dl-3-正丁基苯酞软胶囊治疗轻中度急性缺血性脑卒中的开放临床研究

目的 观察国家Ⅰ类新药dl-3-正丁基苯酞软胶囊对轻中度急性缺血性脑卒中的疗效及安全性。方法对急性缺血性脑卒中患者进行随机对照或开放临床试验，参加随机试验的受试者依服药方法不同再分为3次／d给药（200mg／次）和2次／d给药（200mg／次）两个亚组；开放试验受试者均3次／d给药（200mg／次）。所有受试者基础用药均为复方丹参注射液。分别于治疗后第11天和第21天进行神经功能缺损评分及日常生活活动能力量表评分，观察和记录不良事件。结果（1）随机对照试验共入选28例患者，经dl-3-正丁基苯酞软胶囊治疗后，A组（3次／d给药）有效率为83．33％（15／18），B组（2次／d给药）40．00％（4／10），组间差异有统计学意义（P〈0．05）；A组治疗第11天和第21天神经功能缺损评分和日常生活活动能力量表评分与B组比较，差异有统计学意义（P〈0．05或P〈0．01）。开放试验入选患者34例，与随机试验28例合计进行总体疗效评估。（2）总体疗效评估显示，总有效率为72．58％（45／62）；与治疗前相比，治疗后第11天神经功能缺损评分明显减少，日常生活活动能力量表评分明显增加（均P〈0．01）；治疗后第21天神经功能缺损评分和日常生活活动能力量表评分优于第11天（均P〈0．01）。（3）RE用dl-3-正丁基苯酞软胶囊后的主要不良反应为丙氨酸转氨酶及天冬氨酸转氨酶水平轻中度升高，发生率为4．62％（3／65），停药后可恢复至正常水平。结论dl-3-正丁基苯酞软胶囊对轻中度急性缺血性脑卒中疗效显著，不良反应少且为可逆性，临床应用安全；3次／d用药组疗效优于2次／d用药组。     

丁苯酞软胶囊治疗基底动脉尖综合征的疗效观察

目的 观察丁苯酞软胶囊治疗轻、中度基底动脉尖综合征的临床疗效.方法 将60例轻、中度基底尖动脉综合征患者随机分为治疗组和对照组,每组各30例.对照组予以常规治疗,治疗组在常规治疗基础上加用丁基苯酞软胶囊口服,疗程为14d.采用NIHSS评分与BI评分评价治疗前,治疗后第7天和第14天两组的神经功能与日常生活能力.结果 治疗后两组的NIHSS评分显著降低,BI评分显著增高(P＜0.05).治疗组在治疗后第7天和第14天的NIHSS评分明显低于治疗前及对照组,差异均具有统计学意义(P＜0.05);在治疗后第7天和第14天的BI评分则明显高于治疗前及对照组,差异均具有统计学意义(P＜0.05).结论 丁苯酞软胶囊治疗轻度中度基底动脉尖综合征具有较好的临床疗效.     

dl-3-正丁基苯酞软胶囊与阿司匹林治疗急性缺血性脑卒中的多中心、随机、双盲双模拟对照研究

目的 观察国家一类新药正丁基苯酞(NBP)治疗急性缺血性脑卒中的疗效及安全性.方法 在使用复方丹参静脉点滴的基础上,对197例首次发作72 h以内,NIHSS评分在5～25分的颈内动脉系统急性脑梗死患者进行多中心、随机、双盲、阿司匹林对照研究,分为NBP治疗组和阿司匹林对照治疗组.结果 总有效率(基本痊愈+显著进步)NBP组为74.7%,阿司匹林组为60.9%(CMH检验值为4.0,P=0.047);NIHSS总评分、总评分差值、Barthel指数在治疗后第11天和第21天改善的程度明显优于对照组.两组治疗后血常规和血液生化指标变化无统计学意义.NBP的主要不良反应是氨基转移酶升高,以天冬氨酸氨基转移酶轻度升高为主,两组的异常率分别为4.34%和0.结论 NBP对缺血性脑卒中的急性期治疗有效,临床应用安全.     

dl-3-正丁基苯酞软胶囊治疗急性脑梗死

目的:观察dl-3-正丁基苯酞(恩必普)软胶囊治疗急性脑梗死的临床疗效和安全性。方法:选择87例首次发作的急性脑梗死患者,治疗组40例、对照组47例。治疗组试验药dl-3-正丁基苯酞软胶囊,每次口服200mg,tid。对照组用药为复方丹参注射液,治疗组加用对照组用药。结果:治疗组与对照组治疗后第11和2l天的神经功能评分和生活能力评定差异有显著性。治疗组治疗前、后实验室数据无显著性差异。结论:dl-3-正丁基苯酞软胶囊治疗急性脑梗死的临床疗效明显,对肝和肾功能、血脂、血糖、EKG无明显影响,不良反应少,临床用药安全。     

丁苯酞对轻度认知功能损害患者的治疗作用72机制

目的探讨dl-3-正丁基苯酞软胶囊对轻度认知功能损害患者的治疗作用及初步机制.方法选择60例轻度认知功能损害患者,随机分为治疗组和对照组,每组30例,治疗组给予dl-3-正丁基苯酞软胶囊口服,200mg/次,3次/d;治疗组给予曲克芦丁片口服,180mg/次,3次/d;同时2组均口服脑复康片,1.2/次,3次/d,疗程均为2个月.治疗前后分别对2组患者进行简易智能精神状态量表(mini-mental state examination scale,MMSE)评分,并利用氢质子磁共振波谱(1H-magnetic resonance spectroscopy,1H-MRS)的方法,分别检测左侧颞叶海马区域NAA、mI及Cho物质代谢变化.同时对2组患者治疗前后MMSE评分和NAA、mI及Cho代谢物含量进行相关分析.结果与对照组及同组治疗前(MMSE评分24.87±0.73,NAA/Cr 1.224±0.228)比较,治疗组治疗后MMSE评分28.94±0.89显著增加,左侧颞叶海马区域NAA/Cr1.537±0.315显著升高;mI/Cr和Cho/Cr在各组间均无明显差异.各组患者MMSE评分与NAA/Cr均呈正相关(r=0.709、0.682、0.657、0.673),与mI/Cr及Cho/Cr无明显相关关系.结论 dl-3-正丁基苯酞软胶囊可改善轻度认知功能损害患者认知功能,其机制可能与改善脑内代谢有关.     

不同时间应用丁苯酞注射液对阿替普酶静脉溶栓的影响

目的明确阿替普酶静脉溶栓前或后应用丁苯酞氯化钠注射液对急性缺血性脑卒中预后的影响。方法纳入包头医学院第一附属医院神经内二科2014-01—2018-01接受阿替普酶静脉溶栓联合丁苯酞氯化钠注射液治疗的60例急性缺血性脑卒中患者,其中溶栓前应用丁苯酞氯化钠注射液的患者25例为溶栓前组,溶栓后应用的患者35例为溶栓后组,比较2组14d、90d的NIHSS评分,90d的mRS评分,并作多因素分析。结果 2组14dNIHSS评分分别为(4.56±4.263)分、(5.69±6.876)分,差异无统计学意义(P0.05)。2组90dNIHSS评分分别为(2.44±2.347)分、(2.74±3.127)分,差异无统计学意义(P0.05)。2组90dmRS评分分别为(1.40±0.500)分、(1.51±0.507)分,差异无统计学意义(P0.05)。2组预后多因素比较,年龄、心脏病史可影响缺血性脑卒中预后,丁苯酞使用时间点对预后无影响。结论阿替普酶静脉溶栓前或后应用丁苯酞氯化钠注射液对急性缺血性脑卒中预后无影响,年龄、心脏病史是预后的相关影响因素。     

丁苯酞联合舒血宁注射液治疗脑卒中的临床效果分析

目的丁苯酞联合舒血宁注射液治疗脑卒中的临床效果。方法回顾分析2014-01-2015-01在我院治疗的脑卒中患者100例,随机分为治疗组和对照组,每组50例。对照组行舒血宁注射液治疗,治疗组在对照组的基础上给予丁苯酞,记录治疗后各组患者血清MDA水平、血清SOD水平及NIHSS评分。结果 (1)治疗组1周、2周后血清MDA水平分别为(6.05±1.21)nmol/mL、(2.84±1.47)nmol/mL,优于对照组的(7.59±1.63)nmol/mL、(6.38±0.93)nmol/mL,差异具有统计学意义(P0.05)。(2)治疗组1周、2周后血清SOD水平分别为(78.57±8.05)U/mL、(89.60±9.63)U/mL,优于对照组的(69.73±9.31)U/mL、(75.74±8.52)U/mL,差异具有统计学有意义(P0.05)。(3)治疗1周、2周后,观察组NIHSS评分分别为11.26±1.40、7.29±1.14,优于对照组的14.39±1.85、9.96±1.62,差异具有统计学有意义(P0.05)。结论丁苯酞联合舒血宁注射液治疗脑卒中效果良好,与常规对症处理相比不良反应无显著差异。联合用药方案优于常规治疗,值得临床进一步深入研究和推广。     

dl-3-正丁基苯酞治疗急性缺血性脑卒中：随机双盲对照研究

dl-3-正丁基苯酞（butylphthalide or dinbente）系从芹菜籽挥发油中分离出的左旋体，后经人工合成为消旋体，其商品名为恩必普（NBP软胶囊）。动物实验研究表明，dl-3-正丁基苯酞具有增加缺血区脑血流量和改善缺血脑组织区域微循环。缩小局灶性脑缺血后脑卒中面积及增强线粒体ATP酶活性等作用。该药由中国医学科学院药物研究所研制，石家庄制药集团有限公司生产，是我国第3种化学合成类Ⅰ类新药，亦是中国脑血管研究领域第1项拥有自主知识产权的国家Ⅰ类新药。曾经获得国家科技部“1035”工程重大项目、国家自然科学基金重大项目、国家经济计划委员会“高新技术产业化示范工程”、国家“十五”重大科技专项等多项研究基金资助，拥有14项国际和国内专利发明权。     

恩必普软胶囊改善慢性脑供血不足患者认知功能的临床分析

目的:探讨dl-3-正丁基苯酞软胶囊(恩必普软胶囊)治疗慢性脑供血不足的临床疗效及对慢性脑供血不足病人认知功能改善的影响。方法:将60例慢性脑供血不足病人随机分为治疗组和对照组,每组30例,治疗组口服dl-3-正丁基苯酞软胶囊,每次200毫克,每日3次;对照组口服复方丹参片,每次4片,每日3次,疗程为8周,治疗前后进行疗效评价和P300数据采样,同时给予同步MMSE、HDS量表评分。结果:治疗组总有效率为70%,对照组总有效率为53.3%,2组治疗后比较差异有显著意义(P<0.05);治疗组治疗前、后MMSE和HDS量表得分情况比较,均有明显改善(P<0.01),与对照组治疗后比较差异有显著意义(P<0.05);治疗组治疗前、后P300波潜伏期及P300波幅差异均有显著意义(P<0.05),与对照组治疗后比较均有显著差异(P<0.05)。结论:dl-3-正丁基苯酞软胶囊对慢性脑供血不足病人安全有效。     

西酞普兰治疗惊恐障碍对照研究

目的探讨西酞普兰对惊恐障碍患者的疗效及副作用。方法对46例惊恐障碍患者随机分成西酞普兰治疗组、帕罗西汀对照组,并用HAMA、GAS、SERS对患者治疗前后进行评估。结果除了在治疗第1周末,西酞普兰治疗组的HAMA分值高于对照组外,在第2、4、6周末,两组患者的HAMA、GAS分值差异均无显著性意义。西酞普兰组患者在治疗6周末,治愈率及有效率分别为63.2%、84.2%,而帕罗西汀组分别为68.2%、90.9%,与帕罗西汀组相比差异无显著性意义。西酞普兰组平均剂量(41.87±15.36)mg/d;帕罗西汀组平均剂量(40.91±14.44)mg/d。在副作用方面,两组患者差异也无统计学意义。结论西酞普兰治疗惊恐障碍患者疗效及副作用与帕罗西汀相当。     

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.