异钩藤碱的降压及血流动力学作用(英文)

在清醒正常血压大鼠,iv Isorhy2.5 mg/kg对BP及HR均无明显影响,iv5 mg/kg则使DAP和HR降低,但SAP无变化,剂量加大至10 mg/kg时,上述各项指标均明显降低。经十二指肠内给Isorhy10 mg/kg后20 min出现BP及HR降低,而20mg/kg剂量组于10 min开始出现BP及HR的进一步下降.Isorhy(10mg/kg和2 mg/kg,iv)亦能分别降低肾性高血压清醒大鼠和麻醉犬的BP。icv表明中枢不是降压作用的主要部位,在体条件下无α-受体和神经节阻断作用。Isorhy使清醒大鼠和麻醉犬的LVSP,dP/dt_(max),V_(max)等左室收缩性能指标短暂下降,而BP呈持久性降低。在麻醉犬给药后CO,CI,HR及LVWI下降的同时SV和SI不变,TPVR降低,反映心肌氧耗的TTI明显减少.结果提示Isorhy具有肯定的降压作用,其持续降压与扩张血管及减慢心率导致CO下降有关,而其负性肌力作用亦可能参与了早期的降压机理.Isorhy能减少心肌氧耗对高血压心肌劳损可能有保护意义。     

非洛地平-美托洛尔复方经皮给药系统设计及其降压有效性评价

目的:设计制备非洛地平-美托洛尔复方经皮给药系统,评价其对自发性高血压大鼠的降压作用.方法:50只3月龄自发性高血压大鼠随机分为5组进行长期给药治疗试验:空白贴剂对照组、非洛地平(FEL)-美托洛尔(MET)口服混悬液组(FEL 1 mg·kg-1,MET 10 mg·kg-1,qd)及FEL-MET透皮贴剂低、中、高剂量组[剂量分别为:FEL 1 mg·kg-,MET 10 mg·kg-1;FEL 3 mg·kg-1,MET 30 mg·kg-1;FEL 9 mg·kg-1,MET90 mg·kg-,每隔2 d给药1次],共持续44 d.另设同月龄正常血压Wistar大鼠为正常对照组.以无创性尾套法测定给药后大鼠血压和心率,评价经皮给药系统的降压作用.结果:FEL-MET透皮贴剂降压作用起效快、持续时间长,无耐药趋势,强度具有剂量依赖性.FEL-MET透皮贴剂低、中、高剂量分别使收缩压下降27.3-39.2mmHg(14.78%～21.22%),34.2～49.7 mmHg(18.59%～27.01%)和50.8～68.6 mmHg(27.34%～36.92%);使舒张压下降19.8～32.6 mmHg(12.90%～21.24%),22.7～34.9 mmHg(15.30%～23.52%)和33.7～52.8mmHg(22.74%～35.63%);降压效果显著优于FEL和MET长期口服联用(P＜0.05).结论:FEL-MET经皮给药系统降压效果确切,作用平稳,持效时间长,使用方便,安全性高,适于高血压的长期药物治疗.     

甲基莲心碱的降压作用

甲基莲心碱对麻醉、清醒的正常大鼠,肾性、D0CA盐型高血压大鼠,麻醉猫、清醒正常家兔都能引起快速、剂量依赖性降压作用,猫椎动脉注射及脑室内注射甲基莲心碱0.6mg/kg无明显降压作用。表明甲基莲心碱是一种有效的抗高血压药,对血管平滑肌有直接扩张作用。     

柠檬总提取物对正常大鼠及SHR血压、血脂影响的实验研究

目的:研究安岳柠檬总提取物对正常及自发性高血压大鼠(SHR)血压、血脂水平的影响.方法:柠檬总提取物6.0 g·kg-1、3.6g·kg-1、2.16 g·kg-1连续灌胃给药21 d,颈动脉插管法观察对正常大鼠血压的影响,测定血清葡萄糖(GLU)、甘油三酯(TG)、血清总胆固醇(TC)含量;连续灌胃给药28 d,分别于给药7、14、21、28 d无创法测定SHR的血压,测定给药28 d后血清GLU、TG、TC含量.结果:柠檬总提取物6.0 g·kg-1对正常麻醉大鼠具有降血压作用,但对SHR血压无显著影响;各剂量组对正常大鼠、SHR血清TG含量有显著降低作用.结论:柠檬总提取物具有明确的降低TG含量作用,改善血脂代谢;其降血压作用的发挥可能与给药途径有关,有待进一步验证.     

心压平胶囊治疗高血压病的药效学研究

观察心压平胶囊对正常 SD大鼠和清醒自发高血压大鼠 ( SHR)血压、心率、心肌耗氧量的影响。结果 :十二指肠给药心压平胶囊对正常 SD大鼠有降压作用 ,对清醒 SHR也有降压作用 ;可降低正常麻醉 SD大鼠心率 ;三个剂量组对正常麻醉 SD大鼠和大剂量组 SHR有显著降低心肌耗氧量作用。     

氨氯地平联用松龄血脉康胶囊对大鼠的血药浓度及降压作用的影响

目的 探讨氨氯地平片联用松龄血脉康胶囊对大鼠血药浓度的影响以及协同降压作用.方法 选取15只自发性高血压大鼠(SHR),随机分为氨氯地平片(20 mg· kg-1)组、同时给药组(20 mg· kg-1氨氯地平片+0.9 g·kg-1松龄血脉康胶囊)组、延时给药组(20 mg·kg-1氨氯地平片+0.9 g·kg-1松龄血脉康胶囊,延时30 min);ig给药并于氨氯地平片给药后不同时间点采集血样,HPLC法测定各时间点氨氯地平的血药浓度,采用DAS 2.0软件计算药物动力学参数.另选取SHR大鼠比较同时给药及延时给药的协同降压作用.结果 同时给药组增加了大鼠血浆中的氨氯地平浓度和曲线下面积(P ＜0.05或P＜0.01),达峰时间比氨氯地平片组提前了28.5 min;延时给药组不影响氨氯地平血药浓度,且达峰时间无显著变化.降压实验结果表明:同时和延时给予松龄血脉康均有额外降低自发性高血压大鼠血压作用,但与氨氯地平片组比较均无显著性差异.结论 联合同步给予松龄血脉康可提高氨氯地平的血药浓度,并具有轻微协同降压作用;而延时30 min服用松龄血脉康对氨氯地平的血药浓度及降压效果均无显著性差异.提示两种给药方式均安全有效,但延时30 min后,联用松龄血脉康不影响氨氯地平的血药浓度,可能对控制血压更为有利.     

β1肾上腺素能受体反义寡核苷酸对肾性高血压大鼠血流动力学及心肌肥厚的影响

目的 :观察阳离子脂质体 (DOTAP DOPE)介导的 β1肾上腺素能受体mRNA反义寡核苷酸 (β1 AS ODN)对肾性高血压大鼠血流动力学及心肌肥厚的影响。方法 :建立二肾一夹 (2K1C)肾性高血压大鼠模型 ,随机分为假手术组、模型组、反向寡核苷酸组、反义寡核苷酸组和卡维地洛 (carvedilol)组。ODN与DOTAP DOPE以 1 2摩尔比混合 ,4周末尾静脉注射 0 .5mg·kg-1,卡维地洛 10mg·kg-1·d-1灌胃 4周。定期测血压 ,8周末测血流动力学参数 ,左室重量指数 (LVWI)及血浆内皮素 1(ET 1)浓度 ,并对LVWI与ET 1进行线性相关分析。结果 :与反向寡核苷酸组比 ,β1 AS ODN能降低血压最高达39mmHg并持续 2 7d(30 .4 4± 6 .5 0 ,P <0 .0 1) ,降低左室收缩压 (LVSP) (P <0 .0 5 )、左室舒张末压 (LV EDP) (P <0 .0 1) ,升高左室最大收缩和舒张速率 (±dp dtmax) (P <0 .0 1) ,降低LVWI(P <0 .0 5 )及血浆ET 1(P <0 .0 1) ;与卡维地洛组比 ,各指标均无显著性差异。LVWI与ET 1显著正相关 (r =0 .74 9,P <0 .0 1)。结论 :DOTAP DOPE介导的 β1 AS ODN单剂量静脉注射能持续降压 ,改善血流动力学 ,预防心肌肥厚 ,可能与其降低血浆ET 1有关。     

紫菜降血压肽大鼠体内降压效果研究

目的观察紫菜降血压肽对高血压大鼠(SHR)和京都Wistar大鼠(WKY)的降压效果,并与降压药物卡托普利的作用效果比较。方法分别以500、1 000和1 500 mg.kg-1剂量的紫菜降血压肽一次性给药后,每隔2 h测量大鼠收缩压(SBP),连续测量8 h;长期实验持续4 w,每天1 500 mg.kg-1灌胃一次,每隔1周测量一次SBP、心率及体重。结果 SHR给予紫菜降血压肽后,血压均显著下降;而正常血压大鼠WKY服用紫菜降血压肽后血压没有显著变化,服用卡托普利血压仍保持显著下降的趋势。结论紫菜降血压肽对SHR具有显著的降压效果,长期服用可稳定血压,对正常血压大鼠无明显影响;卡托普利对SHR的降压效果虽高于紫菜降血压肽,但会导致正常大鼠血压过低。     

鲑鱼蛋白水解产物降压作用的研究

目的 以自发性高血压大鼠(spontaneously hypertensive rats,SHR)为模型,研究鲑鱼蛋白术解产物(salmon protein hydrolysates,SMs)的降血压作用.方法 不同剂量的SMs连续灌胃给药4d,每天1次;采用清醒大鼠尾动脉脉搏间接测定法在给药第1天和第4天时,测定大鼠的动脉收缩压(systolic blood pressure,SBP)和心率.结果 给药第1天,SM-1(1.5g·kg-1)和SM-2(1.5g·kg-1)组自发性高血压大鼠的收缩压显著低于对照组大鼠的收缩压;给药第4天所有给药组的收缩压显著低于对照组大鼠的收缩压.结论 海洋生物活性物质SMs具有降低自发性高血压大鼠血压的作用.     

盐酸埃他卡林选择性降压作用的研究

目的 :在清醒正常血压犬和“两肾一夹”肾性高血压犬 (RHD)上 ,观察不同剂量盐酸埃他卡林(iptakalimhydrochloride,Ipt)的降压作用特征 ;在清醒正常血压的Wistar大鼠和脑卒中易感型自发性高血压大鼠 (stroke pronespontaneouslyhypertensiverat,SHRsp)上 ,采用无创心功能监测方法 ,观察Ipt对心功能和血流动力学的作用特征 ,以判断其降压作用和对心功能及血流动力学的影响是否具有选择性。方法 :给清醒正常血压犬和RHD口服不同剂量的Ipt,用听诊法测量移于皮鞘内的颈总动脉血压 ,用触诊法测量心率 ,同时记录Ⅱ导联心电图。给清醒正常血压大鼠和SHRsp静脉注射相同剂量的Ipt,采用清醒无创心功能血流动力学实验方法 ,观察Ipt对对心功能和血流动力学的影响。结果 :在RHD模型上 ,单次口服Ipt0 .1 2 5、0 .2 5、0 .5、1 .0mg·kg- 1 后 ,产生剂量依赖性的降压作用 ,0 .5h开始起效 ,2～ 3h达效应峰值 ,其最大降低SBP幅度分别为 1 3、2 3、2 5、3 6mmHg,降压作用维持时间分别为 4、6、6、1 2h。在清醒正常血压犬上 ,单次口服Ipt 0 .8,3 .2 ,1 2 .8mg·kg- 1 ,其中剂量为 0 .8和 3 .2mg·kg- 1 时 ,血压和心率均无明显变化 ,剂量增至 1 2 .8mg·kg- 1 时 ,在给药后 5h之内可以显著降低收缩压和舒张压 ,其最大降低SB     

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.