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- Ellfolk, Maria, et al.
(författare)
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Regulation of human vitamin D(3) 25-hydroxylases in dermal fibroblasts and prostate cancer LNCaP cells
- 2009
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Ingår i: Molecular Pharmacology. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0026-895X .- 1521-0111. ; 75:6, s. 1392-1399
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we examined whether 1alpha,25-dihydroxyvitamin D(3) (calcitriol), phenobarbital, and the antiretroviral drug efavirenz, drugs used by patient groups with high incidence of low bone mineral density, could affect the 25-hydroxylase activity or expression of human 25-hydroxylases in dermal fibroblasts and prostate cancer LNCaP cells. Fibroblasts express the 25-hydroxylating enzymes CYP2R1 and CYP27A1. LNCaP cells were found to express two potential vitamin D 25-hydroxylases-CYP2R1 and CYP2J2. The presence in different cells of nuclear receptors vitamin D receptor (VDR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR) was also determined. Phenobarbital suppressed the expression of CYP2R1 in fibroblasts and CYP2J2 in LNCaP cells. Efavirenz suppressed the expression of CYP2R1 in fibroblasts but not in LNCaP cells. CYP2J2 was slightly suppressed by efavirenz, whereas CYP27A1 was not affected by any of the two drugs. Calcitriol suppressed the expression of CYP2R1 in both fibroblasts and LNCaP cells but had no clear effect on the expression of either CYP2J2 or CYP27A1. The vitamin D(3) 25-hydroxylase activity in fibroblasts was suppressed by both calcitriol and efavirenz. In LNCaP cells, consumption of substrate (1alpha-hydroxyvitamin D(3)) was used as indicator of metabolism because no 1alpha,25-dihydroxyvitamin D(3) product could be determined. The amount of 1alpha-hydroxyvitamin D(3) remaining in cells treated with calcitriol was significantly increased. Taken together, 25-hydroxylation of vitamin D(3) was suppressed by calcitriol and drugs. The present study provides new information indicating that 25-hydroxylation of vitamin D(3) may be regulated. In addition, the current results may offer a possible explanation for the impaired bone health after treatment with certain drugs.
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- Do, Lan, 1985-
(författare)
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New tools for sample preparation and instrumental analysis of dioxins in environmental samples
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), two groups of structurally related chlorinated aromatic hydrocarbons, are of high concern due to their global distribution and extreme toxicity. Since they occur at very low levels, their analysis is complex, challenging and hence there is a need for efficient, reliable and rapid alternative analytical methods. Developing such methods was the aim of the project this thesis is based upon.During the first years of the project the focus was on the first parts of the analytical chain (extraction and clean-up). A selective pressurized liquid extraction (SPLE) procedure was developed, involving in-cell clean-up to remove bulk co-extracted matrix components from sample extracts. It was further streamlined by employing a modular pressurized liquid extraction (M-PLE) system, which simultaneously extracts, cleans up and isolates planar PCDD/Fs in a single step. Both methods were validated using a wide range of soil, sediment and sludge reference materials. Using dichloromethane/n-heptane (DCM/Hp; 1/1, v/v) as a solvent, results statistically equivalent to or higher than the reference values were obtained, while an alternative, less harmful non-chlorinated solvent mixture - diethyl ether/n-heptane (DEE/Hp; 1/2, v/v) – yielded data equivalent to those values.Later, the focus of the work shifted to the final instrumental analysis. Six gas chromatography (GC) phases were evaluated with respect to their chromatographic separation of not just the 17 most toxic congeners (2,3,7,8-substituted PCDD/Fs), but all 136 tetra- to octaCDD/Fs. Three novel ionic liquid columns performed much better than previously tested commercially available columns. Supelco SLB-IL61 offered the best overall performance, successfully resolving 106 out of the 136 compounds, and 16 out of the 17 2,3,7,8-substituted PCDD/Fs. Another ionic liquid (SLB-IL111) column provided complementary separation. Together, the two columns separated 128 congeners. The work also included characterization of 22 GC columns’ selectivity and solute-stationary phase interactions. The selectivities were mapped using Principal Component Analysis (PCA) of all 136 PCDD/F’s retention times on the columns, while the interactions were probed by analyzing both the retention times and the substances’ physicochemical properties.
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- Willekens, Stefanie M. A., et al.
(författare)
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An MR-based brain template and atlas for optical projection tomography and light sheet fluorescence microscopy in neuroscience
- 2024
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Optical Projection Tomography (OPT) and light sheet fluorescence microscopy (LSFM) are high resolution optical imaging techniques, ideally suited for ex vivo 3D whole mouse brain imaging. Although they exhibit high specificity for their targets, the anatomical detail provided by tissue autofluorescence remains limited.Methods: T1-weighted images were acquired from 19 BABB or DBE cleared brains to create an MR template using serial longitudinal registration. Afterwards, fluorescent OPT and LSFM images were coregistered/normalized to the MR template to create fusion images.Results: Volumetric calculations revealed a significant difference between BABB and DBE cleared brains, leading to develop two optimized templates, with associated tissue priors and brain atlas, for BABB (OCUM) and DBE (iOCUM). By creating fusion images, we identified virus infected brain regions, mapped dopamine transporter and translocator protein expression, and traced innervation from the eye along the optic tract to the thalamus and superior colliculus using cholera toxin B. Fusion images allowed for precise anatomical identification of fluorescent signal in the detailed anatomical context provided by MR.Discussion: The possibility to anatomically map fluorescent signals on magnetic resonance (MR) images, widely used in clinical and preclinical neuroscience, would greatly benefit applications of optical imaging of mouse brain. These specific MR templates for cleared brains enable a broad range of neuroscientific applications integrating 3D optical brain imaging.
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- Brade, Dirk, et al.
(författare)
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Findings from the combined convention on international VV&A standardization endeavors
- 2005
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Ingår i: European Simulation Interoperability Workshop 2005. - 9781622761418 ; , s. 412-421
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Konferensbidrag (refereegranskat)abstract
- Several international working groups develop, evaluate, and harmonize guidelines and a "best practice" for Verification, Validation, and Accreditation (VV&A) with the objective to define common guidelines and standards for VV&A. These working groups include (1) The NATO Modeling and Simulation Group 019, Task Group 016, "Verification, Validation, and Accreditation of Federations"; (2) The International Test Operations Procedure (ITOP) Working Group of Experts (WGE) 7.2 "Verification and Validation"; (3) The Western European Armament Group THALES Joint Program 11.20, "A Common Verification, Validation, and Accreditation Framework for Simulations" (WEAG THALES JP11.20); and (4) The Simulation Interoperability Standardization Organization (SISO) Product Development Group (PDG) "Verification, Validation, and Accreditation of Federations". Although focusing on different aspects of VV&A, these working groups have numerous related topics and areas of interest, which were discussed during the Combined Convention of International VV&A Standardization Endeavors, October 20-23, 2004, Munich. With the above working groups presenting the current state of their work, the convention attracted audience not only from the "VV&A community", but also model developers and program managers. This paper presents the outcomes of the convention, the commonalities and differences of the individual working groups, and a common future perspective on VV&A.
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