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Microtubules are damaged by diethylcarbamazine, anti-filarial drug

Research Project

Project/Area Number 62570178
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 寄生虫学(含医用動物学)
Research InstitutionInstitute of Tropical Medicine, Nagasaki Niversity

Principal Investigator

AOKI Yoshiki  Department of Parasitology, Institute of Tropical Medicine, Nagasaki University, Professor, 熱帯医学研究所寄生虫学部門, 教授 (90039925)

Co-Investigator(Kenkyū-buntansha) FUJIMAKI Yasunori  Department of Parasitology, Institute of Tropical Medicine, Nagasaki University, 熱帯医学研究所寄生虫学部門, 助手 (10209083)
EHARA Masahiko  Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, 熱帯医学研究所病原細菌学部門, 助手 (70124823)
SHIMADA Masaaki  Department of Parasitology, Institute of Tropical Medicine, Nagasaki University,, 熱帯医学研究所寄生虫学部門, 講師 (70124831)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsFilarial worm / Diethlcarbamazine / 微小管 / 糸状虫
Research Abstract

Mak et al. (1983) recently reported an culture system that allows the infective larvae of Brugia pahangi to develop to the fourth stage. Our preliminary study by using the technique of Mak suggested that diethylcarbamazine (DEC) does not kill the larvae of B. pahangi in vitro, even at a high concentration (1 mg/ml), but it inhibits the growth and development of larvae. This results encouraged us to examine the effect of DEC on the feeder cells and filarial larvae.
Firstly the effect of DEC on the feeder cells was studied. The cells used in our study were LLC-MK_2 cells. DEC inhibited proliferation of these cells, and cells grown in the presence of DEC were likely to separate from each other and became round in shape. These results encouraged us to study the cytoplasmic microtubules complex. Immunofluorescence microscopy revealed that the cells exposed to DEC were devoid of the delicate pattern of the cytoplasmic microtubules complex. Subsequently, the effect of DEC on microtubules was s … More tudied by using microtubule protein prepared from porcine brain. DEC inhibited assembly of microtubules and disassembled preformed microtubules in vitro. When the reassembled or disassembled products were examined in the presence of DEC by electron microscopy; ribbon-microtubules were frequently observed. These results strongly suggest that DEC disrupts the function of the feeder cells which support the development of filarial larvae in vitro.
Secondly, a preliminary study was designed to know the effect of DEC on filasial microtubules. The infective larvae were pre-incubated with DEC in vitro in the absence of feede cells and then inoculated into jirds. The animals were necropsied at a given intervals and the larvae recovered were examined for development. The larvae exposed to DEC did not survive long, nor develop. As we know that DEC has direct effect on larvae in vitro, the problem to be solved is whether DEC gives any damage on amphids, phasmids and excretory cells, the specific organs which are rich in microtubules among the organs and tissues of filarial worms. Less

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report

Research Products

(7 results)

All Other

All Publications

  • [Publications] Fujimaki,Y.;Shimada,M.;Kimura,E.;Aoki,Y.: Parasitology Research. 74. 299-300 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Fujimaki,Y.;Ehar,M.;Kimura,E.;Shimada,M.;Aoki,Y.: Parasitology Research.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Fujimaki, Y.; Shimada, M.; Kimura, E.; Aoki, Y.: "DEC-inhibited development of third-stage Brugia pahangi in vitro" Parasitology Research. 74. 299-300 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Fujimaki, Y.; Ehara, M.; Kimura, E.; Shimada, M.; Aoki, Y.: "Diethylcarbamazine, antifilarial drug, inhibits microtubule polymerization and disrupts preformed microtubules"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Fujimaki, Y.; Shimada, M.; Aoki, Y.: "Possible injurious direct action of diethylcarbamazine against third-stage Brugia pahangi"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Fujimaki,Y.;Ehara,M.;Kimura,E.;Shimada,M.;Aoki,Y.: Parasitology Research.

    • Related Report
      1988 Annual Research Report
  • [Publications] Y. Fujimaki;M. Shimada;E. Kimura & Y. Aoki: Parasitology Research. 74. 299-300 (1988)

    • Related Report
      1987 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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