Antiplatelet agents isolated from medicinal plants.

Platelet-vessel wall interaction is an important process in physiological hemostasis and pathological thrombosis. In oriental countries, some medicinal plants have been claimed for uses to improve circulation, induce fibrinolysis or prevent thrombosis. In cooperation with chemists using bioassay-based step-by-step purification, some antiplatelet agents were isolated from plant sources. According to their effects on platelet aggregation, release reaction and signal transductions involved, these antiplatelet agents can be classified into eight groups: 1. platelet-activating factor (PAF) antagonists, 2. collagen-receptor antagonists, 3. thromboxane-receptor antagonists, 4. ADP-receptor agonists, 5. inhibitors of phosphoinositide breakdown, 6. inhibitors of thromboxane formation, 7. agents increasing cyclic nucleotides, and 8. protein kinase C activators. These new pharmacological agents derived from medicinal plant sources may be useful as leads to develop as effective cardiovascular drugs.     

Amyloid and nonfibrillar deposits in mice transgenic for wild-type human transthyretin: a possible model for senile systemic amyloidosis

The human serum protein transthyretin (TTR) is highly fibrillogenic in vitro and is the fibril precursor in both autosomal dominant (familial amyloidotic polyneuropathy [FAP] and familial amyloidotic cardiomyopathy [FAC]) and sporadic (senile systemic amyloidosis [SSA]) forms of human cardiac amyloidosis. We have produced mouse strains transgenic for either wild-type or mutant (TTRLeu55Pro) human TTR genes. Eighty-four percent of C57BI/6xDBA/2 mice older than 18 months, transgenic for the wild-type human TTR gene, develop TTR deposits that occur primarily in heart and kidney. In most of the animals, the deposits are nonfibrillar and non-Congophilic, but 20% of animals older than 18 months that bear the transgene have human TTR cardiac amyloid deposits identical to the lesions seen in SSA. Amino terminal amino acid sequence analysis and mass spectrometry of the major component extracted from amyloid and nonamyloid deposits revealed that both were intact human TTR monomers with no evidence of proteolysis or codeposition of murine TTR. This is the first instance in which the proteins from amyloid and nonfibrillar deposits in the same or syngeneic animals have been shown to be identical by sequence analysis. It is also the first time in any form of amyloidosis that nonfibrillar deposits have been shown to systematically occur temporally before the appearance of fibrils derived from the same precursor in the same tissues. These findings suggest, but do not prove, that the nonamyloid deposits represent a precursor of the fibril. The differences in the ultrastructure and binding properties of the deposits, despite the identical sizes and amino terminal amino acid sequences of the TTR and the dissociation of deposition and fibril formation, provide evidence that in vivo factors, perhaps associated with aging, impact on both systemic precursor deposition and amyloid fibril formation.     

Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium.

We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium.     

柴胡加龙骨牡蛎汤治疗冠状动脉粥样硬化性心脏病合并焦虑抑郁研究进展

冠状动脉粥样硬化性心脏病（CHD）是全球常见的慢性病之一,焦虑和抑郁是其发生不良预后事件的潜在与关键危险因素。柴胡加龙骨牡蛎汤（CLMT）首见于《伤寒论》,为治疗少阳病兼心神逆乱证的经典名方,具备和解少阳、镇惊安神之功效。目前机制研究表明CLMT能通过调控相关信号通路、抑制相关炎症因子表达、改善氧化应激损伤、调节神经递质水平、抑制下丘脑-垂体-肾上腺轴亢进、促进骨髓间充质干细胞动员、抑制血小板活化等多途径对CHD合并焦虑抑郁发挥作用。临床研究表明CLMT对CHD合并焦虑抑郁导致的心绞痛、失眠等症状具有显著改善作用,可有效减轻患者负性情绪、改善中医证候积分、降低炎症因子水平等,且与西医常规治疗相比不良反应少,安全性较高。该文通过归纳整理近15年来中国知网（CNKI）、万方（Wanfang）、维普（VIP）、PubMed等数据库关于CLMT治疗CHD合并焦虑抑郁的文献,对其进行了机制及临床研究的综述,以期为CLMT指导CHD合并焦虑抑郁的进一步研究提供参考。     

HPLC法测定口服5—氨基水杨酸制剂后血浆和尿中的药物及其代谢物

目的建立测定血浆和尿样中5-氨基水杨酸(5-ASA)及代谢物乙酰-5-氨基水杨酸(Ac-5-ASA)浓度的HPLC方法,并进行5-ASA缓释片Pentasa的人体药动学研究.方法使用荧光检测器,以丙酰-4-氨基水杨酸为内标,用衍生化法使样品中的5-ASA丙酰化,甲醇沉淀蛋白后上清液直接进样.色谱柱为PhenomenexLunaTMC18,流动相为0.1mo1/L乙酸溶液乙腈三乙胺(460400.4,V/V/V)的混合液.测定6位健康志愿者口服1000magPentasa后血药浓度和尿药浓度.结果血浆中5-ASA及代谢物的线性范围为0.01～10μg/ml,尿样中为0.2～200μg/ml,血浆和尿中药物与代谢物的回收率在95.3%～106.2%之间,日内日间相对标准差均在052%～9.22%范围内.Pentasa口服后5-ASA和Ac-5-ASA的血药浓度在3～4h内达到峰值,分别为1.55和3.11μg/rl,AUC分别为6.90和26.32μg/(ml@h),60h内尿中排泄了口服剂量37.1%的药物.结论方法简便,灵敏度和准确度高,可用于5-ASA制剂的药物动力学研究.     

Intradialytic systolic blood pressure variation can predict long-term mortality in patients on maintenance hemodialysis

International Urology and Nephrology - It is unclear which time-points of intradialytic blood pressure (BP) best predict prognosis. Thus, it is important to assess the association between different...     

磷脂对HDL3介导大鼠皮肤成纤维细胞内胆固醇流出能力的影响

目的　研讨磷脂对HDL3 介导大鼠皮肤成纤维细胞内胆固醇流出能力的影响。方法　在卵磷脂 (PC)或鞘磷脂 (SPM )存在条件下 ,观察HDL3 介导细胞胆固醇流出量的变化、细胞内磷脂含量变化及游离胆固醇 /胆固醇酯平衡的变化。结果　①BSA组 (对照组 )、HDL3 组、PC组、SPM组、PC HDL3 组和SPM HDL3 组分别介导 4.70 %、31.5 5 %、7.35 %、8.0 6 %、42 .95 %和 46 .98%细胞胆固醇流出 ;②BSA、HDL3 、HDL3 SPM和HDL3 PC组细胞培育后胞内卵磷脂磷含量 (PC p)和鞘磷脂磷含量 (SPM p)分别为 2 0 .0 2、5 .5 6 ,17.5 6、5 .2 8,18.6 2、7.0 0和 2 2 .5 0、5 .5 2 μg/皿 ;③PC和SPM与细胞培育后 ,胞内游离胆固醇 /总胆固醇比值分别为 49.6 5和 5 9.5 7。培育前此比值为 48.6 4。结论　①PC和SPM本身无介导细胞胆固醇流出能力 ,但它们能显著提高HDL3 介导的细胞胆固醇流出能力 ,且后者强于前者 ;②随着细胞胆固醇流出 ,部分胞内PC也流出胞外 ,而胞内SPM无明显变化 ;③SPM促进细胞内胆固醇酯向游离胆固醇转化。     

论高校科技产业的创新与发展

２１世纪是以信息技术和生物工程技术为代表的高瓣技术及其产业迅猛发展的知识经济世纪,本文主要讨论了在新世纪里高校职能的变化及其在知识创新、技术创新和国家经济建设中的地位、作用等问题。作者认为,坚持创新是高校生存和发展的根本需要;高校科技产业则是具有中国特色的知识经济的产物。对完善我国教育体制、提高办学实力、调整我国的知识结构和产业结构都具有十分重要的意义。     

p53反义RNA对肠癌细胞恶性表型的抑制作用

研究ｐ５３反义ＲＮＡ对大肠癌细胞中突变型ｐ５３致癌性的抑制效应,为肿瘤基因治疗提供新思路。方法２．１ｋｂ的人ｐ５３全长ｃＤＮＡ反向插入哺乳动物表达载体ｐＲＥＰ９,得到ｐ５３反义ＲＮＡ表达载体ｐＲＥＰ９－ｐ５３（ＡＳ）,并将其导入人肠癌细胞株ＳＷ１１１６（内源性突变型ｐ５３）,采用ＭＴＴ和ＦＣＭ方法测定ｐＲＥＰ９－ｐ５３（ＡＳ）表达的ｐ５３反义ＲＮＡ对ＳＷ１１１６细胞生长的影响。结果带有ｐＲＥＰ９－ｐ５３（ＡＳ）的ＳＷ１１１６细胞,与对照组ＳＷ１１１６细胞和带ｐＲＥＰ９空载体的ＳＷ１１１６细胞相比,由于ｐ５３反义ＲＮＡ的表达,其增殖速度显著下降,ＦＣＭ的结果也证明带ｐＲＥＰ９－ｐ５３（ＡＳ）的细胞部分受阻于Ｇ０／１期,而带ｐＲＥＰ９空载体的细胞则无明显变化。结论ｐ５３反义ＲＮＡ可以有效地抑制大肠癌细胞中突变型ｐ５３的致癌性,可用于实验性肿瘤基因治疗研究     

Activation by high potassium of a novel voltage-operated Ca2+ channel in rat spleen

1. High potassium produced a concentration-dependent contraction in rat isolated spleen.
2. The high potassium-induced contraction of rat spleen was abolished in Ca²⁺-free Krebs solution containing 1 mM EGTA, and the subsequent addition of 3 mM Ca²⁺ restored the high potassium-induced contraction to the control level.
3. Nifedipine, verapamil, diltiazem, Cd²⁺, Ni²⁺, Co²⁺, R-(+)-Bay K 8644 and pimozide inhibited and relaxed high potassium-induced contraction of rat spleen with IC₅₀ and EC₅₀ values much higher than those values in rat aorta.
4. In addition, high potassium-stimulated contraction of rat spleen was insensitive to ω-conotoxin GVIA, ω-conotoxin MVIIC and ω-agatoxin IVA.
5. The high potassium-induced contraction of rat spleen was also unaffected by tetrodotoxin (TTX), prazosin, chloroethylclonidine (CEC), yohimbine, propranolol, atropine, diphenhydramine, cimetidine, ketanserin, 3-tropanyl-indole-3-carboxylate, saralasin, indomethacin, nordihydroguaiaretic acid, GR32191B, domperidone, naloxone, chlorpromazine, suramin, (±)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione (DNQX), L-659,877, L-703,606, lorglumide, PD 135,158 N-methyl-D-glucamine, benextramine, amiloride, dantrolene, TMB-8, econazole, staurosporine and neomycin.
6. Forskolin and sodium nitroprusside relaxed high potassium-induced contraction of rat spleen with EC₅₀ values of 0.55±0.04 and 20.0±2.7 μM, respectively.
7. It is concluded that high potassium may activate a novel, pharmacologically uncharacterized voltage-operated Ca²⁺ channel in rat spleen.