第三代维甲类化合物丁羟胺酸在体外对蛋白激酶C的抑制作用

丁羟胺酸(R8605)是本所新合成的第三代维甲类化合物。在体外对二乙酰甘油和TPA活化PKC过程有抑制作用;对Ca~(2+)、磷脂和二乙酰甘油非依赖性PKC磷酸化鱼精蛋白有抑制作用。其IC50分别为65、70和100μmol/L。丁羟胺酸对PKC活性的抑制有助于解释其抗促癌作用机理。     

阿司匹林抑制胃癌细胞生长及其机制探讨

目的　研究阿司匹林对 SGC- 790 1胃癌细胞生长的影响 ,并初步探讨其作用的分子机制。方法　采用 3H- Td R法及流式细胞术检测不同浓度阿司匹林对胃癌细胞 DNA合成及细胞周期的影响 ;用免疫细胞化学法检测阿司匹林对胃癌细胞 COX- 2表达的影响 ;Western blotting法及 EMSA法检测阿司匹林对胃癌细胞 c- fos表达及 AP- 1活化的影响。结果　胃癌细胞经不同浓度的阿司匹林作用后 ,其 3H- Td R掺入值明显降低 ,且与阿司匹林浓度呈高度负相关 ( r=- 0 .9,P<0 .0 5 )。细胞周期分析显示 ,阿司匹林主要作用于胃癌细胞 S期。免疫细胞化学染色显示 ,阿司匹林能下调胃癌细胞 COX- 2表达 ,且具有良好的量效关系。Western blotting检测表明 ,阿司匹林能降低胃癌细胞 c- fos蛋白的表达。EMSA分析显示 ,阿司匹林能有效抑制血清刺激的 AP- 1的 DNA结合活性。结论　阿司匹林能有效抑制胃癌细胞的生长 ,这种作用可能是其通过抑制胃癌细胞 c- fos表达以及 AP- 1活化 ,进而抑制COX- 2表达所致     

丙戊酸钠对荷包牡丹硷诱发大鼠海马脑片痫样放电的影响

Experiments were conducted on the rat hippocampal slices in vitro with the superfusion of bicuculline (Bcl, 10 mumol/L) and stimulation of Schaffer collaterals by single pulse to produce epileptiform activity of the pyramidal cells in CA1 area. In these experiments the effect of constant microinjection of sodium valproate onto the surface of slice on the epileptiform activity was studied. The results showed that the valproate, in concentration of 20, 30, 50 and 100 mmol/L, inhibited the Bcl-induced epileptiform activity in a manner of dose-dependence. It was deduced that the inhibition of epileptiform activity by the valproate is possibly related to the recovery of and increase in the inhibition mediated by GABAergic neurons and may be also to the non-synaptic mechanism of the valproate in rat hippocampus.     

Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy

Sodium valproate is often used with phenytoin when epilepsy cannot be controlled by a single drug. Sodium valproate depresses phenytoin protein binding and so invalidates plasma phenytoin monitoring as a means of determining precise phenytoin dosage requirements. Plasma and saliva phenytoin and plasma valproate concentrations were measured in 42 patients with epilepsy receiving both drugs. Phenytoin protein binding was also measured by ultrafiltration in 19 of these patients and 19 patients taking phenytoin alone. Saliva phenytoin concentration bore the same close correlation to unbound (therapeutically active) phenytoin in patients receiving both drugs as it did in patients receiving phenytoin alone, whereas plasma total phenytoin did not. The same therapeutic range for saliva phenytoin (4-9 mumol/1; 1-2 microgram/ml) was therefore valid in both groups. The depression of phenytoin binding was directly related to the plasma concentration of valproate both in random samples taken from the 42 patients and in samples taken throughout the day in two of these patients. This was confirmed in vitro. Even when the concentration of valproate is known the degree of binding cannot be predicted. Saliva rather than plasma monitoring of phenytoin treatment is therefore valuable in the presence of valproate and with reduced phenytoin binding from any cause.     

Propofol combined with diazepam synergistically potentiates the GABA-activated chloride current in rat sensory neurons

γ ａｍｉｎｏｂｕｔｙｒｉｃ ａｃｉｄＡ(ＧＡＢＡＡ)ｒｅｃｅｐｔｏｒｓｉｎｔｈｅｃｅｎｔｒａｌｎｅｒｖｏｕｓｓｙｓｔｅｍ (ＣＮＳ)ａｒｅｔｈｏｕｇｈｔｔｏｂｅａｐｏｔｅｎｔｉａｌｔａｒｇｅｔｓｉｔｅｏｆａｃｔｉｏｎｆｏｒａｖａｒｉｅｔｙｏｆｇｅｎｅｒａｌａｎｅｓｔｈｅｔｉｃｓ 1,2 Ｅｘｔｅｎｓｉｖｅｓｔｕｄｉｅｓｈａｖｅｓｈｏｗｎｔｈａｔｂａｒｂｉｔｕｒａｔｅｓ,ｂｅｎｚｏｄｉａｚｅｐｉｎｅｓ ,ｐｒｏｐｏｆｏｌ,ａｎｄｖｏｌａｔｉｌｅａｎｅｓｔｈｅｔｉｃｓｓｕｃｈａｓｈａｌｏｔｈａｎｅ ,ｉｓｏｆｌｕｒ…     

理气类中药对大鼠离体胃平滑肌条的作用

目的：观察理气类中药对大鼠离体胃平滑肌条运动的影响。方法：将肌条放置在灌流肌槽中，用生理记录仪记录肌条的收缩活动。结果：陈皮、枳实对胃各部位平滑肌条均为抑制效应，香附、薤白、木香、柿蒂、乌药对胃底肌条为兴奋效应，但对其他部位肌条则表现为兴奋或抑制不同的效应，沉香仅降低胃窦环行肌收缩波平均振幅，对其他肌条无影响。结论：理气类中药对大鼠离体胃平滑肌条既有兴奋作用，也有抑制作用。     

健康成年人血浆肉毒碱水平和日尿肉毒碱排出量测定

目的测定健康成年人血浆肉毒碱水平及日尿肉毒碱排出量,为研究疾病状态下肉毒碱代谢改变提供参考依据。方法给予40名健康成年人(男、女各20名)标准饮食,用高效液相色谱法测定其空腹血浆总肉毒碱(TC)、游离肉毒碱(FC)和乙酰肉毒碱(AC)水平及日尿TC、FC和AC排出量。结果血浆和尿液肉毒碱测定的变异系数在9.1%以下,偏差不超过5.6%,标准曲线的相关强度r2≥0.999。给予健康成年人标准饮食后,男性血浆TC、FC和AC水平眼(53.1±8.5)、(41.2±6.1)、(6.2±0.6)μmol/L演高于女性眼(45.4±5.6)、(35.2±4.9)、(5.7±0.7)μmol/L演(P=0.002、0.002、0.035);男性日尿TC、FC和AC排出量眼穴386.1±22.9雪、穴180.5±31.8雪、穴33.8±3.3雪μmol演高于女性眼穴240.1±35.6雪、穴112.7±22.6雪、穴29.3±4.3雪μmol演穴P<0.0005、<0.0005、<0.0005雪。空腹血浆TC、FC和AC水平及日尿TC、FC和AC排出量均与机体瘦体重有关穴r=0.501～0.856雪。男性血浆穴TC-FC雪/FC比值为0.29±0.05,女性为0.29±0.04。结论以高效液相色谱法测定血浆肉毒碱水平和日尿肉毒碱排出量,其重复性好,回收率高。给予健康成年人标准饮食后,空腹血浆肉毒碱水平和日尿肉毒碱排出量均与机体瘦体重呈正相关。     

大鼠肝非实质细胞载脂蛋白CⅢ结合位点（受...

Binding sites of apolipoprotein (apo) C III on non-parenchymal cells (NPC) isolated from rat liver were found. Apo C III was purified from delipided human plasma very low density lipoproteins. 125I-labeled-apo C III was prepared by chloramine-T method. Non-parenchymal cells were isolated from rat liver by collagenase method. Freshly isolated rat liver NPC bound 125I-labeled apo C III in a saturable way with Kd 0.1-0.55 mumol/L and Bmax 18.1-42.0 ng/ml cell protein. There were about 1.0-4.5 x 10(5) specific binding sites of apo C III on each NPC. Unlabeled apo C III, but not apo AI and B100, could inhibit these binding activities. The results demonstrate the presence of saturable and specific apo C III receptors (binding sites) on rat liver NPC, but their nature and biologic properties remain to be investigated.     

Demonstration of specific binding of cocaine to human spermatozoa

Exposure of males to cocaine has been linked to abnormal development of their offspring. To investigate the possible role of sperm, this study examined the interaction of cocaine with human spermatozoa. Washed sperm were incubated with tritiated cocaine (6.7 nmol/L) with or without unlabeled cocaine (670 mumol/L), and the samples were filtered and the remaining radioactivity quantitated. The specific binding was optimal at 20 minutes and 23 degrees C. Competition studies with tritiated cocaine (3.4 to 66.6 nmol/L) indicated the presence of approximately 3.6 x 10(3) binding sites per cell, with a high affinity receptor dissociation constant (Kd = 12.6 nmol/L). Cocaine concentrations as high as 670 mumol/L had no detectable effect on either the motility or viability of the cells. These results support the hypothesis that the sperm may act as a vector to transport cocaine into an ovum. This novel mechanism could be involved in the abnormal development of offspring of cocaine-exposed males.