Updated on 2023/12/21

写真a

 
OKUBO Keisuke
 
Organization
Okayama University Hospital Assistant Professor
Position
Assistant Professor
External link

Degree

  • 博士(歯学) ( 2017.3 )

Research Interests

  • 歯周病学

  • 歯科保存学

  • 歯内療法学

  • ナノ材料

  • 医療機器

Research Areas

  • Life Science / Conservative dentistry  / 歯内療法学

  • Life Science / Conservative dentistry  / 歯周病学

  • Life Science / Regenerative dentistry and dental engineering

  • Life Science / Social dentistry

Professional Memberships

 

Papers

  • Analysis of subgingival microbiota in monozygotic twins with different severity and progression risk of periodontitis. International journal

    Tadashi Yamamoto, Makoto Taniguchi, Kazuyuki Matsunaga, Yusuke Kawata, Mari Kawamura, Keisuke Okubo, Keisuke Yamashiro, Kazuhiro Omori, Shogo Takashiba

    Clinical case reports   10 ( 4 )   e05725   2022.4

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    The study aims to reveal the composition of subgingival bacteria in monozygotic twins with discordant in severity and progression risk of periodontitis. Microbiome analysis indicated that most bacteria were heritable but differed in their abundance and immune response. The dysbiotic bacteria can be considered as risk markers for periodontitis progression.

    DOI: 10.1002/ccr3.5725

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  • Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis. International journal

    Satoru Shindo, Irma Josefina Savitri, Takenobu Ishii, Atsushi Ikeda, Roodelyne Pierrelus, Alireza Heidari, Keisuke Okubo, Shin Nakamura, Umadevi Kandalam, Mohamad Rawas-Qalaji, Elizabeth Leon, Maria Rita Pastore, Patrick Hardigan, Toshihisa Kawai

    International journal of molecular sciences   23 ( 6 )   2022.3

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    Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes.

    DOI: 10.3390/ijms23062938

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  • Evaluation of the simulator with automatic irrigation control system designed for countermeasures of internal contamination in dental unit water lines. International journal

    Keisuke Okubo, Takashi Ito, Kentaro Okamoto, Ichiro Yamamoto, Hajime Mizutani, Yusuke Kawata, Yasuyoshi Shiota, Masahiro Ito, Shin Nakamura, Masako Tai, Tadashi Yamamoto, Shogo Takashiba

    Heliyon   6 ( 6 )   e04132   2020.6

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    UNLABELLED: The prevention of nosocomial infections is an imperative task. The dental chair unit (DCU) is an indispensable device used in dental treatment. However, it is known that the dental unit water line (DUWL) can become contaminated with biofilm, consisting mainly of heterotrophic bacteria (HB). Recently, the International Organization for Standardization specified the methods for testing DUWL contamination management. On these grounds, a simulator reproducing DUWL was prepared to standardize the examination method of the DUWL contamination. OBJECTIVES: To evaluate the reproducibility of the DUWL simulator, monitor the DUWL contamination states, and test the efficacy of a commercial decontaminant for DUWL. METHODS: The DUWL simulator was assembled by a DCU manufacturing company. The simulator's DUWL was filled with tap water (TW), and left for approximately one year. Neutral electrolyzed water (NEW) was used as a decontaminant for DUWL. Both TW and NEW were passed through DUWL in a timely manner simulating daily dental treatment. Water was sampled from the air turbine hand piece weekly for 4 weeks and used for HB culture. Contamination status was evaluated by measuring bacterial adenosine triphosphate release and by culturing on Reasoner's 2A medium. RESULTS: The DUWL released contaminated water had a bacterial count of over 6 × 104 cfu/mL. After passing NEW through DUWL for 1 week, the count drastically decreased to its basal level and remained steady for 4 weeks. However, TW showed no effect on DUWL decontamination throughout the examination periods. CONCLUSIONS: The DUWL simulator could be useful to examine the efficacy of the decontaminant for DUWL and development of new methods in DUWL contamination management.

    DOI: 10.1016/j.heliyon.2020.e04132

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  • Tailoring the interaction between graphene oxide and antibacterial pyridinium salts by terminal functional groups

    R. Fujii, K. Okubo, S. Takashiba, A. Bianco, Y. Nishina

    Carbon   160   204 - 210   2020.4

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    Nanocarbons, especially two-dimensional carbons, have received considerable attention due to their unique structure and physical and chemical properties, which make them promising candidate materials for biomedical applications. In this study, we focus on graphene oxide (GO), which has many oxygenated functional groups and high affinity with water and biomaterials, and the synthesis of GO complexes with antibacterial agents, like cetylpyridinium chloride (CPC) and its derivatives. We found that the sustained release of CPCs from GO can be controlled by changing the terminal functional group of CPC. The prepared GO-CPC complexes were subjected to antibacterial tests against S. mutans. CPC with the carboxy group was degraded by the oxidizing property of GO, resulting in the loss of antibacterial properties. On the other hand, the other CPC derivatives were released from GO and showed antibacterial activities. Finally, we propose a new mechanism describing how GO and CPC form a functional complex, and how CPC is released from this complex. These findings will lead to pioneering the carbon-based functional antibacterial agents designed at the molecular level.

    DOI: 10.1016/j.carbon.2019.11.094

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  • Acceleration of bone regeneration of horizontal bone defect in rats using collagen-binding basic fibroblast growth factor combined with collagen scaffolds. International journal

    Shin Nakamura, Takashi Ito, Kentaro Okamoto, Takehiko Mima, Kentaro Uchida, Yasir D Siddiqui, Masahiro Ito, Masako Tai, Keisuke Okubo, Keisuke Yamashiro, Kazuhiro Omori, Tadashi Yamamoto, Osamu Matsushita, Shogo Takashiba

    Journal of periodontology   90 ( 9 )   1043 - 1052   2019.9

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    BACKGROUND: Basic fibroblast growth factor (bFGF) has been applied for periodontal regeneration. However, the application depends on bone defect morphology because bFGF diffuses rapidly from defect sites. In a previous study, collagen-binding bFGF (CB-bFGF) has been shown to enhance bone formation by collagen-anchoring in the orthopedic field. The aim of this study is to demonstrate the efficacy of CB-bFGF with collagen scaffolds in bone regeneration of horizontal bone defect. METHODS: Cell proliferation activity and collagen binding activity of CB-bFGF was confirmed by WST-8 assay and collagen binding assay, respectively. The retention of CB-bFGF in the collagen sheet (CS) was measured by fluorescence imaging. The rat horizontal alveolar bone defect model was employed to investigate the efficacy of CB-bFGF with collagen powder (CP). After 4 and 8 weeks, the regenerative efficacy was evaluated by microcomputed tomography, histological, and immunohistochemical analyses. RESULTS: CB-bFGF had a comparable proliferation activity to bFGF and a collagen binding activity. CB-bFGF was retained in CS longer than bFGF. At 8 weeks postoperation, bone volume, bone mineral content, and new bone area in CB-bFGF/CP group were significantly increased compared with those in other groups. Furthermore, epithelial downgrowth was significantly suppressed in CB-bFGF/CP group. At 4 weeks, the numbers of osteocalcin, proliferating cell nuclear antigen, and osteopontin-positive cells at the regeneration site in CB-bFGF/CP group were greater than those in other groups. CONCLUSIONS: CB-bFGF/CP effectively promoted bone regeneration of horizontal bone defect possibly by sustained release of bFGF. The potential of CB-bFGF composite material for improved periodontal regeneration in vertical axis was shown.

    DOI: 10.1002/JPER.18-0674

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  • Effectiveness and safety of low-concentrated ozonized water for the reduction of contamination in dental unit water lines. International journal

    Keisuke Okubo, Takashi Ito, Yasuyoshi Shiota, Yusuke Kawata, Tadashi Yamamoto, Shogo Takashiba

    Heliyon   5 ( 8 )   e02306   2019.8

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    UNLABELLED: Contamination of dental unit waterlines (DUWL) with heterotrophic bacteria can cause problems in immune compromised patients (aged, tumor and organ transplantation-patients). We focused on the use of low-concentrated ozonized water (OZW) as the biofilm formation restraint system for DUWL. Here, we examined the effects of low-concentrated OZW on the growth of bacteria and related biofilm formation and harmfulness to dental unit components (DUCs) in vitro. OBJECTIVES: To evaluate the bactericidal effects of OZW on biofilms in DUWL and DUC in vitro. METHODS: Low-concentrated OZW (0.4 mg/L) was generated using an OZS-PTDX generator. Heterotrophic bacterial biofilms in old DUWL tubes and Candia albicans solution (control microbe) were treated with OZW for 1 h with gentle agitation before static culturing for 96 h in Reasoner's 2A liquid media. The control solutions were 0.1% cetylpyridinium chloride (CPC), chlorinated tap water (TW), and phosphate-buffered saline (PBS). Adenosine triphosphate (ATP) amounts of the microbes were measured and the biofilms of these microbes were observed using scanning electron microscopy (SEM). Moreover, surfaces of DUC soaked in OZW and TW were observed by SEM. RESULTS: The OZW reduced ATP levels in microbes to 50% compared to TW and PBS treatment, although CPC reduced it below detection limits. SEM observation revealed deformation of microbes cultured with OZW, whereas no changes were seen on DUC surfaces. CONCLUSIONS: Low-concentrated OZW is bactericidal against heterotrophic bacteria biofilms and it is not harmful to DUC, suggesting that it might be useful in preventing DUWL contamination.

    DOI: 10.1016/j.heliyon.2019.e02306

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MISC

  • 酸化グラフェンを応用した既存抗菌物質の効果持続性向上への挑戦

    加納 玄, 大久保 圭祐, 伊東 孝, 大森 一弘, 仁科 勇太, 高柴 正悟

    岡山歯学会雑誌   42 ( 2 )   34 - 34   2023.12

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  • 歯面のバイオフィルム付着量を定量的に測定する方法の開発の試み

    高本 将司, 大久保 圭祐, 大森 一弘, 髙柴 正悟

    日本口腔検査学会総会・学術大会プログラム・抄録集 16回   55 - 55   2023.11

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  • 歯周炎症が血糖値の日内変動に及ぼす影響 〜マウス歯周炎モデルにおける持続自己血糖測定器を用いた解析〜

    久保田 萌可, 大森 一弘, 永田 千晶, 木山 史子, 坂井田京佑, 平井 公人, 伊東 有希, 大久保 圭祐, 池田 淳史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集 159回   146 - 146   2023.10

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  • 歯科ユニット給水管路(DUWL)内汚染の実際と電解機能水の効果

    上田 彩華, 伊東 有希[信田], 大森 一弘, 伊東 孝, 大久保 圭祐, 平井 公人, 山本 直史, 高柴 正悟

    岡山歯学会雑誌   40 ( 2 )   32 - 33   2021.12

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  • 歯科ユニット給水管路(DUWL)内汚染の実際と電解機能水の効果

    伊東 有希[信田], 大森 一弘, 伊東 孝, 大久保 圭祐, 平井 公人, 山本 直史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   155回   131 - 131   2021.10

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  • 徹底した感染管理が垂直性骨欠損を改善する要因であった重度慢性歯周炎症例

    大久保 圭祐, 高知 信介, 本郷 昌一, 河野 隆幸, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   61 ( 春季特別 )   152 - 152   2019.5

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  • 歯科用ユニット給水管路汚染対策に向けた自動注水型試験機の有効性評価

    岡本 憲太郎, 大久保 圭祐, 伊東 孝, 伊東 昌洋, 田井 真沙子, 中村 心, 山口 唯菜, 塩田 康祥, 河田 有祐, 大森 一弘, 山本 直史, 高柴 正悟

    岡山歯学会雑誌   37 ( 2 )   83 - 84   2018.12

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  • コラーゲン結合型塩基性線維芽細胞成長因子とコラーゲン基剤を用いた複合剤の歯周組織再生への応用

    中村 心, 伊東 孝, 松下 治, 岡本 憲太郎, 美間 健彦, 内田 健太郎, Siddiqui Yasir Dilshad, 伊東 昌洋, 田井 真砂子, 大久保 圭祐, 山城 圭介, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   60 ( 秋季特別 )   115 - 115   2018.10

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  • 歯周病原細菌によるヒトと伴侶動物イヌとの人獣共通感染症検査の研究

    田井 真砂子, 伊東 孝, 平山 晴子, 矢田 範夫, 小川 寛人, 田村 和也, 伊東 有希, 大久保 圭祐, 伊東 昌洋, 中村 心, 岡本 憲太郎, 平井 公人, 山城 圭介, 大森 一弘, 山本 直史, 樅木 勝巳, 高柴 正悟

    日本歯周病学会会誌   60 ( 秋季特別 )   135 - 135   2018.10

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  • 歯科用ユニット給水管路汚染対策用の注水制御シミュレータの評価

    岡本 憲太郎, 大久保 圭祐, 伊東 孝, 山本 一郎, 水谷 元, 伊東 昌洋, 田井 真沙子, 中村 心, 塩田 康祥, 河田 有祐, 大森 一弘, 山本 直史, 高柴 正悟

    日本口腔機能水学会誌   19 ( 1 )   34 - 35   2018.3

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  • 口腔バイオフィルム感染症を制御するパウダー状の天然食品の探索

    伊東 昌洋, 伊東 孝, 河田 有祐, 塩田 康祥, 大久保 圭祐, 田井 真砂子, 中村 心, 岡本 憲太郎, 青木 秀之, 二井 広平, 宮島 彩, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   59 ( 秋季特別 )   190 - 190   2017.11

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  • 口腔細菌の特定と口腔治療が急性椎前部膿瘍の治癒に奏功した症例

    松永 一幸, 山城 圭介, 平田 千暁, 猪原 健, 大久保 圭祐, 磯島 大地, 坂井田 京佑, 大森 一弘, 山本 直史, 高柴 正悟, 竹丸 誠, 下江 豊, 栗山 勝

    日本歯周病学会会誌   59 ( 秋季特別 )   193 - 193   2017.11

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  • 歯科用ユニット給水管路汚染対策用の自動注水制御シミュレータの評価

    大久保 圭祐, 伊東 孝, 山本 一郎, 水谷 元, 伊東 昌洋, 田井 真砂子, 中村 心, 岡本 憲太郎, 塩田 康祥, 河田 有祐, 大森 一弘, 山本 直史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   147回   134 - 134   2017.10

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  • 低濃度オゾン水を応用した歯科用ユニット給水管路内汚染の制御 有効性と安全性の検討

    大久保 圭祐

    岡山歯学会雑誌   36 ( 1 )   1 - 10   2017.6

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    In vitroにおける低濃度オゾン水のデンタルユニット給水管路(DUWL)汚染に関与する微生物およびバイオフィルムに対する殺菌効果、DUWL構成部品に対する影響について検討した。小型発生装置OZS-PTDXから生成した低濃度オゾン水(OZW)を使用し、単一菌種としてCandida albicansを選定した。溶存オゾン濃度の測定、浮遊状態の単一菌種に対する殺菌効果の検討、DUWL内面のバイオフィルムを構成する微生物に対する殺菌効果の検討、DUWL水中の微生物に対する殺菌効果の検討、DUWL構成部品に対する影響の検討を行った。その結果、最大0.4mg/Lの濃度を有するOZWは、DUWL構成部品の表面形状に対する顕著な影響がなく、給水管路汚染に関与する微生物に対して殺菌効果を示したことから、DUWLのバイオフィルム汚染制御に有用であることが示唆された。

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  • 6根管を有する下顎第一大臼歯の根管治療と歯科用コーンビームCTの有用性

    海老沼 孝至, 坪井 綾香, 大久保 圭祐, 下江 正幸, 山本 直史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   145回   115 - 115   2016.10

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  • 口腔細菌感染症を制御する機能性食品の探索

    伊東 昌洋, 大久保 圭祐, 伊東 孝, 河田 有祐, 塩田 康祥, 大森 一弘, 山本 直史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   145回   173 - 173   2016.10

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  • 口腔バイオフィルム抑制用の多糖誘導体リン酸化プルランにおける歯面への付着と薬剤徐放性効果の機序解明

    伊東 孝, 塩田 康祥, 河田 有祐, 大久保 圭祐, 伊東 昌洋, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   58 ( 秋季特別 )   129 - 129   2016.9

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  • ベトナム歯科医療支援でのストリートチルドレンの食生活習慣と口腔衛生管理の実態調査

    須方 佑香, 三宅 香里, 大久保 圭祐, 越宗 朋隆, 飯塚 基晴, 名倉 安紀, 鈴木 里紗, 三浦 留美, 鈴木 康司, 高柴 正悟

    日本歯科衛生学会雑誌   11 ( 1 )   149 - 149   2016.8

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  • 海藻由来レクチンを用いた口腔バイオフィルム感染症の制御

    塩田 康祥, 伊東 孝, 河田 有祐, 大久保 圭祐, 伊東 昌洋, 今村 幸治, 大森 一弘, 山本 直史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   144回   168 - 168   2016.6

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  • 天然多糖プルランリン酸化合物と塩化セチルピリジニウム混合液の口腔ケア剤としての優位性の検討

    河田 有祐, 塩田 康祥, 大久保 圭祐, 伊東 孝, 小出 尚子, 高柴 正悟

    日本歯周病学会会誌   57 ( 秋季特別 )   137 - 137   2015.8

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  • 海藻ミル由来のレクチンを用いた口腔感染制御システムの検討

    塩田 康祥, 伊東 孝, 河田 有祐, 大久保 圭祐, 今村 幸治, 山本 直史, 前田 博史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   141回   151 - 151   2014.10

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  • マッシュルーム粗抽出物による口腔感染制御能を有した機能性食品の開発

    伊東 孝, 今村 幸治, 塩田 康祥, 河田 有祐, 大久保 圭祐, 高知 信介, 峯柴 淳二, 山本 直史, 前田 博史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   140回   200 - 200   2014.6

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  • 低濃度オゾン水を応用した歯科用ユニット給水管路内(DUWL)の微生物汚染抑制システムの検討

    大久保 圭祐, 河田 有祐, 伊東 孝, 塩田 康祥, 松永 一幸, 岡本 大典, 内藤 仁美, 前田 博史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   140回   201 - 201   2014.6

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    Language:Japanese   Publisher:(NPO)日本歯科保存学会  

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  • 歯科用ユニットの給水管路(DUWL)の微生物汚染とその防止

    大久保 圭祐, 河田 有祐, 伊東 孝, 塩田 康祥, 松永 一幸, 前田 博史, 高柴 正悟

    岡山歯学会雑誌   32 ( 2 )   86 - 87   2013.12

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    Language:Japanese   Publisher:岡山歯学会  

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  • オゾン水発生装置を応用した歯科用ユニット給水経路における従属栄養水生細菌バイオフィルムの抑制システムの開発

    大久保 圭祐, 河田 有祐, 伊東 孝, 塩田 康祥, 松永 一幸, 内藤 仁美, 前田 博史, 高柴 正悟

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   139回   64 - 64   2013.10

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    Language:Japanese   Publisher:(NPO)日本歯科保存学会  

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Research Projects

  • カーボンナノシートを応用した口腔バイオフィルム形成抑制剤の効果持続性向上への挑戦

    Grant number:23K19691  2023.08 - 2025.03

    日本学術振興会  科学研究費助成事業  研究活動スタート支援

    大久保 圭祐

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    Grant amount:\2860000 ( Direct expense: \2200000 、 Indirect expense:\660000 )

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  • Search for the antibacterial technology of medical devices using mass-produced graphene oxide as a carrier

    Grant number:17H06881  2017.08 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    OKUBO Keisuke

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    Grant amount:\2730000 ( Direct expense: \2100000 、 Indirect expense:\630000 )

    The purpose of this research is to focus on the features of Graphene Oxide (GO) and to develop new materials that enable medical devices which have not been able to impart antimicrobial activity to maintain antimicrobial components.
    CPC-GO was prepared by reacting GO with cetylpyridinium chloride (CPC), which has already been used as an antibacterial agent. As a result, CPC-GO exhibited higher retention on the test sample (silicon) as compared to CPC alone, and showed sufficient antimicrobial effect. In addition, it was confirmed that CPC was sufficiently introduced into GO, and the appropriate reaction amount in preparation of CPC-GO was elucidated (CPC:GO=1:1). And it was presumed that the chemical bonding pattern of CPC-GO was ionic bonding.

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