Pharmacology

kazunao kondo

  (近藤 一直)

Profile Information

Affiliation
School of Medicine; Faculty of Medicine; Department of Pharmacology, Fujita Health University
Degree
医学博士(浜松医科大学)

J-GLOBAL ID
200901020441806220
researchmap Member ID
1000195073

Major Papers

 58
  • Yui Suganuma, Chiho Sumi-Ichinose, Taiki Kano, Kazuhisa Ikemoto, Taei Matsui, Hiroshi Ichinose, Kazunao Kondo
    Journal of Pharmacological Sciences, 150 173-179, Jun, 2022  Peer-reviewedLast authorCorresponding author
  • Chiho Sumi-Ichinose, Yui Suganuma, Taiki Kano, Kazuhisa Ikemoto, Noriko Ihira, Hiroshi Ichinose, Kazunao Kondo
    Journal of Inherited Metabolic Disease, 45(3) 621-634, Feb, 2022  Peer-reviewedLast author
  • Kazuhisa Ikemoto, Chiho Sumi-Ichinose, Yui Suganuma, Taiki Kano, Noriko Ihira, Toshiharu Nagatsu, Kazunao Kondo
    The Journal of Biochemistry, 170(4) 559-567, Dec 4, 2021  Peer-reviewedLast author
    <title>Abstract</title> Neopterin (NP), biopterin (BP) and monapterin (MP) exist in saliva. The physiological role of salivary NP as well as the pathophysiological role of increased NP in the immune-activated state has been unclear. Saliva is a characteristic specimen different from other body fluids. In this study, we analysed salivary NP and related pterin compounds, BP and MP and revealed some of its feature. High-performance liquid chromatography (HPLC) analysis of saliva and plasma obtained from 26 volunteers revealed that salivary NP existed mostly in its fully oxidized form. The results suggested that salivary NP as well as BP would mostly originate from the oral cavity, perhaps the salivary glands, and that salivary NP levels might not reflect those in the plasma. We also found that a gender difference existed in correlations between concentrations of salivary total concentrations of NP (tNP) and BP (tBP). HPLC analysis of saliva obtained from 5 volunteers revealed that the concentrations of salivary tNP as well as tBP fluctuated in an irregular fashion in various individuals. MP, a diastereomer of NP, might have come from oral cavity NP itself or its precursor. These results indicated that the nature of salivary NP might be different from that of NP in the blood or urine.
  • Taiki Kano, Kazunao Kondo, Jiharu Hamako, Fumio Matsushita, Kazuya Sakai, Taei Matsui
    International Journal of Hematology, 1-6, Apr 4, 2018  Peer-reviewed
    Von Willebrand factor (VWF) is one of the plasma protein carrying ABO(H) blood group antigens, but the combining process of these antigens is not clear. In the present study, we examined whether plasma glycosyltransferase affects the blood group antigens on VWF. VWF expressing H-antigen (H-VWF) from blood group O and bovine serum albumin conjugated with H-antigen (H-BSA) were incubated with recombinant α1-3-N-acetylgalactosaminyltransferase (rA-transferase) and A-plasma with or without an additional UDP-GalNAc. Transformed antigens were detected by western blotting and ELISA, using an anti-A antibody. Both H-VWF and H-BSA acquired the A-antigen after incubation with rA-transferase and UDP-GalNAc. Incubation with A-plasma very weakly converted the H-antigen on BSA and VWF to A-antigen only in the presence of supplemented UDP-GalNAc. This conversion was enhanced on desialylation of H-VWF. These results indicate that sugar chains of plasma VWF can be modified by the external glycosyltransferase, but that plasma glycosyltransferase has no effect on the blood group antigens of VWF due to its low activity and the lack of donor sugars. Further, sialic acid residues of VWF may exert a protective effect against post-translational glycosylation. Our results clearly exclude the possibility that blood group antigens of VWF are constructed extracellularly in plasma.
  • Sumi-Ichinose C, Suganuma Y, Kano T, Ihira N, Nomura H, Ikemoto K, Hata T, Katoh S, Ichinose H, Kondo K
    Physiological Reports, 5(6) e13196-e13196, Feb, 2017  Peer-reviewedLast author
  • Akiko Hirao, Kazunao Kondo, Kazuhiko Takeuchi, Naoki Inui, Kazuo Umemura, Kyoichi Ohashi, Hiroshi Watanabe
    CARDIOVASCULAR RESEARCH, 79(1) 161-168, Jul, 2008  Peer-reviewed
    Aims Denudation and regeneration of the vascular endothelium are important in the pathogenesis of atherosclerosis. The aim of this study is to clarify the mechanisms of functional alterations in remodelled arteries following endothelial injury. Methods and results Non-mechanical endothelial injury was induced by 540-nm light irradiation of rose Bengal in femoral arteries of Wistar rats. Endothelium-dependent vasodilation was assessed by the response to acetylcholine (ACh) 1, 2, and 4 weeks after the injury. In control arteries, ACh-induced relaxation was mainly nitric oxide-dependent at all study time points. In injured arteries, this response was completely restored at 1 week, but was more dependent on KCl-sensitive endothelium-derived hyperpolarizing factor production during the first 2 weeks. Cyclooxygenase (COX) isoforms 1 and 2 were detected in the endothelium of injured arteries, and inhibition of prostanoids production with the non-specific COX inhibitor indomethacin substantially enhanced the ACh-induced vasorelaxation response in injured arteries, but did not affect control arteries. Similar effects were observed with the COX-1 inhibitor SC-560, the COX-2 inhibitor NS-398, the thromboxane (TX) A(2)/prostaglandin (PG) H(2) receptor antagonist SQ29548 and the PGF(2 alpha) receptor antagonist AL-8810. However, the TX synthetase inhibitor OKY-046 had no effect on ACh-induced relaxation in injured arteries. Conclusion In remodelled arteries following photochemical endothelial injury, the vasoconstrictive prostanoids PGH(2) and PGF(2 alpha), but not TXA(2), contribute to changes in endothelium-dependent vascular response via COX-1- and 2-dependent pathways.
  • Ikemoto K, Matsumoto T, Ohtsuki M, Itoh M, Tada S, Udagawa Y, Sumi-Ichinose C, Kondo K, Nomura T
    Biochim Biophys Acta., 1780(7-8) 960-965, 2008  Peer-reviewed
  • Yasuhiro Suzuki, Kazunao Kondo, Yuji Matsumoto, Bing-Qing Zhao, Kenichi Otsuguro, Tetsuya Maeda, Yoshinori Tsukamoto, Tetsumei Urano, Kazuo Umemura
    Life Sciences, 73(10) 1289-1298, Jul 25, 2003  Peer-reviewed
    We have previously demonstrated that natto-extracts containing nattokinase (NK) inactivates plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity. In the present study, we investigated the effects of dietary supplementation with natto-extracts on neointima formation and on thrombolysis at the site of endothelial injury. Endothelial damage in the rat femoral artery was induced by intravenous injection of rose bengal followed by focal irradiation by transluminal green light. Dietary natto-extracts supplementation containing NK of 50 or 100 CU/body was started 3 weeks before endothelial injury and then continued for another 3 weeks. Intimal thickening in animals given supplementation was significantly (P &lt 0.01) suppressed compared with controls and the intima/media ratio in animals with 50 and 100 CU/body NK and control group was 0.09 ± 0.03, 0.09 ± 0.06 and 0.16 ± 0.12, respectively. Although femoral arteries were reopened both in control animals and those treated with NK within 8 hours after endothelial injury, mural thrombi were histologically observed at the site of endothelial injury. In the control group, the center of vessel lumen was reopened and mural thrombi were attached on the surface of vessel walls. In contrast, in NK-treated groups, thrombi near the vessel wall showed lysis and most of them detached from the surface of vessel walls. In conclusion, dietary natto-extracts supplementation suppressed intimal thickening produced by endothelial injury in rat femoral artery. These effects may partially be attributable to NK, which showed enhanced thrombolysis near the vessel wall. © 2003 Elsevier Science Inc. All rights reserved.
  • Jiayi Cheng, Kazunao Kondo, Yasuhiro Suzuki, Yasuhiko Ikeda, Xiansheng Meng, Kazuo Umemura
    Life Sciences, 72(20) 2263-2271, Apr 4, 2003  Peer-reviewedCorresponding author
    Total flavones of Hippophae Rhamnoides L (TFH) are extracted from Sea buckthorn, a Chinese herbal medicine. Sea buckthorn has antioxidant, anti-ulcerogenic and hepato-protective actions, and its berry oil is reported to suppress platelet aggregation. Though it is frequently used for patients with thrombosis, the likely mechanism(s) and effects of TFH on thrombogenesis remain unclear. Thus, we have investigated the effect in-vivo of TFH on thrombogenesis and in vitro on platelet aggregation, comparing them to those of aspirin. We measured thrombotic occlusion time in a mouse femoral artery thrombosis model by the photochemical reaction between intravenously injected rose bengal and green light irradiation. In vitro platelet aggregation in whole blood was measured by single platelet counting. Thrombotic occlusion time was 8.5 ± 0.6 min in the control group. TFH at a dose of 300 μg/kg, intravenously administered 15 min before the rose bengal injection, significantly prolonged it to 11.6 ± 1.0 min (P &lt 0.05), a similar effect on in-vivo thrombogenesis to that of aspirin. TFH at a concentration of 3.0 μg/ml significantly (P &lt 0.01) inhibited in vitro platelet aggregation induced by collagen (2 μg/ml) in a concentration dependent manner, in contrast TFH did not affect aggregation induced by arachidonic acid (80 μM) and ADP (0.3 μM). The results of the present study, in which TFH prevented in-vivo thrombogenesis, probably due to inhibition of platelet aggregation, suggest a possible clinical approach for the prevention of thrombosis. © 2003 Published by Elsevier Science Inc.
  • Yasuhiro Suzuki, Kazunao Kondo, Hideyuki Ichise, Yoshinori Tsukamoto, Tetsumei Urano, Kazuo Umemura
    Nutrition, 19(3) 261-264, Mar 1, 2003  Peer-reviewed
    Although soy foods have been consumed for more than 1000 y, it is only in the past 20 y that they have made inroads into Western diets. We investigated the effect of dietary supplementation with natto extracts produced from fermented soybeans on intimal thickening of arteries after vessel endothelial denudation. Natto extracts include nattokinase, a potent fibrinolytic enzyme having four times greater fibrinolytic activity than plasmin. Intimal thickening was induced in the femoral arteries by intravenous infusion of rose bengal followed by focal irradiation with a transluminal green light. Dietary natto extract supplementation was started 3 wk before endothelial injury and continued for another 3 wk after. In ex vivo studies, euglobulin clot lysis times were measured 3 wk after the initial supplementation. Neointima formation and thickening were also initiated successfully. The intima media ratio 3 wk after endothelial injury was 0.15 ± 0.03 in the control group. Dietary natto extract supplementation suppressed intimal thickening (0.06 ± 0.01 P &lt 0.05) compared with the control group. Natto extracts shortened euglobulin clot lysis time, suggesting that their thrombolytic activities were enhanced. These findings suggest that natto extracts, because of their thrombolytic activity, suppress intimal thickening after vascular injury as a result of the inhibition of mural thrombi formation. © 2003 Elsevier Science Inc. 2003.
  • Kazunao Kondo, Yasuhiro Suzuki, Yasuhiko Ikeda, Kazuo Umemura
    European Journal of Pharmacology, 455(1) 53-57, Nov 22, 2002  Peer-reviewedLead authorCorresponding author
    Diet can be the most important factor that influences risks for cardiovascular diseases. Genistein included in soy is one candidate that may benefit the cardiovascular system. Here, we investigated the inhibitory effects of genistein on thrombotic vessel occlusion in the mouse femoral artery using a photochemical reaction, and in vitro platelet aggregation in whole blood measured by single platelet counting. Genistein (10 mg/kg), intravenously administered 10 min before the rose bengal injection, significantly prolonged the thrombotic occlusion time from 6.1±0.4 to 8.4±0.8 min (P&lt 0.05). Genistein at doses higher than 30 μM significantly (P&lt 0.01) inhibited in vitro platelet aggregation induced by collagen (1 and 3 μg/ml). When 10 mg/kg genistein was intravenously administered, ex vivo platelet aggregation induced by collagen (1 and 3 μg/ml) was significantly suppressed (P&lt 0.01). In conclusion, genistein prevented in vivo thrombogenesis and suppressed in vitro platelet aggregation. These results suggest that dietary supplementation of soy may prevent the progression of thrombosis and atherosclerosis. © 2002 Elsevier Science B.V. All rights reserved.
  • Kazunao Kondo, Kazuo Umemura, Mitsuru Miyaji, Mitsuyoshi Nakashima
    Atherosclerosis, 142(1) 133-138, Jan 3, 1999  Peer-reviewedLead authorCorresponding author
    The effect of milrinone, a phosphodiesterase (PDE) inhibitor, on intimal thickening after endothelial denudation was investigated. Intimal thickening was induced in the femoral arteries of mice by a photochemical reaction between rose bengal and transluminal green light which caused endothelial injury followed by platelet adhesion, aggregation, and formation of an occlusive thrombus in the irradiated segment of the mouse femoral artery. In this model, intimal thickening occurred following spontaneous thrombolysis. The intima/media ratio at 21 days after irradiation was 0.556 ± 0.104 in the untreated group. Oral administration of milrinone (0.3-3.0 mg/kg) for 3-21 days suppressed intimal thickening by up to 56% in a dose- and time- dependent manner. In an in vivo experiment using bromodeoxyuridine incorporation, milrinone suppressed cell proliferation at 1.0 mg/kg p.o. On the other hand, the minimum doses of milrinone for suppression of ex vivo platelet aggregation induced by collagen (0.8 μg/ml) or ADP (0.5 μM) were 3.0 and 10.0 mg/kg, respectively. These results indicate that milrinone may not suppress intimal thickening by inhibiting platelet function but by preventing vascular smooth muscle cell (VSMC) proliferation, probably through a mechanism mediated via 3', 5'-adenosine cyclic monophosphate (cAMP).
  • Kazunao Kondo, Kazuo Umemura, Tomohiro Ohmura, Hisakuni Hashimoto, Mitsuyoshi Nakashima
    Thrombosis and Haemostasis, 79(3) 635-639, Mar, 1998  Lead authorCorresponding author
    Intimal thickening is a major complication following percutaneous transluminal coronary angioplasty, which leads to restenosis and requires reoperation. We have investigated the effect of a 5-lipoxygenase inhibitor, MK-886, a leukotriene B4 (LTB4) receptor antagonist, ONO-4057 or a LTC4 and LTD4 receptor antagonist. ONO-1078, on intimal thickening. Photochemical reaction between green light and systemically administered Rose Bengal produced intimal thickening in the rat femoral artery. Each drug was administered orally, once a day for 7 days, starting just after the endothelial injury. Both MK-886 administration, 10 mg/kg, and ONO-4057 administration, 100 mg/kg, suppressed intimal thickening level examined three weeks after endothelial injury, while similarly administered ONO-1078 did not. In cultured rat-derived smooth muscle cells, LTB4, an active metabolite of 5-lipoxygenase whose biosynthesis in air pouch exudate was suppressed by MK-886, stimulated cell migration. Based on these observations, the 5-lipoxygenase may have a key role in intimal thickening via its metabolites such as LTB4.

Misc.

 29
  • 中島 昭, 近藤 一直, 宮地 栄一, 飯塚 成志, 池本 和久, 石原 悟, 大熊 真人, 金子 葉子, 河合 房夫, 小谷 侑, 菅沼 由唯, 長崎 弘, 原田 信広, 吉田 友昭, 稲垣 秀人, 土田 邦博, 山口 央輝
    医学教育, 48(5) 323-325, Oct, 2017  
  • Yui Suganuma, Taiki Kano, Kazuhisa Ikemoto, Chiho Ichinose, Takahide Nomura, Kazunao Kondo
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 124 132P-132P, 2014  
  • 一瀬 宏, 本間 大悟, 一瀬 鷲見 千穂, 近藤 一直
    自律神経 = The Autonomic nervous system, 50(1) 16-17, Mar 15, 2013  
  • Hiroshi Ichinose, Daigo Homma, Chiho Sumi-Ichinose, Takahide Nomura, Kazunao Kondo
    Advances in Pharmacology, 68 23-35, 2013  
    Tetrahydrobiopterin (BH4) is essential for the biosynthesis of dopamine, noradrenaline, and serotonin, which serve as cofactors for tyrosine hydroxylase (TH) and tryptophan hydroxylase. GTP cyclohydrolase (GCH) is the first and rate-limiting enzyme for BH4 biosynthesis. Genetic defects in an allele of the GCH gene can result in dopa-responsive dystonia due to partial BH4 deficiency. To explore the transcriptional control of the GCH gene, we analyzed the signaling pathway. Bacterial lipopolysaccharide (LPS) greatly enhanced the expression of GCH in RAW264 cells, and the induction of GCH by LPS was suppressed by treatment with either a MEK1/2 inhibitor or an inhibitor for the NF-κB pathway. Next, we analyzed two types of biopterin-deficient transgenic mice. We found that both mice exhibited motor disorders with slight differences. Dopamine and TH protein levels were markedly and concurrently increased from birth (P0) to P21 in wild-type mice, and these increases were abolished in both types of biopterin-deficient mice. Our results suggest that the developmental manifestation of psychomotor symptoms in BH4 deficiency might be attributable at least partially to the high dependence of dopaminergic development on the availability of BH4. © 2013 Elsevier Inc.
  • Akira Ota, Akira Nakashima, Yoko S. Kaneko, Keiji Mori, Hiroshi Nagasaki, Takeshi Takayanagi, Mitsuyasu Itoh, Kazunao Kondo, Toshiharu Nagatsu, Miyuki Ota
    JOURNAL OF NEURAL TRANSMISSION, 119(11) 1327-1342, Nov, 2012  
    Aripiprazole is the only atypical antipsychotic drug known to cause the phosphorylation of AMP-activated protein kinase (AMPK) in PC12 cells. However, the molecular mechanisms underlying this phosphorylation in aripiprazole-treated PC12 cells have not yet been clarified. Here, using PC12 cells, we show that these cells incubated for 24 h with aripiprazole at 50 mu M and 25 mM glucose underwent a decrease in their NAD(+)/NADH ratio. Aripiprazole suppressed cytochrome c oxidase (COX) activity but enhanced the activities of pyruvate dehydrogenase (PDH), citrate synthase and Complex I. The changes in enzyme activities coincided well with those in NADH, NAD(+), and NAD(+)/NADH ratio. However, the bioenergetic peril judged by the lowered COX activity might not be accompanied by excessive occurrence of apoptotic cell death in aripiprazole-treated cells, because the mitochondrial membrane potential was not decreased, but rather increased. On the other hand, when PC12 cells were incubated for 24 h with clozapine at 50 mu M and 25 mM glucose, the NAD(+)/NADH ratio did not change. Also, the COX activity was decreased; and the PDH activity was enhanced. These results suggest that aripiprazole-treated PC12 cells responded to the bioenergetic peril more effectively than the clozapine-treated ones to return the ATP biosynthesis back toward its ordinary level. This finding might be related to the fact that aripiprazole alone causes phosphorylation of AMPK in PC12 cells.

Presentations

 23

Research Projects

 7

教育内容・方法の工夫(授業評価等を含む)

 1
  • 件名(英語)
    Human Biology発表会(M2:中間および最終発表会)
    概要(英語)
    学生座長を指名・事前指導することにより学会形式の発表会を実体験させた(平成21〜25年度副コーディネーターとして)。

作成した教科書、教材、参考書

 1
  • 件名(英語)
    薬理学実習書
    概要(英語)
    実習書作成と適用(平成21〜25年度)

教育方法・教育実践に関する発表、講演等

 1
  • 件名(英語)
    第45回日本医学教育学会総会、千葉2013
    概要(英語)
    口演共同演者「医学科4年生と看護学科4年生との合同PBL-tutorialの試み.」

その他教育活動上特記すべき事項

 3
  • 件名(英語)
    学年担任
    開始年月日(英語)
    2011
    終了年月日(英語)
    2012
  • 件名(英語)
    学生指導委員会
    概要(英語)
    平成21〜24年度委員・25年度副委員長
  • 件名(英語)
    教育WS
    概要(英語)
    (1)学部内WS参加{第28・32・33・34回},(2)学内WS参加{第2・4回医学・医療教育WS},(3)第33回MEDC医学教育セミナーとワークショップ(岐阜大学)参加