophylaxis and treatment. In the ECIL6 Guidelines, it is recommended that the dose of FLCZ for treatment should be established as ≥10 to 15 mg/mL, which is a trough level. We report a patient in whom a specific interval was required until the blood concentration of FLCZ reached a steady state.</p><p>[Case]</p><p>The patient was a 50-year-old male. To treat acute lymphocytic leukemia, remission induction and consolidation therapies were performed. After remission was achieved, umbilical cord blood transplantation was conducted. On Day 18, graft survival was confirmed. A blood culture test on Day 27 detected yeast-like fungus. Micafungin (MCFG) at 150 mg, used for empiric therapy, was switched to liposomal amphotericin B (L-AMB) at 3 mg/kg. On Day 36, renal hypofunction was noted, and L-AMB was switched to MCFG at 150 mg. On Day 65, there was a decrease in the β-D-glucan level from ≥600 to 375.2 pg/mL, and MCFG at 150 mg was switched to FLCZ at 200 mg. On Day 71, the trough level of FLCZ was 21.0 mg/mL, and its concentration 2 hours after administration was 24.4 mg/mL. The β-D-glucan level was 232.1 pg/mL. On Day 79, the trough and 2-hour levels of FLCZ were 30.6 and 32.1 mg/mL, respectively, and the β-D-glucan level was 167.6 pg/mL. On Day 85, the trough level of FLCZ was 38.4 mg/mL, and the β-D-glucan level was 161.4 pg/mL. Subsequently, blood culture was negative, and FLCZ administration was continued until Day 229. During the administration period, the creatinine clearance ranged from 33.0 to 45.9 mL/min.</p><p>[Discussion]</p><p>The half-life of FLCZ is approximately 30 hours. Its clearance depends on the renal function. In the present case, a target trough level was achieved in the early phase, but the blood concentration of FLCZ increased with the prolongation of the administration period. Therefore, the appearance of central nervous toxicity must be considered. In the future, it may be necessary to establish individualized, optimized FLCZ dosimetry in accordance with the renal function for the optimal use of FLCZ.</p>

  • Factorial Analysis of <i>Clostridioides Difficile</i> Colitis and Pseudomembranous Colitis Using JADER

    Takaya Risako, Misawa Kana, Tashiro Sho, Enoki Yuki, Taguchi Kazuaki, Matsumoto Kazuaki

    BPB Reports （公益社団法人 日本薬学会）  3 （ 1 ） 1 - 6 2020年

    その他, 共著

    　概要を見る

    <p><i>Clostridioides difficile</i> (<i>C</i>. <i>difficile</i>) colitis and pseudomembranous colitis are known as healthcare-associated intestinal infections. In this study, the incidence of <i>C. difficile</i> colitis and pseudomembranous colitis was investigated using the Japanese Adverse Drug Event Report (JADER). Using JADER data between April 2004 and September 2017, the patient who developed <i>C. difficile</i> colitis and pseudomembranous colitis were investigated. During the study period, 375 cases of <i>C. difficile</i> colitis and 903 cases of pseudomembranous colitis were reported. The numbers of reported cases of both <i>C. difficile</i> colitis and pseudomembranous colitis were largest in those in their 70s, accounting for 24.7% and 25.6%, respectively. Patients in their 60s-90s comprised the majority of all patients with both <i>C. difficile</i> colitis and pseudomembranous colitis. Both <i>C. difficile</i> colitis and pseudomembranous colitis were caused by antibiotics in many patients, and signals of all antibiotics were detected. In <i>C. difficile</i> colitis, signals of immunosuppressants, corticosteroids, and alkylating drugs were also detected among drugs other than antibiotics. For pseudomembranous colitis, the use of molecularly targeted drugs, antimetabolic drugs, and corticosteroids was reported other than antibiotics. Using JADER, we revealed risk factors for the development of <i>C. difficile</i> colitis and pseudomembranous colitis, and firstly revealed that molecularly targeted drugs other than antibiotics could also be potential risk factors. Our findings may be useful for the early detection of drug-induced <i>C. difficile</i> colitis and pseudomembranous colitis.</p>

  • 土-P2-280 異常ファーマコキネティクスを示したフェニトイン投与患者における要因解析(TDM・投与設計,ポスター発表,一般演題,再興、再考、創ろう最高の医療の未来)

    平田 憲史郎, 猿渡 淳二, 渡邊 博志, 丸山 徹, 福永 栄子, 岩田 一史, 浦田 由紀乃, 四郎園 巧, 上田 賢太郎, 合澤 啓二, 陣上 祥子, 榎木 裕紀, 前田 仁志

    日本医療薬学会年会講演要旨集 （一般社団法人 日本医療薬学会）  23 （ 0 ） 298 2013年

    その他, 共著

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  • 成熟したバンコマイシンのAUC評価　腎長・腎容積を用いた腎機能評価に基づくバンコマイシン適正使用の検討

    枦 秀樹, 並木 孝哉, 横山 雄太, 榎木 裕紀, 松元 一明

    日本化学療法学会雑誌, 

    2024年01月
    , 

    (公社)日本化学療法学会

  • 成熟したバンコマイシンのAUC評価　腎長・腎容積を用いた腎機能評価に基づくバンコマイシン適正使用の検討

    枦 秀樹, 並木 孝哉, 横山 雄太, 榎木 裕紀, 松元 一明

    感染症学雑誌, 

    2024年01月
    , 

    (一社)日本感染症学会

  • 好中球減少マウス大腿部腸球菌感染モデルを用いたバンコマイシンのPK/PD評価

    佐々木 萌, 劉 小茜, 榎木 裕紀, 田口 和明, 松元 一明

    日本化学療法学会雑誌, 

    2024年01月
    , 

    (公社)日本化学療法学会

  • 同種造血幹細胞移植後にポサコナゾール腸溶錠の血中濃度が低値を示した一例

    島村 千陽, 坂本 靖宜, 長谷川 拓也, 榎木 裕紀, 田口 和明, 松元 一明

    日本化学療法学会雑誌, 

    2024年01月
    , 

    (公社)日本化学療法学会

  • バンコマイシン投与で2点採血を実施した患者における1点採血と2点採血の比較

    鈴木 絢子, 佐村 優, 石郷 友之, 伊部 裕太, 相神 智宏, 吉田 博昭, 田中 宏明, 海老原 文哉, 丸山 拓実, 南雲 史雄, 小松 敏彰, 冨澤 淳, 千葉 博暁, 詫間 章俊, 榎木 裕紀, 田口 和明, 浜田 幸宏, 西 圭史, 藤居 賢, 松元 一明, 山口 史博, 藤原 久登

    日本化学療法学会雑誌, 

    2024年01月
    , 

    (公社)日本化学療法学会

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  • 骨格筋由来エクソソームによるサルコペニア合併敗血症増悪機序の解明

    2022年04月
    -
    2025年03月

    科学研究費助成事業, 榎木 裕紀, 若手研究, 未設定

    　研究概要を見る

    サルコペニア(骨格筋の萎縮)を有する患者では、敗血症や感染症の予後が不良であることが知られている。最近になり、骨格筋が感染症病態時に免疫調節作用に関与していることが報告されているが、その詳細な制御機構は未だ不明である。近年、エクソソームと呼ばれる細胞から分泌される小胞が臓器間のコミュニケーション因子として注目されており、疾患との関わりも報告されている。本研究ではサルコペニアによる敗血症増悪機序として骨格筋由来のエクソソームを介した免疫機構に及ぼす影響ついて検証することを目的としている。

  • 筋作動因子-尿毒症物質クロストークを標的としたCKD誘発サルコペニアの治療戦略

    2018年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 榎木　裕紀, 若手研究, 補助金,  研究代表者

    　研究概要を見る

    本研究は、慢性腎臓病誘発サルコペニアにおける筋作動因子および尿毒症物質のプロファイルによる病態構造を基盤としたサルコペニアの予防・診断ならびに新規治療戦略を構築するための基盤的情報を明らかにすることである。そのため、本年は、慢性腎臓病誘発サルコペニアモデルマウスを用いて、骨格筋萎縮病態形成の経過について検討し、それに伴う筋作動因子の変動について検討した。慢性腎臓病モデル作製後、4、8、12週と経過するに伴い、体重、腓腹筋、前脛骨筋、ヒラメ筋の重量が減少した。また骨格筋萎縮関連遺伝子である、atrogin-1遺伝子発現は増加し、骨格筋断面積も減少した。顕著な差は12週から認められたものの、8週目においても上述した筋萎縮関連因子の変動が認められた。また骨格筋ミトコンドリア活性を指標としたコハク酸デヒドロゲナーゼ染色による筋線維タイプの検討において、モデルの経過に従い、ミトコンドリア活性の低下が観察された。慢性腎臓病によって持続的にサルコペニア病態が誘導されていることを確認した。そこで骨格筋における各種筋作動因子の発現について評価した。骨格筋の萎縮や筋タンパク分解との関与が報告されているmyostatinは、経月的に増加していた。しかし炎症因子であるmif発現に変動は認められなかった。一方、骨格筋肥大との関連が報告されている筋作動因子であるirisinについては8週目において一過性の上昇が観察されたものの、12週においては減少していた。また筋肥大作用を有する成長因子であるigf-1に変化はみられなかった。
    慢性腎臓病誘発サルコペニアモデルの作製に成功し、それに伴う筋作動因子の発現について検討できている。すでに尿毒症物質を吸着する活性吸着炭（AST-120）を用いた検討を進めており、今後経過について評価する予定である。以上のことから概ね順調に進展している。
    今後は、現在進行中である慢性腎臓病誘発サルコペニアモデルに対するAST-120投与による筋作動因子への影響について評価を行う。また2次性副甲状腺機能亢進症（SHPT）モデルの作製とSHPT治療薬の筋作動因子の発現に及ぼす影響について検討を進める。In vitro培養細胞を用いた検討により尿毒症物質が筋作動因子発現に及ぼす影響とその発現機序について検討を進める。

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