N-(3’,4’,5’-三甲氧基肉桂酰)邻氨基苯甲酸对抗原诱发的离体豚鼠回肠收缩、大鼠肥大细胞脱颗粒及组胺释放的影响

实验证明 N-(3′,4′,5′-三甲氧基肉桂酰)邻氨基苯甲酸(TOA)管内浓度80μg/ml 能明显抑制抗原诱发的主动致敏豚鼠离体回肠收缩。TOA 管内浓度25和50μg/ml 能显著抑制亲同种细胞抗体介导的大鼠肠系膜肥大细胞脱颗粒和腹腔肥大细胞组胺释放。     

HPLC法测定参芪鸡精中2，3，5，4′—四羟基二苯乙烯—2—O—β—D—葡萄糖苷的含量

采用HPLC法测定参芪鸡精中2，3，5，4′－四羟基二苯乙烯－2－O－β－D－葡萄糖苷的含量。色谱条件：用十八烷基烷键合硅胶为填充剂；乙腈－0.1%（V／V）磷酸（25：75）为流动相，检测波长320nm;8－40μg/ml范围内呈良好的线性关系（r=0.9996）；平均回收率93.5%，RSD＝3.5%(n=5）。     

HPLC法测定人尿中苯妥因及其代谢产物4′—羟基苯妥因

本文建立了RH－HPLC法测定人尿中苯妥因（PHT）及其代谢物4′－羟基苯妥因（HPPH），用乙醚为提取溶剂，5－对甲苯基－5－苯基乙内酰脲（MPPH）为内标。色谱分析用Hil-SilODS柱，含40％乙腈的水溶液为流动相。PHT和HPPH的线性测定范围为0．05－2．0μg/ml和1．0－100μg/ml，相关系数均优于0．99，平均回收率分别为98．9％和99．9％，平均变异系数分别为4．8％和4．7％。应用本法研究了88名健康志愿者PHT的遗传代谢多态性。     

3—（2′，2′，2′—苯基环戊基羟基乙氧基）奎宁环对抗敌敌畏所致的呼吸中枢抑制

以乌拉坦麻醉猫膈神经放电及肋间外肌放电为指标（可分别反映延髓呼吸中枢背侧组DRG和腹外侧组VRG的活动），观察3－（2′，2′，2′－苯基环戊基羟基乙氧基）奎宁环（PCHE）对抗敌敌畏（DDVP）的呼吸中枢抑制作用，椎动脉（iva）注射DDVP2mg，膈神经放电立即被抑制，继之肋间外肌放电也抑制或先短暂兴奋再抑制，再于椎动脉注射阿托品0.2mg，仅少数动物（1/3）的肋间外肌放电开始恢复，当加大剂量至0.25mg时，部分动物的两种放电才恢复（2／6）。注射PCHE0.2mg，可使大部分动物（5／6)的两种放电同时恢复，提示DDVP优势影响DRG，阿托品对VRG的作用要比DRG明显，PCHE对DRG及VRG均有较强的作用；PCHE在低于阿托品剂量就可产生更强的对抗DDVP所致的呼吸中枢抑制作用。     

一些2′-氟-2′-去氧呋喃阿拉伯糖基嘧啶核苷类的合成及其抗疱疹病毒活性

本文报道了一系列5-取代-1-(2-去氧-2-氟-β-D-呋喃阿拉伯糖基)胞嘧啶Ⅰ(a-e)及相应尿嘧啶衍生物Ⅱ_(a-t)的合成。某些2′-氟代核苷在10～100μg/ml浓度时能完全抑制1型单纯疱疹病毒(HSV-1)在单层Vero细胞中的复制。最有效者为5-碘胞嘧啶衍生物I_e,它即使在浓度仅为0.1μg/ml时,对病毒复制的抑制率达99.5％。I_e在培养基中对L5178Y或P815细胞的细胞毒性是最低限度的。经比较I_e及其它已知抗病毒核苷对HSV-1的功效表明,值得进一步在管内及     

二异丁香酚抑制血小板血栓素形成和磷酸肌醇分解

血小板激活或血栓形成与血栓素入有关。血小板激活的首要环节是使磷酸肌醇（phosphoinositides）分解。抑制血小板功能可望预防血栓形成。作者研究了二异丁香酚（diisoeugenol）的抗血小板作用。研究结果发现，当二异丁香酚浓度为20μg／ml时，ADP（20μM）、花生四烯酸（100μM）或胶原（10μg／ml）等诱发的兔血小板聚集被明显抑制（P＜0．05～0．01）2浓度更高时（50μg／ml）则被完全抑制，并显著抑制血小板激活困于（Platelet－activatingfactor，PAF，2ng／ml）和凝血酶（0．1U／ml）诱导的血小板聚集（P＜0．01）。环氧合酶抑制…     

小儿骶管注射咪唑安定镇痛作用探讨

目的 探讨行骶管内注射咪唑安定用于小儿腹股沟斜疝修补术的镇痛效果。方法 60例行腹股沟斜疝修补术患儿，随机分为4组，单次骶管内分别注入1％利多卡因0.8ml/kg、（15利多卡因＋0.25%布比卡因）0.8ml/kg、（1％利多卡因＋0.25%布比卡因）0.8ml/kg 咪唑安定50μg/kg、1％利多卡因0.8ml/kg 咪唑安定50μg/kg，观察镇痛效果及副作用。结果 骶管内注用咪唑安定50μg/kg与注用0.25%布比卡因0.8ml/kg产生相同的镇痛效果，无呼吸抑制和其他副作用。结论 在小儿腹股沟斜疝修补术时骶管内注用咪唑安定具有镇痛作用明显、无副作用的优点。     

胞磷胆碱钠及其注射液的HPLC测定

建立了测定胞磷胆碱钠和有关物质的HPLC法。采用阴离子交换柱（Partisil-5 SAX柱），0．05mol/L磷酸盐缓冲液（pH3．2－3．4）为流动相，流速1．0ml/min，检测波长为280nm。胞磷胆碱钠在20－250μg/ml浓度范围内，线性良好，r＝0．9991；平均回收率为100．2％。胞磷胆碱钠、胞嘧啶核苷、尿嘧啶核苷、5′－磷酸胞苷、磷酸胞苷－酰替吗啉－DDC、5′－磷酸尿苷和5′－尿苷二磷酸胆碱酯的日内与日间精密度均小于2．0％；最低检测限为0．1－5．2ng。     

黄芪有效成分研究：黄芪中清除超氧阴离子成分的分离和检测

本文使用黄嘌呤－黄嘌呤氧化酶－鲁米诺化学发光体系和化学发光检测法研究了黄芪中各成分的清除超氧阴离子自由基的能力，以药物抑制发光强度50％的浓度（IC50）为指标。经研究证明，黄芪总皂甙部分（N）具有较强的活性，IC50为185μg/ml，再经进一步导向分离并鉴定证明，黄芪甙Ⅲ，Ⅳ和Ⅵ的IC50分别为80、50和11μg/ml，从而证明黄芪的抗心力衰竭的有效成分可能为黄芪总皂甙部分。     

联用单磷酸阿糖腺苷和柴胡注射液抑制呼吸道合胞病毒的研究

目的：研究联用单磷酸阿糖腺苷（Ara-AMP)和柴胡注射液对呼吸道合胞病毒（RSV）的抑制作用。方法：用细胞培养法，采用Vero细胞先感染病毒2h后给药法观察细胞病变（CPE），结果：当100μg/ml的Ara-AMP和1000μg/ml的柴胡注射液联用时，对RSV的抑制呈最大协同作用，当3．125μg/ml的Ara-AMP与31．25μg/ml的柴胡注射液联用时则呈最小协同作用。两药联用的治疗指数（TI）为16，部分抑制浓度（FIC）指数为0．5，小于0．75，结论：联用Ara-AMP和柴胡注射液对RSV的抑制呈显著协同作用。     

Metabolism of 2,2',3,3',6,6'-hexachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl by human hepatic microsomes

Since the metabolism of polychlorinated biphenyls (PCBs) is the critical factor that determines whether or not they accumulate in adipose tissue, we have studied the metabolism of two hexachlorobiphenyls (HCBs), 2,2'3,3',6,6'-hexachlorobiphenyl (236-HCB) and 2,2'4,4',5,5'-hexachlorobiphenyl (245-HCB), by human hepatic microsomes. Human microsomes were isolated from patients undergoing liver resection and were found to have cytochrome P-450 levels (0.28 nmoles/mg microsomal protein) and cytochrome P-450-dependent enzymatic activities similar to those reported by other workers. 245-HCB was not metabolized by human microsomes under various conditions, while 236-HCB was metabolized with an apparent Km of 8.8 microM and a Vmax of 5.1 pmoles/mg microsomal protein/min. Two major metabolites were formed and identified by gas chromatography-mass spectrometry as 2,2',3,3',6,6'-hexachloro-4-biphenylol and 2,2',3,3'6,6'-hexachloro-5-biphenylol. [14C]236-HCB equivalents were found to covalently bind to microsomal protein. Addition of 1 or 5 mM reduced glutathione decreased the degree of covalent binding. These data suggest that HCBs are metabolized through an arene oxide. The fact that 245-HCB was not metabolized explains why it is the predominant PCB found in human adipose tissue.     

Postnatal exposure of 2,2',3,3',4,6'-hexachlorobiphenyl and 2,2',3,4',5',6-hexachlorobiphenyl on sperm function and hormone levels in adult rats

Polychlorinated biphenyls (PCBs) are known to affect reproductive system in animals and in accidentally or occupationally exposed humans. Information is lacking on effects of non-dioxin like chlorinated biphenyls (CB) congeners on male reproduction. The aim of this study is to determine whether treatment of postnatal non-dioxin like CB congeners affects sperm function and hormone levels in rats. Male Sprague-Dawley rats received either 2,2',3,3',4,6'-hexachlorobiphenyls (CB 132) or 2,2',3,4',5',6-hexachlorobiphenyls (CB 149) by ip injection of 9.6 or 96 mg/kg at day 21. At 16 weeks, the animals were sacrificed; sperm quality and hormone levels were measured. Body weight, testis and cauda epididymis weights, sperm counts, ROS generation, acrosome reaction rate, serum thyroxine (T(4)), free T(4) and testosterone (TT) concentrations were unaffected. However, treatment of CB 132 and CB 149 caused decreases in sperm motility, curvilinear velocity (VCL), average path velocity (VAP), straight-line velocity (VSL), amplitude of lateral head displacement (ALH) and beat cross frequency (BCF). Serum triiodothyronine (T(3)) level was significantly decreased in CB 132 9.6 mg/kg dose group compared with the controls. On the other hand, a significant decrease was found in free T(3) concentration both in 96 mg/kg of CB 132 and CB 149 groups. In summary, this study showed that CB 132 and CB 149 affects serum levels of triiodothyronine as well as sperm motility, velocity and capability of penetrating oocytes. The mechanism of action and potential effects on human warrant further investigation.     

Toxicity of 3,4,5,3',4',5'-hexabrominated biphenyl and 3,4,3',4'-tetrabrominated biphenyl

Immature male rats were given a single equimolar dose (21.3 mumol/kg body wt) of 3,4,5,3',4',5'-hexabromobiphenyl (HBB) or 3,4,3',4'-tetrabromobiphenyl (TBB) and terminated at various times up to 14 days after treatment. Hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity for the TBB treatment group was maximal at Day 2 and then steadily decreased, whereas this activity was induced in 1 day and remained high for the HBB treatment group. Tissue concentrations of HBB appeared to be unchanged over time whereas tissue concentrations of TBB decreased in a biphasic manner. Rates of in vitro metabolism of TBB with hepatic microsomes from TBB-treated animals showed a similar time-course relationship to AHH induction. HBB caused moderate to severe hepatic changes while TBB-treated rats had only mild hepatic changes. The relative binding of TBB by the hepatic receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was about 10 times that of HBB. The results suggest that even though the receptor-binding affinities imply that TBB should be more toxic than HBB, it is less toxic than HBB because it is metabolized. Studies with the chlorinated analogs of TBB and HBB suggested that PCB behave similarly. These results also suggest that receptor binding and AHH induction do not accurately reflect toxicity for polyhalogenated aromatic hydrocarbons which are metabolized, presumably because continued occupation of the receptor and persistent induction of some enzyme activity are required for toxicity.     

Synthesis and complement inhibitory activity of B/C/D-ring analogues of the fungal metabolite 6,7-diformyl-3',4',4a',5',6',7',8',8a'-octahydro-4,6',7'-trihydroxy- 2',5',5',8a'-tetramethylspiro[1'(2'H)-naphthalene-2(3H)-benzofuran

This paper reports the synthesis and the bioassay of 4-methoxy- and 4-hydroxyspiro[benzofuran-2(3H)-cyclohexane] partial analogues (5) of the complement inhibitory sesquiterpene fungal metabolite 6,7-diformyl-3',4',4a',5',6',7',8',8a'-octahydro-4,6',7'-trihydroxy-2',5',5',8a'-tetramethylspiro[1'(2'H)-naphthalene-2(3H)-benzofuran] (1a, K-76) and its silver oxide oxidized product (1b, K-76COOH). The described target compounds represent spirobenzofuran B/C/D-ring analogues lacking the A-ring component of the prototype structure. The target compounds were evaluated by the inhibition of total hemolytic complement activity in human serum. It was observed that the structurally simplified analogue 4-methoxyspiro[benzofuran-2(3H)-cyclohexane]-6-carboxylic acid (5a) exhibited an IC(50) = 0.53 mM similar to the IC(50) = 0.57 mM that was observed for the natural product derivative 1b. Exhibiting an IC(50) = 0.16 mM, the three-ringed partial structure 6-carboxy-7-formyl-4-methoxyspiro[benzofuran-2(3H)-cyclohexane] (5k)was found to be the most potent target compound. Like the natural product, 5k appears to inhibit primarily at the C5 activation step and inhibits both the classical and alternative human complement pathways. Several other analogues inhibited complement activation in vitro at concentrations similar to those required for inhibition by the natural product 1b.     

Inhibition of 3,3',4,4',5-Pentachlorobiphenyl-Induced Chicken Embryotoxicity by 2,2',4,4',5,5'-Hexachlorobiphenyl

3,3',4,4',5-Pentachlorobiphenyl (pentaCB) caused a dose-dependentinduction of chicken embryolethality, malformations, edema,and liver lesions at doses ranging from 0.5 to 12.0 µg/kg.In contrast, no embryotoxicity was observed after treatmentwith 10, 25, or 50 mg/kg 2,2',4,4',5,5'-hexaCB. In eggs cotreatedwith 2.0 µ/kg, 3,3',4,4',5-pentaCB plus 10, 25, or 50mg/kg 2,2',4,4',5,5'-hexaCB, there was significant protectionfrom 3,3',4,4',5-pentaCB-induced embryo malformations, edema,and liver lesions, whereas no inhibition of embryolethalitywas observed. These results further extend the response-specificnonadditive interactions of binary mixtures of polychlorinatedbiphenyls (PCBs) and should be considered in the developmentof approaches for hazard assessment of PCB mixtures and relatedcompounds.     

Behavioural effects of dibutyryl cyclic 3',5' AMP, noradrenaline and cyclic 3',5' AMP in rats

It was shown that dibutyryl cyclic AMP (DAMP) injected intraventricularly in doses of 100–200 μg in rats causes the increase of locomotor and exploratory activity and convulsions, depending on the dose. DAMP increased excitatory behavioural effects of noradrenaline (NA) injected intraventricularly in doses of 10 or 50 μg. NA in a dose of 200 μg abolished convulsions evoked by DAMP. Cyclic AMP (cAMP) injected intraventricularly in doses of 100–400 μg had no effect on the rat's behaviour. Pretreatment of rats with dimethylsulphoxide and with theophylline caused in some animals behavioural phenomena after injection of cAMP, similar to the behavioural symptoms evoked by DAMP.     

Acute pathologic effects of 3,3',4,4',5,5'-hexabromobiphenyl in rats: comparison of its effects with Firemaster BP-6 and 2,2',4,4',5,5'-hexabromobiphenyl

Male Sprague-Dawley rats were fed diets containing 0, 0.1, 1, 10, or 100 ppm of 3,3′,4,4′,5,5′-hexabromobiphenyl (HBB), 2,2′,4,4′,5,5′-HBB, or Firemaster (FM) BP-6, a commercial mixture of polybrominated biphenyls, for 9 days. Although 3,3′,4,4′,5,5′-HBB is not in FM BP-6, it was used because it is a 3-methylcholanthrene (MC)-type inducer of hepatic drug-metabolizing enzymes. Nearly one-half of FM BP-6 is comprised of 2,2′,4,4′,5,5′-HBB and this congener is strictly a phenobarbital (PB)-type inducer. FM BP-6 has both MC- and PB-type induction capability. Feed consumption and body and organ weights were recorded and histologic and ultrastructural changes were evaluated. Significant effects on feed intake and body weight occurred only at 10 or 100 ppm of 3,3′,4,4′,5,5′-HBB. Therefore, two of six rats given 100 ppm of 3,3′,4,4′,5,5′-HBB were continued on the diet until death occurred at 20 days. Liver weights were increased by each of the three chemicals at 10 and 100 ppm. Hepatocytes were diffusely enlarged and contained lipid vacuoles. The degree of vacuolation was dose related, most prominent in the centrolobular to midzonal area, and most severe in rats given 3,3′,4,4′,5,5′-HBB. Thymic and splenic weights were decreased at 10 and 100 ppm of 3,3′,4,4′,5,5′-HBB and lymphocytic depletion was severe in the thymus. Ultrastructural hepatic lesions were seen with all three chemicals. For 2,2′,4,4′,5,5′-HBB and FM BP-6 at 10 and 100 ppm the changes consisted mainly of increased smooth endoplasmic reticulum and lipid vacuolation. Additional changes seen with 3,3′,4,4′,5,5′-HBB included disorganization of rough endoplasmic reticulum, myelin body formation, and bile ductule hyperplasia. Results indicated that 3,3′,4,4′,5,5′-HBB causes more severe pathologic effects than either FM BP-6 or 2,2′,4,4′,5,5′-HBB.