Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcript...Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5' position on the sugar is an interesting template for the elaboration of new potent anti HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.展开更多
文摘目的 :研究大鼠脑出血周边组织一氧化氮 (N O)含量和一氧化氮合酶 (N OS)活性变化及与细胞凋亡的关系。方法 :1Wistar大鼠 10 4只 ,随机分为对照组、脑出血组、脑出血 +氮硝基左旋精氨酸 (N N L A)组 ,后两组各分为 (4 h、6 h、12 h、1d、3d、7d) 6个时间点。 2测定出血周边组织 N O含量、N OS活性及神经细胞凋亡。结果 :1大鼠脑出血周边组织 N O、诱导型一氧化氮合酶 (i N OS) ,4 h开始升高 ,3d i N OS、N O达峰值。 2大鼠脑出血周边组织 6 h出现凋亡 ,细胞 3d凋亡细胞达峰值 ,与i N OS峰值对应 ,7d时仍存在较多凋亡细胞。 3N N L A干预后 N O含量、i N OS活性及凋亡细胞数量与脑出血组对应时间点比较显著下降 ,差异显著。结论 :大鼠脑出血周边组织神经细胞存在长时间凋亡 ,N O、i N OS可以促进其凋亡 ,N OS抑制剂减少大鼠脑出血周边组织神经细胞凋亡。
文摘Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5' position on the sugar is an interesting template for the elaboration of new potent anti HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.
