妇科恶性肿瘤患者治疗前免疫功能状态评价及临床意义

目的通过测定37例妇科恶性肿瘤患者治疗前外周血中可溶性白介素-2受体（sIL-2R）、白介素-6（IL-6）、γ干扰素（IFN-γ）、淋巴细胞亚群、自然杀伤细胞及淋巴细胞转化试验（LTT）了解其免疫功能状态和临床意义。方法应用ELISA法、间接免疫荧光法及LTT测定了患者外周血sIL-2R、IL-6、IFN-γ浓度变化及淋巴细胞在植物凝血素(PHA)作用后的转化率。结果（1）37例患者治疗前sIL-2R均明显升高（P＜0.05）,以卵巢癌最为突出,显著高于对照组及其它肿瘤（P＜0.01）;（2）IL-6浓度变化主要见于卵巢癌患者（P＜0.01）,且与患者的病期相关（r＝0.8637,P＜0.05）;（3）CD     

支原体肺炎患儿急性期外周血辅助性T淋巴细胞亚群的功能变化

目的 观察支原体肺炎（MPP）患儿急性期外周血辅助性T淋巴细胞（Th）亚群的功能变化，以探讨其在MPP发病机制中的意义。方法 对40例MPP患儿外周血单个核细胞（PBMC）经佛波酯＋Ca^2＋导入剂体外诱导48h，ELISA法检测上清液中IL-4、IFN-γ、转化生长因子-β1（TGF—β1）水平。结果 MPP患儿急性期IFN-γ水平、IFN-γ／IL-4比值显著低于对照组（P〈0．01），IL-4、TGF-β1水平显著高于对照组（P〈0．01）；PBMC培养上清液的TGF-β1水平与IFN-γ、IL-4的水平呈正相关（P〈0．01），而与IFN-γ／IL-4比值呈负相关（P〈0．05）；MPP患儿急性期并发肺外损害组PBMC培养上清液中TGF-β1、IL-4、IFN-γ水平及IFN-γ／IL-4比值与无肺外损害组差异均无统计学意义（P〉0．05）。结论 MPP患儿急性期Th1／Th2失衡，呈现Th2相对优势状态；体内出现保护性或调节性Th3功能增强，但TGF-β1保护性调节不足，使Th1／Th2失衡不能纠正；MPP患儿急性期Th细胞亚群功能变化与其急性期有无肺外损害无关。     

黄芪注射液对银屑病患者T淋巴细胞亚群及细胞因子的影响

目的:探讨黄芪注射液治疗银屑病的机制.方法:对20 例进行期寻常型银屑病患者应用黄芪注射液治疗,10名健康志愿者作为正常对照组,分离外周血淋巴细胞与血清,应用流式细胞仪和ELISA测定,观察患者治疗前后和正常对照组各指标的变化情况.结果:与正常对照组相比,病例组治疗前IL-2,sIL-2R,CD4+T,CD4+T/CD8+T含量升高(P＜0.05),CD8+T,mIL-2R表达下降(P＜0.05);治疗后,IL-2,sIL-2R,CD4+T,CD4+T/CD8+T含量降低(P＜0.05),CD8+T,mIL-2R表达升高(P＜0.05).结论:黄芪注射液是治疗进行期银屑病的一个有效药物,它的治疗作用可能是通过调节细胞因子的表达,抑制T淋巴细胞而实现的.     

妇科恶性肿瘤患者淋巴细胞亚群及相关细胞因子测定的意义

目的测定妇科恶性肿瘤患者治疗前外周血多种细胞因子、淋巴细胞亚群和淋巴细胞转化试验(LTT)并探讨其临床意义。方法应用Elisa法、间接免疫荧光法及LTTI则定了患者外周血中可溶性白介素-2(IL-2)及其受体(sIL-2R)、γ干扰素(IFN-γ)浓度变化及淋巴细胞在植物凝血素(PHA)作用后的转化率。结果42例患者入院时sIL-2R均明显升高,以卵巢癌最为显著(P<0.05)。患者CD4 细胞显著减少,CD4/CD8比例倒置,与对照组相比,外周血淋巴细胞对PHA刺激的反应明显低于正常水平,尤以卵巢癌更为明显(P<0.01),但患者CD16 、CD56 、CD25 和HLA-DR 细胞比例增加(P<0.05)。IL-2和IFN-γ含量则无明显改变。结论测定妇科恶性肿瘤患者的sIL-2、淋巴细胞亚群和LTT有助于预后判断。     

ITP中IFN-γ和IL-4 mRNA表达与其甲基化水平的相关性研究

目的:检测免疫性血小板减少症(ITP)患者的干扰素(IFN)-γ和白细胞介素(IL)-4的mRNA表达水平及其各自基因启动子区DNA甲基化的水平.方法:取36例ITP患者(ITP组)和36例正常对照(对照组)外周血,采用实时定量PCR方法检测IFN-γ和IL-4的mRNA水平;随机抽取2组中的各10例,采用DNA甲基化修饰后测序的方法检测IFN-γ和IL-4基因启动子区的甲基化水平,并计算IFN-γ和IL-4基因的mRNA水平与其基因启动子区DNA甲基化水平的相关性.结果:与对照组相比,ITP组IFN-γ的mRNA水平增高(1.86±0.29 vs 0.83±0.14,P＜0.05),而IL-4的mRNA水平降低(0.78±0.22 vs 1.45±0.40,P＜0.05),Th1/Th2(IFN-γ/IL-4)比值升高(7.11±0.60vs 3.12±1.88,P＜0.01).2组IFN-γ和IL-4基因CpG岛的位点甲基化水平和整体甲基化水平差异均无统计学意义(P＞0.05).ITP组中IFN-γ和IL-4的mRNA表达水平与基因启动子区甲基化水平不存在相关性(均P＞0.05).结论:ITP患者处于Th1极化状态,IFN-γ和IL-4的基因启动子区的甲基化水平对各自基因mRNA水平的表达不起调控作用.     

宫颈鳞癌患者Th1/Th2平衡状态的研究

目的 观察宫颈鳞癌患者T细胞亚群的漂移状态.方法 采用ELISA法,对65例宫颈鳞癌患者和40例正常人群的血清中的IL-2、IFN-γ、IL-4、IL-10进行测定.结果 宫颈鳞癌患者血清中IL-2、IFN-γ水平较正常对照组明显降低(P＜0.01),宫颈鳞癌患者血清中IL-4、IL-10高于对照组,统计处理有显著性差异(P＜0.05).结论 宫颈鳞癌患者存在典型的Th2漂移现象,机体免疫抑制,导致肿瘤发生,同时为宫颈鳞癌的生物治疗提供靶点.     

参附注射液对胃肠道恶性肿瘤患者Th淋巴细胞分化的影响

目的观察体外使用参附注射液对胃肠道恶性肿瘤患者外周血T淋巴辅助(Th)细胞分化的影响。方法 20例拟行择期胃肠道恶性肿瘤手术的患者,麻醉前及手术后24 h抽取外周血分离单个核细胞(PBMC),随机分为两组,分别在培养体系中加入参附注射液(S组)或加入相同体积的生理盐水(C组)。24 h后加入刺激剂植物血凝素(PHA)促进细胞分化。48 h后分析Thl和Th2细胞的比例,测定细胞培养上清液中白细胞介素4(IL-4)和γ干扰素(IFN-γ)浓度。结果手术应激促进Th细胞向Th2方向分化,细胞培养上清液中IFN-γ/IL-4比率降低;参附注射液抑制手术后Th淋巴细胞向Th2方向分化,并改善细胞培养上清液中IFN-γ/IL-4比例。结论参附注射液抑制胃肠道恶性肿瘤患者的Th细胞向Th2方向分化。     

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。     

宫颈癌患者外周血T淋巴细胞亚群及血VEGF水平的临床意义

目的探讨宫颈癌患者外周血T淋巴细胞亚群及血VEGF水平的临床意义。方法采用流式细胞仪(FCM)对34例宫颈癌患者外周血T淋巴细胞亚群进行检测,同时应用ELISA法检测血VEGF水平。随机抽取健康女性20例为对照组,比较两组T淋巴细胞亚群及VEGF。结果宫颈癌患者外周血CD4+、CD4+/CD8+比值较对照组均明显下降(P<0.05),而CD8+水平、IL-6、VEGF显著升高。IFN-γ水平与对照组无明显差异性。肿瘤期别越晚,CD4+/CD8+比值越低,CD8+、IL-6、VEGF水平越高,IFN-γ水平则无明显差异性。结论宫颈癌患者T淋巴细胞亚群改变导致细胞免疫功能降低,肿瘤细胞发生免疫逃逸,促进宫颈癌的发生、发展;VEGF诱导肿瘤血管形成,促进宫颈癌的侵袭、转移。     

生脉注射液对多发伤患者细胞免疫功能的调节作用

目的:探讨生脉注射液对多发伤患者细胞免疫功能的影响。方法:42例多发伤患者随机分为常规组和生脉组,各21例。常规组采用常规基础治疗,生脉组在常规治疗基础上加用生脉注射液。于治疗前及治疗后第14天测定外周血T淋巴细胞亚群CD4+、CD8+、干扰素-γ(IFN-γ)和白细胞介素-4(IL-4)。另外,治疗后42例多发伤患者(多发伤组)与21例健康志愿者(健康对照组)进行外周血T淋巴细胞亚群、IFN-γ和IL-4比较。结果:多发伤组外周血CD4+、CD8+、CD4+/CD8+比值、IFN-γ及IFN-γ/IL-4比值较健康对照组降低,差异有统计学意义(P<0.01);IL-4较健康对照组升高,差异有统计学意义(P<0.01)。治疗后14d,生脉组CD4+、CD4+/CD8+比值、IFN-γ、IFN-γ/IL-4比值较常规组升高,差异有统计学意义(P<0.05或P<0.01);IL-4的表达较常规组降低,差异有统计学意义(P<0.01)。结论:生脉注射液能够改善多发伤患者细胞免疫功能的紊乱状态。     

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.     

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 x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 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.     

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.     

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。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.