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
2

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 11

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
Shinichi Kuriyama Nobuo Yaegashi Fuji Nagami Tomohiko Arai Yoshio Kawaguchi Noriko Osumi Masaki Sakaida Yoichi Suzuki Keiko Nakayama Hiroaki Hashizume Gen Tamiya Hiroshi Kawame Kichiya Suzuki Atsushi Hozawa Naoki Nakaya Masahiro Kikuya Hirohito Metoki Ichiro Tsuji Nobuo Fuse Hideyasu Kiyomoto Junichi Sugawara Akito Tsuboi Shinichi Egawa Kiyoshi Ito Koichi Chida Tadashi Ishii Hiroaki Tomita Yasuyuki Taki Naoko Minegishi Naoto Ishii Jun Yasuda Kazuhiko Igarashi Ritsuko Shimizu Masao Nagasaki Seizo Koshiba Kengo Kinoshita Soichi Ogishima Takako Takai-Igarashi Teiji Tominaga Osamu Tanabe Noriaki Ohuchi Toru Shimosegawa Shigeo Kure Hiroshi Tanaka Sadayoshi Ito Jiro Hitomi Kozo Tanno Motoyuki Nakamura Kuniaki Ogasawara Seiichiro Kobayashi Kiyomi Sakata Mamoru Satoh Atsushi Shimizu Makoto Sasaki Ryujin Endo Kenji Sobue the Tohoku Medical Megabank Project Study Group Masayuki Yamamoto
出版者
日本疫学会
雑誌
Journal of Epidemiology (ISSN:09175040)
巻号頁・発行日
pp.JE20150268, (Released:2016-07-02)
参考文献数
64
被引用文献数
1 28

The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members. The TMM CommCohort Study will recruit participants from 2013 to 2016 and follow them for at least 5 years. The TMM BirThree Cohort Study will recruit participants from 2013 to 2017 and follow them for at least 4 years. For children, the ToMMo Child Health Study, which adopted a cross-sectional design, was also started in November 2012 in Miyagi Prefecture. An integrated biobank will be constructed based on the two prospective cohort studies, and ToMMo and IMM will investigate the chronic medical impacts of the GEJE. The integrated biobank of TMM consists of health and clinical information, biospecimens, and genome and omics data. The biobank aims to establish a firm basis for personalized healthcare and medicine, mainly for diseases aggravated by the GEJE in the two prefectures. Biospecimens and related information in the biobank will be distributed to the research community. TMM itself will also undertake genomic and omics research. The aims of the genomic studies are: 1) to construct an integrated biobank; 2) to return genomic research results to the participants of the cohort studies, which will lead to the implementation of personalized healthcare and medicine in the affected areas in the near future; and 3) to contribute the development of personalized healthcare and medicine worldwide. Through the activities of TMM, we will clarify how to approach prolonged healthcare problems in areas damaged by large-scale disasters and how useful genomic information is for disease prevention.
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 9

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
Akira Sugawara Akira Uruno Masataka Kudo Ken Matsuda Chul Woo Yang Sadayoshi Ito
出版者
The Japan Endocrine Society
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.57, no.10, pp.847-852, 2010 (Released:2010-10-30)
参考文献数
37
被引用文献数
28 29

Peroxisome proliferator-activated receptor (PPAR) γ is a nuclear hormone receptor that is trans-activated by its ligands including insulin-sensitizing thiazolidinediones. PPARγ has recently been reported to demonstrate pleiotropic beneficial effects in the vasculatures, independent of its blood glucose-lowering effects. Firstly, PPARγ ligands have been shown to lower blood pressure in both animals and human. The effect may possibly be mediated via the PPARγ-mediated inhibition of the angiotensin (Ang) II type 1 receptor expression as well as Ang II-mediated signaling pathways, which may result in the suppression of the renin-angiotensin system (RAS). Secondly, the progression of atherosclerosis was also prevented by PPARγ ligands in both animals and human. In addition to the PPARγ-mediated suppression of the RAS and the thromboxane A2 system, protective effects of PPARγ ligands on endothelial function may also be involved. Thirdly, reno-protective effects of PPARγ ligands, especially on reducing urinary albumin, have been observed in both animals and human not only in diabetic nephropathy but also in non-diabetic renal diseases. The reno-protective effects may be mediated, at least in part, via the PPARγ ligand-induced blood pressure-lowering effects, protective effects on endothelial function, and vasodilating effects on the glomerular efferent arterioles. Additionally, anti-cancer effects of PPARγ ligands have recently been reported. Taken together, usefulness and effectiveness of PPARγ ligands on lifestyle related diseases will be increasingly appreciated.
著者
Masahiro Nezu Masataka Kudo Ryo Morimoto Yoshikiyo Ono Kei Omata Yuta Tezuka Yasuhiro Igarashi Shin Hitachi Kei Takase Sadayoshi Ito Fumitoshi Satoh
出版者
The Japan Endocrine Society
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ18-0108, (Released:2018-07-13)

Acromegalic arthropathy is a common complication of acromegaly and harms the quality of life of the patients even after acromegaly is in long-term remission. A recent study demonstrated by knee MRI the characteristic structural features of acromegalic arthropathy. However, the effects of treatment for acromegaly on such structural features are almost unknown. This study was undertaken to analyze the effects of transsphenoidal surgery (TSS) on acromegalic arthropathy and elucidate whether knee MRI findings are reversible or irreversible. We analyzed 22 patients with acromegaly (63.7% females, median age 58 years) by knee MRI at diagnosis. Out of these 22 patients, 16 who underwent TSS (68.9% female, median age 58 years) were also subjected to knee MRI 2 months after TSS. As for X-ray undetectable findings, MRI detected synovial thickening, bone marrow lesion, ligament injury and meniscus injury in 22.7%, 22.7%, 4.7% and 59.1% of the patients, respectively. With respect to the 16 patients who underwent TSS, clinical and structural improvements were observed respectively in 100%, 66.7% and 66.7% of the patients who showed knee joint pain, synovial thickening and bone marrow lesion before TSS. However, no patient showed structural improvement of meniscus injury after TSS. In acromegalic arthropathy, synovial thickening and bone marrow lesions are reversible while meniscus injury is irreversible. Because all those findings are associated with the exacerbation of arthropathy, they may be therapeutic targets for preventing the progression of arthropathy by endocrinological and orthopedic intervention.
著者
Keisuke Nakayama Masaaki Nakayama Hiroyuki Terawaki Yaeko Murata Toshinobu Sato Masahiro Kohno Sadayoshi Ito
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.34, no.6, pp.699-702, 2009-12-01 (Released:2009-12-01)
参考文献数
13
被引用文献数
5 8

Carbonated soft drinks reportedly contain methylglyoxal (MG), which is strongly associated with human carbonyl stress. We sought to evaluate the effects of carbonated drink intake on human carbonyl stress. We measured MG levels in 4 commercial beverage brands, and evaluated the changes in plasma MG in healthy subjects following the intake of carbonated drinks. By 30 min after intake of samples containing high glucose and high MG, the levels of plasma MG, glucose, insulin and uric acid had increased significantly, and then returned to basal levels by 120 min. After intake of the low-calorie carbonated samples containing little MG, there were no increases in plasma MG. Our results suggest that glucose-containing carbonated soft drinks are associated with increases in not only glucose but also carbonyl burden.