Fucoidan对Lewis肺癌荷瘤小鼠抑瘤及免疫调节作用

目的研究褐藻多糖硫酸酯(Fucoidan)对Lewis肺癌小鼠抗肿瘤及免疫调节作用。方法建立Lewis肺癌荷瘤小鼠模型,腹腔注射给予不同浓度Fucoidan连续21d,检测Fucoidan对肿瘤生长、免疫器官指数。采用ELISA法检测荷瘤小鼠细胞因子水平。以CD34血管内皮细胞标记物,采用免疫组化法分析肿瘤内微血管生成情况。结果100和200mg.kg-1 Fucoidan显著抑制Lewis肺癌的生长,抑瘤率分别是42.54%,58.63%(P<0.05); 显著增加荷瘤小鼠脾指数(P<0.05); 50和100mg.kg-1组可提高荷瘤小鼠血清中IL-1β水平,100mg.kg-1可提高IL-2、IL-6和FAS-L水平; 200mg.kg-1组血清IFN-γ水平显著提高(P<0.05); 100和200mg.kg-1组肿瘤组织中微血管密度显著降低(P<0.05)。结论Fucoidan对小鼠Lewis肺癌的生长有抑制作用,可能与增强荷瘤小鼠抗肿瘤免疫、抑制肿瘤血管新生有关。     

注射用紫杉醇(清蛋白结合型)抗肿瘤作用

目的比较自研注射用紫杉醇(清蛋白结合型,PAB)与原研注射用紫杉醇(清蛋白结合型,Abraxane)的体内抗肿瘤作用。方法建立小鼠H22、Lewis和RM-1肿瘤模型,荷瘤小鼠分别静脉注射13.4,20.0,30.0,45.0 mg·kg-1剂量的PAB和20.0和(或)30.0 mg·kg-1剂量的Abraxane,比较给药后PAB组与Abraxane组的抗肿瘤作用。结果 PAB13.4,20.0,30.0,45.0 mg·kg-1剂量组均能显著抑制H22肿瘤生长,PAB 20.0 mg·kg-1剂量组与等剂量的Abraxane组比较对H22肿瘤地抑制作用差异无统计学意义。PAB 20.0,30.0,45.0 mg·kg-1剂量组可剂量依赖性地抑制Lewis和RM-1肿瘤生长,PAB和Abraxane对C57雌性荷瘤小鼠的最大无毒剂量均为20.0 mg·kg-1。PAB各剂量组与等剂量的Abraxane组比较,对RM-1和Lewis肿瘤生长的抑制作用和对荷瘤小鼠的毒性均差异无统计学意义。结论相同给药剂量下,PAB的体内抗肿瘤作用和毒性与原研品Abraxane相同。     

川芎嗪对小鼠Lewis肺癌的治疗作用

目的:研究中药川芎嗪(TMP)对实体肿瘤的疗效及其可能的作用机理。方法:本研究运用Lewis肺癌小鼠模型,观察TMP对小鼠Lewis肺癌的疗效、免疫功能、生存质量及不良反应的影响。结果:TMP治疗小鼠Lewis肺癌能抑制肿瘤的生长,稳定病灶,提高荷瘤小鼠的生存质量,改善免疫功能。结论:TMP对小鼠Lewis肺癌有明显疗效,其作用机理与其本身对Lewis肺癌实体瘤有抑制作用和提高荷瘤小鼠免疫功能有关。     

人参皂苷衍生物AD-1对肺癌A549细胞增殖和荷瘤裸小鼠肿瘤生长的抑制作用研究

目的研究人参皂苷衍生物AD-1对小细胞肺癌A549细胞增殖和荷瘤裸小鼠肿瘤生长的抑制作用。方法采用噻唑蓝(MTT)法观察AD-1对小细胞肺癌A549细胞增殖的抑制作用,流式细胞术测定AD-1对小细胞肺癌A549细胞凋亡及周期的影响,并在裸小鼠人肺癌模型上观察AD-1对荷瘤裸小鼠肿瘤生长的抑制作用。结果 AD-1对A549细胞具有明显的抑制作用并呈剂量和时间依赖性;流式细胞术结果显示,细胞周期被阻滞在G0/G1期,24 h凋亡率分别为(26.37±2.62)%,(29.68±2.59)%和(35.38±2.62)%;荷瘤裸小鼠动物抑瘤试验表明,AD-1对裸小鼠的肿瘤生长也具有明显的抑制作用,抑瘤率分别为19.69%,36.53%和52.28%。结论AD-1对A549细胞的增殖和荷瘤裸小鼠肿瘤的生长具有明显的抑制作用。     

CJ016对人肺癌裸鼠移植瘤的抑制活性研究

目的研究CJ016对人肺癌模型的治疗效果及其作用机制。方法建立人肺腺癌细胞A549裸鼠移植瘤模型,考察CJ016体内抑制肿瘤生长效果;同时将肿瘤进行免疫组化检测,考察其对肿瘤内CD31和细胞凋亡的影响。结果CJ016对A549细胞增殖有明显抑制作用,其IC_(50)值为34.22nmol·L~(-1);动物实验表明其具有较好的肿瘤抑制效果,抑瘤率、T/C%值分别为70.08%和27.75%(20 mg·kg~(-1));同时,CJ016能降低肿瘤细胞内CD31的表达,促进肿瘤细胞凋亡。结论 CJ016能明显抑制A549细胞荷瘤小鼠肿瘤生长,其可能的作用机制是减少血管生成和诱导肿瘤细胞凋亡。     

双环醇对顺铂联合吉西他滨致荷瘤小鼠肝肾损伤的保护作用

目的：建立顺铂（CDDP）联合吉西他滨（GEM）引起小鼠肝肾损伤动物模型,研究双环醇对CDDP/GEM联用致荷瘤小鼠肝肾损伤及骨髓毒性的保护作用。方法参考临床用药方案,建立CDDP/GEM联用致小鼠肝肾损伤模型。在模型建立的基础上,考察双环醇的保护作用：C57/BL小鼠接种Lewis肺癌后第6天开始腹腔注射CDDP（5mg·kg^-1×5）及GEM（50mg·kg^-1×2）,建立大剂量CDDP/GEM联用致小鼠肝肾损伤模型,同时灌胃给予双环醇（150、300mg·kg^-1）,以吉粒芬（100 g·kg^-1）作为阳性对照药。于开始给药后第6天处理动物,取瘤称重,全自动生化分析仪检测血清肝功能及肾功能生化指标,五分类血液分析仪进行血象分析。结果小鼠腹腔注射CDDP（5mg·kg^-1×5）及GEM （50mg·kg^-1×2）,在动物尚未出现大量死亡的情况下,能引起明显的肝肾损伤。双环醇150mg·kg^-1能显著降低上述方案CDDP/GEM引起的血清CR的升高,同时显著升高全血中NEUT和NEUT%。双环醇300mg·kg^-1亦有保护作用,但作用不显著。吉粒芬对CDDP/GEM联用引起的WBC、NEUT、NEUT%降低有显著升高作用。双环醇及吉粒芬与CDDP/GEM合用,对后者的抑瘤活性略有增加作用。结论双环醇在略增加CDDP/GEM抑瘤活性的基础上,150mg·kg^-1剂量对后者引起的荷瘤小鼠肝肾损伤及骨髓毒性具有良好的保护作用,300mg·kg^-1剂量组作用不及150mg·kg^-1剂量组,但均能降低荷瘤小鼠死亡率,值得临床关注。     

扇贝裙边糖胺聚糖的体外抗肿瘤活性及对荷瘤小鼠抗氧化作用的研究

目的:研究扇贝裙边糖胺聚糖(SS-GAG)的体外抗肿瘤活性及对荷瘤小鼠的抗氧化功能的影响。方法:用MTT法观察不同浓度的SS-GAG对体外培养的宫颈癌HeLa、人大肠癌LOVO、肺癌A549、神经胶质瘤U251等肿瘤细胞株增殖活性的影响;观察SS-GAG对小鼠接种S180后30d内的存活时间;通过黄嘌呤氧化酶法、硫代巴比妥酸显色法等多种生化方法观察SS-GAG对荷瘤小鼠血清总抗氧化能力(T-AOC)、超氧化物岐化酶(SOD)活性和丙二醛(MDA)含量的影响,并与对照比较。结果:与对照比较,SS-GAG可明显抑制HeLa、U251细胞生长,对LOVO、A549细胞生长也有一定的抑制作用;SS-GAG能显著延长S180腹水瘤小鼠的生存时间,提高荷瘤小鼠的T-AOC、SOD水平,降低MDA含量(P<0.01或P<0.05)。结论:SS-GAG可抑制肿瘤生长,并有一定的抗氧化作用。     

紫杉醇长循环热敏脂质体对Lewis肺癌荷瘤鼠的药效学

目的:考察紫杉醇长循环热敏脂质体(PLTL)对Lewis肺癌荷瘤小鼠的药效学。方法:构建Lewis肺癌荷瘤肿瘤模型,随机分为5组:对照组、加热组、紫杉醇注射液(PTX)组、紫杉醇普通热敏脂质体(PTL)组和PLTL组。治疗期间观察小鼠生活状态,检测瘤重抑瘤率;将肿瘤组织切片进行HE染色,观察细胞形态学变化;采用流式细胞仪和TUNEL法检测肿瘤细胞的凋亡率;分析荷瘤小鼠生存状况,绘制荷瘤小鼠生存曲线。结果:PTX、PTL组和PLTL组的瘤重抑廇率分别为46.15%、51.48%和70.12%,流式细胞术和TUNEL法显示PTX、PTL和PLTL均可明显抑制荷瘤小鼠肿瘤生长,且凋亡率逐渐增强;肿瘤组织切片HE染色发现,PLTL可明显抑制肿瘤生长,并在肿瘤局部产生炎症反应;生存实验分析显示PLTL可减小紫杉醇的毒副作用,延长小鼠生存期。结论:PLTL与PTX和PTL相比,PLTL具有明显的热敏靶向性,PLTL与局部热疗相结合可显著增强紫杉醇的抗癌活性。     

丹参联合放疗对小鼠Lewis肺癌肿瘤组织微血管的影响

目的探讨丹参联合放疗对小鼠Lewis肺癌肿瘤组织微血管密度(MVD)的影响。方法建立Lewis肺癌荷瘤鼠模型后,60只荷瘤鼠随机均分为模型组、丹参组(低、高剂量)、放疗组、丹参低剂量+放疗组(联合1组)、丹参高剂量+放疗组(联合2组)。各组于接种第二日起每天ip给药,连续12 d,放疗组及联合1、2组于接种第7日起给予钴-60照射肿瘤局部,剂量2 Gy·d-1,连续5 d。末次给药24 h后处死动物,剥离肿瘤组织称重,计算抑瘤率;免疫组化法检测肿瘤组织MVD。结果联合1组的MVD较放疗组和丹参低剂量组明显降低(P<0.05)。结论丹参联合放疗对Lewis肺癌小鼠肿瘤血管的生成有明显的抑制作用。     

20(s)-原人参二醇的抗肿瘤及免疫调节作用研究

目的:探讨20(s)-原人参二醇(Protopanaxdiol,Ppd)的抗肿瘤及免疫调节作用。方法:建立小鼠肝癌H_(22)、Lewis肺癌和黑色素瘤B_(16)三种移植瘤动物模型,小鼠每日灌胃给予Ppd(25,50,100mg·kg~(-1))1次,连续12d,末次药后称取小鼠体重及肿瘤重量,同时测定H_(22)荷瘤小鼠T淋巴细胞转化率、NK细胞杀伤活性及IL-2含量。结果:Ppd 25,50,100mg·kg~(-1)剂量对小鼠肝癌H_(22)的抑瘤率分别为28.85%,43.55%,49.11%;对小鼠Lewis肺癌的抑瘤率分别为23.07%,44.96%,49.61%;对小鼠黑色素瘤B_(16)的抑瘤率分别为30.21%,37.43%,43.20%。Ppd 50,100mg·kg~(-1)可明显提高肝癌H_(22)小鼠的T淋巴细胞增殖能力、NK细胞活性和IL-2含量。结论:Ppd对小鼠三种移植瘤均具有明显的抗肿瘤活性并与免疫调节作用呈相关性,提示其抗肿瘤作用可能与激活体内免疫系统有关。     

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.