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TNO Preventie en Gezondheid (author), Out, R. (author), Kruijt, J.K. (author), Rensen, P.C.N. (author), Hildebrand, R.B. (author), de Vos, P. (author), van Eck, M. (author), van Berkel, T.J.C. (author)The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of high density lipoprotein (HDL) cholesterol esters is well established. However, the potential role of SR-BI in chylomicron and chylomicron remnant metabolism is largely unknown. In the present investigation, we report that the cell association of 160...article 2004
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TNO Preventie en Gezondheid (author), Rensen, P.C.N. (author), van Leeuwen, S.H. (author), Sliedregt, L.A.J.M. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author)A novel glycolipid has been prepared that contains a cluster glycoside with an unusually high affinity for the asialoglycoprotein receptor (ASGPr) and a bile acid moiety that mediates stable incorporation into lipidic particles. The glycolipid spontaneously associated with low-density lipoproteins (LDL) and high-density lipoproteins (HDL) within...article 2004
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Renwick, A.B. (author), Watts, P.S. (author), Edwards, R.J. (author), Barton, P.T. (author), Guyonnet, I. (author), Price, R.J. (author), Tredger, J.M. (author), Pelkonen, O. (author), Boobis, A.R. (author), Lake, B.G. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author)The maintenance of the major hepatic cytochrome P450 (CYP) enzymes has been studied in precision-cut human liver slices cultured for up to 72 h in supplemented RPMI 1640 medium. The relative apoprotein levels of 11 CYP enzymes were determined using a panel of antipeptide antibodes. In addition, 7-ethoxyresorufin O-deethylase, tolbutamide...article 2000
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Edwards, A.J. (author), Price, R.J. (author), Renwick, A.B. (author), Lake, B.G. (author), TNO BIBRA TNO Kwaliteit van Leven (author)The ability of coumarin to induce UDS in male Sprague-Dawley CD rat hepatocytes in vivo was assessed using the unscheduled DNA synthesis (UDS) assay. From a preliminary toxicity study the oral maximum tolerated dose (MTD) of coumarin was determined to be 320mg/kg body weight. For the UDS studies, rats were treated with 0 (corn oil control), 32 ...article 2000
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- TNO Pharma (author), Hoebe, K.H.N. (author), Monshouwer, M. (author), Witkamp, R.F. (author), Fink-Gremmels, J. (author), van Miert, A.S.J.P.A.M. (author) article 2000
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van Puymbroeck, M. (author), Kuilman, M.E.M. (author), Maas, R.F.M. (author), Witkamp, R.F. (author), Leyssens, L. (author), van Miert, A.S.J.P.A.M. (author), Hendriks, L. (author), van der Zande, D.J.M. (author), Adriaensens, P. (author), Jacobs, M.-P. (author), Raus, J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)The metabolism of the illegal growth promoter ethylestrenol (EES) was evaluated in bovine liver cells and subcellular fractions of bovine liver preparations. Incubations with bovine microsomal preparations revealed that EES is extensively biotransformed into norethandrolone (NE), another illegal growth promoter. Furthermore, incubations of...article 1999
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Induction of somatic mutations but not methylated DNA adducts in λlacZ transgenic mice by dichlorvosPletsa, V. (author), Steenwinkel, M.-J.S.T. (author), van Delft, J.H.M. (author), Baan, R.A. (author), Kyrtopoulos, S.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)In order to examine the in vivo genotoxic activity of dichlorvos, λlacZ transgenic mice (Muta(TM)Mouse) were treated i.p. with single (4.4 or 11 mg/kg) or multiple (5x11 mg/kg) doses of this agent and sacrificed 4 h or 14 days post-treatment for DNA adduct measurement or mutant frequency analysis, respectively. Neither methylated DNA adducts nor...article 1999
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- Princen, H.M.G. (author), Gaubius instituut TNO (author) article 1999
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Neele, D.M. (author), de Wit, E.C.M. (author), Princen, H.M.G. (author), Gaubius instituut TNO (author)We have shown previously that retinoids induce apolipoprotein (apo) A-I gene expression in cultured cynomolgus hepatocytes and do not have an effect on apo B-100 synthesis. In the present study, the effect of retinoids on apolipoprotein(a) (apo(a)) synthesis in cultured hepatocytes was investigated. The addition of all-trans retinoic acid (at-RA...article 1999
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Monshouwer, M. (author), van 't Klooster, G.A.E. (author), Nijmeijer, S.M. (author), Witkamp, R.F. (author), van Miert, A.S.J.P.A.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Despite the fact that pigs are increasingly used in pharmacological and toxicological studies, knowledge on the enzymes which metabolize xenobiotics, in particular cytochrome P450 (CYP) enzymes, in pigs is still very limited. Primary cultures of pig hepatocytes were used to characterize CYP enzymes. The characterization was performed at the...article 1998
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Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), van Puymbroeck, M. (author), Kuilman, M.E.M. (author), Maas, R.F.M. (author), Witkamp, R.F. (author), Leyssens, L. (author), van der Zande, D.J.M. (author), Gelan, J. (author), Raus, J. (author)17alpha-Boldenone (17alpha-BOL) and/or 17beta-boldenone (17beta-BOL) appear occasionally in fecal matter of cattle. In addition to 17alpha-BOL, a whole array of boldenone related substances can be found in the same samples. In vitro experiments with microsomal liver preparations and isolated hepatocytes combined with the excretion profiles found...article 1998
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Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), van Puymbroeck, M. (author), Kuilman, M.E.M. (author), Maas, R.F.M. (author), Witkamp, R.F. (author), Leyssens, T. (author), van der Zande, D.J.M. (author), Gelan, J. (author), Raus, J. (author)Current veterinary residue analysis mainly focuses on the monitoring of residues of the administered parent compound. However, it is possible that larger amounts of metabolites are excreted and that they can have a prolonged excretion period. In order to unravel specific metabolic steps and to identify possible biological markers, two in vitro...article 1998
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Arts, J. (author), Kooistra, T. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)Fibrates are widely used drugs in hyperlipidemic disorders. In addition to lowering serum triglyceride levels, fibrates have also been shown to reduce elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels in vivo. We demonstrate that fibrates suppress PAI-1 synthesis in cultured cynomolgus monkey hepatocytes in a concentration...article 1997
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Scherphof, G.L. (author), Velinova, M. (author), Kamps, J. (author), Donga, J. (author), van der Want, H. (author), Kuipers, F. (author), Havekes, L. (author), Daemen, T. (author), TNO Preventie en Gezondheid (author)The authors's recent work on matters pertinent to the in vivo processing of systemically administered liposomes is reviewed. particular emphasis is given to factors influencing blood clearance rates, hepatic and splenic uptake and intrahepatic as well as intrasplenic distribution. In addition to size, liposomal composition plays a crucial role...article 1997
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Lansink, M. (author), van Bennekum, A.M. (author), Blaner, W.S. (author), Kooistra, T. (author), TNO Preventie en Gezondheid (author)Retinoic acid stimulates the expression of tissue-type plasminogen activator (t-PA) in vascular endothelial cells in vitro and enhances t-PA levels in plasma and tissues in vivo. Compared with the in vivo situation, high retinoic acid concentrations are required to induce optimally t-PA expression in vitro. These findings led us to study...article 1997
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Gaubius Instituut TNO Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), Kaptein, A. (author), Neele, D.M. (author), Twisk, J. (author), Hendriks, H.F.J. (author), Kooistra, T. (author), Princen, H.M.G. (author)We showed previously that retinoids stimulate apolipoprotein A-I (apoA- I) synthesis in cultured cynomolgus hepatocytes only after a 24-h lag phase. Here we report on the biochemical background of the slow response, the requirement for high retinoic acid concentrations, and the involvement of different retinoid receptors. The time course of the...article 1997
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Kuiper, J. (author), van 't Hof, A. (author), Otter, M. (author), Biessen, E.A.L. (author), Rijken, D.C. (author), van Berkel, T.J.C. (author), Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratory, P. O. Box 9503, 2300 RA Leiden, Netherlands Gaubius Laboratory, TNO Prevention and Health, P.O. Box 430, 2300 AK Leiden, Netherlands (author)The fibrin-specific thrombolyticum tissue-type plasminogen activator (t-PA) has proven to be a potent drug in several clinical trials, but its clinical application is complicated by the rapid clearance of t-PA from the circulation. The rapid plasma clearance of t-PA results from the uptake of t-PA in the liver. t-PA consists of several domains...article 1996
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TNO Nutrition and Food Research (author), Vethaak, A.D. (author), Jol, J.G. (author), Meijboom, A. (author), Eggens, M.L. (author), Rheinallt, T.A. (author), Wester, P.W. (author), van de Zande, T. (author), Bergman, A. (author), Dankers, N. (author), Ariese, F. (author), Baan, R.A. (author), Everts, J.M. (author), Opperhuizen, A. (author), Marquenie, J.M. (author)Chemicals/CAS: Metals; Polychlorinated Biphenyls; Water Pollutantsarticle 1996
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van Vliet, A.K. (author), van Thiel, G.C.F. (author), Huisman, R.H. (author), Moshage, H. (author), Yap, S.H. (author), Cohen, L.H. (author), TNO Preventie en Gezondheid (author)The three vastatins examined, lovastatin, simvastatin and pravastatin, are equally strong inhibitors of the sterol synthesis in human hepatocytes in culture with IC50-values of 4.1, 8.0 and 2.0 nM, respectively. However, in the human extrahepatic cells: umbilical vascular endothelial cells, retinal pigment epithelial cells, cornea fibroblasts...article 1995
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Twisk, J. (author), Hoekman, M.F.M. (author), Lehmann, E.M. (author), Meijer, P. (author), Mager, W.H. (author), Princen, H.M.G. (author), TNO Preventie en Gezondheid (author)Evidence from in vivo studies indicates that the bile acid pool and bile acid excretion are increased in humans with diabetes mellitus and in experimental diabetic animals, and that both parameters return to normal levels after administration of insulin. To investigate the biochemical background of these changes, the effects of insulin on bile...article 1995