猫海马注射去甲肾上腺素对血浆皮质浓度的影响

In the present experiment, the effect of injection of NE into the different areas of hippocampus on the plasma cortisol level and the kind of NE receptor involved were studied in 83 cats anesthetized with Nembutal. The plasma cortisol level was increased following injection of NE into the ventral hippocampus (VHIP), however, there was no significant change when injection was made into dorsal hippocampus. The NE-VHIP effect can be blocked by injection of phentolamine, yohimbine or prazosin but not by propranolol. Thus, these results show that, in the regulation of the plasma cortisol level, the alpha-receptor system of VHIP is more specifically involved.     

猫隔核损毁对海马内注射去甲肾上腺素诱发皮质醇分泌的影响

实验观察到猫腹侧海马内微量注射去甲肾上腺互能明显地提高血浆皮质醇水平，电解损毁两侧外侧隔核虽不影响血浆皮质醇的基础水平，但可以完全阻断ＶＨＩＰ内注射ＮＥ诱发的皮醇分泌增加反应，而前额皮导毁后并不能阻ＶＨＩＰ内注射ＮＥ的效应，结果提示：ＶＨＩＰ内注射ＮＥ对皮质醇分泌的影响很可能通过了隔核的中间传递过程，进而使下丘脑－肾上腺轴的功能发生改变。     

急性低氧对血浆皮质醇浓度及海马去甲肾上腺素含量的影响

本工作观察不同氧浓度,不同低氧时间猫血浆皮质醇浓度和海马内去甲肾上腺素含量的改变,以分析海马在低氧应激过程中的作用,结果显示,吸入１０．４％及７．９％Ｏ２后,猫血浆皮质醇浓度逐渐升高,分别于４５ｍｉｎ及３０ｍｉｎ达峰值;而低氧３０ｍｉｎ后,海马组织中的ＮＥ含量明显降低,两者与低氧程度无明显关系。     

褪黑素减弱大鼠下丘脑弓状核β-内啡肽免疫反应的强度

为探讨褪黑素（ＭＥＬ）镇痛作用的机制,本文采用免疫组化方法结合计算机图像处理技术,观察了注射ＭＥＬ对大鼠下丘脑弓状核内神经细胞的β－内啡肽免疫反应的影响。实验大鼠分约药组及对照组,分别腹腔注射ＭＥＬ１１０ｍｇ／ｋｇ或配药液,１ｈ后灌注取脑、冰冻切片,进行免疫组化染色,计算机图像处理技术测定染色脑片积分光密度（ＩＯＤ）和平均光密度（ＯＤ）。结果显示,给药组大鼠弓状核内β－内啡肽免疫反应明显减弱,ＩＯ     

褪黑素对大鼠中脑导水管周围灰质内阿片肽释放的影响

本文采用推挽灌流技术、放射免疫测定法,观察褪黑素（ｍｅｌａｔｏｎｉｎ,ＭＥＬ）对大鼠中脑导水管周围灰质（ＰＡＧ）推挽灌流液中β－内啡肽（β－Ｅｐ）、亮氨酸脑啡肽（Ｌ－ＥＫ）含量的影响,以探讨ＭＥＬ镇痛效应的中枢机制。结果显示,给药组大鼠腹腔注射（ｉｐ）ＭＥＬ１１０ｍｇ／ｋｇ后３０－５０ｍｉｎ,ＰＡＧ灌流液中β－Ｅｐ含量显著增加,而Ｌ－ＥＫ含量未见显著变化;在推挽灌流同时用５０℃热水刺激甩尾法测定痛     

侧脑室注射β—内啡肽对大鼠血浆唾液酸水平的影响及其机制探讨

注射微量β－内啡肽入Ｗｓｉｔａｒ大鼠侧脑室,探讨其对血浆唾液酸水平的影响及其可能机制。结果表明：（１）侧脑室注射β－内啡肽后,血浆唾液酸水平对对照组明显降低,而且唾液酸水平降低的时间随β－内啡肽浓度的增加而逐渐缩短;（２）静脉注射酚托拉明后,侧脑室注射β－内啡肽,血浆唾液酸水平明显降低;（３）静脉注射心复宁后,侧脑室注射β－内啡肽血浆唾液酸水平明显降低;（４）静脉注射阿托品后,侧脑室注射β－内啡肽     

猫海马注射去甲肾上腺素对血浆皮质醇浓度的影响

本工作报道了在戊巴比妥钠麻醉猫的海马不同区域注射去甲肾上腺素(NE)时血浆皮质醇浓度的变化及其作用受体。腹侧海马(VHIP)注入NE(4 μg/2μl),血浆皮质醇浓度明显升高,在背侧海马(DHIP)注入NE,则此作用不大。进一步分析表明,注射β受体阻断剂心得安(10μg/2μl),对皮质醇升高效应无明显影响,但此效应可被α受体阻断剂酚妥拉明(10μg/2μl)、α_1受体阻断剂哌唑嗪(2μg/2μl)或α_2受体阻断剂育亨宾(4μg/2μl)所阻断。这些结果表明,VHIP的α受体对于调节血浆皮质醇浓度起着较大的作用。     

海马内注射肾上腺素能受体激动剂对细胞免疫功能的影响

目的 研究肾上腺素能受体激动剂对机体细胞免疫功能的作用及下丘脑-垂体-肾上腺轴(HPA轴)在此作用中的地位.方法以刀豆蛋白A(ConA)刺激脾淋巴细胞的增殖活性为细胞免疫功能指标,检测在正常及去肾上腺大鼠海马内注射去甲肾上腺素(noradrenaline,A)对机体细胞免疫功能的影响.结果①在正常大鼠,A(4 μl,.0×10-3mol/L)、β1受体激动剂杜丁胺 (dobutamine,ob,μl,.0×10-3mol/L) 和β2受体激动剂异丙喘宁(metaproterenol,et, μl,.0×10-3mol/L)均可抑制Con A刺激的脾淋巴细胞增殖反应、降低NK细胞的活性,其中NA的作用最强,et 次之,ob的作用最弱.α及β受体阻断剂酚妥拉明(Phen, μl,.6×10-2mol/L) 和心得安(Prop,μl,.6×10-2mol/L)均可部分阻断NA的免疫抑制作用,且Prop的作用较强.②在去肾上腺组,A的免疫抑制作用不明显.结论海马内NA对机体的细胞免疫功能具有明显的抑制作用,此作用由α及β受体共同介导,其中β受体的作用大于α受体,且β2受体的作用大于β1受体.此外,保持肾上腺结构和功能完整在NA调节机体细胞免疫功能作用中具有重要意义.     

Effect of oxytocin and its antagonist microinjected into the hippocampus on the intravenous self-administration of heroin in rats

The paper deals with the effect of oxytocin (OXT) and its antagonist--oxytocin antiserum (ANT) microinjected in the ventral hippocampus--on learning of heroin intravenous self-administration in rats. OXT weakened the processes of heroin self-administration, while ANT in contrast improved the learning. The results of the study and data analysis suggest that endogenous OXT in the ventral hippocampus is involved in the mechanisms of behavioural reactions.     

Immunoregulatory role of melatonin in cancer

Melatonin is a ubiquitous indole amine that plays a fundamental role in the regulation of the biological rhythm. Disrupted circadian rhythm alters the expression of clock genes and deregulates oncogenes, which finally promote tumor development and progression. An evidence supporting this notion is the higher risk of developing malignancies among night shift workers. Circadian secretion of the pineal hormone also synchronizes the immune system via a reciprocal association that exists between the immune system and melatonin. Immune cells are capable of melatonin biosynthesis in addition to the expression of its receptors. Melatonin induces big changes in different immune cell proportions, enhances their viability and improves immune cell metabolism in the tumor microenvironment. These effects might be directly mediated by melatonin receptors or indirectly through alterations in hormonal and cytokine release. Moreover, melatonin induces apoptosis in tumor cells via the intrinsic and extrinsic pathways of apoptosis, while it protectsthe immune cells. In general, melatonin has a profound impact on immune cell trafficking, cytokine production and apoptosis induction in malignant cells. On such a basis, using melatonin and resynchronization of sleep cycle may have potential implications in immune function enhancement against malignancies, which will be the focus of the present paper.     

New actions of melatonin and their relevance to biometeorology

 Melatonin is not only produced by the pineal gland, retina and parietal but also by various other tissues and cells from vertebrates, invertebrates, fungi, plants, multicellular algae and by unicells. In plants, many invertebrates and unicells, its concentration often exceeds that found in vertebrate blood by several orders of magnitude. The action of melatonin is highly pleiotropic. It involves firstly, direct effects, via specific binding sites in various peripheral tissues and cells of vertebrates, including immunomodulation; secondly, systemic influences on the cytoskeleton and nitric oxide formation, mediated by calmodulin; and thirdly, antioxidative protection, perhaps also in the context of photoprotection in plants and unicells. In some dinoflagellates, melatonin conveys temperature signals. On the basis of these comparisons, melatonin appears to mediate and modulate influences from several major environmental factors, such as the photoperiod, radiation intensity and temperature. Received: 18 March 1997 / Accepted: 16 July 1997     

Corticosterone microinjected into nucleus pontis oralis increases tonic immobility in rats

Tonic immobility (TI) is also known as “immobility response”, “immobility reflex”, “animal hypnosis”, etc. It is an innate antipredatory behavior characterized by an absence of movement, varying degrees of muscular activity, and a relative unresponsiveness to external stimuli. Experimentally, TI is commonly produced by manually forcing an animal into an inverted position and restraining it in that position until the animal becomes immobile. Part of the neural mechanism(s) of TI involves the medullo-pontine reticular formation, with influence from other components of the brain, notably the limbic system. It has been observed that TI is more prolonged in stressed animals, and systemic injection of corticosterone (CORT) also potentiates this behavior. At present, the anatomical brain regions involved in the CORT modulation of TI are unknown. Thus, our study was made to determine if some pontine areas could be targets for the modulation of TI by CORT. A unilateral nucleus pontis oralis (PnO) microinjection of 1 μL of CORT (0.05 μg/1 μL) in rats resulted in clear behavioral responses. The animals had an increased duration of TI caused by clamping the neck (in this induction, besides of body inversion and restraint, there is also clamping the neck), with an enhancement in open-field motor activity, which were prevented by pretreatment injection into PnO with 1 μL of the mineralocorticoid-receptor antagonist spironolactone (0.5 μg/1 μL) or 1 μL of the glucocorticoid-receptor antagonist mifepristone (0.5 μg/1 μL). In contrast, these behavioral changes were not seen when CORT (0.05 μg/1 μL) was microinjected into medial lemniscus area or paramedian raphe. Our data support the idea that, in stressful situations, glucocorticoids released from adrenals of the prey reach the PnO to produce a hyper arousal state, which in turn can prolong the duration of TI.     

Diurnal actions of melatonin on epileptic activity in hippocampal slices of rats

Since melatonin receptors have been found in the hippocampus of mammals it has been suggested that melatonin can modulate neuronal functions of hippocampal cells. The effect of melatonin (10 nM/l and 1 microM/l) on frequency and amplitude of epileptiform field potentials (EFP) elicited by low Mg(2+) or by bicuculline was tested in the CA1 region of hippocampal slices of rats. In the low Mg(2+) model, melatonin, applied in a near physiological concentration of 10 nM/l, exerts no effect on EFP in slices prepared at night or during the day. In a concentration of 1 microM/l, however, melatonin enhances the frequency of EFP to approximately 140% in slices prepared during the day. This effect was suppressed through simultaneous administration of the melatonin receptor antagonist luzindole (10 microM/l). In contrast, melatonin did not affect epileptic activity in slices prepared at night. Epileptiform discharges elicited by blocking the GABAergic inhibition (bicuculline model) were not affected by melatonin, either during the day or at night. The results indicate that melatonin affects epileptic activity in a diurnal manner and that the action of melatonin is different in relation to the epilepsy model.     

抗真菌药物及其作用机制研究

由于唑类药物长期使用,真菌耐药性及其交叉耐药现象不断出现,对临床治疗具有重要威胁。近年来提出新型抗真菌药物的新靶点,并研发出具有高活性强、强疗效的抗真菌药物。本研究对近年来新型抗真菌药的种类、结构和特点进行阐述,并介绍不同型药物对真菌的细胞壁、细胞膜、蛋白质合成、呼吸链等作用新靶点和作用机制的研究进展。     

Potential anticarcinogenic action of melatonin and other antioxidants mediated by antioxidative mechanisms

The complex process of carcinogenesis is, to a large extent, due to oxidative stress. Numerous indicators of oxidative damage are enhanced in the result of the action of carcinogens. Several antioxidants protect, with different efficacy, against oxidative abuse, exerted by carcinogens. Recently, melatonin (N-acetyl-5-methoxytryptamine) and some other indoleamines have gained particular meaning in the defense against oxidative stress and, consequently, carcinogenesis. Some antioxidants, like ascorbic acid, play a bivalent role in the antioxidative defense, revealing, under specific conditions, prooxidative effects. Among known antioxidants, melatonin is particularly frequently applied in experimental models of anticarcinogenic action. In the numerous studies, examining several parameters of oxidative damage and using several in vitro and in vivo models, this indoleamine has been shown to protect DNA and cellular membranes from the oxidative abuse caused by carcinogens. When either preventing or decreasing the oxidative damage to macromolecules, melatonin also protects against the initiation of cancer. The protection provided by melatonin and some other antioxidants against cellular damage, due to carcinogens, make them potential therapeutic supplements in the conditions of increased cancer risk.     

Glutamate decarboxylase activity in the substantia nigra and the hippocampus of rats microinjected with inhibitors of the enzyme

Three inhibitors of glutamate decarboxylase (GAD), acting through different mechanisms, as well as pyridoxal phosphate (PLP), were microinjected unilaterally by stereotaxic procedures into the substantia nigra reticulata or the CA₁ area of the hippocampus of the rat. The inhibitors used were thiosemicarbazide (TSC), -glutamyl hydrazide and the PLP-glutamyl-hydrazone (PLPGH) formed by the combination of the latter with PLP. No behavioral alterations were observed after the administration of any of the drugs used, in any of the two brain regions studied. When measured in the absence of exogenous PLP, GAD activity in the substantia nigra injected with TSC was diminished by about 35%, and no changes were observed with the other drugs. In the CA₁ hippocampal area both TSC and PLPGH inhibited GAD by more than 50%, and this inhibition was not reversed by PLP added in vitro. The results are discussed in terms of the possible explanation for the differences between the drugs used and for the lack of effects of GAD inhibition on the behavior of the animals.Special issue dedicated to Dr. Eugene Roberts.