抗药基因MGMT在人脑星形细胞瘤组织中的表达

6位甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNA methyltransferase,MGM T)主要功能是转移并接受DNA双链中鸟嘌呤O6位上异常的烷基,使受损的DNA恢复正常[1].我们检测了MGMT基因在人脑胶质瘤的表达情况,探讨MGMT表达对人脑星形细胞瘤的意义.     

国产恩替卡韦分散片抗乙型肝炎病毒疗效观察

慢性乙型肝炎患者需要长时间进行抗病毒治疗,恩替卡韦分散片为国产新一代鸟嘌呤核苷类似物,对乙肝病毒(HBV)多聚酶具有抑制作用,对组织学改善及HBV DNA的下降幅度和ALT复常率血清学转换等方面,均有明显作用[1].本研究采用药物治疗慢性乙型肝炎患者,报道如下.     

鸟嘌呤的化学合成

鸟嘌呤(guanine,1),是抗病毒药阿昔洛韦(无环鸟苷)和更昔洛韦的重要中间体。可用发酵所得鸟嘌呤核苷酸(5′-GMP)经水解生成鸟苷,再除去核糖而得到1。此法反     

霉酚酸酯在肾内科的应用

霉酚酸酯(mycophenolate mofetil, MMF),商品名骁悉,是青霉属真菌产生的具有抗代谢的霉酚酸半合成物,是霉酚酸(MPA)的2-乙基酯类衍生物,在体内需水解为MPA才能起效.MPA是高效、选择性、非竞争性、可逆性抑制次黄嘌呤脱氢酶阻断鸟嘌呤核苷酸的起始合成途径,使鸟嘌呤核苷酸耗酶,进而阻断DNA的合成[1].MMF是一种新型免疫抑制剂,自其问世以来,已成功地广泛用于各类器官移植的排斥反应的预防和治疗.近几年来,MMF逐渐应用于非移植领域,在肾脏病的治疗上显示独特的疗效.     

本刊文后参考文献著录格式示例

1期刊著录格式:主要责任者.题名[文献类型标志].刊名,年,卷(期):引文起页-止页.[1]施毅.肺炎的诊断与治疗研究进展[J].东南国防医药,2007,9(6):401-404.[2]刘永才,张霞,张松涛,等.军事训练致下肢疲劳性损伤123例分析[J].人民军医,2007,50(1):4-5.     

本刊文后参考文献著录格式示例

1期刊著录格式:主要责任者.题名[文献类型标志].刊名,年,卷(期):引文起页-止页.[1]施毅.肺炎的诊断与治疗研究进展[J].东南国防医药,2007,9(6):401-404.[2]刘永才,张霞,张松涛,等.军事训练致下肢疲劳性损伤123例分析[J].人民军医,2007,50(1):4-5.     

多西他赛联合奈达铂或顺铂治疗晚期食管癌疗效比较

食管癌占城市恶性肿瘤死亡原因第4位,在农村居第5位[1].食管癌早期诊断困难,中位生存期仅4～8个月[2].既往以顺铂(DDP)和氟尿嘧啶(5-FU)为基础的化疗方案对食管癌的疗效不理想,有效率仅有25％～35％,且消化系统反应及骨髓抑制等副反应重,严重影响患者的生活质量[3].     

本刊文后参考文献著录格式示例

1期刊著录格式:主要责任者.题名[文献类型标志].刊名,年,卷(期):引文起页-止页.[1]施毅.肺炎的诊断与治疗研究进展[J].东南国防医药,2007,9(6):401-404.[2]刘永才,张霞,张松涛,等.军事训练致下肢疲劳性损伤123例分析[J].人民军医,2007,50(1):4-5.[3]Kaneko M,Kato Y,Horiuchi H,et al.Molecular char-acterization of a human monoclonal antibody to Bantigen in ABO blood type[J].Immunol Lett,2003,86(1):45-51.2专著著录格式:主要责任者.题名[文献类型标志].其他责任者(例如翻译者).版本项(1版不著录).出版地:出版者,出版年:引文起页-止页.[1]杨宗城.烧伤治疗学[M].3版.北京:人民卫生出版社,2006:119-120.[2]昂温G,昂温PS.外国出版史[M].陈生铮,译.北京:中国书籍出版社,1988:98-102.[3]Smith GG.Gene and protein[M].4th ed.New Y...     

p38 MAPK mediates cardiovascular and behavioral responses induced by central IL-1β and footshock in conscious rats

INTRODUCTION Sharing characteristics of stress mediators[1], cen-tral interleukin-1β (IL-1β) is very important in cardio-vascular and behavioral responses to stressors[2-4]. Itcan induce similar hypertensive responses to stress viacardiovascular regulatory regions[5]. We observed pre-viously that central IL-1β mediated cardiovascular re-sponses to some stressful stimuli, such as conditionedfear stimuli and footshock[6]. Many stressful stimulimay increase IL-1β mRNA expression and …     

本刊文后参考文献著录格式示例

1期刊著录格式:主要责任者.题名[文献类型标志].刊名,年,卷(期):引文起页-止页.[1]施毅.肺炎的诊断与治疗研究进展[J].东南国防医药,2007,9(6):401-404.[2]刘永才,张霞,张松涛,等.军事训练致下肢疲劳性损伤123例分析[J].人民军医,2007,50(1):4-5.[3]Kaneko M,Kato Y,Horiuchi H,et al.Molecular char-     

毛细管电泳法测定红毛五加茎皮中鸟苷的含量

目的建立毛细管区带电泳法测定红毛五加茎皮中鸟苷含量的方法。方法采用毛细管区带电泳法 ,以未涂层的熔融毛细管 (5 8cm× 5 0 μmID ,有效分离长度为 5 0cm)为分离通道 ,运行缓冲液为 40 0mmol·L-1硼酸 5 0mmol·L-1硼砂 1 2 % (φ)乙腈 ,用氢氧化钠调 pH至 8 8;分离电压2 1kV(恒压 ) ;检测波长 2 5 4nm ;毛细管柱温 2 5℃ ;自动压力进样。结果红毛五加茎皮中鸟苷在0 0 1 8～ 0 3 5mmol·L-1内线性关系良好 (r=0 9997) ,鸟苷的加样回收率为 98%～ 1 0 2 % ,RSD为2 3 % (n =3 )。红毛五加茎皮中鸟苷的平均含量为 0 2 4mg·g-1。结论用毛细管区带电泳法测定红毛五加茎皮中鸟苷含量的方法简便、快捷、可行。     

Inhibition of utilization of hypoxanthine and guanine in cells treated with the carbocyclic analog of adenosine. Phosphates of carbocyclic nucleoside analogs as inhibitors of hypoxanthine (guanine) phosphoribosyltransferase

In cell cultures treated with the carbocyclic analog of adenosine (C-Ado, (+/-)-aristeromycin), the utilization of hypoxanthine and guanine has been observed to be blocked. In an attempt to define the mechanism of this inhibition, we have reexamined the metabolism of C-Ado and its effects on the metabolism of guanine and hypoxanthine. In cultures of L1210 cells, C-Ado at a concentration of 25 microM inhibited the utilization of hypoxanthine and guanine for nucleotide synthesis by more than 90% but produced little or no inhibition of the utilization of these bases in cultures of L1210/MeMPR cells which lack adenosine kinase and cannot phosphorylate C-Ado. In cultures of mammalian cells (L1210, HEp-2, and colon-26 cells), C-Ado was converted to the triphosphate (as previously observed) and also to the triphosphate of the carbocyclic analog of guanosine. The presence of coformycin in the medium at a concentration sufficient to inhibit AMP deaminase almost completely prevented the formation of carbocyclic GTP; thus, the deamination of C-Ado monophosphate is essential for the formation of phosphates of carbocyclic guanosine. Since hypoxanthine (guanine) phosphoribosyltransferase is known to be subject to end product inhibition, it was considered likely that phosphates of carbocyclic guanosine or carbocyclic inosine, present in C-Ado-treated cells, were responsible for inhibition of utilization of hypoxanthine and guanine. The 5'-phosphates of the carbocyclic analogs of inosine and guanosine were synthesized and found to be effective inhibitors of the phosphoribosyltransferase. Carbocyclic GMP was a better inhibitor than carbocyclic IMP and was also superior to GMP and IMP; the concentration of C-GMP that produced a 50% inhibition of GMP formation was approximately 1 microM. It is probable that the presence of phosphates of carbocyclic guanosine accounts for the inhibition of utilization of hypoxanthine and guanine in C-Ado-treated cells.     

杏仁核中一氧化氮对睡眠-觉醒的影响

目的研究杏仁核中一氧化氮（ＮＯ）对大鼠睡眠 觉醒的影响,并分析其作用机制。方法多导睡眠描记和杏仁核微量注射。结果一氧化氮合酶抑制剂Ｌ 硝基精氨酸（Ｌ ＮＮＡ）可增加慢波睡眠（ＳＷＳ）和减少觉醒（Ｗ）,而一氧化氮（ＮＯ）供体硝普钠（ＳＮＰ）可增加Ｗ、减少ＳＷＳ,并可对抗Ｌ ＮＮＡ的促睡眠效应;ＮＯ前体Ｌ 精氨酸（Ｌ Ａｒｇ）对睡眠 觉醒无直接影响,但可对抗Ｌ ＮＮＡ的促睡眠效应。环磷酸鸟苷（ｃＧＭＰ）具有明显的增加Ｗ和减少ＳＷＳ效应,而鸟苷酸环化酶抑制剂亚甲蓝（ＭＢ）增加睡眠、减少觉醒,并可阻断ＳＮＰ的促睡眠效应。结论杏仁核参与睡眠 觉醒调节,杏仁核中ＮＯ具有促进Ｗ、抑制ＳＷＳ效应,这一作用是通过激活鸟苷酸环化酶使ｃＧＭＰ增多实现的。     

Inhibitors of inosinate dehydrogenase activity in Ehrlich ascites tumor cells in vitro

1-Amino guanosine, virazole and mycophenolic acid all inhibit inosinate dehydrogenase activity in intact Ehrlieh ascites tumor cells in vitro, and exert 50 per cent inhibition at concentrations of 500, 50 and < 0.1 μM respectively. At these concentrations, the activity of guanylate synthetase was inhibited by 0, 20 and 10 per cent respectively. 1-Amino 2'-deoxyguanosine was a less potent inhibitor of intracellular inosinate dehydrogenase activity than 1-amino guanosine, and ten other 1-substituted purines tested had little or no activity. 1-Amino guansoine (400 μM) inhibited both the growth of cultured mouse leukemia L1210 cells and inosinate dehydrogenase activity by approximately 50 per cent.     

Pharmacokinetics of guanosine in rats following intravenous or intramuscular administration of a 1:1 mixture of guanosine and acriflavine, a potential antitumor agent

A 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is under evaluation in preclinical studies as a possible antitumor agent. Guanosine is known to potentiate the anti-cancer activity of ACF. We therefore investigated the pharmacokinetics of guanosine following administration of the ACF/guanosine mixture in rats. Rats were given guanosine (1 or 5 mg/kg) or ACF/guanosine (2 or 10 mg/kg) by i.v. bolus; or guanosine (3 or 15 mg/kg) or ACF/guanosine (6 or 30 mg/kg) by i.m. injection. We found that guanosine was rapidly cleared from the blood and transferred to tissues after i.m. administration of ACF/guanosine. The mean plasma half-lives (t_1/2) at the α and β phases were 0.091 and 6.86 h, or 0.09 and 7.51 h at a dose of 1 or 5 mg/kg guanosine, respectively. ACF had no effect on the plasma disappearance of guanosine following either i.v. bolus or i.m. administration of the combination mixture. Moreover, the ACF combination with guanosine did not significantly alter the values of MRT, V_dss, and CL_t of guanosine. Guanosine exhibited linear pharmacokinetics over the dose range from 1 to 5 mg/kg for i.v. doses and 3 to 15 mg/kg for i.m. doses. The bioavailability of guanosine after i.m. administration was 84% for 3 mg/kg dose and 88% for 15 mg/kg dose. ACF had no effects on biliary and urinary excretion of guanosine after i.m. administration. The cumulative amount of guanosine in urine after i.m. administration was about 5-fold larger than that in bile, indicating that guanosine is mostly excreted into the urine. Guanosine was widely distributed in all tissues examined in this study, but was most highly concentrated in the kidney after i.m. administration, followed by slow excretion to bile or urine. ACF had no effect on the tissue distribution of guanosine following i.m. administration. These characterizations of the pharmacokinetics of guanosine after administration of the ACF/guanosine combination will be useful in providing preclinical and clinical bases for the potential application of this combination to the treatment of cancer.     

Effects of Chinese drugs "xiebai" and "dasuan" on human platelet aggregation (Allium bakeri, A. sativum)

Adenosine (1), guanosine (2), and tryptophan (3), as well as beta-sitosterol beta-D-glucoside (4) were isolated from the n-butanol-soluble fraction of Xiebai, the tuber of Allium bakeri Reg., which was recognized to have an anti-platelet aggregation effect. Moreover, 1 and 2 were also isolated from the n-butanol-soluble fraction of Dasuan, the tuber of A. sativum L. Compound 1 showed a significant inhibitory activity against both the primary and secondary wave aggregation of human platelet induced by 2 microM ADP, whereas compounds 2-4 showed no or very low inhibitory effects. The structure-activity relationships on human platelet aggregation with regard to 1, 2 and their derivatives, adenosine 2'-monophosphate (5), adenosine 5'-monophosphate (6), adenosine triphosphate (7), guanosine 3'-monophosphate (8), and guanosine 5'-monophosphate (9), and guanylyl(3'----5')adenosine (10) are discussed. Compounds 5-7 and 10 also inhibited the primary and secondary wave aggregation with a dose-dependent response.     

HPLC法同时测定地黄中的5种核苷和碱基的含量(英文)

建立HPLC法同时测定来自中国不同地区的地黄中次黄嘌呤、尿苷、腺嘌呤、鸟苷、腺苷等5种核苷类成分的含量。采用的色谱柱为Diamonsil C18柱(250 mm×4.6 mm,5μm),流动相为乙腈-0.04 mol.L-1磷酸二氢钾溶液梯度洗脱,流速1 mL.min-1,柱温30℃,检测波长254 nm。次黄嘌呤、尿苷、腺嘌呤、鸟苷和腺苷的质量浓度分别在1.0～16.0μg.mL-1(r2=0.999 8),5.0～80.0μg.mL-1(r2=0.999 8),1.0～16.0μg.mL-1(r2=0.999 5),1.25～20.0μg.mL-1(r2=0.999 8)和1.0～16.0μg.mL-1(r2=0.999 8)内线性关系良好,平均回收率为98.8%～100.7%。结果表明,不同地区的地黄中次黄嘌呤、尿苷、腺嘌呤、鸟苷和腺苷的含量有显著性差异。该方法准确,重复性好,适用于地黄药材中5种核苷类成分的含量测定。     

Synthetic approaches to the guanosine and xanthosine analogues 5-amino-3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazin-7-one and 3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazine-5,7-dione and studies of their antitumor potential

5-Amino-3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazin-7-o ne has been synthesized via cyclization of the appropriately protected pyrazofurin derivatives and subsequent transformations of the heterocyclic moiety. This guanosine analogue was marginally cytotoxic to L1210 cells in vitro. The xanthosine analogue 3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazine-5,7-dione was also synthesized, and was found to be highly cytotoxic. It appeared to act as a prodrug of pyrazofurin.     

5-HT1A receptor agonist properties of antipsychotics determined by [35S]GTPgammaS binding in rat hippocampal membranes

1. 5-Hydroxytryptamine 1A (5-HT1A) receptors have attracted increasing attention as a promising target for antipsychotic therapy. Although many atypical antipsychotic drugs, including the prototype clozapine, have been reported to be partial agonists at 5-HT1A receptors, these results are often fragmental and derived mainly from experiments that used cultured cells. 2. In the present study, [35S]guanosine 5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding assay in rat hippocampal membranes was applied to a series of antipsychotic drugs, especially atypical antipsychotics. 3. Most, but not all, of atypical antipsychotic drugs and the classical antipsychotic drug nemonapride behaved as partial agonists at 5-HT1A receptors with varied potencies and relative efficacies. The most potent compound was perospirone with a mean EC50 of 27 nmol/L, followed by aripiprazole (45 nmol/L) > ziprasidone (480 nmol/L) > nemonapride (790 nmol/L) > clozapine (3900 nmol/L) > quetiapine (26,000 nmol/L). The maximal percentage increases over the basal binding (%Emax) for these antipsychotic drugs were 30-50%, with the exception of perospirone (approximately 15%), whereas 5-HT stimulated the binding to a mean %Emax of 105%. 4. Increasing concentrations of the selective and neutral 5-HT1A antagonist WAY100635 shifted the concentration-response curve of nemonapride-stimulated [35S]GTPgammaS binding to the right and in parallel. 5. The relative efficacy or intrinsic activity of a compound was affected differently by the differing concentrations of guanosine diphosphate (GDP) in the assay buffer, which should be taken into consideration when determining the relative efficacies of these antipsychotics as 5-HT1A receptor agonists. 6. These results provide important information concerning the relevance of 5-HT1A receptor partial agonist properties in the treatment for schizophrenic patients with most, if not all, of atypical antipsychotic drugs.     

Mode of action of oxanosine, a novel nucleoside antibiotic

Oxanosine, a novel nucleoside, inhibits the growth of Escherichia coli K-12 on peptone agar, but not on Nutrient agar. This antibiotic activity was found to be bacteriostatic and was antagonized by guanine, guanosine, and guanylic acid. The growth of leukemia L 1210 cell was also inhibited by oxanosine, and the inhibition was reversed by guanylic acid. Oxanosine was confirmed to be a competitive inhibitor of GMP synthetase (E.C. 6.3.5.2) and the Ki value was 7.4 X 10(-4) M.