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F. Berger U. Borchard D. Hafner T. Kammer T. Weis 《Naunyn-Schmiedeberg's archives of pharmacology》1991,344(6):653-661
Summary The electrophysiologic mode of action and potency of the verapamil derivative YS 035 (N,N-bis-(3,4-dimethoxyphenethyl)-N-methyl amine) were investigated in sheep cardiac Purkinje fibres. Action potential duration measured at a repolarization level of –60 mV (APD-60) and membrane currents recorded with the two-microelectrode voltage-clamp technique were evaluated. At 10 mol/l YS 035 APD-60 was increased to about 115% of reference. Prolongation measured as percentage of the respective control exhibited on the average no dependence on stimulation frequency (0.17–2 Hz). At 100 mol/l membrane became depolarized to about –50 mV and action potentials could no longer be elicited. Further study was focussed on effects on outward currents, mostly activated at a frequency of 0.05 Hz. Transient outward current (ito) was completely blocked at 100 mol/l and half-maximal inhibition occurred at about 14 mol/l. Inwardly rectifying potassium current (iK1) was reduced to 47% of reference at 100 mol/l. An initially activating outward current at positive membrane potentials (iinst) was reduced to 73% at 100 mol/l. Time-dependent (delayed) outward current (iK) was on the average not affected up to 100 ol/l. Besides inhibition of repolarizing outward currents YS 035 completely blocked pacemaker current (if) at 100 mol/l and half-maximal reduction was achieved at 5 mol/l. YS 035 (1–100 mol/l) did not clearly affect time constants of activation at selected test potentials (IK: +35 mV; if: –90 mV) or inactivation (ito: 0 mV). Voltage-dependent control mechanisms of currents (itto, if) were not influenced by YS 035 but the amount of available current was reduced.In conclusion, the verapamil derivative YS 035 inhibited pacemaker current and potassium outward currents which correlated to a prolongation of cardiac action po tentials. Electrophysiological actions of the compound favour it to be tested in vivo as an antiarrhythmic drug candidate.
Send offprint requests to U. Borchard at the above address 相似文献
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Yoon HG Yoon SH Son WY Lee SW Park SP Im KS Lim JH 《Journal of assisted reproduction and genetics》2001,18(6):325-329
Purpose: To demonstrate that human immature oocytes retrieved from women with regular menstrual cycles can undergo maturation and fertilization, and that the resulting embryos can establish pregnancies.Methods: Immature oocytes (n = 568) were retrieved from women with regular menstrual cycle. The intact immature oocytes (n = 506) were allowed to mature in YS medium supplemented with 70% human follicular fluid (hFF); the matured oocytes were fertilized with husband sperm. Two pronuclei oocytes were cocultured with cumulus cells in YS medium supplemented with 10% hFF until 2 or 3 days after insemination. The cleaved embryos were transferred in uteri.Results: Follicles were aspirated on Day 9.2 ± 5.3 of 63 natural cycles from 51 patients (mean age = 34.8 ± 4.0 years). The average number of retrieved immature oocytes was 9.0. The maturation rate was 74.3% (376/506). The two PN and cleavage rates were 72.6% (273/376) and 89.0% (243/273), respectively. Embryo transfer was achieved in 51 cycles and clinical pregnancy rate was 17.6% (9/51).Conclusions: The results suggest that in vitro matured oocytes can undergo fertilization and the resulting embryos may successfully lead to pregnancies. However, further research is needed to improve IVM technique to achieve success rate comparable to gonadotrophin stimulated cycles. 相似文献
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目的:研究YS3004C脑功能(障碍)治疗仪在精神病(精神分裂症、抑郁症和神经衰弱等)治疗中的作用;脑功能治疗为精神病康复的一种物理治疗,该治疗仪由主机、磁疗帽(带)和治疗主电极组成,是采用磁疗和电疗两种治疗方式的医疗设备。方法:通过介绍YS3004C脑功能(障碍)治疗仪的原理以及进行脑功能治疗配合药物治疗的对比研究,分析讨论该仪器对精神病患者的辅助治疗效果。结果:YS3004C脑功能(障碍)治疗仪联合药物治疗有较好的疗效,优于单纯药物治疗,可作为一种有效的辅助治疗方法。结论:YS3004C脑功能(障碍)治疗仪具有科学性、可靠性和良好的治疗效果。 相似文献
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目的建立酶联免疫吸附法(ELISA)以检测海洋真菌多糖YS4108发酵过程中抗肿瘤多糖(YCP)的含量。方法以CDAP(1-氰基-4-二甲胺吡啶四氟硼酸盐)为交联剂制备YCP-BSA偶联产物,利用该偶联产物为包被抗原,YCP为竞争抗原,两者与定量的YCP-McAb反应,建立检测YCP的间接竞争ELISA测定法。结果最佳抗原包被浓度为2.5 mg/L,最佳单抗工作浓度为1∶5 000,HRP-抗小鼠IgG工作浓度为1∶4 000。得到回归方程lg(B/B0%)=-0.171 8 lgCYCP+1.963 8,r=0.991 6,可测量最适范围为1~1 000μg/L,最小检测量为0.1μg/L,批内和批间RSD分别小于5.45%和8.37%。结论建立了快速测定YCP含量的间接竞争ELISA法。 相似文献
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为了能快速、灵敏、较全面反映中西药注射剂临床联合用药相互作用,该文采用等温滴定量热法(isothermal titration calorimetry,ITC),以注射用益气复脉(冻干)为模式药,考察其分别与盐酸肾上腺素和5%葡萄糖注射液的相容性,以热力学参数吉布斯自由能 (ΔG)、焓变 (ΔH)、熵变 (ΔS) 判断溶合反应类型,通过对比不同注射剂混合前后化学指纹图谱特征信息对结果进行佐证。结果表明,注射用益气复脉(冻干)与盐酸肾上腺素滴定过程中测得|ΔH|>T|ΔS|,为焓驱动反应,且释放热量较大,提示两者之间的相互作用以化学反应为主,内在物质发生改变。注射用益气复脉(冻干)与5%葡萄糖溶液溶合时|ΔH|<T |ΔS|,为熵驱动反应,且反应活性谱显示放热较少,提示两者之间的相互作用以物理反应为主,活性成分仅被溶解稀释,未发生质变。ITC法可用于注射用益气复脉(冻干)临床联合用药相互作用表征的研究,亦可用作其他中药注射剂临床联合用药相容性评价。 相似文献
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《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(7-8):1301-1317
Evidence has accumulated that systemic administration of converting enzyme inhibitors (CEI) such as captopril, MK 421 or SA 446 not only produces an inhibition of the plasma renin angiotensin system (RAS), but also of the RAS in various target organs which are relevant for blood pressure (BP) regulation. A potential target organ is the brain, where a local CE inhibition could contribute to the BP lowering action of CEI. CE in the brain can be inhibited by intracerebroventricular (i.c.v.) injection of CEI as evidenced by an inhibition of the pressor and drinking responses to i.c.v. angiotensin I (ANG I) or renin and by potentiation of the pressor responses to i.c.v. bradykinin. Site of the inhibition is not only the cerebrospinal fluid but also periventricular brain tissue such as the hypothalamus. I.c.v. injection of captopril at doses which inhibit brain CE but do not leak into the peripheral blood were shown to lower BP in conscious stroke-prone spontaneously hypertensive rats (SHRSP), but not in normotensive Wistar Kyoto (WKY) controls. Acute peripheral administration of CEI can produce an inhibition of brain CE. This was shown by an attenuation of the drinking responses to i.c.v. ANG I and renin and by direct measurements of CE activity in brain tissue. Chronic oral treatment with CEI produces changes of brain RAS parameters which suggest an inhibition of ANG II formation in the brain. 相似文献
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Isolation of complementary DNA unique to the genome of avian myeloblastosis virus (AMV) 总被引:6,自引:0,他引:6
Avian myeloblastosis virus (AMV) can transform avian cells of hemopoietic origin, such as bone marrow, embryonic yolk sac, and circulating macrophages. The AMV is defective in its replication and can only replicate in the presence of helper viruses. This defectiveness in replication is probably due to a deletion or substitution of nucleotide sequences in its genome. The AMV genome contains no sequences homologous to the src gene, which is responsible for the transforming function of the sarcoma viruses. We attempted to identify the AMV sequences that may contain sequences which are responsible for its transforming function. We isolated a complementary DNA (cDNAAMV) that hybridized preferentially to the RNA of the transforming AMV but not to the RNA of the helper virus. Using this cDNAAMV as a probe, we determined the size of the AMV genome to be 33–34 S with a molecular weight of 2.6 × 106. A similar molecular weight estimation of the AMV genome size was obtained by methylmercury-agarose gel electrophoresis of AMV RNA. In AMV-producer myeloblasts we can detect about 6000–7000 copies per cell of AMV-specific RNA, whereas fewer than 2 copies per cell of AMV RNA are found in helper virus-infected cells. In AMV nonproducer myeloblasts, about 2000 copies of AMV-specific RNA are detected. Furthermore, we find that RNA of AMV NP myeloblasts can only hybridize to 55% of cDNA complementary to helper virus genome. In uninfected hemopoietic cells, e.g., bone marrow cells, about 20 copies per cell of AMV-specific RNA are present, whereas in uninfected chick embryo fibroblasts less than 1 copy per cell is found. 相似文献