Oxytocin induces preservation of social recognition in male rats by activating alpha-adrenoceptors of the olfactory bulb

In this report, a series of four experiments was performed to evaluate the relationship between the olfactory bulb norepinephrine system and intra-olfactory bulb infusion of oxytocin in the preservation of social memory responses. The present data indicate that oxytocin exerts this preservation of social recognition through a specific, receptor-mediated mechanism within the olfactory bulb (experiment 1). The involvement of the olfactory bulb norepinephrine system is revealed by the demonstration that retrodialysis of oxytocin into the olfactory bulb increases norepinephrine release (experiment 4). Our data suggest that the increased output of olfactory bulb norepinephrine resulting from oxytocin appears to activate alpha-adrenoceptors to produce this preservation in recognition because infusions of clonidine into the olfactory bulb preserve recognition responses in a manner similar to that observed with oxytocin (experiment 2). In addition, a co-infusion of oxytocin with phentolamine abolishes recognition responses (experiment 3). Accordingly, this model affords the opportunity to study neuropeptide-catecholamine interactions, link these interactions with a specific behavioural outcome and identify a novel function/site of action for oxytocin in the male.     

Norepinephrine regulation of growth hormone release from goldfish pituitary cells. I. Involvement of alpha2 adrenoreceptor and interactions with dopamine and salmon gonadotropin-releasing hormone

Adrenergic regulation of growth hormone (GH) release in the goldfish was examined in vitro using dispersed goldfish pituitary cells under column perifusion. Norepinephrine and epinephrine suppressed basal GH release from goldfish pituitary cells in a reversible and dose-dependent manner. At high doses, a transient rebound of GH release was observed after termination of norepinephrine and epinephrine treatment. In this study, the dose-dependence of adrenergic inhibition on basal GH release was mimicked by the alpha2 agonists clonidine and UK14304. Basal GH secretion, however, was not affected by the beta agonist isoproterenol and alpha1 agonist methoxamine. In addition, the inhibitory actions of norepinephrine and clonidine on basal GH release were blocked by the alpha2 antagonists yohimbine and RX821002. The beta antagonist propranolol and alpha1 antagonists prasozin and benoxathian were not effective in this respect. Salmon gonadotropin-releasing hormone (sGnRH) and dopamine, two known GH-releasing factors in fish, stimulated GH release from goldfish pituitary cells and their GH-releasing actions were inhibited by simultaneous treatment with norepinephrine. Furthermore, the GH rebound after norepinephrine treatment was significantly enhanced by prior exposure to sGnRH and this effect was not observed with dopamine treatment. These results, taken together, suggest that in the goldfish adrenergic input at the pituitary level inhibit basal GH release through activation of alpha2 adrenoreceptors. This alpha2 inhibitory influence may interact with dopaminergic and GnRH input to regulate GH secretion from goldfish pituitary cells. The 'post-inhibition' GH rebound after NE treatment and its sensitivity to sGnRH potentiation may also represent a novel mechanism for GH regulation in fish.     

Serotonergic and noradrenergic function in depression: clinical correlates

The present study was conducted in order to investigate the relationships between central noradrenergic (NA) and serotonergic (5-HT) function and clinical characteristics of a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We measured growth hormone response (ΔGH) to clonidine (CLO) (an α2 NA agonist), as an index of central NA function, and prolactin response (APRL) to d-fenfluramine (d-FEN) (a specific 5-HT releaser/uptake inhibitor), as an index of central 5-HT function, in 53 medication-free depressed inpatients. On the basis of their CLO and d-FEN test responses, patients were classified into 4 groups. Group 1 (blunted ΔPRL(d-FEN) alone [11 %]) was characterized by a recent violent suicide attempt, a high degree of medical damage, and mild anxiety. Group 2 (blunted ΔGH(CLO) alone [32%]) was characterized by an absence of a history of suicide attempt and by severe anxiety. Group 3 (combination of blunted ΔGH(CLO) and APRL(d-FEN) [18%]) was characterized by a history of suicide attempts, total duration of the illness of over W years, age over 40 years, and more than 3 previous hospitalizations. Group 4 (no abnormality [39%]) had no specific clinical profile. These results suggest that, in depression, specific psychopathological features may be linked to 5-HT and/or NA dysfunction. However, our results also suggest that NA and/or 5-HT dysfunction are less likely to be the primary cause of mood disorders but are more indicative of failure of compensatory mechanisms involved in affective homeostatic processes.     

Particle release in extracorporeal low-density lipoprotein lowering therapies

Release of microparticles into the blood during extracorporeal circulation must be kept low because of possibly serious acute and chronic adverse effects. Concentration and size distribution of microparticles were measured during simulated treatments (n = 7) on original equipment for 2 standard low-density lipoprotein (LDL) elimination procedures (DALI 750, Fresenius AG, St. Wendel, Germany and Liposorber, Kaneka Corporation, Osaka, Japan) and compared to hemofiltration solutions. For both systems as well as in hemofiltration solutions, the mean particle concentrations in 500 ml portions gathered from the efferent blood line stayed below 10% of pharmacopoeia standards for infusion solutions (United States Pharmacopoeia, European Pharmacopoeia) in all measured size classes. Although particle concentrations were comparable in all systems, the mean total number of particles > or =2 microm released per session was lowest in the DALI (167,000) compared to the Liposorber (465,000) and hemofiltration solutions (2,240,000). This was mainly due to different total processed blood volumes necessary to achieve the required LDL reduction.     

十八甲基炔诺酮透皮控释传递系统在人体不同部位皮肤的药物动力学

6名健康妇女分别于上臂、臀部和腹部三部位经皮给予合LNG的透皮控释传递系统（TCDS）后，用放射免疫法测定LNG血清浓度，计算其主要药物动力学参数。结果表明：在TCDS用药期间，三部位的C（max）、T（max）及AUC（0～168h）基本接近，部位间无显著性差异（P＞0．05）；TCDS揭除后，AUC（168～204h）及消除相半衰期T（1／2）（Ke）均以腹部最大，臀部次之，上臂最小，在腹部与上臂间有显著性差异（P＜0．05）。上述结果可归因于TCDS对LNG的控释和人体皮下脂肪的“贮库效应”。     

精制芎归缓释滴丸的制备

目的:筛选水溶性和水不溶性载体的种类、配比,研究缓释滴丸剂的成型处方。方法:以圆整度、硬度、料液的黏度、流动性、易滴制程度、累计释放百分数等为考察指标,采用正交设计试验对精制芎归缓释滴丸的成型处方进行优选。结果与结论:按照选定的处方既能有一定的速释量,还能保证10h持续释药80%以上,达到了释药设计目的。     

Tetanus-induced asynchronous GABA release in cultured hippocampal neurons

Asynchronous GABA release was studied in cultured hippocampal neurons using paired whole-cell recordings. Tetanization of the presynaptic GABAergic neuron was accompanied by a train of IPSCs which showed tetanic depression. Asynchronous IPSCs (asIPSCs) also developed during the train and continued for 1.85±0.3 s after the stimulation. The threshold frequency for evoking asIPSCs was 10 Hz, while maximal asynchronous activity was achieved at 40 Hz. Perfusion with EGTA-AM blocked asIPSCs. The elevation of [Ca²⁺]_i that accompanies presynaptic action potential firing triggers asynchronous release of GABA vesicles, thereby counteracting tetanic depression of synchronous IPSCs.     

NMDA receptor antagonist-induced dopamine release in the ventral pallidum does not correlate with motor activation

The ventral pallidum is the output structure of the nucleus accumbens in the ventral corticostriato-thalamocortical loop. Information processing in this loop is critically involved in motor behavior and reinforcement. The ventral pallidum receives a direct dopaminergic input from the ventral tegmental area, but also glutamatergic input from cortical and limbic areas. It has been assumed that dopamine release in the VP is indeed modulated by glutamate. The present study investigated the effects of NMDA receptor blockade on motor behavior and dopamine release in the ventral pallidum. In a first experiment, rats were implanted with microdialysis probes in the ventral pallidum and were systemically injected or locally perfused via the microdialysis probe with dizocilpine (0.32 mg/kg, 10 and 100 microM, respectively). Effects on dopamine and on locomotion were simultaneously monitored. In a second experiment, ventral pallidum was lesioned by quinolinic acid and the effects of systemic dizocilpine (0.08 and 0.16 mg/kg) on locomotion and stereotyped sniffing behavior were determined. It was found that systemic and local dizocilpine administration increased dopamine release in the ventral pallidum to a similar extent whereas only systemic treatment was accompanied by locomotor stimulation. Lesion of the ventral pallidum did not affect locomotion and stereotyped sniffing behavior induced by systemic dizocilpine treatment. Thus, DA release in the ventral pallidum that is elevated by blockade of NMDA receptors is not relevant for activation of motor behavior.     

可生物降解的聚乳酸羟基乙酸牙周缓释凝胶的研究

目的采用聚乳酸羟基乙酸(PLGA)研制替硝唑牙周缓释凝胶。方法根据聚合物的分子量、浓度、载药量和增塑剂等因素来优选最佳配方。结果聚合物溶液中N-甲基-2-吡咯烷酮(NMP)P、EG400、PLGA(75∶25)的最佳比例为65∶5∶30,5%替硝唑与聚合物溶液均匀混合即得凝胶。凝胶必须在室温下避光保存。结论该凝胶缓释时间长达7d,用于牙周炎的治疗有效。     

2型糖尿病糖耐量实验与胰岛素释放实验关系的探讨

目的 探讨2型糖尿病血糖与胰岛素释放的关系,以及血糖水平对血糖刺激的胰岛素释放的影响.方法 对50例2型糖尿病患者停用口服药24 h后,口服75 g葡萄糖行葡萄糖耐量实验(OGTT)及胰岛素释放实验(IRT).血糖采用cobas Integra 400 plus全自动生化分析仪测定,胰岛素采用美国Becoman Coulter Access2化学发光仪测定.结果 50例2型糖尿病患者按血糖水平与胰岛素释放的变化方向可分为4组:①A组:血糖水平与胰岛素水平曲线平行,均于1 h达峰值16例.②B组:胰岛素水平峰值延迟9例.③C组:血糖水平与胰岛素水平均于2 h达峰值,峰值延迟19例.④D组:血糖峰值延迟6例.结论 血糖水平与血清胰岛素水平呈负相关,但由于胰岛B细胞的个体差异很大,可以出现不同的分离现象,体现了糖尿病发病的异质性或个体差异性.