Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A₂ (PLA₂) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50–100 μM), a selective PLA₂ inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 μM). In contrast, the specific cyclooxygenase blocker indomethacin (100 μM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 μM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA₂ and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.     

斑点免疫渗滤法检测丙肝IgG抗体试剂盒的研制

用基因工程重组的丙肝抗原包被于硝酸纤维素膜，建立了检测丙肝ＩｇＧ抗体的斑点免疫渗滤法。与ＥＬＩＳＡ试剂盒进行双盲式同步测定，二法检验结果差异无显著性。渗滤法简便快速，适用于各级医院，有很强的推广价值。     

冬虫夏草对大鼠小剂量环孢素A慢性肾毒性保护作用的实验研究

为进一步探讨冬虫夏草对环孢素Ａ慢性肾毒性的保护作用和机制，将ＳＤ大鼠分为两组：ＣｓＡ大鼠分为两组：ＣｓＡ组和ＣｓＡ＋冬虫夏草组，实验３个组。结果显示：在实验不同时期冬虫夏草组大鼠血Ｃｒ，ＢＵＮ及血清Ｎａ＾＋，Ｋ＾＋均较对照组为低，实验第３月冬虫夏草组鼠血清血管紧张素Ⅱ（ＡＴ－Ⅱ）水平低于对照组；实验不同阶段尿ＥＧＦ排出量亦较对照组为低；肾组织病理形态改变较对照组明显为轻。本实验证明冬虫夏草对ＣｓＡ     

Vitamin a cost-effectiveness model

To assist in the selection of a preferable vitamin A deficiency control policy, a model has been developed to organize information on program costs and program-related effects. The model was designed to compare three approaches: (1) diet modification; (2) fortification of processed foods; and (3) periodic large doses. Health effects projected are rates of specific eye pathologies associated with vitamin A deficiency (xerophthalmia), and mortalities within age cohorts. Effectiveness is calculated as a function of coverage, biological efficacy, and incidence of vitamin A deficiency. The model was applied to data from the Province of West Java in Indonesia. The results of this application suggest that funding level considerations are an important factor in selecting a preferred control strategy. In addition to determining the relative resource requirements of alternative interventions aimed at reducing the morbidity and mortality effects of vitamin A deficiencies, the model, using marginal cost and marginal effectiveness information, can serve as a guide to the most efficient allocation of resources for each type of intervention.     

竹红菌甲素敏化S-180肿瘤细胞膜的光氧化反应及机理探讨

本文研究了竹红菌甲素(简称甲素)对S-180肿瘤细胞膜的作用。结果表明,甲素结合光照可引起S-180肿瘤细胞膜蛋白质交联、脂质过氧化产物MDA含量增加。但在SDS-PAGE分析中观察到的高分子蛋白质交联带并非由MDA所引起。甲素同样可引起小牛胸腺组蛋白光氧化、发生分子交联,并可敏化色氨酸、酪氨酸和组氨酸的无氧化。     

环孢霉素A滴眼治疗角膜移植排斥反应

应用0.5％环孢霉素A(cyclosporin A,CsA)滴眼治疗穿透性角膜移植术后发生免疫排斥患者16例(16只眼),治愈9只眼,好转6只眼,无效1只眼。随访5～24个月,其中2只眼因停药复发,1只眼于拆线后复发,继续用药或增加给药次数后治愈。研究表明0.5％CsA滴眼剂治疗术前移植床条件较好,角膜移植术后发生免疫排斥的病例可得到良好疗效;而对术前移植床条件较差,角膜移植术后发生免疫排斥的病例有一定的疗效。作者对眼局部应用CsA治疗角膜移植排斥的疗效和作用机理进行了讨论。     

Protein kinase C isozymes that mediate enhancement of neurite outgrowth by ethanol and phorbol esters in PC12 cells

Using PC12 cells to study ethanol's effects on growth of neural processes, we found that ethanol enhances NGF- and basic FGF-induced neurite outgrowth. Chronic ethanol exposure selectively up-regulates δ and ε protein kinase C (PKC) and increases PKC-mediated phosphorylation in PC12 cells. Since PKC regulates differentiation, we investigated the role of PKC in enhancement of neurite outgrowth by ethanol. Like ethanol, 0.3–10 nM phorbol 12-myristate, 13-acetate (PMA) increased NGF-induced neurite outgrowth. However, higher concentrations did not, and immunoblot analysis demonstrated that 100 nM PMA markedly depleted cells of β, δ and ε PKC. PMA (100 nM) also down-regulated β, δ and ε PKC in ethanol-treated cells and completely prevented enhancement of neurite outgrowth by ethanol. In contrast, the cAMP analogue 8-bromoadenosine cAMP did not completely mimic the effectsof ethanol on neurite outgrowth, and ethanol was able to enhance neurite formation in mutant PC12 cells deficient in protein kinase A (PKA). These findings implicate β, δ or εPKC, but not PKA, in the neurite-promoting effects of ethanol and PMA. Since chronic ethanol exposure up-regulates δ and ε, but not βPKC, these findings suggest that δ or εPKC regulate neurite outgrowth.     

石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

环孢素A体外抗曼氏血吸虫作用的观察

ＭＦ１小鼠实验感染曼氏血吸虫尾蚴１周、３周和６周后，分别经肺静脉和门静脉灌注取虫。实验显示，药物体外抗曼氏血吸虫的作用呈时间、剂量和虫龄依赖方式，童虫和雄虫对药物更敏感。     

营养缺乏及补充维生素A对大鼠肺巨噬细胞功能的影响

采用Ｗｉｓｔａｒ大鼠，从怀孕１６天进行限食喂养直到生后４５天，干预组从生后第３６天及第４２天分别给予维生素Ａ灌胃，每次２０００ＩＵ。结果表明，补充维生素Ａ可明显增加大鼠的胸腺重量、肺巨噬细胞的数目、巨噬细胞的吞噬功能及ＮＯ－２的分泌。维生素Ａ可部分纠正营养缺乏导致的免疫缺陷、胸腺萎缩，活化肺巨噬细胞功能，其作用机制有待于进一步研究。