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 DDVP 2 mg,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0.2 mg,仅少数动物(1/3)的肋间外肌放电开始恢复,当加大剂量至0.25 mg 时,部分动物的两种放电才恢复(2/6)。注射 PCHE 0.2mg,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。     

MS-302三道测量分析系统的应用及HI-6在离体膈神经-膈肌上抗梭曼的作用机制探讨

目的 探讨抗神经毒化合物HI-6在离体膈神经．膈肌上抗梭曼的作用机制。方法采用MS．302三道测量分析系统,观察大鼠离体膈神经．膈肌的收缩功能,同时,测定膈肌乙酰胆碱酯酶（AChE）活性,观察药物对膈肌AChE活性的直接影响。结果（I）采用MS．302三道测量分析系统对膈神经．膈肌标本强直收缩曲线下的面积进行测量．较为直接地反映了膈神经．膈肌标本的生理功能,结果精确。（2）HI-610和100μmol／L对正常膈神经．膈肌收缩功能影响不明显,1mmol／L对正常膈神经．膈肌收缩功能有抑制作用。HI-610μmol／L预防和治疗给药时．对梭曼抑制的标本收缩功能既没有保护作用也没有拮抗作用;100μmol／L给药有一定的保护和拮抗作用;剂量增加到1mmol／L时。保护作用和拮抗作用都明显增强,且保护作用在30min内最佳。（3）预先给予HI-6不能减弱梭曼对大鼠离体膈肌AChE的抑制．梭曼中毒后给予HI．6对梭曼抑制的膈肌AChE活性无显著影响。结论HI．6对梭曼抑制的离体膈神经．膈肌收缩功能的恢复可能是直接生理对抗作用,在本实验条件下未见膈肌酶活力有明显的恢复。     

盐酸戊乙奎醚对全子宫切除术患者血浆胃动素的影响

目的评价盐酸戊乙奎醚对全子宫切除术患者血浆胃动素的影响。方法择期行全子宫切除术患者40例,ASAⅠ或Ⅱ级,年龄33～56岁,随机分为2组：盐酸戊乙奎醚组（P组）和阿托品组（A组）,每组20例。P组肌内注射盐酸戊乙奎醚1mg,A组肌内注射阿托品0.5mg。药物注射后45min进行硬膜外麻醉,L2,3部位头侧置管3.5cm,药物选用0.75%罗哌卡因,麻醉期监测心电图（ECG）、血压（BP）、心率（HR）和血氧饱和度（SpO2）。分别于注射前、麻醉前、术后24h和术后72h取血测定血浆胃动素浓度。结果注射前P组与A组的胃动素比较,差异无统计学意义（P（0.05）。麻醉前,A组的胃动素水平低于注射前水平,差异有统计学意义（P〈0.05）,但P组的胃动素水平与注射前比较差异无统计学意义（P（0.05）。P组与A组比较,差异有统计学意义（P〈0.05）。（3）术后24h,2组胃动素水平均低于注射前和麻醉前水平（P〈0.05）,但P组与A组比较,2组差异无统计学意义（P（0.05）。（4）术后72h,P组和A组的胃动素水平已恢复至接近注射前水平,与注射前比较差异无统计学意义（P（0.05）。结论与阿托品比较,盐酸戊乙奎醚不抑制胃动素的分泌。     

M_1，M_2受体激动剂和阻滞剂对犬呼吸的影响

目的：研究Ｍ１和Ｍ２受体激动剂和阻滞剂对犬呼吸的影响．方法：用ＲＭ８６多导生理记录仪通过胸带式呼吸换能器测定ＲＲ，ＴＶ和ＭＶＶ，并取动脉血测ｐＯ２，ｐＣＯ２和ｐＨ．结果：发现Ｍ１Ｒ激动剂Ｐｉｌ和Ｍ２Ｒ激动剂６βＡＮｉｖ或椎动脉给药分别产生呼吸兴奋和抑制，ＲＲ，ＭＶＶ增高或降低（Ｐ＜００５），血气亦出现相应变化．Ｍ１Ｒ阻滞剂Ｐｉｒ，Ｓｃｏ和Ｍ２Ｒ阻滞剂ＡＦＤＸ１１６，Ａｔｒ分别拮抗甚至翻转Ｐｉｌ的呼吸兴奋和６βＡＮ的呼吸抑制作用．结论：激动呼吸中枢Ｍ１Ｒ呼吸兴奋，激动呼吸中枢Ｍ２Ｒ呼吸抑制，阻断之则作用相反．     

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）。     

云芝糖肽对丘脑束旁核神经无痛诱发放电的影响

以刺激大鼠坐骨神经作为伤害性刺激，记录丘脑束旁核（Pf）神经元的伤害性放电为指标，观察云芝糖肽（PSP）对这种伤害性反应的影响，并进行药理学分析。结果如下：1．PSP能明显抑制Pf神经元的伤害性放电（P＜0．05）。2．纳洛酮（1mg／kg）能翻转PSP对Pf神经元的伤害性放电的抑制。3．注射5-羟色胺（5－HT）合成抑制剂对氯苯丙氨酸（PCPA）后，PSP的抑制作用消失。以上结果说明了PSP的镇痛作用可能是通过阿片能神经元系统和5－HT能神经元系统的调制而起作用的。     

治疗婴幼儿腹泻的几种方法

1硫酸阿托品足三里穴位注射[1]硫酸阿托品流射液0．01mg／kg一次加注射用水稀释2ml，垂直刺入足三里穴位约5分～1寸回抽无血后快速推药，每侧各IM，每天1～2次，连续3天。同时给婴儿素散、胃蛋白酶合剂、复合维生素B，脱水者给予口服补液或静脉补液。结果：总有效率达94％。治疗中除出现一过世面部潮红、口干外无其他副作用。2潘生丁治疗婴幼儿腹泻[2]治疗组（A）给予潘生丁3～5mg／（kg·d），分3次口服或肌注，连用5～6天。对照组（B）口服SMZCO或肌往，静注庆大霉素等，连用5～6天。结果：A组80例，显效45例，有效30例，无效5例，显…     

格瑞1号油和2号油对致敏豚鼠抗原攻击后肺机械功能的影响

目的：观察格瑞1号油及2号油对致敏豚鼠抗原攻击后引起肺阻力增高和动脉肺顺应性降低的影响，评估两的平喘作用。方法：采用卵白蛋白10mg和氢氧化铝凝胶200mg后腿部肌内注射致敏豚鼠，3－4周后予以抗原攻击（1％卵白蛋白）引起肺阻力（RL）和动态肺顺应性（Cdyn)变化来观察格瑞1号油和2号油药效。结果：格瑞1号油和2号油4g/kg、8g/kg均能明显抑制抗原攻击引起的RL增高，1号原油8g/kg和2号原油8g/kg能明显抑制抗原攻击引起的Cdyn降低。模型组（0.9%NaCl 4ml/kg于抗原攻击前1h,ig)在抗原攻击后RL非常明显的增高。Cdyn非常明显的降低，攻击后1－10min变化最为明显，10min后趋于逐渐恢复。1号油和2号油4g/kg、8g/kg组和沙丁胺醇4mg/kg组在抗原攻击后5、10、15min均显示出对RL增高有明显抑制作用（与模型组比较P＜0．05）。在抗原攻击后3min及20min，只有1号油8g/kg组和沙丁胺醇4mg/kg组对Cdyn降低有明显抑制作用（与模型组比较P＜0．05），而1号油4g/kg组、2号油4g/kg、2号油8g/kg组有抑制趋向，但无明显差异（P＞0．05）。在抗原攻击后5min，1号油8g/kg组和沙丁胺醇4mg/kg组对Cdyn降低均有明显抑制作用（与模型组比较P＜0．05），而其他组无明显差异（P＞0．05）。从上述结果可以观察到格瑞1号油和2号油在对致敏豚鼠抗原攻击后引起RL和Cdyn变化的高峰期内的作用比较明显，恢复的比较快。结论：格瑞1号油和2号油对致敏豚鼠抗原攻击后建立的哮喘模型呈明显保护作用。     

3，4—二氨基吡啶诱发去甲肾上腺素释放及B—50（GAP—43）磷酸化

在胞外有Ca^2 或无Ca2 时，3，4－二氨基吡啶（3，4－DAP）都能诱发大鼠海马释放去甲肾上腺素，咐 拜醇基酯（phorbol ester) 或多粘菌素B对此诱发释放有加强或抑制作用，在胞外有Ca2 时，3，4－DAP显著地减弱B－50磷酸化，除去胞外Ca2 ,B-50磷酸化完全被抑制，结果表明，B－50磷酸化不参与3，4－DAP诱发海马去甲肾上腺素释放机制。     

盐酸戊乙奎醚作为麻醉前用药的效果观察

目的观察麻醉前应用盐酸戊乙奎醚对患者麻醉期间血压、心率、术后呼吸道分泌物等的影响及不良反应情况，探讨盐酸戊乙奎醚在临床麻醉中应用的效果。方法60例ASAⅠ～Ⅱ级需行择期上腹部手术且无心血管系统和中枢神经系统疾病的患者，随机分为3组各20例。待患者入室安静15 min后，阿托品组肌内注射阿托品0.5 mg，东莨菪碱组肌内注射东莨菪碱0.3 mg，盐酸戊乙奎醚组肌内注射盐酸戊乙奎醚0.5 mg。20 min后进行麻醉诱导和气管插管，术中机械通气，记录用药（指阿托品、东莨菪碱或盐酸戊乙奎醚）前(T0)，用药后10(T1)，20 min(T2)，麻醉诱导前(T3)，气管插管前(T4)，气管插管后即刻(T5)，气管插管后10 min(T6)，手术结束(T7)和气管拔管时(T8)患者的收缩压、舒张压、心率、血氧饱和度。评定镇静程度和焦虑程度，观察有无并发症。结果盐酸戊乙奎醚组患者监测期间血压水平更接近正常范围， T2、T3、T4时收缩压较阿托品组和东莨菪碱组低，且均差异有显著性(均P＜0.05)；T2、T3、T4、T5时舒张压较阿托品组和东莨菪碱组低，且均差异有显著性(均P＜0.05)；盐酸戊乙奎醚组手术过程中呼吸道分泌物较阿托品组少，差异有显著性(P＜0.05)。结论盐酸戊乙奎醚作为术前用药时，对心率和血压影响较小，抑制腺体分泌的作用强于阿托品和东莨菪碱。     

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.     

Pyrazino(1,2-a)- and 1,4-diazepino(1,2-a)- indoles. III. Synthesis of pyrrolo(2',1':3,4)pyrazino(1,2-a)indoles and pyrrolo(2',1':3,4)-1,4-diazepino(1,2-a) indoles; isoindolo(2',1':3,4)pyrazino(1,2-a)-indoles and isoindolo(2',1':3,4)-1,4-diazepino(1,2-a)indoles; pyrazino(3,2,1-jk)- carbazoles and 1,4-diazepino(3,2,1-jk) carbazoles]

Pyrrolo(2',1':3,4)pyrazino (or 1,4-diazepino) (1,2-a)indoles and isoindolo(2',1':3,4)pyrazino (or 1,4-diazepino) (1,2-a)indoles were synthesized by reaction of 1-(2-aminoethyl)indole or 1-(3-aminopropyl)indole with gamma-keto and o-acylbenzoic acids. In addition, a novel synthetic route for the preparation of pyrazino(3,2,1-jk)- and 1,4-diazepino(3,2,1-jk)carbazoles has been realized.     

Synthesis and characterization of oligonucleotides containing 5',8-cyclopurine 2'-deoxyribonucleosides: (5'R)-5',8-cyclo-2'-deoxyadenosine, (5'S)-5',8-cyclo-2'-deoxyguanosine, and (5'R)-5',8-cyclo-2'-deoxyguanosine.

Radiation-induced degradation of purine and pyrimidine nucleosides gave rise to carbon-bridged cyclocompounds. Such cyclonucleosides represent a class of tandem lesions in which modification of both the base and 2-deoxyribose has occurred. A solid-phase synthetic method was designed for the incorporation of both 5'R and 5'S diastereoisomers of 5',8-cyclopurine 2'-deoxyribonucleosides into oligodeoxynucleotides to facilitate the assessment of the biochemical and biophysical features of such lesions. We report the preparation of the phosphoramidite synthons of (5'R)-5', 8-cyclo-2'-deoxyadenosine (2), (5'S)-5',8-cyclo-2'-deoxyguanosine (3), and (5'R)-5',8-cyclo-2'-deoxyguanosine (4). Fully protected compounds 10, 18, and 25 were then inserted into several oligonucleotides by automated procedures. Analysis of modified DNA oligomers 26-31 by electrospray mass spectrometry and enzymatic digestions with exo- and endonucleases confirmed the base compositions and the integrity of free radical-induced tandem lesions 2-4 that were chemically inserted.     

Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein) on the pituitary-thyroid axis in rats

Erythrosine (FD&C Red Dye No.3) is a tetraiodinated derivative of fluorescein. Rats fed a 4% erythrosine diet for 30 months beginning in utero have an increased incidence of thyroid adenomas and adenocarcinomas. These tumors may be secondary to increased stimulation of the thyroid gland by TSH. This study was undertaken to determine if dietary erythrosine disrupts the pituitary-thyroid axis thereby altering serum thyroid hormone levels. TSH levels, or the pituitary's response to TRH. Rats were fed diets containing erythrosine (0.5, 1.0, 4.0%), sodium iodide (0.16%), or fluorescein (1.6%) for 3 weeks after which TRH testing was performed in vivo. Erythrosine produced a dose-dependent increase in serum T4 levels. With the 4% erythrosine diet, serum T4 and T3 levels and the free-T4 index were significantly increased, whereas the free-T3 index were significantly increased, whereas the free-T3 index was unchanged. Rats fed the 4.0% erythrosine diet had an exaggerated TSH response to TRH; 10 min after the TRH injection, serum TSH levels were 80% greater than TSH levels of control rats. Short-term administration of erythrosine to rats decreased hepatic T3 production by decreasing its conversion of T4 to T3, indicating that erythrosine decreases hepatic 5'-deiodinase activity. These data demonstrate that dietary ingestion of 4% erythrosine disrupts the pituitary-thyroid axis as evidenced by an increased TSH response to TRH. This effect is mediated by erythrosine or an iodinated metabolite, since ingestion of its fluorescein nucleus had no effect. Erythrosine's effects were not likely mediated by iodide, because serum T4 and T3 levels were elevated and iodide administration did not increase the TSH response to TRH. These data suggest that erythrosine increases the pituitary's TSH response to TRH by altering thyrotroph cell conversion of T4 to T3. Chronic erythrosine ingestion may promote thyroid tumor formation in rats via chronic stimulation of the thyroid by TSH.     

Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein) on thyroid function in normal men

Erythrosine (Er), a tetraiodinated derivative of fluorescein, is a coloring agent widely used in foods, cosmetics, and pharmaceutical products. Because of its high iodine content and previous reports demonstrating an inhibitory effect of erythrosine on hepatic 5'-monodeiodination, we studied the effects of this compound on thyroid function and serum and urinary iodide concentrations in normal subjects. Thirty normal men, equally divided into three treatment groups, each received a 14-day course of oral Er in doses of 20, 60, or 200 mg/day. Serum thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), thyroid stimulating hormone (TSH), protein-bound iodide (PBI), and total iodide concentrations, serum T3-charcoal uptake, and 24-hour urinary iodide excretion were measured on Days 1, 8, and 15. Thyrotropin-releasing hormone (TRH) tests were performed on Days 1 and 15. There were no significant changes in serum T4, T3, rT3, and T3-charcoal uptake values at any dose. In men receiving 200 mg Er/day, the mean basal serum TSH concentration increased significantly from 1.7 +/- 0.1 (SE) on Day 1 to 2.2 +/- 0.1 microU/ml on Day 15 (p less than 0.05), and the mean peak TSH increment after TRH increased from 6.3 +/- 0.5 to 10.5 +/- 1.0 microU/ml (p less than 0.05). There were no significant changes in basal or peak TSH responses in the men receiving 20 or 60 mg Er/day. Significant dose-related increases in serum total iodide and PBI concentrations occurred during all three doses, and significant dose-related increases in urinary iodide excretion occurred during the 60 and 200 mg/day Er doses. These data suggest that the increase in TSH secretion induced by Er was related to the antithyroid effect of increased serum iodide concentrations, rather than a direct effect of Er on thyroid hormone secretion or peripheral metabolism.     

Oligonucleotide structural parameters that influence binding of 5'-O-triphosphoadenylyl-(2'----5')-adenylyl-(2'----5')-adenosine to the 5'-O-triphosphoadenylyl-(2'----5')-adenylyl-(2'----5')-adenosine dependent endoribonuclease: chain length, phosphorylation state, and heterocyclic base

A number of 2',5'-linked oligoadenylates and their analogues were prepared and evaluated for their ability to interact with the 5'-O- triphosphoadenylyl -(2'----5')-adenylyl-(2'----5')-adenosine (2-5A) dependent endoribonuclease of mouse L cells. The oligonucleotides were assayed for their ability to antagonize the action of 2-5A, to displace a radiolabeled probe from the 2-5A-dependent nuclease, or to inhibit translation in a cell-free system. These experiments demonstrated the following: (1) Three AMP residues in a 5'-phosphorylated oligonucleotide were needed for maximum interaction with the endonuclease, and higher oligomers (greater than or equal to 4 AMP residues) did not show significantly higher binding. (2) The third (2'-terminal) adenosine residue was required for optimal binding activity. (3) 5'-Phosphorylation of the oligonucleotide was necessary for maximum binding to the endonuclease, but the first (from the 5' terminus) internucleotide phosphate of higher unphosphorylated or core oligomers, such as A2'p5'A2'p5'A2'p5'A, may partly replace the requirement for a 5'-monophosphate moiety; in agreement with this, the 5'-methyl ester of 5'pA2'p5'A2'p5'A, i.e., Me-p5'A2'p5'A2'p5'A, was bound to the endonuclease as well as or better than the higher core oligomers but approximately 100 times more effectively than the trimer core, A2'p5'A2'p5'A. (4) Base-modified analogues, such as p5'C2'p5'C2'p5'C, p5'U2'p5'U2'p5'U, or p5'I2'p5'I2'p5'I, were at least 2000 times less effectively bound to the endonuclease than p5'A2'p5'A2'p5'A. (5) The triphosphate ppp5 'I2'p5'I2'p5'I was 10 000 times less active than 2-5A as an inhibitor of translation. These latter two points implied the critical role of the adenine N1-nitrogen and/or exocyclic amino group in the binding of 2-5A to the endonuclease.