Effects of Mahuang (Herba Ephedra Sinica) and Wuweizi (Fructus Schisandrae Chinensis) medicated serum on chemotactic migration of alveolar macrophages and inters regions macrophages in rats

Objective

To observe the effects of serum containing Mahuang (Herba Ephedra Sinica) or Wuweizi (Fructus Schisandrae Chinensis) on the migration of alveolar macrophages (AM) and interstitial macrophages (IM) from normal rats, and to analyze and compare the mechanisms leading to cell migration differences.

Inhibition of acid-induced apoptosis by targeting ASIC1a mRNA with short hairpin RNA

Aim： To study the role of acid-sensing ion channel （ASIC） 1a in the cell death and apoptosis induced by extracellular acid in C6 glioma cells. Methods： The stable ASIC1a-silenced C6 cell line, built with RNA interference technology, were confirmed by RT-PCR and Western blot analysis. The cell viability following acid exposure was analyzed with lactate dehydrogenase （LDH） and 3-（4,5- dimethylthiazol-2-y1）-2, 5-diphenyltetrazolium bromide （MTT） assay. The apoptotic cells dyed with Annexin-V and propidium iodide were measured with a flow cytometer, while the changes of cell cycle were also assayed. Results： The downregulation of ASIC la proteins by stable transfection of short hairpin RNA decreased the cell death percentage and increased cell viability following acid exposure with LDH and the MTT assay. The rate of apoptosis was lower in the ASIC 1a-silenced cell line than that in the wild-type C6 cell line. The percentage of sub-G0 cells was lower in the ASIC 1a-silenced C6 cells than that in the wild-type cells. Conclusion： Extracellular acid induced cell death and apoptosis via ASIC 1a mechanisms in the C6 glioma cells.     

Electrophysiological study on the high K+ sensitivity of rat glomerulosa cells

 Elevation of extracellular potassium concentration by as little as some tenth of mM activates rat adrenal glomerulosa cells. In the present study some factors responsible for this high K⁺ sensitivity were examined. Using whole-cell voltage-clamp technique we found that both T-type and L-type voltage-dependent Ca²⁺ channels have very low threshold potential (–71 and –58 mV, resp.). By means of patch-clamp technique combined with single-cell fluorimetry we also provided evidence that the activation of I_gl, a K⁺-activated inward rectifying current is associated with Ca²⁺ influx. Both the low activation threshold of voltage-dependent Ca²⁺ channels and the function of I_gl contribute to the exceptional K⁺ sensitivity of the glomerulosa cells. Received: 30 September 1997 / Accepted: 4 November 1997     

雌激素对小鼠心室肌细胞ATP敏感性钾离子通道活性的影响

目的从离子通道水平,观察雌激素(17α-ethynylestradiol and 17β-estradiol)对小鼠心室肌细胞ATP敏感性钾离子通道的影响。方法利用急性酶解法分离小鼠心室肌细胞,采用膜片钳制技术细胞膜内向外及细胞吸附记录模式。结果在钳制电压-60 mV细胞膜内向外记录模式下,向浴液中加入0.1μmol/L、1μmol/L及10μmol/L三种不同浓度雌激素,观察到两种雌激素(17α-ethynylestradiol、17β-estradiol)均对KATP通道有抑制作用,而且呈浓度依赖性,其半数有效浓度分别为0.3μmol/L及0.1 nmol/L。在钳制电压-60mV细胞吸附记录模式下,向浴液中加入pinacidil或2,4-dinitrophenol(DNP)活化KATP通道后,观察3 min,通道活性未见明显影响。在钳制电压-60mV细胞膜内向外记录模式下,向浴液中加入phorbol 12,13-dibutyrate(PDBu)0.001 nmol与处理后,观察到雌激素(10-8、10-3和1μmol/L)对于KATP离子通道活性抑制作用减弱。结论雌激素可通过影响心肌细胞KATP通道活性防止心律失常的产生,从而发挥心肌保护作用。     

Distribution of the voltage gated sodium channel Na(v)1.3-like immunoreactivity in the adult rat central nervous system

Voltage-gated sodium channels are transmembrane proteins responsible for the initiation and propagation of action potentials. One subtype, Na_v1.3 (brain type III) is tetrodotoxin sensitive and fast inactivated. Na_v1.3 has been shown to be expressed at low levels in the adult rat, but to be upregulated after sciatic nerve axotomy in the dorsal root ganglia. In the present study, we used immunohistochemistry to look at the distribution of Na_v1.3 in the adult rat central nervous system. We used a polyclonal antibody, raised against residues 511–524. This epitope corresponds to the sequence located in the intracellular loop between domains I and II of Na_v1.3 and is specific for this sodium channel subtype. We found Na_v1.3-like immunoreactivity (-LI) neurons in the cerebral cortex, hippocampal formation, colliculi, and mesencephalic reticular formation. Na_v1.3-LI was observed in fiber tracts such as the corpus callosum, anterior commissure, corticofugal fibers, lateral lemniscus, and cerebellar peduncles. Na_v1.3-LI was particularly intense in sensory nerve tracts such as the mesencephalic trigeminal tract, vestibulospinal tract, or spinal trigeminal tract. In the spinal cord, Na_v1.3-LI was intense throughout the white matter and the dorsal roots. In the spinal cord grey matter, Na_v1.3-LI fibers terminate in the deep laminae of the dorsal horn and in the ventral horn. Na_v1.3-LI was also found in motoneurons as well as in ventral roots. This study shows that Na_v1.3 is present at the protein level in the adult rat.     

Neuroprotective effect of NS-7, a novel Na+ and Ca2+ channel blocker,in a focal ischemic model in the rat

NS-7 is a novel, voltage-dependent Na(+) and Ca(2+) channel blocker. This study evaluated the in vivo neuroprotective effect of NS-7 in a rat transient focal ischemic model when administered during occlusion. Left middle cerebral artery occlusion was induced in adult male Sprague-Dawley rats for 120 min using an intraluminal thread method. The rats received a single intravenous injection of NS-7 or saline (control group) just after the onset of ischemia, and at 30, 60 and 120 min after ischemia. Their brains were removed after 48 h reperfusion, sectioned, and stained with hematoxylin and eosin. Animals were evaluated by neurological examination at 120 min ischemia and 48 h reperfusion. Infarcted cortex and striatum were measured quantitatively and infarction volumes were calculated. Cortical infarction volumes were 128+/-74 (NS-7) and 214+/-64 mm(3) (control) immediately after the ischemia group, 155+/-48 (NS-7) and 225+/-12 mm(3) (control) after the 30 min group, 160+/-54 (NS-7) and 225+/-48 mm(3) (control) after the 60 min group, and 176+/-43 (NS-7) and 223+/-38 mm(3) (control) after the 120 min group. Cortices in NS-7-treated groups were significantly less infarcted than in control groups at all treatment times. There was no significant difference in the striatal infarction volume between the treatment and control groups. Neurological examination showed that hemiparesis and abnormal posture of the NS-7 groups were significantly more improved at 48 h reperfusion than those of the control groups without posture examination in the 120 min group. These observations suggest that NS-7 may be a new potential therapeutic agent for the acute phase of cerebral infarction.     

Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis

BackgroundCystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In this study we assessed the effect of antisense oligonucleotide eluforsen on CFTR biological activity measured by Nasal Potential Difference (NPD) in patients with the most common mutation, F508del-CFTR.MethodsThis multi-centre, exploratory, open-label study recruited adults with CF homozygous or compound heterozygous for the F508del-CFTR mutation. Subjects received intranasal eluforsen three times weekly for 4 weeks. The primary endpoint was the within-subject change from baseline in total chloride transport (Cl-free+iso), as assessed by NPD. Secondary endpoints included within-subject change from baseline in sodium transport.ResultsIn the homozygous cohort (n = 7; per-protocol population), mean change (90% confidence interval) in Cl-free+iso was ?3.0 mV (?6.6; 0.6) at day 15, ?4.1 mV (?7.8; ?0.4, p = .04) at day 26 (end of treatment) and ? 3.7 mV (?8.0; 0.6) at day 47. This was supported by improved sodium transport as assessed by an increase in average basal potential difference at day 26 of +9.4 mV (1.1; 17.7, p = .04). The compound heterozygous cohort (n = 7) did not show improved chloride or sodium transport NPD values. Eluforsen was well tolerated with a favourable safety profile.ConclusionsIn F508del-CFTR homozygous subjects, repeated intranasal administration of eluforsen improved CFTR activity as measured by NPD, an encouraging indicator of biological activity.     

多功能洗消车的研制

本文阐述了一种多功能洗消车的研制过程。该洗消车主要由洗消舱、设备舱、物资储备仓、洗消帐篷舱、车载污水收集处理装置等构成,具有“舱内洗消”与“充气式帐篷内洗消”2种洗消模式,能够实现对被核生化等物质沾染的人员及伤病员的洗消,并能够防止核生化污染的扩散。     

ATP modulation of large conductance Ca-activated K channels via a functionally associated protein kinase A in CA1 pyramidal neurons from rat hippocampus

Using inside-out configuration of patch clamp techniques, ATP modulation of BK(Ca) channels was studied in hippocampal CA1 pyramidal neurons of adult rat. Intracellular ATP application markedly increased BK(Ca) channel activity, and this ATP-produced increase in BK(Ca) channel activity was characterized by a higher opening frequency with no changes in channel open times. In the presence of specific inhibitor against protein kinase A, H-89, ATP did not induce any increase in the channel activity. Furthermore, adding H-89 after addition of ATP reversed the modulation produced by ATP. In contrast, protein kinase C inhibitor chelerythrine exerted no apparent effects on ATP-induced channel activation. The present study suggests that BK(Ca) channels from hippocampal CA1 pyramidal neurons could be modulated by ATP via a functionally associated protein kinase A-like protein.