The effects of paeoniflorin monomer of a Chinese herb on cardiac ion channels / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels.</p><p><b>METHODS</b>Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current (I(Ca-L)), inward rectifier potassium current (I(K1)), and transient outward potassium current (I(to1)) were studied in rat ventricular myocytes and sodium current (I(Na)), slow delayed rectifier current (I(Ks)), and HERG current (I(Kr)) were investigated in transfected human embryonic kidney 293 cells.</p><p><b>RESULTS</b>One hundred µmol/L paeoniflorin reduced the peak I(Ca-L) by 40.29% at the test potential of +10 mV (from (-9.78 ± 0.52) pA/pF to (-5.84 ± 0.89) pA/pF, n = 5, P = 0.028). The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were (-11.22 ± 0.27) mV vs. (-5.95 ± 0.84) mV (n = 5, P = 0.007), respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred µmol/L paeoniflorin completely inhibited the peak I(Na) and the effect was reversible. Moreover, paeoniflorin inhibited the I(K1) by 30.13% at the test potential of -100 mV (from -25.26 ± 8.21) pA/pF to (-17.65 ± 6.52) pA/pF, n = 6, P = 0.015) without effects on the reversal potential and the rectification property. By contrast, 100 µmol/L paeoniflorin had no effects on I(to1), I(Ks) or I(Kr) channels.</p><p><b>CONCLUSIONS</b>The study demonstrated that paeoniflorin blocked I(Ca-L), I(Na), and I(K1) without affecting I(to1), I(Ks), or I(Kr). The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential.</p>

Biological characteristics of arsenic resistance cell chronic arsenic exposure human bone marrow mesenchymal stem cells / 中国地方病学杂志

Objective To study the biological characteristics of arsenic resistance cell model chronic arsenic exposure human bone marrow mesenchymal stem cells (CAsE-hFBMSCs) and discuss the consequence of chronic arsenite exposure to human mesenchymal stem cells (hFBMSCs). Methods hFBMSCs cultivated under general conditions,hFBMSC cell survival rate was detected in 48 hours with arsenite toxicity test under different doses arsenic [0(control),0.25,0.50,1.00,2.00,4.00,8.00,20.00,40.00,80.00,120.00 μmol/L]of the fist 2-generation(P2). According to the test results,1.00 μmol/L sodium arsenite was chosen to stimulate hFBMSCs for 14 weeks as experimental group,simultaneous 0 μmol/L sodium arsenite as the control group. And then,the phenotype was detected by fluorescence-activated cell sorting,and the cell cycle by flow cytometry. Finally,the cell malignant transformation was detected by soft-agar assay. Results Arsenite low than 10 μmol/L promoted cell proliferation,but inhibited cell proliferation when exceeding 10 μmol/L. Half of the lethal dose (LC_(50)) in experimental and control groups were (89.42±0.64),(52.48±0.71)μmol/L. The difference between two groups was statistically significant(t = 123.89,P < 0.05). The phenotype of CAsE-hFBMSCs was CD29,CD90,CD166 positive and CD34,CD45 negative. The phenotype of CAsE-hFBMSCs was the same as the control. Comparing to control group[(8.44±0.45)%,(9.14μ0.14)%,(82.42±0.60)%],G2/M phage[(17.72±5.47)%]and S phage [(25.34±3.36)%]cell increased,G0/G1 phage[(56.96±8.83)%]cell decreased in P2 CAsE-hFBMSCs. The cell cycle became nearly the same as the control group after adaption. CAsE-hFBMSCs did not show clone formation in soft agar clone formation assay. Conclusion Long last and low level exposure to arsenite does not influence the biologic features of hFBMSCs.

Beta2-adrenoceptor gene variant Arg16Gly is associated with idiopathic ventricular outflow-tract tachycardia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Imbalance of the sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia (IVOT). We aimed to investigate whether the major genetic variants in β(1)- and β(2)-adrenoceptors and GNB3 C825T were associated with IVOT and verapamil sensitive idiopathic left ventricular tachycardia (ILVT).</p><p><b>METHODS</b>Patients with IVOT and ILVT from December 2005 to December 2007 were consecutively enrolled into this study. Controls were randomly selected from the community-based inhabitants. Five genetic variants, Ser49Gly and Gly389Arg in the β(1)-adrenoceptor, Arg16Gly and Gln27Glu in the β(2)-adrenoceptor and GNB3 C825T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis.</p><p><b>RESULTS</b>A total of 227 patients with IVOT and 110 patients with ILVT were included. Genotyping revealed that the 16Gly allele of Arg16Gly variant of β(2)-adrenoceptor was associated with a higher risk of IVOT (OR: 1.40, 95%CI: 1.12 - 1.75, P = 0.003 in the addictive model and OR: 1.62, 95%CI: 1.14 - 2.31, P = 0.007 in the dominant model). Patients with Gly16Gln27 haplotype also had a higher risk of IVOT (OR: 1.38, 95%CI: 1.11 - 1.73, P = 0.012). Other four variants, including Ser49Gly and Arg389Gly in β(1)-adrenoceptor, Gln27Glu in β(2)-adrenoceptor and GNB3 C825T, did not differ between patients with IVOT and controls. In patients with ILVT, no significant difference was found in these five variants compared with controls.</p><p><b>CONCLUSIONS</b>Arg16Gly in β(2)-adrenoceptor is significantly associated with IVOT in Chinese Han population. Major genetic variants in β(1)- and β(2)-adrenoceptor and GNB3 C825T may not be associated with ILVT. These data suggest a different arrhythmogenic mechanism in IVOT and ILVT.</p>