钾通道开放剂Pinacidil及其类似物的合成

不同烷基取代的吡啶氰胍类化合物均具一定降压活性,Pinacidil是这类药物的代表,为一新型的降压药物。我们设计并合成了10个3-吡啶取代的类似物(均未见文献报道),并通过元素分析,MS,~1HNMR和IR确定了它们的结构。初步的药理试验表明,大部分化合物均有一定的降压活性,深入的药理工作正在进行之中。     

EFFECT OF ELECTROACUPUNCTURE AND CALCIUM-CHANNEL INHIBITORS ON CYTOPLASMIC FREE CALCIUM CONCENTRATION OF MOUSE BRAIN CELLS

Ithasbeenrecognizedthattheunivalentandbi valentionsareimportanttothenormalactivitiesof thenervoussystem,especially,Ca2+playsakeyrole inthestabilityandpermeabilityofneurilemma,the transmissionofnerveimpulses,releaseoftransmitters ofthenerveendingsandtheirresultantbiologicef fectsthroughthepost synapticmembrane,generation andaftereffectsofthesecondmessenger,etc.[1,4].Manyresearcheshaveshowedthattheanalgesiceffect ofmorphine likedrugsandendogenousmorphine like substances(endorphin,etc)isrealizedb…     

基于Markov模型对2种治疗高血压联合用药方案的药物经济学评价

目的 通过建立Markov模型,对血管紧张素受体拮抗剂（angiotensin receptor blockage,ARB）联合二氢吡啶类钙通道阻滞剂（calcium channel blockers,CCB）、ARB联合噻嗪类利尿剂2种治疗高血压方案进行药物经济学评价,为临床用药提供循证依据。方法 检索Medline及PubMed英文数据库,以“hypertension、calcium channel blockers、diuretics、angiotensin II receptor blocker、randomized controlled trial”及其对应的MeSH词为关键词进行检索。参考药品价格、治疗成本、健康效用值、状态转移概率建立Markov模型,对2种方案的有效性和经济学进行评价,并进行敏感性分析。结果 ARB+CCB组治疗高血压累计成本为32 780.34元,获得6.73质量调整生命年（quality-adjusted life years,QALYs）;ARB+利尿剂组治疗高血压累计成本为31 781.07元,获得6.81QALYs,相比于ARB+CCB组的增量成本效果比为-12 490.88元/QALYs。敏感性分析与原结果一致。结论 与ARB+CCB组相比,ARB+利尿剂组能获得更长的生存结果,其付出的增量成本–效果低于1倍人均GDP,更具有经济学效益。     

HIF-1参与KATP通道对神经元缺氧损伤保护作用

目的 探讨三磷酸腺苷(ATP)敏感性钾通道(K_ATP通道)在缺氧中对海马神经元的保护作用机制。方法 比较对照组、单纯缺氧组、K_ATP通道激动剂+缺氧组、K_ATP通道阻断剂+缺氧组中神经元缺氧诱导因子1α亚基(HIF-1α)的蛋白表达、DNA断裂、以及神经元存活情况。结果 试验持续8,12,24 h后,正常氧分压组细胞存活率为(100±0.98)%,缺氧8,12,24 h后,细胞的存活率分别降至(85.76±3.31)%,(80.13±1.76)%,(72.24±3.87)%,差异均有统计学意义(P<0.05);缺氧12,24 h后,缺氧+二氮嗪组细胞凋亡率分别为(8.1±3.1)%,(18.4±2.3)%,缺氧+甲糖宁组分别为(32.5±1.6)%,(45.7±3.4)%,与单纯缺氧组的(20.3±2.2)%,(31.6±1.7)%比较,差异均有统计学意义(P<0.05)。结论 K_ATP通道可以通过上调HIF-1α的蛋白表达水平,对缺氧中的海马神经元起到保护作用。     

医院建筑应急功能的建设实践

对于区域性、地区性的大型急救中心建设是非常必要的。此类急救中心在应对突发公共急救事件时因能够起到中流砥柱的作用,急救效果往往事半功倍,因而各级政府应给予重视与扶持。     

Time-dependent effects of electroacupuncture at the Ren channel on extracellular signal-regulated kinases 1/2 expression in focal cerebral ischemia rats

BACKGROUND: The onset of focal cerebral ischemia activates extracellular signal-regulated kinases 1 and 2, regulates cell cycle, promotes cell proliferation and differentiation, and affects the normal stage and function of brain cells.OBJECTIVE: To observe the effects of electroacupuncture at the Ren channel on extracellular signal-regulated kinases 1/2 expression in the lateral cerebral ventricle wall of rats with focal cerebral ischemia. The effects were analyzed at different time points after intervention.DESIGN: Randomized controlled study.SETTING: Department of Anatomy, Sun Yat-Sen University. MATERIALS: A total of 60 healthy adult male Wistar rats weighing (250±10) g were provided by the Experimental Animal Center, Medical College of Sun Yat-Sen University. The animal experiment was conducted with confirmed consent by the local ethics committee. The GB6805-Ⅱ electric acupuncture apparatus was provided by Shanghai Medical Equipment High-techno Company. METHODS: The experiment was performed at the Laboratory of Anatomy, Sun Yat-Sen University, from February to July 2007. All experimental animals were randomly divided into the following groups: normal group (n = 6), sham operation group (n = 18), model group (n = 18), and electroacupuncture group (n = 18). Middle cerebral artery occlusion (MCAO) was performed in the model group and electroacupuncture group. Zea Longa's grading standard was used to assess neurological impairment after reperfusion; animals whose grades were between 1 and 4 were included in this study. The normal control group was not exposed to MCAO. In sham operation animals, the right common carotid artery (CCA) was isolated, and the external carotid artery (ECA) was damaged, but no embolism was induced. The electroacupuncture group was given acupuncture on the second day after surgery. The acupoint locations were chosen according to Experimental Acupuncture (People's Publishing House; 1997; First Edition). The Chengjiang, Qihai, and Guanyuan acupoints were labeled and connected to a G6805 electroacupuncture apparatus with sparse-dense waves (sparse waves were 30 Hz, dense waves were 100 Hz), with a frequency of 6-15 V. The duration was 20 minutes. Two days after surgery, the model and sham operation groups were placed with their backs on the operating table, but they received no acupuncture. However, the normal group received acupuncture. The experimental animals under anesthesia were sacrificed on days 7, 14, and 28 post-surgery. Western blot analysis was used to measure expression of extracellular signal-regulated kinases 1/2 in the inferior region of the lateral cerebral ventricle wall. Expression was measured in the normal group at time points corresponding to the sham operation group. MAIN OUTCOME MEASURES: Expression of extracellular signal-regulated kinases 1/2 in the inferior region of the lateral cerebral ventricle wall at different time points after intervention.RESULTS: All 60 rats were included in the final analysis, without any loss. Seven days after MCAO, there was no significant difference in extracellular signal-regulated kinases 1/2 expression in the electroacupuncture group compared to the model group (P > 0.05). However, extracellular signal-regulated kinases 1/2 expression significantly increased in the model group at 14 and 28 days after treatment (P < 0.05).CONCLUSION: Electroacupuncture at the Ren channel can enhance extracellular signal-regulated kinases1/2 expression in the inferior region of the lateral cerebral ventricle wall of rats with focal cerebral ischemia. However, this effect is not apparent until 14 days after electroacupuncture intervention.     

润坦注射液对大鼠局灶性脑缺血再灌注后神经元凋亡的影响

目的研究润坦对局灶性脑缺血再灌注的神经保护效应.方法制备线栓法大脑中动脉闭塞再灌注模型,干预组每天给予润坦3 mg/kg,对照组给予等量生理盐水,每日对大鼠神经功能缺损进行评分,于再灌注12 h、24 h、48 h和5 d处死动物,切片作TUNEL原位凋亡检测.结果润坦可以显著改善术后第2 d大鼠的神经功能缺损(P＜0.05),降低致死率,减少再灌注24 h以后的细胞凋亡数目(P＜0.05).结论润坦可以抑制大鼠脑缺血再灌注后神经元凋亡,对急性期脑梗死可能有神经保护效应.     

Memantine (1-amino-3,5-dimethyladamantane) blocks the serotonin-induced depolarization response in a neuronal cell line

The influence of memantine on several properties of a neuronal cell line was tested. The aim was to get some insight into possible mechanisms of action of this drug which is therapeutically applicable in treatment of spasticity, Parkinson's disease, and cerebral coma. In neuroblastoma X glioma hybrid cells, memantine, at micromolar concentrations, blocked the depolarization induced by iontophoretically applied serotonin (5-hydroxytryptamine, 5-HT). In the hybrid cells, receptors of the 5-HT3 type mediated the depolarization, which was frequently accompanied by a series of action potentials. The inhibition by memantine of the serotonin response occurred fast and was completely reversible, irrespective of whether the cell showed a stable membrane potential or spontaneous action potentials. However, memantine did not alter spontaneous or electrically evoked action potential activity in the hybrid cells, and apparently did not block the underlying ionic conductances. Furthermore memantine did not affect either the cation permeability activated by substance P in the hybrid cells or the K+ channel triggered by bradykinin in a glioma cell line. Thus, memantine appears specifically to suppress the ion channel opened by serotonin in the hybrid cells. The interaction of memantine with serotonin receptors and the associated ion channels reported here, might give an important clue, as to a site of action of memantine in the nervous system.