Effects of tumour necrosis factor-alpha, interleukin-1 alpha, macrophage colony stimulating factor and transforming growth factor beta on trophoblastic matrix metalloproteinases.

The aim of this study was to determine the effects of tumour necrosis factor alpha (TNF), interleukin-1 alpha (IL-1alpha), macrophage colony-stimulating factor (MCSF) and transforming growth factor beta (TGFbeta) on the secretion of matrix metalloproteinases (MMP), human chorionic gonadotrophin (HCG) and fetal fibronectin (fFN) by purified first trimester cytotrophoblastic cells (CTB) in vitro. CTB were obtained from legal abortions and cultured in vitro in the presence or absence of the different cytokines. Secreted gelatinases were analysed in the culture supernatants by zymography, by measurements of the total gelatinolytic activity and by enzyme immunoassays. HCG and fFN were measured by commercially available immunoassays. TNF increased the total gelatinolytic activity by increasing MMP-9 activity (P = 0.025-0.0177) but decreased MMP-2 activity (P < 0.03) and immunoreactivity (P < 0.05), fFN (P < 0.02) and HCG (P < 0.01). IL-1alpha significantly increased the secretion of fFN (P < 0.02), the activity (P < 0.02) and immunoreactivity (P < 0.05) of MMP-9 but had no effect on the other parameters. MCSF increased MMP-9 immunoreactivity (P < 0.05) and moderately decreased HCG. TGFbeta inhibited total gelatinolytic activity, MMP-9 activity and immunoreactivity, but was without effect on MMP-2 concentrations and activity. TGFbeta decreased HCG (P < 0.041) and increased fFN (P < 0.042). Our results indicate that TGFbeta, TNF and IL-1alpha are important regulators of trophoblastic MMP secretion.     

OPTIGOV - A new methodology for evaluating Clinical Governance implementation by health providers

Background  

The aim of Clinical Governance (CG) is to the pursuit of quality in health care through the integration of all the activities impacting on the patient into a single strategy.     

Segmentation by single and combined features involves different contextual influences

Orientation discrimination of a texture line having orientation different from that of static background lines is facilitated when the lines are aligned along their orientation axis and when their separation is small (Experiment 1a). The facilitation by alignment remains when motion is added to the target (Experiment 1b). However, when the motion rather than the orientation has to be judged, alignment reduces sensitivity (d′) regardless of whether the target has orientation the same as (iso-oriented) or different from background elements (Experiment 2). The inhibitory effect of alignment is confirmed when subjects have to discriminate the motion direction of an iso-oriented target (Experiment 3). Such inhibition by alignment is stronger when elements are close and may reflect a property of lateral interactions of motion detectors, since it is only present when observers have to judge the target motion direction. Overall, our results indicate an opposite role of the lateral interactions that facilitate grouping of iso-oriented and collinear elements, in segmentation by orientation contrast and motion contrast. In other words, global grouping (i) facilitates discrimination of orientation contrast, indicating a global process, and (ii) inhibits both detection and discrimination of motion contrast, suggesting the presence of a local process.     

The influence of ubiquinone (Co Q10) on the metabolic response to work

Ubiquinone (Co Q10) is a natural substance suitable for therapeutic use in cardiology and in the treatment of some muscular diseases. It might therefore be used during strenuous exercise (as in athletic competitions), especially in the presence of metabolic modifications which may justify its use. For this purpose, we have evaluated the effect of prolonged treatment with Co Q10 (100 mg/day per os for one month) on the biological changes induced by prolonged work on an ergometer bicycle (equal to about 50% of the single VO2max per 60 m'), immediately followed by exhaustive work (25 watts increase every 2 m'). From the venous blood of 12 healthy untrained subjects (students, volunteers, mean age 25.7 and body mass index 23.3) we examined some biological parameters [free fatty acids (FFA), free glycerol, lactate, glucose, insulin, CK] before, at the end of aerobic work, at the end of exhaustive work, and after 30 and 60 m' of the recovery phase. The same indexes, measured after identical times and work, were evaluated after one month of treatment with Co Q10. The only relevant modifications observed were those concerning FFA: at the end of aerobic work and after the administration of the drug, lower levels were reached (before, 1011 +/- 329 microEq/l; after 790 +/- 392; p less than 0.05); the same trend was observed at the end of the exhaustive work (1031 +/- 320 microEq/l vs 826 +/- 387; p less than 0.05). At the subsequent times, as well as for the other biological parameters examined, we did not observe any variation before or after the period of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

骨髓基质干细胞移植对正常和心肌梗死大鼠心电图及心功能的影响

目的:骨髓基质干细胞移植到心肌梗死的瘢痕心肌组织中可以改善心功能,但以心电图为观察指标的研究不多。实验观察骨髓基质干细胞移植对正常和心肌梗死大鼠心电图及心功能的影响。方法:实验于2004-01/2005-03在哈尔滨医科大学完成。①实验动物:选取4周龄雄性Wistar大鼠80只,随机数字表法分为梗死移植组、正常移植组、梗死非移植组、正常非移植组,20只/组。另选取7d龄Wistar雄鼠30只作为骨髓基质干细胞的来源。②实验方法:采用密度梯度离心法获取鼠骨髓基质干细胞,配成1×109L-1的细胞悬液,使用5-氮胞苷体外诱导培养3～4周,移植前24～48h行Brdu标记。取载有细胞的盖玻片,测定钙释放时将20mmol/L的caffeine快速加在细胞表面。梗死移植组、梗死非移植组大鼠建立心肌梗死模型。造模4周后,梗死移植组将0.25mL诱导的骨髓基质干细胞悬液注射至大鼠心肌梗死后的瘢痕组织,正常移植组同法将骨髓基质干细胞悬液注射至正常心肌组织,梗死非移植组、正常非移植组注射等量不含骨髓基质干细胞的培养液基质。③实验评估:观察骨髓基质干细胞的诱导分化情况及其植入后在瘢痕心肌组织中的生存状态。测定细胞内钙离子浓度。记录术前、冠脉结扎后即刻/细胞移植即刻、术后4周的心电图变化。检测术后4周的超声和血流动力学指标变化。结果:80只大鼠均进入结果分析。①骨髓基质干细胞的诱导分化及其植入后的生存状态:5-氮胞苷诱导3周后,骨髓基质干细胞表达肌钙蛋白Ⅰ和肌凝蛋白重链,细胞内有丰富的肌丝和Z线,细胞器较多。植入4周后在心肌瘢痕组织中分化为心肌细胞。②细胞内钙离子浓度:两组细胞在caffeine刺激下钙离子的释放均呈波峰状,但诱导组应用caffeine后钙离子浓度降低且低于基础状态,钙释放受到抑制,未诱导组不受影响。③心电图观察:与术前比较,梗死移植组QRS波变窄,R波降支出现正常顿挫波,未见显著心律失常。④超声检测及血流动力学分析:术后4周,与梗死非移植组比较,梗死移植组左室收缩末压、左室射血分数和压力变化速率最大值均显著升高(P<0.05或0.01)。结论:骨髓基质干细胞体外诱导后能分化为心肌样细胞,植入到瘢痕心肌组织中生存、增殖良好,可改善心电图及心肌弹性,从而改善心肌梗死大鼠的心功能。     

Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase

Because of their low asparagine synthetase (ASNS) expression and asparagine biosynthesis, acute lymphoblastic leukemia (ALL) cells are exquisitely sensitive to asparagine depletion. Consequently, asparaginase is a major component of ALL therapy, but the mechanisms regulating the susceptibility of leukemic cells to this agent are unclear. In 288 children with ALL, cellular ASNS expression was more likely to be high in T-lineage ALL and low in B-lineage ALL with TEL-AML1 or hyperdiploidy. However, ASNS expression levels in bone marrow-derived mesenchymal cells (MSCs), which form the microenvironment where leukemic cells grow, were on average 20 times higher than those in ALL cells. MSCs protected ALL cells from asparaginase cytotoxicity in coculture experiments. This protective effect correlated with levels of ASNS expression: downregulation by RNA interference decreased the capacity of MSCs to protect ALL cells from asparaginase, whereas enforced ASNS expression conferred enhanced protection. Asparagine secretion by MSCs was directly related to their ASNS expression levels, suggesting a mechanism - increased concentrations of asparagine in the leukemic cell microenvironment - for the protective effects we observed. These results provide what we believe to be a new basis for understanding asparaginase resistance in ALL and indicate that MSC niches in the bone marrow can form a safe haven for leukemic cells.     

不同孔径纳米羟基磷灰石人工骨修复兔桡骨缺损效果比较

目的:纳米级的羟基磷灰石材料与人体内组织成分更为相似,具有更佳的生物性能。评价不同孔径的多孔纳米羟基磷灰石人工骨的骨缺损修复能力,从而筛选出适合的孔径以达到骨传导功能与生物力学性能的良好统一。方法:实验于2005-10/2006-10在深圳市第二人民医院中心实验室完成。①实验材料:纳米羟基磷灰石人工骨以硝酸钙和磷酸二氢铵为原料,采用溶胶-絮凝法制备粉体,运用压力成型、木模成型和浸渍成型分别制得孔隙分布均匀的孔径分别为50～150μm、100～250μm和300～500μm的多孔纳米羟基磷灰石人工骨。②实验动物:雄性新西兰大白兔60只随机分为植入50～150μm孔径材料组、植入100～250μm孔径材料组、植入300～500μm孔径材料组、空白对照组,每组15只。实验过程中对动物处置符合动物伦理学要求。③实验方法:制备双侧桡骨骨缺损动物模型,然后用3种不同孔径的纳米羟基磷灰石人工骨材料植入骨缺损处进行修复,空白对照组不植入任何材料。④实验评估:术后4,8和12周分别行大体标本观察、X射线片观察、扫描电镜观察及生物力学测试,比较各组材料修复骨缺损的能力。结果:实验动物均进入结果分析。①X射线片检查结果:术后4周、8周、12周,植入100～250μm孔径材料组X射线评分高于植入50～150μm,300～500μm孔径材料组,差异有显著性意义(P<0.05)。②生物力学检测结果:术后4周、8周、12周,植入100～250μm孔径材料组生物力学强度高于植入50～150μm,300～500μm孔径材料组,差异有显著性意义(P<0.05)。③扫描电镜观察结果:植入100～250μm孔径材料组成骨效果明显优于植入50～150μm,300～500μm孔径材料组和空白对照组。结论:纳米羟基磷灰石人工骨具有良好的成骨能力,但其骨修复能力受孔径因素的影响,孔径100～250μm的纳米羟基磷灰石人工骨材料成骨能力较好。