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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 陳進庭(Chin-Tin Chen) | |
dc.contributor.author | Yi-Jhen Huang | en |
dc.contributor.author | 黃儀真 | zh_TW |
dc.date.accessioned | 2021-07-11T14:44:46Z | - |
dc.date.available | 2021-10-14 | |
dc.date.copyright | 2016-10-14 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-01 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78175 | - |
dc.description.abstract | 近年來真菌感染的患者日益據增,尤其以白色念珠菌(Candida albicans)最為常見,而抗真菌藥物的過度頻繁使用,也引發抗藥性問題。因此許多研究開始尋找其他的治療方法,像是兩種藥物的合併使用等。光動力殺菌(Photodynamic inactivation, PDI)是不同於以藥物治療微生物感染的方式,透過光反應產生單態氧與自由基對微生物造成傷害。本研究以PDI結合Fluconazole的方式,期望透過PDI增強Fluconazole對白色念珠菌的殺菌效果,降低藥物使用劑量,減少抗藥性產生機會。
在本研究中,發現PDI對於白色念珠菌之懸浮細胞具有殺菌效果,且PDI造成的damage程度越嚴重,菌體需要修復的時間就越長,越晚進入log phase。實驗結果也發現PDI結合Fluconazole能增強對白色念珠菌的殺菌效果,降低藥物使用劑量。進一步發現以TBO 0.1 mM進行PDI後,如果不於2小時內加入Fluconazole,菌體會有修復損傷情形,無法達到增強殺菌效果。類似的增強殺菌效果也在PDI結合Posaconazole的研究中發現。此外,結合PDI和Fluconazole對白色念珠菌的臨床抗藥性菌株,也會有協同性的殺菌效果。最後,應用在白色念珠菌的生物膜殺菌上,無法像在懸浮培養上有明顯的增強殺菌效果。未來將朝向生物膜表面的胞外聚合物破壞程度與藥物作用性質,探討如何進一步結合PDI和Fluconazole來增強對生物膜的殺菌效果。 | zh_TW |
dc.description.abstract | In recent years, infection of pathogenic fungus, especially Candida albicans, has increased gradually in patients. Antifungal drugs have been frequently used to treat these infections; however, side effects of antifungal drugs as well as drug resistance gradually become serious issues. Therefore, it is important to find an alternative treatment modality for fungal infection. Photodynamic inactivation (PDI), combination of a nontoxic photosensitizer (PS) and light, could produce free radicals or singlet oxygen that are toxic to pathogens.
In this study, we found that the combination of PDI and Fluconazole could synergistically increase the antifungal activity against C. albicans. Compared to C. albicans without PDI treatment, the growth curve of C. albicans survived from PDI remained in lag phase longer and this retention correlated with the PDI dose. Furthermore, we found that the augmented antifungal activity will decrease if the addition of Fluconazole was performed two hours after PDI. Similar augment antifungal activity was also found in the combination of PDI and Posaconazole. Although higher TBO concentration is required to exert its PDI efficacy, the synergistic fungicidal efficacy was also found in drug-resistant strains. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T14:44:46Z (GMT). No. of bitstreams: 1 ntu-105-R03b22001-1.pdf: 1128553 bytes, checksum: b74bbe6312e3fc6460fe1cf5ad3da238 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 誌謝 i
摘要 ii Abstract iii 目錄 iv 結果目錄 vi 第一章 緒論 1 1.1人類與微生物 1 1.1.1正常菌叢(Normal microbial flora) 1 1.1.2伺機性感染(Opportunistic infection) 1 1.1.3院內感染(Nosocomial infection) 1 1.2白色念珠菌(Candida albicans) 2 1.2.1念珠菌菌血症(Candidemia) 3 1.2.2念珠菌生物膜 4 1.2.3白色念珠菌生物膜之生成過程 4 1.2.4念珠菌生物膜的抗藥性機制 5 1.3光動力治療(Photodynamic therapy, PDT) 7 1.3.1光動力治療發展與起源 7 1.3.2光動力治療作用機制 8 1.3.3光感物質 9 1.3.4光動力殺菌 10 1.4抗真菌藥物 11 1.4.1抗真菌藥物的種類 11 1.4.2抗真菌藥物的抗藥性 14 1.5研究動機與目的 17 第二章 材料與方法 18 2.1藥品與儀器 18 2.1.1藥品 18 2.1.2儀器 18 2.2菌種來源與保存、活化 19 2.2.1菌種來源 19 2.2.2菌種保存與活化 19 2.3實驗方法 19 2.3.1藥物配製 19 2.3.2白色念珠菌懸浮菌體培養 19 2.3.3光動力殺菌 20 2.3.4白色念珠菌之生長曲線 20 2.3.5單獨Fluconazole殺菌效果 20 2.3.6光動力殺菌結合Fluconazole或Posaconazole 21 2.3.7光動力殺菌後,不同時間點加入Fluconazole培養 21 2.3.8白色念珠菌生物膜的光動力殺菌 21 2.3.9白色念珠菌生物膜光動力殺菌結合Fluconazole 21 2.3.10統計分析 22 第三章 結果 23 3.1光感物質TBO對於白色念珠菌懸浮菌體的殺菌效果 23 3.2光動力作用下,對於白色念珠菌的生長曲線探討 23 3.3不同濃度Fluconazole對白色念珠菌的影響 24 3.4 0.25 g/ml Fluconazole增強光動力殺菌探討 24 3.5先培養Fluconazole後,在進行光動力作用的殺菌效果 25 3.6光動力作用後,Fluconazole加入的時間點探討 25 3.7不同濃度Posaconazole增強光動力殺菌的效果 26 3.8 Fluconazole與Posaconazole增強白色念珠菌抗藥性菌株的光動力殺菌探討 26 3.9光動力作用對白色念珠菌生物膜的殺菌效果 27 3.10 Fluconazole增強光動力在白色念珠菌生物膜的殺菌效果 28 第四章 討論 29 4.1光動力殺菌對於白色念珠菌的殺菌效果探討 29 4.2 Fluconazole增強光動力殺菌的效果探討 29 4.3光動力殺菌結合Posaconazole對白色念珠菌殺菌效果的探討 31 4.4光動力殺菌結合Fluconazole對白色念珠菌抗藥性菌株的影響 31 4.5光動力殺菌結合Fluconazole對白色念珠菌生物膜的殺菌效果探討 32 4.6光動力殺菌和Fluconazole交互作用的探討 33 第五章 結論與未來研究方向 35 結果圖表 36 附錄 48 附錄一、白色念珠菌生物膜形成 48 附錄二、光化學反應 49 附錄三、TBO (Toluidine Blue O)的分子結構 50 附錄四、Fluconazole與Posaconazole的分子結構 51 附錄五、光動力殺菌與Fluconazole對白色念珠菌之間交互作用 52 參考文獻 53 | |
dc.language.iso | zh-TW | |
dc.title | 結合光動力殺菌與Fluconazole在白色念珠菌的治療效果探討 | zh_TW |
dc.title | Investigate the therapeutic potential by combining photodynamic inactivation and Fluconazole against Candida albicans | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林晉玄,吳?承,簡雄飛 | |
dc.subject.keyword | 光動力殺菌,白色念珠菌,甲苯胺藍,氟康唑,生物膜, | zh_TW |
dc.subject.keyword | Photodynamic Inactivation,Candida albicans,TBO,Fluconazole,Biofilm, | en |
dc.relation.page | 58 | |
dc.identifier.doi | 10.6342/NTU201601698 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-02 | |
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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