著者

Eikan Mishima Kazuichi Maruyama Toru Nakazawa Takaaki Abe Sadayoshi Ito

出版者

一般社団法人 日本内科学会

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

vol.56, no.13, pp.1687-1690, 2017-07-01 (Released:2017-07-01)

参考文献数

15

被引用文献数

11

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CYP3A4-inhibitors can potentiate the hypotensive effect of calcium-channel blockers. However, insufficient attention to such drug interactions may result in serious adverse reactions. A 71-year-old hypertensive man prescribed nifedipine was hospitalized for infectious endophthalmitis. Antimicrobial therapy with voriconazole lowered the blood pressure, and then clarithromycin further lowered it through the excessively elevated nifedipine concentration, leading to ischemic acute kidney injury. After the discontinuation of clarithromycin and voriconazole, the blood pressure and renal function were recovered. The combination of CYP3A4-inhibitors such as clarithromycin plus voriconazole can synergistically potentiate calcium-channel blockers. Co-prescription of multiple CYP3A4-inhibitors with calcium-channel blockers increases the risk of hypotension and acute kidney injury.

著者

Takehiro Suzuki Hiroaki Yamaguchi Motoi Kikusato Tetsuro Matsuhashi Akihiro Matsuo Takeya Sato Yuki Oba Shun Watanabe Daichi Minaki Daisuke Saigusa Hiroko Shimbo Nobuyoshi Mori Eikan Mishima Hisato Shima Yasutoshi Akiyama Yoichi Takeuchi Akinori Yuri Koichi Kikuchi Takafumi Toyohara Chitose Suzuki Masahiro Kohzuki Jun-ichi Anzai Nariyasu Mano Shigeo Kure Teruyuki Yanagisawa Yoshihisa Tomioka Masaaki Toyomizu Sadayoshi Ito Hitoshi Osaka Ken-ichiro Hayashi Takaaki Abe

出版者

東北ジャーナル刊行会

雑誌

The Tohoku Journal of Experimental Medicine (ISSN:00408727)

巻号頁・発行日

vol.236, no.3, pp.225-232, 2015 (Released:2015-06-26)

参考文献数

27

被引用文献数

2 34

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Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation of apoptosis, and various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress and depletes ATP in a variety of inherited mitochondrial diseases and also in many other metabolic and neurodegenerative diseases. Mitochondrial diseases are characterized by the dysfunction of the mitochondrial respiratory chain, caused by mutations in the genes encoded by either nuclear DNA or mitochondrial DNA. We have hypothesized that chemicals that increase the cellular ATP levels may ameliorate the mitochondrial dysfunction seen in mitochondrial diseases. To search for the potential drugs for mitochondrial diseases, we screened an in-house chemical library of indole-3-acetic-acid analogs by measuring the cellular ATP levels in Hep3B human hepatocellular carcinoma cells. We have thus identified mitochonic acid 5 (MA-5), 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid, as a potential drug for enhancing ATP production. MA-5 is a newly synthesized derivative of the plant hormone, indole-3-acetic acid. Importantly, MA-5 improved the survival of fibroblasts established from patients with mitochondrial diseases under the stress-induced condition, including Leigh syndrome, MELAS (myopathy encephalopathy lactic acidosis and stroke-like episodes), Leber’s hereditary optic neuropathy, and Kearns-Sayre syndrome. The improved survival was associated with the increased cellular ATP levels. Moreover, MA-5 increased the survival of mitochondrial disease fibroblasts even under the inhibition of the oxidative phosphorylation or the electron transport chain. These data suggest that MA-5 could be a therapeutic drug for mitochondrial diseases that exerts its effect in a manner different from anti-oxidant therapy.

著者

Eikan Mishima Naohiko Anzai Mariko Miyazaki Takaaki Abe

出版者

Tohoku University Medical Press

雑誌

The Tohoku Journal of Experimental Medicine (ISSN:00408727)

巻号頁・発行日

vol.251, no.2, pp.87-90, 2020 (Released:2020-06-12)

参考文献数

20

被引用文献数

47 60

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In light of the recent pandemic, favipiravir (Avigan®), a purine nucleic acid analog and antiviral agent approved for use in influenza in Japan, is being studied for the treatment of coronavirus disease 2019 (COVID-19). Increase in blood uric acid level is a frequent side effect of favipiravir. Here, we discussed the mechanism of blood uric acid elevation during favipiravir treatment. Favipiravir is metabolized to an inactive metabolite M1 by aldehyde oxidase and xanthine oxidase, and excreted into urine. In the kidney, uric acid handling is regulated by the balance of reabsorption and tubular secretion in the proximal tubules. Favipiravir and M1 act as moderate inhibitors of organic anion transporter 1 and 3 (OAT1 and OAT3), which are involved in uric acid excretion in the kidney. In addition, M1 enhances uric acid reuptake via urate transporter 1 (URAT1) in the renal proximal tubules. Thus, favipiravir is thought to decrease uric acid excretion into urine, resulting in elevation of uric acid levels in blood. Elevated uric acid levels were returned to normal after discontinuation of favipiravir, and favipiravir is not used for long periods of time for the treatment of viral infection. Thus, the effect on blood uric acid levels was subclinical in most studies. Nevertheless, the adverse effect of favipiravir might be clinically important in patients with a history of gout, hyperuricemia, kidney function impairment (in which blood concentration of M1 increases), and where there is concomitant use of other drugs affecting blood uric acid elevation.

著者

Yuri Sasaki Eikan Mishima Koichi Kikuchi Takafumi Toyohara Takehiro Suzuki Hideki Ota Kazumasa Seiji Mariko Miyazaki Hideo Harigae Sadayoshi Ito Kei Takase Takaaki Abe

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.5290-20, (Released:2020-08-22)

参考文献数

27

被引用文献数

3

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Angioplasty for cases of chronic total occlusion of renal artery with/without atrophic kidney is generally not recommended. We here report a 57-year-old man who presented with renin-mediated refractory hypertension caused by occlusion of a unilateral renal artery leading to kidney atrophy (length: 69 mm). Angioplasty favorably achieved blood pressure control with normalized renin secretion and enlargement of the atrophic kidney to 85 mm. Timely angioplasty can be beneficial in select patients, even with an atrophic kidney and total occlusion, especially in cases with deterioration of hypertension within six months and the presence of collateral perfusion to the affected kidney.

著者

Eikan Mishima Hideki Ota Takehiro Suzuki Takafumi Toyohara Kazumasa Seiji Sadayoshi Ito Yoshikatsu Saiki Kei Takase Takaaki Abe

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.3855-19, (Released:2020-01-17)

参考文献数

21

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We report a case in which diffusion-weighted magnetic resonance imaging (DWI) demonstrated renal artery stenosis-related renal ischemia and the therapeutic efficacy of revascularization. The patient was a 73-year-old man, who underwent descending thoracic aortic replacement due to DeBakey IIIb chronic aortic dissection, and who showed progressive renal dysfunction due to right renal artery stenosis caused by false lumen thrombosis. DWI demonstrated a decreased apparent diffusion coefficient (ADC) in the right kidney, indicating renal ischemia. Angioplasty with stenting restored renal perfusion and improved the renal function, resulting in the normalization of the decreased ADC in the treated kidney. Thus, DWI can be used to monitor renal ischemia in cases involving advanced renal artery stenosis.

著者

Susumu Ogawa Takaaki Abe Kazuhiro Nako Masashi Okamura Miho Senda Takuya Sakamoto Sadayoshi Ito the DIMS study group

出版者

東北ジャーナル刊行会

雑誌

The Tohoku Journal of Experimental Medicine (ISSN:00408727)

巻号頁・発行日

vol.231, no.1, pp.63-74, 2013 (Released:2013-09-25)

参考文献数

37

被引用文献数

4 19

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Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are ω3-polyunsaturated fatty acids mainly contained in the blue-backed fish oil, and are effective in decreasing the lipids disorder and the cardiovascular incidence among diabetic patients. Moreover, it has been suggested that EPA and DHA may improve the insulin resistance and glucose metabolism. However, the clinical effects of EPA and DHA on glucose metabolism remain unclear. We aimed to clarify the effects of EPA/DHA treatment on glycemic control in type 2 diabetes mellitus. This study was a multicenter prospective randomized controlled trial involving 30 elderly type 2 diabetic patients on a liquid diet. Their exercises were almost zero and the content of their meals was strictly managed and understood well. Therefore, the difference by the individual's life was a minimum. The subjects were divided into two groups: those receiving EPA/DHA-rich liquid diet [EPA/DHA (+)] or liquid diet lacking EPA/DHA [EPA/DHA (−)]. Changes in factors related to glucose and lipid metabolism were assessed after the three-month study. Serum concentrations of EPA rose in EPA/DHA (+), although the levels of DHA and fasting C-peptide remained unchanged in EPA/DHA (+). In addition, there was a significant decline in the fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), fasting remnant-like particles and apolipoprotein (apo) B in EPA/DHA (+), compared with the values in EPA/DHA (−). EPA/DHA-rich diet might improve glucose metabolism in elderly type 2 diabetic patients on a liquid diet. This phenomenon may be due to the improved insulin resistance mediated by the rise in serum EPA concentrations.

著者

Takaaki Abe

出版者

The Japanese Society for Mathematical Economics

雑誌

数理経済学会誌 (ISSN:24363162)

巻号頁・発行日

vol.1, pp.38-66, 2022 (Released:2022-03-31)

参考文献数

12

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Hart and Kurz (1983) introduced four stability concepts, called α-, β-, γ-, and δ-stability. In contrast to the intensive studies on their conceptual aspects, these notions have rarely been adopted to analyze stable coalition structures in an application because the definitions consist of multiple intermediate steps. The purpose of this paper is to solve these practical difficulties. We provide an explicit form for each of the four stability concepts and reformulate each concept without using any intermediate steps. Moreover, we offer some sufficient conditions that guarantee the existence of stable coalition structures and the inclusion relation among the four stability notions. In addition, we propose a new approach to characterize the notions of stability. An application of our results to Cournot oligopoly is also provided.