Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells

Following observations that curcumin inhibited proliferation (IC(50)=1-5 microM), invasiveness and progression through S/G2/M phases of the cell cycle in the non-tumourigenic HBL100 and tumourigenic MDA-MB-468 human breast cell lines, it was noted that apoptosis was much more pronounced in the tumour line. Therefore, the ability of curcumin to modulate signalling pathways which might contribute to cell survival was investigated. After pre-treatment of cells for 20 min, curcumin (40 microM) inhibited EGF-stimulated phosphorylation of the EGFR in MDA-MB-468 cells and phosphorylation of extracellular signal regulated kinases (ERKs) 1 and 2, as well as ERK activity and levels of nuclear c-fos in both cell lines. At a lower dose (10 microM), it also inhibited the ability of anisomycin to activate JNK, resulting in decreased c-jun phosphorylation, although it did not inhibit JNK activity directly. In contrast, the activation of p38 mitogen activated protein kinase (MAPK) by anisomycin was not inhibited. Curcumin inhibited basal phosphorylation of Akt/protein kinase B (PKB) in both cell lines, but more consistently and to a greater extent in the MDA-MB-468 cells. The MAPK kinase (MKK) inhibitor U0126 (10 microM), while preventing ERK phosphorylation in MDA-MB-468 cells, did not induce apoptosis. The PI3K inhibitor LY294002 (50 microM) inhibited PKB phosphorylation in both cells lines, but only induced apoptosis in the MDA-MB-468 line. These results suggest that while curcumin has several different molecular targets within the MAPK and PI3K/PKB signalling pathways that could contribute to inhibition of proliferation and induction of apoptosis, inhibition of basal activity of Akt/PKB, but not ERK, may facilitate apoptosis in the tumour cell line.     

Peptide and nonpeptide antagonist interaction with constitutively active human AT1 receptors

Wild type human AT(1) receptors (WT-AT(1)) and mutant receptors, in which Asn(111) was replaced by glycine (N111G), alanine (N111A) and serine (N111S), or in which Asp(281) was replaced by alanine (D281A) or in which N111G and D281A replacements were combined, were transiently expressed in CHO-K1 cells. While the biphenyltetrazole compound candesartan dissociated slowly and behaved as an insurmountable antagonist for WT-AT(1), it dissociated swiftly and only produced a rightward shift of the angiotensin Ang II- and -IV dose-response curves for inositol phosphate (IP) accumulation in cells expressing N111G. [3H]candesartan competition binding yielded the same potency order of the related biphenyltetrazoles for WT-AT(1) and mutated receptors, i.e. candesartan>EXP3174>irbesartan>losartan. Affinities were equal for WT-AT(1) and D281A and 40- to 400-fold lower for all Asn(111) mutants. Mutations did not affect the affinity of the peptide antagonist [Sar(1)Ile(8)]Ang II (SARILE). Basal IP accumulation in cells with WT-AT(1) was not affected by any biphenyltetrazole antagonists and was increased by SARILE to 19% of the maximal Ang II stimulation. Basal IP accumulation was higher for cells expressing the Asn(111)-mutated receptors. For N111G, this accumulation was partially inhibited by all the biphenyltetrazoles upon long-term (18hr) exposure. In these cells SARILE produced the same maximal stimulation as Ang II. Asn(111)-mutated AT(1) receptors are thought to mimic the pre-activated state of the wild type receptor and comparing the efficacy and affinity of ligands for such mutated receptors facilitate the distinction of partial (SARILE) and inverse (biphenyltetrazoles) agonists from true antagonists.     

高效液相色谱法同时测定三七总皂苷中人参皂苷Rg_1、Re、Rb_1与三七皂苷R_1含量

目的建立高效液相色谱法同时测定三七总皂苷中人参皂苷Rg1、Re、Rb1与三七皂苷R1的方法。方法采用高效液相色谱法 ,固定相为氨基键合相 ,流动相为乙腈 水 ( 81∶1 9,V∶V) ,检测波长2 0 3nm。结果三七总皂苷中人参皂苷Rg1、Re、Rb1和三七皂苷R1与其他成分分离良好 ,保留时间分别约为 5 7min、8 9min、2 5 1min和 9 9min。人参皂苷Rg1在 80～ 2 80mg/L(r =0 9992 )、Re在 2 0～ 1 80mg/L(r=0 9993 )、Rb1在 95～ 2 85mg/L(r=0 9991 )、三七皂苷R1在1 8～ 1 4 6mg/L(r=0 9991 )内线性关系良好 ,人参皂苷Rg1、Re、Rb1和三七皂苷R1的回收率分别为 99 1 %、98 4 %、98 6%和 97 1 % ,RSD分别为 2 1 %、2 0 %、2 2 %、2 8%。结论本法可用于三七的质量控制     

羊蹄根汤与西药合用治疗原发性血小板减少性紫癜28例

目的：比较羊蹄根汤和西药合用与单纯西药治疗原发性血小板减少性紫癜的效果。方法：56例患者随机分为治疗组(中西药结合组：羊蹄根汤合用氨肽素、泼尼松和维生素C)和对照组(单纯西药组：氨肽素、波尼松和维生素C)。结果：治疗组有效率100％(28例)，对照组有效率78．6％(22例)两组间进行比较，有非常显著性差异(P＜0．01)。结论：羊蹄根汤和西药合用治疗原发性血小板减少性紫癜比单纯西药组疗效高。     

Passive antibody administration (immediate immunity) as a specific defense against biological weapons

The potential threat of biological warfare with a specific agent is proportional to the susceptibility of the population to that agent. Preventing disease after exposure to a biological agent is partially a function of the immunity of the exposed individual. The only available countermeasure that can provide immediate immunity against a biological agent is passive antibody. Unlike vaccines, which require time to induce protective immunity and depend on the host's ability to mount an immune response, passive antibody can theoretically confer protection regardless of the immune status of the host. Passive antibody therapy has substantial advantages over antimicrobial agents and other measures for postexposure prophylaxis, including low toxicity and high specific activity. Specific antibodies are active against the major agents of bioterrorism, including anthrax, smallpox, botulinum toxin, tularemia, and plague. This article proposes a biological defense initiative based on developing, producing, and stockpiling specific antibody reagents that can be used to protect the population against biological warfare threats.     

谷胱甘肽对顺铂致猴和大鼠肾细胞毒性的影响

目的 探讨顺铂对猴和大鼠肾小管上皮细胞的毒性及半胱氨酸和GSH合成抑制剂BSO对其影响。方法 从猴和大鼠的肾脏分离培养的肾小管上皮细胞接种于96孔培养板，培养24h后加入一系列浓度的顺铂，或在加入顺铂前16和4h，分别加入GSH合成抑制剂BSO和GSH的前体物半胱氨酸，继续培养，分别在8、24和48h3个时间点用MTT方法检测细胞存活率。结果 顺铂对猴和大鼠肾小管上皮细胞有明显的毒性，在不同的时间点有各自的剂量—反应关系，顺铂对大鼠肾小管上皮细胞在8、24和48h 3个时间点半数抑制浓度(IC50)分别为1105．12、513．25和71．24μmol/L；BSO能使3组IC50均降低，分别为66．00、21．43和7．23μmol/L，而半胱氨酸则使3组IC50均升高，均大于5000μmol/L；顺铂对猴肾小管上皮细胞在3个时间点IC50分别为3026．00、1238．35和664．44μmol/L；BS0使3组ICD分别降为480．10、108．61和31．43μmol/L，而半胱氨酸则可使3组IC50均大于5000μmol/L。结论 顺铂对猴和大鼠肾小管上皮细胞均具有明显毒性作用，对猴的毒性低于大鼠；BS0可增强顺铂的细胞毒性，对大鼠的影响大于猴，而半胱氨酸对两种细胞的保护作用无显著性差异，提示细胞内GSH对顺铂所致肾小管上皮细胞毒性有保护作用。     

薄层扫描法测定冀产红景天中红景天苷的含量

目的　通过冀产 3种红景天中有效成分红景天苷的含量测定 ,评估并比较其质量。方法　薄层扫描法。结果　河北雾灵山产 3种红景天 (红景天 Rhodiola rosea,狭叶红景天 R. kirilowii,小丛红景天 R. dumu-losa)中红景天苷的含量分别为 0 .6 %、0 .32 %、0 .0 0 4 9%。结论　冀产 3种红景天中 ,以红景天中的红景天苷含量最高 ,可进一步开发利用     

肝硬变患者血清可溶性白细胞介素Ⅱ受体测定

作者用酶免疫法检测了３１例肝炎后肝硬变患者血清可溶性白细胞介素Ⅱ受体（ＳＩＬ─２Ｒ）水平，并与３０例正常人进行了比较，结果显示：肝硬变患者血清ＳＩＬ─２Ｒ含量较正常人明显升高（Ｐ＜０．００１），提示淋巴细胞在肝炎后肝硬变患者的发病过程中有非常重要的作用。在肝炎后肝硬变患者存在着淋巴细胞激活状态检测血清ＳＩＬ─２Ｒ对肝炎后肝硬变的活动观察，对治疗的反应及预后估计是一个有用的指标。     

矽肺患者周围血淋巴细胞亚群、TNF-α、sIL-2R水平分析

【摘要】目的分析不同期别矽肺患者周围血淋巴细胞亚群和肿瘤坏死因子（TNF-仅）、血清可溶性白细胞介素_2受体（sIL-2R）的变化,探讨不同期别矽肺患者免疫水平的差异。方法应用直接免疫荧光-流式细胞技术检测86例矽肺患者（I期32例、Ⅱ期30例、Ⅲ期24例）周围血淋巴细胞亚群,同时应用酶联免疫吸附法（ELISA）检测血清中TNF．d和sIL-2R的水平,与30例正常健康人作比较。结果周围血CD3、CIM比例和CD4／CD8水平矽肺患者组低于正常人组（P〈0．05）,随着矽肺期别的升高,CD3、CD4比例和CD4／CD8下降,但无统计学差异（P〉0．05）;各期矽肺患者周围血TNF-α、sIL-2R的水平高于正常对照组（P〈O．05）,随着矽肺期别的升高,sIL-2R明显升高（P〈0．05）,TNF-α明显下降（P〈0．05）。结论矽肺患者周围血细胞免疫功能低下,TNF-α和sIL-2R协同参与矽肺发生和发展过程。     

梅毒患者血清可溶性白介素2受体测定及其临床意义

目的：探讨梅毒患者各期病程中血清可溶性白介素2受体（SIL－2R）的水平及临床意义，方法。采用酶联免疫吸附法（ELISA）测定70例梅患者及其治疗SIL－2R水平，并与20名健康体检者进行比较，结果：所有梅毒患者血清SIL－2R的水平明显高行正常对照组，两组间差异有显著性（P＜0．05），二期和潜伏梅毒患者血清SIL－2R的水平高于一期梅毒（P＜0．05）。青霉素治疗后，判为治疗有效者，测定SIL－2R的水平，比正常粗略高，两者无显著性差异（P＞0．05）。结论：SIL－2R水平的测定对梅毒病理判定及监测治疗有一定的参考价值。