双苄基异喹啉季铵类化合物的合成及肌肉松驰活性

目的：获得起效快、复原快的肌肉松驰剂。方法：1类化合物以汉防乙甲素为原料,经季铵化制得。Ⅱ类以阿曲库铵的结构为模板,对其1－取代基进行结构改造而得,所有目的化合物的结构经IR、^1HNMR、MS鉴定。结果：设计合成了未见文献报道的11个两类双苄基异喹啉季铵类化合物。结论：初步药理试验表明,目的化合物1c的起效剂量、起效时间与汉肌松相当。     

1—（9H—卟唑—4—氧）—3—取代氨基—2—丙醇类化合物的合成及生物活性（Ⅰ）

目的：寻找有-β－受体阻滞活性,且高效低毒的化合物。方法：以β－受体阻滞剂咔唑洛尔为先导化合物,根据药物设计中的结构拼合原理,对其内醇胺侧链进行结构修饰,设计并合成了10个1－（9H－卟唑－4－氧）－3－取代氨基－2－丙醇类化合物V1－V10。结果和结论：所合成的目的物均未见文献报道,结构经红外光谱、核磁共振氢谱、质谱、元素分析或高分辨质谱确证。初步药理筛选结果显示,10个化合物均能够不同程度地拮抗异丙肾上腺素引起的心支过速,其中化合物V1、V3、V4的活性与先导化合物相似。     

中药灯盏细辛化学成分的研究(Ⅱ)

目的：进一步研究灯盏细辛「Ｅｒｉｇｅｒｏｎ ｂｒｅｖｉｓｃａｐｕｓ（Ｖａｎｔ．）Ｈａｎｄ．－Ｍａｚｚ．」的化学成分。方法：采用硅胶柱层析对灯盏细辛的氯仿萃取部分的化学成分进行分离和纯化,应用理化常数和光谱分析（ＩＲ,ＭＳ,＾１ＨＮＭＲ,＾１３ＣＮＭＲ）鉴定其结构。结果：得到６个单体化合物,结构分别为３,４－二羟基肉桂酸（３,４－ｄｉｈｙｄｒｏｘｙ－ｐｈｅｎｙｌ ａｃｒｙｌｉｃ ａｃｉｄ,Ⅶ）,α－甲氧基－γ－吡喃酮（α－ｍｅｔｈｏｘｙ－γ－ｐｙｒａｎｏｎｅ,Ⅷ）、豆甾醇（ｓｔｉｇｍａｓｔｅｒｏｌ,Ⅺ）、胡萝卜甙（β－ｓｉｓｔｏｓｔｅｒｏｌ－３－Ｏ－β－Ｄ－ｇｌｕｃｏｐｙｒａｎｏｓｉｄｅ,Ⅻ）。结论：化合物Ⅶ,Ⅷ,Ⅺ,Ⅻ为首次从本植物中分得。     

胆碱酯酶监测在抢救有机磷农药中毒中的临床意义

目的 探讨胆碱酯酶活性在决定有机磷农药中毒抢救中氯磷定、阿托品的用量,停药时间及对患者预后判断的作用。方法 将口服有机磷农药中毒抢救传统治疗组列为对照组（３２例）,将口服有机磷农药中毒采用胆碱酯酶指导氯磷定、阿托品用量及停药列为观察组（５０例）。结果 观察组阿托品用量和氯磷定用量与对照组阿托品用量和氯磷定用量有显著差异（Ｐ〈０．０１）。观察组治愈５０例,治愈率１００％;对照组治愈２８例,治愈率８７     

The effects of neuroleptic and tricyclic compounds on BKCa channel activity in rat isolated cortical neurones

1. The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca²⁺-activated K⁺ (BK_Ca) channel present in neurones isolated from the rat motor cortex.
2. Classical neuroleptic compounds including chlorpromazine and haloperidol applied to the intracellular surface of inside-out patches produced a concentration-dependent reduction in BK_Ca channel activity. Similar effects were observed when these compounds were applied to the extracellular surface of outside-out patches.
3. In contrast, the atypical neuroleptic compounds clozapine and sulpiride did not affect BK_Ca channel activity (100 nM–1 mM) in either inside-out or outside-out patches, while 10 μM pimozide produced 73% of the inhibition produced by 10 μM chlorpromazine.
4. BK_Ca channel activity was also unaffected by application of structurally related tricyclic compounds including the anti-cholinesterase tacrine and the anti-epileptic carbamazepine. The tricyclic antidepressant drug amitriptyline was found to inhibit BK_Ca channel activity but was much less effective than the classical neuroleptic compounds.
5. It is concluded that compounds belonging to the classical neuroleptic group of drugs inhibit BK_Ca channel activity in the rat motor cortex in a structurally-specific manner. This observation may be of clinical significance as it may contribute to some of the side effects associated with classical neuroleptic drug therapy.

     

Benign and malignant hepatocellular tumors: evaluation of tumoral enhancement after mangafodipir trisodium injection on MR imaging

The aim of this work was to study the ability of mangafodipir trisodium (Mn-DPDP)-enhanced MR imaging in differentiating malignant from benign hepatocellular tumors. Eleven patients with pathologically proved hepatocellular carcinomas, six with focal nodular hyperplasias, and one with a single hepatocellular adenoma were examined by spin-echo and gradient-echo T1-weighted sequences before, 1 h after, and 24 h after intravenous injection of Mn-DPDP (5 μmol/kg). Quantitative analysis including enhancement and lesion-to-liver contrast-to-noise ratio, and qualitative analysis including the presence of a central area and a capsule were done on pre- and post-Mn-DPDP-enhanced images. Enhancement was observed in all the tumors with significant improvement (p < 0.05) in contrast-to-noise ratio 1 h after, and 24 h after intravenous injection of Mn-DPDP. There were no significant differences in the mean enhancement and the mean contrast-to-noise ratio (CNR) between benign and malignant tumors. No enhancement was seen within internal areas observed in 7 hepatocellular carcinomas, and in 5 focal nodular hyperplasias, and within capsules which were observed in 9 hepatocellular carcinomas. In our study, Mn-DPDP increased CNR of both benign and malignant tumors but did not enable differentiation between benign and malignant tumors of hepatocellular nature. Received: 7 October 1997; Revision received: 25 February 1998; Accepted: 10 July 1998     

重组人神经营养因子-4/5蛋白抗三氧化二砷神经毒作用

目的初步观察重组人神经营养因子-4／5（hNT－4／5）蛋白对三氧化二砷毒性的抑制作用。方法利用hNT－4／5蛋白具有抗神经毒性的特点,采用本实验室克隆表达及部分纯化的具有天然hNT－4／5蛋白生物学活性的重组hNT-4／5蛋白,以不同水平的重组hNT4／5蛋白（0－100μl）与不同浓度的As2O3（0－160μmol／L）同时加入各组鸡胚前脑神经细胞和PC12细胞培养液中共同孵育24－48小时,观察其对染毒鸡胚前脑神经细胞存活和PC12细胞突起生长的影响作用。结果在鸡胚前脑神经细胞和PC12细胞中与As2O3共同培养48小时后,对照组与实验组的细胞存活率差异有显著性,而且细胞存活率和突起数目随hNT－4／5浓度增高而提高和增加。结论初步观察到重组hNT4／5蛋白具有抑制As2O3的毒性作用,为从基因工程途径寻找抗环境毒物因子提供了依据。     

坦克作业条件下驾驶室内挥发性有机物定性分析

目的：了解某型坦克作业条件下驾驶室内挥发性有机物的污染状况,为制定防治措施提供科学依据。方法：应用气相色谱－质谱联用技术（ＧＣ－ＭＳ）对某型坦克单纯行进,行进打炮,停车打炮等工作状态下驾驶室内以及废气排放口的挥发性有机物（ＶＯＣｓ）进行了全谱分析,结果：共检出１３４种污染物质,包括脂肪烃类,单环芳烃类,多环芳烃类以及机酸,碱,酯,醛,酮,杂环化合物等。结论：实验结果表明这些物质主要来源于油类蒸汽,     

Inhibition of colony formation in agarose of metastatic human breast carcinoma and melanoma cells by synthetic glycoamine analogs

We studied the influence of 10 synthetic glycoamine analogs on colony formation in 0.3 and 0.9% agarose by metastatic human breast carcinoma (MDA-MB-435) and melanoma (TXM-13) cells. Nine synthetic analogs significantly inhibited the colony formation in 0.9% agarose of MDA-MB-435 human breast carcinoma cells; five compounds caused a 73–83% reduction of colony formation. Seven synthetic glycoamines caused a significant inhibition of colony formation in 0.9% agarose by TXM-13 melanoma cells with the inhibitory effect ranging from 71 to 87%. The 50% inhibition (I₅₀) doses and relative activity rank of the compounds were similar for both breast carcinoma and melanoma cell lines. The murine B16 melanoma cell aggregation assay was employed to elucidate the potential mechanism(s) of the inhibitory activity of synthetic glycoamines. The relative activity ranks of the compounds based on the independently determined I₅₀ doses for both cell aggregation and clonogenic growth assays were very similar for the four most active synthetic analogs and clearly indicated the importance of hydrophobic amino acid in mediating the bioactivity of synthetic glycoamines. In both experimental systems (clonogenic growth in agarose and cell aggregation assay) the leading compound was N-(1-deoxy-d-fructos-1-y1)-d-leucine (Fru-d-Leu) and the least active analog was N-(1-deoxy-d-fructos-1-yl)-glycine (Fru-Gly). These results show that synthetic glycoamines may act by competing for specific carbohydrate-lectin interactions, particularly those involving -galactoside-specific lectins expressed on metastatic cells.     

Reactivating and protective effects of pyridinium compounds in human erythrocyte acetylcholinesterase inhibition by organophosphates in vitro

The reactivation of human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7) inhibited by O-ethyl-S-2-di-isopropylaminoethyl methylphosphonothioate (VX) and the protection against AChE inhibition by O-1,2,2-trimethylpropyl methylphosphonofluoridate (Soman) was studied with sixteen quaternized pyridinium compounds. TMB-4 which is known as a good reactivator of AChE inhibited by organophosphates proved to be the most effective reactivator. Of the tested newly synthetised compounds 3 were fairly good reactivators of methylethoxyphosphonylated AChE. These compounds have 2 pyridinium rings connected by a dimethylether link and a hydroxiiminomethyl group in position 2 of one pyridinium ring, while the radicals of the other pyridinium ring are benzoylcarbonyl, cyclohexylcarbonyl or amidocarbonyl residue.The rate of reactivation with these compounds followed a two-phase pattern, being fast at the beginning and then slowing down to an equilibrium. Kinetic treatment of the first-phase reaction course yielded the second-order rate constants of reactivation. All 3 compounds had similar reactivating efficiency (k _r values range from 0.8×10³ to 3.6×10³ M^–1 min^–1) and in effective concentrations (1 to 100 M) they also inhibited AChE (K _i(app) values range from 0.11 to 0.19 mM). Their reactivating properties were not better than those revealed by TMB-4 (k _r= 19.4×10³ M^–1 min^–1) which was tested as a reference compound.HGG-12, HGG-42 and HI-6 were also found to exert a good protective effect against AChE inhibition by Soman; no protection was obtained with TMB-4.