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滝口祥令

徳島大学

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2024年11月22日更新

職名: 名誉教授 (2022.4)
電話: 研究者総覧に該当データはありませんでした。
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学歴: 1979/3: 静岡薬科大学薬学部製薬学科卒業
1981/3: 静岡薬科大学院薬学研究科修士課程修了
学位: 医学博士 (浜松医科大学) (1988年2月)
職歴・経歴: 1983/7: 浜松医科大学助手
1995/7: 徳島大学助教授，薬学部
1996/4: 徳島大学大学院助教授，薬学研究科医療薬学専攻
2002/11: 徳島大学大学院教授，薬学研究科医療薬学専攻
2004/4: 徳島大学大学院教授，ヘルスバイオサイエンス研究部

専門分野・研究分野: 臨床薬理学 (Clinical Pharmacology)

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2024年11月22日更新

専門分野・研究分野: 臨床薬理学 (Clinical Pharmacology)
担当経験のある授業科目: 研究者総覧に該当データはありませんでした。
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研究者総覧で最新データを確認する

2024年11月22日更新

専門分野・研究分野: 臨床薬理学 (Clinical Pharmacology)

研究テーマ: 血栓症の病態生理機能解析と薬物療法に関する研究, 薬物間相互作用の機序解明と予測法に関する研究, 薬効·安全性評価システムに関する研究, 薬物動態モニタリングシステムに関する研究 (血栓症, 薬物療法, 臨床薬物動態, 薬効評価) (薬物治療をキーワードに
生体での薬の作用·動態に焦点を当てた研究を行っている
いわば''病気と薬の教室''である．主な研究テーマは1)モデル動物を用いた薬効評価を基に
虚血再還流障害や梗塞
血管肥厚の発症·進展に関与する生体内因子の役割解明と新しい薬物療法戦略の確立
2)医薬品の適正使用への貢献を目指す育薬研究として
薬物間相互作用の機序解明と薬物使用状況や薬物動態の特徴を評価できるトータル薬物モニタリングシステムの構築を行っている．)

著書

滝口祥令 :
図解薬害・副作用学改訂2版血液・造血系に作用する薬,
株式会社南山堂, 2017年9月. 滝口祥令 :
図解薬害・副作用学,
株式会社南山堂, 東京, 2013年8月. 植松俊彦, 滝口祥令, 丹羽雅之 :
新体系看護学全書疾病の成り立ちと回復の促進⑤ 薬理学,
株式会社メヂカルフレンド社, 2011年12月. 滝口祥令 :
心臓・血管系疾患,
株式会社南山堂, 東京, 2005年4月. 滝口祥令 :
医学大事典,
株式会社医学書院, 2003年3月. 滝口祥令 :
免疫·アレルギー疾患と治療薬,
医薬ジャーナル社, 大阪, 1999年8月. 滝口祥令 :
心臓·血管系疾患,
株式会社南山堂, 東京, 1999年. Yoshiharu Takiguchi and Toshihiko Uematsu :
Thrombosis model with photochemical reaction in femoral artery.,
Churchill-Livingstone, Jan. 1994. Yoshiharu Takiguchi, Koichiro Wada and Atsuhiro Mizuno :
Evaluation of antithrombotic drugs:Platelet inhibition and anticoagulants.,
Churchill-Livingstone, Jan. 1994. 滝口祥令, 中島光好 :
薬理学からみた動脈硬化ー抗動脈硬化薬とはー,
株式会社メジカルビュー社, 1993年. 滝口祥令, 中島光好 :
交感神経抑制薬とは何かー交感神経抑制薬の種類と薬理作用の特長,
メディカルレビュー社, 1989年.

論文

Yuto Horii, Toshiki Iniwa, Masayoshi Onitsuka, Jun Tsukimoto, Yuki Tanaka, Hironobu Ike, Yuri Fukushi, Haruna Andoh, Yoshie Takeuchi, So-ichiro Nishioka, Daisuke Tsuji, Mariko Ikuo, Naoshi Yamazaki, Yoshiharu Takiguchi, Naozumi Ishimaru and Kouji Itou :
Reversal of neuroinflammation in novel galactosialidosis model mice by single intracerebroventricular administration of CHO-derived human recombinant cathepsin A precursor protein.,
Molecular Therapy. Methods & Clinical Development, Vol.25, No.June, 297-310, 2022.

(徳島大学機関リポジトリ): ● Metadata: 117739
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.omtm.2022.04.001
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.omtm.2022.04.001

(徳島大学機関リポジトリ: 117739, DOI: 10.1016/j.omtm.2022.04.001) Naoshi Yamazaki, Keisuke Kanazawa, Maria Kimura, Hironobu Ike, Makiko Shinomiya, Shouko Tanaka, Yasuo Shinohara, Noriaki Minakawa, Kouji Itou and Yoshiharu Takiguchi :
Use of modified U1 small nuclear RNA for rescue from exon 7 skipping caused by 5-splice site mutation of human cathepsin A gene,
Gene, Vol.677, 41-48, 2018.

(要約): Cathepsin A (CTSA) is a multifunctional lysosomal enzyme, and its hereditary defect causes an autosomal recessive disorder called galactosialidosis. In a certain number of galactosialidosis patients, a base substitution from adenine to guanine is observed at the +3 position of the 7th intron (IVS7 +3a>g) of the CTSA gene. With this mutation, a splicing error occurs; and consequently mRNA lacking the 7th exon is produced. This skipping of exon 7 causes a frame shift of the transcripts, resulting in a non-functional CTSA protein and hence galactosialidosis. This mutation seems to make the interaction between the 5'-splice site of intron 7 of pre-mRNA and U1 small nuclear RNA (U1 snRNA) much weaker. In the present study, to produce properly spliced mRNA from the CTSA gene harboring this IVS7 +3a>g mutation, we examined the possible usefulness of modified U1 snRNA that could interact with the mutated 5'-splice site. Toward this goal, we first prepared a model system using a mutant CTSA mini gene plasmid for delivery into HeLa cells. Then, we examined the effectiveness of modified U1 snRNA on the formation of properly spliced mRNA from this mutant CTSA mini gene. As a result, we succeeded in obtaining improved formation of properly spliced CTSA mRNA. Our results suggest the usefulness of modified U1 snRNA for rescue from exon 7 skipping caused by the IVS7 +3a>g mutation of the CTSA gene.
(キーワード): Cathepsin A / Cell Line, Tumor / Exons / HeLa Cells / Humans / Introns / Mutation / RNA Precursors / RNA Splice Sites / RNA Splicing / RNA, Messenger / RNA, Small Nuclear
(徳島大学機関リポジトリ): ● Metadata: 111998
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.gene.2018.07.030
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30010039; ● Summary page in Scopus @ Elsevier: 2-s2.0-85050244217

(徳島大学機関リポジトリ: 111998, DOI: 10.1016/j.gene.2018.07.030, PubMed: 30010039, Elsevier: Scopus) Shimokawa Yoshihiko, Yoda Noriaki, Kondo Satoshi, Yamamura Yoshiya, Yoshiharu Takiguchi and Umehara Ken :
Inhibitory Potential of Twenty Five Anti-tuberculosis Drugs on CYP Activities in Human Liver Microsomes,
Biological & Pharmaceutical Bulletin, Vol.38, No.9, 1425-1429, 2015.

(要約): The direct inhibitory potential of twenty five anti-tuberculosis drugs on eight CYP-specific reactions in human liver microsomes was investigated to predict in vivo drug-drug interactions (DDIs) from in vitro data. Rifampicin, rifabutin, and thioacetazone inhibited one CYP reaction. Isoniazid and clofazimine had inhibitory effects on four CYP reactions, and rifapentine, ethionamide, and prothionamide widely inhibited CYP reactions. Based on the inhibition constant (Ki) and the therapeutic total inhibitor concentrations [I]max of eight drugs in human plasma, [I]max/Ki values were calculated to evaluate clinical DDIs. The [I]max/Ki values were 0.20 or less for rifampicin, rifabutin, and thioacetazone; 0.15-2.0 for isoniazid; 0.14-1.5 for rifapentine; 0.29-1.4 for ethionamide; 0.41-2.2 for prothionamide; and 0.12-6.3 for clofazimine. The highest [I]max/Ki values were 2.0 for isoniazid on CYP3A4 [testosterone (T)]; 1.5 for rifapentine on CYP3A4 [midazolam (M)]; 1.4 for ethionamide on CYP2C8; 2.2, 1.8, and 1.3 for prothionamide on CYP2B6, CYP2C19, and CYP2C8, respectively; and 6.3 and 5.7 for clofazimine on CYP3A4 (M) and CYP3A4 (T), respectively. These drugs with high [I]max/Ki values lead to clinical DDIs. Considering the drug regimens for tuberculosis (TB) and co-infection with TB and human immunodeficiency virus, the inhibitory potential for CYP3A4 and CYP2B6 is particularly important. These results suggest that clofazimine and prothionamide are likely to cause clinically relevant DDIs when co-administered with products metabolized by CYP3A4 and CYP2B6, respectively. Isoniazid and rifapentine may cause DDIs with drugs metabolized by CYP3A4.
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b15-00313
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26094899; ● Summary page in Scopus @ Elsevier: 2-s2.0-84941037152

(DOI: 10.1248/bpb.b15-00313, PubMed: 26094899, Elsevier: Scopus) Takenori Yamamoto, Mika Ito, Keita Kageyama, Kana Kuwahara, Kikuji Yamashita, Yoshiharu Takiguchi, Seiichiro Kitamura, Hiroshi Terada and Yasuo Shinohara :
Mastoparan peptide causes mitochondrial permeability transition not by interacting with specific membrane proteins but by interacting with the phospholipid phase.,
The FEBS Journal, Vol.281, No.17, 3933-3944, 2014.

(要約): The mastoparan peptide is known as an inducer of the mitochondrial permeability transition. Although mastoparan was suggested to interact with a proteinaceous target in mitochondria to induce this transition, the action sites of mastoparan have not yet been investigated. To clarify whether specific interactions of mastoparan with receptors or enzymes are associated with the induction of this permeability transition, we examined the effects of d-isomeric peptides, which were synthesized using d-amino acids assembled in endogenous (inverso mastoparan) and reverse (retro-inverso mastoparan) orientations. When we added inverso mastoparan to isolated mitochondria, the peptide caused the permeability transition in a partially cyclosporin A-sensitive manner at lower doses and in a cyclosporin A-insensitive manner at higher ones. The manners of action and the potencies of inverso mastoparan were close to those of parent mastoparan, indicating that the targets of mastoparan for induction of the permeability transition were neither receptors, nor enzymes in the mitochondria. Retro-inverso mastoparan also had the same effect on the mitochondria as mastoparan, although the potencies of the effect were weaker. Not only on mitochondria, but also on phospholipid vesicles, mastoparan and inverso mastoparan showed massive permeabilization effects at the same potencies, although retro-inverso mastoparan showed weaker ones. These results indicate that mastoparan interacted with the phospholipid phase of the mitochondrial membrane (and not with specific proteins) to induce the permeabilization in cyclosporin A-sensitive and -insensitive manners.
(キーワード): Animals / Cyclosporine / Male / Membrane Lipids / Mitochondria, Liver / Mitochondrial Membrane Transport Proteins / Mitochondrial Membranes / Peptides / Phosphatidylcholines / Rats / Stereoisomerism / Wasp Venoms
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/febs.12930
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25039402; ● Search Scopus @ Elsevier (PMID): 25039402; ● Search Scopus @ Elsevier (DOI): 10.1111/febs.12930

(DOI: 10.1111/febs.12930, PubMed: 25039402) Takuya Hada, Takenori Yamamoto, Atsushi Yamamoto, Kazuto Ohkura, Naoshi Yamazaki, Yoshiharu Takiguchi and Yasuo Shinohara :
Comparison of the catalytic activities of three isozymes of carnitine palmitoyltransferase 1 expressed in COS7 cells,
Applied Biochemistry and Biotechnology, Vol.172, No.3, 1486-1496, 2014.

(要約): The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine, and three isozymes of it, 1a, 1b, and 1c, have been identified. Interestingly, the 1c isozyme was reported to show no enzymatic activity, but it was not clearly demonstrated whether this inactivity was due to its dysfunction or due to its poor expression. In the present study, we (a) expressed individual CPT1 isozymes in COS7 cells, (b) evaluated quantitatively their expression levels by Western blotting using the three bacterially expressed CPT1 isozymes as standards, and (c) evaluated their catalytic activities. With these experiments, we successfully demonstrated that the absence of the enzymatic activity of the 1c isozyme was due to its dysfunction. In addition, experiments on the preparation of standard CPT1 isozymes revealed that the 1c isozyme did not show the standard relationship between migration in an SDS-PAGE gel and molecular size. We further tried to determine why the 1c isozyme was inert by preparing chimeric CPT1 between 1a and 1c, but no clear conclusion could be drawn because one of the chimeric CPT1s was not sufficiently expressed.
(キーワード): Acyl Coenzyme A / Animals / COS Cells / Carnitine O-Palmitoyltransferase / Cercopithecus aethiops / Electrophoresis, Polyacrylamide Gel / Gene Expression Regulation / Isoenzymes / Kinetics / Mitochondria, Liver
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12010-013-0619-y
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24222496; ● Summary page in Scopus @ Elsevier: 2-s2.0-84896316059

(DOI: 10.1007/s12010-013-0619-y, PubMed: 24222496, Elsevier: Scopus) Yusaku Kikuchi, Naoshi Yamazaki, Noriko Tarashima, Kazuhiro Furukawa, Yoshiharu Takiguchi, Kouji Itou and Noriaki Minakawa :
Gene suppression via U1 small nuclear RNA interference (U1i) machinery using oligonucleotides containing 2'-modified-4'-thionucleosides,
Bioorganic & Medicinal Chemistry, Vol.21, No.17, 5292-5296, 2013.

(要約): Gene suppression via U1 small nuclear RNA interference (U1i) is considered to be one of the most attractive approaches, and takes the place of general antisense, RNA interference (RNAi), and anti-micro RNA machineries. Since the U1i can be induced by short oligonucleotides (ONs), namely U1 adaptors consisting of a 'target domain' and a 'U1 domain', we prepared adaptor ONs using 2'-modified-4'-thionucleosides developed by our group, and evaluated their U1i activity. As a result, the desired gene suppression via U1i was observed in ONs prepared as a combination of 2'-fluoro-4'-thionucleoside and 2'-fluoronucleoside units as well as only 2'-fluoronucleoside units, while those prepared as combination of 2'-OMe nucleoside/2'-OMe-4'-thionucleoside and 2'-fluoronucleoside units did not show significant activity. Measurement of Tm values indicated that a higher hybridization ability of adaptor ONs with complementary RNA is one of the important factors to show potent U1i activity.
(徳島大学機関リポジトリ): ● Metadata: 113344
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bmc.2013.06.023
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23871495; ● Search Scopus @ Elsevier (PMID): 23871495; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2013.06.023

(徳島大学機関リポジトリ: 113344, DOI: 10.1016/j.bmc.2013.06.023, PubMed: 23871495) 滝口祥令 :
実務実習における教育評価法プログラムの現状と課題,
薬学雑誌, Vol.132, No.2, 365-368, 2012年.

(要約): Formative assessment which refers to frequent, interactive assessments of student progress and understanding is one of the most effective strategies for promoting high student performance and developing students' "learning to learn" skills. Portfolio (personal record of learning) is a useful tool for tracking individual student progress toward learning goals. We conducted the questionnaire survey in 14 National Universities on approach to the formative assessment methods and the use of portfolio in the long-term practice experience (pharmacy clerkship) at community pharmacy and hospital pharmacy which was undergone for the first time in 2010. The finding obtained from our questionnaires implicated that portfolio is useful for sharing information among student, tutorial pharmacist and faculty members. All universities have provided tools for visible assessment of student achievement. However, they are not used enough for feedback on student performance, and formative assessment is not practiced systematically. A reason seems to be differences in understanding of it. In addition to improvement of the tools to support formative assessment, promotion of effective assessment practice will need for systematic evaluation.
(キーワード): educational evaluation / practical experience / portfolio / formative assessment
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.132.365
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001206129390080; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.132.365

(DOI: 10.1248/yakushi.132.365, CiNii: 1390001206129390080) S. Nishibayashi, K. Hattori, T. Hirano, K. Uehara, Y. Nakano, M. Aihara, Y. Yamada, M. Muraguchi, F. Iwata and Yoshiharu Takiguchi :
Functional and structural changes in end-stage kidney disease due to glomerulonephritis induced by the recombinant alpha3(IV)NC1 domain.,
Experimental Animals, Vol.59, No.2, 157-170, 2010.

(要約): The aim of this study was to develop and characterize a rat glomerulonephritis model, which progresses to renal fibrosis and renal failure. A single immunization of female WKY rats with more than 10 microg of recombinant alpha3(IV)NC1 protein caused severe proteinuria followed by progressive increases in plasma creatinine and blood urea nitrogen (BUN) level within 42 days. Sequential histopathological evaluation revealed crescent formation in glomeruli followed by tubular dilation and interstitial fibrosis. Hydroxyproline content and expression of type I collagen and smooth muscle actin genes in the renal cortex increased as renal dysfunction progressed. Furthermore, the TGF-beta1 level in the renal cortex also increased. In the evaluation of antinephritic agents in this model, prednisolone and mycophenolate mofetil (MMF) treatment significantly decreased plasma creatinine and BUN, and suppressed renal fibrosis and histological changes involving crescent formation, compared with the vehicle-treated nephritic rats, whereas lisinopril treatment failed to improve renal function and histology. We demonstrated that immunization of female WKY rats with a sufficient dose of recombinant alpha3(IV)NC1 induces end-stage kidney disease accompanied by renal fibrosis. The relatively short period needed to induce the disease and the high incidence of functional and structural changes were considered a great advantage of this model for clarifying the mechanisms of progressive glomerulonephritis and for evaluating agents used to treat renal failure.
(キーワード): Actins / Animals / Autoantigens / Collagen Type I / Collagen Type IV / Creatinine / Disease Models, Animal / Female / Gene Expression / Glomerulonephritis / Hydroxyproline / Immunosuppressive Agents / Kidney Failure, Chronic / Kidney Function Tests / Lisinopril / Mycophenolic Acid / Prednisolone / Rats / Rats, Inbred WKY / Recombinant Proteins / Transforming Growth Factor beta1
(出版サイトへのリンク): ● Publication site (DOI): 10.1538/expanim.59.157
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20484849; ● Search Scopus @ Elsevier (PMID): 20484849; ● Search Scopus @ Elsevier (DOI): 10.1538/expanim.59.157

(DOI: 10.1538/expanim.59.157, PubMed: 20484849) H. Kawazoe, H. Dobashi, T. Kameda, K. Susaki, K. Kittaka, M. Tokuda, N. Fukuoka, Yoshiharu Takiguchi and H. Houchi :
Prospective study to assess the optimal blood concentration of tacrolimus in Japanese patients with rheumatoid arthritis,
Journal of Health Science, Vol.55, No.3, 435-440, 2009.

(キーワード): tacrolimus / rheumatoid arthritis / blood concentration / therapeutic drug monitoring / DOUBLE-BLIND / UNRELATED DONORS / BONE-MARROW / CORD BLOOD / EFFICACY / SAFETY / TRANSPLANTATION / METHOTREXATE / LEUKEMIA / 6-MONTH
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/jhs.55.435
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/jhs.55.435

(DOI: 10.1248/jhs.55.435) Hitoshi Kawazoe, kyoko Takaoka, Hirofumi Shibata, Naokatu Arakaki, Tomihiko Higuti, K Negayama, Hitoshi Houchi, Koichiro Tsuchiya and Yoshiharu Takiguchi :
Comparison of antibacterial activity of fluoroquinolones with their sucralfate-complexes against clinically-isolated bacteria,
Journal of Health Science, Vol.55, No.5, 790-795, 2009.

(要約): Oral fluoroquinolones are widely known to form chelate complexes with metal-containing drugs, resulting in inhibition of their intestinal absorption. However, for intestinal sterilization, the concomitant regimen may be a selective and effective strategy due to decreased absorption of fluoroquinolones result in the retainment of antibiotics at the intestine if the mixture still perpetuated antibacterial activity. Therefore, to clarify whether the mixture of fluoroquinolones and sucralfate affects their antibacterial activity or not, we conducted in vitro study. According from the checkerboard study using a microdilution method with Mueller-Hinton broth, the antibacterial activity of these fluoroquinolones-sucralfate mixtures equaled to the parent fluoroquinolones even in the presence of sucralfate at the molar ratio of [sucralfate: fluoroquinolone] was less than 166, and the minimal inhibitory concentrations for clinical isolated Escherichia coli and Pseudomonas aeruginosa strains were independent of the existence of sucralfate. These data imply that the chelated forms of each fluoroquinolone retain antibacterial activity even in the presence of the recommended therapeutic doses of sucralfate in clinical practice.
(キーワード): fluoroquinolone / interaction / antibacterial activity / chelate / sucralfate
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/jhs.55.790
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282679474052224; ● Search Scopus @ Elsevier (DOI): 10.1248/jhs.55.790

(DOI: 10.1248/jhs.55.790, CiNii: 1390282679474052224) Masahiro Abe, Yoshiharu Takiguchi, Satoshi Ichimaru, Shinichiro Kaji, Koichiro Tsuchiya and Koichiro Wada :
Different effect of acute treatment with rosiglitazone on rat myocardial ischemia/reperfusion injury by administration method.,
European Journal of Pharmacology, Vol.589, No.1-3, 215-219, 2008.

(要約): The present study was undertaken to examine the effect of rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, using different administration methods, on rat myocardial infarct size induced by 30 min of ischemia followed by 4 h of reperfusion. The infarct size was significantly reduced by the continuous infusion of rosiglitazone (0.5 mg/kg/h) from 30 min before occlusion for 2 h. On the other hand, limitation of the infarct size was shown by a bolus injection of 0.75 mg/kg at 5 min before reperfusion, but not by a bolus injection of 1 mg at 30 min before occlusion. The protective effect of rosiglitazone by the bolus injection before occlusion was obtained when an antioxidant, N-acetylcysteine, was concomitantly administered. The cardioprotection by rosiglitazone was associated with the inhibition of increased myeloperoxidase activity, tumor necrosis factor-alpha content and phosphorylation of inhibitor kappaB in the myocardium. The present study demonstrated that the protective effect of rosiglitazone on myocardial ischemia/reperfusion injury occurred most likely by inhibition of the nuclear factor-kappaB pathway through PPAR-gamma activation. However, acute treatment with rosiglitazone is harmful if its concentration is high during ischemia.
(キーワード): Acetylcysteine / Animals / Antioxidants / Computer Simulation / Disease Models, Animal / Dose-Response Relationship, Drug / Drug Administration Schedule / I-kappa B Proteins / Infusions, Intravenous / Injections, Intravenous / Male / Models, Biological / Myocardial Infarction / Myocardial Reperfusion Injury / 心筋 (myocardium) / NF-kappa B / PPAR gamma / Peroxidase / リン酸化 (phosphorylation) / Protective Agents / Rats / Rats, Wistar / Thiazolidinediones / Tumor Necrosis Factor-alpha
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ejphar.2008.05.005
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18571644; ● Search Scopus @ Elsevier (PMID): 18571644; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ejphar.2008.05.005

(DOI: 10.1016/j.ejphar.2008.05.005, PubMed: 18571644) Masahiro Abe, Yoshiharu Takiguchi, Satoshi Ichimaru, Koichiro Tsuchiya and Koichiro Wada :
Comparison of the protective effect of N-acetylcysteine by different treatments on rat myocardial ischemia-reperfusion injury.,
Journal of Pharmacological Sciences, Vol.106, No.4, 571-577, 2008.

(要約): Reactive oxygen species have been known as important contributors to ischemia/reperfusion (I/R) injury. Studies on the beneficial effect of N-acetylcysteine (NAC), a potent antioxidant, on limiting infarct size induced by I/R yielded contrasting results. The present study was undertaken to compare the effect of NAC by different administration methods on infarct size in a rat myocardial I/R model. Rats underwent 30 min of left coronary occlusion followed by 4 h of reperfusion. Treatment with continuous infusion of NAC (150 mg/kg per hour) from 30 min before occlusion for 2 h (until 1 h after the start of reperfusion) produced a significant limitation of the infarct size as a percentage of the ischemic area (8%) compared to the non-treated control (60%). However, bolus injection of 150 mg/kg at 30 min prior to occlusion and 5 min prior to reperfusion failed to reduce it (56%) although the total dose is the same. The decreased total glutathione content and glutathione peroxidase activity in the ischemic region were recovered in the continuous infusion group, but not in the bolus injection group. The increased myeloperoxidase activity and phosphorylation of inhibitor kappaB after I/R were inhibited by the continuous treatment. These results indicate that the protective effect of NAC on myocardial infarction induced by I/R was different depending on the administration method. It is necessary to maintain blood concentration during the early period of reperfusion to obtain the beneficial effect of NAC.
(キーワード): Acetylcysteine / Animals / Antioxidants / Disease Models, Animal / Glutathione / Glutathione Peroxidase / I-kappa B Proteins / Infusions, Intravenous / Injections, Intravenous / L-Lactate Dehydrogenase / Male / Myocardial Reperfusion Injury / 心筋 (myocardium) / Peroxidase / リン酸化 (phosphorylation) / Rats / Rats, Wistar
(出版サイトへのリンク): ● Publication site (DOI): 10.1254/jphs.FP0071664
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18385540; ● Search Scopus @ Elsevier (PMID): 18385540; ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.FP0071664

(DOI: 10.1254/jphs.FP0071664, PubMed: 18385540) 河添仁, 滝口祥令, 井上達也, 山口佳津騎, 田中裕章, 加藤雅人, 辻繁子, 二宮昌樹, 福岡憲泰, 大西宏明, 石田俊彦, 芳地一 :
同種造血幹細胞移植患者における多剤耐性緑膿菌による感染症治療,
薬学雑誌, Vol.128, No.4, 657-661, 2008年.

(要約): Infections caused by multiple-drug-resistant Pseudomonas aeruginosa (MDRP) are a clinically significant problem. We reported here the effective use of combination therapy in a patient with infection caused by MDRP according to an interventional treatment strategy suggested by a pharmacist. The patient was a 70-year-old male who underwent allogeneic hematopoietic stem cell transplantation. On day 45 after transplant, MDRP was newly isolated from urine, but the diagnosis at that time was colonization. On day 61, the patient developed a fever (≧ 38.0℃). In addition, laboratory data showed that C-reactive protein (CRP) was also increased. At the medical team conference, the pharmacist proposed the following treatment strategy for this infection. Aztreonam and amikacin were intravenously administered at doses of 2 g/day and 800 mg/day, respectively. The subsequent clinical course was well controlled, but the infection recurred and was aggravated. Aztreonam and ciprofloxacin were then intravenously administered at doses of 4 g/day and 600 mg/day, respectively, resulting in the alleviation of fever in the patient as well as a decrease in CRP and disappearance of MDRP isolates from urine on day 67; that is, MDRP infection was consequently well controlled. In conclusion, the combination therapy between aztreonam and amikacin, or ciprofloxacin may be clinically useful for severe infections of MDRP in compromised hosts.
(キーワード): Pseudomonas aeruginosa / multiple-drug-resistant / infection / combination therapy
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.128.657
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001206128181376; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.128.657

(DOI: 10.1248/yakushi.128.657, CiNii: 1390001206128181376) 川添仁, 滝口祥令, 田中裕章, 二宮昌樹, 福岡憲泰, 大西宏明, 石田俊彦, 芳地一 :
同種造血幹細胞移植患者におけるニューキノロン系抗菌薬による内因性感染の予防効果, --- 骨髄移植，末梢血幹細胞移植，臍帯血移植の比較 ---,
薬学雑誌, Vol.127, No.8, 1301-1307, 2007年.

(要約): We performed a retrospective study to examine the preventive effects of newquinolones for endogenous infection in patients receiving various allogeneic hematopoietic stem cell transplantation including bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), and cord blood transplantation (CBT). Forty-nine patients were enrolled. Ciprofloxacin or norfloxacin was orally administered for intestinal sterilization from day -14 until engraftment. As a result, the period from transplantation until engraftment was significantly longer in CBT group than in BMT group. The febrile index (the ratio of the febrile (> or =38.0 degrees C) period during neutropenia (< or =500 cells/mm(3)) and C-reactive protein (CRP)-positive index (the ratio of CRP-positive (> or =2.0 mg/dl) period during neutropenia) were comparable among the three groups. In addition, no gram-negative bacteria in stool was isolated in the three groups; that is, an endogenous infection of gram-negative bacteria, a potential pathogen, was well controlled by newquinolones. We should be careful when interpreting the results of this small study; however, newquinolones are clinically effective for endogenous infection of gram-negative bacteria in patients receiving not only BMT, but also PBSCT and CBT.
(キーワード): Adolescent / Adult / Aged / Anti-Bacterial Agents / Antibiotic Prophylaxis / Bone Marrow Transplantation / Cord Blood Stem Cell Transplantation / Female / Gram-Negative Bacterial Infections / Humans / Male / Middle Aged / Peripheral Blood Stem Cell Transplantation / Quinolones / Retrospective Studies / Transplantation, Homologous
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.127.1301
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17666884; ● Search Scopus @ Elsevier (PMID): 17666884; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.127.1301

(DOI: 10.1248/yakushi.127.1301, PubMed: 17666884) Hitoshi Kawazoe, Yoshiharu Takiguchi, Hiroaki Tanaka, Chiaki Doi, Noriyasu Fukuoka, Nobuhiro Kanaji, Shuji Bandoh, Toshihiko Ishida and Hitoshi Houchi :
Preventive effects of low-dose dexamethasone for delayed adverse events induced by carboplatin-based combination chemotherapy,
Journal of the Pharmaceutical Society of Japan, Vol.127, No.6, 1001-1006, 2007.

(要約): We performed a retrospective study to examine the protective effect of low-dose dexamethasone (DEX) on delayed adverse events induced by carboplatin (CBDCA)-based combination chemotherapy in patients with thoracic tumors. Low-dose DEX (4-8 mg/day) was administered on day 1 and after, in addition to a serotonin 5-HT3 receptor antagonist. The acute adverse events (day 1) were well controlled in the patients with or without co-treatment of DEX. On the other hand, the delayed nausea, emesis, anorexia, and fatigue after day 2 failed to be controlled by 5-HT3 antagonist alone. Co-treatment with DEX significantly suppressed the grade of the delayed adverse events during days 2-10. The mean ratio of complete protection during days 2-10 were significantly higher in the DEX-treated group compared with the non-DEX-treated group. These results reveal that low-dose DEX is a clinically effective treatment for the prevention of delayed adverse events induced by CBDCA-based combination chemotherapy.
(キーワード): Adult / Aged / Aged, 80 and over / Anorexia / Antineoplastic Combined Chemotherapy Protocols / Carboplatin / Dexamethasone / Fatigue / Female / Humans / Male / Middle Aged / Nausea / Retrospective Studies / Serotonin 5-HT3 Receptor Antagonists / Time Factors / Vomiting
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.127.1001
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17541251; ● Search Scopus @ Elsevier (PMID): 17541251; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.127.1001

(DOI: 10.1248/yakushi.127.1001, PubMed: 17541251) Hitoshi Kawazoe, Yoshiharu Takiguchi, Hiroaki Tanaka, Noriyasu Fukuoka, Hiroaki Ohnishi, Toshihiko Ishida and Hitoshi Houchi :
Change of the blood concentration of tacrolimus after the switch from fluconazole to variconazole in patients receiving allogeneic hematopoietic stem cell transplantation,
Biological & Pharmaceutical Bulletin, Vol.29, No.12, 2528-2531, 2006.

(要約): The purpose of this study was to assess the impact by switching co-administered triazole antifungal agent from fluconazole (FCZ) to voriconazole (VCZ) on the blood concentration of tacrolimus (FK506) in patients receiving allogeneic hematopoietic stem cell transplantation. We performed a retrospective study presented as case reports. The blood concentration of FK506 was increased after the switch from FCZ to VCZ, resulting in increase of the concentration/dose (C/D) ratio of FK506. Thus, the mean C/D ratios of FK506 with oral administration was surprisingly increased over 4.5-fold after the switch. Therefore, it was necessary to reduce the FK506 dose when co-administered FCZ is switched to VCZ. We should be careful when interpreting the results of these case reports; however, in some patients, it is recommended that the dose of FK506 be reduced to one-fifth after the switch.
(キーワード): Fluconazole / Humans / Immunosuppressive Agents / Pyrimidines / Retrospective Studies / Stem Cell Transplantation / Tacrolimus / Triazoles
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.29.2528
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17142996; ● Search Scopus @ Elsevier (PMID): 17142996; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.29.2528

(DOI: 10.1248/bpb.29.2528, PubMed: 17142996) 川添仁, 久保智美, 飯原なおみ, 土居智明, 奥條真紀子, 福岡憲泰, 藤本さとし, 金地伸拓, 坂東修二, 石田俊彦, 滝口祥令, 芳地一 :
患者参加型癌化学療法副作用モニタリング, --- 患者の治療参加と情報の共有化 ---,
薬学雑誌, Vol.126, No.8, 629-642, 2006年.

(要約): The purpose of this study was to assess patient participation in cancer therapy and the sharing of patient information among the medical care team (physicians, nurses, pharmacists, and especially patients). We monitored the side effects of cancer chemotherapy with patients, and developed two support tools: One scored the points of subjective symptoms (fatigue, anorexia, nausea, etc) by patients, and the other recorded objective symptoms (clinical examination data) by pharmacists. It is most important that they attend each patient at their bedside. At this time, the trial was evaluated by questionnaire survey by inpatients receiving cancer chemotherapy (n=15). As a result, all patients (15/15) responded that this trial was necessary. This trial addressed the following: 1) increased communication between patients and medical staff concerning side effects (14/15), 2) increased interest in side effects (10/15), 3) when a patient tells medical staff about side effects, they act on it (10/15). None of the patients felt inconvenienced by scoring every day (0/15), or anxiety about side effects (0/15). Furthermore, all patients (15/15) responded that "participation of pharmacists in cancer chemotherapy" was necessary. This trial revealed no problems and suggested that patients related to the center of medical care. We should be careful in interpreting results of this small sized trial; however, the following conclusions should be reached: 1) introduction of monitoring side effects of cancer chemotherapy with patients, 2) develop communication among the medical care team.
(キーワード): cancer chemotherapy / side effects monitoring / patient participation / sharing patient information / medical care team
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.126.629
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001206126692608; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.126.629

(DOI: 10.1248/yakushi.126.629, CiNii: 1390001206126692608) Otsuka Toshihiro, Keisuke Izumi, Itsuo Tokunaga, Takako Gotohda, Ipposhi Kaneshige, Yoshiharu Takiguchi, Kaneda Shinya, Nobuo Satake, Takamasa Ohnishi, Seiki Tashiro and Mitsuo Shimada :
Prevention of lethal hepatic injury in Long-Evans Cinnamon(LEC) rats by D-galactosamine hydrochloride,
The Journal of Medical Investigation : JMI, Vol.53, No.1-2, 81-86, 2006.

(要約): Repeated injections of D-galactosamine hydrochloride (GalN) increase the survival rate of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. The aim of the present study was to investigate the mechanism of GalN for prevention of spontaneous lethal hepatic injury in LEC rats. Male LEC rats were given a single subcutaneous injection of 300 mg/kg of GalN or vehicle (0.9% NaCl) at 14 weeks, and killed at 28 weeks of age. Next, 6-week-old male LEC rats were given weekly subcutaneous injections of 300 mg/kg of GalN or vehicle for 3 or 12 weeks, and their hepatic 8-hydroxydeoxy-2'-guanosine (8-OHdG), glutathione peroxidase (GPX), and catalase activities were measured. None of GalN-treated rats died of hepatic injury (0/12), whereas the mortality rate of control rats given 0.9% NaCl was 17% (2/12). GalN administration for 12 weeks decreased the hepatic 8-OHdG, and GalN administration for either 3 or 12 weeks increased the glutathione peroxidase activity. GalN administration increased the serum level of alanine aminotransferase, and accelerated megalocytic degeneration of the hepatocytes. GalN treatment is effective in preventing lethal hepatitis in LEC rats and decrease of oxidative DNA damage by GalN plays an important role in increase of the survival rate.
(キーワード): Animals / Disease Models, Animal / Free Radicals / Galactosamine / Hepatolenticular Degeneration / Humans / Liver / Male / Rats / Rats, Inbred LEC
(徳島大学機関リポジトリ): ● Metadata: 110791
(出版サイトへのリンク): ● Publication site (DOI): 10.2152/jmi.53.81
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16537999; ● Summary page in Scopus @ Elsevier: 2-s2.0-33645835974

(徳島大学機関リポジトリ: 110791, DOI: 10.2152/jmi.53.81, PubMed: 16537999, Elsevier: Scopus) 田島壮一郎, 土屋浩一郎, 大西秀樹, 兼松康久, 玉置俊晃, Ronald Mason, 滝口祥令 :
ラジカル認識抗体を用いた酸化ストレス由来プロテインラジカル検出法,
日本薬理学雑誌, Vol.126, No.4, 246-249, 2005年.

(キーワード): 酸化ストレス / ラジカル / ミオグロビン / チオレドキシン
(出版サイトへのリンク): ● Publication site (DOI): 10.1254/fpj.126.246
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16327204; ● Search Scopus @ Elsevier (PMID): 16327204; ● Search Scopus @ Elsevier (DOI): 10.1254/fpj.126.246

(DOI: 10.1254/fpj.126.246, PubMed: 16327204) Koichiro Tsuchiya, Kaori Akai, Akira Tokumura, Shinji Abe, Toshiaki Tamaki, Yoshiharu Takiguchi and Kenji Fukuzawa :
Oxygen radical photo-induced by ferric nitrilotriacetate complex,
Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1725, No.1, 111-119, 2005.

(要約): This study examined the photo-induced generation of reactive oxygen species (ROS) by the carcinogenic iron(III)-NTA complex. Iron(III)-NTA complex (1:1) has three conformations (type (a) in acidic conditions of pH 1-6, type (n) in neutral conditions of pH 3-9, and type (b) in basic conditions of pH 7-10) with two pK(a) values (pK(a1) approximately 4, pK(a2) approximately 8). The iron(III)-NTA complex was reduced to iron(II) under cool-white fluorescent light without the presence of any reducing agent, and the reduction rates of the three conformations of iron(III)-NTA were in the order type (a)>type (n)>type (b) as reported previously (Akai K. et al., Free Radic. Res. 38, 951-962, 2004). ROS generation was investigated by electron paramagnetic resonance (EPR) spectroscopy with a spin-trapping technique. Apparent EPR signals attributed to PBN/*(13)CH(3) and PBN/*OCH(3) spin adducts were observed after incubation of the iron(III)-NTA complex was mixed with alpha-phenyl-tert-butylnitrone (PBN) and (13)C-DMSO in an aerobic condition. The addition of catalase effectively attenuated the PBN adducts, but superoxide dismutase enhanced them. Taken together, these results indicate that the iron(III)-NTA complex is spontaneously reduced to the iron(II)-NTA complex by light under acidic to neutral pH, and in turn transfers an electron to molecular oxygen to form ROS.
(キーワード): Catalase / Cyclic N-Oxides / Electron Spin Resonance Spectroscopy / Ferric Compounds / Free Radicals / Light / Nitrilotriacetic Acid / Nitrogen Oxides / Oxygen / Photochemistry / Superoxide Dismutase / Time Factors
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbagen.2005.05.001
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15950386; ● Search Scopus @ Elsevier (PMID): 15950386; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbagen.2005.05.001

(DOI: 10.1016/j.bbagen.2005.05.001, PubMed: 15950386) Koichiro Tsuchiya, Yasuhisa Kanematsu, Masanori Yoshizumi, Hideki Ohnishi, Kazuyoshi Kirima, Yuki Izawa, Michiyo Shikishima, Tatsuhiro Ishida, Shuji Kondo, Shoji Kagami, Yoshiharu Takiguchi and Toshiaki Tamaki :
Nitrite is an alternative source of NO in vivo,
American Journal of Physiology, Heart and Circulatory Physiology, Vol.288, No.5, H2163-H2170, 2005.

(要約): In this study, we investigated whether orally administered nitrite is changed to NO and whether nitrite attenuates hypertension in a dose-dependent manner. We utilized a stable isotope of [15N]nitrite (15NO2-) as a source of nitrite to distinguish between endogenous nitrite and that exogenously administered and measured hemoglobin (Hb)-NO as an index of circulating NO in whole blood using electron paramagnetic resonance (EPR) spectroscopy. When 1 mg/kg Na15NO2 was orally administered to rats, an apparent EPR signal derived from Hb15NO (A(Z) = 23.4 gauss) appeared in the blood. The peak blood HbNO concentration occurred at the first measurement after intake (5 min) for treatment with 1 and 3 mg/kg (HbNO: 4.93 +/- 0.52 and 10.58 +/- 0.40 microM, respectively) and at 15 min with 10 mg/kg (HbNO: 38.27 +/- 9.23 microM). In addition, coadministration of nitrite (100 mg/l drinking water) with N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 g/l) for 3 wk significantly attenuated the L-NAME-induced hypertension (149 +/- 10 mmHg) compared with L-NAME alone (170 +/- 13 mmHg). Furthermore, this phenomenon was associated with an increase in circulating HbNO. Our findings clearly indicate that orally ingested nitrite can be an alternative to L-arginine as a source of NO in vivo and may explain, at least in part, the mechanism of the nitrite/nitrate-rich Dietary Approaches to Stop Hypertension diet-induced hypotensive effects.
(キーワード): 一酸化窒素 (nitric oxide) / hypertension / 電子スピン共鳴 (electron paramagnetic resonance)
(出版サイトへのリンク): ● Publication site (DOI): 10.1152/ajpheart.00525.2004
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15626692; ● Search Scopus @ Elsevier (PMID): 15626692; ● Search Scopus @ Elsevier (DOI): 10.1152/ajpheart.00525.2004

(DOI: 10.1152/ajpheart.00525.2004, PubMed: 15626692) Koichiro Tsuchiya, Yoshiharu Takiguchi, Masumi Okamoto, Yuki Izawa, Yasuhisa Kanematsu, Masanori Yoshizumi and Toshiaki Tamaki :
Malfunction of vascular control in lifestyle-related diseases : formation of systemic hemoglobin-nitric oxide Complex(HbNO) From Dietary Nitrite,
Journal of Pharmacological Sciences, Vol.96, No.4, 395-400, 2004.

(要約): Nitric oxide (NO) has many physiological functions. It is believed to be produced from L-arginine by nitric oxide synthase (NOS), and nitrite and nitrate are waste forms of it. By the way, nitrate and nitrite are abundant in vegetables and fruits, especially leafy vegetables and pickled vegetables. Orally-ingested nitrate is changed to nitrite by micro-organelles living in the hypopharynx area, and nitrite is expected to change to NO in the stomach due to its low pH. Indeed, some researchers reported that NO is produced in the gastric cavity, although few reports mentioned the physiological meanings of this NO formation. Therefore, we investigated whether the nitrite-derived NO can shift to the circulation and acts like NOS-derived NO does in tissues. We adopted a stable isotope of nitrite (15NO2-) in order to distinguish between the endogenous nitrite and the exogenously administered one and measured nitrosyl hemoglobin (HbNO) as an index of circulating NO using electron paramagnetic resonance spectroscopy. It appeared that the oral administration of 15N-nitrite formed the Hb15NO in rat blood and decreased the blood pressure of chronic L-NAME treated rats. Our findings suggest that the intake of nitrite (or nitrate)-rich foods such as vegetables and fruits would alter the systemic HbNO dynamism, resulting in the improvement of cardiovascular diseases.
(キーワード): nitric oxide(NO) / hemoglobin-NO adduct / electron paramagnetic resonance / nitrite
(出版サイトへのリンク): ● Publication site (DOI): 10.1254/jphs.FMJ04006X3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15599101; ● Search Scopus @ Elsevier (PMID): 15599101; ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.FMJ04006X3

(DOI: 10.1254/jphs.FMJ04006X3, PubMed: 15599101) 小林睦, 滝口祥令, 横田雅之, 北田徳昭, 関戸聡子, 西山裕美, 黒田和夫 :
経皮的冠動脈形成術(PTCA)施行後の慢性期再狭窄に対するNicorandil投与の影響 -Retrospective解析より,
臨床薬理, Vol.34, No.2, 49-51, 2003年.

(キーワード): nicorandil / restenosis / PTCA / stent implantation / stenosis grade
(出版サイトへのリンク): ● Publication site (DOI): 10.3999/jscpt.34.2_49
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001205339769600; ● Summary page in Scopus @ Elsevier: 2-s2.0-0042158717

(DOI: 10.3999/jscpt.34.2_49, CiNii: 1390001205339769600, Elsevier: Scopus) Yoshiharu Takiguchi, Rie Ishihara, Mayumi Torii, Rinya Kato, Shin Kamihara and Toshihiko Uematsu :
Hair analysis of flecainide for assessing the individual drug-taking behavior.,
European Journal of Clinical Pharmacology, Vol.58, No.2, 99-101, 2002.

(要約): The concentration of flecainide in hair was measured to determine its value as an index of individual drug-taking history. Hair samples obtained from 15 patients treated with flecainide for more than 1 month were cut into 1-cm-long portions successively from its scalp end. The concentration of flecainide in each hair portion was measured using high-performance liquid chromatography. Flecainide was detected in the 1-cm-long hair portion at the scalp end in the concentration range of 38.0-411.9 ng x mg(-1), which significantly correlated with the area under the plasma flecainide concentration versus time curve. The axial centimeter-by-centimeter distribution of flecainide along the hair shaft well reflected the individual history of drug use. The present study suggests the usefulness of determining flecainide in hair to provide retrospective information on the individual drug-taking behavior qualitatively.
(キーワード): Adult / Aged / Anti-Arrhythmia Agents / Area Under Curve / Chromatography, High Pressure Liquid / Female / Flecainide / Hair / Humans / Male / Middle Aged
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00228-002-0450-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12012140; ● Search Scopus @ Elsevier (PMID): 12012140; ● Search Scopus @ Elsevier (DOI): 10.1007/s00228-002-0450-9

(DOI: 10.1007/s00228-002-0450-9, PubMed: 12012140) Mayumi Torii, Yoshiharu Takiguchi, Miyako Izumi, Tokuya Fukushima and Masayuki Yokota :
Carbapenem antibiotics inhibit valproic acid transport in Caco-2 cell monolayers.,
International Journal of Pharmaceutics, Vol.233, No.1-2, 253-256, 2002.

(要約): The concomitant use of carbapenem antibiotics with valproic acid has been prohibited because carbapenems induced a decrease in plasma concentration of valproic acid in epileptic patients during valproic acid therapy. Our previous in vivo study in rats proposed that inhibition by carbapenem of the intestinal absorption of valproic acid might be a possible mechanism for the drug-drug interaction. To demonstrate the hypothesis, we examined the effects of imipenem and panipenem on intestinal transepithelial transport of valproic acid using Caco-2 cell monolayers. Imipenem and panipenem inhibited the transport of [14C]-valproic acid across the Caco-2 cell monolayers from apical-to-basolateral side in a concentration-dependent manner, although they had no effect on the uptake of [14C]-valproic acid by Caco-2 cells. The inhibition by the carbapenems of the valproic acid transport was found even when they were added to only the basolateral side. From these results, the carbapenems may inhibit the absorption of valproic acid at the basolateral membrane of intestinal epithelial cells, which contributes to the decrease in plasma concentration of valproic acid after oral administration.
(キーワード): valproic acid / imipenem / panipenem / Caco-2 cell monolayer / LINE CACO-2
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0378-5173(01)00916-4
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11897429; ● Search Scopus @ Elsevier (PMID): 11897429; ● Search Scopus @ Elsevier (DOI): 10.1016/S0378-5173(01)00916-4

(DOI: 10.1016/S0378-5173(01)00916-4, PubMed: 11897429) Yoshiharu Takiguchi, Rie Ishihara, Rinya Kato, Shin Kamihara, Masayuki Yokota and Toshihiko Uemastu :
Measurement of flecainide in hair as an index of drug exposure.,
Journal of Pharmaceutical Sciences, Vol.90, No.11, 1891-1896, 2001.

(要約): We report a method for measuring the concentration of flecainide in hair. An animal study, in which flecainide (1, 5, and 10 mg/kg/day) was orally administered for 1, 2, and 3 weeks to pigmented rats, showed that flecainide concentration in rat hairs newly regrown after administration significantly correlated with both the daily dose and the dosing period. The part of hair containing flecainide continued to grow upward, retaining the drug within the hair structure that had been formed at the time of drug exposure. Flecainide was also determined in human scalp hairs collected from patients treated with flecainide. The drug content of white hairs was much less than that black hairs collected from the same rats and subjects, suggesting the determinant effect of hair pigment on flecainide accumulation in hair. These findings suggest that the analysis of flecainide in hair may be useful for assessing exposure to drug qualitatively.
(キーワード): Animals / Anti-Arrhythmia Agents / Dose-Response Relationship, Drug / Flecainide / Hair / Humans / Male / Rats / Research Design
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/jps.1138
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11745746; ● Summary page in Scopus @ Elsevier: 2-s2.0-0035171147

(DOI: 10.1002/jps.1138, PubMed: 11745746, Elsevier: Scopus) Seiko Ida, Masayuki Yokota, Makoto Ueoka, Kenji Kiyoi and Yoshiharu Takiguchi :
Mild to severe lithium-induced nephropathy models and urine N-acetyl-β-d-glucosaminidase in rats.,
Methods and Findings in Experimental and Clinical Pharmacology, Vol.23, No.8, 445-448, 2001.

(要約): Long-term treatment with lithium induces functional and/or structural disturbances in the kidneys. However, no procedure has been established for the early diagnosis of lithium intoxication. In this study, we prepared mild to severe lithium-induced nephropathy rat models and examined the usefulness of urine N-acetyl-beta-D-glucosaminidase (NAG) for the early diagnosis of lithium-induced renal insufficiency. Lithium was administered by repeated intraperitoneal injection (1, 2 and 4 mEq/kg/day for 10 days). We also measured the plasma creatinine and paraaminohippuric acid (PAH) clearance, and observed renal histological changes. Lithium pretreatment elevated the plasma creatinine level and decreased PAH clearance in a dose-dependent manner. The NAG level in the lithium 4 mEq/kg group was very high. The levels in the lithium 1 mEq/kg and 2 mEq/kg groups were almost the same and were higher than the control group. A histological examination of the kidney revealed glomerular congestion and/or atrophy and tubular expansion in all of the groups except the control group. These histological changes were dose-dependent. In conclusion, urine NAG may be useful in the early diagnosis of renal side effects caused by lithium therapy. When the urine NAG level becomes high in a patient taking lithium for bipolar disorder, the physician may need to consider lithium-induced renal insufficiency.
(キーワード): Acetylglucosaminidase / Acute Kidney Injury / Animals / Creatinine / Injections, Intraperitoneal / Kidney / Lithium / Male / Rats / Rats, Wistar / Renal Circulation / p-Aminohippuric Acid
(出版サイトへのリンク): ● Publication site (DOI): 10.1358/mf.2001.23.8.662132
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11838319; ● Summary page in Scopus @ Elsevier: 2-s2.0-0035683831

(DOI: 10.1358/mf.2001.23.8.662132, PubMed: 11838319, Elsevier: Scopus) Mayumi Torii, Yoshiharu Takiguchi, Fumiko Saito, Miyako Izumi and Masayuki Yokota :
Inhibition by carbapenem antibiotic imipenem of intestinal absorption of valproic acid in rats.,
The Journal of Pharmacy and Pharmacology, Vol.53, No.6, 823-829, 2001.

(要約): The concomitant use of carbapenem antibiotics with valproic acid has been prohibited because panipenem induced a decrease in plasma concentration of valproic acid in epileptic patients during valproic acid therapy. To clarify the possible mechanism of the carbapenem-valproic acid interaction, we investigated the effect of imipenem on the pharmacokinetic behaviour of valproic acid in rats. Co-administration of imipenem (30 mg kg(-1), i.v.) induced a decrease in the peak plasma concentration of valproic acid after oral administration. However, the imipenem-induced decrease in plasma concentrations of valproic acid was not observed within 60 min after intravenous injection of valproic acid. By utilizing in-situ vascular and luminal perfused small intestine, it was confirmed that absorption of valproic acid from the luminal to the vascular perfusate was decreased in the presence of imipenem (0.5 mM) in the vascular perfusate. The everted gut sac method was used to determine the effect of imipenem on active transport of valproic acid. The accumulation of valproic acid on the serosal side of the intestinal sac against the concentration gradient was reduced by lactic acid that inhibits the carrier-mediated transport of valproic acid across the intestinal brush-border membrane. However, imipenem did not affect the active transport of valproic acid. Therefore, the inhibition by imipenem of valproic acid absorption may be caused by a mechanism different from that of lactic acid. In conclusion, imipenem inhibits the intestinal absorption of valproic acid, which contributes to the decrease in plasma concentration of valproic acid after oral administration.
(キーワード): Administration, Oral / Animals / Anticonvulsants / Biological Transport, Active / Drug Interactions / Imipenem / Infusions, Intravenous / Intestinal Absorption / Male / Rats / Rats, Sprague-Dawley / Thienamycins / Valproic Acid
(出版サイトへのリンク): ● Publication site (DOI): 10.1211/0022357011776171
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11428658; ● Summary page in Scopus @ Elsevier: 2-s2.0-0034988068

(DOI: 10.1211/0022357011776171, PubMed: 11428658, Elsevier: Scopus) Hiroyuki Matsuno, Osamu Kozawa, Masayuki Niwa, Akira Abe, Yoshiharu Takiguchi and Toshihiko Uematsu :
Characterization of simple and reproducible vascular stenosis model in hypercholesterolemic hamsters.,
Lipids, Vol.36, No.5, 453-460, 2001.

(要約): The importance of low-density lipoprotein (LDL) in the etiology of atherosclerosis is well recognized. We have established a reproducible stenosis model in hypercholesterolemic hamsters, and the process of arterial stenosis by thrombus or neointima was studied and compared with that in normal hamsters. The level of plasma LDL was 4.6 times higher in hamsters fed a high-cholesterol diet than in hamsters fed normal food. Endothelial injury in right common carotid arteries was induced using a modified catheter. Arterial blood flow was monitored continuously using a Doppler flow probe. Arterial patency after the initiation of injury in high-cholesterol hamsters was significantly changed as compared with that of normal hamsters. Neointima was observed 2 wk after the vascular injury. The neointimal area of high-cholesterol hamsters was significantly larger than that of normal hamsters. To characterize the stenosis in hypercholesterolemic hamsters, we measured platelet aggregation, thrombin time, activated partial thromboplastin time, and proliferating smooth muscle cells (SMC) in vitro and in vivo. The half-maximal inhibitory concentration value for platelet aggregation induced by thrombin or collagen, the DNA synthesis stimulated by platelet-derived growth factor (PDGF)-BB, and 5-bromo-2-deoxy-uridine labeling indices (proliferating index of SMC in vivo) in high-cholesterol hamsters were each significantly higher than the comparable value from normal hamsters. However, specific binding of PDGF-BB in SMC was not different between the two types of hamsters. Furthermore, we investigated the inhibitory effects of probucol or losartan on neointima formation using this model. Probucol, but not losartan, significantly reduced the neointimal area in hypercholesterolemic hamsters. These findings indicated that high levels of plasma LDL strongly contributed to the development of thrombus and neointima formation via both up-regulation of platelet aggregation and the enhancement of SMC proliferation. This stenosis model may be useful for the investigation of hypercholesterolemia-associated cardiovascular diseases.
(キーワード): Animals / Blood Flow Velocity / Carotid Arteries / Carotid Artery Thrombosis / Cells, Cultured / Cholesterol / Cholesterol, Dietary / Constriction, Pathologic / Cricetinae / DNA / Disease Models, Animal / Endothelium, Vascular / Hypercholesterolemia / Losartan / Male / Mesocricetus / Microscopy, Electron / Muscle, Smooth, Vascular / Platelet Aggregation / Platelet-Derived Growth Factor / Probucol / Proto-Oncogene Proteins c-sis / Reproducibility of Results / Tunica Intima / Vascular Diseases
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s11745-001-0742-4
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11432456; ● Search Scopus @ Elsevier (PMID): 11432456; ● Search Scopus @ Elsevier (DOI): 10.1007/s11745-001-0742-4

(DOI: 10.1007/s11745-001-0742-4, PubMed: 11432456) Hiroshi Yoshioka, Seiko Ida, Masayuki Yokotra, Ayako Nishimoto, Sachiko Shibata, Akiko Sugawara and Yoshiharu Takiguchi :
Effects of litium on the pharmacokinetics of valproate in rats.,
The Journal of Pharmacy and Pharmacology, Vol.52, No.3, 297-301, 2000.

(要約): Combined treatment with lithium and valproate has been used for bipolar disorder. However, the studied interaction between these two drugs has not been fully investigated. We therefore examined the effects of lithium on the pharmacokinetics (plasma disappearance, metabolism and urinary excretion) of valproate in rats. Lithium (2 mEq kg(-1)) was administered intraperitoneally twice a day for ten days. Plasma disappearance curves of valproate (50 mg kg(-1), i.v.), valproate-metabolizing activities of UDP-glucuronosyltransferase (UGT) and cytochrome P450 (CYP) in liver microsomes and urinary excretion of free valproate and valproate-glucuronide were examined. The metabolizing activity of UGT and CYP were determined by enzyme assays and a fluorescence polarization immunoassay system. Urinary valproate-glucuronide was obtained using this system by subtracting the free level from total level, which was determined after deconjugating the sample with heat and NaOH. The half-life of plasma disappearance of valproate was 25% reduced by lithium pretreatment (0.428 +/- 0.031 h with repeated lithium pretreatment vs 0.578 +/- 0.062 h for controls). The valproate-metabolizing activity of UGT and CYP were not altered by lithium although lithium increased the urinary excretion of valproate-glucuronide. In conclusion, lithium pretreatment causes a decrease in plasma valproate levels and an increase in urinary excretion of valproate-glucuronide in rats.
(キーワード): Animals / Antimanic Agents / Cytochrome P-450 Enzyme System / Glucuronates / Glucuronosyltransferase / Lithium Chloride / Male / Metabolic Clearance Rate / Microsomes, Liver / Rats / Rats, Wistar / Time Factors / Valproic Acid
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10757417; ● Summary page in Scopus @ Elsevier: 2-s2.0-0034072077

(PubMed: 10757417, Elsevier: Scopus) Seiko Ida, Masayuki Yokota, Hiroshi Yoshioka and Yoshiharu Takiguchi :
Single exposure to gasoline or ether reduces cytochrom P-450 activities without affecting UDP-glucuronosyltransferase activity in rat liver.,
Journal of Occupational Health, Vol.42, 84-85, 2000.

(出版サイトへのリンク): ● Publication site (DOI): 10.1539/joh.42.84
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-0034017754

(DOI: 10.1539/joh.42.84, Elsevier: Scopus) Yoshikazu Matsumura, Masayuki Yokota, Hiroshi Yoshioka, Sachiko Shibata, Seiko Ida and Yoshiharu Takiguchi :
Acute effects of griseofulvin on the pharmacokinetics of warfarin in rats.,
The Journal of International Medical Research, Vol.27, No.4, 167-175, 1999.

(要約): It has been reported that prothrombin time (PT), which is prolonged by warfarin, is reduced when patients on warfarin also take griseofulvin repeatedly. We investigated the cause of the drug interaction and the initial effects of griseofulvin on warfarin pharmacokinetics. Total cytochrome P-450, and the activities of aminopyrine N-demethylase, aniline p-hydroxylase and 7-ethoxycoumarin O-deethylase, after repeated administration of griseofulvin (100 mg/kg orally daily for 5 days) were examined. Acute effects of single doses of griseofulvin (100 mg/kg) on coagulation activity (prothrombin time) and warfarin pharmacokinetics after administration of warfarin were also studied. Repeated administration of griseofulvin induced warfarin-metabolizing enzymes. In contrast, a single administration of griseofulvin increased prothrombin time and serum warfarin concentrations. The activity of a warfarin-metabolizing enzyme (7-ethoxycoumarin O-deethylase) was reduced when griseofulvin was added to rat liver microsomes. The results suggest that reduced warfarin action after repeated administration of griseofulvin may be due to induction of warfarin-metabolizing enzymes, but that there is also an initial increase in warfarin action.
(キーワード): Animals / Anticoagulants / Cytochrome P-450 Enzyme System / Drug Interactions / Griseofulvin / Isoenzymes / Male / Microsomes, Liver / Prothrombin Time / Rats / Rats, Wistar / Warfarin
(出版サイトへのリンク): ● Publication site (DOI): 10.1177/030006059902700402
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10599028; ● Summary page in Scopus @ Elsevier: 2-s2.0-0032708744

(DOI: 10.1177/030006059902700402, PubMed: 10599028, Elsevier: Scopus) Hiroyuki Matsuno, Osamu Kozawa, Masayuki Niwa, Kumiko Tanabe, Katsuhiko Ichimaru, Yoshiharu Takiguchi, Masayuki Yokota, Hideharu Hayashi and Toshihiko Uematsu :
Multiple inhibition of platelet activation by aurintricarboxylic acid prevents vascular stenosis after endothelial injury in hamster carotid artery.,
Thromb.Haemost., Vol.79, 865-871, 1998. Osamu Kozawa, Toshihiko Uematsu, Hiroyuki Matsuno, Masayuki Niwa, Yoshiharu Takiguchi, Syouzou Matsumonot, Masahiko Minamoto, Yoshito Niida, Masahiro Yokokawa, Satoru Nagashima and Mitsutaka Kanamaru :
Pharmacokinetics and safety of a new parenteral carbapenem antibiotic, biapenem (L-627), in eldery subjects.,
Antimicrobial Agents and Chemotherapy, Vol.42, 1433-1436, 1998. Masamitsu Shimazawa, Yoshiharu Takiguchi, Kazuo Umemura, Kazunao Kondo and Mitsuyoshi Nakashima :
Antithrombotic effects in a rat model of aspirin-insensitive arterial thrombosis of desethyl KBT-3022, the main active metabolite of a new antiplatelet agent, KBT-3022.,
European Journal of Pharmacology, Vol.328, 183-189, 1997. Masamitu Shimazawa, Yoshiharu Takiguchi, Kazuo Umemura and Mitsuyoshi Nakashima :
Antithrombotic effects of KBT-3022, a novel antiplatelet agent, in an arterial thrombosis model in the guinea-pig.,
Drug Develop.Res., Vol.40, 217-222, 1997. Yoshiharu Takiguchi and Keizo Sogabe :
The selective endothelin ETA receptor antagonist FR139317 inhibits neointimal thickening in the rat.,
European Journal of Pharmacology, Vol.309, No.1, 59-62, 1996. Koichiro Wada, Kazuo Umemura, Hiroshi Nishiyama, Abby R Saniabadi, Yoshiharu Takiguchi, Minoru Nakano and Mitsuyoshi Nakashima :
A chemiluminescent detection of superoxide radical produced by adherent leucocyte to the subendothelium following thrombolysis: studies with a photochemically induced thrombosis model in the guinea pig femoral artery.,
Atherosclerosis, Vol.122, No.2, 217-224, 1996.

(要約): Reocclusion following thrombolysis is a major limitation of thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) because denuded vessel wall exposed to blood following thrombolysis is a favourable surface for platelet and leucocyte deposition. We have applied a chemiluminescence technique to detect superoxide radical (0(-2)) produced by leucocytes adherent to the femoral artery 24 h after photochemically induced thrombogenesis in the guinea pig in vivo and subsequent thrombolysis by rt-PA. Intravenous administration of MCLA, a specific chemiluminescence reagent for detecting O(-2), markedly increased photon emission. the photon emission was markedly potentiated by phorbol myristate acetate and was suppressed by superoxide dismutase. Reocclusion 24 h after rt-PA induced thrombolysis was observed in 10 of 16 animals. Histological observations revealed extensive polymorphonuclear leucocytes adherent to the vessel wall at the site of thrombogenesis and thrombolysis. A higher level of 0(-2) could be detected from the arteries in which thrombolysis was induced compared with those without thrombolysis. Further, the level 0(-2) detected was greater in reoccluded arteries compared with those in which reflow was established. These observations suggest that 0(-2) is produced by adherent leucocytes at the site of thrombolysis and that leucocytes are involved in reocclusion after thrombolysis.
(キーワード): Animals / Cell Adhesion / Disease Models, Animal / Endothelium, Vascular / Femoral Artery / Guinea Pigs / Imidazoles / Light / Luminescent Measurements / Male / Neutrophils / Plasminogen Activators / Pyrazines / Recombinant Proteins / Rose Bengal / Superoxides / Thrombolytic Therapy / Thrombosis
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/0021-9150(95)05752-8
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8769684; ● Search Scopus @ Elsevier (PMID): 8769684; ● Search Scopus @ Elsevier (DOI): 10.1016/0021-9150(95)05752-8

(DOI: 10.1016/0021-9150(95)05752-8, PubMed: 8769684) Yoshiharu Takiguchi, Masamitsu Shimazawa and Mitsuyoshi Nakashima :
A comparative study of the antithrombotic effect of aurintricarboxylic acid on arterial thrombosis in rats and guinea-pigs,
British Journal of Pharmacology, Vol.118, No.7, 1633-1638, 1996. Yoshiharu Takiguchi, Fumitoshi Asai, Koichiro Wada and Mitsuyoshi Nakashima :
Comparison of antithrombotic effects of GPIIb-IIIa receptor antagonist and TXA2 receptor antagonist in the guinea-pig thrombosis model:Possible role of TXA2 in reocclusion after thrombolysis.,
Thromb.Haemostas., Vol.73, 683-688, 1995. Yoshiharu Takiguchi, Tomoko Nagano, Masahiko Ikeda and Mitsuyoshi Nakashima :
Early administration of YT-146, an adenosine A2 receptor agonist, inhibits neointimal thickening after rat femoral artery endothelium injury.,
European Journal of Pharmacology, Vol.281, 205-207, 1995. Yoshiharu Takiguchi, Fumitoshi Asai, Koichiro Wada, Hideya Hayashi and Mitsuyoshi nakashima :
Antithrombotic effect of a novel recombinant hirudin analogue, CX-397, in a rat arterial thrombosis model.,
British Journal of Pharmacology, Vol.116, 3056-3060, 1995. 中島光好, 小菅和仁, 梅村和夫, 滝口祥令, 近藤一直, 水野淳宏, 植松俊彦, 渡辺祐二 :
(3),
日本化学療法学会雑誌, Vol.43, 647-654, 1995年. Hiroshi Nishiyama, kazuo Umemura, Abby.R Saniabadi, Yoshiharu Takiguchi, Toshihiko Uematsu and Mitsuyoshi Nakashima :
Enhancement of thrombolytic efficacy of tissue-type plasminogen activator by adjuvants in the guinea pig thrombosis model.,
European Journal of Pharmacology, Vol.264, 191-198, 1994. Koichiro Wada, Abby.R Saniabadi, Kazuo Umemura, Yoshiharu Takiguchi and Mitsuyoshi Nakasima :
UV-dependent quinolone-induced human erythrocyte membrane lipid peroxidation:Studies on the phototoxicity of Y-26611, a new quinolone derivative.,
Pharmacology and Toxicology, Vol.74, 240-243, 1994. Hiroyuki Matsuno, Toshihiko Uematsu, Kazuo Umemura, Yoshiharu Takiguchi, Yoshihiro Asai and Mitsuyoshi Nakashima :
A simple and reproducible cerebral thrombosis model in rats induced by a photochemical reaction and the effect of a plasminogen-plasminogen activator chimera in this model.,
Journal of Pharmacological and Toxicological Methods, Vol.29, No.3, 165-173, 1993.

(要約): In this study a new model of cerebral ischemia, based on a middle cerebral artery (MCA) thrombosis in rats is described. Furthermore, the effect of the novel plasminogen activator (SUN9216), a plasminogen-plasminogen activator chimera, comprising the fibrin kringle 1 domain of a plasminogen, and the two kringles, and the serine protease domains of wild-type tissue plasminogen activator (t-PA), including a modification of the mannose glycosylation site on the kringle 1 of t-PA (PK1de1FE1X), was studied in this model. In the newly described model of thrombotic cerebral ischemia, an occlusive thrombus occurred usually within 8 min in the MCA as a consequence of an endothelial injury subsequent to a photochemical reaction between a systemically administered photosensitive dye (rose bengal) and a transillumination of the MCA with a high-intensity green light with a wavelength of 540 nm. The study was quantitated by means of pathological examination of the MCA and the brain. A platelet-rich thrombus was observed in the MCA using electron microscopical analysis based on ion beam bombardment. At 24 hr after induction of the thrombus, the brain was removed from 13 control animals, nine coronal sections were stained from each brain with triphenyltetrazoliumchloride (TTC), and the ischemic area was quantitated. A constant area of infarction was observed in the cortex and the lateral part of the basal ganglia. In a second group (n = 8), at 1 or 8 weeks after induction of the thrombosis in the MCA, the coronal sections were stained with hematoxylin and eosin.(ABSTRACT TRUNCATED AT 250 WORDS)
(キーワード): Animals / Cerebral Arteries / Cerebral Infarction / Disease Models, Animal / Fibrinolytic Agents / Intracranial Embolism and Thrombosis / Male / 光化学 (photochemistry) / Rats / Rats, Wistar / Reproducibility of Results / Tissue Plasminogen Activator
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/1056-8719(93)90068-P
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8364230; ● Summary page in Scopus @ Elsevier: 2-s2.0-0027247636

(DOI: 10.1016/1056-8719(93)90068-P, PubMed: 8364230, Elsevier: Scopus) Yoshiharu Takiguchi, Koichiro Wada and Mitsuyoshi Nakashima :
Hemodynamic effects on thrombogenesis and platelet aggregation in spontaneously hypertensive rats.,
Clin.Exp.Hypertension, Vol.15, 197-208, 1993. Yoshihiro Hirata, Yoshiharu Takiguchi, Koichiro Wada, Hiroyuki Matsuno, Kazuo Umemura, Toshihiko Uematsu and Mitsuyoshi Nakashima :
Roles of platelet-activating factor, thromboxane A2, ADP and thrombin in thrombogenesis in the guinea pig.,
European Journal of Pharmacology, Vol.231, 421-425, 1993. Koichiro Wada, Yoshiharu Takiguchi and Mitsuyoshi Nakashima :
Changes in platelet aggregation in whole blood, plasma and washed platelets in streptozotocin-induced diabetic rats: Time-dependent change in the antiaggregatory activity of diabetic rat plasma.,
Platelets, Vol.4, No.5, 280-284, 1993.

(要約): Time-dependent changes in platelet aggregation in whole blood, platelet-rich plasma (PRP) and washed platelets were studied in streptozotocin-induced diabetic rats. Collagen-induced aggregation of whole blood and PRP from diabetic rats were significantly reduced within 8 weeks after induction of diabetes, although that in washed platelets were increased from 8 weeks. Plasma from diabetic rats within 8 weeks attenuated platelet aggregation, whereas diabetic plasma at 12 weeks showed no inhibitory effect. Insulin treatment normalized aggregation in whole blood and PRP and abolished the antiaggregatory activity of diabetic plasma. These results suggest the plasma antiaggregating activity appears in the early stage of diabetes, which may contribute to the hypoaggregation in whole blood and PRP. The inhibitory activity disappeared in the later stage. Plasma factor(s) accounting for the antiaggregatory effect of diabetic plasma has not yet characterized.
(出版サイトへのリンク): ● Publication site (DOI): 10.3109/09537109309013229
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21043752; ● Search Scopus @ Elsevier (PMID): 21043752; ● Search Scopus @ Elsevier (DOI): 10.3109/09537109309013229

(DOI: 10.3109/09537109309013229, PubMed: 21043752) Yoshinori Hirata, Kazuo Umemura, Yoshiharu Takiguchi, Toshihiko Uematsu and Mitsuyoshi Nakashima :
A thrombosis model for evaluating thrombolytic agents in the guinea-pig:comparison of t-PA, scu-PA and a novel thrombolytic agent, staphylokinase, on thrombolytic activity.,
Blood Coagulat.Fibrinol., Vol.4, 569-575, 1993. Yoshiharu Takiguchi, Yoshihiro Hirata, Koichiro Wada and Mitsuyoshi Nakashima :
Arterial thrombosis model with photochemical reaction in guinea-pig and its property.,
Thrombosis Research, Vol.67, No.4, 435-445, 1992.

(要約): We have already developed an arterial thrombosis model in the rat femoral artery which utilized photochemical reaction between systemically injected rose bengal and transillumination of a green light with 540 nm wave length from the outside of the vessel. In the present study, we applied this model to guinea-pigs in order to produce a more suitable thrombus model for evaluation of antithrombotic drugs which act on the prostaglandin cascade. In the guinea-pigs, the irradiated femoral artery was completely occluded in 7 min after the injection of rose bengal (10 mg/kg) in a similar manner to the rats. The processes of primary endothelial injury and the subsequent formation of thrombus during this manipulation were observed by the electron microscopy. Pretreatment with aspirin and Y-20811, a thromboxane synthetase inhibitor, significantly prolonged the time required for occlusion in the guinea-pigs, while these drugs were ineffective in the rats. The antithrombotic effect of vapiprost, a thromboxane A2 receptor antagonist, was more pronounced in the guinea-pigs than the rats. In conclusion, this model in guinea-pigs is more suitable for evaluating antithrombotic drugs, particularly, the action of which is exerted involving the prostaglandin cascade.
(キーワード): Animals / Aspirin / Biphenyl Compounds / Disease Models, Animal / Femoral Artery / Fibrinolytic Agents / Guinea Pigs / Heptanoic Acids / Imidazoles / Light / Male / Microscopy, Electron, Scanning / 光化学 (photochemistry) / Platelet Aggregation / Prostaglandins / Rats / Rats, Wistar / Rose Bengal / Thrombosis
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/0049-3848(92)90273-D
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 1412222; ● Search Scopus @ Elsevier (PMID): 1412222; ● Search Scopus @ Elsevier (DOI): 10.1016/0049-3848(92)90273-D

(DOI: 10.1016/0049-3848(92)90273-D, PubMed: 1412222) hiroyuki Matsuno, Toshihiko Uematsu, Kazuo Umemura, Yoshiharu Takiguchi, Koichiro Wada and Mitsuyoshi Nakashima :
Effects of vapiprost, a novel thromboxane receptor antagonist, on thrombus formation and vascular patency after thrombolysis by tissue-type plasminogen activator.,
British Journal of Pharmacology, Vol.106, 533-538, 1992. Yoshiharu Takiguchi, Koichiro Wada and Mitsuyoshi Nakashima :
Comparison of the inhibitory effects of the TXA2 receptor antagonist, vapiprost, and other antiplatelet drugs on arterial thrombosis in rats:Possible role of TXA2.,
Thromb.Haemostas., Vol.68, 460-463, 1992. Yoshiharu Takiguchi, Koichiro Wada and Mitsuyoshi Nakashima :
Effect of aldose reductase inhibitor on the inhibition of platelet aggregation induced by diabetic rat plasma.,
European Journal of Pharmacology, Vol.215, 289-291, 1992. R.P Hof, Yoshiharu Takiguchi, J Nussberger, A Hof, M Klay, T Peters, R Zelis and H.R Brunner :
Baroreflex and atrial natriuretic factor concentration correlate with myocardial infarct size and predict early death in rabbits:Implications for drug studies.,
Journal of Cardiovascular Pharmacology, Vol.18, No.3, 361-368, 1991.

(要約): The severity of myocardial infarction (MI) and its functional consequences are difficult to assess in small animals. We searched for criteria to achieve such an assessment in rabbits 1 week after MI. Thirteen large mongrel rabbits (3-4 kg) were anesthetized with pentobarbitone for ligating a branch of the circumflex coronary artery and 7 rabbits were subject to a sham operation without ligation. All sham-operated rabbits and 12 MI animals survived for 1 week, when blood was obtained for biochemical analyses and the baroreflex was tested. Six animals survived to the third week (survivors) and six died earlier (nonsurvivors). The MI size, measured immediately after death, was 42 +/- 3% of the left ventricular mass in nonsurvivors and 20 +/- 7% in survivors. The plasma atrial natriuretic factor (ANF) concentration was correlated linearly with MI size (r = 0.77) over the whole range of infarct sizes and, like the MI size itself, was associated with the risk of early death (critical limit: 80 pM). Plasma renin activity and catecholamines yielded less prognostic information. The baroreflex control of the heart rate (tested using phenylephrine and nitroprusside) of nonsurvivors was severely impaired and the slopes correlated with MI size (r = 0.90 for phenylephrine and r = 0.67 for nitroprusside). The plasma ANF concentration and the baroreflex both accurately reflected MI size and also correctly classified 11/12 rabbits into survivors and nonsurvivors. An ANF- and baroreflex-based stratification of animals for future studies on therapeutic interventions after MI will reduce the number of animals required by at least 65%, making such studies far more feasible than in the past.
(キーワード): Animals / Atrial Natriuretic Factor / Blood Pressure / Coronary Vessels / Female / Heart Rate / Male / Myocardial Infarction / Nitroprusside / Norepinephrine / Phenylephrine / Pressoreceptors / Rabbits / Radioimmunoassay / Reflex / Renin
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 1720836; ● Search Scopus @ Elsevier (PMID): 1720836

(PubMed: 1720836) Yoshiharu Takiguchi, Koichiro Wada, Hiroyuki Matsuno and Mitsuyoshi Nakashima :
Effect of diabetes on photochemically induced thrombosis in femoral artery and platelet aggregation in rats.,
Thrombosis Research, Vol.63, No.4, 445-456, 1991.

(要約): Effect of diabetes on thrombogenesis was examined by using a thrombus model with photochemical reaction in the rat femoral artery. In streptozotocin-induced diabetic rats for 8 weeks, the formation of thrombus following endothelial injury was significantly slower than that in non-diabetic rats. Insulin treatment normalized the abnormality of thrombogenesis. Aggregation in washed platelets from rats with diabetes was enhanced. However, platelet aggregation in whole blood was reduced in diabetic rats, and plasma from diabetic rats attenuated platelet aggregation. These results suggest that plasma factor(s) and/or other blood cells modify the hyperaggregability of platelets per se in vivo in diabetic rats. Treatment with insulin improved the aggregation in whole blood and washed platelets. In conclusion, diabetes induces the prolongation of thrombogenesis in the rat femoral artery. Hypoaggregability of whole blood is likely to be partly involved in the abnormal thrombogenesis.
(キーワード): Animals / Blood Coagulation / Blood Glucose / Diabetes Mellitus, Experimental / Diabetic Angiopathies / Disease Models, Animal / Femoral Artery / Male / 光化学 (photochemistry) / Platelet Aggregation / Rats / Rats, Inbred Strains / Thrombosis
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/0049-3848(91)90231-K
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 1754997; ● Search Scopus @ Elsevier (PMID): 1754997; ● Search Scopus @ Elsevier (DOI): 10.1016/0049-3848(91)90231-K

(DOI: 10.1016/0049-3848(91)90231-K, PubMed: 1754997) Yi-Ting Wang, Yoshiharu Takiguchi, Toshihiko Uemastu and Mitsuyoshi Nakashima :
Augmented responsiveness to sympathetic nerve stimulation of isolated vas deferens of diabetic rats.,
Arch.Int.Pharmacodyn., Vol.309, 160-169, 1991. Kazuo Umemura, Yoshiharu Takiguchi and Mitsuyoshi Nakashima :
Altered effect of arachidonic acid on inner ear blood flow in rats with streptozotocin-induced diabetes.,
Ann.Otol.Rhinol.Laryngol., Vol.100, 389-393, 1991.

MISC

研究者総覧に該当データはありませんでした。

総説・解説: 滝口祥令, 佐藤智恵美, 土屋浩一郎 :
効果的な実務実習に向けたアクティブ・ラーニングの取り組み,
医薬ジャーナル, Vol.51, No.11, 133-137, 2015年11月. 滝口祥令, 植松俊彦 :
新薬の老年者への適用(17)アルツハイマー型痴呆治療薬,
老年消化器病, Vol.12, 181-183, 2000年. Toshihiko Uematsu and Yoshiharu Takiguchi :
Pharmacokinetic and-dynamic aspects of active agents against anti-biotic-resistant gram-positive cocci,
Recent Res.Devel.Antimicrob.Agents & Chemother., Vol.4, 55-62, 2000. 滝口祥令, 植松俊彦 :
新薬の老年者への適用(18)SSRI(選択的セロトニン再取り込み阻害薬,
老年消化器病, Vol.12, 281-283, 2000年. 滝口祥令, 植松俊彦 :
毛髪中のカフェインは肝機能の指標 -連載「毛髪による薬歴·病歴管理--毛髪一本でここまで分かる」-,
治療, Vol.79, 1747, 1997年. 滝口祥令, 中島光好 :
病気とくすり:狭心症治療薬,
薬局, Vol.45, 197-200, 1994年. 滝口祥令, 中島光好 :
新しい作用機序の薬:Kチャネル開口薬,
日本病院薬剤師会雑誌, Vol.30, 429-432, 1994年. 中島光好, 梅村和夫, 滝口祥令 :
創薬のための新しい病態モデル,
日本薬理学雑誌, Vol.102, 191-199, 1993年. 滝口祥令, 中島光好 :
注目の新薬:カドララジン,
現代医療, Vol.24, No.7, 1975-1979, 1992年7月. 滝口祥令, 中島光好 :
薬理学からみた動脈硬化ー抗動脈硬化薬とはー,
月刊「循環」, Vol.12, 17-20, 1991年. 滝口祥令 :
アスピリンの抗血小板療法ーaspirin dilemmaへのアプローチー,
医学のあゆみ, Vol.155, 103, 1990年. 滝口祥令, 中島光好 :
カリウム保持性利尿薬.,
医学のあゆみ, Vol.153, 951-955, 1990年. 滝口祥令, 中島光好 :
薬理作用に対する前臨床試験,
薬局, Vol.39, 1563-1568, 1988年.
講演・発表: Naoshi Yamazaki, Makiko Shinomiya, Hironobu Ike, Yasuo Shinohara, Noriaki Minakawa, Kouji Itou and Yoshiharu Takiguchi :
Use of modified U1 small nuclear RNA for improved formation of properly spliced mRNA encoding human cathepsin A from the gene having an IVS7 +3a>g mutation,
The 43rd FEBS Congress, Praha, Jul. 2018. Yoshiharu Takiguchi :
Yoshiharu Takiguchi, Shin-ichi Tani, Keisuke Furuta, Naoshi Yamazaki. Implication of endogenous lysophosphatidic acid in intimal thickening in rat injured artery.Implication of endogenous lysophosphatidic acid in intimal thickening in rat injured artery. 18th World Congress of Basic and Clinical Pharmacology,
Kyoto, Jul. 2018. Naoshi Yamazaki, Yasuo Shinohara, Kouji Itou, Noriaki Minakawa and Yoshiharu Takiguchi :
Rescue of mutation-induced exon 7 skipping in human Cathepsin A by using modified U1 small nuclear RNA,
2016 ASCB Annual Meeting, San Francisco, Dec. 2016. Shima Sawako, Takenori Yamamoto, Yasuo Shinohara and Yoshiharu Takiguchi :
Induction of mitochondrial permeability transition by dequalinium,
40th FEBS Congress, Berlin, Jul. 2015. Kuwahara Kana, Harada Kazuki, Yamagoshi Ryohei, Yoshiharu Takiguchi, Takenori Yamamoto and Yasuo Shinohara :
Effects of employment of distinct strategies to capture antibody on antibody delivery into cultured cells,
40th FEBS Congress, Berlin, Jul. 2015. Takenori Yamamoto, Ito Mika, Kageyama Keita, Kuwahara Kana, Kikuji Yamashita, Yoshiharu Takiguchi, Seiichiro Kitamura, Hiroshi Terada and Yasuo Shinohara :
Mastoparan causes mitochondrial permeability transition not by interacting with specific proteins, but by interacting with the phospholipid phase,
The American Society for Cell Biology 2014, Philadelphia, Dec. 2014. Noriko Saito-Tarashima, Kojima Takamitsu, Hashimoto Yosuke, Kazuhiro Furukawa, Naoshi Yamazaki, Hiroshi Kiwada, Tatsuhiro Ishida, Noriaki Minakawa and Yoshiharu Takiguchi :
A novel approach of gene suppression using an intelligent shRNA expressing device (iRed),
9th Annual Meeting of the Oligonucleotide Therapeutics Society, Naples(Italy), Oct. 2013. Y. Kikuchi, Naoshi Yamazaki, Yoshiharu Takiguchi and Noriaki Minakawa :
Gene silencing by 2'-modified-4'-thio oligonucleotides via U1i machinery,
第39回国際核酸化学シンポジウム, Nov. 2012. Koichiro Tsuchiya, Yuya Horinouchi, Yasuhisa Kanematsu, Shinji Abe, Hideki Ohnishi, Soichiro Tajima, Keisuke Ishizawa, Toshiaki Tamaki and Yoshiharu Takiguchi :
Production of nitrosonifedipine radical from nifedipine and its antioxidative activity in cultured cells,
13th annual meeting of society of free radical and biology of medicine, Denver, Nov. 2006. Koichiro Tsuchiya, Yasuhisa Kanematsu, Keisuke Ishizawa, Shinji Abe, Hideki Ohnishi, Soichiro Tajima, Kazuyoshi Kawazoe, Yoshiharu Takiguchi and Toshiaki Tamaki :
Dietary nitrite is an alternative source of NO in vivo,
International Society for Radical Research 13th Biennial Congress, Davos, Switzerland, Aug. 2006. Soichiro Tajima, Koichiro Tsuchiya, Hideki Ohnishi, Yasuhisa Kanematsu, Masanori Yoshizumi, Toshiaki Tamaki, Mason P. Ronald and Yoshiharu Takiguchi :
Immunochemical Dection of Thioredoxin-Derived Radicals Formed by Reaction with Hydrogen Peroxide,
EPR 2005, Columbus, OH, Sep. 2005. Koichiro Tsuchiya, Kaori Akai, Akira Tokumura, Shinji Abe, Toshiaki Tamaki, Yoshiharu Takiguchi and Kenji Fukuzawa :
Oxygen Radicals Photo-induced by Ferric Nitrilotriacetate(FE-NTA) Complex,
EPR 2005, Columbus, OH, Sep. 2005. 川合真央, 植田百花, 山﨑尚志, 滝口祥令 :
ヒトCPT1a mRNAの3'非翻訳領域におけるA-to-I RNA編集部位,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年10月. 宮城さくら, 山﨑尚志, 古藤遼佑, 篠原康雄, 滝口祥令 :
A-to-I RNA編集によるヒトCPT1a発現量の変化,
第59回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2020年11月. 高橋里奈, 植田百花, 小出華永, 川合真央, 山﨑尚志, 月本準, 伊藤孝司, 滝口祥令 :
イントロンやエクソン内の配列と結合する改変U1 snRNAによるCTSAエクソン7スプライス異常の修復,
第58回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2019年11月. 奥村俊樹, 山﨑尚志, 高石誠太郎, 宮城さくら, 滝口祥令 :
ヒトCPT1A mRNAにおけるA-to-I RNA編集の意義の解明,
第58回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2019年11月. 徳橋尚紀, 河口由佳, 山﨑尚志, 宮城さくら, 篠原康雄, 滝口祥令 :
ヒトCPT1A mRNAの3'-UTRにおけるA-to-I RNA編集,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 四宮槙子, 小出華永, 高橋里奈, 山﨑尚志, 月本準, 伊藤孝司, 滝口祥令 :
Exon specific U1 snRNAによる CTSAエクソン7スプライス異常の修復,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 高田元太, 橋本晴香, 山﨑尚志, 滝口祥令 :
トランススプライシングを用いたヒトカテプシンAエクソンスキップ修復の試み,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 四宮槙子, 小出華永, 高橋里奈, 山﨑尚志, 月本準, 伊藤孝司, 滝口祥令 :
Exon specific U1 snRNAを用いたCTSAエクソン7スキッピングの修復,
第91回日本生化学会大会, 2018年9月. 徳橋尚紀, 河口由佳, 山﨑尚志, 宮城さくら, 篠原康雄, 滝口祥令 :
ヒトCPT1A mRNAの3'-UTR中の逆向きAlu配列はADARによってRNA編集を受ける,
第91回日本生化学会大会, 2018年9月. 高田元太, 橋本晴香, 山﨑尚志, 滝口祥令 :
トランススプライシングを用いたヒトカテプシンAエクソン7スキップの修復,
第91回日本生化学会大会, 2018年9月. 四宮槙子, 小出華永, 高橋里奈, 月本準, 山﨑尚志, 伊藤孝司, 滝口祥令 :
改変U1 snRNAによるカテプシンAスプライス異常修復効果の検討,
第59回日本生化学会中国四国支部例会, 2018年5月. 河口由佳, 徳橋尚紀, 山﨑尚志, 篠原康雄, 滝口祥令 :
ヒトCPT1a mRNA 3'-UTR中の逆向きAlu配列はA-to-I RNA編集を受ける,
2017年度生命科学系学会合同年次大会, 2017年12月. 河口由佳, 徳橋尚紀, 山﨑尚志, 篠原康雄, 滝口祥令 :
ヒトCPT1a mRNAの3 '-UTRに存在する逆向きAlu配列とRNA編集,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 齋藤朱里, 四宮槙子, 高橋里奈, 山﨑尚志, 滝口祥令 :
ヒトカテプシンAエクソン7スキッピングにおける3 'スプライスサイトの関与,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 山村桃子, 高田元太, 冨永和也, 山﨑尚志, 滝口祥令 :
ヒトカテプシンAスプライス異常修復を目指したトランススプライシング法の確立,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 井上真緒, 高田元太, 山﨑尚志, 滝口祥令 :
トランススプライシングを用いたヒトカテプシンAスプライシング異常修復の検討,
第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2016年11月. 木村麻里安, 四宮槙子, 池啓伸, 齋藤朱里, 山﨑尚志, 伊藤孝司, 南川典昭, 滝口祥令 :
カテプシンAスプライシング異常の修復を目指した改変U1 snRNA発現系の構築,
第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2016年11月. 滝口祥令 :
シンポジウム「先導的薬剤師養成にめけた実践的アドバンスト教育プログラムの共同開発(H22-H27年度)の中四国国立3大学における実施状況と新事業の展開に向けて」,
第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2016年11月. 木村麻里安, 池啓伸, 斎藤朱里, 山﨑尚志, 伊藤孝司, 南川典昭, 滝口祥令 :
塩基改変したU1 snRNAによるカテプシンAスプライス異常修復効果の検討,
第57回日本生化学会中国四国支部例会, 2016年5月. 滝口祥令 :
シンポジウム先導的薬剤師養成にめけた実践的アドバンスト教育プログラムの共同開発「教育評価手法プログラム及びトランスレーショナルリサーチ・臨床試験プログラム」,
2016年3月. 滝口祥令, 下川義彦, 依田典明, 近藤聡志, 山村佳也, 梅原健 :
結核治療薬の肝CYP酵素阻害活性に関する網羅的検討,
第36回日本臨床薬理学会学術総会, 2015年12月. 三木和也, 山村桃子, 田良島典子, 山﨑尚志, 南川典昭, 滝口祥令 :
新規機能性RNA発現デバイスiRedを用いたmiRNA産生による遺伝子発現抑制効果の検討,
BMB2015 第38回日本分子生物学会年会・第88回日本生化学会大会合同大会, 2015年12月. 木村麻里安, 金澤慶祐, 斎藤朱里, 山﨑尚志, 池啓伸, 伊藤孝司, 南川典昭, 滝口祥令 :
改変U1 snRNAを用いた変異カテプシンAスプライス異常の修復,
BMB2015 第38回日本分子生物学会年会・第88回日本生化学会大会合同大会, 2015年12月. 金澤慶祐, 木村麻里安, 斎藤朱里, 山﨑尚志, 池啓伸, 伊藤孝司, 南川典昭, 滝口祥令 :
改変U1 snRNAを用いたヒトカテプシンAエクソンスキッピングの修復,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年10月. 伊藤優希, 山﨑尚志, 滝口祥令 :
Carnitine palmitoyltransferase 1アイソフォームのSDS-PAGE移動度に違いをもたらす領域の同定,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年10月. 金澤慶佑, 山﨑尚志, 池啓伸, 伊藤孝司, 南川典昭, 滝口祥令 :
改変U1 snRNAによるヒトカテプシンAスプライス異常修復,
遺伝子・デリバリー研究会第15回シンポジウム, 2015年5月. 島佐和子, 山本武範, 榎本麻里子, 山下菊治, 寺田弘, 篠原康雄, 滝口祥令 :
デカリニウムはミトコンドリアに透過性遷移を誘起する,
日本薬学会年会, 2015年3月. 伊藤優希, 井上真緒, 山﨑尚志, 滝口祥令 :
CPTⅠタンパク質のアイソフォーム間におけるSDS-PAGE移動度の違い,
第36回生体膜と薬物の相互作用シンポジウム, 2014年11月. 田中翔子, 金澤慶祐, 山﨑尚志, 池啓伸, 伊藤孝司, 南川典昭, 滝口祥令 :
改変U1 snRNAによるヒトカテプシンAスプライス異常修復の試み,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 三木和也, 山﨑尚志, 吉良太孝, 田良島典子, 古川和寛, 南川典昭, 滝口祥令 :
ナノ核酸デバイスを用いたsiRNAオフターゲット効果の抑制,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 朝倉有紀, 三木和也, 木村麻里安, 山﨑尚志, 滝口祥令 :
改変U1 snRNAによる遺伝子発現抑制効果の検討,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 伊藤美香, 山本武範, 懸山啓太, 桑原かな, 山下菊治, 滝口祥令, 寺田弘, 篠原康雄 :
Mastoparanはミトコンドリアのリン脂質膜に作用して透過性遷移を誘導する,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 池啓伸, 山﨑尚志, 田中翔子, 金澤慶祐, 滝口祥令, 南川典昭, 伊藤孝司 :
改変U1 snRNAによるヒトカテプシンAの遺伝子発現におけるスプライシング異常の修復,
第87回日本生化学会, 2014年10月. 山﨑尚志, 田中翔子, 金澤慶祐, 伊藤孝司, 南川典昭, 滝口祥令 :
改変U1snRNAによるヒトカテプシンAスプライス異常修復の試み,
第55回日本生化学会中国・四国支部例会, 2014年6月. 中西智子, 石澤啓介, 阿部真治, 中瀬真理, 柴田洋文, 佐藤智恵美, 新垣尚捷, 佐藤陽一, 山﨑尚志, 笠原二郎, 東満美, 山﨑哲男, 山内あい子, 滝口祥令, 土屋浩一郎 :
アドバンスト演習を通した問題解決能力向上のための症例解析手法の検討-プロダクトからの分析,
日本薬学会第134年会, 2014年3月. 懸山啓太, 篠原康雄, 山本武範, 山﨑尚志, 滝口祥令 :
ミトコンドリア透過性遷移におけるシクロフィリンDの挙動解析,
第87回日本薬理学会年会, 2014年3月. 山﨑尚志, 阿萬明, 朝倉有紀, 藤原裕士, 南川典昭, 滝口祥令 :
改変U1 snRNAによる遺伝子発現抑制効果の検討,
第23回アンチセンスシンポジウム, 2013年11月. 藤原裕士, 山﨑尚志, 南川典昭, 滝口祥令 :
複数の改変U1 snRNAを用いた遺伝子発現抑制,
第23回アンチセンスシンポジウム, 2013年11月. 藤原裕士, 山﨑尚志, 滝口祥令 :
改変U1 snRNAによる遺伝子発現制御,
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月. 中西智子, 石澤啓介, 阿部真治, 中瀬真理, 柴田洋文, 佐藤智恵美, 新垣尚捷, 佐藤陽一, 山﨑尚志, 笠原二郎, 東満美, 山﨑哲男, 山内あい子, 滝口祥令, 土屋浩一郎 :
アドバンスト演習を通した問題解決能力向上のための症例解析手法の検討,
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月. 門田美香, 山﨑尚志, 滝口祥令 :
CPT1アイソフォームのSDS-PAGE移動度の違い,
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月. 石戸健, 近藤祐未, 橋村慧, 德村彰, 山﨑尚志, 滝口祥令 :
ラット血管肥厚形成への内因性リゾホスファチジン酸の関与,
第122回日本薬理学会近畿部会, 2012年11月. 柳沢未来, 滝口祥令, 山﨑尚志 :
CPT1アイソフォームのSDS-PAGE移動度の違い,
第51回日本薬学会・日本病院薬剤師会中国四国支部学術大会, 2012年11月. 阿萬明, 朝倉有紀, 南川典昭, 滝口祥令, 山﨑尚志 :
改変U1snRNAによる遺伝子発現抑制,
第51回日本薬学会・日本病院薬剤師会中国四国支部学術大会, 2012年11月. 懸山啓太, 篠原康雄, 山本武範, 山﨑尚志, 滝口祥令 :
透過性遷移を誘起したミトコンドリアにおけるシクロフィリンDの挙動の解析,
第121回日本薬理学会近畿部会, 2012年6月. 滝口祥令 :
実務実習における教育評価法プログラムの開発に向けてー現状と課題ーシンポジウム:先導的薬剤師養成に向けた実践的アドバンスト教育プログラムの共同開発,
日本薬学会第132年会, 2012年3月. 菊地優作, 山﨑尚志, 滝口祥令, 南川典昭 :
2'-F-4'-チオヌクレオシドを含むキメラ型オリゴマーの合成と性質,
日本薬学会第132年会(札幌), 2012年3月. 石戸健, 中本淳子, 淺木千佳, 德村彰, 山﨑尚志, 滝口祥令 :
リゾフォスファチジン酸の血管肥厚形成への関与,
第85回日本薬理学会年会, 2012年3月. 新田芳久, 塩田祐子, 下川義彦, 山﨑尚志, 滝口祥令 :
毛髪を用いた肝CYP3A4代謝活性評価に関する基礎的検討,
第50回日本薬学会・日本病院薬剤師会中国四国支部学術大会, 2011年11月. 中本淳子, 板東由佳, 淺木千佳, 德村彰, 山﨑尚志, 滝口祥令 :
ラット血管肥厚形成への内因性リゾホスファチジン酸の関与,
第50回日本薬学会・日本病院薬剤師会中国四国支部学術大会, 2011年11月. 小島孝充, 丸山豪斗, 田良島典子, 山﨑尚志, 滝口祥令, 松田彰, 南川典昭 :
PCRによる4'-チオDNAの合成,
アンチセンス・遺伝子・デリバリーシンポジウム, 2011年9月. 滝口祥令 :
実務実習における教育評価法プログラムの現状と課題ーシンポジウム:先導的薬剤師養成に向けた実践的アドバンスト教育プログラムの共同開発,
日本薬学会第131年会, 2011年3月. 西林政治, 平野隆弘, 上原憲二, 服部克次, 中野善正, 相原美紀, 山田能久, 村口正宏, 岩田房子, 滝口祥令 :
ラットⅣ型コラーゲンの組換えNC1抗原感作誘発糸球体腎炎モデルの作製と腎不全進行の機序に関する基礎的研究,
第118回日本薬理学会近畿部会, 2010年11月. 塩田祐子, 新田芳久, 下川義彦, 山﨑尚志, 滝口祥令 :
毛髪を用いた肝CYP3A4活性評価に関する基礎的研究,
第49回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2010年11月. 梶真一朗, 中本淳子, 山﨑尚志, 滝口祥令 :
PPAR-αおよびγ活性化による心筋虚血再灌流障害抑制効果の比較,
第83回日本薬理学会年会, 2010年3月. 梶真一朗, 中本淳子, 山﨑尚志, 滝口祥令 :
心筋虚血再灌流障害に対するPPAR-γ及びPPAR-α活性化効果の比較,
第48回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2009年11月. 田澤綾香, 木下綾子, 森咲子, 山﨑尚志, 滝口祥令 :
サリチル酸系薬物の吸収に及ぼすカルバペネム系抗生物質の影響,
第48回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2009年11月. 德村彰, 上田香織, 足立美香, 竹永葉月, 盛重淳一, 堤敏彦, 滝口祥令 :
哺乳類体液におけるリゾホスファチジン酸レベルの調節機構ーシンポジウム「生理活性リゾリン脂質研究Update」,
第82回日本生化学会大会, 2009年10月. 梶真一朗, 竹永葉月, 山﨑尚志, 德村彰, 滝口祥令 :
リゾホスファチジン酸の心筋虚血再灌流障害への影響,
第82回日本薬理学会年会, 2009年3月. 梶真一朗, 一丸智司, 阿部真博, 滝口祥令 :
心筋虚血再灌流障害に対するPPAR-γ活性化療法の効果,
第47回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2008年11月. 竹永葉月, 梶真一朗, 松田彩佳, 德村彰, 滝口祥令 :
心筋虚血再灌流障害における脂質メディエーターリゾホスファチジン酸の生理的役割,
第47回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2008年11月. 東満美, 日野出晴美, 柏田良樹, 吉田昌裕, 山﨑尚志, 土屋浩一郎, 山内あい子, 柴田洋文, 新垣尚捷, 滝口祥令, 荒木勉, 吉村好之, 姫田敏樹, 石田竜弘, 辻大輔, 木原勝 :
徳島大学薬学部OSCEトライアル実施体制の確立と検証,
第17回日本医療薬学会年会, 2007年9月. 田岡千明, 土屋浩一郎, 神谷昌樹, 根本尚夫, 石澤啓介, 山口邦久, 滝口祥令, 玉置俊晃 :
水溶性Fenofibrate製剤の作成と中性脂肪低下作用の検討,
第111回日本薬理学会近畿部会, 81, 2007年6月. 神谷昌樹, 中本亜樹, 河村知志, 根本尚夫, 土屋浩一郎, 滝口祥令 :
高脂血症治療薬・フェノフィブラートのBGL Modificationによる中性脂肪低下効果の検討,
日本薬学会第127年会, Vol.31-0567, 2007年3月. 石上まみ, 池平しのぶ, 三好真紀, 土屋浩一郎, 滝口祥令, 高石喜久 :
竹粉末のロペラミン誘発便秘改善作用,
第43回日本薬学会・日本病院薬剤師会中国四国支部学術大会, 2004年11月. 大久保美佐緒, 河野美代, 東満美, 寺岡和彦, 芳地一, 水口和生, 田村祥祐, 仁木稔, 元木宏, 玉田正夫, 山内あい子, 滝口祥令, 木原勝, 原谷明 :
薬学部学生の薬局実務実習についての意識調査∼薬局薬剤師および学生の立場から∼,
第36回日本薬剤師会学術大会, 2003年10月. 福山充俊, 嵩原裕夫, 石橋広樹, 田代征記, 滝口祥令, 岩野淳子, 山内あい子 :
小児における血中セレン濃度の検討-第1報新生児について-,
第15回日本静脈経腸栄養学会, 1999年2月. 山内あい子, 滝口祥令, 横田雅之, 木原勝, 久次米俊秀, 寺岡和彦, 水口和生, 高杉益充 :
徳島大学大学院薬学研究科医療薬学専攻における初年度臨床薬学実習の評価,
日本薬学会第118年会, 1998年3月. 横田雅之, 木原勝, 滝口祥令, 山内あい子 :
学部および大学院における医療薬学教育の実践-実習カリキュラムと学生対象アンケート調査の結果-,
日本薬学会第117年会, 1997年3月.

研究会・報告書: Naoshi Yamazaki, Makiko Shinomiya, Hironobu Ike, Yasuo Shinohara, Noriaki Minakawa, Kouji Itou and Yoshiharu Takiguchi :
Use of modified U1 small nuclear RNA for improved formation of properly spliced mRNA encoding human cathepsin A from the gene having an IVS7 +3a>g mutation,
FEBS Open Bio, Vol.8, No.Supplement 1, ShT.35-1, Jul. 2018.

特許: 研究者総覧に該当データはありませんでした。
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補助金・競争的資金: 生体内における亜硝酸由来NO生成因子の解明 (研究課題/領域番号: 18590235 )
腎虚血-再潅流時の腎臓内亜硝酸由来NO産生の病態生理学的役割の解明 (研究課題/領域番号: 16590196 )
細胞接着分子を標的とした血管肥厚薬物療法の開発 (研究課題/領域番号: 12672217 )
血管肥厚に対する白血球接着阻害療法の有効性に関する基礎的研究 (研究課題/領域番号: 10672151 )
血栓および血管肥厚形成における細胞接着分子の役割解明と薬物療法の確立 (研究課題/領域番号: 08672613 )
チロシンカイネース阻害作用に基づく新しいタイプの抗リュウマチ薬の開発研究 (研究課題/領域番号: 08557136 )
アデノシンの血管肥厚抑制作用に関する基礎的研究 (研究課題/領域番号: 07672459 )
血小板の血栓形成因子としての役割解明と抗血小板薬治療法の確立 (研究課題/領域番号: 05671896 )
病態モデルにおける血栓形成成因の薬理学的解明 (研究課題/領域番号: 03671097 )
患者群での薬動力学パラメータ算出と個別化による個人薬物投与設計に関する基礎的研究 (研究課題/領域番号: 61480440 )
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2024年11月22日更新

専門分野・研究分野: 臨床薬理学 (Clinical Pharmacology)
所属学会・所属協会: 日本薬理学会
日本臨床薬理学会
日本薬学会
日本医療薬学会
委員歴・役員歴: 日本薬理学会 (評議委員)
日本臨床薬理学会 (評議委員)
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Ｊグローバル

Jグローバル最終確認日: 2024/11/16 01:22
氏名（漢字）: 滝口祥令
氏名（フリガナ）: タキグチヨシハル
氏名（英字）: Takiguchi Yoshiharu
所属機関: 徳島大学教授

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researchmap最終確認日: 2024/11/17 01:39
氏名（漢字）: 滝口祥令
氏名（フリガナ）: タキグチヨシハル
氏名（英字）: Takiguchi Yoshiharu
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登録日時: 2002/12/1 00:00
更新日時: 2024/1/17 14:10
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所属ID: 0344020000
所属: 徳島大学
部署: 大学院ヘルスバイオサイエンス研究部
職名: 教授
学位: 医学博士
学位授与機関: 浜松医科大学
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研究者番号: 40163349

所属（現在）: KAKEN APIで取得できませんでした。

所属（過去の研究課題 情報に基づく）*注記: 2007/4/1 : 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授
2006/4/1 : 徳島大学, 大学院ヘルスバイオサイエンス研究科, 教授
2004/4/1 – 2005/4/1 : 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授
1998/4/1 – 2001/4/1 : 徳島大学, 薬学研究科, 助教授
1995/4/1 – 1997/4/1 : 徳島大学, 薬学部, 助教授
1991/4/1 – 1993/4/1 : 浜松医科大学, 医学部, 助手
1988/4/1 : 浜松医科大学, 医学部, 助教授
1986/4/1 – 1987/4/1 : 浜松医科大学, 医学部, 助手

審査区分/研究分野

研究代表者

医学 / 医学一般 / 応用薬理学・医療系薬学

研究代表者以外

医学 / 薬学 / 医薬分子機能学
生物系 / 医歯薬学 / 基礎医学 / 薬理学一般
医学 / 医学一般 / 応用薬理学・医療系薬学

キーワード

研究代表者

血栓形成 / 血小板 / 血管収縮 / 血小板抗体 / TXA_2 / 5-HT / 放出反応 / アデノシン / 血管肥厚 / 血管平滑筋 / 細胞増殖 / cAMP / 細胞接着 / von Willebrand factor / glycoprotein Ib / 血小板粘着 / 血管平滑筋増殖 / 血管内膜肥厚 / 血栓モデル / 血小板凝集能 / 糖尿病 / 高血圧症 / 高脂血症 / ラット / 抗血小板剤 / Thrombogenesis / Thrombosis Model / Platelet Aggregation / Diabetes / Hypertension / Hypercholesterolemia / Rat / 細胞間接着 / 白血球 / セレクチン / VitaminE欠乏 / fucoidin / Vitamin E欠乏 / 血管内膜障害 / Restenosis / Neointimal hyperplasia / Cell adhesion / Platelet / Leukocytes / Fucoidin / Aurintricarboxylic acid / 再狭窄 / P-セレクチン / Mac-1 / Vitamin E / 酸化ストレス / 血管リモデリング / 接着分子 / Neointimal thickening / Leukocyte / P-Selectin / Oxidative stress

研究代表者以外

血管平滑筋 / リュウマチ / トリプトキノン / 一酸化窒素 / 酵素誘導 / カルシウム / 血管内皮 / チロシンキナーゼ / メッセンジャーRNA / Vascular smooth muscle / Rheumatoid arthritis / Trip toquinone / Nitric oxide / Enzyme induction / Calcium / Endothelium / Tyrosine kinase / 亜硝酸 / 虚血 / 腎臓 / 電子スピン共鳴 / EPR / NO / 安定同位体 / nitrite / ischemia / kidney / electron paramagnetic resonance / nitric oxide / フラボノイド / quercetin / iron / Population Pharmacokinetics / ベイズ理論 / アシノクリコシド系抗生物質 / リドカイン / NONMEM / Population pharmacokinetics / アミノグリコシド / 血中濃度予測 / 薬物投与設計 / 薬動力学 / 薬物血中濃度測定 / カフェイン / テオフィリン / Bayesian method / lidocaine

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滝口 祥令

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研究代表者以外

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滝口祥令