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61.
Menadione partially restores NADH-oxidation and ATP-synthesis in complex I deficient fibroblasts 总被引:1,自引:0,他引:1
In this paper we report our studies on the effects of menadione in cultured fibroblasts treated with rotenone to block complex I. A normalization of the lactate to pyruvate ratio after incubation with glucose, an increased production of 14CO2 from [6-14C]glucose and an increased intra-cellular concentration of ATP was observed in the presence of micromolar concentrations of menadione. These results not only demonstrate the potential value of menadione in complex I deficient patients but also suggest that this system can be used advantageously for the in vitro assessment of therapeutic agents for disorders of the mitochondrial respiratory chain. 相似文献
62.
R J Wanders G J Romeyn R B Schutgens J M Tager 《Biochemical and biophysical research communications》1989,164(1):550-555
We investigated the oxidation of L-pipecolate in human liver. The results obtained with L-pipecolate from which traces of D-pipecolate had been removed by a preincubation with D-aminoacid oxidase indicate that a distinct L-pipecolate oxidase rather than D-aminoacid oxidase is responsible for the L-pipecolate dependent H2O2-production in human liver. Importantly, L-pipecolate oxidase was found to be localized in peroxisomes which adds to the growing number of enzymes and metabolic functions which can be ascribed to peroxisomes. 相似文献
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65.
G A Jansen N M Verhoeven S Denis G Romeijn C Jakobs H J ten Brink R J Wanders 《Biochimica et biophysica acta》1999,1440(2-3):176-182
Phytanic acid is broken down by alpha-oxidation in three steps finally yielding pristanic acid. The first step occurs in peroxisomes and is catalysed by phytanoyl-CoA hydroxylase. We have studied the second step in the alpha-oxidation pathway, which involves conversion of 2-hydroxyphytanoyl-CoA to pristanal catalysed by 2-hydroxyphytanoyl-CoA lyase. To this end, we have developed a stable isotope dilution gas chromatography-mass spectrometry assay allowing activity measurements in rat liver homogenates. Cell fractionation studies demonstrate that in rat liver 2-hydroxyphytanoyl-CoA lyase is localised in peroxisomes. This finding may have important implications for inherited diseases in man characterised by impaired phytanic acid alpha-oxidation. 相似文献
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67.
Deborah Lehmann Mary T Tennant Desiree T Silva Daniel McAullay Francis Lannigan Harvey Coates Fiona J Stanley 《BMJ (Clinical research ed.)》2003,327(7412):415-419
Objective To determine the health impact of swimming pools built with the aim of improving quality of life and reducing high rates of pyoderma and otitis media.Design Intervention study assessing prevalence of ear disease and skin infections before and at six monthly intervals after opening of swimming pools.Setting Two remote Aboriginal communities in Western Australia.Participants 84 boys and 78 girls aged < 17 years.Main outcome measures Changes in prevalence and severity of pyoderma and perforation of tympanic membranes with or without otorrhoea over 18 months after opening of pools.Results In community A, 61 children were seen before the pool was opened, and 41, 46, and 33 children were seen at the second, third, and fourth surveys. Equivalent figures for community B were 60, 35, 39, and 45. Prevalence of pyoderma declined significantly from 62% to 18% in community A and from 70% to 20% in community B during the 18 months after the pools opened. Over the same period, prevalence of severe pyoderma fell from 30% to 15% in community A and from 48% to 0% in community B. Prevalence of perforations of the tympanic membrane fell from 32% in both communities to 13% in community A and 18% in community B. School attendance improved in community A.Conclusion Swimming pools in remote communities were associated with reduction in prevalence of pyoderma and tympanic membrane perforations, which could result in long term benefits through reduction in chronic disease burden and improved educational and social outcomes. 相似文献
68.
Florian Streitner Juergen Kuschyk Christian Veltmann Desiree Ratay Nina Schoene Ines Streitner Martina Brueckmann Burghard Schumacher Martin Borggrefe Christian Wolpert 《Cytokine》2009,47(3):166-172
BackgroundSeveral studies have attempted to identify risk factors for the development of an electrical storm (ES), which is defined as ⩾3 separate ventricular tachyarrhythmic (VT/VF) events, but in the majority of studies no triggers have been found. However, little is known about the role of inflammation and NT-proBNP in patients with ES. The aim of this study was therefore to assess the relationship of Interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and NT-proBNP serum concentrations in ICD-patients with or without single spontaneous ventricular tachyarrhythmic events (VT/VF) and in ES.MethodsMarkers were determined in 51 patients without ICD-intervention, in 15 ICD-patients with single VT/VF-episodes during 9-months follow-up and in 20 ICD-patients with ES (blood sampling performed within 60 min after fulfilling ES criteria). VT/VF-episodes were analysed by stored ICD-electrograms.ResultsAll patients had idiopathic dilated cardiomyopathy (n = 23) or coronary artery disease (n = 63). Patients with ES revealed significantly higher mean serum concentrations of all markers (IL-6 15.19 ± 10.34 pg/mL, hs-CRP 20.12 ± 14.4 mg/L, NT-proBNP 4799 ± 4596 pg/mL) compared to baseline values of patients with single VT/VF-events during follow-up (IL-6 8.37 ± 5.8 pg/mL (p = 0.03), hs-CRP 4.7 ± 5.3 mg/dL (p < 0.001), NT-proBNP 1913 ± 2665 pg/mL (p = 0.04)) and compared to baseline values of ICD-patients without device intervention (IL-6 4.62 ± 3.66 pg/mL (p < 0.001), hs-CRP 4.1 ± 3.4 mg/L (p < 0.001), NT-proBNP 1461 ± 2281 pg/mL (p < 0.001)). In 9/20 patients presenting with ES (45%) baseline values were available. All markers were significantly higher during ES compared to event-free determination (IL-6 14.54 ± 10.43 vs. 7.03 ± 2.83 pg/mL (p = 0.04), hs-CRP 19.07 ± 16.07 vs. 6.5 ± 3.9 mg/L (p = 0.02), NT-proBNP 4218 ± 2561 vs. 2099 ± 1279 pg/mL (p = 0.03)).ConclusionsElectrical storm is associated with significantly elevated IL-6, hs-CRP and NT-proBNP serum concentrations in ICD-patients with structural heart disease. Thus, ES may be triggered by proinflammatory activity. Combined intraindividual elevation of determined markers might help to identify patients at risk of impending electrical storm. 相似文献
69.
R.J.A. Wanders S. Ferdinandusse P. Brites S. Kemp 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2010,1801(3):272-280
Peroxisomes play an essential role in cellular lipid metabolism as exemplified by the existence of a number of genetic diseases in humans caused by the impaired function of one of the peroxisomal enzymes involved in lipid metabolism. Key pathways in which peroxisomes are involved include: (1.) fatty acid beta-oxidation; (2.) etherphospholipid biosynthesis, and (3.) fatty acid alpha-oxidation. In this paper we will describe these different pathways in some detail and will provide an overview of peroxisomal disorders of metabolism and in addition discuss the toxicity of the intermediates of peroxisomal metabolism as they accumulate in the different peroxisomal deficiencies. 相似文献
70.
Hagemann IS Narzinski KD Floyd DH Baranski TJ 《The Journal of biological chemistry》2006,281(48):36783-36792
The N terminus of G protein-coupled receptors has been implicated in binding to peptide hormones. We have used random saturation mutagenesis to identify essential residues in the N terminus of the human complement factor 5a receptor (C5aR). In a library of N-terminal mutant C5aR molecules screened for activation by C5a, residues 24-30 of the C5aR showed a marked propensity to mutate to cysteine, most likely indicating that sulfhydryl groups at these positions are appropriately situated to form disulfide interactions with the unpaired Cys(27) of human C5a. This presumptive spatial constraint allowed the ligand to be computationally docked to the receptor to form a model of the C5a/C5aR interaction. When the N-terminal mutant C5aR library was rescreened with C5a C27R, a ligand incapable of disulfide interactions, no individual position in the N terminus was essential for receptor signaling. However, the region 19-29 was relatively highly conserved in the functional mutants, further demonstrating that this region of the C5aR makes a productive physiologic interaction with the C5a ligand. 相似文献