Treatment of mice with the anticoccidial drug Toltrazuril does not interfere with the development of a specific cellular intestinal immune response to Eimeria falciformis

Immunity against Eimeria-infections is highly specific and it depends on cell-mediated effector mechanisms. Infections of BALB/c mice with 1000 sporulated oocysts of Eimeria falciformis led to protection against challenge infections. Treatment with the anticoccidium Toltrazuril, during primary infection, terminated the ongoing disease and did not interfere with the establishment of protective immunity against challenge infections. Mesenteric lymph node cells of infected, treated as well as non-treated and challenged BALB/c mice, showed a similar proliferation upon stimulation with parasite antigen. In contrast, neither cells of the Peyers patches, intraepithelial lymphocytes, nor spleen cells responded to stimulation with parasite antigens. Cells from all compartments and of all investigated groups proliferated and released the cytokines IFN- and IL-4 in response to the mitogen Concanavalin A. The number of cells releasing IFN- or IL-4 was not dependent on the status of infection or previous treatment with Toltrazuril. The serum IgG response against total sporozoite antigens of individual mice showed that in addition, a systemic humoral response developed in infected mice, independent of a previous drug treatment, although the specific IgG antibody concentration was higher in non-treated mice. Thus, Toltrazuril does not impair the parasite specific intestinal cellular and systemic antibody response and does not prevent the development of protection against challenge infection.     

从频率因素分析振动对小白鼠体内~（125）Ⅰ－碘化钠的分布影响

本文系统地观察了不同频率的全身振动引起小白鼠对１２５Ｉ－碘化钠的吸收与分布作用。用放射免疫方法测定小白鼠体内不同组织中碘化钠的分布密度（ｃｐｍ／ｋｇ）。结果发现，振动能明显促进小白鼠对碘化钠的吸收速度。其中，心脏组织、肝脏组织、血液和肾脏组织中碘化钠的分布密度较对照组明显增多。且分布密度的大小依赖于振动频率的高低。同时，振动还能加快碘化钠在小鼠体内的耗散过程。     

不同浓度缺氧预适应小鼠脑匀浆提取液对PC12细胞缺氧耐受性的影响

目的： 探讨缺氧预适应小鼠脑匀浆提取液(HP extract)对PC12细胞缺氧耐受性的影响。方法: 复制小鼠急性重复缺氧模型，制备HP extract。在培养PC12细胞中加入HP extract使其终浓度分别为0.2、0.8、3.2、6.4、12.8 g/L(HP组)。以同浓度正常小鼠脑匀浆提取液(N extract)作为对照组(N组)。缺氧(2%O2) 培养24、48、72 h后, 采用四唑盐（MTT）比色法检测各组细胞活力 (A570值)并检测缺氧24、48、72 h乳酸脱氢酶（LDH）透出率、缺氧24 h早期凋亡率(Annexin V-FITC/PI双染流式细胞仪检测)、缺氧72 h晚期凋亡率(Hoechst33258染色荧光显微镜检测)。结果: HP extract浓度低于6.4 g/L(包括6.4 g/L), 缺氧培养24 h时, HP组A570值显著高于同浓度N组, 其 LDH透出率显著低于同浓度N组。随缺氧时间延长, 高浓度HP extract逐渐失去细胞保护作用。至72 h时浓度高于6.4 g/L(包括6.4 g/L)HP extract有促细胞凋亡作用, 此时HP组A570值显著低于同浓度N组, 其LDH透出率和晚期凋亡率均显著高于同浓度N组。结论: 缺氧预适应小鼠脑匀浆提取液对PC12细胞缺氧耐受性的影响呈浓度依赖性和时间依赖性。     

聪灵胶囊对小鼠软脑膜微循环障碍的改善作用

目的 观察聪灵胶囊对小鼠软脑膜微循环障碍的改善作用。方法 将60只小鼠随机分为聪灵胶囊大、中、小剂量组、阳性对照组和正常对照组，分别于灌胃给药10d后，开颅窗观察小鼠软脑膜微循环，然后在软脑膜局部滴加去甲肾上腺素复制微循环障碍模型，观察微循环障碍时小鼠软脑膜微循环。结果 聪灵胶囊各剂量组均可改善去甲肾上腺素所致的小鼠软脑膜局部微循环障碍．使微动脉扩张，血流增快，每视野交织网点数增多，对血流流态也有一定的改善作用，使血色变红。9min后聪灵胶囊各剂量组软脑膜局部微循环障碍基本恢复，而空白对照组恢复不明显。结论 聪灵胶囊能改善小鼠软脑膜微循环。     

Ro 11-2465 (cyan-imipramine), citalopram and their N-desmethyl metabolites: Effects on the uptake of 5-hydroxytryptamine and noradrenaline in vivo and related pharmacological activities

Ro 11-2465 (cianopramine, cyan-imipramine) and citalopram (CIT), putative antidepressant drugs, are very potent and selective 5-hydroxytryptamine (5-HT) uptake inhibitors in vitro. This study investigated the effects of these drugs and their desmethyl metabolites, Ro 12-5419 (desmethylcianopramine, cyan-desipramine) and desmethylcitalopram (DCIT), respectively, on the uptake of 5-HT and noradrenaline (NA) in vivo [protection against H 77/77 (4, alpha-dimethyl-metatyramine)-induced displacement of 5-HT and NA] and on related pharmacological activities. All the investigated drugs antagonized H 77/77-induced displacement of 5-HT in the rat brain, though the effects of the metabolites were considerably weaker than those of the parent compounds. The H 77/77-induced displacement of brain NA in rats and mice was antagonized only by Ro 12-5419 and Ro 11-2465. All the drugs potentiated the pressor response to 5-HT in pithed rats; however, Ro 12-5419 and particularly Ro 11-2465 could also block the response when used in higher doses (0.1 mg/kg). Only Ro 12-5419 and Ro 11-2465 were able to potentiate the pressor response to NA. Ro 12-5419 also potentiated thyrotropin releasing hormone (TRH) hyperthermia and antagonized reserpine hypothermia in mice; Ro 11-2465 potentiated the TRH hyperthermia only. CIT and DCIT were inactive in both these tests. Of all the four drugs only CIT and Ro 12-5419 considerably stimulated the hind limb flexor reflex in spinal rats. However, whereas the stimulatory effect of CIT was inhibited by the 5-HT antagonists metergoline and cyproheptadine, that of Ro 12-5419 was counteracted by the NA antagonist phenoxybenzamine only. Ro 11-2465, when used in low doses (ca. 1 mg/kg), slightly potentiated the flexor reflex, whereas in higher doses (4–16 mg/kg) it had no effect itself but antagonized the stimulatory action of the 5-HT agonists fenfluramine, quipazine and LSD. The results obtained indicate that Ro 11-2465 and CIT, as well as their desmethyl metabolites, are also potent 5-HT uptake inhibitors in vivo. However, only CIT and DCIT are concurrently devoid of effect on uptake of NA. In contrast, Ro 11-2465 and particularly Ro 12-5419 appear to also inhibit the uptake of NA. Moreover, Ro 11-2465 appears to block central and peripheral 5-HT receptors.The results were presented at the 14th CINP Congress, Florence, June 19–23, 1984     

新洁尔灭对小白鼠抗早孕的病理组织学观察

本文报告用不同剂量的新洁尔灭和同体积生理盐水注入怀孕5天小白鼠的宫腔内,3天后杀死,观察其蜕膜、胚泡、宫内膜腺体和卵巢黄体病理学改变。实验表明:对照组无改变。实验组小白鼠的蜕膜细胞全部退变坏死。病变随着给药量的递增而渐趋严重;同时胚泡亦有退变和坏死。提示:新洁尔灭对早期妊娠小白鼠是有抗早孕效果的。根据实验结果,我们认为新洁尔灭对小白鼠抗早孕的机制,很可能是一个综合因素,有直接的,也有间接的。作者强调在抗早孕机制诸因素中,蜕膜退变坏死是一个重要的因素。     

Benzodiazepine ligands,nociception and ‘defeat’ analgesia in male mice

Recent studies have indicated that defeat experience induces acute non-opioid analgesia in intruder mice. To investigate the potential involvement of benzodiazepine receptors in this biologically-relevant form of environmentally-induced antinociception, we initially assessed the effects of some benzodiazepine ligands on basal nociception (tail-flick assay). Chlordiazepoxide (5–30 mg/kg), midazolam (0.625–5 mg/kg), diazepam (0.5–4 mg/kg), Ro15-1788 (5–80 mg/kg) and CGS8216 (5 mg/kg) were found to be ineffective in altering basal nociception. However, higher doses of CGS8216 (10–20 mg/kg) induced significant analgesia, an effect also observed with the -carboline derivatives FG7142 (5–20 mg/kg) and DMCM (1–2 mg/kg). Time-course analyses revealed that the onset of CGS8216 analgesia was slower than for FG7142 and DMCM, but that all three drugs produced long-lasting elevations in tailflick latencies. The analgesic effects of FG7142 and DMCM were completely reversed by Ro15-1788 (20 mg/kg) and by chlordiazepoxide (20 mg/kg), suggesting mediation by benzodiazepine receptor mechanisms. Although CGS8216 analgesia was also reversed by Ro15-1788, it was unaffected by chlordiazepoxide; however, diazepam (5 mg/kg) did significantly attenuate the reaction. Further studies indicated that the antinociceptive consequences of defeat experience were dose-dependently blocked by Ro15-1788 (10–40 mg/kg) and by diazepam (0.5–2 mg/kg). Surprisingly, however, neither chlordiazepoxide (5–20 mg/kg) nor midazolam (1.25–2.5 mg/kg) blocked defeat analgesia under present test conditions. Although several issues remain unresolved, present findings would not be inconsistent with the proposal that stimuli associated with the acute stress of defeat experience release an endogenous ligand which acts in an inverse agonist-like manner at benzodiazepine sites.     

Effects of fixed-interval duration on the development of tolerance to decreased responding byl-nantradol

The effects of several types of antidepressants in a recently developed behavioural despair model, the tail-suspension test, are described. Drug effects on the automatically recorded duration of immobility and power of movements were measured in three strains of mice. Only in one strain (NMRI) did almost all antidepressants tested showed the expected reduction in duration of immobility. Tranquillizing drugs, but not stimulants, could be distinguished from antidepressants. The power of movements could not definitively be related to the pharmacological profile of the drugs tested. The use of the tail-suspension test as a rapid and highly predictive behavioural primary screen for antidepressant drugs is suggested.     

Effects of ethanol on murine aggression assessed by biting of an inanimate target

The effects of acutely administered ethanol (0, 0.5, 1.0 and 2.0 g/kg, IP) were studied in a tube-restraint/target biting model of aggressive responding using naive group-and individually-housed male Swiss mice. Behavioural measures were the latency to the first bite and the biting frequency. In saline-injected control animals, the levels of responding were significantly higher in group-housed than isolated mice. Animals given alcohol exhibited a dose-dependent suppression of biting frequency, and an increase in biting latency. Mice experienced in the tube-testing situation showed reduced baseline levels of biting, but alcohol produced similar effects to those in naive mice. There was no evidence of a biphasic action of alcohol.     

On the convulsant action of Ro 5-4864 and the existence of a micromolar benzodiazepine binding site in rat brain

The benzodiazepine Ro 5-4864 (60 mg/kg) produced convulsions in mice that could be antagonised either by diazepam (2–4 mg/kg) or by Ro 15-1788 (10–20 mg/kg). In mice and rats subconvulsant doses of Ro 5-4864 were proconvulsant when combined with subconvulsant doses of picrotoxin or pentylenetetrazole. Ro 15-1788 antagonised the tonic convulsions triggered by the drug combinations when it was given at the same time as Ro 5-4864; this antagonism was not observed when the drugs were injected at different times. In contrast to a previous report, we could find no evidence that Ro 5-4864 antagonised seizures induced by electroshock. Using two different ligand-binding techniques, no evidence was seen for the existence in rat brain of the previously reported micromolar benzodiazepine receptor, a suggested site of action of Ro 5-4864.