研究者詳細 - 座間味　義人

論文 - 座間味　義人

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循環器疾患治療薬の相互作用とポリファーマシー高齢者の薬物療法管理ツールを活用した薬剤業務の効率化

泉侑希, 石田俊介, 長谷川結美, 武智研志, 合田光寛, 座間味義人, 桐野靖, 中村敏己, 寺岡和彦, 八木秀介, 佐田政隆, 石澤啓介

日本循環器学会学術集会抄録集 84回チーム医療シンポジウム3 - 5 2020年7月

【薬物動態・薬物相互作用・薬物アレルギーから最適化スペシャル・ポピュレーションの抗菌薬投与設計】(第3章)特殊病態の患者敗血症患者

中馬真幸, 岡田直人, 武智研志, 合田光寛, 近藤正輝, 座間味義人, 楊河宏章, 石澤啓介

薬事 62 ( 10 ) 2048 - 2055 2020年7月

血液凝固因子製剤の在庫適正化に向けた取り組みによる薬剤廃棄額の削減効果

岡田直人, 神農麻里奈, 中村信元, 三木浩和, 渡辺浩良, 合田光寛, 中馬真幸, 武智研志, 座間味義人, 桐野靖, 中村敏己, 寺岡和彦, 安倍正博, 石澤啓介

日本病院薬剤師会雑誌 56 ( 7 ) 803 - 808 2020年7月

循環器疾患治療薬の相互作用とポリファーマシー高齢者の薬物療法管理ツールを活用した薬剤業務の効率化

泉侑希, 石田俊介, 長谷川結美, 武智研志, 合田光寛, 座間味義人, 桐野靖, 中村敏己, 寺岡和彦, 八木秀介, 佐田政隆, 石澤啓介

日本循環器学会学術集会抄録集 84回チーム医療シンポジウム3 - 5 2020年7月

特殊病態・母集団における体内動態からみた抗菌薬投与設計の最適化敗血症における抗菌薬投与設計の最適化に向けて

中馬真幸, 武智研志, 座間味義人, 合田光寛, 岡田直人, 近藤正輝, 石澤啓介, 楊河宏章

日本化学療法学会雑誌 68 ( 3 ) 419 - 419 2020年5月

特殊病態・母集団における体内動態からみた抗菌薬投与設計の最適化敗血症における抗菌薬投与設計の最適化に向けて

中馬真幸, 武智研志, 座間味義人, 合田光寛, 岡田直人, 近藤正輝, 石澤啓介, 楊河宏章

感染症学雑誌 94 ( 3 ) 380 - 380 2020年5月

Fibroblast-specific ERK5 deficiency changes tumor vasculature and exacerbates tumor progression in a mouse model. 査読国際誌

Masaki Imanishi, Yusuke Yamakawa, Keijo Fukushima, Raiki Ikuto, Akiko Maegawa, Yuki Izawa-Ishizawa, Yuya Horinouchi, Masateru Kondo, Masatoshi Kishuku, Mitsuhiro Goda, Yoshito Zamami, Kenshi Takechi, Masayuki Chuma, Yasumasa Ikeda, Koichiro Tsuchiya, Hiromichi Fujino, Koichi Tsuneyama, Keisuke Ishizawa

Naunyn-Schmiedeberg's archives of pharmacology 393 ( 7 ) 1239 - 1250 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The roles of cancer-associated fibroblasts (CAFs) have been studied in the tumor progression, and CAFs are expected to become the new targets for cancer pharmacotherapies. CAFs contribute to tumor cell survival and proliferation, tumor angiogenesis, immune suppression, tumor inflammation, tumor cell invasion and metastasis, and extracellular matrix remodeling. However, detailed mechanisms of how CAFs function in the living system remain unclear. CAFs include α-smooth muscle actin, expressing activated fibroblasts similar to myofibroblasts, and are highly capable of producing collagen. Several reports have demonstrated the contributions of extracellular-signal-regulated kinase 5 (ERK5) in fibroblasts to the fibrotic processes; however, the roles of CAF-derived ERK5 remain unclear. To investigate the roles of CAF-derived ERK5 in the tumor progression, we created mice lacking the ERK5 gene specifically in fibroblasts. Colon-26 mouse colon cancer cells were implanted into the mice subcutaneously, and the histological analyses of the tumor tissue were performed after 2 weeks. Immunofluorescence analyses showed that recipient-derived fibroblasts existed within the tumor tissue. The present study demonstrated that fibroblast-specific ERK5 deficiency exacerbated tumor progression and it was accompanied with thicker tumor vessel formation and the increase in the number of activated fibroblasts. We combined the results of The Cancer Genome Atlas (TCGA) database analysis with our animal studies, and indicated that regulating ERK5 activity in CAFs or CAF invasion into the tumor tissue can be important strategies for the development of new targets in cancer pharmacotherapies.

DOI： 10.1007/s00210-020-01859-5

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薬物療法にかかわる副作用マネジメントのエビデンス確立に向けて薬剤師が実践する向精神薬の副作用対策に向けた臨床研究についてエビデンスをもった効率的な副作用マネジメントを目指して

武智研志, 石田俊介, 坂東寛, 中馬真幸, 座間味義人, 合田光寛, 石澤啓介, 楊河宏章

日本病院薬剤師会雑誌 56 ( 4 ) 373 - 376 2020年4月

シスプラチン誘発性腎障害を予防する既存薬物の同定

濱野裕章, 合田光寛, 座間味義人, 石澤啓介, 池田康将, 堀ノ内裕也, 福島圭穣, 藤野裕道, 岸誠司, 武智研志, 中馬真幸, 宮本理人, 土屋浩一郎, 玉置俊晃

四国医学雑誌 76 ( 1-2 ) 116 - 117 2020年4月

シスプラチン誘発腎障害に対する新規予防薬の探索とその有効性の検証

前川晃子, 吉田愛美, 村井陽一, 新村貴博, 座間味義人, 石澤啓介, 合田光寛, 神田将哉, 濱野裕章, 岡田直人, 石澤有紀, 中馬真幸, 武智研志, 堀ノ内裕也, 池田康将

四国医学雑誌 76 ( 1-2 ) 116 - 116 2020年4月

血管平滑筋細胞石灰化シグナルにおけるRhoキナーゼ-サイクロフィリンA経路の関与

津田達也, 橋本一郎, 堀ノ内裕也, 池田康将, 石澤有紀, 合田光寛, 座間味義人, 石澤啓介

四国医学雑誌 76 ( 1-2 ) 119 - 119 2020年4月

Antibiotic prescriptions for Japanese outpatients with acute respiratory tract infections (2013-2015): A retrospective Observational Study. 査読国際誌

Toshihiro Koyama, Hideharu Hagiya, Yusuke Teratani, Yasuhisa Tatebe, Ayako Ohshima, Mayu Adachi, Tomoko Funahashi, Yoshito Zamami, Hiroyoshi Y Tanaka, Ken Tasaka, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 26 ( 7 ) 660 - 666 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Appropriate antibiotic prescriptions for outpatients with acute respiratory tract infections (ARTIs) are urgently needed in Japan. However, the empirical proof of this need is under-documented. Therefore, we aimed to determine antibiotic prescription rates, and the proportions of antibiotic classes prescribed for Japanese patients with ARTIs. METHODS: We analysed health insurance claims data over 2013-2015 among Japanese patients aged <75 years and determined the following indicators: 1) visit rates for patients with ARTIs and antibiotic prescription rates per 1000 person-years, and 2) proportion of visits by antibiotic-prescribed patients with ARTIs. We defined broad-spectrum antibiotics using the WHO Anatomical Therapeutic Chemical classification 4 level codes. RESULTS: Among 8.65 million visits due to ARTIs at 6859 hospitals and 62,024 physicians' offices, the visit rate and antibiotic prescription rate per 1000 person-years were 990.6 (99% confidence interval [CI], 989.4-991.7) and 532.4 (99% CI, 531.6-533.3), respectively. The visit rates for patients aged 0-17, 18-59, and 60-74 years were 2410.0 (99% CI, 2407.2-2412.9), 683.6 (99% CI, 682.7-684.6), and 682.1 (99% CI, 678.2-686.0), and antibiotic prescription rates were 1093.3 (99% CI, 1091.4-1095.2), 434.1 (99% CI, 433.4-434.9), and 353.4 (99% CI, 350.7-356.1), respectively. The overall proportion of antibiotic prescriptions for ARTI visits was 52.7% and 91.3% of the antibiotics prescribed were broad-spectrum. CONCLUSIONS: Both the visit rates and antibiotic prescription rates for ARTIs were high in this Japanese cohort. The proportion of antibiotic prescriptions exceeded that recommended in the clinical guidelines. Thus, there might be a scope for reducing the current antibiotic prescription rate in Japan.

DOI： 10.1016/j.jiac.2020.02.001

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Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells. 査読

Tatsuya Tsuda, Masaki Imanishi, Mizuho Oogoshi, Mitsuhiro Goda, Yoshitaka Kihira, Yuya Horinouchi, Yoshito Zamami, Keisuke Ishizawa, Yasumasa Ikeda, Ichiro Hashimoto, Toshiaki Tamaki, Yuki Izawa-Ishizawa

Journal of pharmacological sciences 142 ( 3 ) 109 - 115 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Arterial calcification, a risk factor of cardiovascular events, develops with differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Cyclophilin A (CypA) is a peptidyl-prolyl isomerase involved in cardiovascular diseases such as atherosclerosis and aortic aneurysms, and rho-associated protein kinase (ROCK) is involved in the pathogenesis of vascular calcification. CypA is secreted in a ROCK activity-dependent manner and works as a mitogen via autocrine or paracrine mechanisms in VSMCs. We examined the involvement of the ROCK-CypA axis in VSMC calcification induced by inorganic phosphate (Pi), a potent cell mineralization initiator. We found that Pi stimulated ROCK activity, CypA secretion, extracellular signal-regulated protein kinase (ERK) 1/2 phosphorylation, and runt-related transcription factor 2 expression, resulting in calcium accumulation in rat aortic smooth muscle cells (RASMCs). The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation. Recombinant CypA was found to be associated with increased calcium accumulation in RASMCs. Based on these results, we suggest that autocrine CypA is mediated by ROCK activity and is involved in Pi-induced ERK1/2 phosphorylation following calcification signaling in RASMCs.

DOI： 10.1016/j.jphs.2019.12.005

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日本における副作用に起因した死亡率の傾向に関する全国規模の観察研究

船橋智子, 小山敏広, 萩谷英大, 原田洸, 寺谷祐亮, 座間味義人, 建部泰尚, 三上奈緒子, 大島礼子, 四宮一昭, 北村佳久, 千堂年昭, 樋之津史郎, 狩野光伸

日本薬学会年会要旨集 140年会 28X - am11 2020年3月

第4回病院薬剤師が実践するリバーストランスレーショナルリサーチの最前線〜臨床薬剤師の視点から新たな薬物療法を提案する〜医療ビッグデータ解析と基礎研究を融合したオキサリプラチン誘発末梢神経障害に対する予防薬探索

合田光寛, 座間味義人, 新村貴博, 川尻雄大, 武智研志, 中馬真幸, 萱野純史, 濱野裕章, 岡田直人, 小林大介, 島添隆雄, 石澤有紀, 石澤啓介

日本薬学会年会要旨集 140年会 S37 - 3 2020年3月

Trends in Place of Death in a Super-Aged Society: A Population-Based Study, 1998-2017. 査読国際誌

Toshihiro Koyama, Hideharu Hagiya, Tomoko Funahashi, Yoshito Zamami, Miyu Yamagishi, Hiroshi Onoue, Yusuke Teratani, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Journal of palliative medicine 23 ( 7 ) 950 - 956 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background:
Globally, the number of deaths is estimated to increase to 74 million per year by 2030. Place of death (PoD) is increasingly being recognized as an important aspect of end-of-life care. However, recent trends in PoD in Japan, one of the super-aged societies, are unknown.
Objective:
To analyze trends in PoD in Japan over two decades.
Design:
Population-based retrospective observational study.
Setting:
All deaths reported in Japan, 1998-2017. PoD was defined as hospital, nursing home, or own home.
Results:
All Japanese decedents (∼22.6 million) over the past 20 years were analyzed. The proportion of hospital deaths was consistently high (>80%), with a significant decreasing trend from the mid-2000s. Although the proportion of deaths at home decreased in the first half of the study period, they later increased. There was a low proportion of deaths in nursing homes compared to other places of death; however, the proportion increased continually throughout the study period, particularly among women. In 2015, more women died in nursing homes than at home. Although the proportion of hospital deaths declined in the second half of the study period, their overall number continued to increase, reflecting an increase in total deaths in Japan.
Conclusions:
This study highlighted rapid changes in trends in PoD in Japan, and the need to consider affordable end-of-life care in Japan as well as other countries with aging populations. The findings from this long-term epidemiological study provide important insights on this issue.

DOI： 10.1089/jpm.2019.0445

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Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. 査読国際誌

Hirofumi Hamano, Takahiro Niimura, Yuya Horinouchi, Yoshito Zamami, Kenshi Takechi, Mitsuhiro Goda, Masaki Imanishi, Masayuki Chuma, Yuki Izawa-Ishizawa, Licht Miyamoto, Keijo Fukushima, Hiromichi Fujino, Koichiro Tsuchiya, Keisuke Ishizawa, Toshiaki Tamaki, Yasumasa Ikeda

Toxicology letters 318 86 - 91 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Proton pump inhibitors (PPIs) have been used worldwide to treat gastrointestinal disorders. A recent study showed that long-term use of PPIs caused iron deficiency; however, it is unclear whether PPIs affect iron metabolism directly. We investigated the effect of PPIs on the peptide hepcidin, an important iron regulatory hormone. First, we used the FDA Adverse Event Reporting System database and analyzed the influence of PPIs. We found that PPIs, as well as H2 blockers, increased the odds ratio of iron-deficient anemia. Next, HepG2 cells were used to examine the action of PPIs and H2 blockers on hepcidin. PPIs augmented hepcidin expression, while H2 blockers did not. In fact, the PPI omeprazole increased hepcidin secretion, and omeprazole-induced hepcidin upregulation was inhibited by gene silencing or the pharmacological inhibition of the aryl hydrocarbon receptor. In mouse experiments, omeprazole also increased hepatic hepcidin mRNA expression and blood hepcidin levels. In mice treated with omeprazole, protein levels of duodenal and splenic ferroportin decreased. Taken together, PPIs directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation. These findings provide a new insight into the molecular mechanism of PPI-induced iron deficiency.

DOI： 10.1016/j.toxlet.2019.10.016

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Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases. 査読国際誌

Hiromi Hagiwara, Hidekatsu Fukuta, Takahiro Niimura, Yoshito Zamami, Keisuke Ishizawa, Kazunori Kimura, Takeshi Kamiya, Nobuyuki Ohte

International journal of medical sciences 17 ( 6 ) 728 - 733 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Prasugrel inhibits platelet aggregation more potently and exerts therapeutic action faster than clopidogrel. In the global phase III trial conducted in Western and South American countries that excluded Asian countries, prasugrel reduced ischemic events but increased hemorrhagic risk compared with clopidogrel in patients with acute coronary syndrome scheduled for percutaneous coronary intervention. In the Japanese phase III trial for similar patients, the efficacy of prasugrel compared with clopidogrel was comparable to the global trial, but the safety could not be confirmed because of an insufficient number of patients. Furthermore, given the strict enrollment criteria, the results of these trials may not be applicable to routine clinical practice. Accordingly, we compared the hemorrhagic risk of prasugrel and clopidogrel in real-world settings by analyzing adverse drug event reports in post-marketing stages provided by the Japanese regulatory authorities and the U.S. Food and Drug Administration (FDA). Methods: We analyzed a total of 3,970 reports for prasugrel (n = 518) or clopidogrel (n = 3,452) between 2014 and 2017 in the Japanese Adverse Drug Event Report (JADER) and a total of 91,914 reports for either prasugrel (n = 5,992) or clopidogrel (n = 85,922) between 2009 and 2019 in the FDA Adverse Event Reporting System (FAERS). Results: In JADER and FAERS, prasugrel was more frequently and significantly associated with hemorrhagic event reports than clopidogrel. After adjustment for known confounders including age, sex, and concomitant medications (aspirin, anticoagulants, and proton pump inhibitors), the hemorrhagic risk of prasugrel compared with clopidogrel remained significant (adjusted reporting odds ratios [95% CI] for total, intracranial, and gastrointestinal hemorrhagic events = 2.42 [1.97-2.96], 2.45 [1.85-3.24], and 2.27 [1.73-2.97] in JADER, and 2.21 [2.09-2.34], 1.21 [1.09-1.33], and 1.41 [1.29-1.54] in FAERS). Conclusions: The hemorrhagic risk was found to be greater with prasugrel than clopidogrel in real-world patients, including Japanese patients.

DOI： 10.7150/ijms.43168

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シスプラチン腎障害における鉄依存性細胞死の検討

池田康将, 濱野裕章, 堀ノ内祐也, 合田光寛, 座間味義人, 宮本理人, 石澤啓介, 土屋浩一郎

日本薬理学会年会要旨集 93 2 - O-060 2020年

記述言語：日本語出版者・発行元：公益社団法人日本薬理学会

Background: Ferroptosis has been identified as iron-dependent regulated cell death, and it participates with a various disorder including kidney disease. Cisplatin, a classical anti-cancer drug, causes nephrotoxicity, which is inhibited by iron chelator. In the present study, we examined the involvement of ferroptosis on cisplatin-induced nephrotoxicity.Methods: We used male mice with cisplatin-induced nephrotoxicity that were pretreated with vehicle or a ferroptosis inhibitor. Mice were sacrificed at 48 hours later. Results: Cisplatin administration actually augmented ferrous iron and hydroxyl radical production in the kidney. Cisplatin-induced COX-2 expression, as well as lipid peroxide, was increased by cisplatin-treated kidney. An inhibitor of ferroptosis also suppressed cisplatin-induced increased of COX-2 expression and lipid peroxide. Mice with cisplatin administration developed kidney injury with renal dysfunction, and showed augmented oxidative stress, increased apoptosis, and elevated inflammatory cytokines. However, most of these symptoms were suppressed by a ferroptosis inhibitor.Conclusion: Ferroptosis is suggested to involve cisplatin-induced nephrotoxicity.

DOI： 10.1254/jpssuppl.93.0_2-O-060

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Place of death trends among patients with dementia in Japan: a population-based observational study. 査読国際誌

Toshihiro Koyama, Misato Sasaki, Hideharu Hagiya, Yoshito Zamami, Tomoko Funahashi, Ayako Ohshima, Yasuhisa Tatebe, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Scientific reports 9 ( 1 ) 20235 - 20235 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Dementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged ≥65 years and died during 1999-2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999-2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia.

DOI： 10.1038/s41598-019-56388-w

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