双嘧达莫抗肿瘤作用的实验研究

给BALB/c和瑞士种实体瘤小鼠ig双嘧达莫(DIP)100、250和500mg·kg~(-1)·d~(-1)×10d.抑瘤率为34.20％～59.26％。ip DIP50和100mg·kg~(-1).对荷瘤C_(57)BL/6小鼠的抑瘤率分别为27.21％和52.18％;对瑞士种小鼠腹水中瘤细胞增殖抑制率为30.77％和48.92％.并能延长腹水瘤小鼠的存活时间。实验表明:DIP对小鼠S_(180)实体瘤和腹水瘤均有明显抑制作用。     

索布佐生和阿霉素对小鼠白血病P388的协同作用

目的:研究索布佐生(Sob)与阿霉素(Dox)联合应用的抑瘤作用以及Sob对Dox诱导的心脏毒性的影响。方法:DBA/2小鼠接种P388细胞,次日起iv Dox 2mg·kg~(-1)·d~(-1)×3d及4mg·kg~(-1)·d~(-1)×1 d,ig Sob 20mg·kg~(-1)·d~(-1)×7d及40mg·kg~(-1)·d~(-1)×7d,配对联用。统计各组的生命延长率(ILS);电镜观察荷瘤鼠垂死前的心肌毒性表现。结果:联合用药组的ILS分别为48.7％,57.3％,59.0％和62.4％,是Sob和Dox单药应用ILS之和的130％—190％,荷瘤鼠心肌细胞的超微结构损伤较单用Dox组明显减轻。结论:Sob与Dox联用对小鼠白血病P388有显著的抑瘤协同作用;Sob能降低Dox所致的心肌毒性。     

马钱子碱及其脂质体对移植性肝癌Heps小鼠的抗肿瘤作用和毒性的比较

目的:比较马钱子碱(brucine,B)和马钱子碱脂质体(brucine liposome,BL)对移植性肝癌Heps小鼠的抗肿瘤作用和毒性。方法:ICR雄性小鼠接种肝癌Heps瘤株造成移植性肝癌Heps小鼠模型(简称Heps小鼠),测定B(1·61,3·23,6·46 mg·kg~(-1)·d~(-1),ip,8 d)和BL(以B计,1．61和3．23 mg·kg~(-1)·d~(-1),ip,8 d)对实体瘤小鼠的抑瘤率和腹水瘤小鼠的生命延长率;并比较各组实体瘤小鼠的体重、免疫器官(脾和胸腺)指数、血细胞指数(白细胞、红细胞、血小板和血红蛋白)和肝、肾功能指数(AST,ALT和BUN)。结果:低、中、高剂量的B(1．61,3．23,6．46 mg·kg~(-1)·d~(-1))对Heps实体瘤小鼠的抑瘤率分别为35．05%,43．70%,46．09%;同剂量的BL(1．61,3．23 mg·kg~(-1)·d~(-1))的抑瘤率分别为45．41%和58．19%。BL对Heps实体瘤小鼠的肿瘤抑制作用显著强于B,但B和BL对Heps腹水瘤小鼠生存时间均无延长作用。B和BL在1．61,3．23 mg·kg~(-1)·d~(-1)时对Heps实体瘤小鼠的造血、免疫系统以及肝、肾功能不仅无明显的毒性,相反还能提高其免疫器官的重量和指数,显著提高Heps小鼠的白细胞和血小板计数,并能显著降低Heps小鼠的AST,ALT和BUN的异常升高。结论:BL对移植性肝癌Heps小鼠的抗肿瘤活性明显强于B,并且对Heps小鼠造血、免疫系统以及肝肾的毒性低,通过深入研究BL可望成为一种新型的抗癌药物。     

5-Fu多级前体药物的设计合成与体内抗肿瘤作用

目的:设计合成5-Fu的多级前体药物,并进行小鼠体内抗肿瘤作用研究。方法:在5-Fu的N_1和N_3位引入邻甲苯甲酰基,分别合成氟尿嘧啶的邻甲苯甲酰基的单取代(TFu)和双取代(DTFu)前体药物,并考察目标化合物对小鼠S_(180)实体瘤和肝癌实体瘤的抑瘤作用。结果:在相同的给药剂量下(按100 mg·kg~(-1)给药时)DTFu和TFu对的小鼠S_(180)实体瘤的抑瘤率分别为55．88%和57．84%,优于对照药FT-207(抑瘤率为44．12%)。对肝癌实体瘤实验,DTFu抑瘤率与剂量成相关性,50,100和200 mg·kg~(-1)时的抑瘤率分别为37．74%,58．14%和88．74%。DTFu对小鼠灌胃给药的LD_(50)为3 165．77 mg·kg~(-1)。结论:TFu和DTFu具较强抗肿瘤活性且毒性较低。     

扇贝糖蛋白及多糖对S180荷瘤小鼠的抑瘤作用

目的:研究扇贝糖蛋白及扇贝多糖对S180小鼠的抑瘤作用。方法:给小鼠接种S180腹水瘤,用不同剂量扇贝糖蛋白及扇贝多糖治疗,观察瘤重及脾脏重量。结果:40 mg·kg-1扇贝糖蛋白对S180小鼠抑瘤率为47．29％,20 mg·kg-1扇贝多糖抑瘤率为46．97％;扇贝多糖还可明显增加小鼠脾脏重量。结论:扇贝糖蛋白及扇贝多糖抑瘤效果显著,扇贝多糖还具增强免疫功能作用。     

赖氨酸锗和环磷酰胺合用对小鼠S-180肉瘤抑瘤作用

赖氨酸锗(Ge401)是国内新近研制的含微量元素锗有机物。测得小鼠gi LD_(50)为9.26g/kg,ip LD_(50)为5.62g/kg;采用ig、ip、iv途径给药,对小鼠S-180肉瘤均有显著抑瘤作用,其中iv给药的抑瘤率(55%)最高;Ge401(30mg/kg·5d~(-1))和环磷酰胺(30mg/kg·2d~(-1))合用具有明显增强抑瘤作用。     

黄花夹竹桃甙及其与氮芥合用的体内抗肿瘤活性

黄花夹竹桃甙属强心甙类药。１．５ｍｇ·ｋｇ＾－１·ｄ＾－１ｉｐ治疗小鼠腹水瘤Ｈ２２，ＥＡＣ，Ｐ３８８及实体瘤Ｓ１８０，Ｕ１４，Ｌｅｗｉｓ肺癌，仅对实体瘤有效，抑瘤率为４８．７％－５６．７％。ＴＳ与轻度抑瘤作用剂量（０．３，０．５或１．０ｍｇ·ｋｇ＾－１·ｄ＾－１）的氮芥合用，抑瘤活性高于单独给药组，能使腹水瘤小鼠的生存期延长率达到８２．４至＞１２２．１％；对实体瘤的抑瘤率为６５．６％－７２．５％。     

nobiliside A隐形纳米脂质体对小鼠RM-1前列腺癌的抑制作用

目的比较nobiliside A隐形纳米脂质体(NASNL)和nobiliside A普通脂质体(NACL)对小鼠RM-1前列腺癌的抑制作用。方法 RM-1前列腺癌荷瘤小鼠随机分为6组(均n=10):阴性对照组(生理盐水)、阳性对照组(环磷酰胺20 mg·kg~(-1)·d~(-1))、NACL低、高剂量组(1 mg·kg~(-1)·d~(-1)、2 mg·kg~(-1)·d~(-1))和NASNL低、高剂量组(1 mg·kg~(-1)·d~(-1)、2 mg·kg~(-1)·d~(-1)),均尾静脉注射给予相应药物,连续7 d。通过比较各组小鼠的肿瘤生长曲线、抑瘤率、肿瘤组织的病理变化等考察2种脂质体的抑瘤效果。结果 NASNL两剂量组的肿瘤生长速度均低于相应剂量的NACL组(P<0.05)。NASNL两剂量组的抑瘤率均高于相应的NACL组,其中NASNL高剂量组的抑瘤率是NACL高剂量组的2倍。NASNL各组肿瘤细胞坏死程度高于NACL各组。结论 NASNL的肿瘤抑制作用明显优于NACL。     

聚酯型儿茶素的减毒作用研究

目的:研究聚酯型儿茶素(theasinesin,TS)是否具有减毒作用。方法:应用100ng·kg~(-1)环磷酰胺制成小鼠中毒模型,观察不同剂量TS对环磷酰胺所致小鼠毒副反应的影响。结果:1001,200,400 mg·kg~(-1)TS 环磷酰胺所致小鼠ALT和BUN升高均有明显对抗作用,200mg·kg~(-1)TS对环磷磷酰胺所致小鼠外周血白细胞的减少亦有明显对抗作用,200,400 mg·kg~(-1)TS可明显减轻环磷酰胺引起的骨髓有核细胞的降低。结论:聚酯型儿茶素可明显减轻环磷酰胺所致小鼠毒性作用。     

肿节风总黄酮对小鼠肉瘤S_(180)的抑瘤作用

目的观察肿节风总黄酮对小鼠肉瘤S180实体瘤和腹水瘤的作用,为开发高效低毒的抗肿瘤新药提供依据。方法采用动物整体实验方法,观察肿节风总黄酮对S180荷瘤小鼠实体瘤及腹水瘤的抑瘤作用及生命延长率。结果肿节风总黄酮对S180实体瘤的抑瘤率为20.7%～60.1%,对S180腹水瘤的延长率为36.8%。结论肿节风总黄酮有一定的抗肿瘤作用及生命延长率。     

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.