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Feasibility of SPECT-CT imaging to study the pharmacokinetics of antisense oligonucleotides in a mouse model of Duchenne muscular dystrophy

van de Steeg, E. (author), Läppchen, T. (author), Aguilera, B. (author), Jansen, H.T. (author), Muilwijk, D. (author), Vermue, R. (author), van der Hoorn, J.W. (author), Donato, K. (author), Rossin, R. (author), de Visser, P.C. (author), Vlaming, M.L.H. (author)

Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic. We assessed the feasibility of using...

article 2017

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The ultimate radiochemical nightmare: Upon radio-iodination of Botulinum neurotoxin A, the introduced iodine atom itself seems to be fatal for the bioactivity of this macromolecule

van Uhm, J.I.M. (author), Visser, G.W.M. (author), van der Schans, M.J. (author), Geldof, A.A. (author), Meuleman, E.J.H. (author), Nieuwenhuijzen, J.A. (author)

Background: Botulinum neurotoxin A (BoNT-A) is a highly neurotoxic drug and frequently used in patients. Knowledge on the optimal way of administration of BoNT-A and its subsequent distribution is still rather limited. An accurate method for monitoring these processes might be the use of radiolabelled BoNT-A. In this paper, we report our...

article 2015

document

Inflammation and nutritional science for programs/policies and interpretation of research evidence (INSPIRE)

Raiten, D.J. (author), Sakr Ashour, F.A. (author), Ross, A.C. (author), Meydani, S.N. (author), Dawson, H.D. (author), Stephensen, C.B. (author), Brabin, B.J. (author), Suchdev, P.S. (author), van Ommen, B. (author), Ahluwalia, N. (author), Ahmed, T. (author), Allen, L. (author), Beck, M. (author), Blanchard, H. (author), Brindle, E. (author), Brown, K. (author), Calder, P. (author), Checkley, W. (author), Claycombe, K. (author), Coles, C. (author), Esamai, F. (author), Friis, H. (author), Gardner, E. (author), Grinspoon, S. (author), Guerrant, R. (author), Hellerstein, M. (author), Hunt, J. (author), King, J. (author), Klasing, K. (author), Kramer, B. (author), Koski, K. (author), Northrop-Clewes, C. (author), Pfeiffer, C. (author), Prentice, A. (author), Ramirez-Zea, M. (author), van Rheenan, P. (author), Rink, L. (author), Srinivasa, S. (author), Benn, C.S. (author), Stephensen, C. (author), Suchdev, P. (author), Sullivan, K. (author), Thurnham, D. (author), Varadhan, R. (author), Van Der Ven, A. (author), Walston, J. (author), Xia, J. (author)

An increasing recognition has emerged of the complexities of the global health agenda-specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1) the need for a better understanding of the bidirectional relations between nutritional status and...

article 2015

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LDL receptor deficiency results in decreased cell proliferation and presynaptic bouton density in the murine hippocampus

Mulder, M. (author), Koopmans, G. (author), Wassink, G. (author), Mansouri, G.A. (author), Simard, M.-L. (author), Havekes, L.M. (author), Prickaerts, J. (author), Blokland, A. (author), TNO Kwaliteit van Leven (author)

An aberrant cholesterol metabolism in the brain may contribute to the pathogenesis of Alzheimer's disease (AD). The LDL receptor (LDLR) regulates plasma cholesterol levels and recently we and others obtained evidence that it is also involved in regulating brain cholesterol homeostasis. Moreover, we found that LDLR-deficient mice display impaired...

article 2007

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Design and synthesis of novel N-acetylgalactosamine-terminated glycolipids for targeting of lipoproteins to the hepatic asialoglycoprotein receptor

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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Binding and transfer of verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome

te Loo, D.M.W.M. (author), Monnens, L.A.H. (author), van der Velden, T.J.A.M. (author), Vermeer, M.A. (author), Preyers, F. (author), Demacker, P.N.M. (author), van den Heuvel, L.P.W.J. (author), van Hinsbergh, V.W.M. (author), Gaubius instituut TNO (author)

The hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. The role of a verocytotoxin (VT)-producing Escherichia coli has been strongly implicated in the epidemic form of HUS. Although direct toxicity of VT on glomerular endothelial cells has been demonstrated, it remained still unclear how the VT is...

article 2000

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Binding of β-VLDL to heparan sulfate proteoglycans requires lipoprotein lipase, whereas apoE only modulates binding affinity

de Beer, F. (author), Hendriks, W.L. (author), van Vark, L.C. (author), Kamerling, S.W.A. (author), van Dijk, K.W. (author), Hofker, M.H. (author), Smelt, A.H.M. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)

The binding of β-VLDL to heparan sulfate proteoglycans (HSPG) has been reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the present study we investigated the effect of the isoform and the amount of apoE per particle, as well as the role of LPL on the binding of β-VLDL to HSPG. Therefore, we isolated β-VLDL from transgenic...

article 1999

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Fibrinolytic activity of human mesothelial cells is counteracted by rapid uptake of tissue-type plasminogen activator

Sitter, T. (author), Toet, K. (author), Quax, P. (author), Kooistra, T. (author), Gaubius instituut TNO (author)

Background. Human mesothelial cells (HMCs) have an important role in maintaining an adequately functioning fibrinolytic system in the peritoneal cavity by secreting the fibrinolytic enzymes tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), as well as a specific PA inhibitor, PA inhibitor type 1 (PAI-1). In this study, we...

article 1999

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Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

Schalkwijk, C.G. (author), Vermeer, M.A. (author), Stehouwer, C.D.A. (author), te Koppele, J. (author), Princen, H.M.G. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)

In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. α-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with diabetes. We studied the effect of the α-dicarbonyl...

article 1998

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The role of the low-density lipoprotein receptor-related protein (LRP) in the plasma clearance and liver uptake of recombinant single-chain urokinase-type plasminogen activator in rats

van der Kaaden, M.E. (author), Rijken, D.C. (author), Kruijt, J.K. (author), van Berkel, T.J.C. (author), Kuiper, J. (author), TNO Preventie en Gezondheid (author)

Urokinase-type plasminogen activator (u-PA) is used as a thrombolytic agent in the treatment of acute myocardial infarction. In vitro, recombinant single-chain u-PA (rscu-PA) expressed in E. coli is recognized by the Low-Density Lipoprotein Receptor-related Protein (LRP) on rat parenchymal liver cells. In this study we investigated the role of...

article 1997

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Lipolysis of very low density lipoproteins by heparan sulfate proteoglycan-bound lipoprotein lipase

Gaubius Instituut TNO (author), de Man, F.H.A.F. (author), de Beer, F. (author), van der Laarse, A. (author), Smelt, A.H.M. (author), Havekes, L.M. (author)

An in vitro assay to study lipolysis of very low density lipoproteins (VLDL) by heparan sulfate proteoglycan (HSPG-bound lipoprotein lipase (LPL) was developed. Optimal conditions for VLDL lipolysis by HSPG-bound LPL were obtained by incubating plastic wells with 0.5 ug HSPG and 1.5 ug LPL, subsequently. Control experiments with heparinase...

article 1997

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Calculated iodine intake before and after simulated iodization (Dutch Nutrition Surveillance System)

Brussaard, J.H. (author), Hulshof, K.F.A.M. (author), Löwik, M.R.H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

To estimate the effect of possible goitre prophylactic measures on the intake of iodine among population groups, simulation studies, based on the first Dutch National Food Consumption Survey, were carried out. Iodine intake figures and prevalence of low intakes were calculated after fictively iodizing either bread, a combination of industrial...

article 1995

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Low-density lipoproteins are degraded in HepG2 cells with low efficiency

Lombardi, P. (author), Mulder, M. (author), de Wit, E. (author), van Berkel, T.J.C. (author), Frants, R.R. (author), Havekes, L.M. (author), Instituut voor verouderings- en vaatziekten onderzoek TNO (author)

In previous studies we have shown that in HepG2 cells, as compared with fibroblasts, the low-density lipoprotein (LDL) receptor is only weakly down-regulated upon incubation of the cells with LDL. To explain this difference in down-regulation of the LDL-receptor activity, we studied simultaneously the intracellular processing of 125I-labelled...

article 1993

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Characterization of the interaction both in vitro and in vivo of tissue-type plasminogen activator (t-PA) with rat liver cells. Effects of monoclonal antibodies to t-PA

Otter, M. (author), Kuiper, J. (author), Bos, R. (author), Rijken, D.C. (author), van Berkel, T.J.C. (author), Gaubius Laboratory Instituut voor verouderings- en vaatziekten onderzoek TNO (author)

The interaction of 125I-labelled tissue-type plasminogen activator (125I-t-PA) with freshly isolated rat parenchymal and endothelial liver cells was studied. Binding experiments at 4°C with parenchymal cells and endothelial liver cells indicated the presence of 68000 and 44000 high-affinity t-PA-binding sites, with an apparent K(d) of 3.5 and 4...

article 1992

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In vivo and in vitro interaction of high and low molecular weight single-chain urokinase-type plasminogen activator with rat liver cells

Gaubius instituut Instituut voor verouderings- en vaatziekten onderzoek TNO (author), Kuiper, J. (author), Rijken, D.C. (author), Munk, G.A. (author), van Berkel, T.J. (author)

The plasma clearance and the interaction of high (HMW) and low (LMW) molecular weight single-chain urokinase-type plasminogen activator (scu-PA) with rat liver cells was determined. 125I-Labeled HMW- and LMW-scu-PA were rapidly cleared from plasma with a half-life of 0.45 min and a maximal liver uptake of 55% of the injected dose. Liver uptake...

article 1992

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Partial characterization of low density lipoprotein preparations isolated from fresh and frozen plasma after radiolabeling by seven different methods

Gaubius Instituut TNO (author), Atsma, D.E. (author), Kempen, H.J.M. (author), Nieuwenhuizen, W. (author), van 't Hooft, F.M. (author), Pauwels, E.K.J. (author)

Four 99mTc and three 123I labeling methods were evaluated for their suitability to label low density lipoproteins (LDL) for the purpose of scintigraphic biodistribution studies. For 99mTc these methods were: direct incorporation in LDL of 99mTcO4- using sodium dithionite (dithionite method); a method using first N,N-dimethylformamide to prepare...

article 1991

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Evidence for the occurrence of a fast-acting inhibitor for tissue-type plasminogen activator in human plasma

Verheijen, J.H. (author), Chang, G.T.G. (author), Kluft, C. (author), Gaubius Instituut TNO (author)

Human plasma contains a fast-acting t-PA inhibitor, which is not identical with ??2-antiplasmin or ??2-macroglobulin. The concentration of this inhibitor in normal plasma is highly variable, much lower than that of known plasma protease inhibitors, and in the range of physiologically occurring plasma concentrations of t-PA (0-2 IU/ml). The...

article 1984

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Investigation of an iodine-like taste in herring from the Baltic Sea

Bemelmans, J.M.H. (author), den Braber, H.J.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Marinated herring from the Baltic Sea was found to have an offensive odor and taste described as iodine-like and phenolic. Fat isolated from herring was found to contain this taint. The volatiles were isolated from the fat, using a molecular distillation and were subsequently fractionated by gas chromatography. A fraction containing the taint...

conference paper 1983

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Characterization of the components of technically polychlorinated biphenyl mixtures-II

Centraal Instituut voor Voedingsonderzoek TNO (author), Tas, A.C. (author), Kleipool, R.J.C. (author)

article 1972

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Toxicologic and pharmacologic properties of iocetamic acid, a new oral cholecystographic agent

Centraal Instituut voor Voedingsonderzoek TNO (author), Janbroers, J.M. (author), Sanders, J.C. (author), Til, H.P. (author), Feron, V.J. (author), de Groot, A.P. (author)

Studies in rats on iocetamic acid show that the LD50 levels of this compound compare favorably with those of a number of other oral cholecystographic agents. Pathologic effects are not found in rats and cats in studies of the subacute toxicity. Incompatibility with an anesthetic or a tranquilizer is not found. The elimination pattern of...

article 1969