プラズマ照射の効果に基づく住血性原虫の新制御法の確立

• Project Area: Plasma medical innovation
• Project/Area Number: 15H00891
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: 横山 直明 帯広畜産大学, 原虫病研究センター, 教授 (80301802)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: プラズマ / トリパノソーマ / 酸化ストレス / 治療薬 / 原虫 / バベシア / 制御法 / プラズマ医療 / 培養

Outline of Annual Research Achievements

平成28年度では主に以下の研究成果を得た。

トリパノソーマ病はヒトや家畜動物に深刻な病害（発熱、貧血、神経症状等）をもたらす難治性の原虫病である。昨年度は、宿主動物の血液中で増殖するトリパノソーマ原虫に対してプラズマ照射がどのような効果を示すかについて調べた。その結果、原虫の試験管内培養物を直接プラズマ処理に供したとき、または原虫をプラズマ処理培地で間接的に培養したとき、トリパノソーマの増殖は有意に阻害されることが明らかとなった。
本年度では、抗酸化酵素であるカタラーゼを原虫の培養液に添加すると、プラズマ処理培地による増殖阻害効果が消失することが明らかとなった。これらの結果は、プラズマ処理によって引き起こされる酸化ストレス状態が試験管内培養におけるトリパノソーマの増殖を阻害していることを意味している。したがって、プラズマ処理と同様な酸化的ストレス状態を再現できる薬物こそが、トリパノソーマに対する新規治療薬候補となりうる可能性を示唆している。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] 国立獣医学研究所(スリランカ)
• [Int'l Joint Research] モンゴル生命科学大学・獣医学研究所(モンゴル)
• [Int'l Joint Research] サダト大学/マンソウラ大学(エジプト)
• [Int'l Joint Research] 国立獣医学研究所(スリランカ)
• [Int'l Joint Research] モンゴル生命科学大学・獣医学研究所(モンゴル)
• [Int'l Joint Research] マンソーラ大学/ミノウフィア大学/サウスバレー大学(エジプト)
• [Journal Article] Clofazimine inhibits the growth of Babesia and Theileria parasites in vitro and in vivo. (2016)
  • Author(s): Tuvshintulga, B., AbouLaila, M., Davaasuren, B., Ishiyama, A., Sivakumar, T., Yokoyama, N., Iwatsuki, M., Otoguro, K., Omura, S., and Igarashi, I.
  • Journal Title: Antimicrob. Agents Chemother. Volume: 60 Issue: 5 Pages: 2739-46
  • DOI: 10.1128/aac.01614-15
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] RBC Invasion and invasion-inhibition assays using free merozoites isolated after cold treatment of Babesia bovis in vitro culture. (2016)
  • Author(s): Ishizaki, T., Sivakumar, T., Hayashida, K., Tuvshintulga, B., Igarashi, I., and Yokoyama N.
  • Journal Title: Exp. Parasitol. Volume: 166 Pages: 10-15
  • DOI: 10.1016/j.exppara.2016.03.010
  • NAID: 120006390946
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Molecular and biochemical characterization of methionine aminopeptidase of Babesia bovis as a potent drug target. (2016)
  • Author(s): Munkhjargal, T., Ishizaki, T., Guswanto, A., Takemae, H., Yokoyama, N., and Igarashi, I.
  • Journal Title: Vet. Parasitol. Volume: 221 Pages: 14-23
  • DOI: 10.1016/j.vetpar.2016.02.024
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characterization of an epimastigote-stage-specific hemoglobin receptor of Trypanosoma congolense (2016)
  • Author(s): Yamasaki, S., Suganuma, K., Yamagishi, J., Asada, M., Yokoyama, N., Kawazu, S., Inoue, N.
  • Journal Title: Parasites & Vectors Volume: in press Issue: 1 Pages: 299-299
  • DOI: 10.1186/s13071-016-1563-9
  • NAID: 120006390942
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Large-scale drug screening against Babesia divergens parasite using a fluorescence-based high-throughput screening assay. (2016)
  • Author(s): Rizk, M.A., El-Sayed, S.A., AbouLaila, M., Tuvshintulga, B., Yokoyama, N., and Igarashi I.
  • Journal Title: Vet. Parasitol. Volume: 227 Pages: 93-7
  • DOI: 10.1016/j.vetpar.2016.07.032
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Calcium ions are involved in egress of <i>Babesia bovis</i> merozoites from bovine erythrocytes (2015)
  • Author(s): Mossaad, E., Asada, M., Nakatani, D., Inoue, N., Yokoyama, N., Kaneko, O., and Kawazu, S.
  • Journal Title: Journal of Veterinary Medical Science Volume: 77 Issue: 1 Pages: 53-58
  • DOI: 10.1292/jvms.14-0391
  • NAID: 130004693911
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Macrophages are the determinant of resistance to and outcome of nonlethal Babesia microti infection in mice. (2015)
  • Author(s): Terkawi MA, Cao S, Herbas MS, Nishimura M, Li Y, Moumouni PF, Pyarokhil AH, Kondoh D, Kitamura N, Nishikawa Y, Kato K, Yokoyama N, Zhou J, Suzuki H, Igarashi I, Xuan X.
  • Journal Title: Infect Immun. Volume: 83 Issue: 1 Pages: 8-16
  • DOI: 10.1128/iai.02128-14
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Optimization of a Fluorescence-Based Assay for Large-Scale Drug Screening against Babesia and Theileria Parasites. (2015)
  • Author(s): Rizk, M.A., El-Sayed, S.A., Terkawi, M.A., Youssef, M.A., El Said el Sel, S., Elsayed, G., El-Khodery, S., El-Ashker, M., Elsify, A., Omar, M., Salama, A., Yokoyama, N., and Igarashi, I.
  • Journal Title: PLoS One. Volume: 10 Issue: 4 Pages: e0125276-e0125276
  • DOI: 10.1371/journal.pone.0125276
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Asada M, Yahata K, Hakimi H, Yokoyama N, Igarashi I, Kaneko O, Suarez CE, Kawazu SI. Transfection of Babesia bovis by double selection with WR99210 and Blasticidin-S and its application for functional analysis of thioredoxin peroxidase-1 (2015)
  • Author(s): Asada M, Yahata K, Hakimi H, Yokoyama N, Igarashi I, Kaneko O, Suarez CE, Kawazu SI
  • Journal Title: PLOS One Volume: 10(5) Issue: 5 Pages: e0125993-e0125993
  • DOI: 10.1371/journal.pone.0125993
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of inhibitory effect of methylene blue against Babesia and Theileria parasites. (2015)
  • Author(s): Tuvshintulga, B., Sivakumar, T., Salama, A.A., Yokoyama, N., and Igarashi, I.
  • Journal Title: J. Protozool. Res. Volume: 25 Pages: 18-28
  • NAID: 120006391034
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Effect of plasma-treatment on the in vitro growth of Trypanosoma brucei. (2017)
  • Author(s): Yokoyama, N., Sakakida, H., Akimoto, Y., Sivakumar, T., Ishikawa, K., Hori. M., and Ikehara, Y.
  • Organizer: The 1st International Conference on Plasma Medical Science Innovation
  • Place of Presentation: Nagoya University (Nagoya, Japan)
  • Year and Date: 2017-02-27
  • Int'l Joint Research
• [Presentation] トリパノソーマに対するプラズマ照射の効果 (2016)
  • Author(s): Yokoyama, N., Sakakida, H., Akimoto, Y., Sivakumar, T., Ishikawa, K., Hori. M., and Ikehara, Y.
  • Organizer: 第57回日本熱帯医学会大会
  • Place of Presentation: 一橋大学（東京都千代田区）
  • Year and Date: 2016-11-05
• [Presentation] Effect of plasma-treatment on the in vitro growth of Trypanosoma brucei. (2016)
  • Author(s): Yokoyama, N., Sakakida, H., Akimoto, Y., Sivakumar, T., Ishikawa, K., Hori. M., and Ikehara, Y.
  • Organizer: 6th International Conference on Plasma Medicine (ICPM-6)
  • Place of Presentation: FIIT STU (Bratislava, Slovakia)
  • Year and Date: 2016-09-04
  • Int'l Joint Research