雷帕霉素对小鼠脾淋巴细胞走后门殖及产生细胞因子的影响

目的：研究雷帕霉素（RAPA）对ConA、PHA、LPS诱导的小鼠脾细胞增殖反应,混合淋巴细胞反应,脾T淋巴细胞亚型及细胞因子IL-2、IFN-γ、TNF-α含量的影响。方法：MTT法测定淋巴细胞增殖实验、混合淋巴细胞反应,流式细胞法测定脾T淋巴细胞亚型,结晶紫染色法测定TNF-α,E-LASI法测定IL-2,IFN-γ。结果：RAPA可显著抑制ConA、PHA和LPS诱导的小鼠脾细胞增殖和混合淋巴细胞反应（MLR）,对小鼠脾T淋巴细胞亚型无明显影响。RAPA还可明显抑制小鼠脾淋巴细胞分泌IL-2,IFN-γ,但对小鼠腹腔巨噬细胞分泌TNF-α无效。结论：RAPA抑制小鼠免疫功能的作用机制与CsA不同。     

重组人胸腺素α原体外对IFN-γ,IFN-α及TNF-α的影响

目的体外观察重组人胸腺素α原(prothymosin α,Pro Tα)对几种重要细胞因子分泌的影响。方法用脾淋巴细胞、脾巨噬细胞及腹腔巨噬细胞,以ELISA法检测Pro Tα对IFN-γ,IFN-α和TNF-α分泌的影响。结果1×10^-7 mol·L^-1 Pro Tα明显促进脾细胞分泌IFN-γ(P<0.05),该浓度的Pro Tα也明显刺激小鼠脾巨噬细胞分泌IFN-α(P<0.01);在小鼠腹腔巨噬细胞中,Pro Tα能明显刺激IFN-α和TNF-α的分泌(P<0.01)。结论Pro Tα对细胞因子IFN-γ,IFN-α和TNF-α的分泌均有促进作用。     

OX40-OX40L相互作用对C57BL/6小鼠淋巴细胞活性的影响

目的探讨OX40-OX40L相互作用对C57BL/6小鼠脾淋巴细胞增殖及细胞因子表达的影响。方法应用MTT法检测小鼠淋巴细胞增殖;ELISA法检测淋巴细胞表达细胞因子IL-4、IL-2及INF-γ表达。结果与对照组比较,Anti-OX40特异性刺激OX40-OX40L轴后,小鼠淋巴细胞增殖增强,分泌IL-2和INF-γ含量明显增加,48h细胞增殖最佳;IL-4含量无明显变化。应用特异性anti-OX40L抗体阻断OX40-OX40L轴后,淋巴细胞增殖及分泌细胞因子IL-2和INF-γ含量明显受到抑制。结论 OX40-OX40L相互作用能够调控C57BL/6小鼠脾淋巴细胞增殖及促炎性细胞因子表达。     

鲨鱼软骨粉对S_(180)荷瘤小鼠免疫细胞调节功能的影响

目的研究鲨鱼软骨粉(SCP)对S180荷瘤小鼠免疫细胞功能的影响。方法鲨鱼软骨粉300、200、100mg·kg-1小鼠灌胃给药10 d。MTT法检测其对S180荷瘤小鼠脾淋巴细胞增殖功能的影响;流式细胞仪检测T淋巴细胞亚群的变化;ELISA法测定荷瘤小鼠血清中细胞因子TNF-α、IFN-γ含量。结果 SCP能提高小鼠脾淋巴细胞的增殖活性;不同程度地提高小鼠脾细胞CD4+细胞数,增加CD4+/CD8+细胞比值;明显提高小鼠巨噬细胞的吞噬活性;促进外周血清中TNF-α和IFN-γ的分泌水平。结论 SCP能提高T细胞介导的细胞免疫应答,提高巨噬细胞调节免疫应答的功能,促进TNF-α、IFN-γ等细胞因子的分泌,从而发挥其抗肿瘤作用。     

塞隆骨提取物对牛Ⅱ型胶原诱导的小鼠关节炎的治疗作用及机制研究

目的了解塞隆骨水提物(SLG-B)对胶原诱导的小鼠关节炎的治疗作用及治疗机制。方法利用牛Ⅱ型胶原诱导DBA/1小鼠类风湿性关节炎模型即CIA。SLG-B口服给药观察小鼠关节炎指数的变化情况,体外培养关节炎小鼠脾细胞及巨噬细胞,ELISA法测定IL-12、IL-2、IFN-γ、TNF-α几种细胞因子。RT-PCR测定SLG-B对关节炎小鼠巨噬细胞IL-1β、IL-6、iNOS mRNA表达的影响。结果SLG-B能明显的抑制牛Ⅱ型胶原诱导关节炎的发生,能够减轻关节炎的各种症状。SLG-B在加抗原和不加抗原的情况下都能够明显的抑制关节炎小鼠脾细胞的增殖同时发现SLG-B能够抑制IL-2、IFN-γ、L-12p40、TNF-α细胞因子的产生还能够抑制小鼠腹腔巨噬细胞IL-1、IL-6及iNOS mRNA的表达。这可能是SLG-B在小鼠关节炎中表现治疗效果的分子基础。结论SLG-B对小鼠关节炎有很好的治疗效果,其作用机制主要是通过抑制巨噬细胞及脾细胞产生炎性细胞因子和抑制炎性细胞因子mRNA的表达来达到治疗类风湿性关节炎的作用。     

OK-432肿瘤疫苗对DBA/2小鼠脾脏细胞中Th1细胞因子以及TNF-α分泌的影响

目的利用DBA/2小鼠移植舌癌荷瘤模型,探讨OK-432肿瘤疫苗对DBA/2小鼠脾脏细胞中Th1细胞因子以及TNF-α分泌的影响。方法 ELISA定量检测脾脏淋巴细胞所产生的IFN-γ,IL-2,TNF-α等细胞因子的分泌水平。结果 OK-432肿瘤疫苗组中IFN-γ、IL-2以及TNF-α的含量明显高于实验对照组(P<0.05)。结论 OK-432肿瘤疫苗可刺激荷瘤小鼠脾脏细胞Th1细胞及TNF-α的分泌,增强DBA/2小鼠的抗肿瘤免疫功能。     

辅助性T淋巴细胞因子在大肠癌手术治疗前后的作用

目的：检测大肠癌患者手术前后外周血辅助性T淋巴细胞因子的变化,探讨辅助性T淋巴细胞因子1/辅助性T淋巴细胞因子2（Th1/Th2）比值异常的意义。方法空腹抽取45例大肠癌患者（试验组）手术前、后的外周血和20例健康志愿者（对照组）外周血,运用ELISA法和流式细胞技术检测白介素-2（IL-2）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和白介素-4（IL-4）、白介素-6（IL-6）、白介素-10（ IL-10）及Th1/Th2比值并进行比较。结果试验组及不同Ducks分期患者术前IL-2、IFN-γ、TNF-α外周血浓度均显著低于对照组（ P ＜0膊．05）,IL-4、IL-6、IL-10外周血浓度均显著高于对照组（ P ＜0．05）,Th1/Th2比值较对照组差异有统计学意义（ P ＜0．05）;试验组Ducks分期Ⅲ、Ⅳ期患者术前IFN-γ显著高于Ⅱ期患者（ P ＜0．05）,IL-4显著低于Ⅱ期患者（ P ＜0．05）,Th1/Th2比值较II期患者术前差异有统计学意义（ P ＜0．05）。试验组术后IL-2、TNF-α和IFN-γ的水平较术前显著升高（ P ＜0．05）, IL-4、IL-6和IL-10水平较术前显著降低（ P ＜0．05）, Th1/Th2比值较术前差异有统计学意义（ P ＜0．05）。试验组术后IL-2、TNF-α和IFN-γ显著低于对照组（ P ＜0．05）,试验组Ⅲ、Ⅳ期患者术后Th1/Th2比值较试验组Ⅱ期患者及对照组均差异有统计学意义（ P ＜0．05）。结论大肠癌患者手术前外周血中Th1类细胞因子IL-2、IFN-γ、TNF-α水平显著下降,Th2类细胞因子IL-4、IL-6、 IL-10表达显著升高, Th1/Th2比值下降,机体免疫调定点向免疫耐受方向漂移,使机体对体内癌细胞免疫识别机免疫清除能力下降;大肠癌手术后Th1类细胞因子外周血水平显著升高,Th2类细胞因子外周血水平明显降低,Th1/Th2比值趋向正常状态,机体的免疫识别及免疫清除能力增强,机体的抗肿瘤机能有所恢复;大肠癌晚期患者较正常对照组和Ⅱ期大肠癌患者的Th1细胞免疫功能受损更严重。     

毛蚶多肽提取物的体外免疫活性

目的考察毛蚶多肽提取物(PEAS)的体外免疫活性。方法 MTT法测定PEAS对小鼠脾淋巴细胞增殖的影响及对小鼠NK细胞杀伤活性的影响;中性红吞噬法测定PEAS对小鼠腹腔巨噬细胞吞噬功能的影响;流式细胞术测定PEAS所致小鼠脾淋巴细胞周期的变化;双抗体夹心ELISA法测定PEAS对主要细胞因子IFN-γ和IL-4分泌水平的影响。结果 PEAS能够显著促进小鼠脾淋巴细胞增殖(P<0.05或0.01),能够增强小鼠腹腔巨噬细胞吞噬中性红活性和小鼠NK细胞杀伤活性(P<0.05或0.01);PEAS能够促进脾淋巴细胞G0/G1期向DNA合成期(S期)转化;PEAS协同Con A作用,能够增加IFN-γ的分泌(P<0.05或0.01),并且能够抑制IL-4的分泌(P<0.05或0.01)。结论 PEAS体外可促进小鼠脾淋巴细胞、腹腔巨噬细与NK细胞的免疫功能,其机制可能与促进脾淋巴细胞DNA合成,增加IFN-γ的分泌量有关。     

黄芪皂甙Ⅳ对小鼠T、B淋巴细胞增殖和腹腔巨噬细胞功能的影响(英文)

目的:探讨黄芪皂苷Ⅳ(ASI)对小鼠T、B淋巴细胞增殖和腹腔巨噬细胞分泌的细胞因子的影响.方法:采用MTT法检测T、B淋巴细胞的增殖;采用分光光度计测定法检测抗体活性;IL-1活性用胸腺细胞增殖法测定;TNF-α活性用L929细胞杀伤法测定.结果:1)ASI50-200mg/kg ig 7天能够促进T淋巴细胞增殖和抗体生成,而ASI 50-100mg/kg能够促进B淋巴细胞增殖,但是220mg/kg对B淋巴细胞增殖无影响;2)ASI体外仅在100nmol/L对T、B淋巴细胞有促进作用;3)ASI 1 nmol/L可以促进腹腔巨噬细胞分泌IL-1,而100-1000nmol/L则抑制腹腔巨噬细胞分泌IL-1;4)ASI体外可以抑制LPS刺激或无LPS刺激下的腹腔巨噬细胞分泌TNF-α.结论:ASI能够促进小鼠T、B淋巴细胞的增殖和抗体生成,同时可以抑制腹腔巨噬细胞体外分泌IL-1和TNF-α.     

低剂量白藜芦醇增强小鼠免疫反应

目的:研究低剂量白藜芦醇的免疫调节作用.方法:用ConA和Sac分别刺激T淋巴细胞和抗原细胞并诱导细胞因子产生;[~3H]-胸腺嘧啶核苷掺入法检测淋巴细胞增殖;ELISA法检测IL-2,IL-12,IL-10和IFN-γ;用DNFB诱导小鼠迟发型超敏反应(DTH),小鼠耳肿胀作为DTH反应指标;流式细胞仪检测小鼠脾淋巴细胞亚群的变化.结果:白藜芦醇(0.75-6μmol/L)剂量依赖性地促进小鼠T淋巴细胞的增殖和IL-2的产生;白藜芦醇还剂量依赖性地促进脾脏淋巴细胞IFN-γ和IL-12的生成,同时抑制IL-10的产生;白藜芦醇(4 mg/kg)灌胃给药能对抗乙醇(16％,w/v)对小鼠DTH反应的抑制作用;白藜芦醇对脾脏淋巴细胞亚群无明显改变,但能逆转乙醇对脾淋巴细胞中巨噬细胞数量和 MHC-II分子表达的下调作用.结论:低剂量白藜芦醇能促进小鼠细胞介导的免疫反应,促进Th1细胞因子产生及影响巨噬细胞功能是其可能的机制.     

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.