3-乙基-3-甲基戊二酰亚胺致癫痫大鼠糖皮质激素及其受体水平变化

目的：探讨糖皮质激素及其受体与癫痫发病的关系。方法：选用SD雄性大鼠以3-乙基-3-甲基戊二酰亚胺背部皮下注射急、慢性致癫痫(每组20只)，同时建立生理盐水对照组(n=20)，检测血浆皮质醇及海马、大脑皮质糖皮质激素受体的变化。结果：血浆皮质醇水平在急性致痫组[(5．99&;#177;1．27)μg／L]明显高于正常对照组[(3．82&;#177;0．91)μg／L]，差异有显著性意义(t=7．07，P&;lt;0．01)；在慢性致病组[(2．68&;#177;0．52)μg／L]明显低于正常对照组，差异有显著性意义(t=4．87，P&;lt;0．01)。顶叶大脑皮质、海马CA1区及齿状回糖皮质激素受体阳性细胞数(每12．5mm^2)，在急性致病组明显减少(11．50&;#177;2．17，10．50&;#177;2．64，24．00&;#177;3．94)，在慢性致病组明显增多(26．30&;#177;5．21，29．00&;#177;3．37，58．10&;#177;6．97)，与正常对照组(18．50&;#177;3．00，21．90&;#177;5．10，46．70&;#177;6．93)比较，差异有非常显著性(t=5．18—19．33。P&;lt;0．01)。结论：糖皮质激素及其受体的变化可能与癫痫发病有关。     

急性脑梗死患者血清胰岛素样生长因子-1含量变化与神经功能缺损评分的关系

目的:观察急性脑梗死患者的血清胰岛素样生长因子-1(insulin-likegrowthfactor-1,IGF-1)的含量变化并分析与神经功能缺损评分的关系。方法:采用酶联免疫吸附法(ELASA法)测定57例急性脑梗死患者的血清IGF-1水平和神经功能缺损评分(chineseneurologicfunctionalscale,CNFS),并与26例正常对照组比较。结果:急性脑梗死组IGF-1水平犤(99.48±33.76)μg/L犦显著低于对照组犤(179.90±35.47)μg/L犦,差异有显著性意义(t=2.14,P<0.05)。大梗死组IGF-1水平犤(71.41±22.37)μg/L犦显著低于中梗死组犤(107.99±23.15)μg/L犦(q=3.05,P<0.05)及小梗死组犤(134.96±25.24)μg/L犦,差异有显著性意义(q=5.44,P<0.01)。中梗死组IGF-1水平显著低于小梗死组(q=3.21,P<0.05)。病情重度组IGF-1水平犤(74.57±22.54)μg/L犦显著低于中度组犤(102.11±23.07)μg/L犦(q=2.91,P<0.05)及轻度组犤(131.58±23.89)μg/L犦(q=6.25,P<0.01)。病情中度组IGF-1水平显著低于轻度组(q=3.26,P<0.05)。CNFS差者IGF-1水平低,急性脑梗死组言语功能评分和肢体运动功能评分与IGF-1水平呈显著负相关(r=-0.67和-0.55,P<0.01)。结论:IGF-1参与了急性脑梗死的病理生理过程。IGF-1与CNFS关系密切,监测IGF-1的变化对判断病情轻重及估计预后均有临床意     

实验性癫痫大鼠脑电调制与侧脑室注射催产素的作用

目的:观察催产素对大鼠癫痫的作用效应并探讨其可能的作用机制。方法:实验在武汉大学医学院生理学电生理实验室完成。采用青霉素诱发的大鼠癫痫模型,动物随机分为6组,每组6只,第1组为对照组,第2,3,4组分别侧脑室注射催产素1,10,100ng,第5组注射催产素受体拮抗剂犤d(CH2)5-OVT犦1μg,第6组注射犤d(CH2)5-OVT犦1μg+催产素100ng。同步观察大脑额叶皮质和海马CA3区脑电图痫样波的发放频率、幅度以及放电形式的变化。结果:催产素100ng可明显增加痫样放电的频率犤由(22.83±0.70)次/min升至(39.67±2.53)次/min,t=5.777,P<0.01犦和幅度犤由(428.50±40.88)μV升至(540.24±71.12)μV,t=3.168,P<0.05犦;催产素10ng可使痫样放电的幅度增加犤(538.90±55.95)μV,t=4.004,P<0.05犦;犤d(CH2)5-OVT犦可阻断催产素的易化效应。结论:侧脑室注射一定剂量的催产素,可通过其受体作用加重实验性癫痫大鼠痫样放电。     

褪黑素对戊四氮致癫痫大鼠海马谷氨酸受体和γ-氨基丁酸受体的影响

目的:探讨褪黑素抗癫痫的机制。方法:应用SP法研究戊四氮致癫痫大鼠和褪黑素抗癫痫大鼠海马谷氨酸受体ζ1(N-methyl-D-aspartaterecepterζ1,NMDAζ1)和γ-氨基丁酸受体Aα1(r-aminobutyricacid-Arecepterα1,GABAARα1)的变化。结果:海马NMDAζ1表达在戊四氮致癫痫组明显高于正常对照组(q吸光度=6.34,P<0.01;q阳性率=9.394,P<0.01),褪黑素抗癫痫组明显低于戊四氮致癫痫组(q吸光度=6.01,P<0.01;q阳性率=9.000,P<0.01),褪黑素抗癫痫组与正常对照组之间差异无显著性意义(q吸光度=0.032,P>0.05;q阳性率=0.4015,P>0.05);海马GABAARα1表达在戊四氮致癫痫组明显低于正常对照组(q吸光度=4.65,P<0.01;q阳性率=5.3,P<0.01),褪黑素抗癫痫组明显高于戊四氮致癫痫组(q吸光度=4.58,P<0.01;q吸光度=5.21,P<0.01),褪黑素抗癫痫组与正常对照组之间差异无显著性意义(q吸光度=0.07,P>0.05;q吸光度=0.097,P>0.05)。结论:褪黑素可能通过抑制海马兴奋性神经递质受体NMDAζ1和激活海马抑制性神经递质受体GABAARα1的活性与表达,降低大脑皮质的兴奋性,抑制癫痫的形成及发展来发挥抗癫痫作用。     

军人创伤后应激障碍患者脑诱发电位的3种变异

目的:探讨军人创伤后应激障碍(post-traumaticstressdisorder,PTSD)患者3种脑诱发电位(brainevokedpotential,BEP)的变异。方法:应用美国NicoletBravo型脑诱发电位仪,采用光、声刺激和Click短声刺激,检测75例PTSD患者(研究组)和46名健康军人(对照组)的视觉诱发电位(visualevokedpotential,VEP)、听觉诱发电位(auditoryevokedpotential,AEP)和脑干听觉反应(auditorybrainstemresponse,ABR)。结果:①VEP:Cz脑区的P2波幅研究组低于对照组犤(4.4±4.1)和(9.0±5.2)μV,t=5.40,P<0.01犦,Pz脑区的P3波幅研究组低于对照组犤(5.1±4.0)和(8.1±4.5)μV,t=3.82,P<0.01犦。②AEP:Oz脑区的P3潜伏期研究组长于对照组犤(330.2±30.7)和(298.1±27.4)ms,t=5.81,P<0.01犦,Cz脑区的P2波幅研究组低于对照组犤(2.8±1.7)和(4.5±1.8)μV,t=5.22,P<0.01犦,Cz脑区的P3波幅研究组高于对照组犤(4.2±2.1)和(2.2±1.0)μV,t=6.05,P<0.01犦。③ABR:Pz脑区的波Ⅴ绝对潜伏期研究组长于对照组犤(5.8±0.3)和(5.4±0.2)ms,t=8.01,P<0.01犦,Oz脑区的波Ⅴ绝对潜伏期研究组短于对照组犤(6.4±0.3)和(6.9±0.3)ms,t=8.90,P<0.01犦。Pz脑区的波Ⅳ绝对波幅研究组低于对照组犤(0.24±0.12)和(0.40±0.10)μV,t=7.57,P<0.01犦,Oz脑区的波Ⅱ绝     

催产素对癫痫大鼠大脑皮质和海马热休克蛋白70表达的影响

目的:探讨青霉素诱导大鼠癫痫发作中催产素对神经元代谢活动有关的持续性癫痫发作的标志-热休克蛋白70表达的影响。方法:实验于2005-02在武汉大学医学院生理实验室完成。取健康3月龄雄性SD大鼠18只,随机分为3组,即对照组、青霉素致痫组与催产素处理组,每组6只。青霉素致痫组腹腔注射青霉素30万U;催产素处理组腹腔注射催产素20μg,30min后再腹腔注射青霉素30万U;对照组腹腔注射等量的生理盐水。各组动物均于给药24h后用100g/L氨基甲酸乙酯(1g/kg)腹腔注射麻醉,断头取脑,切取冠状脑片。免疫组化方法观察青霉素诱导大鼠癫痫发作及催产素干预后大鼠大脑皮质和海马内热休克蛋白70的表达。每只动物脑切片标本抽取3张,每张切片随机选取5个高倍镜视野(SP×200),测定每个视野下阳性反应的吸光度。以每只动物脑切片标本15个视野的平均吸光度为该例的测量值。结果:18只大鼠均进入结果分析。①大鼠给予青霉素后10min左右出现不同程度的癫痫发作症状。表现为不动、凝视、蹲伏、湿狗样抖等。②对照组大脑皮质和海马神经元胞内偶见散在分布的棕黄色颗粒,热休克蛋白70表达弱;青霉素致痫组大脑皮质和海马神经元胞内出现密集的深棕黄色颗粒,热休克蛋白70表达呈强阳性;催产素处理组大脑皮质及海马神经元胞内出现密集的棕黄色颗粒,热休克蛋白70表达呈阳性,但表达量较见青霉素致痫组减少。③青霉素致痫组热休克蛋白70阳性神经元的平均吸光度明显高于对照组,差异有显著性意义眼(0.6652±0.0261),(0.1030±0.0040),t=-51.158,P<0.001演鸦催产素处理组降为(0.5692±0.0645),与青霉素致痫组比较差异有显著性意义(t=5.092,P<0.05)。结论:在癫痫发作过程中,预先用催产素可通过抑制热休克蛋白质70的合成而降低大脑皮质与海马热休克蛋白70的表达。     

番茄汁对D-半乳糖衰老模型大鼠海马神经元的抗衰老作用

目的:探讨番茄汁对衰老模型大鼠海马神经元的抗衰老作用。方法:采用随机数字表将30只Wistar大鼠随机分成3组,建立D-半乳糖亚急性衰老模型,采用生化、光镜和电镜等方法,观察番茄汁对衰老大鼠海马神经元的影响。结果:番茄汁组大鼠大脑丙二醛含量犤(3.41±0.36)μmol/g犦,与乳糖组犤(4.01±0.27)μmol/g犦相比显著降低(P<0.05),超氧化物歧化酶(SOD)活性犤(25.06±1.86)NU/mg犦与D-半乳糖组犤(20.63±2.52)NU/mg犦相比明显增高(P<0.01);海马神经元形态结构衰老征象明显减轻。结论:番茄汁可延缓海马神经元的衰老进程,具有一定的抗衰老作用。     

黄芩素甙对沙土鼠脑缺血再灌注损伤的影响

目的:研究黄芩素甙对脑缺血再灌注损伤的作用及其对三磷酸腺苷(ATP)及羟自由基含量的影响。方法:沙土鼠前脑缺血再灌注模型,缺血时间10min。动物分为假手术组、对照组、黄芩素甙Ⅰ组(45mg/kg,腹腔注射)、黄芩素甙Ⅱ组(90mg/kg,腹腔注射)。高倍镜下计数海马CA1区存活锥体细胞数目,ATP及羟自由基含量测定采用高效液相法。结果:再灌注4d时,对照组海马CA1区存活锥体细胞数目仅为假手术组的5%犤(5±2),(96±12)×104/mm2,t=8.607,P<0.01犦,而黄芩素甙Ⅰ组和Ⅱ组分别为假手术组的23%和42%,明显多于对照组犤(22±8),(40±9),(5±2)×104/mm2,t=1.747,3.622,P<0.01犦。再灌注60min,黄芩素甙Ⅰ组和Ⅱ组ATP含量均高于对照组,犤(0.70±0.08),(0.81±0.15),(0.51±0.19)mmol/kg,t=1.277,1.562,P<0.05犦,但两组间差异无显著性意义。缺血末和再灌注60min,黄芩素甙Ⅱ组羟自由基含量低于对照组犤(0.43±0.12),(0.65±0.16)mmol/L,t=1.871,P<0.05;(0.42±0.15),(0.72±0.13)mmol/L,t=2.747,P<0.01犦。结论:黄芩素甙(45mg/kg和90mg/kg)可减轻脑缺血再灌注损伤,其机制可能与其减轻细胞能量代谢障碍和减少羟自由基产生有关。     

托吡酯对发育期大鼠癫痫模型脑神经元损伤的保护作用

目的:探讨托吡酯对发育期大鼠癫痫发作引起的脑神经元损伤的保护作用。方法:戊四氮点燃发育期大鼠癫痫模型,随机分为正常对照组、点燃模型组和托吡酯治疗组,每组27只,观察大鼠惊厥发作频率、发作程度、血清神经元特异性烯醇化酶(neuron-specificenolase,NSE)水平变化及海马区病理改变。结果:正常对照组大鼠无惊厥发作,血清NSE水平在正常范围,海马区无神经元死亡;点燃模型组大鼠惊厥出现时间早(第3天即有发作),发作程度重(第1周2级以上惊厥14只,并有3只死于惊厥),血清NSE水平犤第7,14,21天分别为(23.4±2.7),(33.4±7.8),(27.7±7.2)μg/L犦及海马区神经元死亡程度明显高于其他两组(F=1.710～5.255,P<0.05);托吡酯治疗组大鼠惊厥出现时间晚,发作程度轻(第1周2级以下轻度发作13只,2～4级中度发作4只,无重度发作),血清NSE水平犤第7,14,21天分别为(18.6±3.7),(14.9±3.7),(12.8±3.2)μg/L犦及海马区神经元死亡程度略高于正常对照组而低于点燃模型组(F=1.710～5.255,P<0.05)。结论:托吡酯对癫痫发作引起的脑神经元损伤有保护作用。     

电针对大鼠慢性脊髓损伤热休克蛋白70及诱导型一氧化氮合酶表达的影响

目的:研究电针对大鼠慢性脊髓损伤热休克蛋白70(heatshockprotein70,HSP70)及诱导型一氧化氮合酶(induciblenitricoxidesynthase,iNOS)表达的变化及对脊髓功能的影响,探讨针刺治疗慢性脊髓损伤的作用机制。方法:40只2个月龄SD大鼠,随机分为对照组10只,实验组30只。实验组随机分为3组:持续压迫组,减压组,电针组(n=10),采用大鼠后路渐进性脊髓压迫动物模型,然后手术减压,并进行电针治疗。观察联合行为评分(combinedbehavioralscore,CBS)和HSP70及iNOS的免疫组织化学变化。结果:脊髓损伤后HSP70和iNOS在神经元表达均增强,经过电针治疗后,HSP70在神经元的表达进一步增强,电针组犤(130.35±18.98)个犦与减压组犤(42.76±13.45)个犦比较,差异有非常显著性意义(t=11.907,P<0.01),iNOS在神经元的表达下降。电针组犤(8.21±3.76)个犦与减压组犤(13.24±2.71)个)比较,差异有非常显著性意义t=(3.432,P<0.01)。CBS值显示,电针组明显优于减压组,电针组犤(12.29±6.05)分犦与减压组犤(20.24±8.88)分犦比较,差异具有显著性意义(t=2.34,P<0.05)。结论:电针治疗可以促进脊髓损伤大鼠的行为功能恢复,HSP70介导了电针的治疗过程,保护了脊髓神经细胞并减轻继发性脊髓损伤,与促进行为功能恢复有关。     

3-Methylcrotonylglycine excretion in 3-hydroxy-3-methylglutaric aciduria

1. 3-Methylcrotonylglycine was identified in urine from an infant with 3-hydroxy-3-methylglutaric aciduria. 2. The concentration of 3-methylcrotonylglycine in urine was approximately one sixth of that of the other metabolite of 3-methylcrotonyl-CoA, 3-hydroxyisovaleric acid. 3. The presence of both metabolites in the infant's urine indicates an inhibition of 3-methylcrotonyl-CoA carboxylase activity in tissues of the infant.     

3-Hydroxy-3-methylglutaric aciduria: 3-hydroxy-3-methylglutaryl-coenzyme A lyase levels in leucocytes.

3-Hydroxy-3-methylglutaryl-coenzyme A lyase activity in leucocytes from a baby with 3-hydroxy-3-methylglutaric aciduria is markedly deficient when compared to controls. Both parents have reduced levels of the enzyme in leucocytes.     

Pharmacokinetics of 3''-fluoro-3''-deoxythymidine and 3''-deoxy-2'',3''-didehydrothymidine in rats.

Concentrations of 3'-fluoro-3'-deoxythymidine (FDT) and 3'-deoxy-2',3'-didehydrothymidine (D4T) in plasma declined in a biexponential fashion. Total clearance of D4T (1.75 +/- 0.22 liters/h/kg; mean +/- standard deviation) was significantly greater than that of FDT (1.19 +/- 0.19 liters/h/kg) owing to greater renal and nonrenal clearances of the former. Steady-state volumes of distribution of FDT (1.20 +/- 0.12 liters/kg) and D4T (1.07 +/- 0.15 liters/kg) were similar.     

Pharmacokinetics of 3''-fluoro-3''-deoxythymidine and 3''-deoxy-2'',3''-didehydrothymidine in rhesus monkeys.

3'-Fluoro-3'-deoxythymidine and 3'-deoxy-2',3'-didehydrothymidine are nucleoside analogs which inhibit human and simian immunodeficiency virus in vitro. The pharmacokinetic properties of these compounds in rhesus monkeys after intravenous, oral, and subcutaneous administration of the drug were compared. Half-lives, total clearances, and steady-state volumes of distribution of the two drugs were determined. The half-lives for the drugs by the different routes were between 0.58 and 1.4 h. Oral bioavailability of 3'-deoxy-2',3'-didehydrothymidine was incomplete, with an average of 42% +/- 15% of the dose reaching the systemic circulation. Absorption of 3'-fluoro-3'-deoxythymidine after oral administration was variable, with bioavailability ranging from 21 to 95%. Bioavailability after subcutaneous administration ranged from 59 to 77% for 3'-deoxy-2',3'-didehydrothymidine and from 52 to 59% for 3'-fluoro-3'-deoxythymidine. The ratio of concentrations in cerebrospinal fluid and serum for the drugs was about 0.15 at 1 h after drug administration and was independent of the route of administration, suggesting that a nucleoside carrier-mediated process is involved in the transport of these compounds to the central nervous system. Because of the similar metabolism of nucleoside analogs in monkeys and humans, the potential glucuronide formation was assessed. Whereas the glucuronide of 3'-fluoro-3'-deoxythymidine was readily detected in urine, the amount of 3'-deoxy-2',3'-didehydrothymidine glucuronidated was small or not detectable in one-half of the urine samples. Pharmacokinetic parameters for the two drugs were similar to each other and analogous to those for 3'-azido-3'-deoxythymidine in monkeys, suggesting that the same dose and scheduling of the drug can be used for all three compounds in prophylactic and therapeutic efficacy drug studies in rhesus monkeys.     

Elevated γ:γ globin chain ratio in homozygous beta thalassemia

G gamma:A gamma chain ratios were determined in homozygous beta thalassemia and cord blood samples using triton-urea polyacrylamide gel electrophoresis. The mean G gamma/G gamma + A gamma proportion in the two groups were 0.62 +/- 0.10 and 0.72 +/- 0.03, respectively. There was no significant correlation of the gamma chain composition in either fetal hemoglobin or total hemoglobin levels; this suggests that these two factors do not influence gamma chain ratios. There was also no marked variation in the G gamma:A gamma ratios in beta thalassemia patients when they were divided into higher fetal hemoglobin (greater than 50%) and lower fetal hemoglobin (less than 50%) groups. These observations are consistent with the finding of a selective advantage of G gamma chains over A gamma chains in disorders where the erythropoietic stress is higher than normal, and may be inherited as a specific genetic entity in haplotypic polymorphism.     

Cross-training in 3-D

With 3 hospitals and 10 perinatal nursing units, nurse leaders developed a cross-training program to unify staff for maximum flexibility, greater job satisfaction, and savings.     

Coexistence of light-induced photoluminescence enhancement and quenching in CH3NH3PbBr3 perovskite films

Lead halide perovskites are promising semiconductors for various optoelectronic devices working in a wide photo-excitation density regime. However, photo-induced instability, attributed to illumination-activated mobile ions, has been an obstacle to their application. Herein, we use the time evolution of photoluminescence (PL) to investigate the light illumination effects of CH₃NH₃PbBr₃ perovskite films under relatively high excitation (up to 4.5 W cm⁻²). We demonstrate that continuous illumination can lead to both PL enhancement and PL quenching simultaneously, with their weight ratios depending on the excitation density. The experimental data can be well described and interpreted by considering the coexistence of and competition between the photo-induced annihilation and the formation of long-living filled trap states. Our study may provide in-depth insight into the photo-induced instability of perovskite films and help to improve the performance of perovskite-based optoelectronic devices.

Light illumination with relatively high intensity can result in photoluminescence enhancement and quenching simultaneously in lead halide perovskites.