975 resultados para Radikalfänger, Isoselenazole, Hydroxylradikale, Cox, Lox


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Composites of recycled carbon fiber (CF) with up to 30 wt % loading with polyethylene (PE) were prepared via melt compounding. The morphology of the composites and the degree of dispersion of the CF in the PE matrix was examined using scanning electron microscopy, and revealed the CF to be highly dispersed at all loadings and strong interfacial adhesion to exist between the CF and PE. Raman and FTIR spectroscopy were used to characterize the surface chemistry and potential bonding sites of recycled CF. Both the Young's modulus and ultimate tensile stress increased with increasing CF loading, but the percentage stress at break was unchanged up to 5 wt % loading, then decreased with further successive addition of CF. The effect of CF on the elastic modulus of PE was examined using the Halpin-Tsai and modified Cox models, the former giving a better fit with the values determined experimentally. The electrical conductivity of the PE matrix was enhanced by about 11 orders of magnitude on addition of recycled CF with a percolation threshold of 7 and 15 wt % for 500-mu m and 3-mm thick samples. (c) 2007 Wiley Periodicals, Inc.

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The book chapter examines the history of New Orleans cemeteries and their popular image, especially in regard to the tourism industry.

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Objective To investigate the association between periodontitis and mortality from all causes in a prospective study in a homogenous group of 60- to 70-year-old West European men. Methodology A representative sample of 1400 dentate men, (mean age 63.8, SD 3.0 years), drawn from the population of Northern Ireland, had a comprehensive periodontal examination between 2001 and 2003. Men were divided into thirds on the basis of their mean periodontal attachment loss (PAL). The primary endpoint, death from any cause, was analysed using Kaplan-Meier survival plots and Cox's proportional hazards model. Results In total, 152 (10.9%) of the men died during a mean follow-up of 8.9 (SD 0.7) years; 37 (7.9%) men in the third with the lowest PAL (<1.8 mm) died compared with 73 (15.7%) in the third with the highest PAL (>2.6 mm). The unadjusted hazard ratio (HR) for death in the men with the highest level of PAL compared with those with the lowest PAL was 2.11 (95% CI 1.42-3.14), p < 0.0001. After adjustment for confounding variables (age, smoking, hypertension, BMI, diabetes, cholesterol, education, marital status and previous history of a cardiovascular event) the HR was 1.57 (1.04-2.36), p = 0.03. Conclusion The European men in this prospective cohort study with the most severe loss of periodontal attachment were at an increased risk of death compared with those with the lowest loss of periodontal attachment.

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Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict paclitaxel responses in women presenting with high-grade serous EOC.

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To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta-analysis of published results.

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Introduction: The prevalence of comorbidities in incident renal replacement therapy (RRT) patients changes with age and varies between ethnic groups. This study describes these associations and the independent effect of comorbidities on outcomes. Methods: Adult patients starting RRT between 2003 and 2008 in centres reporting to the UK Renal Registry (UKRR) with data on comorbidity (n ¼ 14,909) were included. The UKRR studied the association of comorbidity with patient demographics, treatment modality, haemoglobin, renal function at start of RRT and subsequent listing for kidney transplantation. The relationship between comorbidities and mortality at 90 days and one year after 90 days from start of RRT was explored using Cox regression. Results: Completeness of comorbidity data was 40.0% compared with 54.3% in 2003. Of patients with data, 53.8% had one or more comorbidities. Diabetes mellitus and ischaemic heart disease were the most common conditions seen in 30.1% and 22.7% of patients respectively. Current smoking was recorded for 14.5% of incident RRT patients in the 6-year period. Comorbidities became more common with increasing age in all ethnic groups although the difference between the 65–74 and 75+ age groups was not significant. Within each age group, South Asians and Blacks had lower rates of comorbidity, despite higher rates of diabetes mellitus. In multivariate survival analysis, malignancy and ischaemic/neuropathic ulcers were the strongest independent predictors of poor survival at 1 year after 90 days from the start of RRT. Conclusion: Differences in prevalence of comorbid illnesses in incident RRT patients may reflect variation in access to health care or competing risk prior to commencing treatment. At the same time, smoking rates remained high in this ‘at risk’ population. Further work on this and ways to improve comorbidity reporting should be priorities for 2010–11.

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Introduction: The prevalence of 13 comorbid conditions and smoking status at the time of starting renal replacement therapy (RRT) in England, Wales and Northern Ireland are described. Methods: Adult patients starting RRT between 2002 and 2007 in centres reporting to the UK Renal Registry (UKRR) and with data on comorbidity (n¼13,293) were included. The association of comorbidity with patient demographics, treatment modality, haemoglobin, renal function at start of RRT and subsequent listing for kidney transplantation were studied. Association between comorbidities and mortality at 90 days and one year after 90 days from start of RRT was explored using Cox regression. Results: Completeness of data on comorbidity returned to the UKRR remained poor. Of patients with data, 52% had one or more comorbidities. Diabetes mellitus and ischaemic heart disease were the most common conditions seen in 28.9% and 22.5% of patients respectively. Comorbidities became more common with increasing age (up to the 65–74 age group), were more common amongst Whites and were associated with a lower likelihood of pre-emptive transplantation, a greater likelihood of starting on haemodialysis (rather than peritoneal dialysis) and a lower likelihood of being listed for kidney transplantation. In multivariable survival analysis, malignancy and ischaemic/neuropathic ulcers were the strongest predictors of poor survival at 1 year after 90 days from start of RRT. Conclusions: The majority of patients had at least one comorbid condition and comorbidity is an important predictor of early mortality on RRT.

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This study investigates age-related shifts in the relative importance of systolic (SBP) and diastolic (DBP) blood pressures as predictors of stroke and whether these relations are influenced by other cardiovascular risk factors. Using 34 European cohorts from the MOnica, Risk, Genetics, Archiving, and Monograph (MORGAM) Project with baseline between 1982 and 1997, 68 551 subjects aged 19 to 78 years, without cardiovascular disease and not receiving antihypertensive treatment, were included. During a mean of 13.2 years of follow-up, stroke incidence was 2.8%. Stroke risk was analyzed using hazard ratios per 10-mm Hg/5-mm Hg increase in SBP/DBP by multivariate-adjusted Cox regressions, including SBP and DBP simultaneously. Because of nonlinearity, DBP was analyzed separately for DBP =71 mm Hg and DBP

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Correlation analyses were conducted on nickel (Ni), vanadium (V) and zinc (Zn) oral bioaccessible fractions (BAFs) and selected geochemistry parameters to identify specific controls exerted over trace element bioaccessibility. BAFs were determined by previous research using the unified BARGE method. Total trace element concentrations and soil geochemical parameters were analysed as part of the Geological Survey of Northern Ireland Tellus Project. Correlation analysis included Ni, V and Zn BAFs against their total concentrations, pH, estimated soil organic carbon (SOC) and a further eight element oxides. BAF data were divided into three separate generic bedrock classifications of basalt, lithic arenite and mudstone prior to analysis, resulting in an increase in average correlation coefficients between BAFs and geochemical parameters. Sulphur trioxide and SOC, spatially correlated with upland peat soils, exhibited significant positive correlations with all BAFs in gastric and gastro-intestinal digestion phases, with such effects being strongest in the lithic arenite bedrock group. Significant negative relationships with bioaccessible Ni, V and Zn and their associated total concentrations were observed for the basalt group. Major element oxides were associated with reduced oral trace element bioaccessibility, with Al2O3 resulting in the highest number of significant negative correlations followed by Fe2O3. spatial mapping showed that metal oxides were present at reduced levels in peat soils. The findings illustrate how specific geology and soil geochemistry exert controls over trace element bioaccessibility, with soil chemical factors having a stronger influence on BAF results than relative geogenic abundance. In general, higher Ni, V and Zn bioaccessibility is expected in peat soil types.

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Potentially toxic elements (PTEs) including nickel and chromium are often present in soils overlying basalt at concentrations above regulatory guidance values due to the presence of these elements in underlying geology. Oral bioaccessibility testing allows the risk posed by PTEs to human health to be assessed; however, bioaccessibility is controlled by factors including mineralogy, particle size, solid-phase speciation and encapsulation. X-ray diffraction was used to characterise the mineralogy of 12 soil samples overlying Palaeogene basalt lavas in Northern Ireland, and non-specific sequential extraction coupled with chemometric analysis was used to determine the distribution of elements amongst soil components in 3 of these samples. The data obtained were related to total concentration and oral bioaccessible concentration to determine whether a relationship exists between the overall concentrations of PTEs, their bioaccessibility and the soils mineralogy and geochemistry. Gastric phase bioaccessible fraction (BAF %) ranged from 0.4 to 5.4 % for chromium in soils overlying basalt and bioaccessible and total chromium concentrations are positively correlated. In contrast, the range of gastric phase BAF for nickel was greater (1.4–43.8 %), while no significant correlation was observed between bioaccessible and total nickel concentrations. However, nickel BAF was inversely correlated with total concentration. Solid-phase fractionation information showed that bioaccessible nickel was associated with calcium carbonate, aluminium oxide, iron oxide and clay-related components, while bioaccessible chromium was associated with clay-related components. This suggests that weathering significantly affects nickel bioaccessibility, but does not have the same effect on the bioaccessibility of chromium.

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The role of hydrogen sulfide (H2 S) in inflammation remains unclear with both pro- and anti-inflammatory actions of this gas described. We have now assessed the effect of GYY4137 (a slow-releasing H2 S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro. We have also examined the effect of GYY4137 in a complete Freund's adjuvant (CFA) model of acute joint inflammation in the mouse. GYY4137 (0.1-0.5 mM) decreased LPS-induced production of nitrite (NO2 (-) ), PGE2 , TNF-a and IL-6 from HFLS and HAC, reduced the levels and catalytic activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced LPS-induced NF-?B activation in vitro. Using recombinant human enzymes, GYY4137 inhibited the activity of COX-2, iNOS and TNF-a converting enzyme (TACE). In the CFA-treated mouse, GYY4137 (50 mg/kg, i.p.) injected 1 hr prior to CFA increased knee joint swelling while an anti-inflammatory effect, as demonstrated by reduced synovial fluid myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activity and decreased TNF-a, IL-1ß, IL-6 and IL-8 concentration, was apparent when GYY4137 was injected 6 hrs after CFA. GYY4137 was also anti-inflammatory when given 18 hrs after CFA. Thus, although GYY4137 consistently reduced the generation of pro-inflammatory mediators from human joint cells in vitro, its effect on acute joint inflammation in vivo depended on the timing of administration.

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A downstream target of the Wnt pathway, neurone glial-related cell adhesion molecule (Nr-CAM) has recently been implicated in human cancer development. However, its role in colorectal cancer (CRC) pathobiology and clinical relevance remains unknown. In this study, we examined the clinical significance of Nr-CAM protein expression in a retrospective series of 428 CRCs using immunohistochemistry and tissue microarrays. Cox proportional hazards regression was used to calculate hazard ratios (HR) of mortality according to various clinicopathological features and molecular markers. All CRC samples were immunoreactive for Nr-CAM protein expression, compared to 10 / 245 (4%) matched normal tissue (P <0.0001). Of 428 CRC samples, 97 (23%) showed Nr-CAM overexpression, which was significantly associated with nodal (P = 0.012) and distant (P = 0.039) metastasis, but not with extent of local invasion or tumor size. Additionally, Nr-CAM overexpression was associated with vascular invasion (P = 0.0029), p53 expression (P = 0.036), and peritoneal metastasis at diagnosis (P = 0.013). In a multivariate model adjusted for other clinicopathological predictors of survival, Nr-CAM overexpression correlated with a significant increase in disease-specific (HR 1.66; 95% confidence interval 1.11-2.47; P = 0.014) and overall mortality (HR 1.57; 95% confidence interval 1.07-2.30; P = 0.023) in advanced but not early stage disease. Notably, 5-fluorouracil-based chemotherapy conferred significant survival benefit to patients with tumors negative for Nr-CAM overexpression but not to those with Nr-CAM overexpressed tumors. In conclusion, Nr-CAM protein expression is upregulated in CRC tissues. Nr-CAM overexpression is an independent marker of poor prognosis among advanced CRC patients, and is a possible predictive marker for non-beneficence to 5-fluorouracil- based chemotherapy.

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In this experimental study, diamond turning of single crystal 6H-SiC was performed at a cutting speed of 1 m/s on an ultra-precision diamond turning machine (Moore Nanotech 350 UPL) to elucidate the microscopic origin of ductile-regime machining. Distilled water (pH value 7) was used as a preferred coolant during the course of machining in order to improve the tribological performance. A high magnification scanning electron microscope (SEM FIB- FEI Quanta 3D FEG) was used to examine the cutting tool before and after the machining. A surface finish of Ra=9.2 nm, better than any previously reported value on SiC was obtained. Also, tremendously high cutting resistance was offered by SiC resulting in the observation of significant wear marks on the cutting tool just after 1 km of cutting length. It was found out through a DXR Raman microscope that similar to other classical brittle materials (silicon, germanium, etc.) an occurrence of brittle-ductile transition is responsible for the ductile-regime machining of 6H-SiC. It has also been demonstrated that the structural phase transformations associated with the diamond turning of brittle materials which are normally considered as a prerequisite to ductile-regime machining, may not be observed during ductile-regime machining of polycrystalline materials.

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FLT3-ITD mutations are prevalent mutations in acute myeloid leukaemia (AML). PRL-3, a metastasis-associated phosphatase, is a downstream target of FLT3-ITD. This study investigates the regulation and function of PRL-3 in leukaemia cell lines and AML patients associated with FLT3-ITD mutations. PRL-3 expression is upregulated by the FLT3-STAT5 signalling pathway in leukaemia cells, leading an activation of AP-1 transcription factors via ERK and JNK pathways. PRL-3-depleted AML cells showed a significant decrease in cell growth. Clinically, high PRL-3 mRNA expression was associated with FLT3-ITD mutations in four independent AML datasets with 1158 patients. Multivariable Cox-regression analysis on our Cohort 1 with 221 patients identified PRL-3 as a novel prognostic marker independent of other clinical parameters. Kaplan-Meier analysis showed high PRL-3 mRNA expression was significantly associated with poorer survival among 491 patients with normal karyotype. Targeting PRL-3 reversed the oncogenic effects in FLT3-ITD AML models in vitro and in vivo. Herein, we suggest that PRL-3 could serve as a prognostic marker to predict poorer survival and as a promising novel therapeutic target for AML patients.