乳腺癌患者血清胰岛素样生长因子-1及结合蛋白-3的变化及意义

目的探讨乳腺癌患者血清胰岛素样生长因子-1（IGF-1）、胰岛素样生长因子结合蛋白-3（IGFBP-3）和两者比率的变化及临床意义。方法80例良性乳腺肿瘤和135例乳腺癌患者术前采集空腹血分离血清-30℃冻存，用ELISA法测定标本的IGF-1和IFGBP-3浓度，用免疫组化法检测乳腺癌标本nm23基因。结果乳腺癌和良性乳腺肿瘤两组间IGF-1浓度和IGF-1：IFGBP-3呈高度显著差异（P〈0．01）．而IGFBP-3差异无显著意义（P〉0．05）。乳腺癌患者绝经前后IGF-1差异有显著意义（P=0．04），绝经前或有淋巴结转移的乳腺癌患者IGF-1：IGFBP-3明显高于绝经后或无淋巴结转移的乳腺癌患者。nm23阳性和阴性的乳腺癌之间血清IFGBP-3浓度差异有显著意义（P=0．01），但IGF-1浓度差异无显著意义。结论检测血清IGF-1、IGFBP-3有助于筛选和确定乳腺癌高危患者，从而有利于早期诊断及判断预后。     

小于胎龄儿血清IGF-1、IGFBP-3检测的临床意义（附26例分析）

目的探讨小于胎龄儿血清胰岛素样生长因子-1（IGF-1）、胰岛素样生长因子结合蛋白-3（IGFBP-3）检测的临床意义。方法46例新生儿分成小于胎龄（SGA）儿26例（A组）;适于胎龄（AGA）儿20例（B组）,新生儿均于生后3天内抽取股静脉血,采用放射免疫法检测血清IGF-1、IGFBP-3。结果A组血清IGF-1、IGFBP-3浓度明显低于B组,差异有统计学意义（分别P〈0．01和P〈0．05）。结论小于胎龄儿生后3天内IGF-1、IGFBP-3仍呈低水平。     

糖尿病视网膜病变血清IgG型抗内皮细胞抗体检测

目的：探讨血清IgG型抗内皮细胞抗体（AECA）的阳性表达及其在不同分型糖尿病视网膜病变（DR）间的变化趋势。方法：根据荧光素眼底血管造影（FFA）将糖尿病视网膜病变患者分为增殖型糖尿病视网膜病变（PDR）组、背景型糖尿病视网膜病变（BDR）组、糖尿病无视网膜病变（NDR）组及正常对照组。用体外培养的人脐静脉内皮细胞（HUVEC）作为抗原，采用间接免疫荧光（IIF）法检测不同分型患者血清IgG型抗内皮细胞抗体阳性率的变化，并与正常对照组进行对比。结果：血清IgG型AECA阳性表达BDR组和PDR组均高于NDR组和正常对照组（P〈0．05），而BDR组和PDR组间阳性率差别无统计学意义（P〉0．05），NDR组和正常对照组间阳性率差别无统计学意义（P〉0．05）。结论：随着由正常眼底向DR的转变，血清IgG型AECA阳性率呈增高趋势，表明AECA与DR存在内在关联。     

糖尿病视网膜病变患者血清PlGF和VEGF水平的变化及其临床意义

目的探讨糖尿病视网膜病变（DR）患者血清胎盘生长因子（P1GF）水平的变化及其临床意义。方法采用ELISA法检测51例DR患者血清P1GF和VEGF的变化,其中,非增生性DR（NPDR）22例,增生性DR（PDR）29例。并与54例非糖尿病视网膜病变（NDR）患者进行比较,同时以40例健康者作为对照。结果DR患者血清P1GF和VEGF水平明显高于对照组（t值分别为1．907和2．942,P〈0．05）;PDR患者P1GF和VEGF水平明显高于NPDR患者（t值分别为19．024和16．319,P〈0．05）。结论血清P1GF和VEGF水平变化参与了DR的发生与发展,且与病变严重程度有关。     

2型糖尿病视网膜病变血清相关因素分析

目的探讨2型糖尿病血清中生化指标水平（Serum biochemical indexes）与糖尿病视网膜病变（DR）发生发展之间的关系。方法 88例2型糖尿病患者按照糖尿病视网膜病变分级标准,再将其分为3个亚组,30例健康者为对照组,免疫抑制比浊法测定糖化血红蛋白,记录相关的临床和生化指标。结果视网膜病变组患者血清Hb A1c水平,显著高于对照组（P〈0.01）;增生性糖尿病视网膜病变组（PDR组）血清Hb A1c水平、非增生性糖尿病视网膜病变组（BDR组）血清Hb A1c水平显著高于无糖尿病视网膜病变组（NDR组）（P〈0.01）。DR组血清FPG水平高于对照组,差异有统计学意义（P〈0.05）;PDR组血清FPG水平、BDR组血清FPG水平显著高于NDR组（P〈0.01）。DR的严重程度与Hb A1c、FPG、d BP成正相关。结论 2型糖尿病Hb A1c、FPG水平增高与DR的发生、发展密切相关。     

多囊卵巢综合征早期自然流产患者IGFBP-1水平测定及临床意义

目的探讨胰岛素样生长因子结合蛋白1（IGFBP-1）在多囊卵巢综合征（polycysticovarysyn—drome,PCOS）早期自然流产患者中的表达及临床意义。方法选择妊娠〈12周的PCOS流产患者77例为试验组,同期正常妊娠〈12周要求人工流产者68例为对照组。2组均于孕3～5周、孕6～8周和孕9～11周采用酶联免疫吸附法（enzyme—linkedimmunosorbentassay,ELISA）检测早期外周静脉血中IGFBP-1、IGF-1、人性激素结合球蛋白（SHBG）、空腹胰岛素、空腹血糖、睾酮和游离睾酮,同时采用流式细胞术检测蜕膜组织中IGFBP-1和IGF-1的表达。结果试验纽孕3～5周和孕9—11周空腹血清胰岛素水平及孕3～5周空腹血糖显著高于对照组（P〈0．01）,但孕6—8周血清胰岛素水平及孕6—8周和孕9～11周空腹血糖与对照组比较差异无统计学意义（P〉0．05）。不同孕周试验组睾酮和游离睾酮均显著高于对照组（P〈0．01）,IGFBP．1和SHBG水平显著低于对照组（P〈0．05或〈0．01）,IGF．1水平与对照组比较差异无统计学意义（P〉0．05）。以B—actin作为内参照,试验组不同孕周蜕膜组织中IGFBP—l蛋白的表达显著低于对照组（P〈0．05）,而IGF-1蛋白的表达显著高于对照组（P〈0．05）。结论PCOS早期自然流产患者血清中IGFBP-1、SHBG水平降低以及流产蜕膜组织中IGFBP-1、IGF-1蛋白表达的减少,提示子宫内膜上皮及间质功能障碍可能是PCOS患者发生流产的重要环节。     

可溶性血管细胞黏附分子-1与2型糖尿病视网膜病变的相关性研究

目的研究2型糖尿病视网膜病变患者血清可溶性血管细胞黏附分子-1（sVCAM-1）水平的变化与糖尿病病程、视网膜病变程度、糖化血红蛋白、胰岛索、血糖及血脂之间的相关性。方法选取2型糖尿病不伴视网膜病变患者[无视网膜病变组（NDR）]20例、2型糖尿病伴背景型视网膜病变患者[背景型视网膜病变组（BDrt）]20例、2型糖尿病伴增殖型视网膜病变患者[增殖型视网膜病变组（PDR）]20例和健康体检（健康组）20例作为健康对照组。应用酶联免疫吸附法（ELISA）测定各组受试者血清sVCAM-1水平,微柱法测定HbAle,放免法测定空腹INS,同时测定FBG、血脂等,并收集糖尿病患者的病程、糖化血红蛋白、胰岛素、直糖、血脂资料,采用单因素方差分析、SNK-q检验和Pearson相关分析比较各组间sVCAM-1水平,sVCAM-1水平与各代谢指标间的相关性。结果PDR组、BDR组和NDR组患者的血清中sVCAM-1的浓度明显增高,与健康对照组比较差异均有统计学意义（均P〈0．001）;PDR组患者血清sVCAM-1的增高较BDR组、NDR组增高明显,差异均有统计学意义（均P〈0．001）;BDR组与NDR组患者血清sVCAM-1浓度相比较差异均无统计学意义（P〉0．05）。糖尿病患者血清sVCAM．1与病程呈正相关（r=0．338,P〈0．05）,与HbAlc、FBG、CHO、TG、LDL、空腹INS均无相关关系。结论糖尿病视网膜病变不同时期血清sVCAM-1水平有不同程度的增高,提示sVCAM-1在视网膜病变的发生发展中起重要作用,并可能成为监测视网膜病变病情变化的有效指标之一。     

2型糖尿病患者脂联素与视网膜病变的相关性研究

目的研究2型糖尿病（T2DM）患者血浆脂联素（APN）水平及脂联素基因启动子区-11377位点单核苷酸多态性（SNP）与糖尿病视网膜病变（DR）之间的关系。方法运用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术,对200例T2DM患者[无DR（NDR）组82例、非增殖型DR（NP-DR）组72例、增殖型DR（PDR）组46例],检测APN基因启动子SNP-11377C→G多态性,同时检测血浆APN浓度、血脂、血糖、空腹胰岛素,比较各组基因型和等位基因频率,并分析各指标间的相关性。结果①APN水平随视网膜病变程度呈递增趋势NDR、NPDR、PDR各分别为（6.11±2.77）,（7.49±3.84）,（9.83±4.97）mg/L,其中PDR组显著高于NDR和NPDR组（P〈0.01）,NPDR组显著高于NDR组（P〈0.05）;②APN水平与HOMA-IR呈负相关（r=-0.203,P〈0.01）;③APN基因启动子SNP-11377C→G的基因型和等位基因频率分布在NDR组、DR组间差异无统计学意义（P〉0.05）。基因型（CC型、CG型和GG型）的血清APN水平差异无统计学意义（P〉0.05）。结论T2DM患者血APN水平随糖尿病视网膜病变进展而增高。未发现福建地区T2DM患者APN基因启动子区-11377C→G多态性与DR明显相关。     

前列腺癌患者血清IGF-Ⅱ水平表达及临床意义

目的：检测前列腺癌（PCA）患者血清胰岛素生长因子-Ⅱ（IGF-Ⅱ）的水平变化,探讨其与肿瘤的分级、分期的关系。方法：采用酶联免疫法（ELISA）测定45例前列腺癌（PCA）患者血清IGF-Ⅱ和前列腺特异性抗原（PSA）水平,并以32例良性前列腺增生（BPH）作对照。结果：PCA组血清IGF-Ⅱ（768．75±65．84）ng／ml高于BPH组（P〈O．01）。Ⅲ期＋Ⅳ期PCA血清IGF-Ⅱ（879．73±58．25）ng／m]高于I期＋Ⅱ期（P〈O．05）。G3-4级患者IGF-I水平（785．46±77．29）ng／ml高于G1＋G2（P〈0．05）。结论：血清IGF-Ⅱ与前列腺癌的临床分期和病理分级有关,其检测对术前前列腺癌恶性程度评价和筛选中晚期前列癌患者有一定意义。     

2型糖尿病视网膜病变患者脂联素和高敏C反应蛋白水平及其相关性研究

目的探讨糖尿病视网膜病变（DR）患者血清脂联素和高敏c反应蛋白（hs—CRP）的浓度变化及其相关关系。方法120例2型糖尿病DR患者依据DR眼底病变分为单纯型DR组（SDR组）、增殖型DR组（PDR组）和非DR（NDR）的糖尿病组（NDR组）,各40例。采用酶联免疫吸附测定法和散射速率比浊法检测各组受试者血清脂联素和hs-CRP浓度的变化,并与NDR组及40例正常对照者（正常对照组）进行比较。结果SDR组和PDR组患者血清脂联素浓度明显低于正常对照组和NDR组[（0．46±0．21）、（0．31±0．13）pg／L比（0．91±0．51）、（0．89±0．48）pg／L],hs—CRP浓度明显高于正常对照组和NDR组[（3．9±1．0）、（5．5±2．2）pg／L比（1．7±0．4）、（2．0±0．6）pg／L],差异均有统计学意义（P〈0．01）,PDR组患者血清脂联素浓度明显低于SDR组患者,hs-CRP浓度明显高于SDR组患者,差异均有统计学意义（均P〈0．05）。DR患者血清脂联素与hs·CRP浓度呈负相关（r=-0．543,P〈0．01）。结论血清脂联素和hs—CRP参与DR的发生与发展,且与病情严重程度有关。     

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.