The role of technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) in the detection of cardiovascular involvement in systemic lupus erythematosus patients with non-specific chest complaints

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题名:	The role of technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) in the detection of cardiovascular involvement in systemic lupus erythematosus patients with non-specific chest complaints
作者:	Sun, SS;Shiau, YC;Tsai, SC;Lin, CC;Kao, A;Lee, CC
贡献者:	附設醫院核子醫學部;China Med Coll Hosp, Dept Nucl Med, Taichung 404, Taiwan;China Med Coll Hosp, Dept Family Med, Taichung 404, Taiwan;China Med Coll Hosp, Dept Med Res, Taichung 404, Taiwan;Far Eastern Mem Hosp, Dept Nucl Med, Taipei, Taiwan;Natl Taiwan Univ, Coll Elect Engn, Inst Biomed Engn, Taipei 10764, Taiwan;Show Chwan Mem Hosp, Dept Nucl Med, Chunghua, Taiwan
日期:	2001
上传时间:	2010-09-24 14:36:17 (UTC+8)
出版者:	OXFORD UNIV PRESS
摘要:	A novel strategy was developed for the synthesis of N-7-purine acyclic nucleosides 9 and 14. The key step involved the reaction between [2-(p-methoxyphenyloxy)ethoxylmethyl chloride and N-9-tritylated nucleobases 6 or 11 followed by concomitant self-detritylation. N-7-Guanine acyclic nucleoside 9 exhibited antiviral activity, but was phosphorylated by both HSV and Vero cell thymidine kinases. Thus, it showed more potent cellular toxicity than acyclovir (2). N-7-Adenine acyclic nucleoside 14 was found to be an excellent antiviral agent as well as a good inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows for a greater expression of antiviral activity of antiviral agents, such as N-9-adenine acyclic nucleoside 1 and ara-A (3). Compound 14 was phosphorylated neither by herpes simplex virus (HSV) thymidine kinase nor by Vero cell thymidine kinase, yet it enhanced the rate constant for the monophosphorylation of acyclovir (2) by HSV thymidine kinase. Consequently, the combination of acyclovir (2) and 14 exhibited greater antiviral activity than acyclovir alone. 7-[2(Phosphonomethoxy)ethyl] adenine (20) was also synthesized. The key step involved the reaction of 9-(2-cyanoethyl)adenine (15) with methyl iodoacetate in the presence of lithium 2,2,6,6-tetramethylpiperidine in THF. Unlike 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA, 4), the N-7-isomer 20 was not phosphorylated effectively by 5-phosphoribosyl 1-pyrophosphate synthetase (PRPP synthetase). Thus, it did not exhibit pronounced antiviral activity. Dinucleotide 5'-monophosphate 24 and its butenolide ester 25 were also synthesized. Compound 24 showed substrate activity toward PRPP synthetase and exhibited notable activity against DNA viruses. The antiviral activity of the ester derivative 25 was found to be higher than that of the parent molecule 24. Dinucleotide 5'-monophosphate 24 is suseptible to degradation by snake venom and spleen phosphodiesterases. However, its respective butenolide ester derivative 25 was completely resistant to snake venom and spleen enzymes. Butenolide ester derivatives 28 and 29 were also synthesized and exhibited notable anti-DNA virus and anti-retrovirus activity in vitro. Compounds 2, 4, 9, 14, 20, 24, 25, and 28 were also evaluated for their inhibitory effect on HSV-1-induced mortality in NMR1 mice. N-7-adenine acyclic nucleoside 14 [LD50 (intraperitoneal, ip) 950 mg/kg], nucleotide-containing butenolide 25 [LD50 (ip) 675 mg/kg], and butenolide 28 [LD50 (ip) 710 mg/kg] were found to be potent anti-HSV-1 agents in vivo. In addition, butenolide 28 efficiently decreased tumor formation induced by Moloney murine sarcoma virus (MSV) in NMRI mice while significantly increasing the survival time of MSV-infected mice.
關聯:	RHEUMATOLOGY 40(10):1106-1111
显示于类别:	[台中附設醫院] 期刊論文

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