原发胃癌恶性表型与患者自发淋巴细胞微核形成的关系

目的 探讨淋巴细胞微核形成与胃癌恶性度的关系.方法 术前取外周血采用体内微核实验方法检测130例胃癌患者(胃癌组)、13例良性胃肠病变(良性病变组)及59例正常人(对照组)淋巴细胞微核率(MNF).结果 胃癌组淋巴细胞MNF为(1.93±0.93)‰,明显高于良性病变组的(0.62士0.49)‰和对照组的(0.51±0.45)‰(P＜0.01);MNF随着胃癌组分化度降低及淋巴结转移率的增加而逐渐上升(P＜0.01).结论 淋巴细胞微核形成与胃癌恶性度密切相关,为胃癌患者的术前恶性度的判断和高危人群筛查提供了一个有用的生物学标志物.     

安多霖对肿瘤放疗患者辐射损伤高微核率的预防作用

目的 研究在放射治疗过程中同时使用安多霖胶囊，观察其对放疗导致的辐射损伤高微核率的预防作用。方法 对65例经病理证实首程治疗的鼻咽癌患者进行前瞻性随机分组研究。在接爱放疗的同时配合口服安多霖（治疗组）或参芪片（对照组），于疗前及放疗中（30GY）分别检测外周血淋巴细胞微核值（MNF），观察两组MNF值的变化。结果 疗前两组MNF值相似（P＞0.10），有可比性。用药治疗组MNF值明显低于对照组，且上升幅度也明显低于对照组，有非常显著差异（P＜0.01）。结论 安多霖对放疗所导致的辐射损伤高微核率有预防或减轻作用，在保证肿瘤放疗患者的生活质量方面有一定的临床价值。     

放射工作人员外周血淋巴细胞微核分析

目的 对425名放射工作人员进行微核率的观察.方法 微核测定采用常规培养法,判断标准依据.结果 观察组与对照组的微核细胞率和微核率分别为1.07‰和1.11‰及O.40‰和0.42‰,两组比较差异有统计学意叉,P<0.01.结论 淋巴细胞微核率是评价放射工作人员所受辐射损伤的一项非常有意叉的指标.     

肝癌患者一级亲属微核率的调查

本文报告应用微核技术,研究肝癌患者及其一级亲属的外周淋巴细胞(PBL)微核出现率。结果表明,肝癌患者组自发微核率显著高于肝癌患者一级亲属组(P<0.001);肝癌患者一级亲属组自发微核率显著高于对照组(P<0.001)。提示肝癌患者一级亲属是一组肝癌高危人群,具有遗传易感性。     

极低频电磁场对小鼠血细胞影响的实验研究

目的:观察不同照度极低频电磁场对小鼠血细胞成分的影响及淋巴细胞微核发生的关系.方法:将100只小鼠随机分为对照组和曝磁组.曝磁组小鼠分1、2、3和4四组,分别置于微机产生的极低频电磁场中,每天照射分别为20min、40min、60min、6h,对照组不接触极低频电磁场,4个月后检测各组小鼠外周血血细胞计数和淋巴细胞微核率.结果:随小鼠每天曝磁时间的增加,其血液中的RBC、WBC、PLT数量及Hb含量呈逐渐下降、淋巴细胞微核率呈逐渐增高的趋势, 中性粒细胞、嗜酸性粒细胞、单核细胞比值逐渐增高,淋巴细胞比值逐渐下降,以曝磁4组表现最为显著.RBC、Hb数量和淋巴细胞微核率与对照组结果之间存在显著性差异(P＜0.05或P＜0.01).结论:长时间接触极低频电磁场对小鼠血细胞数量和不同WBC比值存在明显的影响, 同时可诱发淋巴细胞微核的发生.     

大肠癌淋巴结转移56例临床病理分析

目的分析大肠癌淋巴结转移相关临床病理因素。方法以2014年1~8月收治的大肠癌患者56例为调查研究对象,分析大肠癌淋巴结转移的相关临床病理因素。结果大肠癌淋巴结转移与性别及肿瘤位置无关,与肿瘤大小、分化程度、浸润深度以及术前癌胚抗原状况存在明显的关系,差异有统计学意义(P<0.05)。结论大肠癌淋巴结转移明显跟患者的年龄大小、肿瘤的大小、分化程度的高低以及浸润的实际深度存在明显的联系。     

大黄素-8-O-β-D-葡萄糖苷的体内外遗传毒性评价

目的:评价大黄素-8-O-β-D-葡萄糖苷(EG)的体内外遗传毒性,并比较体外细胞试验及大鼠体内实验评价结果的差异。方法:采用体外二维(2D)、三维(3D)细胞培养法分别构建2D、3D HepaRG细胞模型,造模成功后,分别将2D、3D HepaRG细胞分为空白对照组[0.5%二甲基亚砜(DMSO)]、丝裂霉素C组(阳性对照,0.1μg/mL)和EG低、中、高剂量组(10、50、200μg/mL),然后检测各组HepaRG细胞的微核形成率和尾DNA百分含量。将SD大鼠分为空白对照组(0.5%羧甲基纤维素钠)、甲磺酸乙酯组(阳性对照,200 mg/kg)和EG低、中、高剂量组(100、300、1 000 mg/kg),每组6只,连续灌胃给药15 d,每天1次;15 d后检测各组大鼠骨髓嗜多染红细胞、肝细胞的微核形成率及外周血淋巴细胞、肝细胞的尾DNA百分含量、尾距。结果:在体外2D HepaRG细胞模型中,与空白对照组比较,丝裂霉素C组HepaRG细胞的微核形成率和尾DNA百分含量均显著升高(P<0.01),EG各剂量组HepaRG细胞的微核形成率和尾DNA百分含量差异无统计学意义(P>0.05);在3D HepaRG细胞模型中,与空白对照组比较,丝裂霉素C组HepaRG细胞的微核形成率和尾DNA百分含量均显著升高(P<0.01或P<0.001),EG高剂量组HepaRG细胞的尾DNA百分含量显著升高(P<0.01)。在大鼠体内实验中,与空白对照组比较,甲磺酸乙酯组大鼠骨髓嗜多染红细胞、肝细胞的微核形成率和外周血淋巴细胞、肝细胞的尾DNA百分含量、尾距均显著升高(P<0.01),EG高剂量组大鼠外周血淋巴细胞尾DNA百分含量显著升高(P<0.01),EG各剂量组大鼠骨髓嗜多染红细胞、肝细胞的微核形成率和肝细胞尾DNA百分含量、尾距差异无统计学意义(P>0.05),但随剂量增加有升高趋势。结论:本研究结果提示在2D细胞模型中,EG未导致染色体断裂及DNA损伤,但3D细胞模型长期给药和体内重复给药结果均显示EG存在一定DNA损伤风险,故3D HepaRG细胞模型的评价结果更接近大鼠体内实验结果。     

大肠癌患者血清IL-8水平检测及其临床意义分析

目的 分析大肠癌患者血清IL-8水平检测及其临床意义.方法 将我院110例大肠癌患者根据治疗前后分别抽血,进行血清IL-8水平检测,并根据大肠癌Dukes分期与临床病理分型进行对比分析.结果 我院110例大肠癌患者按Dukes分期治疗后血清IL-8水平A期与B期结果 均能将至正常水平,而C期与D期下降水平相对较慢.大肠癌患者肿瘤恶性程度高的血清IL-8水平越高,治疗后血清IL-8水平下降越慢.结论 大肠癌患者术前血清IL-8水平与Dukes 分期、肿瘤恶性程度、远处淋巴结转移及预后密切相关,这为提高大肠癌临床分期与恶性程度的准确性和综合判定患者的临床预后提供了可靠的依据.     

二甲基甲酰胺对接触工人外周血淋巴细胞微核率的影响

目的探讨二甲基甲酰胺(N,N-dimethylformamide,DMF)对接触工人外周血淋巴细胞微核率的影响。方法气相色谱法(GC-FID法)测定车间空气中的二甲基甲酰胺的浓度;气相色谱-质谱联用法(GC-MS法)测定接触者班后尿样中甲基甲酰胺(NMF)的含量;外周血淋巴细胞微核试验法检测接触工人外周血淋巴细胞微核率。结果接触DMF的作业工人外周血淋巴细胞微核率与对照组相比有显著差异(方差分析,p<0.01).接触的作业工人的2～3年组、4～5年组与6～7年组相比有显著性差异(p<0,01),2～3年组与4～5年组比,无统计学差异。结论长期接触DMF可引起遗传物质的损伤,且损伤程度随着接触年限的延长有加重的趋势。     

MRP与LRP在大肠癌组织中的表达及临床意义

目的 探讨多药耐药相关蛋白（MRP）与肺耐药相关蛋白（LRP）在大肠癌组织中的表达特点及临床意义.方法 采集山西大同大学附属医院2008年至2013年收治的大肠癌患者共计58例,留取手术切除的新鲜癌组织制成蜡块儿.同时收集30例正常大肠组织的标本.采用免疫组化的方法检测MRP与LRP在大肠癌组织中以及正常大肠黏膜组织中的表达情况.同时检测其表达与肿瘤细胞分化程度及淋巴结转移的关系.结果 MRP与LRP在大肠癌组织中的表达均明显高于正常大肠组织（P＜0.01）.在不同分化程度的大肠癌中,MRP与LRP的表达水平不同,其中高分化腺癌组与中分化、低分化腺癌组比较均有统计学意义（P＜0.05）;中分化与低分化腺癌组比较无统计学意义（P＞0.05）.在伴有淋巴结转移的大肠癌组织中MRP与LRP的阳性表达率均较不伴有淋巴结转移者为高（P＜0.05）.结论 MRP与LRP均在大肠癌组织中有一定程度的表达,且与其肿瘤细胞分化程度、淋巴结转移情况相关.     

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.