Beneficial effects of vitamin C and vitamin E on reserpine-induced oral dyskinesia in rats: critical role of striatal catalase activity

Oral dyskinesias are implicated in a series of neuropathologies and have been associated to an increase in oxidative stress. Several antioxidants, including vitamin E, decrease reserpine-induced oral dyskinesia (OD) in rodents and we have described a protective role of striatal catalase against the development of OD. The aim of this study was to verify the effects of vitamin C alone or in combination with vitamin E on reserpine-induced OD as well as to determine a possible role of catalase in the antidyskinetic property of these vitamins. Different doses of vitamin C attenuated reserpine-induced increase in OD. A similar treatment with an effective dose of vitamin C concomitant to an effective dose of vitamin E potentiated the antidyskinetic effect of both vitamins when administered alone. The administration of these vitamins alone produced an increase in striatal catalase activity that likewise was potentiated by their combined administration. In addition, the antidyskinetic property of vitamin E and vitamin C was abolished by a concomitant treatment with the catalase inhibitor aminotriazole. These results indicate a beneficial effect of these vitamins and reinforce the critical role of striatal catalase against the development of oral dyskinesias.     

社区复方制剂抗高血压治疗研究:2年干预效果分析

目的:观察复方利血平氨苯喋啶片(北京降压0号)和复方利血平片(复方降压片)长期治疗轻、中度高血压的效果、安全性和依从性。方法 :选取2008-10至2009-01北京7个农村社区的轻、中度原发性高血压患者766例,年龄45~75岁,随机分成2组,分别服用北京降压0号(降压0号组,393例)和复方降压片(复降片组,373例),北京降压0号的剂量为0.5~1片/次,1次/d,复方降压片的剂量为1~2片/次,3次/d,观察时间为24个月。结果 :共710例患者完成试验,降压0号组与复降片组患者收缩压/舒张压下降幅度[(24.7±13.9/13.2±8.8)mm Hg vs(23.0±14.2/11.9±9.5)mm Hg,1 mm Hg=0.133 k Pa]、总有效率(89.0%vs 84.5%)、不良反应发生率(0.5%vs 1.34%)差异均无统计学意义(P0.05)。对于2级高血压患者,服药后1、6、12、24个月降压0号组舒张压的下降幅度均高于复降片组,差异有统计学意义(P0.05);降压0号组患者在服药24个月末依从性高于复降片组[(99.2±4.8)%vs(98.2±6.5)%],差异有统计学意义(P0.05)。结论 :北京降压0号依从性和对2级高血压的降压幅度高于复方降压片。两组不良反应差异不明显,均未见明显的不良作用。     

复方利血平片中盐酸异丙嗪的含量测定及含量均匀度考察

目的建立测定复方利血平片中盐酸异丙嗪含量的高效液相色谱法。方法采用AgilentTCC18柱（250mm×4．6mm,5μm）,以乙腈-0．3％十二烷基硫酸钠溶液-磷酸（60：40：0．02．用三乙胺调pH至3．3）为流动相,流速为1．0mL／min,检测波长为250nm。结果盐酸异丙嗪进样量在0．504～1．176μg范围内与峰面积线性关系良好,r=0．9999（n=5）,平均回收率为98．71％,RSD=0．80％（n=9）。结论该法适用于复方利血平片中盐酸异丙嗪的含量测定。     

利血平与优降宁对动物痛阈和吗啡镇痛作用影响因素探讨

采用三种测痛方法,观察了利血平、优降宁对小鼠、大鼠正常痛阈和吗啡镇痛作用的影响,结果表明:ip利血平2 mg/kg,优降宁100 mg/kg均能明显抑制小鼠扭体反应;ip利血平1 mg/kg能明显提高小鼠热板反应时间,但ip优降宁75 mg/kg无明显影响;ip利血平6 mg/kg,优降宁75 mg/kg对大鼠甩尾反应时间均无明显影响;利血平(小鼠0.5～1.0 mg/kg,大鼠2 mg/kg ip)能明显对抗吗啡镇痛作用;优降宁(小鼠35 mg/kg,大鼠50 mg/kg ip)能明显增强吗啡镇痛作用,并能“逆转”利血平对抗吗啡镇痛作用。其“逆转”作用的强弱取决于利血平、优降宁给药的先后次序。     

Reserpine and the suppression of both edema formation and cellular infiltrate of the contact sensitivity reaction in the mouse

Summary Reserpine treatment in doses of 1.0 and 5.0 mg/kg body weight, given 6 h before antigen challenge significantly suppresses the contact sensitivity reaction to picryl chloride in sensitized mice. The suppression involves both the edema formation, measured as ear swelling, and the accumulation of inflammatory cells at the test site. This is probably mediated through inhibition of the release of vasoactive amines from local mast cells.     

利血平对多巴胺所致PC12细胞程序性死亡的影响

目的 :探讨帕金森病黑质多巴胺神经元的死亡机制。　方法 :用MTT法及流式细胞仪检测和观察囊泡单胺类转运体 (VMAT)抑制剂利血平对多巴胺所致的毒性作用和细胞程序性死亡的影响。　结果 :利血平 ( 10 0 0nmol/L)作用于大鼠嗜铬细胞瘤 (PC12 )细胞 96h ,对细胞无毒性效应 ;多巴胺 ( 0 .4mmol/L)作用于PC12细胞 4 8h即出现毒性效应 ;利血平 ( 10 0 0nmol/L)与多巴胺能够明显增强多巴胺 ( 0 .4mmol/L)的毒性效应 (P <0 .0 1) ,二者的协同毒性效应还具有时间依赖性。当多巴胺浓度 ( 0 .2mmol/L)较低时 ,协同毒性效应在药物作用 96h才显现出来。同时毒性效应主要是通过诱导细胞程序性死亡来实现的。　结论 :VMAT功能下降加重或触发多巴胺的内源性毒性 ,诱导多巴胺神经元的程序性死亡 ,可能参与帕金森病的发病机制。     

Effects of intracerebroventricular administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the motor activity and reserpine-induced hypothermia in murines

We investigated the effects of i.c.v. administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the spontaneous motor activity and reserpine-induced hypothermia in murines. The administration of PACAP (1 or 2 nmol) caused a dose-dependent increase in both spontaneous motor activity and rearing behavior in the rat. The peptide (0.1 or 0.2 nmol) counteracted reserpine-induced hypothermia in a dose-dependent manner in mice. On the other hand, i.c.v. injection of vasoactive intestinal polypeptide, which is structurally similar to PACAP, at a dose similar to that of PACAP (2 nmol in rats, 0.2 nmol in mice) did not show a significant effect on either behavior or body temperature. Therefore, the stimulating effect of PACAP observed here may be mediated by PACAP-specific (type I) receptors. PACAP was more potent and longer-lasting than a known potent stimulating peptide, thyrotropin-releasing hormone, in both stimulating motor activity and counteracting reserpine-induced hypothermia. Results of the present study, in combination with those of previous studies identifying endogenous PACAP in the brain, suggest that PACAP may play an important role in the CNS as a stimulant in regulating motor activity and body temperature.     

Lack of effect of reserpine-induced dopamine depletion on the binding of the dopamine-D3 selective radioligand, [C]RGH-1756

The effect of reserpine induced dopamine depletion on the binding of the putative dopamine-D3 receptor ligand, [¹¹C]RGH-1756 was examined in the monkey brain with positron emission tomography (PET). In a previous series of experiments, we have made an attempt to selectively label D3 receptors in the monkey brain using [¹¹C]RGH-1756. Despite high selectivity and affinity of RGH-1756 in vitro, [¹¹C]RGH-1756 displayed only low specific binding to D3 receptors in vivo. The aim of the present study was to examine whether low specific binding of [¹¹C]RGH-1756 is caused by insufficient in vivo affinity of the ligand, or by high physiological occupancy of D3 receptors by endogenous dopamine (DA). PET experiments were performed in three monkeys under baseline conditions and after administration of reserpine (0.5 mg/kg). The results of the baseline measurements corresponded well to our earlier observations with [¹¹C]RGH-1756. Reserpine caused no evident change in the regional distribution of [¹¹C]RGH-1756 in the monkey brain, and no conspicuous regional accumulation of activity could be observed. After reserpine treatment there was no evident increase of specific binding and binding potential (BP) of [¹¹C]RGH-1756. The lack of increased [¹¹C]RGH-1756 binding after reserpine treatment indicates that competition with endogenous DA is not the predominant reason for the failure of the radioligand to label D3 receptors. Therefore, the low binding of [¹¹C]RGH-1756 could largely be explained by the need for very high affinity of radioligand for D3 receptors in vivo, to obtain a suitable signal for the minute densities of D3 receptors expressed in the primate brain.     

Immunocytochemical survey of haloperidolinduced immunoreactive changes of [Met]enkephalin-Arg-Gly-Leu in the rat forebrain

It has already been demonstrated that chronic treatment with the dopamine receptor blocker, haloperidol, results in an increase of proenkephalin-A-derived peptides in the caudate-putamen (CP). To examine this phenomenon at the cellular level, we used immunocytochemistry to investigate the effects of haloperidol on [Met]enkephalin-Arg⁶-Gly⁷-Leu⁸ (MEAGL) immunoreactivity in the rat forebrain. After daily haloperidol (5 mg/kg, IP, for 6 days) or haloperidol decanoate (70 mg/kg, IM, given once or twice) treatment, immunoreactive neurons appeared diffusely in the whole CP and in the core part of the nucleus accumbens (Acb) and less frequently in the outer shell part of the Acb and the cell-dense layer of the tuberculum olfactorium (TuO). Increase of MEAGL-immunoreactive fibers in the CP, Acb and TuO was also detected after these treatments, a particularly prominent increase being found in the striopallidal terminals in the globus pallidus and ventral pallidum. Haloperidol or haloperidol decanoate had no effect on MEAGL immunoreactivity in the cerebral cortex, amygdala, or hypothalamus. Reserpine treatment (5 mg/kg, IP, for 6 days) caused similar effects on the dorsal and ventral striopallidal system and the direct injection of 6-hydroxydopamine (10 μ/5 μl) into the CP led to the appearance of MEAGL-immunoreactive neurons in accordance with the depleted dopaminergic terminal area. These findings suggest that haloperidol influences enkephalinergic neurons region specifically and that in the dorsal and ventral striopallidal enkephalinergic system haloperidol increases MEAGL immunoreactivity in cell bodies, fibers and terminals by blocking intrastriatal dopaminergic neurotransmission.