Cytoskeleton mediates inhibition of the fast Na+ current in respiratory brainstem neurons during hypoxia

Whole-cell Na+ currents (INa) were recorded in inspiratory neurons in a medullary slice preparation from neonatal mouse that contains the functional respiratory network. Hypoxia and metabolic poisoning with KCN rapidly inhibited INa by reducing the number of Na+ channels available for opening during depolarization. Application of agents specific for G-proteins, protein kinase C and A, intracellular Ca2+ and pH did not prevent the hypoxic inhibition of INa. The effects of hypo-osmolarity and hypoxia were additive, whereas hyperosmolarity partially prevented a subsequent hypoxic inhibition of INa. Cytochalasin B and colchicine decreased, and taxol or phalloidin increased INa and reduced its hypoxic inhibition. We conclude that cytoskeleton rearrangements during hypoxia are responsible for suppression of a fast INa in brainstem respiratory neurons, which could be mediated by the uncoupling of channel inactivation gates from cytoskeletal elements.     

氟罗沙星葡萄糖注射液处方工艺改进

目的　制备符合注射剂质量要求的 2 g· L-1氟罗沙星葡萄糖注射液。方法　去掉原处方中作为抗氧剂的维生素 C,而加入 0 .0 5 g·L-1EDTA- 2 Na作为金属离子络合剂 ;原处方中含量为 2 7.5 g· L-1的葡萄糖调整为 5 0 g· L-1。结果　改进后的 2 g· L-1氟罗沙星葡萄糖注射液质量符合要求。结论　改进后的处方合理 ,制备工艺简单 ,质量稳定。临床用药安全、有效     

Isoform-specific effects of a novel BmK 11(2) peptide toxin on Na channels.

BmK 11(2) is a 7216Da polypeptide toxin purified from the venom of the scorpion Buthus martensii Karsch. Nanomolar concentrations of the toxin prolong amphibian nerve action potentials without attenuation of the amplitude. The pharmacological action of the toxin and its sequence similarity to other alpha-scorpion toxins suggest that BmK 11(2) selectively alters voltage-gated Na channels. In order to test whether BmK 11(2) preferentially modulates the gating or kinetics of certain channel isoforms, we applied BmK 11(2) to muscle, heart and neuronal Na channels. 100nM BmK 11(2) increased the peak current amplitude of skeletal muscle (micro1) and neuronal (N1E-115) Na currents by 40 and 20%, respectively, and reduced the cardiac Na (hH1) current by 15%. The toxin slowed current decay of all isoforms, most prominently in N1E-115 (tau(BmK)/tau(Control)=12), micro1 (11), and less so for hH1 (1.3). BmK 11(2) shifted the voltage dependence of activation of micro1 and N1E-115 currents. BmK 11(2) had no effect on steady-state inactivation, use-dependent availability, and the kinetics of entry into slowly recovering inactivated states.     

胆红素对神经突触膜Na^＋,K^＋—ATP酶影响的实验研究

为了研究胆红素的神经毒性作用，对５９只出生２天的ＳＤ大白鼠分别予以腹腔注射不同剂量胆红素制造高胆红素血症动物模型，不连续密度梯度法分离提取脑神经元突触膜，测定Ｎａ＋，Ｋ＋－ＡＴＰ酶活力。结果：随着血清胆红素浓度的逐渐增加，脑组织中胆红素沉积量也逐渐增加，神经元突触膜Ｎａ＋，Ｋ＋－ＡＴＰ酶活力逐渐降低，Ｎａ＋，Ｋ＋－ＡＴＰ酶活力与脑组织中沉积的胆红素量呈负相关（ｒ＝－０．３４，Ｐ＜０．０１）。提示：胆红素对Ｎａ＋，Ｋ＋－ＡＴＰ酶具有抑制作用。     

兔眼外伤性前部PVR睫状体Na+,K+-ATP酶和碳酸酐酶活性改变

目的　研究外伤性前部PVR睫状体Na ,K ATP酶和碳酸酐酶活性变化 ,进一步探讨外伤性前部PVR导致慢性低眼压的机制。方法　制作外伤性前部PVR导致慢性低眼压兔眼模型 ,伤后分别于 2、4、8、16周测量眼压后取眼球 ,部分睫状体做普通病理切片 ,HE染色观察 ,部分睫状体做Na ,K ATP酶活性测定和碳酸酐酶组织化学观察。结果　伤后实验组Na ,K ATP酶活性下降 ,而对照组变化不很明显 ,2组间比较有显著性差异 ;实验眼睫状体上皮碳酸酐酶组织化学显色部分区域为浓棕黑色 ,表明这部分上皮碳酸酐酶活性接近正常水平 ,而上皮破坏区域 ,酶组织化学显色比较弱 ,接近于阴性对照睫状体上皮的颜色 ,为淡黄褐色 ,表明这部分上皮碳酸酐酶活性较低。结论　外伤性前部PVR睫状体Na ,K ATP酶和碳酸酐酶活性降低 ,是导致房水分泌减少及慢性低眼压的一个重要原因。     

长期使用敌鼠钠盐地区杀灭黄胸鼠的效果评价

目的评价长期使用敌鼠钠盐的地区敌鼠钠盐对黄胸鼠的毒杀效果。方法现场使用不同浓度毒饵进行7d饱和投药。结果0.10%和0.16%稻谷毒饵的盗食率分别为35.99%和26.21%,灭效分别为79.44%和92.70%。0.10%小麦毒饵的盗食率和灭效分别为38.36%和85.92%。2种稻谷毒饵的盗食率差异有显著性(χ2=12.97,P<0.01),灭效差异无显著性(χ2=0.32,P>0.05)。相同浓度的敌鼠钠盐稻谷和小麦毒饵之间盗食率和灭效差异均无显著性(χ2=0.64,P>0.05;χ2=0.03,P>0.05)。结论该地使用敌鼠钠盐防制黄胸鼠仍有良好效果,不宜盲目提高药物的使用浓度,但灭鼠药物的轮换使用应予以重视。     

固相萃取HPLC法测定豆芽中4-氯苯氧乙酸钠

目的:建立固相萃取HPLC法测定豆芽中4-氯苯氧乙酸钠残留的检测方法。方法:豆芽样品经稀碱提取后,用50%的H3PO4溶液调至酸性,经OasisR○HLB柱富集,甲醇洗脱。以甲醇+0.01 mol/L磷酸盐缓冲液(40+60)为流动相,采用ZORBAX SB C18柱(250 mm×4.6 mm×5μm)分离,UV 228 nm检测,外标法定量。结果:豆芽中4-氯苯氧乙酸钠的线性范围在0.20~6.0 mg/L,回收率在92.0%~95.0%,RSD均小于6%,最低定量检出限为0.04 mg/kg。结论:该方法具有快速、灵敏、简便、准确等优点,能满足实际工作的需要。     

The interactions of phenytoin and its binding site in DI‐S6 segment of Na+ channel voltage‐gated peptide by NMR spectroscopy and molecular modeling study

Abstract: Nuclear magnetic resonance (NMR) spectra of a model peptide (BL‐DIS6), in the presence of anticonvulsant diphenyl drug, phenytoin (DPH), were measured to obtain the interactions between the selected drug and the model peptide. BL‐DIS6's sequence corresponds to the S6 segment in domain I of rat brain type IIA Na⁺‐channel. NMR studies have demonstrated that the magnitude of the chemical shifts of amide‐ and α‐protons can be used as a measurement of the complex stability and binding site of the peptide. Our NMR results propose a 3₁₀‐helical structure for BL‐DIS6, and suggest a binding cavity for DPH that involves the hydrophobic particles of residues Ans‐7, Leu‐8, Val‐11, and Val‐12. Furthermore, molecular modeling was performed to provide a possible complex conformation that the phenyl portion of DPH is accommodated in the proximity of the C‐terminal residues Ala‐11 and Val‐12, and simultaneously the heterocyclic amine ring of DPH is perching at the residue Asn‐7 periphery and stabilizing the phenyl portion deep insertion into the peptide.     

周络通对糖尿病周围神经病变大鼠坐骨神经功能影响

目的:研究周络通(黄芪,桂枝,当归,生地,细辛等)对链脲佐菌素(STZ)糖尿病大鼠坐骨神经功能和多元醇代谢通路的影响.方法:动物ig给药,连续8周,观察药物对链脲佐菌素糖尿病大鼠坐骨神经形态学改变、神经传导速度、坐骨神经Na ,K -ATP酶和醛糖还原酶活性及山梨醇、肌醇、果糖、葡萄糖、甘露糖等多元醇含量的影响.结果:周络通对链脲佐菌素糖尿病大鼠坐骨神经形态学改变有明显保护作用,坐骨神经传导速度明显性提高,Na ,N -ATP酶活性增强、醛糖还原酶活性降低,山梨醇、葡萄糖含量降低.结论:周络通可改善糖尿病大鼠周围神经组织的代谢,改善神经组织功能,对STZ糖尿病大鼠周围神经病变具有防治作用.     

不同厂家的银杏叶制剂对冷水负重游泳模型小鼠保护作用的比较研究

目的观察不同厂家银杏叶制剂(天保宁片和金纳多片)对冷水负重游泳模型小鼠的保护作用.方法小鼠8℃冷水负重游泳5min,测定模型小鼠的断头喘气持续时间,并采用分光光度法测定其脑组织生化代谢的改变.结果与空白对照组相比,模型小鼠脑组织乳酸(LA)含量明显增加,乳酸脱氢酶(LDH)、Na -K -ATP酶、Ca2 -Mg2 -ATP酶活力明显降低(P＜0.01);而2个EGB组均可以明显逆转模型小鼠上述生化指标的改变(P＜0.05,P＜0.01).结论不同厂家生产的EGB制剂均对冷水负重游泳模型动物具有保护作用,且在对模型小鼠脑组织生化代谢的影响上未显示出明显差异,故均可以作为耐缺氧研究的阳性药物.