多药耐药蛋白对大鼠皮层细胞外液卡马西平和苯妥英钠影响的研究

目的观察多药耐药蛋白(multidrugresistance-associatedprotein,MRP)拮抗剂丙磺舒对大鼠大脑皮层细胞外液卡马西平和苯妥英钠含量的影响,证明MRP能够减少皮层内抗癫痫药物的浓度,探讨脑内表达MRP和难治性癫痫多药耐药的关系。方法在健康大鼠大脑皮层内安置微透析探针,腹腔注射卡马西平(20mg/kg)和苯妥英钠(50mg/kg),在给药后不同时间点收集透析液,并用高效液相检测其中的药物浓度,通过微透析探针局部给于丙磺舒,观察后者能否提高大鼠大脑皮层细胞外液卡马西平和苯妥英钠的浓度。结果丙磺舒升高了皮层细胞外液中卡马西平和苯妥英钠的药物浓度,前者在给药后45min～120min显著增高(P<0.05),后者在给药后30min～150min显著增高(P<0.05)。结论MRP具有限制卡马西平和苯妥英钠通过血脑屏障的作用,引起抗癫痫药物在大鼠大脑皮层细胞外液中分布减低,MRP表达增加可能参与了难治性癫痫多药耐药机制的形成。     

多药转运蛋白对匹罗卡品癫(癎)大鼠模型脑内拉莫三嗪浓度的影响

目的 观察多药转运蛋白[P-糖蛋白(P-glycoprotein,PGP)和多药耐药相关蛋白(multi-drug resistance associated protein,MRP)]对匹罗卡品慢性癫(癎)大鼠模型海马内拉莫三嗪浓度的影响,探讨PGP和MRP在难治性癫(癎)多药耐药机制中的作用.方法 建立匹罗卡品慢性癫(癎)动物模型,在模型大鼠海马内安置微透析探针,腹腔注射拉莫三嗪(10mg/kg)后于不同时间点收集透析液,并用高效液相色谱检测其中的药物浓度.通过微透析探针局部分别给予PGP拮抗剂维拉帕米和MRP拮抗剂丙磺舒,观察维拉帕米和丙磺舒对模型鼠海马内神经元细胞外液拉莫三嗪浓度的影响.结果 维拉帕米明显升高了癫(癎)大鼠海马细胞外液拉莫三嗪的药物浓度,在给药后60、90、120、150 min(0.65±0.11、0.84±0.09、0.70±0.09和0.58±0.08)与模型组(0.41±0.10、0.50±0.04、0.39±0.09和0.30±0.06)比较差异有统计学意义(F=5.01、8.61、10.23、7.89,P<0.05),丙磺舒也提高了海马内拉莫三嗪的浓度,给药后90、120、150 min(0.75±0.09、0.58±0.10和0.49±0.07)与模型组比较差异有统计学意义(F=6.58、4.56、4.75,P<0.05).结论 PGP和MRP均能够限制拉莫三嗪通过癫(癎)大鼠血脑屏障,从而降低了海马内拉莫三嗪的药物浓度,上述机制可能参与了难治性癫(癎)耐药的发生.     

维拉帕米对耐苯妥英钠和卡马西平癫(癎)模型大鼠电生理和行为的影响

目的 观察P-糖蛋白(PGP)拮抗剂维拉帕米对耐苯妥英钠(PHT)和卡马西平(CBZ)癫(癎)大鼠电生理指标和行为学的影响.方法 建立慢性杏仁核点燃癫(癎)大鼠模型,筛选出耐药组和治疗有效组,给予维拉帕米,观察其对各组大鼠后放电阈值(after discharge threshold,ADT)、后放电时程(after discharge duration,ADD)等电生理指标和行为学的影响.结果 相对于耐药对照组,耐药组大鼠在预先给予维拉帕米后,使用抗癫(癎)药物后ADT[(238.0±32.2)μA]明显高于耐药对照组[(177.0±23.3)μA,P＜0.05];ADD时程明显缩短,Racine行为分级明显下降(P＜0.05).结论 维拉帕米可以协助抗癫(癎)药物(AEDs)改善耐药大鼠的电生理活动,降低点燃后发作分级,提示有效抑制PGP有助于改善多药转运体高表达导致的癫(癎)耐药.     

多药转运蛋白对癫痫大鼠脑内奥卡西平浓度的影响

目的 观察多药转运蛋白家族的成员P-糖蛋白(P-glycoprotein,PGP)和多药耐药蛋白(multi-drug re-sistance associated protein,MRP)对匹罗卡品慢性癫痫大鼠模型海马内神经元细胞外液中奥卡西平浓度的影响,证明奥卡西平是否为PGP和MRP的底物,探讨PGP和MRP参与难治疗性癫痫耐药的机制.方法 建立匹罗卡品慢性癫痫动物模型,将32只大鼠分为对照组、模型组、维拉帕米干预组、丙磺舒干预组(每组8只),于腹腔注射奥卡西平(80 mg/kg)后30、60、90、120、150 min,通过微透析及高效液相色谱技术,检测大鼠海马神经元细胞外液中的药物浓度.结果 维拉帕米干预后,癫痫大鼠海马细胞外液中奥卡丙平的浓度于给药后90～120 min(1.26±0.09、0.93±0.10)明显高于模型组(0.87±0.06、0.66 4±0.04),两组比较有统计学差异(P<0.05);丙磺舒干预后60～150 min,大鼠海马内细胞外液中奥卡两平的浓度(1.07±0.11、1.32±0.13、1.02±0.10、0.87±0.08)显著高于模型组(0.81±0.08、0.87±0.06、0.66±0.04、0.58±0.06)(P<0.05).结论 奥卡西平是PGP和MRP的底物,PGP和MRP能够选择性的将奥卡西平泵出血脑屏障外,降低癫痫病灶内的药物浓度,上述机制可能参与了难治性癫痫患者对奥卡西平产生耐药.     

中国汉族癫（癎）患者中CYP3A4＊1G基因多态性与卡马西平药物浓度的相关性研究

目的 观察CYP3A4＊ 1G基因多态性与中国汉族癫（癎）患者卡马西平稳态药物浓度的相关性.方法 检测177例中国汉族癫（癎）患者卡马西平单药治疗的稳态药物浓度,采用LDR-PCR测序分型检测CYP3A4＊ 1 G基因多态性.结果 CYP3A4＊ 1G基因AA型的卡马西平标准化浓度为（0.23±0.065） μg·mL-1,AG型为（0.25±0.065） μg·mL-1,GG型为（0.28±0.074）μg·mL-1.3种基因型间标准化血药浓度差异有统计学意义（P＜0.01）,且AA型低于GG型（P＜0.01）,AG型低于GG型（P＜0.05）,AA型低于AG型（P＜0.01）,差异均有统计学意义.结论 CYP3A4＊ 1G基因型影响中国汉族癫（癎）患者的卡马西平药物浓度,可能是卡马西平药物浓度个体差异的影响因素.     

中国汉族癫癇患者中CYP3A41G基因多态性与卡马西平药物浓度的相关性研究

目的观察CYP3A4*1G基因多态性与中国汉族癫癇患者卡马西平稳态药物浓度的相关性。方法检测177例中国汉族癫癇患者卡马西平单药治疗的稳态药物浓度,采用LDR-PCR测序分型检测CYP3A4*1G基因多态性。结果 CYP3A4*1G基因AA型的卡马西平标准化浓度为(0.23±0.065)μg·mL-1,AG型为(0.25±0.065)μg·mL-1,GG型为(0.28±0.074)μg·mL-1。3种基因型间标准化血药浓度差异有统计学意义(P0.01),且AA型低于GG型(P0.01),AG型低于GG型(P0.05),AA型低于AG型(P0.01),差异均有统计学意义。结论 CYP3A4*1G基因型影响中国汉族癫癇患者的卡马西平药物浓度,可能是卡马西平药物浓度个体差异的影响因素。     

卡马西平加重癫鼠失神发作的机制探讨

目的探讨卡马西平加重癫癎失神发作的机制。方法13周龄雌性CEARS鼠14只分为2组,用微导管在双侧丘脑网状核(Rt)或丘脑腹侧基底核(VB)各注射0．2μL卡马西平(含卡马西平15nMOL)或溶剂。注射药物后即刻记录90min脑电图并分析。结果在VB注射卡马西平与注射溶剂相比,脑电图癫癎失神发作的累积时间和频率明显增加(P=0．01,n=7和P=0．03,n=7)。而在Rt注射卡马西平组与溶剂组比较,两组间各项指标均无统计学差异。结论在VB注射卡马西平可加重癫癎鼠的失神发作,而注射于Rt对其无影响。提示卡马西平加重癫癎鼠失神发作的神经解剖部位在VB。     

卡马西平加重癫癎鼠失神发作的机制探讨

目的探讨卡马西平加重癫癎失神发作的机制.方法13周龄雌性GEARS鼠14只分为2组,用微导管在双侧丘脑网状核(Rt)或丘脑腹侧基底核(VB)各注射0.2μL卡马西平(含卡马西平15 nMOL)或溶剂.注射药物后即刻记录90 min脑电图并分析.结果在VB注射卡马西平与注射溶剂相比,脑电图癫癎失神发作的累积时间和频率明显增加(P=0.01,n=7和P=0.03,n=7).而在Rt注射卡马西平组与溶剂组比较,两组间各项指标均无统计学差异.结论在VB注射卡马西平可加重癫癎鼠的失神发作,而注射于Rt对其无影响.提示卡马西平加重癫癎鼠失神发作的神经解剖部位在VB.     

中国汉族癫患者CYP3A5*3基因多态性与卡马西平药物浓度的相关性研究

目的:观察CYP3A5*3基因多态性与中国汉族癫患者卡马西平稳态药物浓度的相关性。方法:检测采用177例卡马西平单药治疗的中国汉族癫患者的稳态药物浓度,LDR-PCR测序分型检测CYP3A5*3基因多态性。结果:CYP3A5*3基因AA型的卡马西平标准化浓度为(0.23±0.066)μg.mL-1,AG型为(0.24±0.053)μg.mL-1,GG型为(0.31±0.073)μg.mL-1。3种基因型间标准化血药浓度差异有统计学意义(P<0.000 1),且AA型低于GG型(P<0.000 1),AG型低于GG型(P<0.000 1),差异均有统计学意义。AA型虽有低于AG型趋势,但差异无统计学意义(P=0.087)。CYP3A5*3各基因型间血药浓度、剂量校正浓度间差异与上述结果类似。结论:CYP3A5*3基因型影响中国汉族癫患者的卡马西平药物浓度,是造成卡马西平药物浓度个体差异的可能因素。     

奥卡西平与卡马西平单药治疗儿童部分性癫(癎)的对照研究

目的 比较奥卡西平与卡马西平单药治疗儿童部分性癫(癎)的疗效.方法 71例新诊断的儿童部分性癫(癎)患者按单双号顺序分为奥卡西平组(35例)和卡马西平组(36例),并给予相应的药物治疗;6个月后进行疗效评价,观察不良反应.结果 奥卡西平组和卡马西平组分别有25例及29例完成6个月治疗;脑电图改善率分别为44.0%及44.8%;显效率分别为92.0%及86.2%;不良反应发生率分别为22.2%及41.2%,两组间比较差异无统计学意义(均P>0.05);卡马西平组2例出现严重不良反应.结论 奥卡西平与卡马西平单药治疗新诊断的儿童部分性癫(癎)均有很好的疗效,不良反应及耐受性相似,但奥卡西平组未见严重的不良反应.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Effects of prevention of afferentation of the development of the chick optic lobe

BONDY, S. C., M. E. HARRINGTON AND C. L. ANDERSON. Effects of prevention of afferentation on the developmentof the chick optic lobe. BRAIN RES. BULL. 3(5) 411–413, 1978.—The effects of unilateral extirpation of the right optic cup of the three-day incubated chick embryo upon the rate of synthesis and the stability of DNA in the non-innervated optic lobe, have been studied. This surgical procedure prevents innervation of the optic lobe contralateral to the removed eye, while the other optic lobe is normally innervated by retinal ganglion cells of the remaining eye. At the 20th day of incubation, the DNA content of the non-innervated lobe was below that of the paired lobe receiving normal innervation. This deficiency of cell number was caused by two events; death of an excess number of neurons formed early in embryogenesis and a reduced rate of glial proliferation in the later stages of incubation.     

帕金森病运动症状进展分析

目的分析帕金森病(PD)患者运动症状进展特点。方法采用PD统一评分量表(UPDRS)Ⅲ对912例PD患者进行评估。结果与病程1年的患者比较,除病程1~2年的患者外,其他病程患者的UPDRSⅢ评分、强直分、姿势或步态异常分、轴性症状总分、言语分、步态分显著升高(均P0.05),病程5~6年及14年患者的震颤分,病程5~6年、7~8年、9~13年、14年患者的运动迟缓分、姿势分显著升高(P0.05~0.01)。轴性症状进展速度高于UPDRSⅢ评分。结论 PD患者病程早期UPDRSⅢ评分进展快,震颤症状进展独立于其他症状,轴性症状评分较UPDRSⅢ更敏感地反映疾病加重趋势。     

Frequency of accumulation of filaments in adaxonal cytoplasm of Schwann cells of myelinated fibers of rat spinal roots

Summary The frequency of accumulation of 6-nm filaments in the adaxonal cytoplasm of Schwann cells in the 6th lumbar dorsal and ventral roots was evaluated in 4-, 8-, 26- and 45-week-old Sprague-Dawley rats. The frequency was higher in 4- and 8-week-old (growing) rats than in 26- and 45-week old (mature) rats, and also higher in ventral than in dorsal roots in 4-, 8- and 26-week old rats. There were no clusters on certain groups of myelinated fibers according to the size of transverse axonal area, in both the ventral and dorsal roots. Therefore, this accumulation may reflect certain functions of the adaxonal cytoplasm of Schwann cell during natural growth and maturation of the axon and myelin sheath.     

Function of circle of Willis

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress.     

Modelling of movement of the lamprey: Control of oscillators

This article discusses the control methods of the central pattern generator (CPG). First a control model of the CPG is presented using 2 oscillators, and we suggest that phasic modulation to the CPG by means of phasic information is effective for controlling the phase difference between oscillators. Next, two models for controlling the CPG of a lamprey are proposed. One model describes a control system from the brain stem, in which the reticulospinal neurons control the CPG by receiving feedback signals and sending control signals to the neck region of the CPG. The other is a model for learning an localized control system to generate a desired motor pattern. By means of these models, a role of the efference copy is suggested.     

广西农村壮族妇女精神分裂症患者生活质量状况调查

目的研究农村壮族妇女精神分裂症患者的生活质量及影响因素。方法前瞻性的队列研究。采用随机分层抽样法分为农村壮族妇女精神分裂症组、农村汉族妇女精神分裂症组、农村正常妇女对照组,应用“世界卫生组织生存质量测定报告”(WHOQOL-100)及PANSS量表调查其生活质量和疾病的严重程度。结果农村壮族妇女精神分裂症患者生活质量明显低于农村汉族妇女精神分裂症患者,影响其生活质量的相关因素是生活环境及精神支柱/个人信仰。结论经济贫困、环境条件、缺乏有效的医疗服务和社会保障是农村壮族妇女精神分裂症患者生活质量低的关键。因此,建立农村壮族社区精神卫生服务网络势在必行。     

《绵阳市社会心理服务工作管理办法》解读

2018年,国家卫生健康委员会等10部委联合发布《关于印发全国社会心理服务体系建设试点工作方案的通知》,四川省绵阳市被列为全国第一批试点地区。绵阳市人民政府依据《中华人民共和国精神卫生法》等相关法律法规和文件精神,结合前期调查研究和社会心理服务工作的试点实际,编制出台了《绵阳市社会心理服务工作管理办法》,并于2021年12月25日起施行。本文围绕社会心理服务的相关概念、办法总则、重点内容、保障措施等方面进行解读,以期为社会心理服务工作的规范、持续和有效开展提供参考。     

利培酮对精神分裂症患者生活质量的影响

目的：比较利培酮与氟哌啶醇对精神分裂症患者生活质量的影响。方法：对门诊72例服用氟哌啶醇及74例服用利培酮的精神分裂症患者用生活质量综合评定问卷（GQOLI）、阳性与阴性症状量表（PANSS）、副反应量表（TESS）进行评定。结果：利培酮组患者治疗后生活质量有所提高，而氟哌啶醇组患者生活质量有所下降。结论：利培酮治疗有利于患者提高生活质量。