Ligustrazine inhibits high voltage-gated Ca~(2+) and TTX-resistant Na~+ channels of primary sensory neuron and thermal nociception in the rat:a study on peripheral mechanism

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinoci-ceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency ( PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.     

银质针灸治疗下腰部软组织疼痛

Chronicsofttissuelesionisaspeciallymedicalterm，andanimportantpathologicalchangesofdiseases，suchaschronicoveruseinjuriesandconversionofacuteinjuriesinlowbackorfrominter－vertebraldiscprotrusion，anddislocationofintervertebraljointsaswell，whichmainlycauseseverepaininlowback犤１犦．Manypresentmethods（oralmedicine，massage，anestheticblock，physicalthera－piesetc．）havebeenusedforrelievingthepain，whichdemandsagreatfiscalsupportannually．Unfortunately，thereportsonthemechanismsandeffectofthem…     

A Clinical Study of Reversing Left Ventricular Hypertrophy in Hypertensive Patients by Adalat

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80例健康青年分别经针刺或艾灸肺俞穴后的肺功能变化

目的：探讨针刺与艾灸肺俞穴对健康人肺功能的影响。方法：我们选择了20－22岁健康男性80例，随机分为针刺组和艾灸组各40例，于针刺，艾灸前和针刺，艾灸后10min测试用力肺活量（FVC），用力呼气量（FEV1．0），最大呼气中段流速（MMF），最大呼气流量（PEFR），75％，50％，25％肺活量时的最大呼气流速（V75，V50，V25），结果：显示经针刺和艾灸肺俞穴后2组FVC，FFV1．0均显著增加，P＜0．05，2组间比较针刺组FVC明显高于艾灸组，P＜0．05，而且艾灸组MMF，V25亦显著降低P＜0．05，结论：健康人经针刺和艾灸肺俞穴后均可使大气道阻力减少，肺容量增加，提示一定量的艾燃烧后的烟雾可使健康人肺功能受到影响，使肺的小气道收缩，出现阻塞性改变。     

钾通道阻断剂对低氧/复氧诱导的培养海马神经元死亡的防护作用

目的研究钾通道阻断剂对单纯低氧/复氧诱导的培养海马神经元死亡的防护作用。方法培养8 d的海马神经元置于低氧环境(95% N2/5% CO2)6 h,复氧再培养直至72 h,复氧后0.5 h培养液内分别给予不同钾通道阻断剂,用细胞计数及MTT比色法检测神经元死亡情况。结果低氧/复氧诱导培养海马神经元出现迟发性死亡;四乙铵以剂量依赖性的方式防护低氧/复氧诱导的培养海马神经元免于死亡;大电导钙激活钾通道(BK通道)阻断剂iberiotoxin(IbTX)可完全消除低氧/复氧诱导的神经元死亡(P<0.001);A型钾通道阻断剂4-氨基吡啶不能防护低氧/复氧诱导的神经元免于死亡(P>0.05)。结论钾通道阻断剂四乙铵和IbTX能防护低氧/复氧诱导的培养海马神经元免于死亡,提示某些类型的钾通道尤其是BK通道活动增强可能参与了低氧/复氧诱导的培养海马神经元死亡。     

Ineffectiveness of organic calcium channel blockers in antagonizing long-term potentiation

Evidence has accumulated suggesting that the presence of calcium is critical for development of hippocampal long-term potentiation (LTP). However, there is a paucity of information about whether calcium's role in LTP is pre- or postsynaptic. In the present study, we examined the effectiveness of nitrendipine, verapamil, flunarizine and the benzodiazepine diazepam in: blocking voltage-dependent calcium channels; blocking synaptic transmission; and preventing development of LTP. Using the in vitro slice preparation, we obtained intracellular and extracellular recordings from guinea pig hippocampal CA1 pyramidal cells. At the cellular level, all 4 drugs were ineffective in blocking voltage-dependent calcium spikes (TTX resistant) and the calcium-dependent afterhyperpolarization. Verapamil and diazepam appeared to antagonize synaptic transmission, as reflected in smaller population spike amplitudes. Development of long-term potentiation was not affected by the presence of verapamil, flunarizine and diazepam. Nitrendipine appeared to reduce the percentage of slices exhibiting LTP; however, ethanol, the vehicle used to dissolve nitrendipine, was shown in separate experiments to reduce the percentage of slices exhibiting LTP. These results suggest that neither the organic calcium channel blockers--nitrendipine, verapamil, and flunarizine--nor micromolar concentrations of diazepam are potent blockers of extrasynaptic voltage-sensitive calcium channels in hippocampus. They thus cannot be used to demonstrate a specific pre- or postsynaptic calcium role in LTP.     

艾灸联合弥可保治疗糖尿病周围神经病变40例

目的评价艾灸联合弥可保治疗糖尿病周围神经病变的疗效。方法对糖尿病周围神经病变患者80例按1∶1比例等分为联合组和对照组,两组基于等同的基础治疗之上,联合组用艾灸联合弥可保治疗,对照组单纯用弥可保治疗,疗程3个月,比较治疗前后的神经传导速度变化和症状改善情况。结果联合组和对照组神经传导速度均改善,以联合组改善更明显;联合组和对照组显效、有效、无效分别是52.5%、32.5%、15.0%和35.0%、27.5%、37.5%,组间差异有统计学意义(P<0.01或P<0.05)。结论建立于基础治疗之上的艾灸联合弥可保治疗糖尿病周围神经病变优于单纯弥可保治疗。     

Molecular basis of severe myoclonic epilepsy in infancy

Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies.     

ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels.

The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels.     

单刺十七椎对原发性痛经患者止痛作用时效规律的观察

目的观察单刺十七椎对原发性痛经患者止痛作用的时效规律。方法单刺十七椎,留针30min,分别记录针刺前即时和留针5min、10min、20min、30min及起针后30min、60min、120min的VAS读值,然后进行统计分析。结果留针30min条件下,单刺十七椎的止痛作用持续加强,直至起针;起针50min后,针刺止痛作用衰减为接近峰值的一半。结论单独针刺十七椎,留针30min的止痛作用优于留针短于30min的止痛效果。针刺十七椎时,留针30min条件下的半衰期较短,对于痛经持续时间在1d左右或更长的患者,针刺频次以每天针刺2次为宜。