前胡丙素对分离的成年鼠正常及肥厚心室肌细胞内游离钙的影响(英文)

目的:研究分离的成年大鼠正常及肥厚左室肌细胞[Ca~(2 )]_i及前胡丙素的作用.方法:用Fura 2-AM测定单细胞[Ca~(2 )]_i.结果:外钙为1.0mmol·L~(-1)时,正常左室肌细胞静息钙87±4 nmol·L~(-1),肥厚细胞123±7 nmol·L~(-1).肥厚心肌细胞中,加入KCl 20,40,60 mmol·L~(-1),[Ca~(2 )]_i增加29％,78％和185％,幅度高于正常细胞.前胡丙素1,10,100 μmol·L~(-1)浓度依赖地抑制KCl及去甲肾上腺素诱导[Ca~(2 )]_i增加.作用与硝苯啶相似.结论:肥厚心肌细胞静息钙高于正常细胞;前胡丙素抑制激动剂引起的[Ca~(2 )]_i升高源于其钙通道阻断作用.     

TMB-8抑制神经递质引起的单个脑细胞内游离钙的升高(英文)

目的:研究TMB-8对神经递质引起的单个脑细胞内游离钙升高的作用。方法:应用AR-CM-MIC阳离子测定系统测定游离大鼠单个脑细胞内钙离子浓度。结果:当细胞外液Ca~(2 )浓度为1.3mmol·L~(-1)时,TMB-8 30μmol·L~(-1)能降低谷氨酸,组织胺,5-羟色胺引起的脑[Ca~(2 )]_i浓度的升高。而当细胞外液无钙时,TMB-8能降低细胞内静息[Ca~(2 )]_i;TMB-8 10μmol·L~(-1)则几乎完全抑制了组织胺和5-羟色胺引起的脑[Ca~(2 )]_i升高作用。结论:TMB-8能降低谷氨酸,组织胺,5-羟色胺引起的脑[Ca~(2 )]_i升高。     

钾通道开放剂降低血管平滑肌细胞内游离钙浓度(英文)

目的:研究PCO—Pin,Nic,Lem及RP对VMSC内[Ca~(2 )]_i的改变及其可能机制。方法:VSMC加入Fura-2 AM 2.5μmol·L~(-1)37℃下孵育50min,[Ca~(2 )]_i用荧光分光光度计检测。结果:4种PCO能较弱地抑制K~ 30 mmol·L~(-1)诱导的[Ca~(2 )]_i增加,但明显抑制ATP 0.1mmol·L~(-1)诱导的[Ca~(2 )]_i峰相及持续相增加,且呈剂量依赖性。格列苯脲完全阻断Pin,Lem及RP的作用,只部分抑制Nic的作用。无钙液中先给4种PCO,能显著抑制ATP诱导的[Ca~(2 )]_i峰相增加。结论:4种PCO均抑制ATP诱导的[Ca~(2 )]_i增加,此作用与减少细胞外钙内流及细胞内钙释放有关。     

甲基黄酮醇胺对分离的胎鼠脑细胞内游离钙浓度的影响(英文)

目的:观察甲基黄酮醇胺(MFA)对胎鼠脑细胞内游离钙浓度在静息以及激动剂存在时的作用。方法:用钙离子荧光染料Fura 2-AM负载后,测定分离的胎鼠脑细胞内游离钙浓度([Ca~(2 )]_i)及其变化。结果:在含钙1.3mmoL·L~(-1)的Hanks’液中,[Ca~(2 )]_i为197±20nmol·L~(-1)(n=44)。MFA0.15mmol·L~(-1)对静息脑细胞内钙浓度无明显影响。在细胞外钙1.3mmol·L~(-1)条件下,MFA(0.03—0.3 mmoL·L~(-1))浓度依赖性地抑制高钾去极化导致的[Ca~(2 )]_i升高,IC_(50)为0.14(95％可信限:0.05—0.42)mmoL·L~(-1)。在较高浓度时,MFA(0.15—0.3mmoL·L~(-1))也可抑制谷氨酸兴奋所引起的[Ca~(2 )]_i,IC_(50)为0.20(95％可信限:0.01—3.40)mmoL·L~(-1)。结论:MFA抑制高钾去极化引起的[Ca~(2 )]_i升高,在较高浓度时也拮抗谷氨酸兴奋所致的[Ca~(2 )]_i升高。     

小檗胺对高钾、去甲肾上腺素及咖啡因引起大鼠心肌细胞内钙动员的拮抗作用(英文)

目的:研究小檗胺(Ber)对氯化钾、NE及咖啡因引起大鼠培养心肌细胞[Ca~(2 )]_i动员的影响,方法:Fluo 3-AM负载后,共聚焦法测定心肌细胞[Ca~(2 )]_i荧光强度的变化。结果:Ber对心肌细胞静息[Ca~(2 )]_i水平无影响,但可剂量依赖性地抑制KCl60mmol·L~(-1)及NE 30 μmol·L~(-1)引起的内钙动员(P<0.01),此作用与维拉帕米相似.Egtazic acid3 mmol·L~(-1)并不能增强Ber对NE引起的[Ca~(2 )]_i升高的抑制作用,无外钙时,咖啡因80-160μmol·L~(-1)的[Ca~(2 )]_i动员不受Ber的影响(P>0.05),结论:Ber与维拉帕米相似,对大鼠心肌细胞靠电压依赖性和受体操纵性钙通道而升高的胞[Ca~(2 )]_i有拮抗作用,并不影响[Ca~(2 )]_i释放。     

大蒜新素对分离大鼠脑细胞内游离Ca~(2 )的影响

目的:观察大蒜新素对不同刺激剂所致分离大鼠脑细胞内游离钙的影响。方法:以Fura 2-AM为细胞内游离钙的荧光指示剂,用AR-CM-MIC阳离子测定系统,直接测定了分离新生大鼠脑细胞内游离钙([Ca~(2 )]_i)值,观察了大蒜新素的影响。结果:大蒜新素对脑细胞静息[Ca~(2 )]_i无明显影响,大蒜新素1-100μmol·L~(-1)能剂量依赖性地抑制高K~ 和谷氨酸引起的[Ca~(2 )]_i升高,其中IC_(50)分别为59.7和69.9μmol·L~(-1),高剂量大蒜新素100μmol·L~(-1)能抑制去甲肾上腺素引起的[Ca~(2 )]_i升高。结论:大蒜新素对高K~ 、去甲肾上腺素及谷氨酸引起的[Ca~(2 )]_i升高的抑制作用可能是其抗脑缺血作用机制之一。     

小檗胺对培养的HeLa细胞内游离钙浓度的作用(英文)

目的:研究Ca~(2 )信号传导是否参与Hela细胞的信号传导过程以及小檗胺(Ber)对HeLa细胞内钙浓度([Ca~(2 )]_i)变化的影响。方法:Fluo 3-AM负载HeLa细胞,共聚焦法测定[Ca~(2 )]_i,结果以荧光强度(FI)表示。结果:(1)有外钙时,HeLa细胞静息FI为186±44,KCl、NE、Cal,及咖啡因均升高HeLa细胞的[Ca~(2 )]_i。(2)Ber处理后,静息FI无影响,但抑制KCl、NE和Cal引起的[Ca~(2 )]_i升高(P<0.01),FI变化的速率减慢,达峰值的时间延长。(3)无外钙时,咖啡因诱导的[Ca~(2 )]_i升高不被Ber抑制。(4)Ber的上述作用与Ver的作用相似。结论:HeLa细胞属于非兴奋性细胞,但部分生物学特征与兴奋性细胞相似,Ca~(2 )同样在其信息转导中发挥重要作用。     

L-焦谷氨酸对抗谷氨酸钠诱发的大鼠皮层神经元损伤

目的:在大鼠皮层神经元研究L-吡咯烷酮羧酸(L-PGA)对谷氨酸钠(Glu)诱发神经毒性的拮抗作用。方法:原代培养的皮层神经元取自16d龄的胎鼠,与Glu作用30分钟,24小时后测定神经元的存活及培养介质中亚硝酸盐的浓度;以Fura 2-AM为细胞内[Ca~(2 )]_i荧光探针,AR-CM-MIC阳离子测定系统测定[Ca~(2 )]_i。结果:L-PGA 10-80μmol·L~(-1)浓度依赖地抑制Glu 500μmol·L~(-1)引起的神经损伤,其IC_(50)为(41±9)μmol·L~(-1),95％可信区间:(30.3-54.7)μmol·L~(-1)。L-PGA也能浓度依赖地降低Glu引起的NO释放。L-PGA 1,3,10,30,100μmol·L~(-1)对Glu 100μmol·L~(-1)引起的[Ca~(2 )]_i升高的抑制率分别为20.5％,34.4％,47.7％,70.6％,80.4％。结论:L-PGA可能通过抑制NO形成或细胞内Ca~(2 )浓度的升高而拮抗Glu的神经毒性。     

MK-447对家兔凝血酶诱导的血小板聚集,ATP释放及细胞内游离钙动员的影响(英文)

目的:研究MK-447对家兔凝血酶诱导的血小板聚集释放反应及单细胞内钙水平的影响.方法:利用浊度法及测定PRP中ATP的含量评价聚集和释放反应,以荧光图像法分析细胞内钙浓度.结果:MK-447仅使兔多血小板血浆(PRP)透光度降低(DLT),即血小板变形,单血小板[Ca~(2 )]_i轻度增加(160 nmol·L~(-1)),并不被依他酸3 mmol·L~(-1)抑制.MK-447消除凝血酶诱导的DLT,聚集和ATP释放增强,呈剂量依赖性,且凝血酶介导的[Ca2 ]_i由369 ±45 nmol·L~(-1)增加到621±121 nmol·L~(-1).结论:MK-447的血小板变形与其[Ca~(2 )]_i释放有关.MK-447增强凝血酶的血小板聚集和ATP释放.MK-447的这一作用可能于[Ca2 ]_i的协同作用有关.     

槲皮素降低大鼠心率和心肌钙振荡频率和抑制小鼠心肌肥厚(英文)

目的:研究槲皮素对心肌兴奋收缩耦联及构型重建的影响。方法:经动脉插管记录大鼠血流动力学;缩窄小鼠腹主动脉致心肌肥厚;检测Fura 2-AM负载的培养大鼠心肌细胞内游离钙([Ca~(2 )]_i)及钙振荡,结果:槲皮素剂量相关地降低大鼠窦性心率,而动脉血压、左室压及其微分改变轻微;10-250 μmol·L~(-1)时浓度依赖性降低培养心肌自发钙振荡频率,100μmol·L~(-1)时预防异丙肾上腺素及哇巴因加速钙振荡频率,但不抑制静息[Ca~(2 )]_i.和自发钙振荡及二药增高的振荡幅度,槲皮素还抑制血管紧张素Ⅱ而非高钾的升[Ca~(2 )]_i作用,槲皮素120 mg·kg~(-1)·d~(-1)5 d灌胃不改变假手术鼠的心室与体重之比,但显著抑制腹主动脉结扎小鼠的心室肥大,结论:槲皮素降低心肌钙振荡频率和心肌肥厚但不直接影响心脏兴奋收缩耦联。     

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.