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FacultyDepartment of Pharmacy
Commentator Guide
Last Updated :2020/08/11

Education and Career


  •  - 1990 , Osaka University, Graduate School, Division of Pharmaceutical Sciences
  •  - 1988 , Osaka University, Faculty of Pharmaceutical Science
  •   1984 04  - 1988 03 , Osaka University, School of Pharmaceutical Sciences

Academic & Professional Experience

  •   2010 04 ,  - 現在, Professor, Faculty of Pharmacy, Kindai University
  •   2004 04 ,  - 2010 03 , Associate Professor, School of Pharmaceutical Sciences, Mukogawa Women's University
  •   2003 03 ,  - 2004 03 , Visiting Scholar, Feinberg School of Medicine, Northwestern University
  •   1997 09 ,  - 2004 03 , Assistant Professor, School of Pharmaceutical Sciences, Mukogawa Women's University
  •   1990 04 ,  - 1997 08 , Research Division, The Green Cross Corporation
  •   1992 04 ,  - 1994 03 , Researcher, School of Medicine, Kinki University

Research Activities

Research Areas

  • Life sciences, Clinical pharmacy
  • Life sciences, Pharmacology
  • Life sciences, Clinical pharmacy
  • Life sciences, Pharmacology
  • Life sciences, Pharmaceuticals - health and biochemistry
  • Informatics, Statistical science

Research Interests

  • Cell Biology

Published Papers

  • Changing Role of Pharmacist in Revision of Medical Fee, Atsushi Murase, Manabu Kitakoji, Toru Otori, Sumio Matzno, J Community Pharm Pharm Sci, J Community Pharm Pharm Sci, 11(2), 165 - 172, Oct. 2019 , Refereed
    Summary:In order to examine the role of the pharmacist in medical care, we analyzed “arrangement of the previous discussions related to the revision of medical service fees for 2014, 2016 and 2018”. Co-occurrence network analysis suggested that “hospital”, “patient” and “reevaluation” formed strongly connected cluster. “Patient” was also connected with other two groups. One group included “pharmacy”, “drug” and “management” and the other included “home”, “visit” and “nursing”. Furthermore, correspondence analysis suggested that 2014 had relations to “hospital” and “home”, 2016 had relations to “hospital”, “care” and “outpatients” and 2018 had relations not only to “doctor” and “drugs” but also “area”, “visit” and “support”. Therefore, the government’s policy to shift the role of the pharmacist from hospitals to home medical care was clarified.
  • The usefulness of self-evaluation rubric table as a component of a learning management system for a course in statistics, MATZNO Sumio, HACHIKEN Hiroko, 2, 159 - 166, Jan. 2019
    Summary:A self-evaluation rubric system was introduced to statistical classes for university students in order to investigate the relationship between students’ satisfaction and their grades. Two items, “understanding” and “computer skill”, were reviewed according to rubric tables. Principal component analysis revealed that most evaluations patterns indicated the same direction and students could be characterized into three groups. Whereas two factors of “teaching skill” and “students’ activity” were extracted from the post-course questionnaire. Finally, multiple regression analysis revealed that final examination results were well correlated with the evaluation rubric. This suggests that an evaluation rubric system is helpful to predict students’ achievement in class.
  • 婦人科悪性腫瘍におけるパクリタキセル・カルボプラチン療法での後発品製剤安全性の検討(An Analysis of Generic Drug Safety in Paclitaxel and Carboplatin Chemotherapy for Gynecologic Malignancies), 藤本 伸一郎, 柳江 正嗣, 淺野 肇, 武田 朋也, 椿 正寛, 藤原 季美子, 月岡 康行, 松野 純男, 森嶋 祥之, 西田 升三, ジェネリック研究, ジェネリック研究, 12(2), 74 - 79, Dec. 2018
  • 統合失調症患者における抗精神病薬の副作用発現因子に関する検討, 松浦 正佳, 阪口 寛子, 高蓋 由美子, 竹中 凛代, 大鳥 徹, 松野 純男, 岩城 正宏, 北小路 学, 東 司, 薬局薬学, 薬局薬学, 10(1), 148 - 155, Apr. 2018
  • Development of hemiacetal esterified levofloxacin to prevent chelation with metal-containing drugs, Toru Otori, Sumio Matzno, Atushi Kawase, Masahiro Iwaki, Tetsutaro Kimachi, Keiji Nishiwaki, William C. Figoni, Ryuta Tominaga, Mai Asahide, Mayumi Nishikata, Yoshikazu Ishii, Kenji Matsuyama, JOURNAL OF PHARMACY AND PHARMACOLOGY, JOURNAL OF PHARMACY AND PHARMACOLOGY, 68(12), 1527 - 1534, Dec. 2016 , Refereed
    Summary:ObjectivesTo avoid the chelate formation between levofloxacin (LVFX) and aluminium hydroxide in gastrointestinal tract, an ethoxycarbonyl 1-ethyl hemiacetal ester of levofloxacin (LVFX-EHE) was synthesised as a prodrug. MethodsThe effects of aluminium hydroxide on the bioavailability of LVFX following oral administration of LVFX-EHE were investigated in rats. Furthermore, the effects of aluminium hydroxide on small intestinal absorption of LVFX and LVFX-EHE when subjected to a hydrolysis experiment using in situ everted gut sac were investigated, and the minimal inhibitory concentrations (MICs) of LVFX and LVFX-EHE for various intestinal bacteria were measured. Key findingsWhen LVFX-EHE was co-administered with and without aluminium hydroxide, the AUC(0-4 h) values of LVFX hydrolysed from LVFX-EHE were similar to that of LVFX alone. In everted gut sac experiments, LVFX-EHE was efficiently absorbed even in the presence of aluminium ions after 1 h of incubation, whereas the absorption of LVFX decreased significantly in the presence of aluminium ions. MIC values of LVFX-EHE were far higher than LVFX. ConclusionsThis study suggests the benefit of ethoxycarbonyl 1-ethyl hemiacetal esterification of the carboxyl group of new quinolone as a prodrug which is able to avoid chelate formation.
  • Skb5, an SH3 adaptor protein, regulates Pmk1 MAPK signaling by controlling the intracellular localization of the MAPKKK Mkh1, Yuki Kanda, Ryosuke Satoh, Saki Matsumoto, Chisato Ikeda, Natsumi Inutsuka, Kanako Hagihara, Sumio Matzno, Sho Tsujimoto, Ayako Kita, Reiko Sugiura, JOURNAL OF CELL SCIENCE, JOURNAL OF CELL SCIENCE, 129(16), 3189 - 3202, Aug. 2016 , Refereed
    Summary:The mitogen-activated protein kinase (MAPK) cascade is a highly conserved signaling module composed of MAPK kinase kinases (MAPKKKs), MAPK kinases (MAPKK) and MAPKs. The MAPKKK Mkh1 is an initiating kinase in Pmk1 MAPK signaling, which regulates cell integrity in fission yeast (Schizosaccharomyces pombe). Our genetic screen for regulators of Pmk1 signaling identified Shk1 kinase binding protein 5 (Skb5), an SH3-domain-containing adaptor protein. Here, we show that Skb5 serves as an inhibitor of Pmk1 MAPK signaling activation by downregulating Mkh1 localization to cell tips through its interaction with the SH3 domain. Consistent with this, the Mkh13PA mutant protein, with impaired Skb5 binding, remained in the cell tips, even when Skb5 was overproduced. Intriguingly, Skb5 needs Mkh1 to localize to the growing ends as Mkh1 deletion and disruption of Mkh1 binding impairs Skb5 localization. Deletion of Pck2, an upstream activator of Mkh1, impaired the cell tip localization of Mkh1 and Skb5 as well as the Mkh1-Skb5 interaction. Interestingly, both Pck2 and Mkh1 localized to the cell tips at the G1/S phase, which coincided with Pmk1 MAPK activation. Taken together, Mkh1 localization to cell tips is important for transmitting upstream signaling to Pmk1, and Skb5 spatially regulates this process.
  • 薬剤師の禁煙支援に関する意識調査の多変量解析による問題点の抽出, 高橋 直子, 松野 純男, 伊藤 栄次, 高橋 裕子, 禁煙科学, 禁煙科学, 10(2), P1 - P12, Feb. 2016
  • 中心静脈栄養法(TPN)施行時に脂肪乳剤が血清アルブミン値へ与える影響, 森住 誠, 坂本 千代子, 石原 美加, 松田 光弘, 松野 純男, 北小路 学, 日本病院薬剤師会雑誌, 日本病院薬剤師会雑誌, 51(6), 747 - 750, Jun. 2015
    Summary:静脈栄養時における脂肪乳剤の併用は、糖質の投与量や、総水分量を抑えた高エネルギー投与が可能となる。このようなメリットがあるにもかかわらず、我が国での脂肪乳剤併用率は低いのが実状である。そこで我々は、4週間以上の中心静脈栄養法(TPN)施行患者を対象に、脂肪乳剤の血清アルブミン(albumin:以下、Alb)値に影響を与える因子を重回帰分析にて探索した。その結果、Alb値に影響を与える因子として、非蛋白熱量(non-protein calorie:以下、NPC)における脂肪含有率、開始時Alb値、開始時C-reactive protein(以下、CRP)値、4週間後CRP値が挙げられた。以上の結果から、中心静脈栄養法開始時に低Alb血症でない場合や何らかの炎症性疾患を有する場合でのAlb値改善は困難だが、単に総エネルギー量を上げるのではなく、NPCにおける脂肪含有率がAlb合成に関与することを確認した。本研究から、静脈栄養時における脂肪乳剤の併用は栄養状態の改善に寄与する因子の1つであると考えられた。(著者抄録)
  • An Evaluation of Usage and Utilization of Generic Drugs by Clinical Medicine Departments Using a Questionnaire of Chain Community Pharmacies in Japan, Nagai Noriaki, Kim Yusei, Matzno Sumio, Matsuyama Kenji, Otori Toru, Jpn.J.Drug Inform., Jpn.J.Drug Inform., 16(3), 137 - 142, Nov. 2014
    Summary:The creation of the National Health Insurance program has greatly contributed to giving Japan the world's highest level of life expectancy.  However, the cost of medical care in Japan has increased as a result of an aging society.  In response to this reality, the Japanese government initiated a campaign to promote the use of generic drugs (GEs).  In order to clarify some of the trends that contribute to different clinical medicine department usages of GEs, we carried out a survey of 400 pharmacies.  The survey data was analyzed using linear regression analysis.  Analysis of linear equations derived "utilization" that indicated ease of use of GEs, and a "saturation acceptable value (maximum allowed)" that indicated usage of GEs.  The breakdown for different clinical medicine department usages of GEs was determined as the following: psychosomatic medicine or psychiatry was 11±0.13%, internal medicine was 29±0.18%, orthopedics was 18±0.14%, ophthalmology or otolaryngology was 15±0.14%, other departments was 17±0.15%.  Furthermore, the highest utilization derived by linear regression analysis was orthopedics.  The highest acceptable saturation value was for psychosomatic medicine or psychiatry, while the lowest acceptable saturation value was orthopedics.  The results of the study confirm the importance of establishing evaluation methods for GE usage, and that linear regression analysis is a powerful tool for revealing trends in GE usage among different departments.  Additionally, the study suggests that determining GE spread measures is valuable, since they can serve as an aid to future pharmaceutical administration consideration.
  • Multivariate Quantification of Acupuncture and Moxibustion Treatment in Combination with Questionnaire and Salivary Stress Markers, Sumio Matzno, Chie Ikeda, Kazuomi Watanabe, Ryohei Nakamura, Hanae Takamatsu, Jun Haginaka, Kenji Matsuyama, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 134(5), 655 - 663, May 2014 , Refereed
    Summary:Pain and stress alleviation after acupuncture treatment was assessed in this study. Patients responded to a questionnaire designed to determine the amount of stress they were experiencing, and data were obtained for patient salivary amylase, cortisol, secretary IgA (s-IgA), and leptin receptor (OBRb). As a part of this study on acute pain, 6 factors were extracted from the questionnaire. The second factor (pain removal) was well correlated with salivary amylase activity in patients with cervico-omo-brachial syndrome. An evaluation of cumulative acupuncture treatments showed that salivary cortisol increased and s-IgA decreased. In addition, a decreased s-IgA level significantly correlated with chronic pain removal. The questionnaire correlated well with measurements of salivary markers suggesting that they can be taken as indices of therapeutic efficacy in acupuncture treatment.
  • FTY720 stimulated ROS generation and the Sty1/Atf1 signaling pathway in the fission yeast Schizosaccharomyces pombe, Kanako Hagihara, Aya Mizukura, Yuki Kitai, Mariko Yao, Kouki Ishida, Ayako Kita, Tatsuki Kunoh, Takashi Masuko, Sumio Matzno, Kenji Chiba, Reiko Sugiura, GENES TO CELLS, GENES TO CELLS, 19(4), 325 - 337, Apr. 2014 , Refereed
    Summary:Fingolimod hydrochloride (FTY720) is the first-in-class immune modulator known as sphingosine 1-phosphate (S1P) receptor agonists. FTY720 has also been reported to exert a variety of physiological functions such as antitumor effect, angiogenesis inhibition, and Ca2+ mobilization. Here, we show that FTY720 treatment induced reactive oxygen species (ROS) accumulation, and investigated the effect of FTY720 on the stress-activated MAP kinaseSpc1/Sty1, a functional homologue of p38 MAPK, using a Renilla luciferase reporter construct fused to the CRE, which gives an accurate measure of the transcriptional activity of Atf1 and thus serves as a faithful readout of the Spc1/Sty1 MAPK signaling in response to oxidative stresses. FTY720 stimulated the CRE responses in a concentration-dependent manner, which was markedly reduced by deletion of the components of the Spc1/Sty1 MAPK pathway. The blockade of ROS production by NAC (N-acetyl-l-cysteine) significantly reversed the FTY720-induced ROS accumulation, subsequent activation of the Spc1/Sty1 MAPK pathway, and inhibition of cell proliferation. Cells lacking the components of the Spc1/Sty1 MAPK exhibited higher sensitivity to FTY720 and higher ROS levels upon FTY720 treatment than in wild-type cells. Thus, our results demonstrate the usefulness of fission yeast for elucidating the FTY720-mediated signaling pathways involving ROS.
  • Effect of Obesity and Administration Period on Serum Concentrations of Amiodarone and Desethylamiodarone, 堀部 明美, 松山 賢治, 松野 純男, 薬局薬学, 薬局薬学, 6(1), 37 - 42, 2014
  • 後発医薬品の使用状況に関するアンケートの多変量解析による問題点の抽出, 大鳥徹, 長井紀章, 橋本佳幸, 金裕生, 松野純男, 松山賢治, 医薬品情報学, 医薬品情報学, 15(3), 124 - 132, Nov. 30 2013
  • Stability of Polaprezine-containing oral rinse and its clinical effectiveness against radiotherapy-induced oral mucositis, Nakayama M, Fujiwara M, Nakamura T, Azuma T, Matzno S, Kamikonya N, Kimura T, Matsuyama K, Kawabata A, Jpn. J. Drug Inform., Jpn. J. Drug Inform., 15(3), 133 - 138, Nov. 2013 , Refereed
  • 病院薬剤師を対象とした漢方意識調査による効果的な生涯教育の提案, 草薙みか, 岩政かおり, 門間智恵, 山本倫数, 西山和香子, 高田充隆, 松野純男, 大里恭章, 日本病院薬剤師会雑誌, 日本病院薬剤師会雑誌, 49(11), 1181 - 1186, Nov. 01 2013
  • A Search for the Risk Factors for Hiccups and Evaluation of Antiemetic Therapy in CDDP-Based Chemotherapy, Using Cluster Analysis, ASANO HAJIME, WATANABE MIZUKI, KAWAGUCHI AKINORI, YANAE MASASHI, FUNAKAMI YOSHINORI, WADA TETSUYUKI, MATSUNO SUMIO, YAMAZOE YUZURU, NISHIDA SHOZO, ICHIDA SEIJI, 癌と化学療法, 癌と化学療法, 40(8), 1031 - 1036, Aug. 15 2013 , Refereed
  • Fingolimod (FTY720) stimulates ca(2+)/calcineurin signaling in fission yeast., Hagihara K, Kita A, Mizukura A, Yao M, Kitai Y, Kunoh T, Masuko T, Matzno S, Chiba K, Sugiura R, PloS one, PloS one, 8(12), e81907, 2013 , Refereed
  • Evaluation of injectable generic drugs using thermogravimetry and the influence of d-mannitol on the stability of gabexate mesilate, Otori T, Matzno S, Hyodo M, Sugimoto S, Kimura T, Matsuyama K, Intl. J. Pharm.Tech., Intl. J. Pharm.Tech., 4(2), 4549 - 4559, Feb. 2012 , Refereed
  • Evaluation of higher clearance of serum vancomycin (VCM) after treatment of dilated cardiopathy with left ventricular assist system (LVAS) together with carperitide, Horibe A, Matzno S, Matsuyama K, Kurosawa N, Nakamura I, Yamashita D, Wada K, Okada H, Kohara N, Nakatani T, Jpn J.TDM, Jpn J.TDM, 28(1), 7 - 13, Jan. 2011
  • Effect of Quinine Solutions on Intracellular Ca Levels in Neuro-2a Cells -Conventional Physiological Method for the Evaluation of Bitterness-, Biological & Pharmaceutical Bulletin, Biological & Pharmaceutical Bulletin, 26(1), 1637 - 1640, 2010
  • The potential of vitamin K(3) as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway, Takeshi Akiyoshi, Sumio Matzno, Mika Sakai, Noboru Okamura, Kenji Matsuyama, CANCER CHEMOTHERAPY AND PHARMACOLOGY, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 65(1), 143 - 150, Dec. 2009 , Refereed
    Summary:We tried to clarify the cytotoxic mechanism of VK(3) using the breast cancer cell line MCF-7. Cytotoxicity was measured via intracellular esterase activity. DNA fragmentation was assessed by agarose gel electrophoresis. JC-1 staining was applied to measure mitochondrial dysfunction. Caspase activation and reactive oxidative species (ROS) generation were also measured. VK(3) exhibited cytotoxicity that caused DNA fragmentation in MCF-7 cells with an IC(50) of 14.2 mu M. JC-1 staining revealed that VK(3) caused mitochondrial dysfunction including a disappearance of mitochondrial membrane potential. Additional investigation showed that the mitochondrial damage was induced by the generation of ROS and the subsequent activation of caspase-7 and -9. Our findings demonstrate that VK(3)-induced apoptosis is selectively initiated by the mitochondria-related pathway and might be useful in breast cancer chemotherapy.
  • Synergistic action of statins and nitrogen-containing bisphosphonates in the development of rhabdomyolysis in L6 rat skeletal myoblasts, Sumio Matzno, Tomoko Nishiguchi, Takeshi Akiyoshi, Setsuko Anami, Toshikatsu Nakabayashi, Kenji Matsuyama, JOURNAL OF PHARMACY AND PHARMACOLOGY, JOURNAL OF PHARMACY AND PHARMACOLOGY, 61(6), 781 - 788, Jun. 2009 , Refereed
    Summary:Objectives Nitrogen-containing bisphosphonates, which are widely used to treat osteoporosis, act as inhibitors of farnesyl pyrophosphate synthase, one of the key enzymes of the mevalonate pathway, and thus may have the potential to enhance the effect of statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase). In this study, we evaluated the synergistic effect of two nitrogen-containing bisphosphonates, alendronate and risedronate, in statin-induced apoptosis in rat skeletal L6 myoblasts. Methods L6 rat myoblasts were differentiated with drugs. DNA fragmentation was measured and small GTPase was detected by immunoblotting. Key findings Alendronate and risedronate caused dose-dependent apoptosis of L6 myoblasts. Risedronate induced detachment of rho GTPase from the cell membrane, followed by activation of the caspase-8-related cascade. Risedronate-induced apoptosis was synergistically enhanced with atorvastatin and significantly reduced by addition of geranylgeraniol. By contrast, alendronate did not reduce membrane GTPases and the apoptosis was caspase independent. Conclusions These results suggest that risedronate-induced apoptosis is related to geranylgeranyl pyrophosphate depletion followed by rho detachment, whereas alendronate affects are independent of rho. Our results suggest a risk of synergistic action between nitrogen-containing bisphosphonates and statins in the development of rhabdomyolysis when treating osteoporosis in women with hyperlipidaemia.
  • Effect of glutamine or alkaline ionized water on late diarrhea induced by irinotecan hydrochloride in Gunn rats, Asian Journal of Pharmaceutical Sciences, Asian Journal of Pharmaceutical Sciences, 4(2), 96 - 105, 2009
  • Methods of preventing vinorelbine-induced phlebitis: an experimental study in rabbits., Kohno E, Murase S, Nishikata M, Okamura N, Matzno S, Kuwahara T, Matsuyama K, International journal of medical sciences, International journal of medical sciences, 5(4), 218 - 223, Jul. 2008 , Refereed
  • An attempt to evaluate the effect of vitamin K-3 using as an enhancer of anticancer agents, Sumio Matzno, Yuka Yamaguchi, Takeshi Akiyoshi, Toshikatsu Nakabayashi, Kenji Matsuyama, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 31(6), 1270 - 1273, Jun. 2008 , Refereed
    Summary:The possibility of vitamin K-3 (VK3) as an anticancer agent was assessed. VK3 dose-dependently diminished the cell viability (measured as esterase activity) with IC50 of 13.7 mu M and Hill coefficient of 3.1 in Hep G(2) cells. It also decreased the population of S phase and arrested cell cycle in the G(2)/M phase in a dose-dependent manner. G(2)/M arrest was regulated by the increment of cyclin A/cdk1 and cyclin A/cdk2 complex, and contrasting cyclin B/cdk1 complex decrease. Finally, combined application demonstrated that VK3 significantly enhanced the cytotoxicity of etoposide, a G(2) phase-dependent anticancer agent, whereas it reduced the cytotoxic activity of irinotecan, a S phase-dependent agent. These findings suggest that VK3 induces G(2)/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G(2) phase-dependent drugs in hepatic cancer chemotherapy.
  • The possibility of simvastatin as a chemotherapeutic agent for all-trans retinoic acid-resistant promyelocytic leukemia, Naoki Tomiyama, Sumio Matzno, Chihiro Kitada, Eri Nishiguchi, Noboru Okamura, Kenji Matsuyama, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 31(3), 369 - 374, Mar. 2008 , Refereed
    Summary:In this study, the authors evaluated the possible use of 3-hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in anti-leukemic chemotherapy. Cytotoxic potency against HL-60 was as follows; simvastatin (SV)>atorvastatin>cerivastatin>fluvastatin. Interestingly, HL-60-R2, an all-traits retinoic acid (ATRA)-resistant HL-60 variant, was twice as sensitive to SV than HL-60. Further studies revealed the particular mechanism of action of SV induced apoptosis in leukemia. SV directly and rapidly disordered mitochondria with a loss of its membrane potential, reactive oxygen species (ROS) generation and subsequent irreversible damage with cytochrome c leakage and, finally, SV induced apoptosis through caspase-9 activation, whereas several studies have shown that other statins induced apoptosis to leukemia by the depletion of isoprenoids used for the prenylation of small GTPases, which are essential for cellular signal transduction. Our findings suggest that the mitochondrial pathway plays an important role in the higher potency of SV as a new class of agents for anti-leukemic therapy alone and/or in combination with agents.
  • Effects of quinine on the intracellular calcium level and membrane potential of PC 12 cultures, Takeshi Akiyoshi, Naoko Tanaka, Tomoko Nakamura, Sumio Matzno, Kazumasa Shinozuka, Takahiro Uchida, JOURNAL OF PHARMACY AND PHARMACOLOGY, JOURNAL OF PHARMACY AND PHARMACOLOGY, 59(11), 1521 - 1526, Nov. 2007 , Refereed
    Summary:The mechanism for the perception of bitterness appears to be quite complicated, even for quinine, which is a model bitter substance, and thus has yet to be completely elucidated. To investigate the possibility of being able to predict the bitterness of quinine solutions, we examined the effects of quinine on intracellular calcium ion concentration ([Ca2+]i) and membrane potentials in PC 12 cultures. [Ca2+]i and membrane potentials were analysed by fluorescence confocal microscopic imaging using the Ca2+-sensitive probe Calcium Green 1/AM and the membrane potential-sensitive probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC(4)(3)). Quinine elicited an increase in the membrane potential along with a concentration-dependent increase in [Ca2+]i. These increases were inhibited by extracellular Ca2+-free conditions, thapsigargin, which is a Ca2+-pump inhibitor, and U73122, which is a phospholipase C inhibitor. The quinine-induced increase in [Ca2+]i levels was inhibited by nifedipine, an L-type Ca2+-channel blocker, conotoxin, a T-type Ca2+-channel blocker, and BMI-40, which is a bitterness-masking substance. These results suggest that responses in PC 12 cultures may be used as a simple model of bitterness perception.
  • Flow cytometric evaluation of synergistic pro-apoptotic effects of statins and clofibrates in im-9 human lymphoblasts, Naoki Tomiyama, Noriko Yasuda, Chihiro Iwano, Sumio Matzno, Kenji Matsuyama, CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 34(9), 876 - 880, Sep. 2007 , Refereed
    Summary:In the present study, we evaluated fibrate-mediated potentiation of statin-induced apoptosis in IM-9 human lymphoblasts. The pro-apoptotic effects of statin and fibrate were measured by flow cytometry with biotin-annexin V, followed by addition of avidin-fluorescein isothiocyanate and propidium iodide. Apoptosis was confirmed using karyopyknotic staining, as well as detection of DNA fragmentation and caspase 3 activation. Incubation of IM-9 cells with both 0.1 mu mol/L cerivastatin and 200 mu mol/L clofibrate had a synergistic effect compared with 0.1 mu mol/L cerivastatin alone or 200 mu mol/L clofibrate alone. The magnitude of apoptosis induced by various combinations of statins and clofibrate were as follows: cerivastatin (0.1 mu mol/L) + clofibrate (200 mu mol/L) > atorvastatin (0.1 mu mol/L) + clofibrate (200 mu mol/L) > pravastatin (100 mu mol/L) + clofibrate (200 mu mol/L). Other fibrates (bezafibrate and clinofibrate) did not show any synergistic effect. Furthermore, karyopyknotic staining, caspase 3 activation and DNA fragmentation demonstrated synergistic pro-apoptotic effects of statin and fibrate. The results of the present study suggest that simultaneous treatment with statins and clofibrate could provide improved therapeutic efficacy in leukaemia patients.
  • Integrin beta 4 regulates migratory behavior of keratinocytes by determining laminin-332 organization, Bernd U. Sehgal, Phillip J. DeBiase, Sumio Matzno, Teng-Leong Chew, Jessica N. Claiborne, Susan B. Hopkinson, Alan Russell, M. Peter Marinkovich, Jonathan C. R. Jones, JOURNAL OF BIOLOGICAL CHEMISTRY, JOURNAL OF BIOLOGICAL CHEMISTRY, 281(46), 35487 - 35498, Nov. 2006 , Refereed
    Summary:hether alpha 6 beta 4 integrin regulates migration remains controversial. beta 4 integrin-deficient (JEB) keratinocytes display aberrant migration in that they move in circles, a behavior that mirrors the circular arrays of laminin (LM)-332 in their matrix. In contrast, wild-type keratinocytes and JEB keratinocytes, induced to express beta 4 integrin, assemble laminin-332 in linear tracks over which they migrate. Moreover, laminin-332-dependent migration of JEB keratinocytes along linear tracks is restored when cells are plated on wild-type keratinocyte matrix, whereas wild-type keratinocytes show rotation over circular arrays of laminn-332 in JEB keratinocyte matrix. The activities of Rac1 and the actin cytoskeleton-severing protein cofilin are low in JEB keratinocytes compared with wild-type cells but are rescued following expression of wild-type beta 4 integrin in JEB cells. Additionally, in wild-type keratinocytes Rac1 is complexed with alpha 6 beta 4 integrin. Moreover, Rac1 or cofilin inactivation induces wild-type keratinocytes to move in circles over rings of laminin-332 in their matrix. Together these data indicate that laminin-332 matrix organization is determined by the alpha 6 beta 4 integrin/actin cytoskeleton via Rac1/cofilin signaling. Furthermore, our results imply that the organizational state of laminin-332 is a key determinant of the motility behavior of keratinocytes, an essential element of skin wound healing and the successful invasion of epidermal-derived tumor cells.
  • Statistical analysis of the adverse effects of glycopeptide antibiotics, based on pharmacokinetics and toxicokinetics (PK/TK)., Yoshida M, Matzno S, Namba H, Nishikata M, Matsuyama K, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 12(3), 114 - 118, Jun. 2006 , Refereed
  • Clofibrate-induced apoptosis is mediated by Ca2+-dependent caspase-12 activation, S Matzno, S Yasuda, Y Kitada, T Akiyoshi, N Tanaka, S Juman, K Shinozuka, T Nakabayashi, K Matsuyama, LIFE SCIENCES, LIFE SCIENCES, 78(16), 1892 - 1899, Mar. 2006 , Refereed
    Summary:The mechanism of fibrate-induced myopathy was investigated in this report. When clofibrate (30 to 300 mu M) was applied to L6 rat skeletal myoblasts, dose-dependently apoptosis was observed within 24 h. In the apoptotic myoblasts, a caspase-12 cleavage was observed at 2 It and with following caspases-9 and -3-related cascade activation. In contrast, the neutral protease calpain, that is a key enzyme in ER stress-related apoptosis via caspase-12 activation, was significantly decreased during apoptosis. Next, the authors evaluated a role of calcium-dependent signal(s). When clofibrate was added into medium, cytosolic calcium concentration was rapidly and persistently increased. On the other hand, an addition of 10 mM EGTA depressed sustained calcium phase, and concurrent myoblasts apoptosis was completely inhibited. Taken together, our findings indicate that the clofibrate-induced myopathy is triggered by Ca2+ influx, then activated cytosolic caspase-12 through calpain-independent cascade, and consequently caused apoptotic DNA fragmentation. (c) 2005 Elsevier Inc. All rights reserved.
  • Statin-induced apoptosis linked with membrane farnesylated Ras small G protein depletion, rather than geranylated Rho protein, S Matzno, S Yasuda, S Juman, Y Yamamoto, N Nagareya-Ishida, K Tazuya-Murayama, T Nakabayashi, K Matsuyama, JOURNAL OF PHARMACY AND PHARMACOLOGY, JOURNAL OF PHARMACY AND PHARMACOLOGY, 57(11), 1475 - 1484, Nov. 2005 , Refereed
    Summary:Rhabdomyolysis is a severe adverse effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). This myopathy is strongly enhanced by the combination with statins and fibrates, another hypolipidaemic agent. We have evaluated the initial step of statin-induced apoptosis by the detection of membrane flip-flop using flow cytometric analysis. L6 rat myoblasts were treated with various statins (atorvastatin (3 mu M), cerivastatin (3 mu M), fluvastatin (3 mu M), pravastatin (3 mm), or simvastatin (3 mu M)) for 2, 4 or 6 h followed by reacting with FITC-conjugated annexin V for the detection of initial apoptosis signal (flip-flop). Various statin-treated myoblasts were significantly stained with FITC-annexin V at 6h, whereas they were not detected at 2h. Moreover, immunoblot analysis indicated that when the cells were treated with cerivastatin (3 pm), membrane-associated Ras protein was activated and detached until 6 h, resulting in cell death through the consequent activation of caspase-8. On the other hand, since cytosolic Ras activation did not activate, there is still an unknown mechanism in statin-related Ras depletion. In conclusion, statin-induced apoptosis in muscular tissue was directly initiated by the farnesyl-anchored Ras protein depletion from cell membrane with subsequent apoptosis.
  • Evaluation of apoptosis and necrosis induced by statins using fluorescence-enhanced flow cytometry, N Yasuda, S Matzno, C Iwano, M Nishikata, K Matsuyama, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 39(3-4), 712 - 717, Sep. 2005 , Refereed
    Summary:The purpose of this study was to evaluate the apoptosis, and necrosis induced by five kinds of statins in IM-9 human lymphoblasts with fluorescence-enhanced flow cytometry using avidin-biotin complex. IM-9 human lymphoblasts (2 x 10(4) cells/cm(2)) were seeded into tissue culture plates and incubated with five kinds of statins. Statin-treated cells were first incubated with biotin-annexin V, followed by addition of avidin-FlTC and propidium iodide, and then subjected to flow cytometry. The fluorescence intensity was enhanced using an avidin-biotin complex system, resulting in successful separate determination of the statin-induced apoptosis and necrosis by flow cytometry, which enabled us to quantitatively evaluate the statin-induced cell damage. Flow cytometric analysis results in the intensity of statin-induced apoptosis in IM-9 cells as follows: atorvastatin = cerivastatin > fluvastatin > simvastatin > pravastatin. The intensity of statin-induced necrosis in IM-9 cells was expressed as follows: atorvastatin = cerivastatin > fluvastatin = sunvastatin > pravastatin. The total damage of IM-9 cells induced by five kinds of statins were expressed as the sum of both percentages of apoptosis and necrosis as follows: atorvastatin =. cerivastatin > fluvastatin = simvastatin > pravastatin. Our studies show that fluorescence enhancement with avidin-biotin complex is useful for the identification and quantitation of annexin-positive apoptosis cells and thus, the fluorescence-enhanced flow cytometry was shown to be applicable for screening of statins as new anti-leukemia agents. (c) 2005 Elsevier B.V. All rights reserved.
  • Effect of quinine solutions on intracellular Ca2+ levels in neuro-2a cells - Conventional physiological method for the evaluation of bitterness, T Nakamura, T Akiyoshi, N Tanaka, K Shinozuka, S Matzno, T Nakabayashi, K Matsuyama, M Kashiwayanagi, T Uchida, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 26(11), 1637 - 1640, Nov. 2003
    Summary:The purpose of the present study was to examine the effect of quinine on intracellular Ca2+ ([Ca2+](i)) levels in cultured neuro-2a cells, and to investigate the possibility of using [Ca2+](i) levels to predict the bitterness of quinine solutions. [Ca2+](i) levels in neuro-2a cells increased following stimulation by quinine in a concentration-related manner. There was a good linear correlationship between the quinine-induced increase in [Ca2+](i) levels increase and the bitterness scores of the quinine solutions as assessed in human gustatory sensation tests (r(2)=0.918). The quinine-induced increase in [Ca2+](i) levels was inhibited by thapsigargin (an inhbitor of the Ca2+ pump into intracellular stores), U73122 (an inhibitor of phospholipase C) and omega-conotoxin (an N-type Ca2+- channel blocker), but not by nifedipine (an L-type Ca2+-channel blocker).
  • Risk of rhabdomyolysis by the concomitant use of vitamin supplements and HMG-CoA reductase inhibitors, Tazuya-Murayama Keiko, Matzno Sumio, Yamada Kazuko, Nakabayashi Toshikatu, Uchida Takahiro, Matsuyama Kenji, Mishima Motohiro, Japanese journal of food chemistry, Japanese journal of food chemistry, 10(2), 78 - 84, Aug. 29 2003
    Summary:HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase (EC inhibitors (statins) are used for hypercholestemia. HMG-CoA reductase is the rate-limiting enzyme of cholesterol biosynthesis. Rhabdomyolysis is one of the most serious side effects by statins. On the other hand, vitamins are used widely and easily for supplements of nutrition in daily use. Statins are one of the most marketable drugs for hypercholesterolemia. Vitamins are taken without prescription as supplements of nutrition ; the patient who prescribed statins may take vitamins. So the interaction with statins and vitamins were studied by using the in vitro assay system with L6 rat myoblasts. The myopathy was increased by the presence of vitamin A, vitamin D and nicotinic acid. Especially the severe injury was induced to the cells by vitamin A and vitamin D. The other vitamins, vitamin B_1, B_6, B_<12>, vitamin C and vitamin E did not show the reaction on the L6 cells. Taking vitamins together with statins increase the risk of rhabdomyolysis. The results of this study suggest that it is desirable for the person takes statins not to take vitamin A, vitamin D and nicotinic acid.
  • Evaluation of the synergistic adverse effects of concomitant therapy with statins and fibrates on rhabdomyolysis, S Matzno, K Tazuya-Murayama, H Tanaka, S Yasuda, M Mishima, T Uchida, T Nakabayashi, K Matsuyama, JOURNAL OF PHARMACY AND PHARMACOLOGY, JOURNAL OF PHARMACY AND PHARMACOLOGY, 55(6), 795 - 802, Jun. 2003 , Refereed
    Summary:Rhabdomyolysis is a severe adverse effect of hypolipidaemic agents such as statins and fibrates. We evaluated this muscular cytotoxicity with an in-vitro culture system. Cellular apoptosis was determined using phase-contrast and fluorescein microscopic observation with Hoechst 33342 staining. L6 rat myoblasts were treated with various statins and bezafibrate under various conditions. With statins only, skeletal cytotoxicity was ranked as cerivastatin>fluvastatin>simvastatin>atorvastatin> pravastatin in order of decreasing potency. Combined application of fibrates enhanced atorvastatin-induced myopathy, which causes little apoptosis alone. These results suggest that statins and fibrates synergistically aggravate rhabdomyolysis.
  • Calcium channel blocking and vasodilating actions of the novel dihydropyridine derivative AE0047, M Nishikawa, M Gohda, H Shinyama, S Matzno, K Yamanaga, H Kido, N Nakamura, CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 25(5), 347 - 354, May 1998
    Summary:1. The pharmacological characteristics of AE0047, a newly synthesized dihydropyridine (DHP) derivative, were investigated in vitro. 2. In bovine aortic membrane, AE0047 and other DHP calcium channel blockers (nitrendipine, nicardipine) displayed concentration-dependent antagonism to specific [H-3]-PN200-110 binding sites with the following values for inhibition constants (K-i) obtained: 20.8+/-8.9, 12.3+/-4.5 and 3.9+/-1.0 nmol/L for AE0047, nitrendipine and nicardipine, respectively, 3. In guinea-pig ventricular myocytes, AE0047 blocked the L-type calcium current, with values for the dissociation constant (K-d) and Hill coefficient of 11.4+/5.7 nmol/L and 0.852+/-0.061, respectively, indicating in the terms of Hill's hypothesis that one drug molecule blocks one calcium channel molecule. 4. In rat aorta, AE0047 inhibited Ca-45 uptake induced by high K+ (100 mmol/L) by 55%. 5. AE0047 and nitrendipine concentration dependently relaxed rat aortic strips contracted with 30 mmol/L KCl. The response to nitrendipine reached a plateau within 60 min and disappeared after drug washing, Interestingly, AE0047 required 5 h or more to produce a plateau of response, with no effect of drug washing, This confirmed the slow onset and long duration of its vasodilating action, 6. With AE0047, tissue content in rat aorta increased more slowly than with nitrendipine and release of AE0047 from tissue was also slower. 7. The data suggest that AE0047 is incorporated slowly into smooth muscle membranes, approaches receptors slowly through the membrane bilayer and accumulates in the membrane because of its high lipophilicity, resulting in an antihypertensive action that is slow in onset and of long duration.
  • Possible mechanism for the anti-atherosclerotic action of the calcium channel blocker AE0047 in cholesterol-fed rabbits, K Hayashi, T Imada, T Yamauchi, H Kido, H Shinyama, S Matzno, N Nakamura, Y Kagitani, CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 25(1), 17 - 25, Jan. 1998
    Summary:1, The present study was designed to investigate the antiatherosclerotic effect of AE0047, a calcium channel blocker, and to compare it with that of nilvadipine in cholesterol-fed rabbits, Furthermore, the effects of AE0047 on low-density lipoprotein (LDL) oxidation were studied in vitro, 2, A 7 week treatment period with AE0047 (3 and 10 mg/kg, p.o.) led to a dose-dependent reduction in the lipid deposition area by Oil Red-O staining (surface index) without affecting serum lipid levels, There was no reduction in the surface index following treatment with the same dose of nilvadipine (10 mg/kg), 3, In a vehicle-administered high-fat diet group of rabbits, levels of total cholesterol (TC) and esterified cholesterol (EC) and calcium content in the aorta were increased approximately two-to three-fold over those of the normal diet group, Increased levels of TC and EC and calcium content were reduced to the same levels as the normal diet group by AE0047 treatment, whereas nilvadipine did not affect TC and EC levels, 4, In an in vitro study, AE0047 (10 mu mol/L) inhibited LDL oxidation and the aggregation of apolipoprotein (Ape) B-100 induced by Cu2+, Furthermore, AE0047 inhibited the degradation of oxidized LDL by macrophages. In contrast, the same dose of nilvadipine (10 mu mol/L) did not inhibit either LDL oxidation or the aggregation of ApoB-100, 5, In summary, AE0047 inhibited LDL oxidation, resulting in a decrease of its uptake into macrophages and an inhibition of cholesterol esterification. This leads to an anti-atherosclerotic effect of AE0047, Thus, AE0047 may have therapeutic potential in preventing cardiovascular disease in hypertensive patients.
  • Inhibition of cholesterol biosynthesis by squalene epoxidase inhibitor avoids apoptotic cell death in L6 myoblasts, S Matzno, T Yamauchi, M Gohda, N Ishida, K Katsuura, Y Hanasaki, T Tokunaga, H Itoh, N Nakamura, JOURNAL OF LIPID RESEARCH, JOURNAL OF LIPID RESEARCH, 38(8), 1639 - 1648, Aug. 1997
    Summary:The relationship between the inhibition of cholesterol biosynthesis and occurrence of myopathy was studied in L6 myoblasts using two lines of cholesterol biosynthesis inhibitors, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (simvastatin) and squalene epoxidase inhibitors (TU-2078 and NB-598). All inhibitors completely inhibited the cholesterol synthesis in L6 myoblasts at doses of 1 and 3 mu M. Simvastatin (3 mu M) inhibited the fusion reaction of L6 myoblasts followed by the severe cellular damage. The myoblasts also had failed actin fiber formation and creatinine phosphokinase (CPK) production. Additionally, this agent also caused apoptotic cell death in differentiated L6 muscle fiber, indicating that skeletal myopathy by HMG-CoA reductase inhibitors seems to occur not only in differentiating immature myoblasts but also in matured skeletal myotubes. In contrast, TU-2078 and NB-598 had no effect on the fusion reaction of differentiating myoblasts or on the cellular viability of muscle fiber at 3 mu M, enough to completely inhibit cholesterol biosynthesis. It is conceivable that the mevalonate depletion and subsequent failure of ras farnesylation induced by simvastatin might cause the defects in differentiation and maintenance of the muscle fiber. Squalene epoxidase inhibitors did not show this adverse effect presumably because of the enzyme inhibition downstream of farnesyl synthesis. The present findings suggest the safe use of squalene epoxidase inhibitors in lipid-lowering therapy.
  • Possible mechanism of action of AE0047, a calcium antagonist, on triglyceride metabolism, K Hayashi, M Gohda, S Matzno, Y Kubo, H Kido, T Yamauchi, N Nakamura, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 282(2), 882 - 890, Aug. 1997
    Summary:We evaluated the effect of AE0047, a dihydropyridine-type calcium antagonist, on the plasma lipid levels of obese Zucker rats, In rats treated orally with 3 to 10 mg/kg/day AE0047 for 7 days, plasma triglyceride CTG) and TG-rich lipoprotein levels dose-dependently decreased, whereas those of high-density lipoprotein cholesterol increased. Total cholesterol and low-density lipoprotein levels did not change. To elucidate the mechanism by which AE0047 decreases plasma TG levels, we examined the effect of AE0047 on the synthesis and secretion of TG-rich lipoproteins in human intestinal cell line Caco-2, as well as on the association and degradation of very low density lipoprotein (VLDL) in human hepatoblastoma cells HepG2. When Caco-2 cells were grown on a membrane filter and C-14-oleic acid was added to the apical side, 10(-5) and 10(-6) M AE0047 inhibited basolateral secretion of C-14-TG. AE0047 also suppressed the basolateral secretion of apolipoprotein B. In HepG2 cells, AE0047 increased the cellular uptake of I-125- VLDL. These results suggested that AE0047 decreased plasma TG level by the inhibition of intestinal chylomicron secretion and the enhancement of hepatic uptake of VLDL. AE0047 may be beneficial for the treatment of hypertensive patients with hypertriglyceridemia to reduce the risk factors of coronary heart disease.
  • AL0671, a new potassium channel opener, inhibits nonenzymatic glycation of protein and LDL oxidation, T Yamauchi, S Matzno, T Imada, M Eda, Y Inoue, N Nakamura, GENERAL PHARMACOLOGY, GENERAL PHARMACOLOGY, 27(2), 257 - 262, Mar. 1996
    Summary:1. The effects of AL0671, a navel potassium channel opener, on protein glycation and low density lipoprotein (LDL) oxidation were tested. 2. AL0671 dose dependently inhibited both fluorescence development of bovine serum albumin and cross linking of lysozyme. These inhibitory effects for glycation were no less potent than aminoguanidine. 3. AL0671 dose dependently inhibited both increase in negative charge and apo B-100 fragmentation during incubation of LDL with Cu2+. In addition, AL0671 significantly decreased the LDL degradation in rat peritoneal macrophages. 4. Neither pinacidil nor levcromakalim inhibited protein glycation and LDL oxidation. 5. Antioxidant properties of AL0671 might be due to its potent electron donating ability, and this agent is expected to be useful for hypertensive diabetes.
  • Synthesis and pharmacological evaluation of N-(6-functionalized-amino-3-pyridyl)-N'-bicycloalkyl-N''-cyanoguanidines as antihypertensive agents, M Eda, T Takemoto, T Okada, H Sakashita, S Matzno, M Gohda, K Hayashi, N Nakamura, C Fukaya, CHEMICAL & PHARMACEUTICAL BULLETIN, CHEMICAL & PHARMACEUTICAL BULLETIN, 44(2), 307 - 313, Feb. 1996
    Summary:A series of amino acid conjugates of N-(6-amino-3-pyridyl)-N'[exo-bicyclo[2.2.1]hept-2-yl]-N ''-cyanoguanidine (4) were prepared and evaluated as antihypertensive agents. The parent compound 4 showed potent potassium channel-opening and antihypertensive activities, but with undesirable changes of the urinary balance of electrolytes. However, alanine and histidine congeners (9,19) reduced this undesirable side effect of 4 through improved pharmacokinetics without loss of antihypertensive activity. They also provided additional information on the structural requirements for pinacidil-type potassium channel openers.
    Summary:1. We evaluated the mechanism of activation by AL0671, a novel potassium channel opener, of potassium current in rat aortic smooth muscle cells. 2. Under conditions of whole cell recording, AL0671 (1-1000 mu M) markedly increased potassium current with a Hill coefficient of 2 and dissociation constant of 1.5 x 10(-4) M. This activation was completely inhibited by intracellular ATP. 3. Under inside-out patch conditions, the ATP-sensitive K+ channels (K-ATP) treated with AL0671 (100 mu M) showed prolongation of the slower open time component and shortening of the slower closed time component without modification of channel conductance.
    Summary:Antihypertensive drugs are expected to have a lipid-lowering effect for use in treating ischemic heart disease. We evaluated the effect of (+)-N-(6-amino-3-pyridil)-N'-[(1S,2R,4R)-bicyclo-[2.2.1]hept-2-yl]-N''-cyanoguanidine hydrochloride (AL0671), a newly synthesized cyanoguanidine-derivative potassium channel opener, on serum lipid and lipoprotein levels in obese Zucker rats, a genetically engineered model of type IV hyperlipidemia. AL0671 dose-dependently decreased systolic blood pressure in obese Zucker rats. Serial administration (for 1 or 2 weeks) of AL0671 (5 mg/kg/day) significantly decreased serum total triglyceride, chylomicron and very-low-density lipoprotein levels with increasing high-density lipoprotein cholesterol, whereas low-density lipoprotein levels did not change. AL0671 (5 mg/kg/day) increased lipoprotein lipase activities 4-fold and hepatic triglyceride lipase activities 3-fold in postheparin plasma. Another urea-derivative compound, AL0674, whose potassium channel-opening activity is diminished, did not affect serum lipid and lipoprotein levels. These results suggested that AL0671 activates both lipoprotein lipase and hepatic triglyceride lipase activities through its potassium channel-opening activity followed by decreasing triglyceride-rich lipoproteins in genetically obese hyperlipemic rats. Therefore, AL0671 might be beneficial in the treatment of hypertensive patients with hypertriglyceridemia (probably with insulin resistance).
    Summary:The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N''-cyanoguanidine derivatives, from among which three compounds were selected as potent potassium-channel openers. In the present study, selected compounds were tested for antagonism of potassium-induced contraction of rat aorta, hypotensive activity in normotensive rats, and diuretic activity in spontaneously hypertensive rats. This led to further evaluation of compound (+/-)-10 and selection of (+)-N-(6-amino-3-pyridyl)-N'-[(1S,2R,4R)-bicyclo[2.2.1]hept-2-yl]-N''-cyanoguanidine ((+)-10) (AL0670) for development as an antihypertensive agent. Although AL0670 is regarded as a pinacidil-type K+-channel opener, it showed different pharmacological and conformational profiles from pinacidil.
    Summary:This report describes the synthesis and pharmacological evaluation of a series of novel potassium channel openers related to the pinacidil-type compounds. Thioureas, cyanoguanidines, and pyridine N-oxides were systematically evaluated for their effects on both the inhibition of spontaneous mechanical activity in rat portal vein (in vitro) and their antihypertensive activity (in vivo), and the structure-activity relationship for this series of compounds was discussed. Good correlation between in vitro and iv antihypertensive activity was observed for these compounds. Among them, cyanoguanidines bearing a conformationally rigid unit such as a norbornyl group generally possessed potent activity in both in vitro and in vivo studies. Especially, N-(6-amino-3-pyridyl)-N'-cyano-N''-(1-methyl-2-norbornyl)guanidine (23d) was identified as a more potent potassium channel opener in vitro (EC(100) = 3 x 10(-8) M) than pinacidil (EC(100) = 10(-7) M).
    Summary:A monoclonal antibody (MAb) against human acrosome-reacted sperm was attached to paramagnetic polystyrene beads. Human sperm prepared by the swim-up method were 1) incubated in m-BWW, 2) incubated and ionophore treated, or 3) incubated with 5% seminal fluid. After treatment, sperm were mixed with the beads and incubated for 1 hr. Variously treated sperm showed different binding abilities to the beads. Sperm bound to the beads were collected by a magnet and subjected to triple staining. Most of the collected sperm were acrosome reacted. The results suggested that the beads can be used to estimate the acrosomal status of sperm, and that the use of antibody-coated paramagnetic beads provides a convenient way of collecting acrosome-reacted sperm. The acrosomal status detected by the beads was also compared with the ability of sperm to fuse with zona-free hamster eggs. It was found that greater bead-binding ability correlated with more sperm fusing with zona-free hamster eggs.

Conference Activities & Talks

  • 多職種連携における医療・介護従事者のコミュニケーション能力向上のためのアンガーマネジメント研修, 高橋直子, 高橋直子, 高橋直子, 松野純男, 伊藤栄次, 日本薬学会年会要旨集(CD-ROM),   2019
  • 地域の多職種連携における医療・介護従事者のコミュニケーション能力向上のためのアンガーマネジメント研修, 高橋直子, 高橋直子, 高橋直子, 松野純男, 伊藤栄次, 日本プライマリ・ケア連合学会学術大会抄録集,   2019
  • 学校での心臓突然死を防ぐための小中校生および教職員を対象とした一次救命処置教育と小学校救命ラリー教育, 高橋直子, 高橋直子, 高橋直子, 岸田洋平, 岸田洋平, 野村順二, 笹山周平, 保坂恵里奈, 安東貞喜, 安東貞喜, 竹内あずさ, 竹内あずさ, 松野純男, 伊藤栄次, 日本プライマリ・ケア連合学会学術大会抄録集,   2019
  • Prediction of side effects by deep learning using drug side effect database (JADER), 松井大樹, 松野純男, 小野田良, 大星直樹, 電子情報通信学会技術研究報告,   2018 12 08
  • クラウド上に構築した災害時医薬品管理システムとその評価, 北小路学, 石渡俊二, 村瀬惇, 井上知美, 大鳥徹, 松野純男, 小竹武, 日本薬学会年会要旨集(CD-ROM),   2018
  • 薬剤師の医療コミュニケーション能力向上のためのアンガーマネジメント研修, 高橋直子, 高橋直子, 高橋直子, 高橋直子, 松野純男, 伊藤栄次, 日本薬学会年会要旨集(CD-ROM),   2018
  • 学校での心臓突然死を防ぐための高校生を対象とした一次救命処置教育, 高橋直子, 高橋直子, 高橋直子, 高橋直子, 竹内あずさ, 竹内あずさ, 野村順二, 笹山周平, 保坂恵里奈, 保坂恵里奈, 安東貞喜, 岸田洋平, 岸田洋平, 松野純男, 伊藤栄次, 日本プライマリ・ケア連合学会学術大会抄録集,   2018
  • 新規院内製剤セレン含有口腔内崩壊錠の作製と実用化についての検討, 中尾元紀, 松尾世為子, 大橋香菜子, 田邨保之, 永井聡子, 覺野律, 中村明美, 福永聖子, 川端成佐, 寺倉智子, 松野純男, 緒方文彦, 川崎直人, 大竹裕子, 長井紀章, 国立病院総合医学会(Web),   2018
  • 薬学部学生の薬剤師在宅医療参画に関する問題点の抽出, 村瀬 惇, 松野 純男, 長楽 寿子, 大鳥 徹, 北小路 学, 社会薬学,   2017 09
  • 薬学部学生の薬剤師在宅医療参画に関する問題点の抽出, 村瀬 惇, 松野 純男, 長楽 寿子, 大鳥 徹, 北小路 学, 社会薬学,   2017 09
  • 2016年度薬学共用試験報告, 石川 さと子, 伊藤 智夫, 中村 明弘, 増野 匡彦, 伊藤 喬, 橋詰 勉, 宮崎 智, 前田 定秋, 山口 政俊, 出口 芳春, 石塚 忠男, 三田 智文, 入江 徹美, 野田 幸裕, 飯島 史朗, 松野 純男, 奥 直人, 医学教育,   2017 08
  • 薬学共用試験CBTの結果解析(2016), 石川 さと子, 伊藤 智夫, 中村 明弘, 増野 匡彦, 伊藤 喬, 宮崎 智, 前田 定秋, 山口 政俊, 出口 芳春, 石塚 忠男, 三田 智文, 飯島 史朗, 松野 純男, 奥 直人, 日本薬学会年会要旨集,   2017 03
  • ヒューマニズム教育の一環としての人体臓器観察の有用性, 和田 哲幸, 中村 武夫, 伊藤 栄次, 松野 純男, 大内 秀一, 八軒 浩子, 日本薬学会年会要旨集,   2017 03
  • 早期体験学習を通しての地域薬局見学における学生の意識調査, 八軒 浩子, 伊藤 栄次, 中村 武夫, 大内 秀一, 和田 哲幸, 松野 純男, 日本薬学会年会要旨集,   2017 03
  • ポリスチレンスルホン酸ナトリウム製剤の適正使用に関する検討, 中田 美樹, 片峰 祐矢, 飯田 浩子, 松野 純男, 中野 行孝, 片岡 裕美, 田鶴谷, 村山) 惠子, 日本薬学会年会要旨集,   2017 03
  • 高カリウム血症治療薬としてのポリスチレンスルホン酸ナトリウムの適正使用に関する検討, 飯田 浩子, 田鶴谷 惠子, 山, 中田 美樹, 片峰 裕矢, 松野 純男, 中野 行孝, 日本腎臓病薬物療法学会誌,   2016 10
  • 2015年度薬学共用試験CBT報告, 石川 さと子, 奥 直人, 中村 明弘, 増野 匡彦, 伊藤 喬, 宮崎 智, 伊藤 智夫, 前田 定秋, 山口 政俊, 出口 芳春, 石塚 忠男, 三田 智文, 飯島 史朗, 松野 純男, 山元 弘, 医学教育,   2016 07
  • 3Dプリンタを用いた医薬品分子模型出力の有用性, 中谷明嗣, 松野純男, 大星直樹, 情報処理学会全国大会講演論文集,   2016 03 10
  • 薬学共用試験CBTの結果解析 2015, 石川 さと子, 奥 直人, 中村 明弘, 増野 匡彦, 伊藤 喬, 宮崎 智, 伊藤 智夫, 前田 定秋, 山口 正俊, 出口 芳春, 石塚 忠男, 三田 智文, 飯島 史朗, 松野 純男, 山元 弘, 日本薬学会年会要旨集,   2016 03
  • 多職種連携における医療・介護従事者のコミュニケーション向上のためのアンガーマネジメント, 高橋 直子, 安藤 俊介, 松野 純男, 伊藤 栄次, 高橋 裕子, 日本薬学会年会要旨集,   2016 03
  • 薬学部学生を対象としたコーチングスキル教育実践のための検討, 幸松健二, 幸松健二, 岡本千絵, 坂原通仁, 松本彰布, 松本彰布, 北小路学, 松野純男, 日本薬学会年会要旨集(CD-ROM),   2016 03
  • 人体臓器観察(早期体験学習)を通してのヒューマニズム教育の検証, 和田哲幸, 中村武夫, 伊藤栄次, 松野純男, 大内秀一, 八軒浩子, 日本薬学会年会要旨集(CD-ROM),   2016 03
  • 地域薬局薬剤師による早期体験学習参加学生の評価およびその解析, 八軒浩子, 伊藤栄次, 松野純男, 大内秀一, 和田哲幸, 中村武夫, 日本薬学会年会要旨集(CD-ROM),   2016 03
  • 薬剤師の在宅医療への取り組みに対する介護職の認識調査, 北小路学, 堀野智美, 大鳥徹, 松野純男, 日本薬学会年会要旨集(CD-ROM),   2016 03
  • 3Dプリンタを用いた分子模型作成システムの構築と医薬品構造理解に関する有用性, 中谷明嗣, 松野純男, 大星直樹, 前川智弘, 日本薬学会年会要旨集(CD-ROM),   2016
  • 基礎薬学分野の知識定着を志向した参加型学修システム構築の試み, 大内秀一, 松野純男, 和田哲幸, 仲西功, 前川智弘, 多賀惇, 伊藤栄次, 大鳥徹, 川崎直人, 西田升三, 日本薬学会年会要旨集(CD-ROM),   2016
  • 免疫抑制薬FTY720の遺伝子発現プロファイリングの解析, 北井 佑樹, 萩原 加奈子, 水庫 彩, 八百 麻里子, 石田 紘基, 喜多 綾子, 佐藤 亮介, 益子 高, 松野 純男, 千葉 健治, 杉浦 麗子, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集,   2015 12
  • ワルファリンと静注用脂肪乳剤の併用によるRT‐INR値の減少について, 黒川建吾, 汐見紘明, 湊聖一郎, 松野純男, 北小路学, 日本医療薬学会年会講演要旨集,   2015 10 23
  • 腎機能推算式に用いる血清クレアチニン値補正方法の前向き研究での検討, 森住誠, 松野純男, 松宮美沙, 今岡寛美, 池田理沙, 金丸絵理, 石原美加, 松田光弘, 北小路学, 日本医療薬学会年会講演要旨集,   2015 10 23
  • 2014年度薬学共用試験CBT報告, 石川 さと子, 奥 直人, 中村 明弘, 増野 匡彦, 伊藤 喬, 宮崎 智, 伊藤 智夫, 前田 定秋, 山口 政俊, 出口 芳春, 石塚 忠男, 三田 智文, 飯島 史朗, 松野 純男, 山元 弘, 医学教育,   2015 07
  • 2014年度薬学共用試験CBTの結果解析, 石川 さと子, 奥 直人, 中村 明弘, 増野 匡彦, 伊藤 喬, 宮崎 智, 伊藤 智夫, 前田 定秋, 山口 政俊, 出口 芳春, 石塚 忠男, 三田 智文, 飯島 史朗, 松野 純男, 山元 弘, 日本薬学会年会要旨集,   2015 03
  • テキストマイニングによる早期体験学習レポートの年度変化の解析, 松野 純男, 八軒 浩子, 伊藤 栄次, 中村 武夫, 大内 秀一, 日本薬学会年会要旨集,   2015 03
  • 人命救助意識の向上を指向した早期体験学習の教育効果, 八軒 浩子, 伊藤 栄次, 松野 純男, 大内 秀一, 中村 武夫, 日本薬学会年会要旨集,   2015 03
  • 構造活性相関と分子構造の理解における3Dアニメーションの有効性の検討, 中谷 明嗣, 松野 純男, 大星 直樹, 日本薬学会年会要旨集,   2015 03
  • 薬学生の災害時支援・救援活動への参加意識, 中村 武夫, 伊藤 栄次, 松野 純男, 大内 秀一, 八軒 浩子, 日本薬学会年会要旨集,   2014 03
  • 薬学共用試験 CBT/OSCEの現状と課題, 伊藤 智夫, 奥 直人, 前田 定秋, 中村 明弘, 山口 政俊, 増野 匡彦, 伊藤 喬, 石塚 忠男, 三田 智文, 出口 芳春, 入江 徹美, 木内 祐二, 橋詰 勉, 宮崎 智, 飯島 史朗, 松野 純男, 石川 さと子, 山元 弘, 日本薬学会年会要旨集,   2014 03
  • 初期救命救急講習を通しての救命意識の向上, 八軒 浩子, 伊藤 栄次, 松野 純男, 大内 秀一, 中村 武夫, 日本薬学会年会要旨集,   2014 03
  • 入職5年次におむる薬剤師研修制度の評価, 草薙みか, 村尾奈苗, 加藤貴由, 橋詰めぐみ, 宮森勇昌, 山本哲也, 奥野健一, 西村知朗, 近藤薫, 亀本浩司, 岸井昭人, 松浦靖, 橋本昌幸, 松野純男, 大里恭章, 日本医療薬学会年会講演要旨集,   2013 08 28
  • 薬剤師の在宅医療参画に関する薬学部生の意識~実務実習前後及び実習中の在宅医療体験による相違~, 長楽寿子, 堀野智美, 大和幹枝, 李繭花, 岸田充生, 松野純男, 北小路学, 高田充隆, 医療薬学フォーラム講演要旨集,   2013 07
  • 加速度センサを用いた調剤技能の動作解析, 松野純男, 朝倉南美, 齊藤美穂, 波部斉, 細見光一, 大星直樹, 高田充隆, 日本薬学会年会要旨集(CD-ROM),   2013
  • 心肺蘇生講習を通してのヒューマニズム教育, 中村武夫, 伊藤栄次, 松野純男, 桑島博, 日本薬学会年会要旨集(CD-ROM),   2013
  • 全国徳洲会グループの薬剤師を対象とした漢方薬意識調査―効果的な漢方教育の実現に向けて―, 岩政かおり, 草薙みか, 門間智恵, 山本倫数, 西山和香子, 松野純男, 大里恭章, 日本薬学会年会要旨集(CD-ROM),   2013
  • 学校薬剤師における薬物乱用防止教育講師養成に関する意識調査, 高橋直子, 松野純男, 伊藤栄次, 藤垣哲彦, 日本薬学会年会要旨集(CD-ROM),   2013
  • 生命倫理の参加型学習による薬学生の死生観の変化, 伊藤栄次, 中村武夫, 松野純男, 日本薬学会年会要旨集(CD-ROM),   2013
  • Evaluation of the generic drug of the nafamostat mesilate preparation using thermogravimetry, Hara A, Ohtori A, Matzno S, Kimura T, Matsuyama K,   2012 08
  • 院内製剤「ポラプレジンク含嗽液」の使用感に関する調査, 中山 雅裕, 冨士原 将之, 中村 豪志, 東 剛史, 松野 純男, 川畑 篤史, 松山 賢治, 上紺屋 憲彦, 木村 健, 日本医薬品情報学会総会・学術大会講演要旨集,   2012 06 , (一社)日本医薬品情報学会
  • 在宅医療実施による薬剤師の意識変化 テキストマイニングによるあぶり出し, 李 繭香, 堀野 智美, 大和 幹枝, 高橋 直子, 岸田 充生, 細見 光一, 藤垣 哲彦, 松野 純男, 北小路 学, 高田 充隆, 日本薬学会年会要旨集,   2012 03 , (公社)日本薬学会
  • 薬局薬剤師の在宅医療への参画の現状 主要な問題点の抽出とその原因の解析, 李 繭香, 北小路 学, 岸田 充生, 高橋 直子, 細見 光一, 松野 純男, 高田 充隆, 日本薬学会年会要旨集,   2011 03 , (公社)日本薬学会
  • Analysis of the questionnaire survey on the continuing education seminar 2010 at Kinki University Faculty of Pharmacy,   2011 03
  • P-34 Mechanism of change of the flower color of Hibiscus mutabilis f. versicolor, Mishima Ayumi, Takahashi Yumi, Oku Hisae, Matuno Sumio, Jyuman Sachiko, Nakabayashi Toshikatu, Ishiguro Kyoko,   2005 09 15
    Summary:The petal of Hibiscus mutabilis L. f. versicolor MAKINO shows a white color after the flowering, and it gradually changes in the red. Though it is reported that the color changes are due to the storage of the anthocyanin in the petal vacuole, the mechanism has not been clarified. Thus, the mechanism of the color change was elucidated by expression analysis of mRNA of anthocyanidin synthetase (ANS) in the petal. Extraction and purification of mRNA: petals of white, pink and red organization of freezed fresh H. mutabilis were crushed in the liquid nitrogen and total RNA was extracted using the CTAB method, followed by the refinement of each mRNA by Purification Kit (TaKaRa). The several kinds of primer of actin and ANS were designed from the homology with other plants respectively and then RT-PCR was done using these primers. On cDNA fragment amplified by RT-PCR, the base sequence was analyzed by the conventional mannner. Using the primer which efficiently amplified the cDNA fragment, the expression of mRNA of the ANS with the change of the flower color was examined by RT-PCR. The amplified fragment of about 600bps was assigned to that of actin and the amplified fragment of about 500bps expressed only in the deep red petal was assigned to that of the ANS of H. mutabilis, referring to the sequence of actin and the ANS respectively. The amino acid sequence of mRNA of actin of H. mutabilis showed a homology over 91% with those of the other type plant and that of the ANS showed a homology over 82%. The expression level of mRNA of the ANS was consistent with the increase in the deep red from the white color. Furthermore, the color change was dependent on temperature but not the light.
  • 村山恵子、吉元広美、岩佐容子、松野純男、中林利克、内田享弘、松山賢治,   2004 03
  • The search for essential cytomembrane receptors during differentiation of pluripotential stem cells to myoblasts, Juman S, Nomizu M, Nakabayashi T, Matzno S,   2003 10
  • 幹細胞から骨格筋への分化とα7 integrinの関係, 十万 佐知子, 宮川 幸子, 中安 香代, 松尾 香代子, 野水 基義, 中林 利克, 松野 純男, 日本薬学会年会要旨集,   2003 03 , (公社)日本薬学会
  • Comparative study on statins induced apoptosis in L6 myoblasts with or without fibrates, Yasuda N, Nishikata M, Tanaka T, Yasuda S, Matzno S, Murayama K, Nakabayashi T, Uchida T, Matsuyama K,   2002 08
  • Effect of AL0671, a novel potassium phannel opener, on potassium current in rat aortic smooth muscle cell", Matzno S, Sato R, Takai H, Aida Y, Karasaki S, Oyaizu M, Katori R, 37th Annual Meeting, Biophysical Society, Washington DC, Matzno S, Sato R, Takai H, Aida Y, Karasaki S, Oyaizu M, Katori R, 37th Annual Meeting, Biophysical Society, Washington DC,   1993 02
  • HMG-CoA reductase inhibitors-induced apoptosis is coupled with membrane farnesylated Ras depletion in L6 myocytes, S Yasuda, S Matzno, H Tanaka, K Tazuya-Murayama, Y Yamamoto, T Uchida, T Nakabayashi, K Matsuyama, JAPANESE JOURNAL OF PHARMACOLOGY,   2002 , JAPANESE PHARMACOLOGICAL SOC

Research Grants & Projects

  • Ministry of Education, Culture, Sports, Science and Technology, Grants-in-Aid for Scientific Research(基盤研究(C)), Possible mechanism of action of metabolic syndrome induction in patients treated with atypical antipsychotic agents, In this study, the authors evaluated the effect of atypical antipsychotic agents (SGAs) on metabolic syndrome induction. Using neuroblastoma cell lines, one of SGAs, olanzapine, induced 5HT_<2C> mRNA transcription in PC12 autonomic neuroblastoma. Furthermore, olanzapine also induced PPAR_γ translation and subsequent fat accumulation in 3T3L1 mouse adipoblastoma cell line. These results suggest that olanzapine induces metabolic syndrome by synergistic effect of both an activation of sympathetic nervous system and an elevation of direct differentiation of adipose tissues.
  • Ministry of Education, Culture, Sports, Science and Technology, Grants-in-Aid for Scientific Research(基盤研究(C)), Evaluation of New Agents modified Vitamin K of anticancer which inhibited cdc 25 phosphatase, The possibility of vitamin K3 (VK3) as an anticancer agent was assessed. VK3 dose-dependently diminished the cell viability (measured as esterase activity) with 1050 of 13. 7mM and Hill coefficient of 3. 1 in Hep G2 cells. It also decreased the population of S phase and arrested cell cycle in the G2/M phase in a dose-dependent manner. G2/M arrest was regulated by the increment of cyclin A/cdk1 and cyclin A/cdk2 complex, and contrasting cyclin B/cdk1 complex decrease. Finally, combined application demonstrated that VK3 significantly enhanced the cytotoxicity of etoposide, a G2 phase-dependent anticancer agent, whereas it reduced the cytotoxic activity of irinotecan, a S phase-dependent agent. These findings suggest that VK3 induces G2/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G2 phase-dependent drugs in hepatic cancer chemotherapy. (Biol Pharm. Bull 31(6) 1270-1273 (2008))
  • Study of the mechanism of myopathy by drugs
  • Study of the regulation process on skeletal muscle differentiation

Educational Activities

Teaching Experience

  • Clinical Trial, Kindai University