70 research outputs found
Improving quantification and identification in metabolomics
Get PDFChapter 1 introduces and discusses metabolomics and related analytical techniques such as NMR, direct infusion-MS, GC-MS, and LC-MS. Next LC-MS-based untargeted metabolomics, including metabolite sample collection and preparation and untargeted LC-MS analysis platforms, are discussed. Chapter 2 apply the dynamic mass error theory to improve the quantification of metabolites. The aim of this project is the implementation of the dynamic binning algorithm, which considers the exact width broadening of a peak in mass spectra to construct extracted ion chromatograms (EICs), and which provides more accurate quantification than using EIC constructed with linear or constant thresholds implemented in the most widely used metabolomics software, XCMS. Chapter 3 describes applying dynamic thresholds to improve untargeted metabolite identification and includes the PEP score and q-value calculation to provide an estimated ensemble and individual error for untargeted metabolomics identification. Chapter 4 includes lipid identification and quantification. The transcriptomic data show that Vitamin B12, cofactor biosynthesis pathways, and ribosomal proteins are activated upon CP treatment. Especially the genes related to phospholipid biosynthesis and fatty acid are differentially expressed. These changes upon CP were further affirmed by the cell membrane’s composition change of fatty acids and phospholipids, as shown by both phospholipid composition and the membrane fluidity measurements. The growth inhibition of F. prausnitzii upon CP exposure can be explained by the cell membrane lipid composition and fluidity changes. Chapter 5 describes an R package with a graphic user interface, which enables untargeted metabolomics data pre-processing and analysis without programming skills
Clinical chemistry of serotonin and catecholamines. Contributions to carcinoid tumours, phaeochromocytoma and Parkinson's disease
Get PDFThe scope of the thesis was to further develop assays of serotonin, catecholamines and their metabolites, and to investigate their usefulness in diagnosis and follow-up of patients with carcinoid tumours, further elucidation of catecholamine metabolism, and experimental therapies of Parkinson's disease. ...
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Clinical chemistry of serotonin and catecholamines. Contributions to carcinoid tumours, phaeochromocytoma and Parkinson's disease
Get PDFClinical chemistry of serotonin and catecholamines. Contributions to carcinoid tumours, phaeochromocytoma and Parkinson's disease
Get PDFClinical chemistry of serotonin and catecholamines. Contributions to carcinoid tumours, phaeochromocytoma and Parkinson's disease
Get PDFThe protective effect of 1-methyltryptophan isomers in renal ischemia-reperfusion injury is not exclusively dependent on indolamine 2,3-dioxygenase inhibition
Get PDFBACKGROUND AND PURPOSE: Indolamine 2,3-dioxygenase (IDO), an enzyme that catalyses the metabolism of tryptophan, may play a detrimental role in ischemia-reperfusion injury (IRI). IDO can be inhibited by 1-methyl-tryptophan, which exists in a D (D-MT) or L (L-MT) isomer. These forms show different pharmacological effects besides IDO inhibition. Therefore, we sought to investigate whether these isomers can play a protective role in renal IRI, either IDO-dependent or independent.EXPERIMENTAL APPROACH: We studied the effect of both isomers in a rat renal IRI model with a focus on IDO-dependent and independent effects.KEY RESULTS: Both MT isomers reduced creatinine and BUN levels, with D-MT having a faster onset of action but shorter duration and L-MT a slower onset but longer duration (24 h and 48 h vs 48 h and 96 h reperfusion time). Interestingly, this effect was not exclusively dependent on IDO inhibition, but rather from decreased TLR4 signalling, mimicking changes in renal function. Additionally, L-MT increased the overall survival of rats. Moreover, both MT isomers interfered with TGF-β signalling and epithelial-mesenchymal transition. In order to study the effect of isomers in all mechanisms involved in IRI, a series of in vitro experiments was performed. The isomers affected signalling pathways in NK cells and tubular epithelial cells, as well as in dendritic cells and T cells.CONCLUSION AND IMPLICATIONS: This study shows that both MT isomers have a renoprotective effect after ischemia-reperfusion injury, mostly independent of IDO inhibition, involving mutually different mechanisms. We bring novel findings in the pharmacological properties and mechanism of action of MT isomers, which could become a novel therapeutic target of renal IRI.</p
Assessment and clinical implications of functional vitamin B6 deficiency
Get PDFVitaminen zijn essentieel voor een gezond en lang leven. Tegenwoordig worden vitaminesupplementen dan ook veelvuldig gebruikt om het algemeen welbevingen te verbeteren en aandoeningen te verlichten of te voorkomen. Echter, bij veel groepen mensen, zoals patiënten met fibromyalgie en het chronisch vermoeidheidssyndroom, ontbreekt de wetenschappelijke basis hiervoor met als gevolg dat men mogelijk onnodig risico loopt op vitaminetoxiciteit, zoals onlangs met vitamine B6 is gebleken bij Sven Kramer. In dit proefschrift laten wij zien dat het tot nu toe uitgevoerde onderzoek naar een mogelijk verband tussen vitaminen en de ziekteactiviteit van fibromyalgie en het chronisch vermoeidheidssyndroom laag van kwaliteit is en dat er op basis van dit onderzoek geen duidelijk verband tussen vitaminen en ziekteactiviteit aanwijsbaar is. Hiermee hebben wij laten zien dat er vooralsnog geen goede wetenschappelijke basis bestaat voor het gebruik van vitaminesupplementen ter verlichting van de symptomen van fibromyalgie en het chronisch vermoeidheidssyndroom. Verder hebben wij aangetoond dat een vitamine B6 tekort relatief vaak voorkomt bij niertransplantatiepatiënten en dat dit tekort bepaalde intracellulaire processen op moleculair niveau lijkt te verstoren. Bovendien wijzen onze data erop dat vitamine B6 deficiënte niertransplantatiepatiënten en vrouwen uit de algemene bevolking een hogere kans hebben op voortijdige sterfte ten gevolge van cardiovasculaire aandoeningen, vergeleken met personen met een adequate vitamine B6 status. Wij concluderen dan ook dat niertransplantatiepatiënten en vrouwen mogelijk baat zouden kunnen hebben bij vitamine B6 supplementen. Voordat dit in de richtlijnen opgenomen kan worden, dienen interventiestudies met vitamine B6 supplementen echter eerst sluitend bewijs te leveren
Framing Immigrant Integration
No full textDebates on immigrant integration often center on "national models of integration," a concept that reflects the desire of both researchers and policy makers to find common ground. This book challenges the idea that there has ever been a coherent or consistent Dutch model of integration and asserts that though Dutch society has long been seen as exemplary for its multiculturalism-and argues that the incorporation of migrants remains one of the country's most pressing social and political concerns. In addition to an analysis of how immigration is framed and reframed through diverse dialogues, the author provides a highly dynamic overview of integration policy and its evolution alongside migration research
Serotonin, cortisol, and stress-related psychopathology : from bench to bed
Get PDFStress has been implicated in the etiology of many psychiatric disorders, the most common stress-related disorder being major depressive disorder. However, stressful events do not automatically lead to psychopathology, important is the interaction between the stressor and someone’s vulnerability to stress and psychiatric disorders. This vulnerability is individual and likely to be determined by genetic, psychosocial, and biological factors. Two biological systems that have been related to the development of stress-related psychiatric disorders are the hypothalamus-pituitary-adrenal(HPA)-axis and the serotonergic system. In the present thesis, the interaction of these systems on coping with stress in rats and vulnerability to psychopathology in humans was investigated. The results indicate that changes in serotonergic activity and HPA-axis activity as a consequence of a disease process, treatment condition or other environmental factors may have behavioral consequences in both animals and humans. For example, low serotonergic activity may increase susceptibility to stress and HPA-axis activity, which in combination with individual genetic make-up may result in psychiatric symptoms. Impaired HPA-axis function is associated with more severe symptoms of major depressive disorder. We plead for the inclusion of a separate “serotonergic” symptom profile list in psychiatric questionnaires, and future incarnations of the DSM.
Methods and kits for determining protein-bound biomarkers
No full textThe invention relates to the field of diagnostic methods, in particular to detection of biological molecules using mass spectroscopy (MS).Provided is an automated high-throughput method for quantitating a low molecular weight protein-bound biomarker directly in an isolated biological sample, comprising the steps of: (a) automated prepurification of the sample using an effective amount of an acid protease under conditions that allow for digestion of one or more binding proteins; (b) applying said protease-digested sample onto an on-line SPE column to capture at least part of said biomarker, followed by sequential washing of the solid phase; (c) eluting a fraction comprising said biomarker directly onto a liquid chromatography (LC) column comprising an apolar stationary phase and subjecting it to LC-MS or LC-MS-MS measurements to determine the amount of at least one biomarker; and (d) quantitating the biomarker(s).Also provided are kits for use in such method, for instance in the determination of vitamin D derivatives, testosterone and/or or melatonin
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