Effects of age on reserpine-induced orofacial dyskinesia and possible protection of diphenyl diselenide

Acute reserpine administration produces persistent oral dyskinesia in rats, an alleged animal model of tardive dyskinesia. The pathophysiology of the syndrome remains unclear, but experimental evidence suggests that neurodegeneration in the basal ganglia caused by oxidative stress plays a pivotal role in TD development. In this paper, the authors examined whether diphenyl diselenide, an organochalcogen with antioxidant properties, changes the behavioral and neurochemical effect of acute reserpine administration in old rats. The basal vacuous chewing movements (VCMs) and facial twitching (FT) duration was higher in old rats (15 months of age), when compared with adult rats (3 months of age; 0.01). Basal thiobarbituric acid-reactive species (TBARS) levels were increased only in the cortex of old rats, when compared to adult animals (p < .05). Reserpine injection (1mg/kg, s.c. for 3 days every other day) caused a significant increase on the tongue protusion (TP) frequency (p < .01) and facial twitching duration (p < .01) in old rats. Diphenyl diselenide (10 mg/kg, i.p. for 4 days, starting the day before reserpine) reversed only reserpine-induced TP increase (p < .01). Reserpine caused a significant increase in striatal TBARS levels (p < .01) and diselenide reversed (p < .01) the effect of reserpine on TBARS levels in the striatum. In subcortical parts, isolated reserpine or diselenide administration significantly increased (p < .01) the levels of TBARS, while simultaneous treatment with reserpine and diselenide reverted this effect (p < .01). The results of the present study confirmed the effects of age on orofacial dyskinesia. Diphenyl diselenide, an organochalcogen with antioxidant properties, showed modest effects on reserpine-induced orofacial dyskinesia. However, additional studies are still necessary to establish whether this compound can be considered an effective antioxidant in other models of neurotoxicity.     

Influence of eicosanoids on serotonin release in the rat brain: inhibition by prostaglandins E1 and E2

Summary Cardiac alpha- and beta-adrenoceptor sensitivities were examined after chronic pretreatment of rats with reserpine. Increases in sensitivity would indicate that the receptor is under the influence of the sympathetic innervation, removal by catecholamine depletion with reserpine of the tonic effect of neurotransmitter release would permit receptor upregulation. The positive inotropic responses of paced left atria and papillary muscles and the positive chronotropic responses of spontaneously beating right atria were recorded. A concentration-response curve to isoprenaline (beta-adrenoceptor-mediated) was followed, in the presence of beta-blockade, by one to methoxamine (alpha-adrenoceptor-mediated). Methoxamine exerted positive inotropy of left atria and papillary muscles, the maxima being 43.2 ± 2.7 and 26.8 ± 4.4% of the isoprenaline maxima. A small positive chronotropy (16.5 ± 5.6% maximum) of right atria occurred. After pretreatment with reserpine (1.0 mg kg^–1 i.p. daily) for 7 days, the three preparations displayed supersensitivity to isoprenaline, revealed as a significant displacement (P < 0.05) of the concentration-response curves to the left of those for control rats. Reserpine pretreatment, however, had no effect on the sensitivity to methoxamine. The increase in beta-adrenoceptor sensitivity to isoprenaline after reserpine pretreatment was accompanied by a significant 41.3% increase (P < 0.05) in the number of [³H]-dihydroalprenolol ([³H]-DHA) binding sites (B _max) in ventricular membranes, although the dissociation constant (_{K D}) was unaffected. There were more alpha-adrenoceptor [³H]-prazosin binding sites in ventricular than atrial membranes. However, there was no difference in K _D or B _max between reserpine-pretreated and control tissues. It is proposed that the increase in beta-adrenoceptor sensitivity and binding sites arises from the depletion-induced loss of neuronal noradrenaline release onto the beta-adrenoceptors which are therefore directly under the influence of the neurotransmitter. The failure of cardiac alpha-adrenoceptors to exhibit supersensitivity and increased numbers suggests that they are not directly affected by the sympathetic innervation. Send offprint requests to K. J. Broadley at the above address     

利血平所致大鼠脾虚证代谢组学研究

目的 运用代谢组学方法研究利血平所致脾虚大鼠血清和尿液代谢表型的变化,鉴定与脾虚相关的代谢标志物以探讨脾虚相关代谢途径.方法 利用核磁共振氢谱(1H-NMR)技术建立大鼠血清和尿液的代谢指纹谱.应用正交偏最小二乘判别分析研究对照组和模型组之间的代谢物谱差异,并通过变量重要性投影在血清和尿液中选取生物标志物.结果 利血平所致的脾虚大鼠血清和尿液代谢表型发生明显的变化,在血清和尿液中分别鉴定了与脾虚相关的12种和10种生物标志物.结论 脾虚大鼠机体糖代谢、脂质代谢、氨基酸代谢和氨代谢紊乱,同时,转甲基作用被抑制.该研究为探讨脾虚证的本质、诊断的客观化和脾虚证动物模型的评价提供了一种新方法.     

纳洛酮对失血性休克的治疗作用与交感-肾上腺髓质系统的关系

吗啡受体阻断剂纳洛酮(NAL,3mg/kg)可使失血性休克大鼠血压、脉压及呼吸率显著增加,并提高24h生存率。α受体阻断剂或肾上腺摘除可取消NAL对出血性休克的升压抗休克作用。利血平耗竭外周交感神经系统儿茶酚胺不能取消NAL的升压抗休克作用。利血平化后再切除肾上腺可取消NAL的升压抗休克作用。提示NAL主要通过肾上腺髓质使儿茶酚胺释放增加而引起血压升高。NAL不能使离体灌流肾上腺儿茶酚胺释放增加,说明NAL促进儿茶酚胺释放可能不是对髓质嗜铬细胞直接作用的结果。     

人参皂甙对中枢儿茶酚胺昼夜节律影响的余弦法分析

用荧光分光计法测定小鼠脑内去甲肾上腺素(NE)和多巴胺(DA)含量的正常昼夜节律变化以及人参总皂甙和利血平等药物对中枢儿茶酚胺昼夜节律的影响。小鼠脑内NE和DA呈现明显的生理节律,峰值期均在暗期出现,而光期含量均较低。人参皂甙(GS)对中枢儿茶酚胺的作用强弱或有无依给药昼夜时辰而异。在暗期ip GS使NE明显降低,而在光期投药则否。对于DA,只有12:00时投药有升高作用,而在其余时间投药则无明显影响。为验证上述结果,ip利血平耗竭脑内单胺类递质,则NE和DA的水平在昼夜不同时辰均展示明显降低,但仍然呈现出有意义的昼夜节律变化。此外,乙醇对中枢儿茶酚胺亦有降低作用。     

Accumbal noradrenaline that contributes to the alpha-adrenoceptor-mediated release of dopamine from reserpine-sensitive storage vesicles in the nucleus accumbens is derived from alpha-methyl-para-tyrosine-sensitive pools

Alpha-adrenoceptors in the nucleus accumbens are known to inhibit accumbal dopamine release from reserpine-sensitive pools. The aim of this study was to test our previously reported hypothesis that accumbal noradrenaline that controls the dopamine release from these storage vesicles is derived from alpha-methyl-para-tyrosine-sensitive pools. The sensitivity of accumbal alpha-adrenoceptors to noradrenergic agents depends on the amount of noradrenaline that is available in the synapse. In case the synaptic noradrenaline levels decrease, the conformation of alpha-adrenoceptors changes into a state that makes these receptors more sensitive to its agonists. The effects of alpha-methyl-para-tyrosine, respectively reserpine, on the alpha-adrenoceptor-agonist-induced changes of accumbal dopamine release were investigated. Alpha-methyl-para-tyrosine, but not reserpine, made accumbal postsynaptic alpha-adrenoceptors more sensitive to phenylephrine. These results indicate that noradrenaline that inhibits the release of dopamine from reserpine-sensitive storage vesicles, via stimulation of accumbal postsynaptic alpha-adrenoceptors, is derived from alpha-methyl-para-tyrosine-sensitive pools. The clinical impact of these data is discussed.     

妊娠期高血压疾病降压治疗的安全性探讨

目的对降压治疗妊娠期高血压疾病的安全性及有效性进行探讨。方法对2010年5月～2011年11月在本院就诊的100例妊娠期高血压患者的病例资料进行回顾性分析。通过随机方式将100例患者分为试验组和对照组,试验组患者40例,对照组患者60例。对照组接受传统常规降压药物进行治疗,试验组则通过静脉滴注和口服肼苯哒嗪及利血平等药物进行降压治疗。并对两组患者产后出血以及凝血功能情况进行及时的观察和记录。结果试验组40例患者经治疗后在产后出血以及凝血功能等方面均好于对照组,证明其治疗的安全性和有效性要好于传统方法。结论治疗妊娠期高血压疾病采用肼苯哒嗪、利血平等药物治疗效果较好,安全性高,值得应用。     

The sea urchin embryo, an invertebrate model for mammalian developmental neurotoxicity, reveals multiple neurotransmitter mechanisms for effects of chlorpyrifos: therapeutic interventions and a comparison with the monoamine depleter, reserpine

Lower organisms show promise for the screening of neurotoxicants that might target mammalian brain development. Sea urchins use neurotransmitters as embryonic growth regulatory signals, so that adverse effects on neural substrates for mammalian brain development can be studied in this simple organism. We compared the effects of the organophosphate insecticide, chlorpyrifos in sea urchin embryos with those of the monoamine depleter, reserpine, so as to investigate multiple neurotransmitter mechanisms involved in developmental toxicity and to evaluate different therapeutic interventions corresponding to each neurotransmitter system. Whereas reserpine interfered with all stages of embryonic development, the effects of chlorpyrifos did not emerge until the mid-blastula stage. After that point, the effects of the two agents were similar. Treatment with membrane permeable analogs of the monoamine neurotransmitters, serotonin and dopamine, prevented the adverse effects of either chlorpyrifos or reserpine, despite the fact that chlorpyrifos works simultaneously through actions on acetylcholine, monoamines and other neurotransmitter pathways. This suggests that different neurotransmitters, converging on the same downstream signaling events, could work together or in parallel to offset the developmental disruption caused by exposure to disparate agents. We tested this hypothesis by evaluating membrane permeable analogs of acetylcholine and cannabinoids, both of which proved effective against chlorpyrifos- or reserpine-induced teratogenesis. Invertebrate test systems can provide both a screening procedure for mammalian neuroteratogenesis and may uncover novel mechanisms underlying developmental vulnerability as well as possible therapeutic approaches to prevent teratogenesis.     

胃肠宁对利血平所致大鼠脾虚模型的影响

目的 观察胃肠宁对大鼠脾虚证模型的影响.方法 36只大鼠随机分为正常对照组、脾虚模型组、四君子汤组和胃肠宁组,每组9只.采用利血平复制大鼠脾虚模型,连续灌胃14 d后,处死大鼠,分离肝、十二指肠和血清,测定各组大鼠血浆LDH、AKP、AchE、CK和肝组织匀浆中SOD、MDA、GSH-Px、NOS含量变化,并观察各组大鼠肝和十二指肠病理变化.结果 与正常对照组相比,脾虚模型组大鼠LDH、AchE、CK、SOD、GSH-Px、NOS含量明显降低,而AKP、MDA含量明显升高;与脾虚模型组相比,胃肠宁组LDH、AchE、CK、SOD、GSH-Px、NOS含量显著升高,而AKP、MDA含量显著降低;脾虚模型组大鼠肝组织发生广泛性颗粒变性和空泡变性;十二指肠上皮及绒毛明显脱落,大量炎性细胞浸润,杯状细胞数量明显减少,胃肠宁组与脾虚组相比,肝和十二指肠病理变化明显减轻.结论 胃肠宁对利血平所致大鼠脾虚具有较好的治疗作用.     

复方利血平片质量标准的研究

目的：提高完善复方利血平片的质量标准.方法：采用化学方法建立了处方中利血平、氢氯噻嗪、盐酸异丙嗪、维生素B1维生素B6、KCl、泛酸钙、三硅酸镁的鉴别项,并对其作空白对照,专属性良好;采用HPLC法建立了利血平、氢氯噻嗪、盐酸异丙嗪三个成分的含量测定项目.结果：定性定量准确、专属性强、重现性好.结论：提高后的质量标准可有效地控制该产品的内在质量.