Preferential resistance of dopaminergic neurons to glutathione depletion in a reconstituted nigrostriatal system

Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson's disease (PD), and could initiate dopaminergic neuronal degeneration. Nevertheless, we have previously demonstrated that mesencephalic dopaminergic neurons in primary monolayer cultures are more resistant to the toxicity of glutathione depletion than nondopaminergic neurons. To extend this finding to a system that more closely resembles the in vivo situation, we characterized the effects of glutathione depletion on reaggregate cultures derived from ventral mesencephalic and their striatal target neurons, as well as supporting elements including glia. Dopaminergic neurons were found to be more resistant to the toxicity of buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis, than other nigrostriatal neurons, while striatal target cells exhibited an intermediate susceptibility when examined after 48 h. Glutathione depletion, however, decreased the intracellular content of catecholamines after 48 h and eventually led to the loss of dopaminergic neurons after 7 days. Our data indicate that the intrinsic resistance of dopaminergic neurons to the toxicity of glutathione depletion occurs in a variety of experimental paradigms, and suggest that global glutathione depletion alone is unlikely to account for the selective loss of dopaminergic neurons in PD. Rather, it is more likely that either the selective loss of glutathione from dopaminergic neurons, or the combination of glutathione loss with other insults contributes to the preferential death of dopaminergic neurons in PD.     

运用彗星试验检测麝香酮对苯并(a)芘致DNA损伤的影响

[目的]研究麝香酮在体内试验条件下 ,对苯并(a)芘致小鼠肝和肺细胞核DNA损伤的影响。[方法]SENCAR雄性成年小鼠灌胃 ,分别单独给予苯并(a)芘125、250、500mg/(kg·bw·d)和用麝香酮250、500mg/(kg·bw·d)预处理后再给予苯并(a)芘125mg/(kg·bw·d) ,处死动物后分离小鼠肝和肺组织细胞核做彗星测试 ,采用CCD成像分析系统分析彗星 ,取尾相 (olivertailmoment,OTM)值判断DNA损伤强度。[结果]苯并(a)芘各浓度组均出现小鼠肝和肺细胞OTM值的明显增加 ,高浓度麝香酮[500mg/(kg·bw·d)]可引起小鼠肝细胞OTM值的轻度增加。用高浓度麝香酮预处理小鼠后再给予苯并(a)芘 ,所观察到的肝、肺的DNA损伤 (肝OTM值为7.6、肺为11)较之苯并(a)芘单独染毒引起的DNA损伤(肝OTM值为5.1、肺为6.9)增加更明显。[结论]麝香酮能明显增强苯并(a)芘所致的DNA损伤作用     

4-[2-(N-甲基,N-(2-吡啶基)氨基)-乙氧基]苯甲醛的合成方法改进

目的:改进罗格列酮的关键中间体4-[2-(N-甲基,N-(2-吡啶基)氨基)-乙氧基]苯甲醛的合成方法。方法:以2-[N-甲基,N-(2-吡啶基)氨基]乙醇为原料,分别与对氟苯甲醛发生威廉森成醚反应(以乙腈作溶剂,KOH作去酸剂)及与对羟基苯甲醛发生脱水缩合反应,合成目标化合物。结果:得到目标化合物,其结构经1HNMR和MS验证。结论:两种改进的合成方法操作简便,适于工业化生产。     

Serial changes in N-isopropyl-p[125I]-iodoamphetamine in mouse lung observed with a confocal laser scanning microscope

Serial changes in N-isopropyl-p[125I]-iodoamphetamine (125I-IMP) in mouse lungs were observed with a confocal laser scanning microscope. Male mice were intravenously injected with 125I-IMP and subjected to autoradiographic procedures 20 minutes, and 3 and 24 hours after injection. Differential interference contrast (DIC) images and confocal images were obtained with a confocal laser scanning microscope, and superimposed images were evaluated. Large numbers of silver grains were observed in the interstitium, bronchioles, and alveolar sacs 20 minutes after the injection, and lamellar distribution of the grains was observed on the ciliary surface. The numbers of silver grains in the interstitium and bronchioles had decreased 3 hours after the injection of 125I-IMP, but the numbers of silver grains in the alveolar spaces had not. Although small numbers of silver grains remained in both the bronchioles and alveolar sacs 24 hours after the injection, most of them had washed out. Confocal laser scanning microscopy is considered to be a useful procedure for studying the distribution of radioisotopes by microautoradiography, because it allows clear autoradiographs to be obtained in which tissues and silver grains are perfectly matched and all silver grains are in focus.     

Convenient synthesis of D‐threo‐[dichloroacetyl 1–14C] chloramphenicol

A convenient synthesis of chloramphenicol labelled with carbon‐14 in the dichloroacetyl group at the 1 position is described. It was prepared as part of a 4‐step sequence from [1 ‐ ¹⁴C] glycine and the product was purified by preparative HPLC. A radiochemical yield of 47% was obtained based on [1 ‐ ¹⁴C] glycine and the product had a specific activity of 0.47 mCi/mmol. The procedure can be employed for the synthesis of high specific activity [¹⁴C] chloramphenicol, labelled at 1, 2 or both the positions of dichloroacetyl group. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of [14C]‐radiolabelled entecavir

Radiolabelled [¹⁴C]entecavir, ( 1 ), was prepared in 12 steps from (1S,2R,3S,5R)‐3‐(benzyloxy)‐2‐(benzyloxymethyl)‐6‐oxa‐bicyclo[3.1.0]hexane 2 . The chemical yield of [¹⁴C]entecavir was 14% from the epoxide 2 . Introduction of [¹⁴C] radiolabel was achieved by elaboration of 4,5‐diaminopyrimidine 8 with triethyl[¹⁴C]orthoformate to purine derivative 9 . The radiochemical yield of [¹⁴C]entecavir from triethyl[¹⁴C]orthoformate was 11.3%. Radiochemical purity of [¹⁴C]entecavir determined by HPLC was 99.8%. The specific activity of [¹⁴C]entecavir was 108 µCi/mg (29.9 mCi/mmol). Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis and evaluation of [11C]RU40555, a selective glucocorticoid receptor antagonist

We demonstrated the synthesis of carbon‐11 labeled 17‐α‐hydroxy‐11‐β‐/4‐/[methyl]‐[1‐methylethyl]‐aminophenyl/‐17α‐[prop‐1‐ynyl]esta‐4‐9‐diene‐3‐one (RU40555), a selective glucocorticoid receptor (GR) antagonist, and examined the in vivo profile of [¹¹C]RU40555. [¹¹C]RU40555 was synthesized by direct N‐methylation with [¹¹C]CH₃OTf at 60°C for 5 min and an injectable solution of [¹¹C]RU40555 was obtained in 31 min at the end of bombardment. The decay‐corrected radiochemical yield was 19%, the specific radioactivity was 57.5±14.0 GBq/µmol, and the radiochemical purity was more than 99% as determined by HPLC. In rat experiments, the effects of adrenalectomy (ADX) on brain accumulation of [¹¹C]RU40555 were examined. ADX significantly decreased plasma corticosterone levels, and significantly increased brain accumulation of [¹¹C]RU40555. We succeeded in developing a rapid automated synthesis method for [¹¹C]RU40555, a GR antagonist, and showed [¹¹C]RU40555 had a potential as a PET tracer for mapping GR. Copyright © 2005 John Wiley & Sons, Ltd.     

4-[4-(吡啶-3-基)咪唑-1-基]丁胺的合成

以3-乙酰基吡啶为起始原料,经肟化、磺酰化、氧化、环合、还原得到3-(咪唑-4-基)吡啶,再经与N-(4-溴丁基)邻苯二甲酰亚胺缩合及肼解等反应制得抗菌剂泰利霉素的特定侧链化合物4-[4-(吡啶-3-基)咪唑-1-基]丁胺,总收率24%.     

卟啉及其类似物在HPLC固定相中的应用

介绍了卟啉及其类似物衍生固定相的特征和制法,综述了这类固定相在HPLC中的应用和分离机制.     

用血清药理学方法观察毛茛提取液对家兔主动脉平滑肌细胞内钙的影响

目的:观察毛茛提取液含药血清对培养家兔主动脉平滑肌细胞内游离钙浓度的影响.方法:体外培养家兔主动脉平滑肌细胞(VSMC),用荧光指示剂INDO-AM负载细胞,灌胃给予不同浓度药物,观察不同稀释浓度含药血清及不同时相药物血清对由NE诱导细胞内游离钙浓度([Ca2 ]i)增加的影响.结果:毛茛提取液各含药血清组均能降低由NE诱发的细胞内[Ca2 ]i的升高.结论:毛茛提取液含药血清能减少VSMC细胞内[Ca2 ]i.