不同5-HT3受体拮抗剂预防腹腔镜术后恶心呕吐的临床观察

观察使用不同5-HT3受体拮抗剂预防全麻下腹腔镜手术术后恶心呕吐的临床效果。选择160例气管内插管全身麻醉下腹腔镜手术,随机分四组,每组40例,手术结束前30min分别静脉注射昂丹司琼4mg（A组）;托烷司琼2mg（B组）;格拉司琼3mg（C组）;D组为对照组。记录术后2h、6h、12h、24h患者恶心、呕吐出现的例数。结果四组患者术后恶心呕吐的发生率是一个逐渐下降的趋势,A、B、C三组与D组相比较有显著性差异（P〈0．05）;术后2h、6h、12hB组与A组、C组相比较有显著性差异（P〈0．05）;而术后24hA、B、C三组差异无统计学意义,A、B、C三组抑制恶心呕吐的有效率分别为67．5％、87．5％和70．0％,与对照组比较差异有统计学意义（P〈0．05）,随访患者24h内无与药物相关的不良反应。结论：三种药物都能有效地预防术后恶心呕吐,但12h内托烷司琼的有效性更为明显。     

晚期非小细胞肺癌TKIs治疗：关注与思考

以表皮生长因子受体（EGFR）为靶点的酪氨酸激酶抑制剂（TKIs）对晚期非小细胞肺癌EGFR突变患者的治疗效果令人瞩目。本文分析总结近年国内外相关研究,指出低剂量TKIs的应用虽有待进一步证实,但优于标准剂量组,并从安全性、改善肿瘤血管结构和功能、与细胞毒化疗的关系三方面探讨大剂量TKIs的应用效果。进一步分析指出大剂量联合小剂量TKIs能够最大程度地防止或延迟耐药的发生,进而控制疾病的进展。从而,为晚期非小细胞肺癌EGFR突变患者的TKIs治疗选择提供参考。     

前列腺素E2及其在肾脏调控中的作用

前列腺素E2(PGE2)是最主要的前列腺素化合物,参与几乎所有的细胞代谢活动并介导多种不同的生理病理功能。PGE2的生物学效应是通过与不同的EP受体结合从而激活不同的信号转导通路来实现的。因为各类EP受体在肾脏的高分布,所以近来PGE2在肾脏中的作用日趋引起人们的重视。     

维生素D_3及其受体的临床意义

1,25-(OH)2D3是维生素D在体内发挥生理作用的活性形式。活性维生素D3通过与细胞内特异性维生素D受体结合,除了具有调节钙磷代谢的功能外,还发现其可预防和治疗骨质疏松、心血管疾病、自身免疫性疾病和一些肿瘤等。然而,维生素D缺乏在人群中非常普遍。     

Behavioral profile of L–741,741, a selective D4 dopamine receptor antagonist,in social encounters between male mice

Although the role of dopamine D1–D2–D3 receptors in the modulation of aggression has been extensively documented, there is not information with respect to the implication of D4 receptor. The aim of this study was to examine the acute effects of L–741,741 (0.75, 1.5 and 3 mg/kg, i.p), a selective D4 receptor antagonist, on social encounters between male mice using an ethopharmacological approach. Ten min of diadic interactions were staged between a singly housed and an anosmic mouse in a neutral area. These encounters were videotaped and the accumulated time allocated by subjects to ten broad behavioral categories was estimated. Besides other behaviors, the aggressive and motor behaviors were evaluated 30 min after injection using an ethologically based analysis. L–741,741 did not affect significantly offensive behaviors (threat and attack), as compared with the control group. Likewise, motor and anxiety‐related behaviors (such as social investigation, avoidance/flee or defense submission) were not altered after drug administration. These results suggest that dopamine D4 receptor is not involved in the modulation of aggressive behavior. Aggr. Behav. 29:552–557, 2003. © 2003 Wiley‐Liss, Inc.     

Depotentiation of vdccLTP Requires NMDAR Activation

Long-term potentiation is an enduring increase in synaptic efficacy following repeated stimulation of afferent fibers that is thought to underlie memory. In area CA1 of the hippocampus at least two forms of synaptic potentiation coexist at the same synapses; nmdaLTP and vdccLTP. NmdaLTP is induced by Ca2+ entry through NMDARs and is dependent on serine/threonine kinase activation, while vdccLTP is induced through Ca2+ entry through VDCCs and is dependent on tyrosine kinase activation. Depotentiation is a mechanism known to reverse nmdaLTP through phosphatase activation. The depotentiation of vdccLTP has not been previously investigated. We used hippocampal slices (area CA1) from male Long-Evans rats to induce vdccLTP with a 200-Hz tetanus in the presence of 50 microM APV. The 200-Hz tetanus resulted in a slowly developing vdccLTP that remained stable for at least 30 min. Thirty minutes after vdccLTP was induced, a low-frequency tetanus (3, 10, 20, 30, or 40 Hz) was applied in the presence of APV in an attempt to depotentiate vdccLTP. The 3- and 10-Hz low-frequency tetani resulted in no depotentiation. The 20- and 30-Hz tetani partially depotentiated vdccLTP (by approximately 13%), whereas the 40-Hz tetanus resulted in further potentiation. When APV was washed out prior to the 3-Hz low-frequency tetanus, the vdccLTP was completely depotentiated--presumably by NMDAR mechanisms. Our results indicate that vdccLTP is resistant to depotentiation under low-frequency stimulation conditions that readily depotentiate nmdaLTP. As tetanus frequencies are increased a small depotentiation is observed, suggesting that vdccLTP can be depotentiated to a small extent. When NMDARs are unblocked, vdccLTP can be completely depotentiated by a 3-Hz low-frequency tetanus, suggesting that vdccLTP can be depotentiated via activation of NMDAR mechanisms.     

Role of cholinergic system on the construction of memories: taste memory encoding

There is a large body of evidence suggesting that cholinergic activity is involved in memory processes. It seems that cholinergic activity is essential to learn several tasks and recent works suggest that acetylcholine plays an important role during the early stages of memory formation. In this review, we will discuss the results related to taste memory formation, focusing particularly on the conditioned taste aversion paradigm. We will first give evidence that nucleus basalis magnocellularis is involved in taste memory formation, due to its cholinergic projections. We then show that the cholinergic activity of the insular (gustatory) cortex is related to the taste novelty, and that the cholinergic signals initiated by novelty are crucial for taste memory formation. Then we present recent data indicating that cortical activation of muscarinic receptors is necessary for taste trace encoding, and also for its consolidation under certain circumstances. Finally, interactions between the cholinergic and other neuromodulatory systems inducing intracellular mechanisms related to plastic changes will be proposed as important processes underlying gustatory memory trace storage.     

Contribution of acetylcholine to visual cortex plasticity

Acetylcholine is involved in a variety of brain functions. In the visual cortex, the pattern of cholinergic innervation varies considerably across different mammalian species and across different cortical layers within the same species. The physiological effects of acetylcholine in the visual cortex display complex responses, which are likely due to cholinergic receptor subtype composition in cytoplasm membrane as well as interaction with other transmitter systems within the local neural circuitry. The functional role of acetylcholine in visual cortex is believed to improve the signal-to-noise ratio of cortical neurons during visual information processing. Available evidence suggests that acetylcholine is also involved in experience-dependent visual cortex plasticity. At the level of synaptic transmission, activation of muscarinic receptors has been shown to play a permissive role in visual cortex plasticity. Among the muscarinic receptor subtypes, the M(1) receptor seems to make a predominant contribution towards modifications of neural circuitry. The signal transduction cascade of the cholinergic pathway may act synergistically with that of the NMDA receptor pathway, whose activation is a prerequisite for cortical plasticity.     

Characterization of the discriminative stimulus effects of lorcaserin in rats

Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5‐HT)_2C receptors and might also have agonist properties at other 5‐HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague–Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed‐ratio 5 schedule for food. Lorcaserin (0.178‐1.0 mg/kg) dose‐dependently increased lorcaserin‐lever responding. The 5‐HT_2C receptor agonist mCPP and the 5‐HT_2A receptor agonist DOM each occasioned greater than 90% lorcaserin‐lever responding in seven of eight rats. The 5‐HT_1A receptor agonist 8‐OH‐DPAT occasioned greater than 90% lorcaserin‐lever responding in four of seven rats. The 5‐HT_2C receptor selective antagonist SB 242084 attenuated lorcaserin‐lever responding in all eight rats and the 5‐HT_2A receptor selective antagonist MDL 100907 attenuated lorcaserin‐lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5‐HT_2C receptors, lorcaserin also has agonist properties at 5‐HT_2A and 5‐HT_1A receptors. Because some drugs with 5‐HT_2A receptor agonist properties are abused, it is important to fully characterize the behavioral effects of lorcaserin while considering its potential for treating substance use disorders.     

Synchrnoic consciousness from a neurological point of view: the philosophical foundations for neuroethics

Daniel Kolak’s theory of synchronic consciousness according to which the entire range of dissociative phenomena, from pathologies such as MPD and schizophrenia to normal dream states, are best explained in terms of consciousness becoming simultaneously identified as many selves, has revolutionary therapeutic implications for neurology and psychiatry. All these selves, according to Kolak—even the purely imaginary ones that exist as such only in our dreams—are not just conscious but also self-conscious, with beliefs, intentions, living lives informed by memories (confabulatory, in the case of the fictional ones) and personal histories. Kolak’s derivation of psychiatrically relevant aspects of his theory—a neurological rendition of a Kantian transcendental argument—can be given a straightforward neurological, and therefore open to scientific scrutiny, interpretation that would then more easily lend itself to the clinical setting in which these perplexing phenomena, along with their purveyors, must live and cope. This will be the main focus of this paper.