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藥學科技上課心得:周書全

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(1)

SciFinder 使用心得

B303098006 藥三 A 班 周書全

1. 資料庫的使用和學習心得:

我的天啊!!!Scifinder 的功能真的是太強大了,而且最難能可貴的是他平易近

人的操作與簡明的操作介面,以下是我擷取的幾張圖來說明 Scifinder 的方便

再用於找一些特出限制、特定作者、特定條件的研究時,非常好用

(2)

即便一開始沒有設定好搜尋條件,進入搜尋畫面以後還是可以更改設定

(3)

有別於一般專業的資料庫,不只資料豐富,操作介面的設計也下了不少功夫

非常感謝老師安排時間讓我們能了解這套好用的資料庫,原來學校有這麼好

的資源,只是我們都不知道,相信以後我們做報告時都能更輕鬆且不失內容

的豐富度與專業度。

2. 自定題目-cyclosporin A

研究動機:

由於近期藥理剛好教到免疫製劑,而 cyclosporin A 又是免疫製劑中不可不提到

的重點藥物,且 cyclosporin A 作用機轉多元,老師在上課時有特別提到

cyclosporin A 除了免疫抑制劑外,還有成為其他的藥物的潛能,因此變萌發使

用 scifinder 來查詢 cyclosporin A 的想法。

研究成果:

cyclosporin A

(4)

目前主要作用:器官移植抗排斥藥物、乾癬治療藥物、風濕性關節炎治療藥物

論文一:

A calcineurin-independent mechanism of angiogenesis inhibition by

a nonimmunosuppressive cyclosporin A analog

By: Nacev, Benjamin A.; Low, Woon-Kai; Huang, Zhennian; Su, Tina T.; Su, Zhuang; Alkuraya, Hisham; Kasuga, Dan; Sun, Woong; Trager, Mario; Braun, Manfred; Fischer, Gunter; Zhang, Kang; Liu, Jun O.

Cyclosporin A (CsA) is a widely used immunosuppressant drug. Its immunosuppressive activity occurs through the inhibition of the protein phosphatase calcineurin via formation of a ternary complex with cyclophilin A (CypA). CsA also inhibits endothelial cell proliferation and angiogenesis. This has been thought to occur through calcineurin inhibition as well. However, CsA is also a potent inhibitor of cyclophilins, a class of prolylisomerases. Because calcineurin inhibition requires binding, and therefore inhibition of CypA, the relative contributions of calcineurin and cyclophilin inhibition in antiangiogenesis have not been addressed. We have taken a chem. biol. approach to explore this question by dissocg. the two activities of CsA at the mol. level. We have identified a nonimmunosuppressive analog of CsA that does not inhibit calcineurin but maintains inhibition of endothelial cell proliferation and in vivo

angiogenesis. The same analog also maintains inhibition of all cyclophilin isoforms

tested. We also show that a second, structurally distinct, cyclophilin inhibitor is sufficient to block endothelial cell proliferation. These results suggest that the inhibition of cyclophilins may play a larger role in the antiangiogenic activity of CsA than previously believed, and that cyclophilins may be potential antiangiogenic drug targets.

(5)

論文二:

Topical cyclosporine prevents seasonal recurrences

of vernal keratoconjunctivitis in a randomized,

double-masked, controlled 2-year study

This study was approved and funded by the Italian Agency for Drug Administration (AIFA-AgenziaItaliana del Farmaco) to support independent drug research for the National Health System.

It was performed in 2 Italian centers between March 2006 and November 2008. The study protocol was approved by both the AgenziaItalianadelFarmaco and by local ethics committees. Written informed consent for participation was obtained from parents according to local requirements.

Patients with VKC were screened for enrollment. They were eligible for randomization if they were given a diagnosis of VKC (ie, if they had a positive clinical history of allergic diseases and a history of

recurrences of conjunctival inflammation with itching, conjunctival tarsal and/or limbal papillae, and the presence of eosinophils in conjunctival scrapings). Patients in the active phase of VKC (itching and/or conjunctival hyperemia scores >2) at the time of screening, the baseline examination, or both were excluded. Other exclusion criteria were contact lens wear, the presence of any other ocular disease, use of any other ophthalmic or systemic therapy, a history of ocular surgery in the preceding 6 months, and pregnancy or breast-feeding. No age and sex limits were defined. This study was registered

at http://clinicaltrials.gov on January 2007 (registration no. NCT00426023).

論文三:

Therapeutic approaches in the treatment of juvenile

dermatomyositis in patients with recent-onset disease and in

those experiencing disease flare: an international multicenter

PRINTO study

HasijaRachana; Pistorio Angela; Ravelli Angelo; DemirkayaErkan; KhubchandaniRaju; GuseinovaDinara; Malattia Clara; Canhao Helena; HarelLiora; Foell Dirk; WoutersCarine; De Cunto Carmen; Huemer Christian; Kimura Yukiko; ManggeHarald; Minetti Carlo; Nordal Ellen Berit; Philippet Pierre; Garozzo Rosaria; Martini Alberto; RupertoNicolino

OBJECTIVE: To evaluate response to therapy over a 24-month period in a large prospective international cohort of patients with juvenile dermatomyositis (DM). METHODS: The study included 145 patients with recent-onset juvenile DM and 130 juvenile DM patients experiencing disease flare, all of whom were <18 years old. Disease activity parameters and therapeutic approaches in 4 geographic areas were analyzed at baseline and at 6, 12, and 24

(6)

months. Response was assessed according to the Pediatric Rheumatology International Trials Organization (PRINTO) juvenile DM response criteria, and data were reported "as observed" and in the intent-to-treat (ITT) population. RESULTS: Patients with recent-onset juvenile DM at baseline had higher baseline disease activity and greater improvement over 24 months when compared to juvenile DM patients experiencing disease flare at baseline. Methotrexate (MTX) or high-dose corticosteroids were administered more frequently to patients with recent-onset juvenile DM, compared to juvenile DM patients experiencing disease flare, who were more likely to receive cyclosporine. Compared to patients from Western and Eastern Europe, a higher proportion of patients from South and Central America and North America received pulse steroids, and the average steroid dosage was higher in the North American and South and Central American patients. The use of MTX was similar in all 4 regions, while cyclosporin A was more frequently used in Western Europe. In the "as observed" analysis, 57.9% of the patients with recent-onset juvenile DM and 36.4% of the patients experiencing disease flare (P<0.001) reached at least a 70% response by PRINTO criteria at 6 months; these proportions had increased at month 24 to 78.4% and 51.2%, respectively (P<0.001). Corresponding results of the ITT analysis were much lower, with only one-third of the patients able to maintain the initial assigned therapy over 24 months. CONCLUSION: Patients with recent-onset juvenile DM are more likely to achieve significant clinical improvement over 24 months, when compared to patients experiencing flares of juvenile DM. Internationally, various therapeutic approaches are used to treat this disease.

總結:

cyclosporin A 不只能當免疫抑制劑還有許多其他的功能,例如以上三篇論文有

提到的:

內皮細胞增殖和血管生成、季節性復發型角膜炎、幼年型皮肌炎…等,

僅列出以上三種,在 SciFinder 的資料庫中還有近千篇關於

cyclosporin A 其他

療效

的研究論文,盡管效果還不進理想,但可見

cyclosporin A 擁有開發成其他

藥品的強大潛力。

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