Antiplatelet effect of amlodipine: a possible mechanism through a nitric oxide-mediated process.

The effect of amlodipine, a novel calcium channel blocker of the dihydropyridine type, on rabbit platelet aggregation, and the possible antiaggregatory mechanisms of amlodipine, especially on the nitric oxide (NO) guanosine 3',5'-cyclic monophosphate (cyclic GMP)-mediated pathway, were investigated. Other effects of amlodipine on thromboxane B2 (TXB2) formation in platelets also were examined. Amlodipine concentration-dependently inhibited rabbit platelet aggregation induced by collagen (10 microg/mL) or thrombin (0.1 U/mL) with an IC50 range of 32-69 microM. Along with this inhibition, our results also demonstrated that in the presence of L-arginine (100 IM), amlodipine (50 microM) increased nitric oxide synthetase (NOS) activity (from the resting activity of 2.05+/-0.36 to 7.11+/-0.95 pmol/mg protein/min) and NO release (by 80%), accompanied by an elevation of the cyclic GMP level (from the resting platelet level of 1.27+/-0.12 to 6.21+/-0.55 pmol/10(9) platelets) induced by collagen (10 microg/mL). However, the antiaggregatory effect of amlodipine (50 microM) could be attenuated significantly by oxyhemoglobin (5 microM), a NO scavenger, or N(G)-nitro-L-arginine methyl ester (100 microM), a specific NOS inhibitor. In addition, the TXB2 production in platelets induced by collagen or thrombin was concentration-dependently inhibited by amlodipine. Therefore, we propose that the antiaggregatory mechanisms of amlodipine might be mediated, in part, by a NO-cyclic GMP process accompanied by the inhibition of TXB2 formation in platelets.     

Discovery and structure-activity relationships of imidazole-containing tetrahydrobenzodiazepine inhibitors of farnesyltransferase

2,3,4,5-Tetrahydro-1-(imidazol-4-ylalkyl)-1,4-benzodiazepines were found to be potent inhibitors of farnesyltransferase (FT). A hydrophobic substituent at the 4-position of the benzodiazepine, linked via a hydrogen bond acceptor, was important to enzyme inhibitory activity. An aryl ring at position 7 or a hydrophobic group linked to the 8-position through an amide, carbamate, or urea linkage was also important for potent inhibition. 2,3,4, 5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2-(t rifluo romethoxy)benzoyl]-1H-1,4-benzodiazepine (36), with an FT IC(50) value of 24 nM, produced 85% phenotypic reversion of Ras transformed NIH 3T3 cells at 1.25 microM and had an EC(50) of 160 nM for inhibition of anchorage-independent growth in soft agar of H-Ras transformed Rat-1 cells. Selected analogues demonstrated ip antitumor activity against an ip Rat-1 tumor in mice.     

Aggregation inhibitory activity of minor acetophenones from Paeonia species

Two minor acetophenones, 2,5-dihydroxy-4-methoxy-acetophenone (2) and 2,5-dihydroxy-4-methylacetophenone (7) from Paeonia species were found to selectively inhibit the aggregation of rabbit platelets induced by arachidonic acid. They were more potent than the major compound, paeonol (1), and 7 also inhibited the formation of TXA2 and PGD2 from arachidonic acid.     

中药川芎中无机阴离子和有机酸成分的研究

目的：研究中药川芎中有机酸和无机阴离子的同时分析方法。方法：采用非抑制型阴离子交换色谱法,色谱柱为ＳｈｉｍｐａｃｋＩＣＡ１,流动相为０８ｍｍｏｌ·Ｌ－１邻苯二甲酸氢钾。结果：川芎提取液中３种有机酸和３种无机阴离子得到了较好的分离。结论：该方法分析速度快,准确,灵敏度高。     

口服Ⅱ号避孕药对血小板功能及血液凝固的影响

为了解口服Ⅱ号避孕药对血小板功能及血液凝固性的影响,本文对65名连续服药妇女进行了研究。她们的年龄为27～45(平均36.5)岁。服药期限1～17(平均6.7)年。测定项目有纤维蛋白原,血小板粘附率,血小板聚集率,Ⅷ因子相关抗原,抗凝血酶活力等。20例未服药妇女作对照。测定结果服药组血小板粘附率、聚集率及纤维蛋白原比对照组明显增高(P<0.001)。Ⅷ因子相关抗原略增高,但无统计学意义。抗凝血酶活力显著降低(P<0.001)。本文就急性心肌梗塞及血栓栓塞的潜在可能性等问题进行了讨论,并对预防此类并发症提出了建议。     

Syntheses and in vitro evaluation of water-soluble "cationic metalloporphyrin-ellipticine" molecules having a high affinity for DNA

The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of linker (7-13 bonds), the chemical nature of the linking group (with a carboxamido or an ether function), the position of amino group between the two parts of hybrid molecules, the number of intercalator moieties (ellipticinium) covalently attached to the metalloporphyrin, and the nature of the central metal atom (Mn, Fe, Zn) on the biological activity of these hybrid molecules were studied. In addition, these molecules have a high affinity for double-stranded DNA (affinity constant of hybrid molecule 9Mn,Me = 2.3 x 10(9) M-1 for poly[d(A-T)] and 2.8 x 10(8) M-1 for poly[d(G-C)] and are cytotoxic against murine leukemia cells L1210 in vitro (IC50 of 9Mn,Me = 0.8 microM). Their cytotoxicities are dependent on the nature of central atom. Iron derivatives are less active than manganese analogues and the corresponding zinc derivatives are nearly inactive despite their same affinity for nucleic acids. These highly water-soluble hybrid molecules could be considered as efficient bleomycin models based on a cationic metalloporphyrin.     

社区糖尿病患者量化饮食和运动治疗的疗效观察

目的通过对糖尿病患者进行量化饮食治疗和运动治疗,探索社区糖尿病管理的有效模式,以有效控制血糖,降低医疗费用。方法选取社区内空腹血糖小于11.1mmol/L的2型糖尿病患者129人,按病情匹配分为强化管理组(64例)和普通管理组(65例)。强化管理组采用一对一的指导和监督,量化饮食和运动治疗,有针对性的进行健康教育和心理疏通。普通管理组为一般的健康教育和门诊治疗。观察两组干预一年后的病情控制情况和医药费用的情况。结果强化管理组平均空腹血糖为5.8mmol/L,比普通管理组的7.1mmol/L有明显降低,糖化血红蛋白强化管理组为5.9%,普通管理组为7.0%。强化管理组医药费平均每人每月下降32.25元,下降幅度为20.12%,普通管理组平均每人每月下降12.47元,下降幅度为4.54%。结论量化饮食和运动治疗在社区糖尿病干预中疗效优于普通干预组,且医药费用明显降低。     

针灸对胰岛素抵抗影响研究的概况

本文系统回顾了近年来胰岛素抵抗的针灸治疗的研究概况。发现针灸在调节高血压、糖尿病、中风、肥胖症等的胰岛素抵抗方面有显著的疗效．对于胰岛素抵抗可致的各方面的病理生理改变均有不同程度改善。     

CVLM咪唑啉-I和α_2-肾上腺素受体共同参与可乐定的降压效应

目的　探讨大鼠尾端延髓腹外侧区 (CVLM)咪唑啉 I受体 (I1R)和α2 肾上腺素受体 (α2 AR)在介导可乐定中枢降压机制中的作用。方法　在氨基甲酸乙酯麻醉SD大鼠中 ,观察CVLM内局部给予I1R和α2 AR阻断剂后对基础血压(BP)、心率 (HR)以及外周给予可乐定导致降压效应的变化。结果　双侧CVLM分别微量注射选择性α2 AR阻断剂育亨宾 (单侧剂量 5 0 0 pmol·L-1,10 0nl,n =8)或I1R和α2 AR混合性阻断剂idazoxan(单侧剂量 2nmol·L-1,10 0nl,n =10 )后不仅明显降低BP和HR(P <0 0 1) ,而且能明显减弱静脉给予可乐定 (5 μg·kg-1)导致的降压效应 (P <0 0 1) ,此外 ,idazoxan对可乐定降压效应的减弱作用高于育亨宾 (P <0 0 1)。结论　CVLM内I1R和α2 AR共同参与维持紧张性心血管活动和介导可乐定的降压效应     

氨茶碱对三磷酸腺苷诱发兔窦房结电生理反应的抑制作用

目的　分析氨茶碱对三磷酸腺苷 (ATP)诱发兔窦房结电生理反应的抑制作用。方法　细胞内微电极技术记录兔离体窦房结细胞动作电位。结果　ATP( 0 3～ 3 0mmol/L)单次槽内注入给药 ,浓度依赖性减慢窦房结自发搏动速率 2 2 %～ 4 3% ,降低舒张期除极速率 4 2 9%～ 6 6 7% ,增大动作电位幅值 7 1%～ 9 2 % ,加快最大除极速率 32 0 %～ 75 5 % ,使动作电位复极 5 0 %和 90 %的时程 (APD50 和APD90 )缩短 7 1%～ 11 8%和7 3%～ 9 3%。P1受体阻断剂氨茶碱 ( 0 1mmol/L)显著拮抗ATP的作用 ,P2受体阻断剂反应蓝 2( 0 0 5mmol/L)则不影响ATP的作用。结论　ATP的上述电生理学效应可能通过P1受体介导