苏郁胶囊对小鼠抑郁症模型的影响

目的:研究苏郁胶囊对小鼠抑郁模型的影响。方法:采用小鼠强迫游泳,小鼠悬尾应激,利血平所致小鼠行为学缺损、体温下降及眼脸下垂,小鼠慢性应激孤养等抑郁模型,观察苏郁胶囊的抗抑郁作用。结果:苏郁胶囊能显著缩短小鼠强迫游泳(P<0．001)及悬尾的不动时间(P<0．05),剂量为5．7 g·kg-1时,作用最佳;苏郁胶囊具有拮抗利血平致小鼠体温降低(P<0．001)及小鼠眼睑下垂作用(P<0．01),并呈一定的量效关系;苏郁胶囊高、中剂量(22．8,11．4 g·kg-1)能明显改善利血平致小鼠行为学缺损(P<0．05);苏郁胶囊能显著增加慢性应激孤养抑郁模型小鼠大脑内单胺类神经递质(DA,NA,5-HT)及其代谢物(5-HIAA)含量(P<0．001),并呈现一定的量效关系。结论:苏郁胶囊具有一定的抗小鼠实验性抑郁作用,其抗抑郁作用可能与增加脑内单胺类神经递质的含量有关。     

苏郁胶囊对双侧嗅球损伤抑郁模型大鼠行为学及下丘脑-垂体-肾上腺轴的影响

目的：探讨苏郁胶囊对双侧嗅球损伤抑郁模型大鼠行为学及下丘脑-垂体-肾上腺（HPA）轴的影响。方法：48只雄性大鼠随机分为假手术组、模型组、苏郁胶囊高、中、低剂量组（22．8、11．4、5．7g／kg）及氯米帕明组（0．02g／kg）。应用双侧嗅球损伤复制大鼠抑郁模型,敞箱法及跳台法测定大鼠的行为学指标;放射免疫方法测定大鼠血浆促肾上腺皮质素释放激素（CRH）、促肾上腺皮质激素（ACTH）及皮质醇（CORT）的水平。结果：苏郁胶囊可不同程度降低双侧嗅球损伤大鼠敞箱实验的水平运动次数与垂直运动次数;增加双侧嗅球损伤大鼠跳台实验的潜伏期及减少错误次数;同时降低双例嗅球损伤大鼠血浆CRH、ACTH和CORT含量。结论：苏郁胶囊能逆转双侧嗅球损伤抑郁模型大鼠的行为异常,其可能与苏郁胶囊有效地拮抗HPA轴功能亢进相关。     

苏郁胶囊改善慢性应激抑郁行为与抗氧化作用

目的：研究苏郁胶囊改善慢性应激抑郁行为与抗氧化作用。方法：将48只雄性大鼠分为正常组、模型组、苏郁胶囊高、中、低剂量组（22．8、11．4、5．7g／kg）及氯米帕明组（0．02g／kg）。采用长期不可预见中等强度应激结合孤养造成大鼠抑郁模型，测定各组大鼠体重增长克数，Open-field法和糖水消耗实验测定各组大鼠的行为变化；测定各组大鼠血清及大脑组织中超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量。结果：苏郁胶囊可不同程度增加慢性应激大鼠的体重增长速度及糖水消耗量，改善大鼠行为缺损，同时提高血清及大脑中SOD活性，降低MDA含量。结论：苏郁胶囊能够改善慢性应激抑郁大鼠行为；其抗抑郁作用机制可能与清除体内过多自由基及抗脂质过氧化作用有关。     

苦马豆素的抑瘤和免疫增强作用

目的研究苦马豆素(SW)的抑瘤和免疫增强作用。方法采用小鼠移植瘤模型,灌胃给药21 d,分别观察SW对小鼠S180肉瘤的抑瘤率和对EAC腹水癌小鼠的生命延长率,并测定SW对S180荷瘤小鼠的免疫机能的调节作用。结果SW 0．31和0．62 g·kg-1剂量组对小鼠S180肉瘤的抑瘤率分别为33．30％和32．48％(P<0．01);病理组织学检查显示SW 0．62 g·kg-1剂量组的肿瘤组织坏死面积明显大于荷瘤对照组(P<0．01)。SW对小鼠EAC艾氏腹水癌的生命延长率为10．17％～11．44％(P<0．05)。SW 0．155 g·kg-1剂量组的脾指数以及SW 0．155和0．31 g·kg-1剂量组的胸腺指数均明显高于荷瘤对照组(P<0．05);0．31和0．62 g·kg-1剂量组的淋巴母细胞和过渡型细胞百分率均显著增加(P<0．01);0．62 g·kg-1剂量组的吞噬指数κ明显高于荷瘤对照组(P<0．05)。结论SW对小鼠移植性S180实体瘤具有明显的抑制作用。其抗癌作用机制与苦马豆素能明显促进荷瘤小鼠机体的免疫功能有关。     

苏郁胶囊对慢性应激抑郁模型大鼠海马神经细胞凋亡的影响

目的探究苏郁胶囊抗抑郁的作用机制。方法将96只Open-F ield评分相近的成年SD雄性大鼠随机分为正常组、模型组、苏郁胶囊高、中、低剂量组(22.8g/kg、11.4g/kg、5.7g/kg)及氯米帕明组(0.02g/kg)。采用长期不可预见中等强度应激结合孤养造成大鼠抑郁模型。Open-F ield法和糖水消耗实验测定各组大鼠的行为变化;用TUNEL试剂盒检测海马CA3区神经细胞凋亡情况,免疫组化法检测Bc l-xl蛋白的表达;应用钙离子荧光指示剂Fura-2/AM测定海马突触体内游离Ca2 浓度。结果与正常组比较,模型组大鼠出现明显的行为异常,糖水消耗明显减少;海马CA3区TUNEL阳性细胞数增加明显,Bc l-xl蛋白表达减少明显;海马突触体内游离Ca2 浓度明显升高。苏郁胶囊高中治疗组能明显增加抑郁大鼠的糖水消耗量,改善其行为异常;苏郁胶囊高中低治疗组能明显减少海马CA3区TUNEL阳性细胞数,上调海马CA3区Bc l-xl蛋白表达,减少海马突触体内游离Ca2 浓度,并具有一定的量效关系。结论苏郁胶囊能改善大鼠的抑郁样行为;抑制抑郁大鼠海马神经细胞凋亡。其可能与苏郁胶囊抑制海马神经细胞外Ca2 大量内流,阻止Ca2 超载,上调海马Bc l-xl蛋白表达相关。     

皂荚皂苷对大鼠心肌缺血的影响

目的:研究皂荚皂苷对大鼠急性心肌缺血的防治作用。方法:采用结扎大鼠左冠状动脉的方法,造成急性心肌缺血模型,通过对大鼠标准Ⅱ导联心电图,心肌梗死面积及血清中天冬氨酸转氧酶(AST)、肌酸激酶(CK)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)和丙二醛(MDA)的测定,探讨皂荚皂苷对大鼠心肌缺血的影响。结果:皂荚皂苷25,50,100 mg·kg-13个剂量组大鼠预防性灌胃给药5 d,与模型组比较,都不周程度降低心电图标准Ⅱ导联ST段抬高幅度(P<0．05,P<0．01):皂荚皂苷25,50,100 mg·kg-1剂量组的心肌梗死面积分别为(28±s 8)％,(24±10)％和(19±6)％,均显著小于模型组大鼠[(38±9)％,P<0．05．P< 0．01];模型组大鼠的血清AST,CK,LDH活力明显高于假手术组(P<0．01),而升高的酶活力可以被预先给予各给药剂量的皂荚皂苷所降低(P<0．05,P<0．01);与模型组比较,增加了血清中SOD活性及降低血清中 MDA含量(P<0．05,P<0．01)。结论:皂荚皂苷对结扎大鼠左冠状动脉造成的急性心肌缺血有显著的防治作用。     

人参皂苷Rg1的抗抑郁作用及对突触超微结构的影响

目的观察人参皂苷Rg1的抗抑郁作用及慢性应激对额前皮质区突触超微结构的改变。方法采用慢性温和不可预见性应激(chronic unpredictable mild stress,CUMS)的方法建立大鼠抑郁模型。造模同时给予人参皂苷Rg1(5、10和20 mg·kg-1)和度洛西汀(10 mg·kg-1),每天1次,连续28 d。用强迫游泳和糖水消耗的行为学方法检测大鼠的抑郁行为学变化,电子显微镜观察应激后大鼠额前皮质区突触超微结构的变化。结果与对照组相比,慢性应激大鼠在强迫游泳实验中的不动时间明显增加(P<0.01),糖水偏好实验中的糖水消耗百分比明显降低(P<0.01);电镜观察结果显示模型组大鼠额前皮质区突触超微结构异常,突触前膜的突触囊泡密度减小,突触后膜致密物厚度也减少。与模型组相比,人参皂苷Rg1能明显改善慢性应激大鼠的抑郁行为,改善大鼠额前皮质区突触超微结构。结论人参皂苷Rg1对CUMS诱导的大鼠抑郁行为和额前皮质区突触超微结构的异常有明显的改善作用。     

苏郁胶囊对慢性应激抑郁模型大鼠海马神经细胞凋亡的影响

目的探究苏郁胶囊抗抑郁的作用机制。方法将96只Open-Field评分相近的成年SD雄性大鼠随机分为正常组、模型组、苏郁胶囊高、中、低剂量组(22.8g/kg、11.4g/kg、5.7g/kg)及氯米帕明组(0.02g/kg)。采用长期不可预见中等强度应激结合孤养造成大鼠抑郁模型。Open-Field法和糖水消耗实验测定各组大鼠的行为变化;用TUNEL试剂盒检测海马CA3区神经细胞凋亡情况,免疫组化法检测Bc l-xl蛋白的表达;应用钙离子荧光指示剂Fura-2/AM测定海马突触体内游离Ca²⁺浓度。结果与正常组比较,模型组大鼠出现明显的行为异常,糖水消耗明显减少;海马CA3区TUNEL阳性细胞数增加明显,Bc l-xl蛋白表达减少明显;海马突触体内游离Ca²⁺浓度明显升高。苏郁胶囊高中治疗组能明显增加抑郁大鼠的糖水消耗量,改善其行为异常;苏郁胶囊高中低治疗组能明显减少海马CA3区TUNEL阳性细胞数,上调海马CA3区Bc l-xl蛋白表达,减少海马突触体内游离Ca²⁺浓度,并具有一定的量效关系。结论苏郁胶囊能改善大鼠的抑郁样行为;抑制抑郁大鼠海马神经细胞凋亡。其可能与苏郁胶囊抑制海马神经细胞外Ca²⁺大量内流,阻止Ca²⁺超载,上调海马Bcl-xl蛋白表达相关。     

七味开心颗粒对脑损伤-嗅球破坏模型大鼠行为及血浆中ACTH、COR含量的影响

目的 :研究七味开心颗粒的药理作用。方法 :采用脑损伤 -嗅球破坏模型 ,将实验大鼠分为正常组、假手术组、模型组、盐酸氯米帕明组、七味开心颗粒 (高、中、低剂量 )组 ,观察各组大鼠行为学变化及其血浆中促肾上腺皮质激素 (ACTH )和皮质醇 (COR)含量的变化。结果 :在敞箱实验和避暗实验中 ,模型组大鼠行为出现明显变化 ,七味开心颗粒组和盐酸氯米帕明组均可显著拮抗大鼠行为变化 ;模型组大鼠血浆中ACTH、COR含量显著升高 (P<0 01) ,七味开心颗粒组和盐酸氯米帕明组都可抑制ACTH、COR含量的升高 (P<0 01)。结论 :七味开心颗粒可能通过作用于下丘脑 -垂体 -肾上腺皮质轴而发挥抗抑郁作用。     

桂枝茯苓胶囊对实验大鼠血浆内雌二醇、黄体酮、催乳素的影响

目的 :探讨桂枝茯苓胶囊对实验性高雌、孕激素大鼠血浆内雌二醇、黄体酮、催乳素的影响。方法 :取雌性SD大鼠 10 0只给大鼠腹腔注射 ,苯甲酸雌二醇及黄体酮制作高雌二醇、黄体酮大鼠模型 ,将大鼠随机分成 5组 ,空白对照组、模型组 ,他莫昔芬对照组及桂枝茯苓胶囊 2 0 0 ,4 0 0mg·kg- 1组 ,每组2 0只 ,空白对照组和模型组给等体积蒸馏水 ,其余组分别给桂枝茯苓胶囊混悬液 2 0 0 ,4 0 0mg·kg- 1和他莫昔芬 3mg·kg- 1,每日灌胃 ,共 30d。用放射免疫方法测定各组实验性大鼠模型血浆内雌二醇、黄体酮、催乳素的含量。结果 :桂枝茯苓胶囊 2 0 0与4 0 0mg·kg- 1组可明显降低高雌、孕激素大鼠模型血浆雌二醇和黄体酮 ,2组雌二醇分别为 (12 7±s5 2 )ng·L- 1和 (15 3± 4 9)ng·L- 1,黄体酮分别为 (12± 8) μg·L- 1和 (13± 7) μg·L- 1,与模型组雌二醇(2 71± 10 3)ng·L- 1和黄体酮为 (2 1± 15 ) μg·L- 1比较 ,差异均有显著意义 ,P <0 .0 5 ,但对血浆催乳素影响不大。结论 :桂枝茯苓胶囊能够显著降低异常升高的实验性高雌、孕激素大鼠模型的雌二醇、黄体酮的血浓度。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.