卡巴拉汀治疗阿尔茨海默病患者的临床研究

目的：评价卡巴拉汀治疗中国轻中度阿尔茨海默病（AD）患者的有效性和安全性,方法：多中心、随机、开放、对照试验,共有124例50例以上轻中度AD患者,简易精神状态检查表（MMSE）得分在10－26分之间,并随机分为两组（卡巴拉汀组和多奈哌齐组各62例）。治疗时间16周。疗效评价使用MMSE量表、Blessed-Roth量表和总体衰退量表（GDS）在筛查和16周末进行。用Hachinski缺血积分量表鉴别AD和血管性痴呆（VD）,安全性检查包括生命体征,实验室及心电图检查,每4周1次。结果：两组的人口统计学有可比性（P＞0．05）。两组MMSE、GDS和Blessed-Roth评分均有显著改善（P＜0．01）。Blessed-Roth分值自身对比发现卡巴拉汀组显著改善日常生活能力（P＜0．01）;治疗前后的差值比较也发现卡巴拉汀组在社会活动能力方面稍优于多奈哌齐组（P＝0．0592）其他量表指标两组间差异无显著意义（P＜0．05）。总的不良反应率在12．9％－28．8％之间,两组间无显著差异,药物对病人生命体征及实验室指标无影响,结论：卡巴拉汀可显著改善AD患者的临床症状,且安全性和耐受性良好,是AD治疗的理想药物之一。     

卡巴拉汀与多奈哌齐治疗轻中度阿尔茨海默病患者的比较研究

目的　比较卡巴拉汀和多奈哌齐治疗轻中度阿尔茨海默病 (AD)患者的疗效和安全性。方法　将 40例轻中度 AD患者随机均分为两组 ,用卡巴拉汀和多奈哌齐治疗 16周。采用简易精神状态量表 (MMSE)、Blessed-Roth量表和总体衰退量表 (GDS)评定疗效。安全性检查包括生命体征、实验室及心电图检查 ,每 4周 1次。结果　两组治疗前后 MMSE、GDS和 Blessed-Roth评分均有显著改善 (P<0 .0 5)。但两组治疗前后相关量表总分差值的 t检验均无显著意义 (P>0 .0 5)。两组治疗前后 Blessed-Roth各亚项分数差值比较无显著性 (P>0 .0 5) ,仅在社会活动能力方面卡巴拉组汀稍优于多奈哌齐组 (P>0 .0 5)。不良反应为胃肠道反应 ,发生率在 15.0 %～ 2 9.5%之间 ,以卡巴拉汀组多见。结论　卡巴拉汀和多奈哌齐可显著改善 AD患者的认知功能、痴呆程度和日常生活能力 ,疗效相当 ,较为安全 ,耐受性好     

长春西汀联合脑蛋白水解物治疗血管性痴呆的疗效观察

目的观察长春西汀注射液联合脑蛋白水解物治疗血管性痴呆(VD)的临床疗效。方法 128例血管性痴呆患者随机分为2组,观察组和对照组各64例。治疗前和治疗后1个月进行简易智能检查(MMSE)和日常生活能力量表(ADL)评分,并进行对比分析。结果 2组治疗后MMSE和ADL评分均有明显改善(P0.05),观察组改善情况优于对照组(P0.05)。结论长春西汀注射液联合脑蛋白水解物治疗能明显改善血管性痴呆患者的认知功能和生活能力,疗效优于单纯脑蛋白水解物治疗,且安全性高。     

天智颗粒治疗血管性痴呆的临床观察

目的观察天智颗粒改善血管性痴呆(VD)认知能力的疗效。方法选择57例血管性痴呆患者,随机分为观察组和对照组,对照组常规治疗,观察组加用天智颗粒冲服。应用韦氏记忆量表(MQ)、简易智能状态量表(MMSE)、长谷川痴呆量表(HDS)、日常生活能力量表(ADL)等评价临床疗效。结果治疗前2组MMSE、MQ、HDS、ADL评分比较差异均无统计学意义(P>0.05),治疗后治疗组MMSE MQ HDSADL评分优于对照组(P<0.05)。结论天智颗粒治疗血管性痴呆可有效改善患者的认知功能,提高日常生活能力。     

养血清脑颗粒治疗血管性痴呆60例疗效观察

目的 观察养血清脑颗粒对血管性痴呆(VD)患者认知功能和行为能力的改善作用.方法 将VD患者120例随机分为治疗组与对照组各60例,治疗组采用养血清脑颗粒,对照组采用脑复康片.2组病人在治疗前后分别用简易智力状态检查量表(MMSE)及长谷川痴呆量表(HDS)进行认知功能评价,用日常生活能力(ADL)量表进行日常行为能力评价.结果 治疗组患者治疗后认知、行为能力均较治疗前明显改善(P<0.05).结论 养血清脑颗粒对VD患者认知、行为能力有明显改善作用.     

电针智三针对血管性痴呆患者认知功能和行为能力的影响

目的探讨电针智三针对血管性痴呆的疗效,为临床应用提供依据。方法采用随机数字表法将56例血管性痴呆(VD)患者随机分为电针组(电针治疗4周)和药物组(尼莫通,30mg,3次/d,治疗4周),治疗前后进行简易智能状态检查量表(MMSE)、长谷川痴呆修改量表(HDS)、日常生活能力(ADL)和P300等监测,观察2组治疗前后的变化。结果MMSE、HDS、ADL评分和P300监测均显示2组治疗后比治疗前明显改善,差异有统计学意义(P0.05);电针组的疗效优于药物治疗组(P0.01)。结论电针智三针可改善VD患者的认知功能和生活行为能力,疗效优于尼莫通。     

重复经颅磁刺激治疗抑郁症负性认知及情绪的疗效观察

目的探讨药物治疗基础上联合重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)对抑郁症患者负性认知及情绪的影响。方法将抑郁症患者60例随机分为研究组(n=30,在氟西汀治疗的基础上联合rTMS)及对照组(n=30,单用氟西汀治疗),在治疗前、治疗2周、4周、6周末,采用汉密尔顿抑郁量表24项版本(Hamilton rating scale for depression,HAMD-24)评估患者抑郁程度,采用自动思维量表(automatic thoughts questionnaire,ATQ)评估患者负性认知情况。结果重复测量方差分析显示,HAMD-24评分的组别×时间交互作用无统计学意义(F=0.455,P=0.586),组别主效应(F=11.754,P=0.001)与时间主效应(F=787.600,P0.001)均有统计学意义,随时间推移,两组HAMD评分降低均有统计学意义(P0.001)。治疗6周末研究组的HAMD减分率高于对照组(77.1%±6.8%vs.72.4%±9.7%,t=2.152,P=0.036)。ATQ评分的组别×时间交互作用有统计学意义(F=6.512,P=0.004),治疗后两组ATQ评分降低均有统计学意义(P0.001),且研究组在治疗2周末、4周末、6周末的评分均低于对照组(P0.05)。结论药物联合rTMS不仅有助于改善抑郁症患者的抑郁情绪,也有利于改善其负性认知。     

虚拟现实技术对抑郁患者注意功能疗效分析

目的 分析评价虚拟现实技术(Virtual reality,VR)治疗抑郁发作患者的临床疗效及注意功能改善情况。方法 将118例符合第10版国际疾病分类抑郁发作诊断标准的患者随机分为VR治疗联合药物治疗组(n=58)和常规药物治疗组(n=60),进行为期8周的临床观察。使用临床疗效总评量表和汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)分别在基线、4周末和8周末评估有效率和临床治疗效果。在基线和8周末评定MATRICS共识认知成套测验(MATRICS Consensus Cognitive Battery,MCCB)评价认知功能改善状况。使用药物不良反应量表评价安全性。结果 基线时两组一般资料无显著差异。8周末治疗组和对照组有效率分别为91.38%和90.00%,两组比较P=0.676,无统计学意义。基线时两组HAMD评分无统计学差异(P>0.05),第4周末、第8周末两组间比较差异有统计学意义(t=2.325,P=0.022;t=2.682,P=0.008)。治疗前两组间MCCB评分无统计学差异(P>0.05),治疗后MCCB评分两...     

尼莫同片治疗血管性痴呆的疗效观察

目的 评价尼莫同片对血管性痴呆(VD)患者的疗效.方法 128例VD患者分为观察组66例和对照组62例,均正规口服脑复康片3周,0.8g/次,3次/d.观察组同时口服尼莫同片,30mg/次,每日3次;对照组应用胞二磷胆碱0.75g.以神经功能缺损评分,Folstein简易精神状态检查(MMSE),日常生活能力量表(ADL)、记忆力、认知功能及精神神经功能作为疗效评定指标.结果 治疗4周后观察组神经功能缺损评分较对照组明显减少(P＜0.01).治疗前后MMSE比较,治疗组明显提高,差异有显著性(P＜0.01).治疗前后ADL积分比较,治疗组明显下降(P＜0.01),日常生活能力显著改善.观察组轻度、中度老年性痴呆患者记忆功能、认知功能和精神神经功能改善较为明显,与对照组比较有明显差异(P ＜0.05),重度患者临床疗效较差.结论 VD所致痴呆在某些功能上是可逆的,应用尼莫同片治疗可以延缓病情恶化,减轻症状,改善记忆、认知功能和提高患者日常生活能力.     

血管性痴呆及其药物干预的影像学研究

目的利用磁共振波谱分析(magnetic resonance spectroscopy, MRS)技术研究脑卒中后血管性痴呆(vascular dementia, VD)患者颞叶海马区细胞代谢水平及给予胆碱酯酶抑制剂后,细胞代谢水平的改变及其与临床症状的关系.方法脑卒中非VD组20例,男17例,女3例,平均年龄(71.7±4.7)岁.脑卒中VD组23例,男20例,女3例,平均年龄(72.9±5.1)岁,符合痴呆的诊断与统计手册第4次修改本(DSM-IV-R)诊断标准.对照组20名,男18名,女2名,平均年龄(70.9±4.8)岁.脑卒中VD组服用胆碱酯酶抑制剂重酒石酸卡巴拉汀,半年后复查头颅MRI、磁共振波谱分析(MRS)及认知功能.结果双侧颞叶海马区乙酰天门冬氨酸盐(NAA)与肌酸(Cr)的比值(NAA/Cr)在脑卒中VD组最低,胆碱(Cho)与肌酸的比值(Cho/Cr)在脑卒中VD组最高,其次为脑卒中非VD组,对照组NAA/Cr比值最高,Cho/Cr比值最低.相关回归分析发现脑卒中VD组简易精神状态量表(MMSE)评分与颞叶海马区细胞代谢水平呈线形相关,与左右颞叶海马区NAA/Cr比值的相关回归系数分别为0.48(P=0.024)及0.60(P=0.003);与左右颞叶海马区Cho/Cr比值的相关回归系数分别为-0.36(P=0.102)及-0.53(P=0.012).给予重酒石酸卡巴拉汀治疗后颞叶海马区NAA/Cr比值上升,Cho/Cr比值下降,均达到统计学差异(P<0.05).结论 MRS技术可能会有助于辅助诊断脑卒中后痴呆;从影像学角度证明重酒石酸卡巴拉汀可能有调节血管性痴呆患者脑内胆碱水平作用,是否对神经元有保护作用还有待探讨.     

Pregabalin effect on steady-state pharmacokinetics of carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, and tiagabine

By reducing neuronal excitability through selective binding to the α(2)δ subunit of voltage-dependent calcium channels, pregabalin effectively treats epilepsy, chronic pain, and anxiety disorders. To evaluate if pregabalin coadministration affects pharmacokinetics of other antiepileptic drugs, population pharmacokinetic analyses using NONMEM software were performed on data from three epilepsy trials involving seven antiepileptic drugs with pregabalin as add-on therapy. Results demonstrated that pregabalin did not alter the steady-state plasma concentrations of carbamazepine, lamotrigine, phenobarbital, phenytoin, tiagabine, topiramate, and valproate. Furthermore, the small percent change in the population estimate of antiepileptic drug plasma clearance values (-2% to +7%) suggests that pregabalin coadministration exerted no significant effect on the pharmacokinetics of these antiepileptic drugs, with the possible exception of tiagabine (+34.9%). These findings are in agreement with those of previously published reports. A further clarification study is necessary for tiagabine. In conclusion, it appears that pregabalin can be coadministered with other antiepileptic drugs without concern for significantly altering their pharmacokinetic profiles.     

Consecutive Gas Chromatographic Determination of Phenytoin, Phenobarbital, Primidone, Phenylethylmalondiamide, Carbamazepine, Trimethadione, Dimethadione, Ethosuximide, and Valproate from the Same Serum Specimen

A quantitative gas-liquid chromatographic procedure is described for the consecutive determination of phenytoin, phenobarbital, primidone, phenylethylmalondiamide, carbamazepine, trimethadione, dimethadione, ethosuximide and valproate from a single serum specimen of 1.2 ml. After extraction from serum by two different procedures, the anticonvulsants are chromatographed without further purification on a 3% OV 17 column either with or without derivative formation by means of "on-column" methylation. Multiple internal standards are employed in order to enhance the reproducibility of drug-concentration measurement.     

Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer''s disease

Recently, apoptosis has been implicated in the selective neuronal loss of Alzheimer's disease (AD). Apoptosis is regulated by the B cell leukemia-2 gene product (Bcl-2) family (Bcl-2, Bcl-x, Bax, Bak and Bad) and the caspase family (ICH-1 and CPP32), with apoptosis being prevented by Bcl-2 and Bcl-x, and promoted by Bax, Bak, Bad, ICH-1 and CPP32. In the present study, we examined the levels of these proteins in the membranous and cytosolic fractions of temporal cortex in AD and control brain. In the membranous fraction, the levels of Bcl-2, Bcl-x_L, Bcl-x_β, Bak and Bad were increased in AD. In the cytosolic fractions, the level of Bcl-x_β was increased, while Bcl-x_L, Bax, Bak, Bad and ICH-1_L were unchanged. CPP32 was not detected in AD or control brain. These findings demonstrate a differential involvement of cell death-regulatory proteins in AD and suggest that Bak, Bad, Bcl-2 and Bcl-x are upregulated in AD brains.     

中国汉族人群SCA1、2、3、6、7、8、10、12、17亚型和齿状核-红核-苍白球-路易体萎缩亚型频率分布

目的 研究中国汉族人群中脊髓小脑性共济失调(SCAs)不同基因亚型的频率分布.方法 运用聚合酶链反应、变性聚丙烯酰胺凝胶电泳、Southern blot、T载体克隆重组DNA技术结合直接测序等技术对559例临床诊断为SCA的患者(363例常染色体显性遗传先证者,196例散发患者)进行了SCA1、SCA2、SCA3/MJD、SCA6、SCA7、SCA8、SCA10、SCA12、SCA17和齿状核-红核-苍白球-路易体萎缩(DRPLA)致病基因多核苷酸病理重复突变检测分析.结果 在363个常染色体显性遗传的SCA(AD-SCA)家系中,发现有15个SCA1家系(4.13%),26个SCA2家系(7.16%),187个SCA3/MJD家系(51.52%),6个SCA6家系(1.65%),7个SCA7家系(1.93%),1个SCA12家系(0.28%)和1个SCA17家系(0.28%),120个SCA家系未明确基因分型(33.06%);在196例散发SCA患者中,发现有2例SCAI患者(1.02%),3例SCA2患者(1.53%),15例SCA3/MJD患者(7.65%),3例SCA6患者(1.53%),173例SCA患者未明确基因分型(88.27%);未发现SCA8、SCA10和DRPLA型患者.结论 在中国汉族人群中SCA3/MJD为最常见的SCA亚型,其次为SCA2、SCA1、SCA7和SCA6,SCA12和SCA17比较少见,SCA8、SCA10和DRPLA罕见,SCA17亚型为国内首次报道.部分AD-SCA家系存在其他致病基因的作用,大部分散发SCA患者除遗传因素外还存在其他致病因素.     

Plant inhibitors of serine proteinases: Hageman factor fragment, kallikreins, plasmin, thrombin, factor Xa, trypsin, and chymotrypsin

Numerous plants were tested for inhibitors of human Hageman factor fragment (HF_f), plasma kallikrein, urinary kallikrein, plasmin, thrombin, porcine pancreatic kallikrein, and bovine Factor X_a, trypsin, and chymotrypsin. Pumpkin seeds and iris bulbs contain trypsin inhibitors which specifically inhibit HF_f. Flower bulbs—especially those of tulip, lily, hyacinth, and calla—are hitherto unrecognized rich sources of inhibitors with different inhibitory spectrums and physicochemical properties.     

Mass spectrometric identification of Cu, Zn, Fe, Co, Mn, Mg, and Pb in mammalian brain.

Combining the techniques of thin-layer chromatography (TLC) and mass spectrometry, we unambiguously identified the trace metals Cu, Zn, Fe, Pb, Mn, Co, and Mg in the brain of a female human who had no evidence of any pathologic disease in the central nervous system, and in brains from mouse, rat, guinea pig, and rabbit. These trace metals were also found in anatomic regions of human brain: cortex (gray), cortex (white), caudate nucleus, putamen, hippocampus, and thalamus, and in anatomic regions of rat brain: hypothalamus, cerebellum, stem striatum, and "the rest." The metals were characterized from the color and Rf values of their tetraphenylporphyrin chelates on TLC and from the mass and pattern of molecule ion cluster of the mass spectrum. The unexpected presence of lead in the brain is discussed.