著者

中村 和則 城村 綾子 織田 実 猪 好孝 内山 浩之 大谷 尚也 宮崎 裕行 来海 正輝 秋澤 有四郎 岡 俊範

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.115, no.3, pp.201-212, 1995-03-25 (Released:2008-05-30)

参考文献数

28

被引用文献数

3 7

---

Inhibitory activities of FUT-187 on trypsin-like serine proteases were compared using camostat mesilate (camostat), and 4-(4-guanidino benzoyloxy)-phenyl acetic acid methanesulfonate (GBPA) known as an active metabolite of camostat in the blood. Ki values of FUT-187 on the competitive inhibition mechanism were 0.097 μM for trypsin, 0.029 μM for pancreatic kallikrein, 0.61 μM for plasma kallikrein, 0.57 μM for plasmin, 2.5 μM for thrombin, 20.4 μM for factor Xa and 6.4 μM for Clr. However, FUT-187 acted as a noncompetitive inhibitor for factor XIIa and an uncompetitive inhibitor for Cls, and Ki values for these proteases were 0.021 and 0.18 μM, respectively. Ki values of camostat for these proteases were in the range of 0.037 to 96.4 μM, and those of GBPA for the above proteases except trypsin and plasma kallikrein were higher than those of FUT-187. The inhibitory activity of FUT-187 on trypsin was not reduced by the addition of the serum at 10%, whereas, that of GBPA was reduced (4.3 fold) in terms of IC50 values. The concentration of FUT-187 required to double APTT (activated partial thromboplastin time) was 1.09 μM, while GBPA, by concentrations up to 1 mM failed to double APTT. The kinin formation by glandular kallikrein in the rat plasma was inhibited by FUT-187 with IC50 value of 0.024 μM, while camostat revealed no inhibition by concentrations up to 1 μM. The complement-mediated hemolyses in the classical and alternative pathways were also inhibited by FUT-187 with IC50 values of 0.17 and 3.5 μM, respectively, the corresponding values for camostat being 350 and 150 μM, respectively. It is concluded that FUT-187 is a potent and selective inhibitor of trypsin-like serine proteases, and its inhibitory activities are stronger than those of camostat on glandular kallikrein, factor XIIa and Cls in complement pathway.

著者

佐々木 信行 緑川 淳 荒川 勝雅

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.112, no.8, pp.544-550, 1992-08-25 (Released:2008-05-30)

参考文献数

8

---

FUT-187 (I), 6-amidino-2-naphthyl 4-[(4, 5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, is a new synthesized proteinase inhibitor. Decomposition kinetics and photoreactivity of I in aqueous solution were studied. In aqueous solution, I was hydrolyzed to its moieties, [4-(4, 5-dihydro-1H-imidazol-2-yl)amino] benzoic acid (IABA) and 6-amidino-2-naphthol (AN). The hydrolysis followed a pseudo-first order reaction. I was stable under acidic condition between pH 2 and pH 3 and decomposed by irradiation from xenon light to form IABA, AN and compound II. The structure of II was studied by nuclear magnetic resonance, infrared, mass and ultraviolet spectra and identification tests. It was shown that II was 6-amidino-2-hydroxy-1-naphthyl[4-(4, 5-dihydro-1H-imidazol-2-yl)amino]-phenyl ketone, benzophenone derivative, produced by photorearrangement reaction of I.

著者

Satoshi Kodera Hiroyuki Morita Arihiro Kiyosue Jiro Ando Tomoyuki Takura Issei Komuro

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.82, no.10, pp.2602-2608, 2018-09-25 (Released:2018-09-25)

参考文献数

39

被引用文献数

2 12

---

Background: The addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy reduces the rate of cardiovascular events. This study examined the cost-effectiveness of PCSK9 inhibitor+statin compared with standard therapy (statin monotherapy) in the treatment of triple-vessel coronary artery disease (CAD) in Japan. Methods and Results: A Markov model was applied to assess the costs and benefits associated with PCSK9 inhibitor+statin over a projected 30-year period from the perspective of a public healthcare payer in Japan. The incremental cost-effectiveness ratio (ICER), expressed as the quality-adjusted life-years (QALYs), was estimated. The effects on survival and numbers of events were based on the FOURIER trial and the CREDO Kyoto registry. The ICER of PCSK9 inhibitor+statin over standard therapy was 13.5 million (95% confidence interval 7.6–23.5 million) Japanese Yen (JPY) per QALY gained for triple-vessel CAD. The probability of the cost-effectiveness of PCSK9 inhibitor+statin vs. standard therapy was 0.0008% at a cost-effectiveness threshold of 5 million JPY. In patients with poorly controlled familial hypercholesterolemia (FH) with triple-vessel CAD, the ICER was 3.4 million JPY per QALY gained. Conclusions: PCSK9 inhibitor plus statin did not show good cost-effectiveness for triple-vessel CAD; however, it showed good cost-effectiveness for patients with triple-vessel CAD and poorly controlled FH in Japan.

著者

E.C. Pielou

出版者

Wiley

巻号頁・発行日

1984

著者

多比良 和基 安田 行寛 新藤 恭司 三谷 鳴夫 赤沢 明

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.100, no.3, pp.272-279, 1980-03-25 (Released:2008-05-30)

参考文献数

19

被引用文献数

2 2

---

The biological fate of 4-butyl-4-(β-carboxypropionyloxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione : suxibuzone (SB) was studied in rats and beagle dogs. Furthermore, the effects of SB on liver microsomal drug metabolizing enzyme systems in rats were compared with those of phenylbutazone (PB), after daily oral administration of SB or PB for 1 week. 1) The biological fate of SB was different in rats and dogs and in the former a sex difference was noted. 2) Liver microsomal drug metabolizing enzyme systems were induced especially in male. 3) No difference between the two drugs was noted. However, when a single oral dose of SB was administered, keeping the PB schedule the same as above, the plasma half-life of PB was markedly shortened and maximum plasma levels of metabolites were rapidly reached. These results suggest that the biological fate of SB was stimulated by the enhancement or induction of liver microsomal drug metabolizing enzyme systems due to PB and its metabolites after daily oral administration.

著者

新藤 恭司 安田 行寛 多比良 和基 三谷 鳴夫 神田 敦弘 赤沢 明

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.99, no.12, pp.1186-1200, 1979-12-25 (Released:2008-05-30)

参考文献数

20

被引用文献数

4 5

---

The biological fate of 4-butyl-4-(β-carboxypropionyl-oxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione (Suxibuzone, SB) was compared with that of phenylbutazone (PB) in rats, rabbits, beagle dogs and rhesus monkeys. The results obtained were as follows ; 1) When SB was administered orally, the main metabolites in the plasma were PB, oxyphenbutazone (Oxy-PB) and γ-hydroxyphenylbutazone (γ-Hydroxy-PB) in all species, though species differences were observed in the maximum plasma levels of the respective metabolites. Only in dogs and monkeys, was a small amount of SB detected in the plasma during the early time of dosing. 2) The metabolites and their maximum levels in plasma after the administration of SB were almost identical with those observed after the administration of PB. 3) After administration of SB, the main metabolites found in urine were PB, Oxy-PB, γ-Hydroxy-PB and their conjugates in all species, while species differences were observed in the percent excreted. In the dogs and monkeys, urinary excretion as the form of SB and 4-hydroxymethylphenylbutazone (4-HM-PB) glucuronides was observed in small amount for 0-12 hours. 4) There were no significant differences in the metabolites and their excreted percent in urine between SB and PB administration. 5) Differences between male and female in maximum plasma levels of PB and γ-Hydroxy-PB and in urinary excreted percent of γ-Hydroxy-PB were observed only in rats. 6) Species differences were observed in esterase activity on SB in vitro. 7) SB was bound to the albumin fraction as in the case of PB, but its binding percent was about 1/2 lower than that of PB. 8) SB showed anti-edematous action on carrageenin-induced edema and its activity was almost similar to that of PB. Anti-edematous activity of Oxy-PB was weaker than that of SB and γ-Hydroxy-PB had no effect on its action.

著者

大橋 秀行

出版者

日経BP社

雑誌

日経コミュニケーション (ISSN:09107215)

巻号頁・発行日

no.622, pp.8-10, 2015-11-01

---

2015年7月末の着任から間もなく、安倍晋三首相が「家計への負担感が大きい」と指摘した携帯電話料金を見直す政策立案の任を負った。首相の指示は「総務省も検証すべき課題だと捉えていた」と考えの一致を強調する。では現状の何が問題か。

著者

村山 史康 清水 泰子 高木 秀蔵

出版者

公益社団法人 日本水産学会

雑誌

日本水産学会誌 (ISSN:00215392)

巻号頁・発行日

vol.81, no.1, pp.107-114, 2015 (Released:2015-02-02)

参考文献数

42

被引用文献数

5 11

---

海水中の栄養塩濃度と乾海苔単価との関係を調べるため,岡山県ノリ漁場の栄養塩濃度を分析するとともに,色彩色差計を用いて生ノリおよび乾海苔の色調(L∗値と a∗値)を測定し,栄養塩濃度,ノリの色調および乾海苔単価の関係を調べた。その結果,本海域におけるノリの色落ちの原因は DIN であり,濃度が 3 μM 以下になると生ノリの色調が急激に低下することが明らかになった。また,DIN 濃度と生ノリの L∗値と a∗値,生ノリの L∗値および a∗値と乾海苔の L∗値,乾海苔の L∗値と乾海苔単価に有意な相関が見られた。

著者

谷垣 禎一 井上 裕

出版者

日経BP社

雑誌

日経ビジネス (ISSN:00290491)

巻号頁・発行日

no.1323, pp.44-46, 2006-01-09

---

問 企業業績の回復や雇用環境の改善で、民間部門はようやく自力で安定成長を追える状況になってきました。しかし国の財政が悪すぎる。財政は一国の経済の土台です。担当大臣としてどのような現状認識をお持ちですか。 答 2005年度末で国債の発行残高は536兆円に上ります。地方を合わせると700兆円を超える長期債務残高水準は経済協力開発機構(OECD)諸国の中でも一番高い。

著者

景山 孝正 大野 文俊 安田 行寛 新藤 恭司 三谷 鳴夫 丸伝 章 赤沢 明

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.10, no.4, pp.525-533, 1979-12-30 (Released:2010-06-28)

参考文献数

9

被引用文献数

1 1

---

The biological fate of suxibuzone (SB), a new non-steroidal anti-inflammatory agent, was studied in healthy male volunteers with single oral doses and compared with that of phenylbutazone (PB) by a cross-over test, with the following results:1) PB, oxyphenbutazone (Oxy-PB), and γ-hydroxy-phenylbutazone (γ-Hydroxy-PB) were identified in plasma after oral administration of SB. Moreover these metabolites, their glucuronides, SB-glucuronide, 4-hydroxymethyl-phenylbutazone (4-HM-PB)-glucuronide, and p, γ-dihydroxy-phenylbutazone (p, γ-DH-PB) were found in urine.2) Peak plasma concentration of the metabolites was obtained 4 hrs after a single oral dose of 426 mg of SB when the concentration of PB, the main metaboliteof SB, was 36μg/ml, much the same as the corresponding level in the volunteers receiving PB. On the other hand, there was no difference between volunteers receiving SB and PB interms of the concentration of Oxy-PB. But the concentration of γ-Hydroxy-PB was higher after oral SB than after oral PB.3) Urinary excretion of the metabolites was about 8% of the administered dose up to 16 8hrs after oral doses of SB or PB, but in the period shortly after oral doses of SB, Oxy-PB-glucuronide and γ-Hydroxy-PB were excreted to ag reater extent than after oral doses of PB.4) From these results in the plasma and urine after oral doses of SB, it was found that SB may be characterized as a prodrug of PB.5) During the experiment, no side effects or abnormalities were observed in the medical examination and laboratory test except for a slight decrease in the uric acid level in plasma.

著者

Hideki Ishii Toyoaki Murohara

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.82, no.10, pp.2481-2482, 2018-09-25 (Released:2018-09-25)

参考文献数

11

著者

龍 瀟

出版者

京都大学大学院人間・環境学研究科 社会システム研究刊行会

雑誌

社会システム研究 = Socialsystems : political, legal and economic studies (ISSN:13434497)

巻号頁・発行日

vol.18, pp.115-138, 2015-03-27

著者

Hiroyuki Tsutsui Shin-ichi Momomura Yoshihiko Saito Hiroshi Ito Kazuhiro Yamamoto Tomomi Ohishi Naoko Okino Toshihito Kitamura Weinong Guo

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.82, no.10, pp.2575-2583, 2018-09-25 (Released:2018-09-25)

参考文献数

17

被引用文献数

1 15

---

Background: The objective of the present analyses was to describe the baseline characteristics and treatment of the Japanese patients with HFrEF in THE PARALLEL-HF study. Methods and Results: Key demographic, clinical and laboratory findings, along with treatment, were reported and compared with patients enrolled in the PARADIGM-HF trial and other contemporary randomized clinical trials and registries of Japanese patients with HFrEF. In addition, the MAGGIC and EMPHASIS-HF risk scores were calculated. A total of 225 Japanese patients were randomized in PARALLEL-HF with a mean age of 67.9 years and the majority of the patients being male (85.8%) and in NYHA Class II (93.8%). Key baseline characteristics in PARALLEL-HF were generally comparable with PARADIGM-HF, and other contemporary clinical trials and registries of Japanese HFrEF patients. Patients enrolled in PARALLEL-HF were well treated with conventional evidence-based therapy at baseline (angiotensin-converting enzyme inhibitor inhibitor/angiotensin receptor blocker, 62.7%/37.3%; β-blockers, 94.7%; mineralocorticoid receptor antagonist, 59.1%). Despite the evidence-based treatment and most patients being in NYHA Class II, these patients had a low LVEF (mean 28.1%) and were at high risk of cardiovascular mortality and morbidity as assessed by the MAGGIC and EMPHASIS-HF risk scores. Conclusions: Overall, the patients in PARALLEL-HF were largely representative of contemporary ambulatory patients with HFrEF who are well treated with evidence-based therapies. PARALLEL-HF will determine whether sacubitril/valsartan provides similar improvements in clinical outcomes in Japanese HFrEF patients as observed in the PARADIGM-HF study.

著者

橋本 真太郎 杉本 洋平 濱本 昂 石濱 直樹 Hashimoto Shintaro Sugimoto Yohei Hamamoto Ko Ishihama Naoki

出版者

宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)

雑誌

平成29年度 宇宙科学情報解析シンポジウム=Space Science Informatics Symposium FY2017

巻号頁・発行日

2018-02 (Released:2018-02-00)

---

会議情報: 平成29年度宇宙科学情報解析シンポジウム(2018年2月16日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)), 相模原市, 神奈川県 Meeting Information: Space Science Informatics Symposium FY2017 (February 16, 2018. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (JAXA)(ISAS)), Sagamihara, Kanagawa Japan

著者

井沢義雄 著

出版者

弥生書房

巻号頁・発行日

1958

著者

河合 典彦

出版者

エヌ・ティー・エス

雑誌

遺伝 (ISSN:03870022)

巻号頁・発行日

vol.62, no.2, pp.78-83, 2008-03

被引用文献数

2

著者

河合 典彦

出版者

エヌ・ティー・エス

雑誌

遺伝 (ISSN:03870022)

巻号頁・発行日

vol.62, no.3, pp.103-108, 2008-05

被引用文献数

1

著者

小川 力也

出版者

日本魚類学会

雑誌

魚類學雜誌 (ISSN:00215090)

巻号頁・発行日

vol.55, no.2, pp.144-148, 2008-11-25

参考文献数

13

著者

岡崎 登志夫 渡辺 昌和 稲村 修 北川 忠生 田部 雅昭 長田 芳和

雑誌

DNA多型 = DNA polymorphism

巻号頁・発行日

vol.14, pp.276-280, 2006-05-30

参考文献数

11

著者

浅野 竣一

出版者

裳華房

雑誌

遺伝 (ISSN:03870022)

巻号頁・発行日

vol.38, no.12, pp.p53-57, 1984-11