子宫内膜异位症中单核-巨噬细胞分泌 IL-1α、IL-1β、IFN-γ的研究

目的:探讨子宫内膜异位症(内异症)患者腹腔液巨噬细胞、外周血单核细胞分泌白细胞介素(IL)-1α、IL-1β和干扰素(IFN)-γ的水平与内异症发病机制的关系。方法:以术后病理诊断为子宫内膜异位症的患者40例作为内异症组,以子宫肌瘤、卵巢良性肿瘤患者30例作为对照组,分离、培养各组外周血单核细胞和腹腔液巨噬细胞,用酶联免疫吸附试验(ELISA)测定其培养上清液中IL-1α、IL-1β和IFN-γ的浓度。结果:内异症组单核-巨噬细胞分泌IL-1α、IL-1β的水平均高于对照组,但与月经周期及疾病分期无关。两组分泌IFN-γ的水平差异无统计学意义。结论:内异症患者分泌IL-1水平升高,而分泌IFN-γ的相对不足,与内异症的发生、发展密切相关。     

子宫内膜异位症患者腹腔液中IFN-γ和IL-4水平的关系

目的:探讨子宫内膜异位症(内异症)患者腹腔液中Th细胞分泌γ干扰素(IFN-γ)和白细胞介素(IL)-4水平与内异症发病的关系。方法:选取经手术后病理证实为内异症的24例患者为内异症组;以子宫肌瘤或卵巢良性肿瘤患者24例为对照组。分别分离、培养2组腹腔液的Th细胞,用酶联免疫吸附试验(ELISA)检测其培养的上清液中IFN-γ和IL-4水平,并计算IFN-γ/IL-4的比值。结果:内异症组腹腔液Th细胞培养上清液IFN-γ的水平低于对照组(P<0.01);而IL-4的水平高于对照组(P<0.05)。内异症组IFN-γ/IL-4的比值低于对照组(P<0.01)。结论:内异症患者腹腔液Th细胞培养上清液中IFN-γ/IL-4比值的变化揭示Th1/Th2的失衡状态,可导致异位内膜逃避免疫监视,造成异位内膜种植。     

25例不孕症伴有子宫内膜异位症患者腹腔液CA125、E2、P含量的测定

目的测定不孕症伴有子宫内膜异位症(内异症)患者腹腔液CA125、E2、P的含量并探讨其与不孕症伴有子宫内膜异位症的关系.方法病例选自因不孕症入我院行腹腔镜检查或治疗的患者共73例,其中有25例伴有内异症,余48例为慢性盆腔炎作为对照组,应用ELISA测定两组腹腔上清液CA125的含量,磁酶免测定两组腹腔上清液E2、P含量.结果各期内异症患者腹腔液CA125的浓度比较及其与对照组比较,差异均无显著性(P＜0.05).两组间腹腔液E2、P浓度比较差异无显著性,Ⅰ期内异症与Ⅱ期内异症腹腔液E2、P的浓度相比,Ⅱ期明显高于Ⅰ期,差异有显著性(P＜0.05).结论腹腔液中CA125浓度的测定特异性不高,E2、P是否为促使内异症进展的关键因素及其与不孕的关系,还有待于进一步研究.     

PEDF与VEGF在子宫内膜异位症发生发展中的作用

目的:探讨色素上皮衍生因子(Pigment epithelium derived factor,PEDF)与血管内皮生长因子(Vascular endothelial growth factor,VEGF)在子宫内膜异位症(内异症)患者子宫在位内膜,异位内膜及正常对照组内膜组织中的表达,并探讨二者在内异症患者的新生血管生成过程中的作用。方法:采用免疫组织化法检测34例内异症患者异位内膜,及在位内膜组织中PEDF与VEGF表达的蛋白含量,并与对照组进行比较。结果:研究组在位及异位子宫内膜组织均有PEDF和VEGF的蛋白表达,PEDF的蛋白表达异位内膜高于在位内膜,高于同期对照组正常内膜。VEGF的蛋白表达异位内膜低于在位内膜,对照组正常内膜低于在位内膜,差异有统计学意义(P<0.05)。PEDF在对照组分泌期内膜表达低于增生期,而对照组分泌期内膜VEGF的表达高于增生期,二者均呈现出周期性变化。但研究组在位内膜,异位内膜PEDF及VEGF的表达失去了周期性变化,差异无统计学意义。结论:内异症患者PEDF在异位内膜的表达比在位宫内膜及对照组正常子宫内膜高,VEGF在位内膜的表达比异位内膜及对照组正常子宫内膜高。根据r-AFS分期法,PEDF在III、IV期患者在异位内膜的表达比I、II高,VEGF表达高低与r-AFS分期无明显关系。二者在EMT患者的在位内膜,异位内膜上的表达,可能参与内异症异位病灶的形成,而且二者与内异症患者的新生血管生成可能有关。     

子宫内膜异位症腹腔液中IL-2、IL-6的变化

目的探讨腹腔液中细胞因子在子宫内膜异位症内异症发病中的作用。方法采用酶联免疫吸附试验,检测内异症患者40例（内异症组,Ⅰ期12例,Ⅱ期15例,Ⅲ期9例,Ⅳ期4例）、非内异症患者10例（对照组）腹腔液中白介素-6（IL-6）、IL-2的含量;并对内异症患者腹腔液中细胞因子浓度与美国生育协会修正标准分期（AFSr）及痛经评分进行相关性分析。结果内异症患者腹腔液中IL-6含量与对照组差异有统计学意义（P〈0．01）;IL-2含量差异也有统计学意义（P〈0．01）;IL-6与R-AFS评分呈正相关（r=0．643。P〈0．05）。2个细胞因子与痛经评分均无相关性（r=0．241,P〉0．05）。结论内异症组腹腔液中异常水平的IL-6及IL-2是腹腔免疫动态环境失衡的部分原因。     

子宫内膜异位症患者血清及腹腔液HMGB1的表达及意义

目的探讨子宫内膜异位症(内异症)患者血清及腹腔液中高迁移率簇蛋白B1(HMGB1)的表达及其在内异症发病中的作用。方法选择2010年3月至2011年9月在我院经妇科腹腔镜手术及术后病理诊断为内异症的40例患者并进行分期,其中早期(I、II期)18例,晚期(III、IV)22例;并选择同期间在我院行妇科腹腔镜手术的非内异症患者(输卵管性不孕、卵巢畸胎瘤)25例。所有患者均在术前采集上肢静脉血,术中采集腹腔液,采用ELISA方法测定血液和腹腔液中HMGB1的表达,并对内异症患者血清和腹腔液中HMGB1表达做相关性分析。结果①内异症组血清、腹腔液中HMGB1水平均比对照组明显增高(P<0.05);②内异症晚期组组血清、腹腔液中HMGB1水平均比内异症早期组明显增高(P<0.05);③内异症组血清HMGB1与内异症组腹腔液HMGB1水平之间呈明显正相关(r=0.026,P<0 05)。结论内异症患者血清及腹腔液中HMGB1水平明显增高,尤其是内异症晚期患者,HMGB1可作为评判内异症严重程度的一个指标。     

Ang-2、Tie-2与ER-α在子宫内膜异位症中的表达及意义

目的:探讨血管生成素2(Ang-2)及其酪氨酸蛋白激酶受体2(Tie-2)和雌激素受体α(ER-α)在子宫内膜异位症(内异症)发病中的表达.方法:选择30例内异症患者的在位内膜作为内异症组,30例卵巢其他良性肿瘤患者的子宫内膜作为对照组,增殖期和分泌期各15例,应用免疫组织化学SP法检测Ang-2、Tie-2和ER-α在其中的表达.结果:Ang-2和Tie-2主要在子宫内膜的腺上皮表达,血管内皮和间质也有少许表达,但较腺上皮表达少,定位于细胞浆.ER-α在子宫内膜腺上皮和间质均有表达,定位于细胞核.内异症组的增殖期和分泌期内膜中Ang-2表达,分泌期时Tie-2的表达,增殖期ER-α的表达均显著高于对照组(P<0.05或P<0.01).2组增殖期时Tie-2的表达,分泌期时ER-α的表达差别无统计学意义(P>0.05).Ang-2及Tie-2在2组中的表达均是分泌期高于增殖期,ER-α则是增殖期高于分泌期(P<0.05).结论:内异症在位内膜分泌期的Ang-2和Tie-2及增殖期ER-α高表达可能与内异症的发病有密切关系.     

子宫内膜异位症患者腹腔液中血管内皮生长因子、卵巢癌抗原水平的变化及临床意义

目的 观察子宫内膜异位症(endometriosis,EMS)腹腔液中血管内皮生长因子(vascular endothelial cell growth factor,VEGF)和卵巢癌抗原(CA125)水平变化情况,探讨其临床意义.方法 采用酶联免疫法和放射免疫法检测术后病理确诊的EMS 20例(EMS组)和同期手术的子宫肌瘤26例(对照组)腹腔液中VEGF和CA125水平.结果 EMS组腹腔液中VEGF和CA125水平均高于对照组(P＜0.05);EMS组增生期VEGF水平高于分泌期(P＜0.05),CA125水平无周期性变化(P＞0.05);对照组VEGF和CA125水平均无周期性变化(P＞0.05);增生期VEGF和CA125水平EMS组均显著高于对照组(P<0.01);分泌期VEGF和CA125水平两组比较差异均无统计学意义(P＞0.05).结论 EMS腹腔液中VEGF和CA125水平升高,与EMS的发生发展密切相关.     

内异症患者皮质醇与受体、应激指标的相关性研究

目的研究子宫内膜异位症患者血浆皮质醇浓度与外周血淋巴细胞糖皮质激素受体(GR)表达的相互关系,探究慢性应激在内异症疾病的发生发展中的作用。方法对89例子宫内膜异位囊肿患者(内异症组)和92例卵巢成熟囊性畸胎瘤患者(对照组)分别测定其血浆皮质醇含量和淋巴细胞内GR表达情况。术前两组均完成压力知觉量表调查问卷,评估患者感知压力水平。结果内异症患者血浆皮质醇含量显著低于对照组,内异症患者淋巴细胞内的GR含量则较对照组明显增高,血浆皮质醇含量与GR表达呈负相关性。内异症组感知压力水平得分高于对照组(P <0.05)。结论内异症患者血浆皮质醇水平与GR存在对应关系,感知压力水平增高。内异症患者的免疫状态及慢性应激与病情密切相关。     

可溶性血管细胞粘附因子-1在子宫内膜异位症患者血清中的变化及意义

目的　探讨子宫内膜异位症 (内异症 )患者血清中可溶性血管细胞粘附因子 1(sVCAM 1)水平的变化及意义。方法　采用酶联免疫吸附法 (ELISA)检测 15例内异症及 15例对照组患者血清sVCAM 1水平。结果　①内异症组与对照组血清sVCAM 1水平相比差异有显著意义 (P <0 0 1)。②内异症Ⅰ～Ⅱ期患者与Ⅲ～Ⅳ期患者血清sVCAM 1水平之间差异有显著意义 ,而内异症组与对照组相比患者增殖期及分泌期血清sVCAM 1差异无显著意义。结论　可溶性血管细胞粘附因子 1(sVCAM 1)在子宫内膜异位症的发病中有一定作用。     

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.