Different dependence of lithium and valproate on PI3K/PKB pathway

Objectives: Acute treatment with valproate (VPA) or lithium (Li⁺) protects cerebellar granule cells (CGC) against apoptosis induced by low potassium (K⁺) (5 mM). As the protection induced by VPA is absolutely dependent on insulin, in contrast to the observed effects of Li⁺, we decided to study the different role of the PI3K/PKB pathway in the neuroprotective effects of both drugs.

Methods: We have studied the neuroprotection elicited by Li⁺ or VPA in cultures of rat CGC. We induced the apoptosis by switching to a medium with a low concentration of K⁺ or by adding C₂-ceramide to the cultures. We studied the effect of Li⁺ and VPA on viability and on the regulation of the PI3K/PKB pathway.

Results and conclusions: Insulin also protects against low K⁺-induced apoptosis in CGC, probably through its interaction with an insulin-like growth factor receptor. Moreover, whereas Li⁺ protects against the apoptosis induced by C₂-ceramide, VPA cannot, probably due to the inhibition of protein kinase B (PKB) caused in this apoptotic stimulus. These results suggest that VPA protects against low K⁺-induced apoptosis by acting on the PI3K/PKB pathway; however, VPA does not affect the increase of PKB activity caused by insulin in these cells. The protection by Li⁺ is independent of this transduction pathway. Moreover, Li⁺ blocks the caspase 3 activation induced by low K⁺, whereas neither VPA nor insulin affects this activation.     

The total numbers of cerebellar granule neurons in young and aged Fischer 344 and Wistar-Kyoto rats do not change as a result of lengthy ethanol treatment

It is generally accepted that long term chronic ethanol consumption by young rats will lead to significant losses of cerebellar granule neurons (GN). A recent study in this laboratory showed, however, that 40 weeks of chronic ethanol consumption had no effect on the total numbers of GN in aged Fischer 344 rats (F344). The goals of the present study were to determine whether F344 GN were resistant to ethanol toxicity only in aged rats and whether resistance of GN in aged rats to ethanol toxicity occurred only in the F344 strain. To accomplish those goals, young and aged adult F344 and Wistar-Kyoto (WKY) rats were treated chronically with ethanol for 40 weeks during the first or second half of their life span. In each rat the total numbers of GN were estimated with the optical fractionator and the volumes of the GN layer were estimated according to Cavalieri's theorem. After the 40 weeks of ethanol, there were significant age-related differences in the total numbers of GN in the F344 rats. There were also significant strain-related differences in the total numbers of GN and volumes of the GN layer. There were no significant ethanol-related differences, however, in numbers of cerebellar GN or volumes of the GN layer in F344 rats or WKY rats. The results presented here show that consumption of ethanol over long periods of time had no effect on the total numbers of cerebellar GN or the granular layer volumes in young or aged F344 or WKY rats.     

扶正抑瘤颗粒对乳腺癌核转录因子-kB及细胞周期的影响

目的:研究扶正抑瘤颗粒(FYK)对乳腺癌肿瘤组织核转录因子-κB(NF-κB)和细胞周期的影响及其临床意义。方法:55例乳腺癌患者,随机分为治疗组和对照组,两组均用常规化疗,治疗组同时口服FYK,1个月后取肿瘤组织用流式细胞仪检测NF-κB的表达情况及肿瘤细胞周期各时相的比例。结果:治疗组与对照组比较,NF-κB的表达明显提高(P<0.01);G_(0/1)期细胞比例明显升高(P<0.01),S期细胞比例及细胞增殖指数(PI)明显下降(P<0.01)。结论:FYK可提高乳腺癌组织NF-κB表达水平;能升高G_(0/1)期细胞比例,降低S期细胞比例及PI值,对乳腺癌患者的预后起积极作用。     

Protoporphyrin IX production and its photodynamic effects on glioma cells, neuroblastoma cells and normal cerebellar granule cells in vitro with 5-aminolevulinic acid and its hexylester

5-Aminolevulinic acid (ALA) has shown promising in photodynamic detection and therapy of brain tumor. However, the knowledge on selective accumulation of ALA-induced protoporphyrin IX (PpIX) in brain tumor tissue is still fragment. In the present study, the rat C6 glioma cells, human SK-N-SH neuroblastoma cells, and rat normal cerebellar granule cells (RCG) were used to investigate the PpIX production and photocytotoxicity in vitro. The C6 cells and SK-N-SH cells showed a similar kinetics of PpIX accumulation after exposure to ALA or ALA hexyl ester (ALA-H), with an initial increase up to 6–8 h and then saturated. In the case of RCG cells, the PpIX accumulation slowly increased until 12 h studied. However the cellular PpIX content was more than 10 times higher in the C6 and SK-N-SH cells than that in the normal RCG cells. The intracellular localization of PpIX measured by cofocal laser scanning microscopy was in same pattern in the C6 glioma cells and RCG normal cells with a diffuse cytoplasm distribution. The sensitivity of the C6 cells and SK-N-SH cells to ALA or ALA-H PDT was similar. It appears that ALA-H could achieve similar or slightly better results than ALA with respect to PpIX production and photoinactivation of cells, although a 10 times lower concentration of ALA-H was used.     

头痛平的主要药效学研究

用压尾、热板及扭体等方法对头痛平进行了药效学实验研究。结果表明：大剂量的头痛平能提高小鼠尾痛阈值，在热板及扭体法实验中，大、小剂量均显示有镇痛作用，并证明方中加羚羊粉对镇痛作用影响不大。     

真龙冲剂对小鼠前列腺增生的抑制作用

以１０～４０ｇ／ｋｇ灌胃真龙冲剂，能抑制幼年小鼠的前列腺生长，减轻前列腺组织湿重和降低前列腺的ＤＮＡ含量；能减轻丙酸睾丸素与植入胎鼠尿生殖窦所致小鼠前列腺的增生，并降低血清酸性磷酸酶活性。     

大蒜素对不同中医证型不稳定性心绞痛的作用及与血脂和GMP-140的关系

目的 :观察大蒜素注射液对不稳定性心绞痛的临床疗效及与中医证型的关系。方法 :将 5 5例不稳定性心绞痛患者随机分为治疗组(3 4例)和对照组(2 1例) ,每组依中医辨证再分为偏寒和偏热型及重度瘀血和轻度瘀血型。治疗组和对照组分别每天静脉滴注大蒜素 60mg和硝酸甘油5mg,疗程 1 0天。根据疗程前后症状和心电图变化评定疗效 ,并测定血脂、脂蛋白、载脂蛋白和血小板α颗粒膜蛋白(GMP 1 40 )。结果 :大蒜素组疗效与对照组相比无显著性差异 ;大蒜素对偏寒型的疗效明显优于偏热型 (P <0 0 1 ) ,并显著升高偏寒型患者的高密度脂蛋白与低密度脂蛋白比值和载脂蛋白A1 水平(P <0 0 5 ) ,偏热型出现相反趋势 ;大蒜素可使轻度瘀血型的GMP 1 40明显降低 (P <0 0 5 )。结论 :大蒜素对不稳定性心绞痛有较好的疗效 ,对寒瘀型的不稳定性心绞痛患者 ,疗效更佳。其机理与改善血脂和促进血小板活化有关。     

宫宁颗粒剂治疗使用宫内节育器出血副反应的临床研究

应用宫宁颗粒剂治疗使用宫内节育器出血副反应60例,用药后月经血量、经期天数较用药前均明显减少(P均<0.01),周期天数、血红蛋白较用药前均显著增加(P均<0.01)。对照组仅月经血量明显减少(P<0.01),治疗组用药后血清及经血纤维蛋白裂解产物较用药前明显下降(P均<0.01);经血前列腺素PGF_(1α)与血栓素B_2的比值用药后恢复正常。     

颈椎舒冲剂治疗椎动脉型颈椎病的临床与实验研究

颈椎舒冲剂治疗椎动脉型颈椎病总有效率为94.94％。治疗后病人甲皱微循环、血液流变学指标有较明显改善,椎动脉、颈内动脉异常增高的血流速度减低。该药对兔离体颈动脉血管条有较明显的扩张作用,并能抑制去甲肾上腺素对血管的收缩作用。