Acute dose-effect relationships of caffeine and mental performance,EEG, cardiovascular and subjective parameters

The present study investigated the dose-effect relationship of caffeine on mental performance using a caffeine-sensitive rapid information processing task (RIP) in a pre/post cross-over design. Twenty female nonsmoking regular coffee drinkers received 0, 1.5, 3 and 6 mg/kg caffeine in a balanced order and the measurements were extended to cardiovascular, EEG and mood parameters. Surprisingly, the dose-effect curves for the different parameters were rather heterogeneous. Whereas increasing effects with increasing caffeine doses were observed for - and -EEG frequencies, anxiety, wakefulness, and some coffee ratings, negative dose-effect relationships were obtained for RIP processing rate and blood pressure. No apparent dose-effect relationships were seen for reaction time and motor activity. Thus, it was concluded that the dose-response relationships are rather shallow and heterogeneous and that the different parameters have different ranges in which they are sensitive to caffeine. The caffeine doses which might have beneficial behavioral effects are at the lower end of the tested dose range and comparable to those found in caffeine-containing beverages.     

益骨胶囊对成骨细胞增殖影响的时效及量效关系研究

目的 :运用中药血清药理学方法 ,观察益骨胶囊含药血清对新生大鼠颅骨成骨细胞 (OB)体外增殖的影响 ,并探讨用于OB药效观察的益骨胶囊含药血清制备条件。方法 :雌性 12月龄SD大鼠 80只 ,随机分为生理盐水组、益骨胶囊低剂量 (11 6g/kg)、中剂量 (34 8g/kg)、高剂量 (10 4 4g/kg)组 ,每日灌胃一次 ,连续 12天 ,分别在灌胃后的 0 5h、1h、1 5h、2h采血 ,分离血清 ,用含不同浓度益骨胶囊的血清培养SD新生大鼠颅骨OB ,MTT法检测细胞增殖情况。结果 :末次灌胃后 1 5h采血组的吸收度 (A)值明显高于各组其它时间 (P <0 0 5 ) ;不同剂量各浓度的益骨胶囊含药血清对体外培养的OB增殖均有显著的促进作用 ,其中以高剂量组的稀释比为 2 5 %的血清浓度最佳。结论 :益骨胶囊含药血清对OB增殖具有明显的促进作用 ;益骨胶囊用于OB药效观察的大鼠含药血清制备条件以人等效剂量 9倍连续 12天灌胃、末次灌胃后 1 5h采血 ,血清添加浓度以 2 5 %为宜。     

人骨髓基质干细胞在不同诱导环境下向软骨细胞的分化

目的：探索重组人骨形态发生蛋白-2（rhBMP-2）诱导建系的人骨髓基质干细胞（hBMSC，专利名缩写为MSCxj）生成软骨的可行性、最佳剂量及适宜的诱导环境。方法：rhBMP-2分为六组：空白组、100ng／ml组、200ng／ml组、400ng／ml组、600ng／ml组和800ng／ml组。血清浓度分为三组：无血清组、2％血清组和5％血清组。根据rhBMP~和血清不同浓度间的组合，设计18种诱导模式。一部分Mscxj制成微球，模拟三维模式进行细胞爬片培养，另一部分MSCxj直接用96孔板培养，10d后，检测MSCxj的数量、总蛋白生成量和碱性磷酸酶生成量，并行甲苯胺蓝染色及Ⅱ型胶原mRNA检测，利用MPS60病理图像软件分析各组Ⅱ型胶原mRNA染色后的灰度，比较各组Ⅱ型胶原mRNA的生成量。结果：血清浓度越高细胞生成的数量越多，细胞合成的总蛋白无显著差异，rhBMP-2对细胞数量和总蛋白的合成无明显影响。2％的血清浓度比其他血清浓度更利于软骨生成。在该血清浓度下rhBMP-2为400ng／ml时，细胞特异性基质Ⅱ型胶原生成最多（F=19．56，P〈0．05）。结论：rhBMP-2能诱导Mscxi生成软骨，在血清浓度为2％、自身浓度为400ng／ml水平下诱导Mscxj生成软骨能力最强。     

镉对未成年雌性小鼠子宫增重作用的剂量-效应关系

目的通过研究镉对未成年小鼠子宫增重作用的剂量-效应关系,为探讨镉的雌激素样活性提供实验依据。方法将64只未成年雌性昆明种小鼠按体重分层,随机分为8组(阴性对照组,雌二醇阳性对照组和1.25、5、20、80、320、1 280μg/kg氯化镉剂量组),采用腹腔注射染毒方法,每天注射1次,注射容积为0.25 ml/10(g.d),连续注射3 d,最后1次腹腔注射24 h后称重,颈椎脱臼处死小鼠,取子宫称重。结果各染镉剂量组子宫增重与阴性对照组比较,差异无显著性(P>0.05),雌二醇阳性对照组子宫增重显著(P<0.05),实验中各染镉剂量与子宫脏器系数之间无剂量-效应关系。结论在该实验镉剂量范围内,未检测到镉对未成年雌性小鼠子宫有增重作用。     

Dose-effect relationship for cataract induction after single-dose total body irradiation and bone marrow transplantation for acute leukemia

PURPOSE: To determine a dose-effect relationship for cataract induction, the tissue-specific parameter, alpha/beta, and the rate of repair of sublethal damage, mu value, in the linear-quadratic formula have to be known. To obtain these parameters for the human eye lens, a large series of patients treated with different doses and dose rates is required. The data of patients with acute leukemia treated with single-dose total body irradiation (STBI) and bone marrow transplantation (BMT) collected by the European Group for Blood and Marrow Transplantation were analyzed. METHODS AND MATERIALS: The data of 495 patients who underwent BMT for acute leukemia, who had STBI as part of their conditioning regimen, were analyzed using the linear-quadratic concept. The end point was the incidence of cataract formation after BMT. Of the analyzed patients, 175 were registered as having cataracts. Biologic effective doses (BEDs) for different sets of values for alpha/beta and mu were calculated for each patient. With Cox regression analysis, using the overall chi-square test as the parameter evaluating the goodness of fit, alpha/beta and mu values were found. Risk factors for cataract induction were the BED of the applied TBI regimen, allogeneic BMT, steroid therapy for >14 weeks, and heparin administration. To avoid the influence of steroid therapy and heparin on cataract induction, patients who received steroid or heparin treatment were excluded, leaving only the BED as a risk factor. Next, the most likely set of alpha/beta and mu values was obtained. With this set, the cataract-free survival rates were calculated for specific BED intervals, according to the Kaplan-Meier method. From these calculations, cataract incidences were obtained as function of the BED at 120 months after STBI. RESULTS: The use of BED instead of the TBI dose enabled the incidence of cataract formation to be predicted in a reasonably consistent way. With Cox regression analysis for all STBI data, a maximal chi-square value was obtained for alpha/beta = 1.75 Gy and mu = 0.75 h(-1). When Cox regression analysis was applied for patients who had no steroid treatment after BMT, a maximal chi-square value was obtained for alpha/beta = 1 Gy and mu = 0.6 h(-1). Cox regression analysis was repeated using the data of patients who had not received posttransplant steroid treatment and also no heparin administration; we found alpha/beta = 0.75 Gy and mu= 0.65 h(-1). An increased cataract incidence was observed after steroid treatment of >14 weeks and heparin administration. CONCLUSION: The alpha/beta value of 0.75 Gy and mu value of 0.65 h(-1) found for the eye lens are characteristic for late-responding tissues. The incidence of cataract formation can now be quantified, taking into account the values calculated for alpha/beta and mu, TBI dose, and dose rate. Also, the reduction in cataract incidence as a result of lens dose reduction by eye shielding can be estimated.     

巨噬细胞移动抑制因子抑制剂对妊娠晚期大鼠急性坏死性胰腺炎胰腺及胎盘损伤的保护作用及量效关系

目的 探讨巨噬细胞移动抑制因子(MIF)抑制剂ISO-1腹腔注射给药对妊娠晚期大鼠急性坏死性胰腺炎(ANP)大鼠胰腺和胎盘的保护作用及其量效关系.方法 SPF级妊娠晚期SD大鼠30只,随机(随机数字法)分为5组(n=6):假手术组(SO组)、ANP组、ISO-1预处理低剂量组(1.75 mg/kg,T1组)、中剂量组(3.5 mg/kg,T2组)和高剂量组(7.0 mg/kg,T3组).胆胰管逆行注射5％牛磺胆酸钠制备ANP模型.预处理组于造模前30 min经腹腔按低、中、高剂量注射溶解IOS-1的10％DMSO(2 mL/kg)溶液,SO组、ANP组于造模前30 min经腹腔注射10％ DMSO(2 ml/kg),术后6 h处死大鼠.测定大鼠血清中AMY、LIP、ALT及AST水平,光镜下观察大鼠胰腺、胎盘的组织病理变化.多个样本均数比较采用单因素方差分析,两组间比较采用t检验.结果 ANP组AMY、LIP、ALT和AST的水平(U/L)分别为(7 101.4±1 032.3)、(2 939.0±638.8)、(240.3±50.3)和(472.6 ±27.5),高于SO组的(2 268.7±293.8)、(681.1±109.9)、(56.4±15.3)和(110.9±15.5),差异具有统计学意义(P＜0.05);T1组AMY、LIP、ALT、AST的水平(U/L)为(4 349.5±439.5)、(1 968.9±515.2)、(155.0±41.8)和(373.7 ±64.9),低于ANP组,差异具有统计学意义(P＜0.05);T2组AMY、LIP、ALT、AST的水平(U/L)为(3 459.7±459.2)、(1 268.6±367.8)、(110.5±20.6)和(281.8±66.8),低于T1组,差异具有统计学意义(P＜0.05);T3组AMY、LIP、ALT、AST的水平(U/L)为(3 288.4±583.7)、(1198.1 ±328.5)、(100.6±13.2)和(272.9±66.5),同T2组比较差异无统计学意义(P＞0.05).ANP组胰腺、胎盘的病理评分分别为(12.3±1.5)分和(6.3±0.8)分,高于SO组(4.7±1.2)分和(0.5±0.5)分,差异具有统计学意义(P＜0.05);T1组胰腺、胎盘病理评分为(10.5±1.6)分和(5.1±0.7)分,低于ANP组,差异具有统计学意义(P＜0.05);TT2组胰腺、胎盘病理评分为(8.3±1.0)分和(3.0±0.6)分,低于T1组,差异具有统计学意义(P＜0.05);T3组胰腺、胎盘病理评分为(8.0±1.4)分和(2.8±0.8)分,同T2组比较差异无统计学意义(P＞0.05).结论 腹腔给予MIF抑制剂ISO-1对妊娠晚期大鼠A NP大鼠胰腺及胎盘具有保护作用,T2组(3.5 mg/kg)为改善妊娠晚期ANP大鼠胰腺及胎盘损伤安全、有效的最佳剂量.     

益气活血方对大鼠胸部照射肺组织SOD活性、MDA及HP含量的影响

目的：探讨不同剂量益气活血方对大鼠胸部照射肺组织超氧化物歧化酶（superoxide dismutase,SOD）活性、丙二醛（malondiadehyde,MDA）及羟脯氨酸（hydroxyproline,HP）含量的影响,寻找最佳治疗剂量,为临床治疗提供实验依据。方法：100只雄性SD大鼠随机分成：正常对照组（A组）,单纯照射组（B组）,小剂量治疗组（C组）,中剂量治疗组（D组）,大剂量治疗组（E组）,每组20只。A组不照射,B、C、D、E组行6 Mv X线2O Gy单次胸部照射,C、D、E组照射后每日分别给予一次小（30 g/kg）、中（60 g/kg）、大剂量（120 g/kg）益气活血方灌胃治疗。A、B组给予等容积生理盐水灌服。照射后第7、14、30、45、60 d行肺组织SOD、MDA、HP含量检测。结果：肺组织生化指标：照射后30 d SOD逐渐下降到低谷,以B组降低最明显,C、D、E组明显高于B组（P〈0.01）;肺组织MDA照射后逐渐上升,30 d达到高峰,以B组升高最明显,C组低于B组而高于D、E组;照射后HP升高,B组高于C、D、E组,而C组高于D、E组。结论：益气活血方对大鼠胸部照射可提高肺组织SOD活性,降低MDA、HP的含量;益气活血方中剂量为最佳剂量。     

丙泊酚复合麻醉时神经外科手术患者雷米芬太尼的量效关系

目的 探讨丙泊酚复合麻醉时神经外科手术患者雷米芬太尼的量效关系.方法 择期额颞部开颅手术患者15例,先行靶控输注(TCI)阿泊酚,设定效应室靶浓度为3 μg/ml,维持PErCO2为35～45 mmHg,待达到丙泊酚靶浓度后开始TCI雷米芬太尼,设定效应室靶浓度分别为2、3、4、5、6、7、8ng/ml,雷米芬太尼达不同效应事浓度时给予50 mA、50 Hz、5 s强直电刺激,记录电刺激前后BP、HR及脑电双频指数(BIS)的变化.结果 随着雷米芬太尼效应室浓度的增加,BP逐渐降低,HR逐渐减慢(P<0.05或P<0.01);强直电刺激后BP升高幅度、HR加快幅度也逐渐降低(P<0.05或P<0.01).雷米芬太尼效应室浓度达(5.13±0.92)ng/ml时,强直电刺激后MAP升高幅度<5%,95%可信区间为3.33～6.93 ng/ml.与基础值比较,随着雷米芬太尼的效应室浓度逐渐增加,BIS逐渐降低(P<0.01),电刺激前后BIS无明显变化.结论 随雷米芬太尼效应室浓度的增加,镇痛强度逐渐增强,电刺激-循环反应逐渐减弱;雷米芬太尼效应室浓度大于(5.13±0.92)ng/ml时,95%可信区间为3.33～6.93ng/rnl,50 mA强直电刺激-循环反应变化小再明显.     

城乡儿童血铅含量对智力、行为、学习影响及“剂量-效应”关系的研究

目的研究城乡儿童血铅水平的差异;血铅水平对儿童智力、行为、感觉统合发育、学习成绩等影响的“剂量－效应”关系。方法随机整群抽取城市和农村1所小学三～五年级儿童各100名作为研究对象,在严格质量控制下,测定全静脉血铅含量,同时进行儿童行为、智力、儿童感觉统合能力评定并进行学习成绩评价。结果高血铅检出率为23％,其中城市儿童检出率为29％,农村儿童检出率为17％,城市儿童血铅含量高于农村儿童（P〈0．001）;高血铅组儿童行为异常检出率41．3％,非高血铅儿童行为异常检出率为10．39％,有非常显著性差异（P〈0．01）。高血铅对总智商损害：200－499μg／L组重于100～199μg／L（P〈0．001）;对语言智商的损害：200～499μg／L组重于100～199μg／L组（P〈0．01）;对操作智商损害：100～199μg／L重于〈99gg／L组（P〈0．01）。儿童感觉统合失调发生率血铅％99μg／L组、100～199μg／L、200～499μg／L组分别为7．5％、40．26％、100％。对学习成绩的影响：血铅100～199μg／L组重于血铅〈99μg／L组（P〈0．01）;当血铅在100～199μg／L,200～499μg／L时数学成绩均明显低于语文成绩（P〈0．001;P〈0．05）。结论城市在校小学生的血铅含量水平明显高于农村在校小学生的血铅含量水平;高血铅含量对操作智商损害早于言语智商;对数学成绩的影响早于对语文成绩的影响;血铅含量对智力、行为、感觉统合发育、学习成绩的影响存在明显的“剂量－效应”关系。     

钪—46内污染复合小剂量X射线全身外照射后 小白鼠骨髓有核细胞染色体畸变与剂量关系的研究

本文定量描述了钪—46内污染复合小剂量X射线全身外照射24h以后,小白鼠骨髓有核细胞染色体畸变与剂量的关系。结果表明,内外复合照射以后,染色体畸变率低于单纯内、外照射畸变率之和,但高于其中单一照射的畸变率,直线回归方程为y_6=7.9511+0.00099D_3,即呈正相关。染色体畸变率随时间变化规律为三项指数函数模式y(t)=2.9078exp~(0.27668t)+2.3786exp~(-0.017788t)+2.3786exp~(-0.1788t),1≤t≤30。经适宜性验证,各公式所得理论值的90％机率分布在实际测得值中。