Two selective 5-HT1A receptor antagonists, WAY-100 635 and NDL-249, stimulate locomotion in rats acclimatised to their environment and alter their behaviour: a behavioural analysis

The aim was to study firstly, the motor effects of a new 5-HT_1A antagonist, NDL-249 [(R)-3-(N-cyclopentyl-N-propylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide hydrochloride] and of the reference 5-HT_1A antagonist WAY-100 635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride], in comparison to the 5-HT_1A agonist (±)-8-OH-DPAT [(8-hydroxy-2-(di-N-propylamino) tetralin, hereafter 8-OH-DPAT], in rats acclimatised to the automated activity cages; secondly, to study whether the behavioural effects of NDL-249 and 8-OH-DPAT are sensitive to the 5-HT depleting effects of p-chlorophenylalanine (PCPA); thirdly, to characterise the nature of the antagonist-induced activation seen in the automatic activity cages with the aid of a behavioural observation analysis; fourthly, to examine the interaction between the 5-HT_1Areceptors mediating the behavioural effects and dopamine (DA) receptors. NDL-249 was found to bind in vitro to rat hippocampal 5-HT_1A receptors with high affinity and selectivity. In second messenger studies, it was devoid of agonist-like effects. In the locomotor activity studies, each antagonist significantly increased the incidence of horizontal activity, peripheral activity and rearing. 8-OH-DPAT, while significantly increasing peripheral and horizontal activities, decreased the incidence of rearing. PCPA blocked the motor effects of NDL-249 but did not affect those of 8-OH-DPAT. Observational analyses indicated that NDL-249 induced significant increases at one or more doses in sniffing, rearing and locomotion together with a significant reduction in stillness. WAY-100 635 significantly increased the incidence of rearing, intense grooming and vacuous chewing. The significant increases in sniffing, grooming and intense grooming and the significant decrease in stillness induced by the DA D₁ agonist, SK&F 38393 [(±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride], were not altered by concomitant pre-treatment with NDL-249. Pre-treatment of rats with either the DA D₁ antagonist SCH-23390 (2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) or the DA D₂ antagonist, raclopride, blocked the reduced stillness and increased sniffing and rearing induced by NDL-249. In conclusion, 5-HT_1A antagonists including the new selective antagonist, NDL-249, induce mild behavioural activation in rats, which is mediated probably indirectly via DA systems. Received: 3 April 1997/Final version: 23 February 1998     

下体负压作用下心率变异性的线性和非线性动力学分析

为了评估下体负压作用下心率变异性的变化，本文应用了时域，频域分析和复杂度分析了ＨＲＶ。受试者为１５名健康男性。下体负压作用的强度和时间分别为－２．７ｋＰａ，２ｍｉｎ；－４．０ｋＰａ，３ｍｉｎ；－５．３ｋＰａ，５ｍｉｎ；－６．７ｋＰａ，１０ｍｉｎ。     

胃微小腺癌的组织发生研究

从２１０５例胃癌癌旁组织中找出微小腺癌３１例（〈０．１ｃｍ），观察其组织发生的特征，发现胃腺癌的发生有８种形式：①腺颈部干细胞癌变；②表面上皮癌变；③腺上皮癌变；④肠化生上皮癌变；⑤微腺囊癌变；⑥溃疡边缘上皮癌变；⑦扁平腺瘤癌变；⑧贲门交界处柱状上皮癌变。     

江苏省肾综合征出血热单价灭活疫苗中期免疫效果观察

观察HFRS单价灭活疫苗中期免疫效果。方法：采用IFAT法及MCPENT法检测荧光抗体及中和抗体。结果：3个试区加强接种人数分别为4052、4407和6354人。加强后，Ⅰ型苗荧光抗体阳性率为72．73％，GMT为14.14；中和抗体阳性率为54．55％，GMT为6．67。D型苗荧光抗体阳性率为75.00％，GMT为11.85；中和抗体阳性率为60％，GMT为9．44。加强后1年，Ⅰ型苗年均保护率为65．52％，Ⅱ型苗则为94．24％。同期，Ⅰ型苗荧光抗体阳性率维持在40％，中和抗体维持在35．00％；Ⅱ型苗荧光抗体阳性率降至10．34％，中和抗体维持在53．85％。结论：两型疫苗均有较好的中期防病效果。     

“C”型曲线的中耳声学特性改变与鼓室积液的关系

对40耳声导抗检查为“C”型曲线患耳进行中耳系统共振频率点测试并进行鼓室穿刺抽液,结果表明:共振频率点低于600Hz,患耳鼓室积液阳性率为82.1%,高于600Hz患者鼓室和液阳性率16.7%,提示依据鼓室导抗图和共振频率点测定可初步判断“C”型曲线患耳鼓室积液的可能.     

响洪甸放射性废物坑放射卫生学调查及评价

本文调查了一个铀水冶厂放射性废物坑的污染情况,发现该坑周围农田及坑附近淠史杭大灌渠水、泥等均受到不同程度污染。这表明,即使处理小型铀水冶厂的放射性废物,在选址、掩埋等各个环节也都应严格做到科学、合理,并且还要做好掩埋后的管理工作。     

Pulsed magnetization transfer spin-echo MR imaging

Cross relaxation between macromolecular protons and water protons is known to be important in biologic tissue. In magnetic resonance (MR) imaging sequences, selective saturation of the characteristically short T2 macromolecular proton pool can produce contrast called magnetization transfer contrast, based on the cross-relaxation process. Selective saturation can be achieved with continuous wave irradiation several kilohertz off resonance or short, intense 0° pulses on resonance. The authors analyze 0° binomial pulses for T2 selective saturation, present design guidelines, and demonstrate the use of these pulses in spin-echo imaging sequences in healthy volunteers and patients. Using the phenomenologic Bloch equations modified for two-site exchange, the authors derive the analytic expressions for water proton relaxation under periodic pulsed saturation of the macromolecular protons. This relaxation is shown to be monoexpo-nential, with a rate constant dependent on the saturation pulse repetition rate and the individual and cross-relaxation rates.     

头孢托仑酯随机双盲对照治疗细菌性感染临床评价

为评价头孢托仑酯（ＭＥ１２０７）治疗细菌性感染的有效性和安全性，采用随机双盲对照试验和开放试验方法共治疗８０例患者，其中ＭＥ１２０７（Ａ药）与头孢克肟（Ｂ药）随机双盲各治疗２０例（呼吸系统和泌尿系统各１０对），ＭＥ１２０７开放试验治疗４０例（呼吸系统２０例、泌尿系统１０例、皮肤软组织感染１０例）。每日４００ｍｇ，疗程７～１４ｄ。ＭＥ１２０７痊愈率和有效率在对照试验中为８０％和９５％，在开放试验中为７５％和９２．５％，总痊愈率为７６．７％，总有效率为９３．３％，细菌培养阳性率为１００％，细菌清除率在对照试验和开放试验中分别为９５％和９２．５％。纸片法药敏试验中ＭＥ１２０７敏感株百分率为１００％，与头孢哌酮相同，而优于头孢克肟和头孢克洛，明显优于阿莫西林（４８．８％）。ＭＥ１２０７６０例中６例出现不良反应，表现为消化道反应３例，转氨酶升高２例，凝血酶原时间延长１例。与对照药头孢克肟相比在痊愈率、有效率、细菌清除率及不良反应发生方面均无显著性差异（Ｐ＞０．０５）。ＭＥ１２０７在每日４００ｍｇ剂量下治疗轻、中度细菌感染安全、有效。     

The Alkaloids of Melodinus acutiflorus. Rhyzicine N-Oxide

From the leaves of MELODINUS ACUTIFLORUS a new alkaloid, rhazicine N-oxide ( 2), and two known compounds, deacetylakuammiline ( 3) and 16- EPI-rhazinaline ( 4) were isolated. The structure of 2 was determined by spectral analysis and chemical correlation with rhazicine ( 1).     

Dose-response curves of homovanillic acid in pre-frontal cortex and caudate following antipsychotic drugs: relation to clinical potencies

Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol fluphenazine > loxapine > trifluoperazine > thiothixene > molindone > clopenthixol > chlorpromazine > metoclopramide > thioridazine > clozapine > sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre-frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose.