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Interaction of digitalis-like compounds with liver uptake transporters NTCP, OATP1B1, and OATP1B3

Gozalpour, E. (author), Greupink, R. (author), Wortelboer, H.M. (author), Bilos, A. (author), Schreurs, M. (author), Russel, F.G.M. (author), Koenderink, J.B. (author)

Digitalis-like compounds (DLCs) such as digoxin, digitoxin, and ouabain, also known as cardiac glycosides, are among the oldest pharmacological treatments for heart failure. The compounds have a narrow therapeutic window, while at the same time, DLC pharmacokinetics is prone to drug-drug interactions at the transport level. Hepatic transporters...

article 2014

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Optimization of hydroxyl radical scavenging activity of exopolysaccharides from Inonotus obliquus in submerged fermentation using response surface methodology

Chen, H. (author), Xu, X. (author), Zhu, Y. (author), TNO Kwaliteit van Leven (author)

The objectives of this study were to investigate the effect of fermentation medium on the hydroxyl radical scavenging activity of exopolysaccharides from Inonotus obliquus by response surface methodology (RSM). A two-level fractional factorial design was used to evaluate the effect of different components of the medium. Corn flour, peptone, and...

article 2010

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Clearance and clearance inhibition of the HIV-1 protease inhibitors ritonavir and saquinavir in sandwich-cultured rat hepatocytes and rat microsomes

Treijtel, N. (author), Eijkeren, J.C.H.v. (author), Nijmeijer, S. (author), van der Greef de - Sandt, I.C.J. (author), Freidig, A.P. (author), TNO Kwaliteit van Leven (author)

The metabolism and active transport of ritonavir and saquinavir were studied using sandwich-cultured rat hepatoyctes and rat liver microsomes. For ritonavir four comparable metabolites were observed in the sandwich-culture and in microsomes. For saquinavir eight metabolites were observed in sandwich-culture and 14 different metabolites in...

article 2009

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HNF/HTPB propellants: Influence of HNF particle size on ballistic properties

van der Heijden, A.E.D.M. (author), Leeuwenburgh, A.B. (author), TNO Defensie en Veiligheid (author)

The burning rate characteristics of solid composite propellants can be modified via different methods. One of these is the application of different oxidizer particle sizes in the propellant. The effect of the use of fine and coarse particles of the oxidizer hydrazinium nitroformate (HNF) in hydroxyl-terminated polybutadiene (HTPB)-based...

article 2009

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Testosterone 15β-hydroxylation by solvent tolerant Pseudomonas putida S12

Ruijssenaars, H.J. (author), Sperling, E.M.G.M. (author), Wiegerinck, P.H.G. (author), Brands, F.T.L. (author), Wery, J. (author), de Bont, J.A.M. (author), TNO Kwaliteit van Leven (author)

A steroid 15β-hydroxylating whole-cell solvent tolerant biocatalyst was constructed by expressing the Bacillus megaterium steroid hydroxylase CYP106A2 in the solvent tolerant Pseudomonas putida S12. Testosterone hydroxylation was improved by a factor 16 by co-expressing Fer, a putative Fe-S protein from Bacillus subtilis. In addition, the...

article 2007

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Human cytochrome P450 enzyme specificity for the bioactivation of estragole and related alkenylbenzenes

Jeurissen, S.M.F. (author), Punt, A. (author), Boersma, M.G. (author), Bogaards, J.J.P. (author), Fiamegos, Y.C. (author), Schilter, B. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)

Human cytochrome P450 enzymes involved in the bioactivation of estragole to its proximate carcinogen 1′-hydroxyestragole were identified and compared to the enzymes of importance for 1′-hydroxylation of the related alkenylbenzenes methyleugenol and safrole. Incubations with Supersomes revealed that all enzymes tested, except P450 2C8, are...

article 2007

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Evidence for large average concentrations of the nitrate radical (NO3) in Western Europe from the HANSA hydrocarbon database

Penkett, S.A. (author), Burgess, R.A. (author), Coe, H. (author), Coll, I. (author), Hov, O. (author), Lindskog, A. (author), Schmidbauer, N. (author), Solberg, S. (author), Roemer, M. (author), Thijsse, T. (author), Beck, J. (author), Reeves, C.E. (author), TNO Bouw en Ondergrond (author)

The nitrate radical (NO3) was first measured in the atmosphere in the 1970s and suggestions were made that it could play a major role in oxidising many unsaturated hydrocarbons, such as those emitted from the biosphere. Analysis of the hydrocarbon mix over the North Atlantic Ocean suggested subsequently that the influence of NO3 radical...

article 2007

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Achilles tendinosis: Changes in biochemical composition and collagen turnover rate

de Mos, M. (author), van El, B. (author), de Groot, J. (author), Jahr, H. (author), van Schie, H.T.M. (author), van Arkel, E.R. (author), Tol, H. (author), Heijboer, R. (author), van Osch, G.J.V.M. (author), Verhaar, J.A.N. (author), TNO Kwaliteit van Leven (author)

Background: Understanding biochemical and structural changes of the extracellular matrix in Achilles tendinosis might be important for developing mechanism-based therapies. Hypothesis: In Achilles tendinosis, changes occur in biochemical composition and collagen turnover rate. Study Design: Descriptive laboratory study. Methods: From 10 patients...

article 2007

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A sandwich-cultured rat hepatocyte system with increased metabolic competence evaluated by gene expression profiling

Kienhuis, A.S. (author), Wortelboer, H.M. (author), Maas, W.J. (author), van Herwijnen, M. (author), Kleinjans, J.C.S. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)

A rapid decline of cytochrome P450 (CYP450) enzyme activities remains a drawback of rat hepatocyte-based in vitro cultures. Consequently, judgment of the toxic potential of compounds that need bioactivation by CYP450s may not be adequate using this model. In the present study, an improved hepatocyte-based in vitro system was developed with...

article 2007

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Human cytochrome P450 enzymes of importance for the bioactivation of methyleugenol to the proximate carcinogen 1′-hydroxymethyleugenol

Jeurissen, S.M.F. (author), Bogaards, J.J.P. (author), Boersma, M.G. (author), ter Horst, J.P.F. (author), Awad, H.M. (author), Fiamegos, Y.C. (author), van Beek, T.A. (author), Alink, G.M. (author), Sudhölter, E.J.R. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)

In vitro studies were performed to elucidate the human cytochrome P450 enzymes involved in the bioactivation of methyleugenol to its proximate carcinogen 1′-hydroxymethyleugenol. Incubations with Supersomes, expressing individual P450 enzymes to a high level, revealed that P450 1A2, 2A6, 2C9, 2C19, and 2D6 are intrinsically able to 1′...

article 2006

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Characterization of some synthetic Ru and Ir complexes by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Lou, X. (author), van Buijtenen, J. (author), Bastiaansen, J.J.A.M. (author), de Waal, B.F.M. (author), Langeveld, B.M.W. (author), van Dongen, J.L.J. (author), TNO Industrie en Techniek (author)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was applied to the analysis of Ru(OCOCF 3)2(CO)(PPh3)2, Ru(OCOC 3F7)2(CO)(PPh3)2, Ir(tBuppy)3 and Ir(ppy)2(acac) complexes. A troublesome problem in the MALDI-TOFMS characterization of these metal complexes is the possible replacement of complex ligands by...

article 2005

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Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: Implications for collagen cross-linking and treatment of fibrosis

Zuurmond, A.M. (author), Slot van der-Verhoeven, A.J. (author), van Dura, E.A. (author), de Groot, J. (author), Bank, R.A. (author), TNO Kwaliteit van Leven (author)

Collagen deposits in fibrotic lesions often display elevated levels of hydroxyallysine (pyridinoline) cross-links. The relation between the occurrence of pyridinoline cross-links and the irreversibility of fibrosis suggests that these cross-links contribute to the aberrant accumulation of collagen. Based on its inhibitory effect on lysyl...

article 2005

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A novel mutation in the lysyl hydroxylase 1 gene causes decreased lysyl hydroxylase activity in an ehlers-danlos VIA patient

Walker, L.C. (author), Overstreet, M.A. (author), Siddiqui, A. (author), de Paepe, A. (author), Ceylaner, G. (author), Malfait, F. (author), Symoens, S. (author), Atsawasuwan, P. (author), Yamauchi, M. (author), Ceylaner, S. (author), Bank, R.A. (author), Yeowell, H.N. (author), TNO Preventie en Gezondheid (author)

The clinical diagnosis of a patient with the phenotype of Ehlers-Danlos syndrome type VI was confirmed biochemically by the severely diminished level of lysyl hydroxylase (LH) activity in the patient's skin fibroblasts. A novel homozygous mutation, a single base change of T1360 → G in exon 13 of the LH1 gene, predicted to result in W446G, was...

article 2005

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Amylomaltase of Pyrobaculum aerophilum IM2 produces thermoreversible starch gels

TNO Kwaliteit van Leven TNO Voeding (author), Kaper, T. (author), Talik, B. (author), Ettema, T.J. (author), Bos, H. (author), van der Maarel, M.J.E.C. (author), Dijkhuizen, L. (author)

Amylomaltases are 4-alpha-glucanotransferases (EC 2.4.1.25) of glycoside hydrolase family 77 that transfer alpha-1,4-linked glucans to another acceptor, which can be the 4-OH group of an alpha-1,4-linked glucan or glucose. The amylomaltase-encoding gene (PAE1209) from the hyperthermophilic archaeon Pyrobaculum aerophilum IM2 was cloned and...

article 2005

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Structural requirements for the flavonoid-mediated modulation of glutathione S-transferase P1-1 and GS-X pump activity in MCF7 breast cancer cells

van Zanden, J.J. (author), Geraets, L. (author), Wortelboer, H.M. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Voeding (author)

The objective of this study was to investigate the structural requirements necessary for inhibition of glutathione S-transferase P1-1 (GSTP1-1) and GS-X pump (MRP1 and MRP2) activity by structurally related flavonoids, in GSTP1-1 transfected MCF7 cells (pMTG5). The results reveal that GSTP1-1 activity in MCF7 pMTG5 cells can be inhibited by some...

article 2004

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An integral biochemical analysis of the main constituents of articular cartilage, subchondral and trabecular bone

van der Harst, M.R. (author), Brama, P.A.J. (author), van de Lest, C.H.A. (author), Kiers, G.H. (author), de Groot, J. (author), van Weeren, P.R. (author), TNO Kwaliteit van Leven (author)

Objective: In articular joints, the forces generated by locomotion are absorbed by the whole of cartilage, subchondral bone and underlying trabecular bone. The objective of this study is to test the hypothesis that regional differences in joint loading are related to clear and interrelated differences in the composition of the extracellular...

article 2004

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Phenotypic and molecular characterization of Bruck syndrome (Osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2

TNO Preventie en Gezondheid (author), Ha-Vinh, R. (author), Alanay, Y. (author), Bank, R.A. (author), Campos-Xavier, A.B. (author), Zankl, A. (author), Superti-Furga, A. (author), Bonafé, L. (author)

Bruck syndrome (BS) is a recessively-inherited phenotypic disorder featuring the unusual combination of skeletal changes resembling osteogenesis imperfects (OI) with congenital contractures of the large joints. Clinical heterogeneity is apparent in cases reported thus far. While the genes coding for collagen 1 chains are unaffected in BS, there...

article 2004

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Extracellular matrix changes in early osteochondrotic defects in foals: A key role for collagen?

Gaubius Instituut TNO (author), van de Lest, C.H.A. (author), Brama, P.A.J. (author), van El, B. (author), de Groot, J. (author), van Weeren, P.R. (author)

Osteochondrosis (OC) is the most important developmental orthopaedic disease in the horse. Despite some decades of research, much of the pathogenesis of the disorder remains obscure. Increasing knowledge of articular cartilage development in juvenile animals led to the presumption that the role of collagen in OC might be more important than...

article 2004

document

Identification of PLOD2 as Telopeptide Lysyl Hydroxylase, an Important Enzyme in Fibrosis

TNO Preventie en Gezondheid (author), van der Slot, A.J. (author), Zuurmond, A.M. (author), Bardoel, A.F.J. (author), Wijmenga, C. (author), Pruijs, H.E.H. (author), Sillence, D.O. (author), Brinckmann, J. (author), Abraham, D.J. (author), Black, C.M. (author), Verzijl, N. (author), de Groot, J. (author), Hanemaaijer, R. (author), te Koppele, J.M. (author), Huizinga, T.W.J. (author), Bank, R.A. (author)

The hallmark of fibrotic processes is an excessive accumulation of collagen. The deposited collagen shows an increase in pyridinoline cross-links, which are derived from hydroxylated lysine residues within the telopeptides. This change in cross-linking is related to irreversible accumulation of collagen in fibrotic tissues. The increase in...

article 2003

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Quantitation and localisation of (in vitro) transglutaminase-catalysed glutamine hydroxylation using mass spectrometry

Piersma, S.R. (author), van de Pijpekamp, A. (author), Wijngaards, G. (author), Gruppen, H. (author), Boumans, H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

A mass spectrometric approach was chosen to quantify and localise in vitro enzymatically modified glutamine (Gln) residues in a glutamine-rich protein. This protein (named dB1), a cloned domain of the high molecular weight wheat glutenin subunit Dx5, was modified by microbial transglutaminase (TGase) using hydroxylamine as the amine donor. Using...

article 2002