全身麻醉剂对发育期大脑神经元凋亡的影响及其机制

动物实验发现全身麻醉剂可引起发育期大脑神经元广泛凋亡和长期神经认知功能障碍。内源性及外源性凋亡途径均参与麻醉药物引起的细胞凋亡,而信号传导机制尚不明确,某些药物可能减轻麻醉引起的神经细胞凋亡。然而全麻药物神经毒性作用的临床研究证据尚不充分,尚需进一步多中心、大样本人类研究的支持。     

全身麻醉药的安全性研究

全身麻醉药是抑制中枢系统的药物,分为吸入和静脉麻醉药,能使患者意识、感觉和反射暂时消失,有利于外科手术的进行,其临床使用安全性越来越受到人们的关注。本文对几种常见全麻药的安全性进行探讨,确保广大医务人员能合理有效使用该类药品,保证人民的生命健康。     

N-甲基-D-天冬氨酸受体与全身麻醉药对发育期大脑的神经毒性

N-甲基-D-天冬氨酸(NMDA)受体是一类对Ca2+高度通透性配体门控离子通道。NMDA受体在脑发育突触可塑性、学习记忆方面都起到重要作用,也是全身麻醉药作用的主要靶点之一。全身麻醉药诱导发育期大脑神经毒性,进而影响成年期认知功能发育,这是否由NMDA受体介导,尚待进一步研究予以证实。     

全身麻醉药物对发育期大脑影响的争鸣

麻醉药物作用于N-甲基-D-天冬氨酸(NMDA)受体和(或)γ氨基丁酸(GABA)引起发育期动物大脑神经退行性变和成年后认知功能障碍,且神经元凋亡或功能受损具有年龄、接触时间和剂量的依赖性。然而麻醉药物诱导神经细胞凋亡的假说仍存在争议。麻醉药物引起的凋亡是病理性凋亡还是生理性凋亡及其与与神经认知功能障碍间的因果关系尚不清楚。动物实验中不同种属动物麻醉/镇痛所需要的药物剂量、发育易感期各不相同,因此动物实验结果不能直接应用于临床。临床上全麻药物对婴幼儿神经毒性的临床研究证据尚不充分,仍需进一步获取多中心、大样本人类研究数据,以证实麻醉药物与发育期大脑退行性变的因果关系,阐述其机制,指导临床医师的工作。本文综述了全身麻醉药物对发育期大脑影响的研究进展。     

麻醉药对发育期神经系统的毒性作用及机制研究进展

麻醉在外科手术中不可或缺,但越来越多的研究证实其对发育期神经系统存在一定的毒性作用,且日益受到社会各界重视。本文就麻醉药物对发育期神经系统毒性作用的临床前研究及临床研究进行了简单的介绍,并从分子机制(钙稳态失衡、tau蛋白磷酸化、m6a基因修饰)、亚细胞结构(突触可塑性受损、线粒体功能障碍)、神经细胞凋亡、脑整体功能等几个方面对其机制进行阐述,为临床指导麻醉药物的使用提供依据,以提高婴幼儿麻醉的安全性。     

麻醉药的不良反应与相互作用

全身麻醉药分为吸入麻醉药和静脉麻醉药。吸入麻醉药有两种：一种是挥发性液体,如乙醚、异氟烷等;另一种是气体,如氧化亚氮。静脉麻醉药为非挥发性的全麻药,主要由静脉给药。局部麻醉药：在临床上应用第一个局麻药是可卡因（1884年）,由于吸收生毒性较大,使用上受到很大限制。     

全身麻醉药的离子通道药理学研究进展

离子通道在生命科学研究中占有相当重要的地位,特别是对作用于离子通道药物的研究更是方兴未艾.我们试就全身麻醉药离子通道药理学方面的研究进展作一综述.     

全身麻醉药的离子通道药理学研究进展

离子通道在生命科学研究中占有相当重要的地位,特别是对作用于离子通道药物的研究更是方兴未艾。我们试就全身麻醉药离子通道药理学方面的研究进展作一综述。     

对比不同静脉和吸入麻醉药的肌肉松弛作用

目的:观察不同静脉和吸入麻醉药的肌肉松弛作用.方法:40例择期手术女性病人,随机分为4组,分别静脉用2%普鲁卡因(1mgkg-1min -1)、异丙酚(4mgkg-1h-1)或吸入安氟醚(17%)、异氟醚(13%),维持30分钟,观察TOF的T1的抑制程度.结果:4组药物条件下,T1的抑制程度分别是92 1%、90 3%、83 7%、85 2%.2组静脉麻醉药和2组吸入麻醉药间有显著差异.结论:与静脉麻醉药相比,2种吸入麻醉药具有更强的肌松作用.     

The Effects of General Anesthetics on Synaptic Transmission

General anesthetics are a class of drugs that target the central nervous system and are widely used for various medical procedures. General anesthetics produce many behavioral changes required for clinical intervention, including amnesia, hypnosis, analgesia, and immobility; while they may also induce side effects like respiration and cardiovascular depressions. Understanding the mechanism of general anesthesia is essential for the development of selective general anesthetics which can preserve wanted pharmacological actions and exclude the side effects and underlying neural toxicities. However, the exact mechanism of how general anesthetics work is still elusive. Various molecular targets have been identified as specific targets for general anesthetics. Among these molecular targets, ion channels are the most principal category, including ligand-gated ionotropic receptors like γ-aminobutyric acid, glutamate and acetylcholine receptors, voltage-gated ion channels like voltage-gated sodium channel, calcium channel and potassium channels, and some second massager coupled channels. For neural functions of the central nervous system, synaptic transmission is the main procedure for which information is transmitted between neurons through brain regions, and intact synaptic function is fundamentally important for almost all the nervous functions, including consciousness, memory, and cognition. Therefore, it is important to understand the effects of general anesthetics on synaptic transmission via modulations of specific ion channels and relevant molecular targets, which can lead to the development of safer general anesthetics with selective actions. The present review will summarize the effects of various general anesthetics on synaptic transmissions and plasticity.     

Effects of General Anesthetics on Synaptic Transmission and Plasticity

General anesthetics depress excitatory and/or enhance inhibitory synaptic transmission principally by modulating the function of glutamatergic or GABAergic synapses, respectively, with relative anesthetic agent-specific mechanisms. Synaptic signaling proteins, including ligand- and voltage-gated ion channels, are targeted by general anesthetics to modulate various synaptic mechanisms, including presynaptic neurotransmitter release, postsynaptic receptor signaling, and dendritic spine dynamics to produce their characteristic acute neurophysiological effects. As synaptic structure and plasticity mediate higher-order functions such as learning and memory, long-term synaptic dysfunction following anesthesia may lead to undesirable neurocognitive consequences depending on the specific anesthetic agent and the vulnerability of the population. Here we review the cellular and molecular mechanisms of transient and persistent general anesthetic alterations of synaptic transmission and plasticity.     

两种局部麻醉药在口腔门诊的临床应用效果观察

目的比较复方阿替卡因和盐酸利多卡因在口腔局部麻醉的临床效果.方法将3690例患者随机分成两组,分别应用复方阿替卡因和盐酸利多卡因进行局部浸润麻醉和神经阻滞麻醉,对其注射时、术时疼痛程度、麻醉起效和麻醉中可能引发的并发症进行分析.结果复方阿替卡因进行局部浸润麻醉和神经阻滞麻醉时注射、治疗疼痛程度明显小于盐酸利多卡因;阻滞麻醉或局部浸润麻醉时麻醉持续时间明显长于盐酸利多卡因;并无明显的毒性副作用.结论复方阿替卡因局部渗透力强,麻醉安全、有效,具有广阔的应用前景.     

Developmental Phase Specificity and Dose-Response Effects of 2-Methoxyethanol in Rats

Methoxyethanol (ME) produces embryotoxic effects in rodents,rabbits, and nonhuman primates. Mechanistic evaluations of MEdysmorphogenesis have focused mainly on developmental insultsand chemical disposition in the mouse. These assessments inmice were based on developmental phase specificity (DPS) anddose response relationship (DRR) of ME. DPS and DRR indicatedtreatments for selectively inducing defects to study ME dispositionand expressed dysmorphogenesis. This study was conducted toestablish DPS and DRR of ME in the rat. DPS was determined byinjecting 500 mg ME/kg (6.6 mmol/kg) into the tail vein on GestationalDay (gd; sperm-positive day = gd 0) 10, 11, 12, 13, 14, or 15(n=6 dams/gd; saline controls on gd 12). On gd 20, embryolethalityincidence was 100% after gd 10 dosing; at gd 11 through 15,it was 50, 32, 15, 2, and 5%, respectively (control, 2%). Incidencesof external defects in live fetuses exposed on gd 11–15were 97, 98, 100, 44, and 0% and those of viscera were 100,62, 44, 10, and 0%, respectively. The predominant anomaliesobserved were ectrodactyly and renal agenesis. DRR was determinedon gd 13, when live embryos/litter and external malformations(ectro and syndactyly, micromelia) were maximal. Dams (n=8/dosegroup) were injected intravenously with 0, 100, 250, 350, or500 mg ME/kg. On gd 20, fetal defect rates were 0, 0, 82.5,83.0, and 100% at these concentrations, respectively. Basedon these studies, appropriate ME doses, times of maternal exposure,and critical phases of development in the rat model are availablefor reproducing selective defects to investigate biochemicaland pharmacokinetic determinants underlying their expression.     

2002年～2004年广东省全麻药用药分析

麻醉药是指能引起机体的一部分或全部暂时失去对外界刺激性反应的一类药物；麻醉药是一类配合外科手术的常用药。其中又分为全身麻醉药和局部麻醉药两种，全身麻醉药对中枢神经系统能产生较广泛的抑制，使人意识、感觉和反射逐渐消失，骨骼肌部分或全部松弛，主要用于深部大手术。麻醉药属于一般性管理药品，在管理上无特殊要求。笔者对2002～2004年度广东地区的全麻药使用情况进行总结、统计和分析，在此基础上，就临床麻醉药的应用动态进行讨论，为临床合理使用麻醉药提供有益的参考。     

Nicotine Addiction Causes Unique Detrimental Effects on Women's Brains

ABSTRACT

Nicotine addiction produces diverse physiological effects common to both men and women because of activation of the nicotinic acetylcholine receptors. In addition to these effects, nicotine reduces circulating estrogen (the female sex hormone) levels and leads to early onset of menopause in women. Nicotine's effect on estrogen metabolism has potential far-reaching consequences because endogenous circulating estrogen helps prevent cerebrovascular diseases in premenopausal women. In this article, the author presents a survey of literature showing that nicotine addiction causes unique deleterious effects in women's brains by inhibiting estrogen signaling, which makes the brain more susceptible to ischemic brain damage.     

麻醉药抗抑郁作用的研究进展

抑郁症是当今社会常见的严重危害人类身心健康的心理疾病,是自杀的首要原因。新近的研究发现临床上常用的部分麻醉药具有一定的抗抑郁效果,本文就麻醉药的抗抑郁作用及其可能机制进行综述。     

吸入麻醉剂浓度及作用时间对人离体精子活率的影响

目的:研究吸入麻醉剂浓度及作用时间对人离体精子活率的影响。方法:选择人精液20份,上游法优化处理后随机分为异氟醚实验组和七氟醚实验组,各10份。分别观测5个时间点(0.5 h、1 h、2 h3、h4、h)及5个浓度水平(0、1.4%、2.8%、4.2%、5.6%)异氟醚和相似浓度七氟醚对精子活率的影响,精子运动功能采用计算机辅助精子分析系统分析。结果:1.4%~5.6%异氟醚作用于精子0.5~4 h后,精子活率显著升高,其变化趋势符合S型曲线,相同浓度异氟醚组,精子活率随放置时间的延长成直线下降。类似浓度七氟醚对精子活率无显著影响。结论:临床浓度异氟醚作用于人离体精子,可以显著升高精子活率。类似浓度七氟醚对精子活率无显著影响。     

Potential Human Developmental Toxicants and The Role of Animal Testing in Their Identification and Characterization

Many modern cosmetic or sunscreen products contain nano-sized components. Nanoemulsions are transparent and have unique tactile and texture properties; nanocapsule, nanosome, noisome, or liposome formulations contain small vesicles (range: 50 to 5000 nm) consisting of traditional cosmetic materials that protect light-or oxygen-sensitive cosmetic ingredients. Transdermal delivery and cosmetic research suggests that vesicle materials may penetrate the stratum corneum (SC) of the human skin, but not into living skin. Depending on the physical/chemical properties of the ingredient and the formulation, nano-sized formulations may enhance or reduce skin penetration, albeit at a limited rate. Modern sunscreens contain insoluble titanium dioxide (TiO₂) or zinc oxide (ZnO) nanoparticles (NP), which are colorless and reflect/scatter ultraviolet (UV) more efficiently than larger particles. Most available theoretical and experimental evidence suggests that insoluble NP do not penetrate into or through normal as well as compromised human skin. Oral and topical toxicity data suggest that TiO₂ and ZnO NP have low systemic toxicity and are well tolerated on the skin. In vitro cytotoxicity, genotoxicity, and photogenotoxicity studies on TiO₂ or other insoluble NP reporting uptake by cells, oxidative cell damage, or genotoxicity should be interpreted with caution, since such toxicities may be secondary to phagocytosis of mammalian cells exposed to high concentrations of insoluble particles. Caution needs to be exercised concerning topical exposure to other NP that either have characteristics enabling some skin penetration and/or have inherently toxic constituents. Studies on wear debris particles from surgical implants and other toxicity studies on insoluble particles support the traditional toxicology view that the hazard of small particles is mainly defined by the intrinsic toxicity of particles, as distinct from their particle size. There is little evidence supporting the principle that smaller particles have greater effects on the skin or other tissues or produce novel toxicities relative to micro-sized materials. Overall, the current weight of evidence suggests that nano-materials such as nano-sized vesicles or TiO₂ and ZnO nanoparticles currently used in cosmetic preparations or sunscreens pose no risk to human skin or human health, although other NP may have properties that warrant safety evaluation on a case-by-case basis before human use.