Effects of mycophenolic acid on IL-6 expression of human renal proximal and distal tubular cells in vitro.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine which regulates immune responses and host defence mechanisms. IL-6 has been found to be increased in certain inflammatory conditions of the kidney, in which tubular epithelial cells play a pivotal role. Human renal tubular cells express IL-6. Until now no data about the effect of the immunosuppressant drug mycophenolic acid (MPA) on IL-6 expression were available. METHODS: Proximal and distal tubular epithelial cells (PTC/DTC) have been isolated immunomagnetically. Confluent monolayers were stimulated with interleukin-1beta (IL-1beta; 25 U/ml), IL-1beta+ MPA (0.25-50 micro M) or MPA alone for 48 h. Release of IL-6 protein into the supernatant was evaluated with an enzyme immunoassay, IL-6 mRNA expression was evaluated using the Quantikine mRNA kit. RESULTS: After IL-1beta stimulation, a highly significant 2.6- (PTC) and 3.8-fold (DTC) upregulation of IL-6 expression was detectable. IL-6 mRNA was upregulated by IL-1beta [1.57- (PTC) and 2.03-fold (DTC)]. MPA inhibited this cytokine-induced IL-6 expression in a dose-dependent manner. Incubation with the lowest MPA concentration had no effect on the stimulated upregulation, whereas all higher doses significantly decreased IL-6 expression. Dexamethasone significantly inhibited the cytokine-induced IL-6 protein release in PTC, but not in DTC. CONCLUSIONS: In this study we demonstrated for the first time an inhibitory effect of MPA on the stimulated IL-6 expression of renal tubular epithelial cells. In contrast to older data, which showed a synergistic upregulation of the expression of a CC-chemokine by a combination of cytokines and MPA, in the present study we could demonstrate an immunosuppressive effect of MPA on the expression of an important cytokine.     

白细胞介素-6对椎间盘细胞中蛋白多糖代谢影响的实验研究

目的:研究白细胞介素-6(interleukin-6,IL-6)对椎间盘纤维环和髓核细胞中蛋白多糖代谢的影响。方法:自然流产的胎儿4例,4h内无菌取出椎间盘,分别进行纤维环和髓核细胞的体外培养。在纤维环细胞的培养液中分别加入IL-60(对照组)、400、800ng/ml,培养24h后,用Alcian法检测培养液中硫酸软骨素的含量。在培养中的髓核细胞中加入IL-60(对照组)、100、400、800ng/ml,培养24h,然后测量培养液中硫酸软骨素的含量。结果:在纤维环细胞中加入IL-6组较不加IL-6对照组培养液中硫酸软骨素的含量增加,在髓核细胞组中加入IL-6组和对照组的差别无显著性。结论:IL-6可以刺激椎间盘纤维环细胞中蛋白多糖的合成,但对髓核细胞中蛋白多糖的合成没有明显的作用。     

羊水粪染与羊膜腔感染的关系

【摘要】 目的 :探讨羊水粪染与羊膜腔感染的关系。方法 :选择未临产且胎膜完整的剖宫产产妇 5 6例 ,根据术中所见羊水性状分为羊水清亮组、羊水Ⅰ～II度粪染组和羊水III度粪染组。于剖宫产术中取羊水用双抗体夹心ELISA法测IL 6含量 ,取胎盘胎膜做病理检查以了解有无炎性细胞浸润 ,并记录新生儿Apgar评分 ,观察产妇术后有无产褥感染。结果 :3组羊水中IL 6含量差异无显著性 ,3组胎盘标本病理检查示炎性细胞浸润之差异亦无显著性 ,而羊水粪染组新生儿窒息发生率较清亮组明显增加 (P <0 .0 5 )。结论 :羊水粪染尤其是III度粪染是胎儿窘迫的标志 ,而与羊膜腔感染无明显相关性。     

FKBP6基因278C/A单核苷酸多态性与原发无精症相关研究

目的对FKBP6基因第3、4外显子进行突变和多态性筛查,研究第3外显子278C/A位点及第2内含子C/T位点(rs7797242)在无精症患者和正常男性中的多态性,初步探讨与原发无精症的相关性。方法采用变性高效液相色谱和聚合酶链反应-限制性片段长度多态性方法,对第3、4外显子进行突变和多态性筛查,对177例无精症患者和231名正常男性的278C/A和C/T(rs7797242)多态性进行基因分型。结果278C和278A等位基因频率符合Hardy-Weinberg平衡。无精症患者278A显著低于正常对照,差异有统计学意义(P<0.05)。C/T多态性在两组中均未检出,第3、4外显子未筛查到新的变异。结论278A等位基因可能与原发无精症相关。C/T(rs7797242)及370G/A,430G/C,467T/C,468G/A在中国人群中非常罕见。     

The electrophysiological properties of substantia nigra pars compacta neurones recorded from 6-hydroxydopamine lesioned guinea-pigs in vitro

Summary Intracellular recordings were made from substantia nigra pars compacta neurones in vitro from animals with partial unilateral 6-hydroxydopamine lesions of the nigrostriatal tract. Lesions were assessed and grouped according to the severity of the strital dopamine depletion. No differences were seen between neurones from control and lesioned side nigrae as regards their membrane properties, firing rates, burst activity or percentage of quiescent neurones in any of the lesioned categories. It is concluded that following partial lesioning, the remaining substantia nigra zona compacta neurones in vitro, are functioning normally.     

Identification of a Membrane Receptor for Retinol-Binding Protein Functioning in the Cellular Uptake of Retinal

Retinol-binding protein (RBP) is the transport protein that carries retinol in the circulation from the liver to its target tissues. The existence of a cell-surface receptor on the target cells, which mediates the uptake of retinol from RBP, has been known since 1975. Recently, it was identified as an integral transmem-brane protein named STRA6 that is inducible by retinoic acid in certain cancer cells. The receptor was found to be highly specific for RBP, with high affinity, and to be localized in all tissues known to require retinol for their function, particularly the pigment epithelium of the eye.     

血液透滤清除血清IL-6在重症急性胰腺炎治疗中的应用研究

目的探讨血液透滤清除IL-6在重症急性胰腺炎治疗中的作用及机理。方法根据诊断标准对2002年7月至2006年6月来我院就诊的178例重症急性胰腺炎患者随机分组：血滤组（HF组）85人,非血滤组（NHF组）93人。比较两组患者局部和全身表现,观察各时相点促炎细胞因子血清IL-6的测定值的差异。结果HF组与NHF组比较：腹痛腹胀持续时间为（18.8±4.2）hvs（89.7±28.1）h（P〈0.05）;治疗后第10天APACHEⅡ积分为（5.5±3.6）分vs（13.8±3.8）分（P〈0.05）;住院天数和医疗费为（28.2±12.4）天vs（42.4±11.2）天和（4.38±2.8）万元vs（7.46±2.2）万元,（P〈0.05）。治疗后各时相点血清IL-6检测结果：HF组较NHF组显著降低（P〈0.05）;MODS发病率和病死率分别为12.47%vs.36.28%和4.28%vs.12.82%,两者差异有统计学显著意义（P〈0.05）。结论早期短时血滤有利于纠正重症急性胰腺炎患者血清促炎细胞因子过度释放,使病情减轻,降低MODS发病率和病死率,提高疗效。     

CD44v6、P27蛋白在乳腺癌组织中的表达及意义

目的 探讨乳腺癌中CD44v6、p27蛋白表达的意义。方法 应用免疫组化S-P法检测65例乳腺癌中CD44v6、p27蛋白表达。结果 65例乳腺癌中CD44v6、p27蛋白表达总阳性率分别为58.4％、38.4％。CD44v6蛋白阳性表达率与乳腺癌组织学类型、腋淋巴结转移呈正相关(P<0.05,P<0.01),与预后呈负相关(P<0.01),与组织学分级无明显相关性(P>0.05);p27蛋白阳性表达与乳腺癌组织学类型、组织学分级及腋淋巴结转移呈负相关(P<0.05),与预后呈正相关(P<0.05)。结论 CD44v6、p27蛋白表达与乳腺癌浸润、转移及预后显著相关,检测乳腺癌中CD44v6、p27蛋白表达水平,对判断乳腺癌恶性程度、复发转移潜能,评估患者预后及术后选择合理治疗方案有一定参考价值。     

Role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation and the effect of bifidobacterial supplement on gut barrier function following burns

Early multiple organ dysfunction syndrome appears to be facilitated with bacterial translocation in severely burn injury, yet the mechanisms of bacterial translocation remains in dispute. The aim of this study was to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation following burns and the effects of bifidobacterial supplement on gut barrier. Methods: Wistar rats were randomly divided into burn group (Burn, n=60),sham burn group (SB, n=10) in experiment Ⅰ , and burn + saline group (BS, n=30), burn + bifidobacteria group (BB, n=30), and sham-burn + saline group (SS, n= 10) in experiment Ⅱ. Animals in BB group were fed bifidobacterial preparation (5 × 109 CFU/ml) after burns, 1.5ml,twice daily. Animals in BS and SS were fed saline. Samples were taken on days 1, 3, and 5 in burn groups, and on day 3 in sham-burn groups. The incidence of bacteria/endotoxin translocation and counts of Bifidobacterium, Fungi and Escherichia coli in gut mucosa were determined with standard methods. The levels of sIgA in mucus of small intestine were measured by RIA. The positive sIgA expression in lamina propria and ileum mucosal injury was evaluated light microscopically by blinded examiners. Results: Our results showed that the incidence of bacterial translocation was increased after burns, which was accompanied by significant decrease in number of bifidobacteria but significant increase in E. coli and fungi in gut mucosa, and elevation of levels of plasma endotoxin and IL-6 (P<0. 001).The incidence of bacterial translocation was markedly reduced after 3- and 5-day supplementation of bifidobacteria compared with control group (P<0.05). The counts of mucosal bifidobacteria were increased by 4- to 40-fold,while E. coli and fungi were decreased by 2- to 30-fold and 10- to 150-fold, respectively, after bifidobacterial supplementation in contrast to control group. The damage of mucosa tended to be less pronounced after 3-day bifidobacteria-supplemented formula compared with control group [grade 2(0-6) vs. grade 4(3-6), P<0.05]. Moreover, the expression and release of sIgA was markedly augmented after 3-day bifidobacteria-supplementation formula and it returned to normal range on day 5. Conclusion: The decrease in counts and proportion of bifidobacteria in mucous membrane flora may play an important role in the development of bacteria/endotoxin translocation following thermal injury. The supplement of exogenous bifidobacteria could per se improve gut barriers, and attenuate bacteria/endotoxin translocation secondary to major burns.     

The insulin-like growth factor-II/mannose-6-phosphate receptor: structure, distribution and function in the central nervous system

The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a multifunctional single transmembrane glycoprotein which, along with the cation-dependent M6P (CD-M6P) receptor, mediates the trafficking of M6P-containing lysosomal enzymes from the trans-Golgi network (TGN) to lysosomes. Cell surface IGF-II/M6P receptors also function in the degradation of the non-glycosylated IGF-II polypeptide hormone, as well as in the capture and activation/degradation of extracellular M6P-bearing ligands. In recent years, the multifaceted role of the receptor has become apparent, as several lines of evidence have indicated that in addition to its role in lysosomal enzyme trafficking, clearance and/or activation of a variety of growth factors and endocytosis-mediated degradation of IGF-II, the IGF-II/M6P receptor may also mediate transmembrane signal transduction in response to IGF-II binding under certain conditions. However, very little is known about the physiological significance of the receptor in the function of the central nervous system (CNS). This review aims to delineate what is currently known about IGF-II/M6P receptor structure, its ligand binding properties and role in lysosomal enzyme transport. It also summarizes the recent data regarding the role of the receptor in the CNS, including its distribution, possible importance for normal and activity-dependent functioning as well as its implications in neurodegenerative disorders such as Alzheimer's disease (AD).