生物陶瓷微颗粒引发的细胞和组织损害

为论证生物陶瓷烧结不完全形成的微颗粒（〈5μm）引发细胞和组织损害的假设，对该类颗粒在体内和体外的细胞和组织损害进行了研究：（1）对4种双相生物陶瓷（BCP）进行细胞毒性试验。试验发现所有的浸出液出现细胞毒性，但是浸出液经离心后，毒性消失；（2）对羟基磷灰石（HA）、p磷酸三钙（pTCP）和40％pTCP／60％HA混合物微颗粒进行细胞抑制实验。结果显示随着微颗粒的浓度增加，成纤维细胞活力下降；而当微颗粒浓度达到一万个／细胞时，细胞活力和增殖能力完全消失；（3）HA，pTCP和BCP陶瓷颗粒（500-1500um）被植入到兔子股骨远端，种植12周后β-TCP的降解率为40％，BCP为5％，但是HA接近不降解。新骨形成在β-TCP（21％）和HA（18％）比BCP（12％）更为明显。同时BCP颗粒的周围有很多的微颗粒形成，可见吞噬细胞吞噬微颗粒，形成吞噬体。以上结果提示，微颗粒可能是局部炎症和细胞损害的首要原因，而且有可能影响骨形成。因此，我们必须注意生物陶瓷烧结的重要性，它们的烧结不良就可形成微颗粒，引发细胞和组织的损害。特别是BCP陶瓷含有两种需要不同烧结温度的粉体，它的烧结难度较高，很易形成微颗粒。     

Serum and tissue trace elements in Iranian camels (Camelus dromedarius)

There were 26 male and female (nonpregnant and nonlactating) apparently healthy adult (5 to 10 years) field camels (Camelus dromedarius) studied to provide data regarding the normal values of trace elements in serum and different tissues. Blood samples were collected by jugular venepuncture and serum was separated by centrifugation. Tissue samples (liver, heart, striated muscle, spleen, kidney, and hair) were collected during postmortem examinations. All the samples were digested and analyzed for copper, iron, cobalt, and molybdenum using atomic absorption spectrophotometry. The results showed that the highest concentration of iron was present in the spleen and that the concentrations of this element in the liver and kidney were higher than those in the heart, striated muscle, serum, and hair (p<0.05). The lowest mean iron concentration was observed in the serum (p<0.05). The mean copper concentration was highest in liver in comparison to other tissues (p<0.05). No significant differences in cobalt concentrations were detected among different compartments. The mean molybdenum concentration of striated muscle, heart, kidney, spleen, and liver were significantly higher than those of serum and hair (p<0.05). No difference due to sex was detected in different tissue and serum concentrations of trace elements.     

Lead in blood and tissues of mice after administration of low lead doses

Lead levels in whole blood could be determined reliably up to a lower limit of 2 g/100 ml blood, using a modified micromethod of the graphite tube furnace technique. Lead contents of various tissues were also determined by using the automated graphite tube furnace after wet ashing of the organs with nitric acid in autoclaves.Animal experiments with mice showed no measurable increase in blood lead level after a single, 10- or 30-days oral administration of lead in doses of 10–1000 g lead acetate/kg body weight/day. However, these doses led to a rise in tissue lead content. There was a clear dependence of tissue lead content on type of organ examined, lead dose and duration of lead exposure.According to our experiments, the threshold dose which leads to a long-term increase in tissue lead content is assumed to be about 100 g lead acetate/kg body weight/day, orally administered.We are thankful to Prof. Dr. H. Rüssel, Hannover and Dr. M. Fleischer, Saarbrücken for helping in comparison studies.We would also like to thank Mr. H. Dick and Miss. Ch. Hecker for the technical and laboratory assistance.     

微 RNA-21和微 RNA-146a 在结直肠肿瘤中的表达及临床意义

目的探讨结直肠肿瘤患者组织和血清中 miRNA-21和 miRNA-146a 的表达情况,并分析其临床意义。方法收集100例结直肠癌、80例结直肠腺瘤患者和65名健康对照者的内镜活检组织,同时收集其血清标本,应用实时荧光定量 PCR 检测 miRNA-21和 miRNA-146a 的表达水平,分析其表达与临床病理特征间的关系,并评估血清差异表达的 miRNA 在结直肠肿瘤诊断中的价值。组间比较采用 Mann-WhitneyU 检验和 Kruskal-Wallis 检验;Spearman 相关性检验用于分析组织和血清中 miRNA 表达的关联性。结果在结直肠癌和结直肠腺瘤患者病变组织中 miRNA-21的表达分别为8．573±0．898和7．746±1．183,显著高于健康对照者的6．160±0．835（U ＝120．129、33．230,P 均＜0．01）;在结直肠癌和结直肠腺瘤患者血清中的表达分别为1．829±0．303和1．624±0．226,也高于健康对照者的1．391±0．221（U ＝40．353、15．512,P 均＜0．01）;miRNA-21在结直肠癌患者组织中和血清中的表达均高于结直肠腺瘤患者（U＝11．384、10．189,P 均＜0．01）。miRNA-21在结直肠癌患者中的高表达与肿瘤临床分期、淋巴结转移有关;miRNA-21在结直肠腺瘤中的表达水平与病理类型有关。Spearman 分析结果示,miRNA-21在结直肠癌患者组织和血清中的表达呈正相关（r ＝0．459,P ＜0．01）。miRNA-146a 在结直肠癌患者组织中为2．556±0．351,血清中为0．249±0．038,低于健康对照者的3．428±0．328和0．279±0．053（U ＝102．134、30．111,P 均＜0．01）;其在结直肠腺瘤患者组织中为3．255±0．332,血清中为0．290±0．036,与健康对照者比较差异无统计学意义（U＝3．936、3．180,P 均＞0．05）。miRNA-146a 在结直肠癌患者组织中和血清中的表达均低于结直肠腺瘤患者（U＝73．809、21．123,P 均＜0．01）。结直肠癌患者miRNA-146a 的下降程度与肿瘤临床分期、肿瘤分化程度有关,而在结直肠腺瘤中的表达与临床特征间无明显关系。根据 ROC 曲线分析,鉴别结直肠癌与健康者,血清 miRNA-21、miRNA-146a 及二者联合检测 ROC 的 AUC 分别为0．889、0．791和0．863;鉴别结直肠腺瘤与健康者,其 AUC 分别为0．784、0．692和0．761;鉴别结直肠癌与结直肠腺瘤患者,其 AUC 分别为0．705、0．820和0．713。结论血清 miRNA-21和 miRNA-146a 的差异表达在结直肠癌的早期诊断中具有潜在的价值。     

甲苯二异氰酸酯氧化损伤作用机制的研究

研究了在不同浓度下甲苯二异氰酸（TDI）对小鼠脂质过氧化物及有关酶活性影响。用分光光度法检测了小鼠血、肺和肝中MDA及GSH含量和SOD活性变化的变化，为阐明甲苯二异氰酸酯对小鼠组织损害机制提供实验依据。在1／2LC50、1／4LC50染毒组中MDA含量明显上升，SOD活性明显下降，GSH含量有所降低。对比雌雄差异，雌鼠在1／8LC50、1／4LC50染毒组中低剂量组受氧化损伤程度低于雄鼠，1／2LC50染毒组中雌鼠和雄鼠受氧化损伤程度的性别差异并不十分显著。     

BRCA2在散发性乳腺癌组织中的表达及意义

目的:探讨乳腺癌易感基因2(BRCA2)在散发性乳腺癌组织中的表达及意义,了解BRCA2蛋白的表达与雌激素受体(ER)、孕激素受体(PR)及原癌基因C-erbB-2之间的相关性。方法:采用免疫组化法(SABC)对32例乳腺癌患者癌组织、癌旁组织及正常乳腺组织中BRCA2、C-erbB-2、ER、PR蛋白的表达进行检测并结合年龄、病理组织学分级、腋淋巴结转移情况进行相关性分析。结果:BRCA2在乳腺癌组织中表达的阳性率为56%,而在癌旁及正常乳腺组织中无阳性表达(P<0.05)。BRCA2蛋白的表达在乳腺癌不同组织学分级中有差异(r=0.372 8,P<0.05);与腋下淋巴结转移之间比较差异有显著性(r=0.362 2,P<0.05),但与发病年龄、ER、PR、C-erbB-2表达之间未见相关性。结论:BRCA2蛋白的表达与组织学分级高、腋淋巴结转移相关。BRCA2蛋白的检测有可能成为评估乳腺癌生物学行为和预后的新指标。     

Pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers in rats by HPLC

The differences in pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers were investigated in rats. In high-performance liquid chromatographic method, an achiral ODS column (150 mm x 4.6 mm i.d.) with the mobile phase consisting of methanol-water (73:30, v/v) was used for the determination of the concentration for racemic verapamil, and a Chiralcel OJ column (250 mmx4.6 mm i.d.) with the mixture of n-haxane-ethanol-triethylamine (85:15:0.2, v/v/v) as mobile phase was used to determine the concentrations of verapamil enantiomers. A fluorescence detector in the analytical system was set at excitation and emission wavelengths of 275 nm and 315 nm. The differences between enantiomers were apparent in the pharmacokinetics in rats. The area under the concentration-time curve (AUC) of S-(-) verapamil was higher than that of R-(+) verapamil. The half-distribution time (T 1/2(alpha)) of S-(-) verapamil which distributing to tissue from blood was shorter than that of R-(+) verapamil, but the elimination half-time (T 1/2(beta)) was longer in rat following oral administration of racemic verapamil. At 1.3 h after oral administration of racemic verapamil, however, there were no significant differences between enantiomers for the distributions in major tissues such as heart, cerebrum, cerebellum, liver, spleen and kidney.     

成纤维细胞生长因子对组织损伤保护作用的研究进展

成纤维细胞生长因子(FGF)在体内分布广泛,对中胚层和神经外胚层来源的组织细胞具有促进分裂增殖和损伤修复的作用。目前已发现的有24种,外源性的aFGF、bFGF、MaFGF是目前应用研究的主要形式,它们通过与组织细胞的表面受体结合,抑制脂质过氧化,拮抗自由基损伤,稳定细胞酶活性,在心血管、肾、神经及肠等器官的机械性或药物性损伤方面发挥保护作用。这提示FGF在组织损伤保护作用方面将有广阔的临床应用前景。     

Direct analysis of genetic variability in Trypanosoma cruzi populations from tissues of Colombian chagasic patients

The clinical symptoms of Chagas disease are highly variable and are correlated with geographical distribution and parasite genetic group. Trypanosoma cruzi group I is associated with chagasic cardiomyopathy in Colombia and other countries in northern South America. However, in southern South America, T cruzi group II predominates and is associated with cardiomyopathy and digestive forms of the disease. The aim of this work was to determine the correlation between the genetic profiles of T cruzi groups circulating in the biological cycle and those present in tissues from patients with Chagas disease. We genotyped T cruzi in 10 heart tissue samples from patients with cardiomyopathy from a highly endemic area of Colombia. The genotyping was performed using nuclear and mitochondrial genes and low-stringency single-specific primer polymerase chain reaction. As expected, the predominant genetic group was T cruzi group I; however, we also detected T cruzi group II. Microsatellite analyses suggested a predominance of monoclonal populations, and sequence alignments showed similarities with Colombian strains. In addition, kinetoplast DNA signatures obtained by low-stringency single-specific primer polymerase chain reaction allowed us to group strains into the 2 genetic groups. Thus, we conclude that both T cruzi genetic groups are producing severe cases of Chagas disease in Colombia. We did not observe any correlation between low-stringency single-specific primer polymerase chain reaction profiles, histopathologic findings, clinical forms, and severity of Chagas disease.     

子宫颈癌患者血清及组织中尿激酶型纤溶酶原激活物受体检测及其临床意义

 目的　探讨子宫颈癌血清与组织尿激酶型纤溶酶原激活物受体（uPAR）与患者病理特征的关系及其临床意义。方法　免疫组织化学染色（SABC法）检测50例子宫颈癌组织与正常子宫组织 uPAR表达;酶联免疫吸附测定（ELISA）法检测68例子宫颈癌组织及血清uPAR水平。结果　50例子宫颈癌组织中33例uPAR表达,阳性表达率66 %,正常组织无表达。子宫颈癌组织uPAR[（70.92±28.55）ng／100 mg蛋白]、血清uPAR[（2.38±0.29）ng／ml]高于癌旁组织[（11.01±5.40）ng／100 mg蛋白]、对照组[（0.50±0.16）ng／ml]（均P＜0.001）; 组织uPAR水平与患者临床分级、淋巴结转移及分化程度相关,而与肿瘤浸润、癌栓形成无关。术前子宫颈癌患者血清uPAR水平与临床分级、淋巴结转移、癌栓、浸润深度有关（P＜0.05～P＜0.01）;与分化程度无关。多元逐步回归分析提示,影响术前血清uPAR的因素是临床分期、盆腔淋巴结转移、肌层侵犯深度（均P＝0.001）。与术前比较,术后子宫颈癌患者血清uPAR水平下降,差异有统计学意义（P＜0.001）。血清与组织uPAR含量呈正相关（r＝0.801,P＜0.001）。结论　uPAR在子宫颈癌组织及血清中高表达,血清uPAR与患者临床分级、盆腔淋巴结转移及肿瘤浸润有关,可作为子宫颈癌诊断、病情检测及预后评判的一项标志物。