半夏泻心汤对偏头痛大鼠神经递质及早快基因表达的影响

目的 研究半夏泻心汤(BXXXT)对实验性偏头痛模型大鼠神经递质及早快基因表达的影响.方法 将60只SD健康大鼠随机分为正常组、模型组、阳性组、BXXXT高、中、低剂量组.ig生理盐水予正常组、模型组大鼠,其余各组大鼠ig BXXXT,连续7d,末次给药后1h皮下注射硝酸甘油10 mg·kg-1造模.用ELISA法测定大鼠血清中5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)的含量;HE染色观察大鼠脑干组织细胞形态学的变化;免疫组化染色测定大鼠脑干中c-jun基因的表达.结果 与模型组比较,BXXXT可升高大鼠血浆中DA、NE、5-HT的水平,降低5-HIAA水平和大鼠脑干中c-jun基因的表达.结论 BXXXT对实验性偏头痛大鼠具治疗作用.     

抗氧化剂硫辛酸对实验性偏头痛大鼠细胞外信号调节激酶1/2的作用

目的探讨α-硫辛酸(alpha-lipoid acid,α-LA)对硝酸甘油诱发的实验性偏头痛大鼠细胞外信号调节激酶1/2的作用。方法 48只SD大鼠随机分为正常对照组、模型组、α-LA组、溶剂组,采用皮下注射硝酸甘油(glyceryl trinitrate,GTN)法制作偏头痛大鼠模型。α-LA组在造模后30 min腹腔给予α-LA(60 mg·kg-1),观察大鼠行为学变化。采用Western blot印迹法和免疫组化法测定三叉神经节及三叉神经颈复合体、硬脑膜细胞外信号调节激酶1/2(ERK1/2)、磷酸化ERK1/2(p-ERK1/2)表达。结果模型组大鼠p-ERK1/2蛋白表达明显高于正常对照组;与模型组相比,α-LA组大鼠行为症状明显改善,p-ERK1/2蛋白表达下降,模型组与α-LA组组间比较有统计学意义(P<0.05)。结论α-LA可减弱偏头痛大鼠模型中p-ERK1/2的表达,α-LA可能有防治偏头痛的作用。     

重组葡激酶溶栓作用的研究

目的　研究重组葡激酶的溶栓作用。方法　通过测定家兔血浆优球蛋白溶解时间 (ELT)、纤维蛋白原降解产物(FDP)的含量及纤维蛋白原 (Fg)的含量 ,以观察重组葡激酶对家兔纤维溶解活性的影响。采用家兔动静脉旁路血栓形成法、家兔肺栓塞法及大鼠体外血栓形成法模型 ,以观察重组葡激酶的溶栓作用。结果　重组葡激酶 (6 2 5 0U·kg-1,1 2 5万U·kg-1)可明显缩短ELT ,增加FDP含量 ,对Fg含量无明显影响 ;重组葡激酶 (8333U·kg-1,2 5万U·kg-1,7 5万U·kg-1)在 3种血栓形成模型上 ,均有溶栓作用。结论　重组葡激酶具有明显的溶栓作用。     

银杏叶提取物EGb761对硝酸甘油型大鼠偏头痛的作用及机制

目的:研究银杏叶提取物EGb761对硝酸甘油型大鼠偏头痛的影响并初步探讨其机制。方法:SD大鼠随机分为正常对照组、假手术组、模型组、EGb761低、中、高剂量组,EGb761组以相应剂量EGb761灌胃一周,假手术组和模型组给予等量纯化水灌胃,正常对照组不做处理。末次给药后皮下注射硝酸甘油建立偏头痛大鼠模型,假手术组注射等量生理盐水,记录小鼠前肢搔头的次数,测定血浆血小板聚集率(platelet aggregation rate,PAR)、5-羟色胺(5-hydroxytryptamine,5-HT)和一氧化氮(nitric oxide,NO)的含量和脑组织中5-HT和NO的含量。结果:与模型组相比,EGb761可显著减少偏头痛模型大鼠前肢搔头次数(P<0.01),可明显降低血浆中PAR和NO含量(P<0.01;P<0.001)和脑组织中NO含量 (P<0.01),同时,EGb761可明显升高血浆和脑组织中5-HT含量(P<0.001;P<0.01)。结论:EGb761可以调节偏头痛大鼠PAR、NO、5-HT的水平,这可能是EGb761治疗偏头痛的机制之一。     

归辛颗粒对硝酸甘油诱发的实验性大鼠偏头痛的作用

目的：探讨归辛颗粒（GXG）对硝酸甘油诱发的实验性偏头痛大鼠行为症状的影响及其可能的机制。方法：采用SD大鼠，氟桂利嗪（西比灵胶囊）作为阳性对照，与归辛颗粒高、中、低三个剂量组同步按照各要求剂量灌胃给药7d，大鼠右肩皮下注射硝酸甘油9mg／kg造模，观察各组行为学差异并采用荧光分光光度法测定其血浆和脑组织中5-羟色胺（5-HT）含量的变化。结果：归辛颗粒组大鼠行为症状的改善明显优于模型组，血浆及脑组织中5-HT显著升高，与模型组比较差异有统计学意义（P〈0．05或P〈0．01）。结论：归辛颗粒可能通过升高偏头痛大鼠血浆及脑组织中5-HT含量发挥防治偏头痛作用。     

褪黑素对海洛因依赖大鼠催促戒断症状的治疗作用

目的··:研究褪黑素对海洛因依赖大鼠催促戒断症状的治疗效果。方法··:大鼠按剂量递增法连续皮下注射海洛因42d,用纳洛酮催促成瘾的大鼠,给予不同剂量的褪黑素治疗。结果··:褪黑素保护组、褪黑素单剂量治疗组在剂量为25mg·kg-1、250mg·kg-1时,能缓解大鼠的戒断症状(与海洛因对照组比较,P<0.05);褪黑素50mg·kg-1、75mg·kg-1、125mg·kg-1单剂量给药组能明显缓解大鼠的戒断症状(与海洛因对照组比较分别为P<0.01、P<0.01、P<0.001)。结论··:褪黑素能控制海洛因依赖大鼠的戒断症状;在剂量为25-125mg·kg-1范围内存在一定的剂量依赖关系。     

丹参素和泮托拉唑对肝硬化大鼠肝部分切除术后肝再生的影响研究

目的以肝硬化大鼠为动物模型,研究药物对肝硬化大鼠肝部分切除术后肝再生的影响。方法取健康的Wistar雄性大鼠64只,以60%CCl4油溶液0.3ml/100g皮下注射,同时饮用5%酒精溶液,45d后制成肝硬化动物模型。模型大鼠随机分为4组,16只/组。全麻下均行左、中叶肝切除术。术后各组按以下方案处理:对照组皮下注射生理盐水1mg·kg-1·d-1,丹参素组腹腔注射18mg·kg-1·d-1,泮托拉唑组皮下注射0.2mg·kg-1·d-1,两药合用组同时给予丹参素(tanshinol)腹腔注射18mg·kg-1·d-1,泮托拉唑(pantoprazole)皮下注射0.2mg·kg-1·d-1,连续给药2周,抽取静脉血样,取肝脏组织,检测肝功能、有丝分裂指数(MI)、增生细胞核抗原(PCNA)、细胞核DNA含量。结果丹参素组、泮托拉唑组及两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于对照组(P<0.05),两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于丹参素组、泮托拉唑组(P<0.05),但各组间肝功能变化无明显差异。结论丹参素、泮托拉唑及两药合用均对肝硬化大鼠肝部分切除术后肝细胞再生有促进作用。     

血管紧张素Ⅱ1型受体拮抗剂用于脓毒症大鼠的实验研究

目的观察血管紧张素Ⅱ1型受体拮抗剂氯沙坦对内毒素诱导的脓毒症大鼠的干预效果。方法 SD大鼠30只随机分成生理盐水对照组(Control组,n=10)、脓毒症组(LPS组,LPS 12 mg·kg-1,iv,n=10)和氯沙坦组(LOS组,氯沙坦50 mg·kg-1 ip,30 min后LPS 12 mg·kg-1 iv,n=10)。LPS注射6 h后抽血检测一氧化氮(NO)、丙二醛(MDA)及IL-1β、TNF-α血浆浓度,随即处死大鼠,分离胸主动脉,测定各组胸主动脉核因子κB抑制蛋白(inhibitor ofNF-κB,IκB)mRNA和蛋白的表达。结果 LPS组NO、MDA、IL-1β及TNF-α血浆浓度较对照组明显升高(P<0.01),经LOS干预后上述指标明显降低(P<0.01);大鼠胸主动脉IκB mRNA和蛋白在LPS组中的表达较对照组均明显降低(P<0.01),而LOS组中IκB的mRNA和蛋白表达较LPS组明显回升(P<0.01)。结论血管紧张素Ⅱ1型受体拮抗剂氯沙坦对内毒素诱导的脓毒症大鼠有抗炎作用。     

注射用尖吻蝮蛇凝血酶对兔凝血功能的影响

目的研究注射用尖吻蝮蛇凝血酶(Hem)对兔凝血功能的影响,为临床应用提供实验依据。方法于日本大耳白兔耳静脉分别一次性iv给予Hem 0.25,0.5和1.0 U·kg-1和阳性对照药注射用血凝酶(HAI)1.0克氏单位(KU)·kg-1,于给药前(0 min)和给药后10 min,30 min,2 h和12 h分别采血,应用Lee-White试管法测定全血凝血时间(CT),血球计数仪测定血小板计数(PLT),C2000-4高性能血凝仪测定凝血酶原时间(PT)、凝血酶时间(TT)、血浆纤维蛋白原(FIB)和鞣花酸活化部分凝血活酶时间(APTT)。结果正常对照组不同时间点各指标均无明显变化。与给药前比较,CT在给予Hem 0.25,0.5和1.0 U·kg-1和HAI 1.0 KU·kg-1后10 min～12 h明显缩短(P<0.05);PLT在Hem 1.0 U·kg-1给药后10～30 min明显增加(P<0.05);APTT在Hem 1.0 U·kg-1(10 min～2 h)和HAI 1.0 KU·kg-1(30 min～12 h)明显降低(P<0.05);PT在Hem 0.25 U·kg-1(10 min),0.5 U·kg-1(10 min～2 h)和1.0 U·kg-1(10～30 min)及HAI 1.0 KU·kg-1(10～30 min)明显降低(P<0.05);TT在Hem 1.0 U·kg-1(10 min～12 h)和HAI 1.0 KU·kg-1(30 min)明显降低(P<0.05);FIB在Hem 0.25 U·kg-1(30 min),0.5 U·kg-1(10～30 min)和1.0 U·kg-1(10 min～2 h)及HAI 1.0 KU·kg-1(10～30 min)明显升高(P<0.05)。结论Hem 1.0 U·kg-1在给药后10 min即有促凝血作用,TT缩短可持续12 h。     

氟桂利嗪对硝酸甘油造模大鼠硬脑膜、三叉神经节及脑干区JNK1、PAR2表达的影响

目的观察硝酸甘油造模大鼠丝裂原活化蛋白激酶家族c-Jun氨基末端激酶-1（JNK1）和G-蛋白耦联受体家族蛋白酶激活受体-2（PAR2）在硬脑膜、三叉神经节及脑干区的表达以及钙通道阻滞剂氟桂利嗪对其影响。方法成年SD大鼠随机分为4组：正常对照组、模型组、氟桂利嗪治疗组、氟桂利嗪预防组,免疫组化法分别观察各组在硬脑膜、三叉神经节及脑干区JNK1,PAR2的表达。结果模型组中JNK1,PAR2的表达较其余3组均有较明显增多（P〈0.05）。氟桂利嗪治疗组、预防组和正常对照组之间无统计学意义（P〉0.05）。结论①硝酸甘油造模大鼠在硬脑膜、三叉神经节及脑干区JNK1,PAR2表达均增多。②氟桂利嗪可通过下调JNK1,PAR2的表达防治偏头痛。     

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.