Side Effects and Ways to Avoid Them

Pilocarpine, a parasympathomimetic drug used in the treatment of glaucoma, produces a variety of ocular and systemic adverse reactions. Ocular side effects include miosis, accommodative spasm, frontal headaches, twitching lids, conjunctival injection, cataractous changes, allergic reactions, iris cysts, retinal detachment, increased permeability of the blood-aqueous barrier, anterior chamber narrowing, and the potential for inducing an acute angle-closure attack. Systemic side effects include nausea, vomiting, tenesmus, abdominal spasm, salivation, lacrimation, sweating, pulmonary edema, and bronchial spasm. The systemic side effects can best be minimized initially through proper use of the medication and nasolacrimal occlusion. The Ocusert,® a long-acting pilocarpine-incorporated ocular insert, is a recent advance in delivery technique that offers an adequate hypotensive action with fewer side effects. Pilopex® is a promising new experimental pilocarpine polymer salt presently being studied in Israel. Photomydriasis, a process involving the use of a laser to enlarge miotic pupils also offers help for these patients. N-demethylated carbachol is a new parasympathomimetic drug currently under study for glaucoma therapy. Initial results show that it may have considerable ocular hypotensive action with fewer adverse effects.     

Chronic paroxysmal hemicrania. IX. On the mechanism of attack-related sweating

In eight patients with chronic paroxysmal hemicrania (CPH), forehead sweating was measured after various provocation tests-body heating, exercise, and subcutaneous pilocarpine administration (0.1 mg/kg body weight). Evaporation was measured bilaterally on the forehead with an Evaporimeter (in g/m²/h). This was carried out in a thermo room under standardized conditions. There was no definite deficit in heat-induced or exercise-induced sweating on the symptomatic side of the forehead, contrary to findings in cluster headache. Neither did pilocarpine lead to any marked initial, temporary predominance of sweating on the symptomatic side, which has previously been found in cluster headache. In cluster headache there may be denervation supersensitivity of the sweat glands in the forehead of the symptomatic side. The present study does not therefore provide evidence for supersensitivity phenomena which could explain the homolateral forehead sweating increase seen during attacks in some CPH patients. The localized sweating increase in the forehead during attacks of CPH may possibly be a result of direct sympathetic stimulation.     

激活血管内皮细胞非神经性M受体对不同亚型G蛋白基因表达的影响

目的研究G蛋白各亚型在内皮细胞上的表达分布,以及氨甲酰胆碱和毛果芸香碱的调节作用。方法培养大鼠主动脉内皮细胞,用氨甲酰胆碱和毛果芸香碱10-4mol.L-1分别孵育,6 h后提取细胞总RNA,RT-PCR方法测定G蛋白不同亚型mRNA的表达。结果G蛋白4个亚家族中的Gq/11、Gs、G i在内皮细胞有表达,而G12/13未见表达,氨甲酰胆碱和毛果芸香碱分别作用6 h后,Gs、G i家族、Gq/11家族中的G11蛋白基因表达均未发生变化,只有Gq/11家族中的Gq蛋白在氨甲酰胆碱10-4mol.L-1作用下,基因表达上调了72.7%,而相同浓度的毛果芸香碱却不影响Gq蛋白的基因表达。结论氨甲酰胆碱激活NNMR后,G蛋白4个亚家族中只有Gq/11家族中的Gq蛋白基因表达发生了变化,可以推测Gq蛋白在NNMR的信号转导中发挥了主要的作用。     

代谢型谷氨酸受体亚型5拮抗剂MPEP、亚型8兴奋剂S-DCPG联合用药在小鼠癫痫治疗中的作用

目的：观察2-甲基-6-苯基乙炔嘧啶（2-methyl-6-phenylethynyl-pyridine,MPEP）与S-二羧基苯基甘氨酸（S-3,4-Dicarboxyphenylglycine,S-DCPG）联合用药在毛果芸香碱诱导的癫痫小鼠动物模型中的抗抽搐及对大脑神经元的保护作用.方法：取5-6周龄瑞士雄性小鼠行颈静脉插管.插管后第3天腹腔注射毛果芸香碱诱导小鼠癫痫模型.待癫痫发作1h通过颈静脉插管给予四种不同剂量的MPEP＋S-DCPG（100＋100mg/kg、100＋200mg/kg、200＋100mg/kg、200＋200mg/kg）,观察其抗癫痫活性.给药后24h断头取脑行病理观察,并计算海马齿状回门区中间神经元的密度.结果：四种剂量组在癫痫发作后1h给药均有明显的抗抽搐活性,并随剂量的增加有增加的趋势,对海马齿状回门区中间神经元亦有一定的保护作用,虽然前两种剂量组与实验对照组比较P＞0.05,但其神经元的密度明显高于实验对照组,后两种剂量组与实验对照组相比P＜0.05.结论：MPEP＋S-DCPG对毛果芸香碱诱导的癫痫小鼠模型有明显的抗抽搐活性,对海马齿状回门区中间神经元亦有明显保护作用,并在实验剂量范围内随着剂量的增加有明显的增加趋势.     

The polarity and properties of radial glia‐like neural stem cells are altered by seizures with status epilepticus: Study using an improved mouse pilocarpine model of epilepsy

In the adult mouse hippocampus, new neurons are produced by radial glia‐like (RGL) neural stem cells in the subgranular zone, which extend their apical processes toward the molecular layer, and express the astrocyte marker glial fibrillary acidic protein, but not the astrocyte marker S100β. In rodent models of epilepsy, adult hippocampal neurogenesis was reported to be increased after acute and mild seizures, but to be decreased by chronic and severe epilepsy. In the present study, we investigated how the severity of seizures affects neurogenesis and RGL neural stem cells in acute stages of epilepsy, using an improved mouse pilocarpine model in which pilocarpine‐induced hypothermia was prevented by maintaining body temperature, resulting in a high incidence rate of epileptic seizures and low rate of mortality. In mice that experienced seizures without status epilepticus (SE), the number of proliferating progenitors and immature neurons were significantly increased, whereas no changes were observed in RGL cells. In mice that experienced seizures with SE, the number of proliferating progenitors and immature neurons were unchanged, but the number of RGL cells with an apical process was significantly reduced. Furthermore, the processes of the majority of RGL cells extended inversely toward the hilus, and about half of the aberrant RGL cells expressed S100β. These results suggest that seizures with SE lead to changes in the polarity and properties of RGL neural stem cells, which may direct them toward astrocyte differentiation, resulting in the reduction of neural stem cells producing new granule cells. This also suggests the possibility that cell polarity of RGL stem cells is important for maintaining the stemness of adult neural stem cells.     

硝酸毛果芸香碱滴眼前后原发性闭角型青光眼前房角的变化

目的:研究原发性闭角型青光眼患者使用硝酸毛果芸香碱眼液前后前房角的变化。方法:诊断为原发性闭角型青光眼的患者47例68眼,使用前节OCT进行眼前节的测量,点用硝酸毛果芸香碱眼液前后比较房角开放距离(AOD)和小梁下-虹膜空间面积(TISA)等监测指标。结果:在上方的房角中,点用硝酸毛果芸香碱眼液前后AOD无显著差异(P>0.05),TISA差异显著(P<0.05),在下方的房角中,点用硝酸毛果芸香碱眼液前后各项差异均不显著(P>0.05)。结论:硝酸毛果芸香碱眼液对较窄的房角可以起到开放房角,改善小梁功能的作用。     

小剂量反复注射匹罗卡品制备颞叶癫癎大鼠模型

目的 :探讨氯化锂 -匹罗卡品所致癫大鼠模型的新制备方法。方法 :利用小剂量多次注射匹罗卡品的方法制备颞叶癫大鼠模型后 ,测取慢性模型组大鼠脑电 ,计算病灶处的相关维数 (Dc值 )。结果 :此方法使急性期大鼠病死率降至35 % ,且癫持续状态的发生率提高到接近100 %。模型组大鼠病灶处脑电Dc值明显降低。结论 :小剂量多次注射匹罗卡品是一种更好的颞叶癫大鼠模型制备方法     

匹罗卡品脂质体与凝胶缩瞳作用的实验研究

目的　研究 1%匹罗卡品脂质体与 4 %匹罗卡品凝胶对兔眼的缩瞳作用。方法　家兔 2 4只 ,随机分为 4组 ,每组 6只 ,按 1%匹罗卡品脂质体滴眼液 ,4 %匹罗卡品凝胶 ,1%匹罗卡品滴眼液 ,空白对照分为四组 ,给药后观察兔眼的刺激反映情况并间隔一定时间测量其瞳孔大小。结果　 4组兔眼滴药前瞳孔直径左右眼比较 ,差异无显著性 (P >0 .0 5 )。 1%匹罗卡品滴眼液组滴药后 0 .2 5h ,缩瞳作用最大 (P <0 .0 1) ,滴药后 1h瞳孔开始散大 ,滴药后 5h ,左右眼差异无显著性 (P >0 .0 5 ) ;1%匹罗卡品脂质体滴眼液组 ,滴药后 0 .5h缩瞳作用最大 (P <0 .0 1) ,滴药后 3h瞳孔开始散大 ,滴药后 7h ,左右眼差异无显著性 (P >0 .0 5 ) ;4 %匹罗卡品凝胶组 ,滴药后 0 .5h缩瞳作用最大 (P <0 .0 1) ,滴药后 4h瞳孔开始散大 ,滴药后 5h左右眼差异无显著性(P >0 .0 5 ) ;空白对照组在观察的 7h内左右眼差异无显著性 (P >0 .0 5 )。结论　 1%匹罗卡品脂质体滴眼液具有缓慢释药 ,延长作用时间的优点。其作用时间长于 4 %匹罗卡品凝胶。     

辐射聚合制备毛果芸香碱—水凝胶释放体系的研究

本文研究的药膜是在室温条件下将含药的单体放在模具中进行辐射交联聚合。该法工艺简便,药膜纯度高不带任何引发剂残余物。我们研究了基质含水率,药物含量、辐射剂量率及总剂量对药物释放速率的影响。结果表明:药物的释放量随着基质含水率及药含量的增加而增加;随着交联剂用量及辐照剂量率和总剂量的增加而降低。药物在剂量率为6.46×10~3Rad/sec及总剂量为1.28×10~6ad条件下辐照与未经辐照处理的药物进行了红外及紫外对比试验,结果表明;辐照对药物结构没有明显的影响。     

匹罗卡品诱导颞叶癫痫大鼠齿状回苔藓纤维出芽及突触重建

目的：探讨匹罗卡品致痫鼠大脑海马齿状回苔藓纤维出芽、突触重建及其与颞叶癫痫发生的关系。方法：急性诱导癫痫持续状态及慢性颞叶癫痫形成后,采用Neo-Timm银染观察苔藓纤维出芽及突触重建,并用原位杂交方法检测苔藓纤维出芽标志物生长相关蛋白（GAP-43）mRNA,用免疫组织化学方法检测突触重建标志物突触体素（P38）的动态变化。结果：癫痫持续状态后6~12 h,海马齿状颗粒细胞GAP-43 mRNA表达显著增高;从第7 d开始,P38免疫反应性在齿状回内分子层呈进行性增加,与Neo-Timm显示的异常苔藓纤维出芽一致,而此时颗粒细胞GAP-43 mRNA表达显著减少。结论：匹罗卡品癫痫发作后,在海马形成了异常的兴奋性环路从而为慢性高兴奋性产生及癫痫形成提供了结构基础。