苯妥英钠、苯巴比妥钠诱导建立难治性癫(癎)动物模型

目的探索性应用苯妥英钠（PHT）、苯巴比妥钠（PB）诱导建立难治性癫痫动物模型，并研究其多药耐药机制。方法将60只大鼠随机分为实验组50只和对照组10只；实验组给予亚抽搐剂量戊四氮腹腔注射，其中45只大鼠确定点燃．将其随机分为给药组35只和未给药组10只。给药组应用较大剂量PHT、PB腹腔注射，其间注射小剂量戊四氮．根据Racine行为分级以及脑电图改变，从中筛选出耐PHT和PB的难治性癫痫动物模型。应用免疫组化法观察比较P糖蛋白（Pgp）在各组脑组织中的表达。结果12只大鼠制成难治性癫痫动物模型（耐药组），11只为药物有效组，12只死亡。耐药组大鼠脑组织Pgp表达较对照组、未给药组和药物有效组增强，差异有高度统计学意义（P〈0．01）。结论应用较大剂量PHT和PB诱导点燃大鼠制作难治性癫痫的动物模型．方法可行。该模型可以用于研究难治性癫痫脑内PgP的表达。PgP的高表达与难治性癫痫发生密切相关。     

Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene

Around 6% of infants born to mothers taking anticonvulsants have malformations, including neural tube defects, and a further proportion show developmental delay in later childhood. Three commonly used anticonvulsants, carbamazepine, phenytoin and sodium valproate, interfere with folic acid metabolism. We investigated the common 677 C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in samples from 57 patients and their parents and 152 controls to determine its contribution to the risk of fetal anticonvulsant syndrome. The 677 C>T mutation frequency was significantly higher in the mothers than in the controls, but there was no significant difference in 677 C>T frequency in the patients or in the fathers. Genotype frequencies in the mothers were significantly different from controls, there being an excess of 677 C>T homozygotes. Amongst the patients, there was an apparent excess of heterozygotes (not statistically significant), and the fathers were not significantly different from controls. Mutation in the MTHFR gene in a mother taking sodium valproate, phenytoin or carbamazepine during pregnancy is associated with fetal anticonvulsant syndrome in her offspring. The skewed distribution of genotypes in the affected children probably reflects the association of fetal anticonvulsant syndrome with the maternal genotype.     

Psychomotor impairment and anticonvulsant therapy in adult epileptic patients

Summary Using a battery of simple tests, psychomotor performance was assessed in 11 healthy subjects, 14 untreated epileptic patients and 66 epileptics on chronic anticonvulsant medication. Significant differences were found between controls and untreated patients for choice reaction time, card sorting and Simple Simon memory game. Treated patients performed less well than both untreated epileptics and controls in choice reaction time (p<0.05; p<0.001), card sorting (p<0.01; p<0.001), Simple Simon (p<0.05; p<0.001) and finger tapping (p<0.05; p<0.001). Patients with centrencephalic epilepsy were slower than those with discrete focal EEG abnormalities in reaction time and card sorting. Patients receiving treatment with carbamazepine, phenytoin or sodium valproate alone all performed similarly to each other and to those patients taking anticonvulsant polypharmacy. Monotherapy patients with potentially toxic plasma anticonvulsant concentrations did no worse than those within or below the therapeutic range. Both the disease and its treatment reduce psychomotor performance. All major anticonvulsants appear to cause a similar degree of impairment across a wide range of concentrations. The effect of chronic anticonvulsant medication on quality of life should not be neglected in the pursuit of perfect seizure control.     

Serotonin in mania and in the mechanism of action of mood stabilizers: a review of clinical studies

Objectives: Serotonin (5-hydroxytryptamine, 5-HT) was implicated in the pathophysiology of manic-depressive illness as early as 1958. Although extensive evidence has accumulated since then to support 5-HT's role in depression, relatively fewer studies examined its role in mania. The purpose of this paper was to review and summarize the current state of knowledge on the role of 5-HT in mania and its treatment.

Methods: We systemically reviewed clinical studies of 1) 5-HT function in mania and 2) 5-HT in the mechanism of action of mood stabilizers, including lithium and anticonvulsants.

Results: Review showed that cerebrospinal fluid, postmortem, platelet, neuroendocrine challenge, and tryptophan depletion studies provided some evidence to support the hypothesis that a 5-HT deficit is involved in mania and that enhancement of 5-HT neurotransmission exerts a mood-stabilizing effect.

Conclusions: There is some evidence from clinical studies for the contribution of 5-HT in mania and in the mechanism of action of mood stabilizers. However, it is very likely that other neurotransmitters also play important roles. Future directions for research include 1) in vivo study of 5-HT receptor subtypes using positron emission tomography, 2) investigation of the interaction between 5-HT and other neurotransmitter systems, and 3) determination of the relationships between diagnostic subtypes of mania and 5-HT function and other neurotransmitter systems.     

Pharmacotherapeutic options for complex regional pain syndrome

Introduction: Complex regional pain syndromes (CRPS) are rare painful conditions characterized by considerable variability in possible triggering factors, usually traumatic, and in the clinical scenario. The limited knowledge of the pathophysiological mechanisms has led to countless treatment attempts with multiple conservative and surgical options that act by different mechanisms of action.

Areas covered: In this narrative review, the authors discuss key points about CRPS definitions, diagnostic criteria and pitfalls, pathophysiological hypotheses, and treatment strategies with particular reference to pharmacotherapy. The article was based on a literature search using PubMed while the available guidelines for the management of CRPS were also examined.

Expert opinion: According to the quality of evidence, pharmacological interventions for CRPS seem to be more effective all the more so when they act on peripheral mechanisms, particularly on nociceptive pain, and when applied early in the disease, while reliable evidence about central mechanisms of chronic pain in CRPS is lacking. In our opinion, drug therapy should be preferred as early as possible, particularly in warm forms of CRPS to prevent significant functional limitation, psychological distress, and social and economic fallout.     

Effect of gabapentin pretreatment on propofol consumption,hemodynamic variables,and postoperative pain relief in breast cancer surgery

Study objectiveGabapentin is an inhibitory neurotransmitter of the central nervous system. This prospective randomized double-blind study was conducted to evaluate the effects of gabapentin on intraoperative propofol requirements, hemodynamic variables, and postoperative pain relief in breast cancer patients.Materials and methodsForty adult females of the American Society of Anesthesiologists (ASA) Grade I-II physical status, undergoing total mastectomy for breast cancer were included. Patients were randomly allocated into two groups. Two hours prior to surgery the gabapentin group received gabapentin 600 mg and the control group received placebo. Anesthesia was induced with intravenous fentanyl, propofol, and vecuronium, and maintained with propofol infusion titrated according to the bispectral index. Postoperative analgesia was provided with intramuscular diclofenac sodium and intravenous morphine on demand.ResultsThe intraoperative propofol consumption was significantly less in the gabapentin group as compared with the control group (p = 0.009), whereas there was no difference in fentanyl and vecuronium requirements. Patients in the gabapentin group had lower pain scores at 30 minutes, 1 hour, and 2 hours postoperatively (p < 0.001). The postoperative morphine consumption was also less in the gabapentin group compared with the control group (p = 0.006). No significant adverse effects were noticeable.ConclusionPreoperative administration of gabapentin reduced intraoperative propofol requirements and postoperative analgesic consumption in breast cancer patients undergoing total mastectomy.