HPLC法测定地西泮和艾司唑仑的血药浓度

建立ＨＰＬＣ法同时测定地西泮和艾司唑仑血药浓度。方法：以Ｕｌｔｒａｓｐｈｅｒｅ－ＯＤＳ５μｍ４．６ｍｍ＊２５ｃｍ色谱柱为分离柱,流动相：甲醇－乙腈－水（４０：２０：４０）;检测波长为２５４ｎｍ,以外标法峰面积定量。结论本法可用于血药浓度测定。     

间氯苯哌嗪诱导的小鼠明暗箱焦虑模型 一种新的经济简便抗焦虑药筛选模型

目的　建立经济简便的抗焦虑药模型。方法　用间氯苯哌嗪 (mCPP)诱导产生焦虑 ,观察ddy小鼠和ICR小鼠在明暗箱的行为表现。结果　mCPP在sc 1～ 4mg·kg-1的剂量下即可显著降低ddy小鼠在明箱的活动次数 ,而对暗箱的活动次数影响不显著 ;mCPP在sc 2～ 10mg·kg-1的剂量下对ICR小鼠在明箱的的活动次数影响不明显 ;用地西泮对该模型进行验证 ,发现只用较小的样本量即可得出显著结果。结论　ddy小鼠可取代Wistar大鼠进行mCPP诱导焦虑的明暗箱模型 ,且简便易得 ,经济有效。     

论自然环境因子变化对中药药性形成的影响

中药药性是中药理论的核心,是根据中医传统认识,与疗效有关的药物的性质或属性。药性功效的发挥是通过药材得以体现的,而药材的形成受到了外部环境的影响,包括药物生长的温度、湿度、降水、风、地形、土壤、微生物等因素。本文从中药药性形成的历代医籍考证入手,结合现代研究的认识和结果,剖析了中药生成禀受元素与自然环境因子之间的关系,探讨自然环境因子的变化对中药药性形成的影响,指出中药药性是中药秉承了自然环境中各元素的变化而形成的,是气候、土壤、生物、地形等各环境因子综合作用的结果。     

Cognitive interference as a possible therapeutic strategy to prevent expression of benzodiazepine withdrawal

Benzodiazepines are usually prescribed for anxiety and sleep disorders in long‐term schedules that may cause drug dependence. Discontinuation after prolonged administration may lead to withdrawal expression, being anxiety the most predominant sign. The context‐dependent associative learning process that underlies diazepam dependence can be interfered by pre‐exposure to the drug administration context, an effect known as latent inhibition. Considering this background, the primary aim of the present investigation is to develop a therapeutic strategy to prevent diazepam withdrawal in male Wistar rats by interfering with this learning process. Nitric oxide is a crucial player in learning and memory, hippocampal synaptic transmission and in diazepam withdrawal. Then, a secondary goal is to determine how latent inhibition could alter functional plasticity and neuronal nitric oxide synthase enzyme (NOS‐1) expression within the hippocampus, by using multi‐unitary cell recordings and Western blot, respectively. Our results indicate that chronic diazepam treated animals under latent inhibition did not show anxiety, or changes in hippocampal synaptic transmission, but a significant reduction in NOS‐1 expression was observed. Accordingly, pharmacological NOS‐1 inhibition resembles behavioral and electrophysiological changes induced by latent inhibition. Contrary, diazepam treated animals under Control protocol expressed anxiety and evidenced an increased hippocampal‐plasticity, without alterations in NOS‐1 expression. In conclusion, manipulation of the contextual cues presented during diazepam administration may be considered as an effective non‐pharmacological tool to prevent the withdrawal syndrome. This behavioral strategy may influence hippocampal synaptic transmission, probably by alterations in nitric oxide signaling pathways in this structure.     

Pharmaco‐electroencephalographic responses in the rat differ between active and inactive locomotor states

Quantitative electroencephalography from freely moving rats is commonly used as a translational tool for predicting drug‐effects in humans. We hypothesized that drug‐effects may be expressed differently depending on whether the rat is in active locomotion or sitting still during recording sessions, and proposed automatic state‐detection as a viable tool for estimating drug‐effects free of hypo‐/hyperlocomotion‐induced effects. We aimed at developing a fully automatic and validated method for detecting two behavioural states: active and inactive, in one‐second intervals and to use the method for evaluating ketamine, DOI, d‐cycloserine, d‐amphetamine, and diazepam effects specifically within each state. The developed state‐detector attained high precision with more than 90% of the detected time correctly classified, and multiple differences between the two detected states were discovered. Ketamine‐induced delta activity was found specifically related to locomotion. Ketamine and DOI suppressed theta and beta oscillations exclusively during inactivity. Characteristic gamma and high‐frequency oscillations (HFO) enhancements of the NMDAR and 5HT_2A modulators, speculated associated with locomotion, were profound and often largest during the inactive state. State‐specific analyses, theoretically eliminating biases from altered occurrence of locomotion, revealed only few effects of d‐amphetamine and diazepam. Overall, drug‐effects were most abundant in the inactive state. In conclusion, this new validated and automatic locomotion state‐detection method enables fast and reliable state‐specific analysis facilitating discovery of state‐dependent drug‐effects and control for altered occurrence of locomotion. This may ultimately lead to better cross‐species translation of electrophysiological effects of pharmacological modulations.     

Differential impacts on multiple forms of spatial and contextual memory in diazepam binding inhibitor knockout mice

Learning and memory are fundamental processes that are disrupted in many neurological disorders including Alzheimer’s disease and epilepsy. The hippocampus plays an integral role in these functions, and modulation of synaptic transmission mediated by γ-aminobutyric acid (GABA) type-A receptors (GABA_ARs) impacts hippocampus-dependent learning and memory. The protein diazepam binding inhibitor (DBI) differentially modulates GABA_ARs in various brain regions, including hippocampus, and changes in DBI levels may be linked to altered learning and memory. The effects of genetic loss of DBI signaling on these processes, however, have not been determined. In these studies, we examined male and female constitutive DBI knockout mice and wild-type littermates to investigate the role of DBI signaling in modulating multiple forms of hippocampus-dependent spatial learning and memory. DBI knockout mice did not show impaired discrimination of objects in familiar and novel locations in an object location memory test, but did exhibit reduced time spent exploring the objects. Multiple parameters of Barnes maze performance, testing the capability to utilize spatial reference cues, were disrupted in DBI knockout mice. Furthermore, whereas most wild-type mice adopted a direct search strategy upon learning the location of the target hole, knockout mice showed higher rates of using an inefficient random strategy. In addition, DBI knockout mice displayed typical levels of contextual fear conditioning, but lacked a sex difference observed in wild-type mice. Together, these data suggest that DBI selectively influences certain forms of spatial learning and memory, indicating novel roles for DBI signaling in modulating hippocampus-dependent behavior in a task-specific manner.     

Comparison of treatment modalities in burning mouth syndrome

Background: Burning mouth syndrome (BMS) is characterized by a spontaneous burning pain in the oral mucosa without known organic cause or standardized treatment. The aims of this study were to assess and compare the efficacy of clonazepam and diazepam in relieving the symptoms associated with BMS and evaluate for which patients this treatment might be effective by correlating treatment efficacy with underlying psychological status. Methods: The medical records of BMS patients attending an oral medicine private practice (1999–2004) were reviewed. The patients were then contacted and asked to complete a short questionnaire regarding their response to diazepam/clonazepam drug therapies. A second group of patients attending the above clinic (n = 30) were asked to fill out a hospital anxiety and depression assessment form in an attempt to correlate treatment success with underlying psychological status. Results: A total of 71.4 per cent of patients treated with clonazepam had partial or complete resolution of their oral symptoms, while 55.1 per cent of patients treated with diazepam had improvement of their oral symptoms. There was no correlation between underlying anxiety or depression and efficacy of benzodiazepine medication. Conclusions: A greater percentage of patients taking clonazepam reported either partial or complete relief of symptoms compared to diazepam. However, the differences were not statistically significant. There was no correlation found between underlying psychopathology and treatment success with benzodiazepines.     

Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study

Background and purpose: Evidence‐based data to guide the management of status epilepticus (SE) after failure of primary treatment are still scarce and the alternate needs to be found when phenytoin (PHT) is not available or contraindicated. Comparison of intravenous (IV) valproate (VPA) and diazepam (DZP) infusion has not been conducted in adults with SE. This prospective randomized controlled trial is thus designed to evaluate the relative efficacy and safety of IV VPA and continuous DZP infusion as second‐line anticonvulsants. Methods: After failure of first‐line anticonvulsants treatment, patients with generalized convulsive status epilepticus (GCSE) were randomized to receive either IV VPA or continuous DZP infusion. Primary outcome was the proportion of patients with effective control. Side effects were also evaluated. Results: There were 66 cases enrolled, with the mean age of 41 ± 21 years. Seizure was controlled in 56% (20/36) of the DZP group and 50% (15/30) of the VPA group (P = 0.652). No patient in the VPA group developed respiratory depression, hypotension, or hepatic dysfunction, whereas in the DZP group, 5.5% required ventilation and 5.5% developed hypotension. Time (hour) for regaining consciousness after control was near‐significantly longer in the DZP group [13(3.15–21.5)] than in the VPA group [3(0.75–11)] (P = 0.057). Virus encephalitis and long duration of GCSE were independent risk factors of drug resistance. Conclusions: Both IV VPA and continuous DZP infusion are effective second‐line anticonvulsants for GCSE. IV VPA was well tolerated and free of respiratory depression and hypotension, which may develop in the DZP group. Outcome parameters were not significantly different between groups.     

Anxiolytic‐like Effect of α‐Asarone in Mice

The effects of α‐asarone in four assays predictive of anxiolytic activity in male mice were studied, with diazepam as a positive anxiolytic control. The use of the elevated plus‐maze test revealed that diazepam (2 mg/kg) or α‐asarone (3.5 mg/kg) increased the percentage of entries into open arms and of the time spent on open arms. In the light/dark transition test, as with 2 mg/kg diazepam, 7 mg/kg α‐asarone increased the time spent in the light area and the number of transitions between the two compartments. In the novel food consumption test, α‐asarone (3.5, 7 and 14 mg/kg) caused significant increases in food intake during 5 min as well as diazepam (0.5 mg/kg). In the marble burying test, α‐asarone also produced a significant inhibition of marble burying at doses of 14 and 28 mg/kg, as did diazepam (5 mg/kg). Thus, these findings indicated that α‐asarone exhibited an anxiolytic‐like effect. Further studies will be required to assess the generality of the present findings to other species and behavioral paradigms. Copyright © 2012 John Wiley & Sons, Ltd.     

64层螺旋CT冠状动脉成像患者应用地西泮联合美托洛尔干预心率的效果观察

目的 观察64层螺旋CT冠状动脉成像患者应用地西泮联合美托洛尔干预心率的效果.方法 在造影检查前对受检者进行详细的健康教育,并让其在安静环境下休息15 min后,心率≥90次/min且≤110次/min的患者纳入研究.按预约检查先后顺序随机交替分组,观察组遵医嘱给予联合应用地西泮注射液及盐酸美托洛尔片;对照组单纯口服盐酸美托洛尔片.观察两组受检者心率控制时间及检查时心率波动范围、检查成功率.结果 观察组受检者心率控制时间明显比对照组短,检查过程中心率波动幅度>10次/min的发生率明显比对照组低,检查成功率明显比对照组高,差异均有统计学意义.结论 适当联合应用地西泮注射液及盐酸美托洛尔片可快速有效地控制受检者的紧张情绪,增强控制心率效果,优化工作流程,使设备、人力资源得到最大程度利用.