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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳進庭 | |
dc.contributor.author | Yan-Jia Wu | en |
dc.contributor.author | 吳妍佳 | zh_TW |
dc.date.accessioned | 2021-06-07T18:07:04Z | - |
dc.date.copyright | 2012-08-09 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-23 | |
dc.identifier.citation | 1. Baron, S., Medical microbiology. 4th ed, Galveston, Tex.: University of Texas Medical Branch at Galveston. 1996.
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Morschhauser, Targeted gene disruption in Candida albicans wild-type strains: the role of the MDR1 gene in fluconazole resistance of clinical Candida albicans isolates. Mol Microbiol, 2000. 36(4): p. 856-65. 41. Sanglard, D., et al., Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. Antimicrob Agents Chemother, 1996. 40(10): p. 2300-5. 42. Perlin, D.S., Resistance to echinocandin-class antifungal drugs. Drug Resist Updat, 2007. 10(3): p. 121-30. 43. Polak, A. and H.J. Scholer, Mode of action of 5-fluorocytosine and mechanisms of resistance. Chemotherapy, 1975. 21(3-4): p. 113-30. 44. Clinical and Laboratory Standards Institute. John H. Rex, M., FACP , et al., Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved standard, 3rd ed, CLSI document M27-A3 . 2008. 45. 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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16258 | - |
dc.description.abstract | 近年來伺機性真菌對於免疫不全患者致病性增加,已成為醫院院內感染主要感染病源,而目前常用的抗真菌藥物,有些副作用過強、有些則是易使菌產生抗藥性,例如Fluconazole,導致治療效果降低,因此開發新型之藥物有其必要性。
本研究發現3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC)之衍生物9個與12個長碳鏈(BMVC-9C、BMVC-12C)對於念珠菌屬具有殺菌效果,並由藥物敏感性測試實驗結果得知BMVC-12C對標準念珠菌菌株與臨床的抗藥性菌株Candida krusei、Candida glabrata與Candida tropicalis具有類似殺菌效果。 透過共軛焦顯微鏡觀察結果,BMVC的衍生物中較不具殺菌效果的BMVC-4C、BMVC-8C,與BMVC一樣主要是存在細胞核。而BMVC-9C及BMVC-12C具殺菌效果的BMVC衍生物則會進入念珠菌的粒線體。因此推測這兩個衍生物殺菌機制,可能與粒線體功能的破壞相關。故本研究發現BMVC-12C具有潛力發展成抗真菌藥物。 | zh_TW |
dc.description.abstract | In recent years, infection of opportunistic pathogenic fungus has increased in patients with immunodeficiency, which has become the main source of nosocomial infection. Presently, antifungal drugs have been used to treat the infection but side effects as well as drug resistance become serious issues. Therefore the development of new drugs is necessary.
In this study, we found that 3,6-bis (1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) derivatives, BMVC-9C and BMVC-12C, have the antifungal effect against Candida species. Using drug susceptibility test, BMVC-12C shows antifungal effect against standard Candida strains and clinical drug-resistant strains of Candida krusei, Candida glabrata and Candida tropicalis. Under confocal microscopy analysis, BMVC derivatives (BMVC, BMVC-4C, BMVC-8C) which have no antifungal effect localize in the nucleus of Candida. BMVC-9C and BMVC-12C which have antifungal effect were found to localize in the mitochondria of Candida. Our results indicate that the antifungal mechanism of BMVC-9C and BMVC-12C might relate to the destruction of mitochondrial function suggesting the potential of BMVC-12C as an antifungal agent. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T18:07:04Z (GMT). No. of bitstreams: 1 ntu-101-R98b47411-1.pdf: 1138972 bytes, checksum: 87806ec6869aaed47916f9aeab941d20 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 第一章 緒論 1
1.1 微生物與人類關係 1 1.1.1正常菌叢(Normal microbial flora) 1 1.1.2 院內感染(Nosocomial infection) 1 1.2 念珠菌屬(Candida species) 2 1.2.1念珠菌感染症(Candidiasis) 3 1.2.2念珠菌生物膜 4 1.2.3念珠菌生物膜之生成 5 1.2.4念珠菌生物膜之抗藥機制 5 1.3 抗真菌藥物 7 1.3.1常用抗真菌藥物種類介紹 7 1.3.2目前常用抗真菌藥物的抗藥性 8 1.3.3 抗真菌藥物的抑菌效果體外測試 11 1.4 BMVC與其衍生物 13 1.4.1 BMVC與其衍生物的介紹 13 1.4.2 BMVC與其衍生物的應用 13 1.5研究動機與目的 15 1.6研究架構 16 第二章 材料與方法 17 2.1 藥品與儀器 17 2.1.1 藥品 17 2.1.2 儀器 17 2.2 菌種來源與保存、活化 18 2.2.1 菌種來源 18 2.2.2 菌種保存、活化 18 2.3 實驗方法 18 2.3.1 BMVC與其衍生物的原液配製 18 2.3.2 白色念珠菌懸浮菌體培養 19 2.3.3 BMVC與其衍生物之對懸浮念珠菌體殺菌效果測試 19 2.3.4 白色念珠菌生物膜培養 19 2.3.5 Fluconazole和BMVC-12C對於標準念珠菌菌株與臨床菌株的藥物敏感性測試 19 2.3.6棋盤格殺菌試驗(Checkerboard method) 20 2.3.7 以穿透式顯微鏡觀察BMVC與其衍生物對於懸浮念珠菌體 21 2.3.8 以雷射共軛焦顯微鏡觀察BMVC與其衍生物對於念珠菌懸浮念珠菌體 22 第三章 結果 23 3.1 BMVC-12C對於白色念珠菌懸浮菌體的殺菌效果測試 23 3.2 BMVC-12C對於白色念珠菌懸浮菌體殺菌效果的機制探討 23 3.2.1 BMVC-12C對於白色念珠菌懸浮菌體不同培養時間的殺菌效果 23 3.2.2觀察BMVC-12C對於白色念珠菌懸浮菌體在不同培養時間的作用位置 24 3.2.3 BMVC和其衍生物對白色念珠菌殺菌作用 24 3.2.4 BMVC和其衍生物對白色念珠菌懸浮菌體的作用位置 25 3.2.5 BMVC-8C、BMVC-9C、 BMVC-12C對於念珠菌懸浮菌體培養後的菌體觀察 26 3.3 BMVC-12C對於念珠菌生物膜的殺菌效果測試 26 3.4藥物感受性測試 27 3.4.1 Fluconazole和BMVC-12C對於標準念珠菌菌株的藥物感受性測試 27 3.4.2 Fluconazole和BMVC-12C對於臨床念珠菌菌株的藥物敏感性測試 28 3.5 合併Fluconazole和BMVC-12C對於標準與臨床念珠菌菌株的抑菌效果探討 28 第四章 討論 30 4.1 BMVC-12C對於懸浮念珠菌殺菌效果的探討 30 4.2 BMVC-12C對於念珠菌之生物膜殺菌效果的探討 31 4.3 Fluconazole和BMVC-12C的藥物感受性測試的探討 32 4.4 BMVC-12C對於抗藥性念珠菌之殺菌效果的探討 32 4.5 BMVC-12C與Fluconazole交互作用的探討 33 第五章 結論與未來研究方向 35 圖 36 表格 45 附圖 48 參考文獻 50 | |
dc.language.iso | zh-TW | |
dc.title | BMVC衍生物對於念珠菌的殺菌效果 | zh_TW |
dc.title | The Antifungal Activity of BMVC Derivatives against Candida spp. | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃慶璨,許瑞祥,張大釗 | |
dc.subject.keyword | Candida,BMVC 衍生物,Fluconazole,抗藥性, | zh_TW |
dc.subject.keyword | Candida,BMVC derivatives,Fluconazole,Drug resistance, | en |
dc.relation.page | 55 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2012-07-24 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
顯示於系所單位: | 生化科技學系 |
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