药物性生理失调的后果-畅销镇痛药罗非昔布另解

Selective cyclo-oxygenase-2(COX-2) inhibitor, VI-OXX(rofecoxib), was voluntarily withdrawn worldwide from drugstores by its maker Merck & Co., Inc. on Sep-tember 30, 2004, for its potential lethal side effects of heart attack or stroke.     

Anticonvulsant efficacy of topiramate in phenytoin-resistant kindled rats

PURPOSE: We evaluated the anticonvulsant efficacy of topiramate (TPM), a structurally novel antiepileptic drug (AED), in amygdala kindled rats that had been preselected with respect to their response to phenytoin (PHT). METHODS: Anticonvulsant response was tested by determining the afterdischarge threshold (ADT; i.e., a sensitive measure for drug effects on focal seizure activity). By repeated testing with the PHT prodrug fosphenytoin (FOS) three groups of kindled rats were separated: rats in which consistent anticonvulsant effects were obtained (PHT responders), rats that showed no anticonvulsant response (PHT nonresponders), and rats with variable responses (variable PHT responders). The latter, largest group was used to evaluate at which doses and pretreatment times TPM exerted significant anticonvulsant effects on ADT. For this purpose, TPM was tested at four doses (20, 40, 80, 160 mg/kg i.p.) and two pretreatment times (1 and 4 h). The most effective treatment protocol was then used for TPM testing in PHT responders and nonresponders. RESULTS: TPM proved to be an effective AED in the kindling model. At 40 mg/kg, significant ADT increases were obtained after both 1 and 4 h after administration. In addition to the effect on focal seizure threshold, seizure severity and duration recorded at ADT were decreased by TPM, indicating that this drug acts on both seizure threshold and seizure spread. In PHT nonresponders, TPM significantly increased ADT, which is in line with its proven efficacy in patients with refractory partial epilepsy in whom phenytoin has failed. However, TPM was more efficacious in increasing ADT in PHT responders than in nonresponders, substantiating that the difference between these groups of kindled rats extends to other AEDs. Repeated testing of kindled rats with TPM indicated that, similar to PHT, there are individual kindled rats without anticonvulsant response to TPM (i.e., TPM nonresponders). CONCLUSIONS: The data of this study substantiate that PHT nonresponders are a unique model for the search of new AEDs with improved efficacy in refractory partial epilepsy.     

Conduct of trials in private clinical practice

PURPOSE: Trials of antiepileptic medications are usually based in tertiary referral centers with teaching hospital resources. Epilepsy Research & Services (ERS) is part of a private outpatient neurological clinic that is involved in research as part of multicenter clinical trials, adhering to Good Clinical Research Practice. ERS is subject to external monitoring and auditing, but does so outside of the teaching hospital environment. METHODS: The clinic is operated by a neurologist supported by a research assistant, administrative and nursing staff and has no formal university attachment. Patients are recruited for trials from routine referrals for clinical care. The center has formal ties with the ethics committee of the local teaching hospital, but none of the team is formally attached to that hospital. RESULTS: The center conducted trials of zonisamide, oxcarbazepine, gabapentin, remacemide, tiagabine, vigabatrin, felbamate, and lamotrigine both as add-on trials in refractory seizure disorders and as monotherapy trials in de novo epilepsy. More than 200 patients have been recruited for trials at ERS (with some patients being involved in more than one trial). External review endorsed ERS as a superior environment for such research and as a model for other centers. CONCLUSIONS: Private practice is a viable alternative for the conduct of clincial trials and should be considered when establishing such protocols. Simplicity of administration and clinical practice, which more closely mirrors standard patient care, may enhance recruitment and management.     

The dopamine D3 receptor antagonist nafadotride inhibits development of locomotor sensitization to amphetamine

Behavioral sensitization is a well-studied model of behavioral plasticity mediated at least in part by dopaminergic systems believed to play an important role in several psychiatric conditions. In the rodent, locomotion is regulated by the opposing balance of D3 and D2 receptors, with D2 activation increasing and D3 stimulation inhibiting locomotion. However, receptor occupancy of D3 dopamine receptors is far greater than D2 or D1 occupancy at typical post-stimulant dopamine concentrations. We therefore hypothesized that tolerance of D3 receptor inhibition of locomotion contributes to the development of sensitization. To test this hypothesis, we examined the effect of the D3 receptor antagonist nafadotride on sensitization. As predicted, nafadotride inhibits augmentation of the locomotion response to repetitive amphetamine. This finding is consistent with the proposed model of adaptive down-regulation of D3 dopamine receptor function contributing to the development of behavioral sensitization.     

Randomised double-blind comparison of fentanyl, mivacurium or placebo to facilitate laryngeal mask airway insertion

In a double-blind randomised study, we compared conditions during insertion of the laryngeal mask airway in 150 patients who received either fentanyl 1 microg.kg-1, mivacurium 0.04 mg.kg-1 or normal saline, before induction of anaesthesia with propofol 2 mg.kg-1. Insertion conditions, including mouth opening, swallowing, gagging or coughing, head or limb movement and ease of insertion, were each graded using a three-point scale. The median (interquartile range) summed insertion scores were more favourable with the use of fentanyl [8.0 (7.0-9.0)] and mivacurium [7.5 (6.8-8.3)] than with normal saline [9.0 (7.8-10.3); p < 0.01]. Fentanyl and mivacurium decreased swallowing and head or limb movement, and mivacurium improved mouth opening. Insertion conditions were similar between fentanyl and mivacurium, while both prolonged apnoea. Fentanyl and mivacurium are equally effective in facilitating insertion of the laryngeal mask airway following anaesthetic induction with propofol.     

Airway Reactivity to Bronchoconstrictor and Bronchodilator: Assessment Using Thin-Section and Volumetric Three-Dimensional CT

Objective

To determine the extent to which thin-section and volumetric three-dimensional CT can depict airway reactivity to bronchostimulator, and to assess the effect of different airway sizes on the degree of reactivity.

Materials and Methods

In eight dogs, thin-section CT scans were obtained before and after the administration of methacholine and ventolin. Cross-sectional areas of bronchi at multiple levels, as shown by axial CT, proximal airway volume as revealed by three-dimensional imaging, and peak airway pressure were measured. The significance of airway change induced by methacholine and ventolin, expressed by percentage changes in cross-sectional area, proximal airway volume, and peak airway pressure was statistically evaluated, as was correlation between the degree of airway reactivity and the area of airways.

Results

Cross-sectional areas of the bronchi decreased significantly after the administration of methacholine, and scans obtained after a delay of 5 minutes showed that normalization was insufficient. Ventolin induced a significant increase in cross-sectional areas and an increase in proximal airway volume, while the effect of methacholine on the latter was the opposite. Peak airway pressure increased after the administration of methacholine, and after a 5-minute delay its level was near that of the control state. Ventolin, however, induced no significant decrease. The degree of airway reactivity did not correlate with airway size.

Conclusion

Thin-section and volumetric spiral CT with three-dimensional reconstruction can demonstrate airway reactivity to bronchostimulator. The degree of reactivity did not correlate with airway size.     

海洋岩虫抗菌肽筛选及抗癌活性的初步研究

将岩虫匀浆液经反相浓缩、凝胶过滤和亲和柱层析获得活性组分，在体外用MTS／PMS(氮兰四唑盐／吩嗪硫酸甲酯)方法筛选抗菌肽，再分别用MTS／PMS方法和ELISA—AFP(甲胎蛋白)方法检测其对人肝癌细胞株HepG2增殖、AFP分泌及对正常大鼠成骨细胞株MC3T3-E1增殖的影响。结果表明，纯化的岩虫抗菌肽为组成型碱性蛋白(MW8．1kDa，pI8．6)，不同浓度抗菌肽对肝癌细胞增殖和AFP的分泌均有抑制作用，抑制作用大小与抗菌肽浓度呈正相关性；对正常成骨细胞未见明显的抑制和杀伤作用。     

多器官保存液的研究进展(Ⅰ)

本文综述了30年来多器官保存液的基础研究和临床应用的状况及进展。论述了器官保存的关键点。对现有的多器官保存液,包括:组氨酸-色氨酸-α-酮戊二酸溶液、威斯康星大学溶液、高渗枸橼酸盐腺嘌呤溶液、自制长征-1号溶液、Celsior溶液、Euro-Collins溶液、Carolina rinse溶液、St.ThomasⅡ溶液、乳果糖-组氨酸-聚蔗糖溶液、上海多器官溶液及其他器官保存液的成分及其特点进行分析,评估了上述器官保存液对脏器的保存效果,简述了中药在器官保存液中的应用。     

我国“审方药师”的现状分析与建议

目的:培养合格的审方药师,确保患者合理用药。方法:分析我国审方药师的现状,提出培养合格审方药师的具体建议。结果:目前,我国审方药师队伍普遍存在学历、职称偏低,专业知识、医学知识不足,成员匮乏等现象。结论:必须充分认识审方药师的重要性,提高审方药师的准入条件,制订审方药师的业务标准,明确审方药师的责任,加大审方药师的培养力度及增加审方药师的数量,方可确保患者合理用药。