载药带膜型镍钛金属支架体外溶出度试验

目的 考察载药带膜镍钛金属支架中粉防己碱体外溶出度。方法 模拟人体食道环境，用紫外分光光度法测定了载药带膜镍钛合金支架中药物的体外溶出度。结果 释药方程log(100Rn)=0．011 5t 2．1730(t=0～168h)，r=0.9805，T50=41．39h，Td=53．01h，Kr=0．0115(h-1)。结论 该支架体外释药符合一级释药模式，具有缓释特点，能满足治疗需要。     

Cognition and Paroxysmal EEG Activities: From a Single Spike to Electrical Status Epilepticus during Sleep

Summary:  Epileptic EEG paroxysms can interfere with cognitive processes producing transitory effects, such as those related to a single spike, as well as long-lasting effects, such as in electrical status epilepticus during slow-wave sleep (ESES). Focal spike-related disruption of cortical functions can produce transitory cognitive impairment, with neuroanatomical specificity between the site of the epileptic focus and the impaired cognitive tasks. ESES represents a model of the long-lasting effects of continuous spike-wave activity on higher cortical functions. The duration of ESES and the localization of interictal foci seem to play a major role in influencing the degree and type of cognitive dysfunction, suggesting that the ESES clinical picture results from a localized disruption of EEG activity caused by focal epileptic activity during sleep. Recently, Giulio Tononi's group reported that a local increase of slow-wave activity (SWA) during sleep after learning is associated with improved performance of the learned task after sleep (Huber et al., Nature 2004;430:78–81). On the basis of these findings, we can speculate that prolonged focal epileptic activity during sleep (as occurring in ESES) interferes with local SWA at the site of the epileptic focus, impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions.     

盐酸利多卡因缓释胶丸的药代动力学研究

目的　研究盐酸利多卡因缓释胶丸 (简称缓释胶丸 )的动物药代动力学。方法　用高效液相色谱分别测定缓释胶丸的释药动力学、血药浓度及组织分布浓度。结果　家兔皮下植入缓释胶丸 40mg·kg-1·丸 -1·只 -1后第 3 60min ,仍有近 1/ 3残留率。缓释胶丸 2 0、40和 80mg·kg-13组的Ta1/2 分别比对照组 (盐酸利多卡因水溶液 10mg·kg-1皮下浸润注射 )明显延长 ;Te1/2 与对照组接近 ;随着剂量增大 ,缓释比提高 ,Tr1/2 明显延长。缓释胶丸 3组的Tmax比对照组明显延长 ,40mg·kg-1组的Cmax比对照组还低 ,80mg·kg-1组的Cmax接近或达到人的中毒浓度。大鼠皮下植入缓释胶丸 40mg·kg-1后 ,局部皮肤组织的药物浓度明显升高 ,肝脏中较低 ,肾脏中较高。结论　皮下植入缓释胶丸能使局部组织内利多卡因保持长时间、高浓度 ,以满足术后切口镇痛的需要     

Agreement of Visual Scoring of Sleep Stages among Many Laboratories in Japan: Effect of a Supplementary Definition of Slow Wave on Scoring of Slow Wave Sleep

Abstract: The purpose of this study was to elucidate the agreement of visual scoring of all-night polysomnographic recordings among many scorers from different laboratories. Ten scorers including the author from different laboratories in Japan scored the same paper recordings of two young male subjects. We calculated the agreement rate for each stage using an epoch by epoch analysis. In both records, the agreement rates for stages 2 and R were high; on the contrary, those for stages 3 and 4 were low. After adding a supplementary definition of high voltage slow wave in deep sleep, we scored the first NREM period of another subject. The mean agreement rate for stage 3 among 10 scorers was significantly higher than those of the two former subjects. However, the agreement for stage 4 did not change so much. This result demonstrates that there is much interrater (laboratory) variability of visual scoring, especially in slow wave sleep. When the result of automatic scoring is compared to that of the visual scoring to evaluate the reliability of automatic scoring, these findings must be considered.     

Local control of axonal properties by Schwann cells: neurofilaments and axonal transport in homologous and heterologous nerve grafts.

A number of axonal properties, including slow axonal transport and neurofilament phosphorylation, are altered in a mutant mouse strain with a Schwann cell deficiency, the Trembler. The Trembler phenotype is associated with poor myelination and reduced axonal caliber in the peripheral nervous system, but the genetic lesion has not yet been identified. To determine whether changes in axonal properties resulted from a direct action of Schwann cells on the axon, a segment of sciatic nerve from myelin-deficient Trembler mouse was grafted into the sciatic nerve of a normal mouse and normal axons were allowed to regenerate. Normal axons surrounded by Trembler Schwann cells are reduced in diameter, but resume their original diameter distal to the graft. Neurofilament transport was also affected locally in sciatic nerves with Trembler grafts into normal nerve. The velocity of neurofilament transport was not significantly different from controls in portions of the nerve proximal to the Trembler graft, but there was a reduction in neurofilament transport rates upon entering the Trembler graft. This was accompanied by an increase in the ratio of neurofilament over tubulin in the case of the Trembler graft, suggesting both a slowing of the neurofilament and an increase in the rate of tubulin transport. Using heterologous grafts of Trembler nerve segments into wildtype nerves, Schwann cells were shown to locally influence axonal caliber, neurofilament organization, and slow axonal transport. These observations emphasize the importance of glial cells in modulating neuronal structure and functions, as well as focusing attention on the role of glia in the etiology of neuropathologies that alter the neuronal environment.     

Peptidyl and azapeptidyl methylketones as substrate analog inhibitors of papain and cathepsin B

Peptidyl methylketones containing Phe, Tyr, Tyr(I), Tyr(I₂), Leu and Ile in P₂ were synthesized and tested as substrate analog reversible inhibitors of papain and bovine spleen cathepsin B. The most effective cathepsin B inhibitor contained Tyr(I₂) and displayed an inhibition constant of 4.7 μM at pH 6.8 and 25°C, while Leu or Ile gave practically inert analogs. Replacement of the amino acids in P₂ with the analogous α-azaamino acids, as well as the glycine in P₁ with α-azaglycine, led to complete loss of inhibiting activity. Introducing alkoxy substituents at the methyl adjacent to the ketone group generally resulted in more effective inhibitors, with inhibition constants in the micromolar range for both papain and cathepsin B.     

Magnetic Source Imaging of Abnormal Low-Frequency Magnetic Activity in Presurgical Evaluations of Epilepsy

Summary: Purpose: Regional cortical dysfunction associated with epileptogenic activity was predicted from interic-tal localized abnormal low frequency neuromagnetic activity (ALFMA) using Magnetic Source Imaging (MSI). ALFMA can be detected in patients who show no interictal spikes. Methods: A large array biomagnetometer was used in a blinded, rapid screening protocol. The MSI procedure required no alteration in epileptic medications. MSI results were compared with the presumed epileptogenic region as determined by a consensus of standard techniques, which included MR and electroclinical monitoring. Results: One or more sites of localized abnormality were detected by MSI ALFMA in 29 of the 33 epileptic patients. ALFMA mapped with MSI showed a 48.5% specificity with respect to the presumed epileptogenic region. MSI ALFMA was in agreement with the final consensus as often as was ictal noninvasive video EEG monitoring, and was exceeded in specificity overall only by invasive ictal video EEG monitoring, which was required for conventional localization in 21 of the 33 patients tested with MSI. Conclusions: ALFMA measurements with MSI may augment the array of noninvasive methods used for reaching a consensus for epilepsy surgery.     

"泻剂结肠"大鼠结肠肌电活动及其对乙酰胆碱反应的变化

目的 探讨慢传输型便秘(Slow transit constipation，STC)的发生机制。方法 建立大鼠“泻剂结肠”模型，测定大鼠结肠肌电生理活动及其对乙酰胆碱(Ach)的反应变化。结果 “泻剂结肠”大鼠结肠慢波的频率减慢与振幅降低；结肠对Ach的反应性明显减弱。结论 长期服用接触性泻剂，对结肠ENS有损害作用，在STC的发生机制中具有重要意义。     

Differential Effects of Bupivacaine on Cardiac K Channels: Role of Channel Inactivation and Subunit Composition in Drug—Channel Interaction

Mechanisms of Bupivacaine's Actions on K Channels. Introduction : We examined the effects of a nonspecific ion channel blocker, bupivacaine, on K channels encoded by hERG, rKvl.4, rKv4.3, and hKvLQTI along with hIsK. Their native counterparts in the heart are important for the function of I_Kr, I_to, and I_Ks and, thus, play an important role in repolarization.
Methods and Results : To elucidate the mechanisms and sites of bupivacaine's actions, we correlated the voltage and time dependencies of drug effects with those of channel gating. We also studied the effects of altering the C-type (hERG) or N-type (rKvl.4) inactivation process or the subunit composition (hKvLQT1 with or without hIsK) on bupivacaine's actions. The results suggest that, except for hKvLQT1 co-expressed with hIsK, bupivacaine binding occurred at depolarized voltages coinciding with channel activation. With hKvLQT1 co-expressed with hIsK, bupivacaine bound preferentially at negative voltages when channels were in the closed state, and unbound at depolarized voltages when channels opened. The C-type inactivation of hERG enhanced, whereas the N-type inactivation of rKv1.4 hindered, bupivacaine's effects.
Conclusion : We propose that bupivacaine's actions on these K channels can be described as a nonspecific pore blockade in the inner mouth region. However, the apparent binding affinity and voltage dependence of binding can be differentially influenced by the inactivation processes occurring at two ends of the pore (C-type inactivation at the outer end and N-type inactivation at the inner end), or by the interaction between hIsK and hKvLQT1 subunits.