Effects of hypercholesterolemia on the nucleotide content in human blood cells

In hypercholesterolemia significant changes in the nucleotide pattern of erythrocytes and lymphocytes as determined by high performance liquid chromatography were found. The decrease in ATP of lymphocytes in hypercholesterolemia from 10.4 +/- 0.3 to 7.0 +/- 0.4 nmol mg-1 protein (n = 8) was associated with an increase in ADP from 2.2 +/- 0.2 to 4.0 +/- 0.2 nmol mg-1 protein (P less than 0.005). The pattern of guanosine phosphates likewise was found to be changed in hypercholesterolemia. Akin to lymphocytes, red blood cells displayed marked changes in nucleotide levels. No such changes were observed in platelets. Cultured lymphocytes incubated with human plasma low density lipoproteins (LDL) (140 mg cholesterol dl-1) displayed a reversible fall in ATP and an increase in ADP by about 40% and 160%, respectively, with high density lipoproteins (HDL) or very low density lipoproteins (VLDL) being essentially ineffectual. It is concluded that in hypercholesterolemia a significant change in the nucleotide pattern of blood cells is exerted by the increase in LDL. Possible pathophysiological implications are discussed.     

血小板ADP-P2Y12受体拮抗剂研究进展

血小板在动脉粥样硬化斑块破裂后血栓形成发病机制中发挥关键作用,因而针对血小板激活途径的药物成为抗栓治疗的主要手段。循证医学表明,抗血小板治疗可以有效地预防动脉粥样硬化疾病患者发生严重的心血管事件。已经成为防治急性冠脉综合征的主要方法。     

HPLC法测定术后疲劳综合征大鼠骨骼肌ATP,ADP,AMP的含量

目的:建立改良的高效液相色谱(HPLC)法测定术后疲劳综合征(POFS)大鼠骨骼肌5’-三磷酸腺苷(ATP)、5’-二磷酸腺苷(ADP)、5’-磷酸腺苷(AMP)的含量。方法:采用色谱柱Hypersil ODS2(4.6 mm×150 mm,5μm),柱温25℃;流动相为100 mmol.L-1磷酸盐缓冲液(含12 mmol.L-1的磷酸氢二钠和88 mmol.L-1的磷酸二氢钠,pH=6.5)-甲醇(99.9∶0.1,体积比);流速1.0 mL.min-1;紫外波长为254 nm;进样量20μL。结果:ATP、ADP、AMP色谱峰在10 min内得到了较好的分离,在测定范围内均呈良好的线性关系,r分别为1.000,0.9996,0.9994;精密度试验日内RSD≤4.1%,日间RSD≤3.5%;稳定性试验RSD≤4.8%;重复性试验RSD≤2.3%;回收率在97.1%～105.4%之间,RSD≤4.8%。应用改良的方法对模型组大鼠和对照组大鼠骨骼肌ATP、ADP、AMP的含量进行检测。结果显示,与对照组相比,模型组大鼠骨骼肌ATP含量在术后第1,3 d明显下降(P<0.05),ADP含量在术后第7 d明显升...     

噻吩并四氢吡啶衍生物的合成及其抗血小板聚集活性研究

为了寻找新型的ADP受体拮抗剂类抗血栓药物, 合成了18个未见文献报道的噻吩并四氢吡啶衍生物, 化合物结构经¹H NMR和MS确证。大鼠体内抗血小板聚集活性研究表明, 化合物C1的活性优于阳性对照药噻氯匹定, 值得进一步深入研究; 化合物A4、B2、C4和C7均有不同程度的抑制血小板聚集的活性。     

昆布多糖对家兔血小板聚集和释放的影响

目的 观察昆布多糖对家兔血小板聚集和释放的影响.方法 采用体内试验,比浊法观察昆布多糖对血小板活化因子(PAF)诱导的家兔血小板聚集作用的影响,双抗夹心放射免疫法测定血浆血小板颗粒膜蛋白(GMP-140)含量.结果 昆布多糖能抑制血小板活化因子诱导的家兔血小板聚集,与生理盐水组相比有显著差异(P＜0.05或P＜0.01),并能降低血小板颗粒膜蛋白含量(P＜0.01).结论 昆布多糖具有抗血小板活化因子诱导的血小板聚集作用,能抑制血小板的聚集和释放.     

ADP受体抑制剂在急性冠状动脉综合征应用中的研究进展

抗血小板聚集药物的使用是治疗急性冠状动脉综合征的关键环节,作为ADP受体抑制剂之一,氯吡格雷是临床广泛应用的抗血小板聚集药物。随着一系列关于抗血小板循证医学实验结果的披露,其他新型的ADP受体抑制剂(如替卡格雷、普拉格雷等)在抗血小板方面显示出与氯吡格雷不同的特点。     

Toxicity evaluation of some traditional African spices on breast cancer cells and isolated rat hepatic mitochondria

Background

Fagara leprieuri (FL), Fagara xanthoxyloïdes (FX), Mondia whitei (MW) and Xylopia aethiopica (XA) are used in many African countries as food spices or in traditional medicine to treat several maladies. In this work, we (a) investigate whether the crude spice extracts present selective cytotoxicity for breast cancer cell lines and (b) investigate whether the same extracts affect the bioenergetics and calcium susceptibility of isolated liver mitochondrial fractions.

Results

All extracts were cytotoxic to the cell lines studied, with the exception of MW, which was less toxic for a normal cell line. Interestingly, some of the extracts did not depolarize mitochondria in intact breast cancer MCF-7 cells, although this effect was observed in a normal breast cancer cell line (MCF-12A). All extracts increased hepatic mitochondrial state 2/4 respiration and decreased the respiratory control ratio and the transmembrane electric potential. Also, the extracts induced the mitochondrial permeability transition (MPT).

Conclusions

Mitochondrial toxicity may be part of the mechanism by which the spices tested cause inhibition of proliferation and death in the cell lines tested. This study also warrants caution in the excessive use of these spices for human consumption.     

l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes

l-Theanine is a unique amino acid in green tea. We here evaluated the protective effects of l-theanine on ethanol-induced liver injury in vitro and in vivo. Our results revealed that l-theanine significantly protected hepatocytes against ethanol-induced cell cytotoxicity which displayed by decrease of viability and increase of LDH and AST. Furthermore, the experiments of DAPI staining, pro-caspase3 level and PARP cleavage determination indicated that l-theanine inhibited ethanol-induced L02 cell apoptosis. Mechanically, l-theanine inhibited loss of mitochondrial membrane potential and prevented cytochrome c release from mitochondria in ethanol-treated L02 cells. l-Theanine also prevented ethanol-triggered ROS and MDA generation in L02 cells. l-Theanine restored the antioxidant capability of hepatocytes including GSH content and SOD activity which were reduced by ethanol. In vivo experiments showed that l-theanine significantly inhibited ethanol-stimulated the increase of ALT, AST, TG and MDA in mice. Histopathological examination demonstrated that l-theanine pretreated to mice apparently diminished ethanol-induced fat droplets. In accordance with the in vitro study, l-theanine significantly inhibited ethanol-induced reduction of mouse antioxidant capability which included the activities of SOD, CAT and GR, and level of GSH. These results indicated that l-theanine prevented ethanol-induced liver injury through enhancing hepatocyte antioxidant abilities.