Simultaneous determination of five anti-epilepsy drugs in human plasma using liquid chromatography-mass spectrometry

A new liquid chromatography-mass spectrometry method for the determination of carbamazepine,clonazepam,alprazolam,estazolam and phenytoin in human plasma has been developed by using diazepam as an internal standard.Chromatographic separation was performed on a Zorbax SB-C18 column(30 mm × 2.1 mm,3.5 ?m) with a mobile phase consisting of methanol and aqueous 25 mM ammonium acetate using gradient elution.A diethyl ether extraction method was used for the extraction of five anti-epilepsy drugs.The final extract was injected for analysis by LC-MS/MS.The method was validated within the concentration range of 50-5000 ng mL-1 for five anti-epilepsy drugs.The precision of the assay(RSD%) was less than 10% at all concentration levels within the tested range.The method recoveries for all samples were more than 90%.The results indicate that the method is specific,sensitive and accurate,and suitable to study the pharmacokinetics,to adjust the dosage for individual administration,and to monitor the drug-concentration and drug abuse of the five anti-epilepsy drugs.

A review of studies on the therapeutic effect of vagus nerve stimulation

BACKGROUND： Vagus nerve widely innervates in the human body, and it has diverse physiological functions. Many new physiological functions are gradually found. Studies on its action mechanism have been gradually deepened. Vagus nerve stimulation （VNS） has been used for treatment of epilepsy and depression in clinic. OBJECTIVE： To retrospectively investigate the therapeutic effects and mechanism of VNS. RETRIEVE STRATEGY： A computer-based online research in Pubmed with the key words of ＂vagus nerve stimulation＂ published between February 1990 and October 2006 in English were systemically reviewed. Totally 583 articles were collected and primarily selected. Inclusive criteria： the mechanism of therapeutic effects of VNS-related literatures. Exclusive criteria： repetitive study. LITERATURE EVALUATION： According to inclusive criteria, of the 57 articles, which met the inclusive criteria, 42 were associated with the therapeutic function of VNS, and 15 with the mechanism of these related functions. DATA SYNTHESIS： Vagus nerve has special nerve innervation and wide projection with extensive physiological effects. Till now, VNS has been used in the therapy of epilepsy and depression, and exact clinical effects have been obtained. Further studies have discovered other functions of VNS, such as the effect on the memory power, cognition, and perception to pain. Thus, the studies about VNS become diverse. Just because of the special physiological functions of vagus nerve, VNS can bring some adverse reactions such as foreign body sensation, hoarseness, trigeminal neuralgia, etc. The mechanism of therapeutic function of VNS is still under exploration. CONCLUSION： As a mature surgical technique, VNS has been widely used in the therapy of epilepsy, depression, inflammation, analgesia, relieving itching, etc. Although the mechanism is still unclear, it brings obvious clinical effects.

S1-1 Xenon Exerts Antiepileptic Effects via Increased Autophagy on Kainic Acid-Induced Acute Generalized Seizures in Rats

Objective:Xenon is an inhalation anesthetic with a favorable safety profile,and previous studies have demonstrated the neuroprotective efficacy of xenon in Alzheimer’s disease,spinal cord ischemia/reperfusion injury,intrauterine asphyxia and neonatal asphyxia.Further studies confirmed the inhibition of uptake and efflux of glutamate and mediating the neuroprotective effect through the inhibition of excessive excitation and anti-apoptosis.However,whether xenon plays a role in epilepsy remains unclear.This study aimed to investigate the role of xenon treatment in kainic acid(KA)-induced acute generalized epileptic seizures in male Sprague-Dawley rats.Methods:All rats were treated with KA(1 mg/0.8 ml,0.65μl/rat),which was injected into the lateral ventricle through the cannula.Seizure severity was staged as 1~5 based on Racine’s criteria.Rats in the xenon group were treated with xenon mixture(70%xenon/30%oxygen)for 1 h immediately after KA injection,while rats in the control group were treated with 70%nitrogen/30%oxygen.In order to assess the role of autophagy in the antiepileptic effects induced by xenon,the inhibitors of autophagy(3-methyladenine,3-MA or bafilomycin A1,BafA1)and the inducer of autophagy(rapamycin)were administered before xenon

Changes of glucocorticoid receptor mRNA expression in basolateral amygdale-kindled rats

Background Glucocorticoid receptor （GR） is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model. Methods Firstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance （ANOVA） was employed for comparing means of multiple groups, followed Fisher＇s least significant difference （LSD） for paired comparison. Results The rats were successfully kindled after an average of （13.50＋3.99） times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups （P 〈0.001）. The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs （P 〈0.001 compared with the epilepsy group）, accompanied by attenuation of seizures and improvement of electroencephalograms. Conclusions Down-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change.