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Innovative pharmaceutical interventions in cardiovascular disease: Focusing on the contribution of non-HDL-C/LDL-C-lowering versus HDL-C-raisingA systematic review and meta-analysis of relevant preclinical studies and clinical trials

Kühnast, S. (author), Fiocco, M. (author), van der Hoorn, J.W.A. (author), Princen, H.M.G. (author), Jukema, J.W. (author)

Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their primary goals. This...

article 2015

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Novel non-systemic inhibitor of ileal apical Na+-dependent bile acid transporter reduces serum cholesterol levels in hamsters and monkeys

Kitayama, K. (author), Nakai, D. (author), Kono, K. (author), van der Hoop, A.G. (author), Kurata, H. (author), de Wit, E.C. (author), Cohen, L.H. (author), Inaba, T. (author), Kohama, T. (author), TNO Preventie en Gezondheid (author)

1-{7-[(1-(3,5-Diethoxyphenyl)-3-{[(3,5-difluorophenyl)(ethyl)amino]carbo nyl}-4-oxo-1,4-dihydroquinolin-7-yl)oxy]heptyl}-1-methylpiperidinium bromide, R-146224, is a potent, specific ileum apical sodium-dependent bile acid transporter (ASBT) inhibitor; concentrations required for 50% inhibition of [3H]taurocholate uptake in human ASBT-expressing...

article 2006

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Species differences in hepatic peroxisome proliferation, cell replication and transforming growth factor-β1 gene expression in the rat, Syrian hamster and guinea pig

Lake, B.G. (author), Rumsby, P.C. (author), Price, R.J. (author), Cunninghame, M.E. (author), TNO BIBRA TNO Kwaliteit van Leven (author)

The objective of this study was to evaluate species differences in the hepatic effects of three potent rodent peroxisome proliferators, namely methylclofenapate (MCP), ciprofibrate (CIP) and Wy-14,643 (WY), particularly with respect to effects on replicative DNA synthesis and transforming growth factor-β1 (TGF-β1) gene expression. Male Sprague...

article 2000

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Inhibition of tolbutamide 4-methylhydroxylation by a series of non-steroidal anti-inflammatory drugs in V79-NH cells expressing human cytochrome P4502C10

Kappers, W.A. (author), de Groene, E.M. (author), Kleij, L.A. (author), Witkamp, R.F. (author), Zweers-Zeilmaker, W.M. (author), Feron, V.J. (author), Horbach, G.J. (author), TNO Voeding (author)

1. To study the role of cytochrome P4502C10 in the metabolism of the non-steroidal antiinflammatory drugs (NSAIDs) diclofenac, phenylbutazone, fenoprofen, ibuprofen, flurbiprofen, ketoprofen and naproxen, a cell line was developed stably expressing CYP2C10 cDNA. A retroviral vector construct, containing a human CYP2C10 cDNA, was transfected in...

article 1996

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Influence of growth factors and medium composition on benzo[a]pyrene- and vitamin A-induced cell proliferation and differentiation in hamster tracheal epithelium in organ culture

Wolterbeek, A.P.M. (author), Ciotti, M.A.L.T. (author), Schoevers, E.J. (author), Roggeband, R. (author), Baan, R.A. (author), Feron, V.J. (author), Rutten, A.A.J.J.L. (author), TNO Voeding (author)

Tracheal organ cultures and isolated tracheal epithelial cells are frequently used to study effects of carcinogens and retinoids on both proliferation and differentiation of respiratory tract epithelial cells. For each of these in vitro models, optimal culture conditions have been established, varying in type of culture medium and composition of...

article 1996

document

Expression of receptors for gut peptides in pancreata of BOP-treated and control hamsters

Tang, C. (author), Biemond, I. (author), Appel, M.J. (author), Visser, C.J.T. (author), Woutersen, R.A. (author), Lamers, C.B.H.W. (author), TNO Voeding (author)

The growth of pancreatic cancers may be influenced by certain gut peptides. However, the alteration of gut peptide receptors in the progress of pancreatic carcinogenesis is largely unknown. With storage phosphor autoradiography, this study visualized and characterized receptors for cholecystokinin (CCK), somatostatin (SST), bombesin (BBS),...

article 1996

document

Detection of adducts formed upon treatment of DNA with cisplatin and carboplatin

Fichtinger-Schepman, A.M.J. (author), Welters, M.J.P. (author), van Dijk-Knijnenburg, H.C.M. (author), van der Sterre, M.L.T. (author), Tilby, M.J. (author), Berends, F. (author), Baan, R.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

In order to determine the nature of the cytotoxic lesion(s) formed by the antitumour drugs cisplatin and carboplatin, a comparative study was made of bifunctional DNA-adduct formation by these drugs. The kinetics of bifunctional cisplatin adduct formation were studied with DNA in vitro and in cultured Chinese hamster ovary (CHO) cells. Prior to...

bookPart 1996

document

Polymyopathy in a Syrian golden hamster

Wijnands, M.V.W. (author), Woutersen, R.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

A Syrian golden hamster suffered from general swelling of skeletal muscles. At microscopical observation the muscle tissue exhibited degeneration and necrosis, as well as regenerative features. The inflammatory response was very slight. The histopathological lesions were diagnosed as polymyopathy.

article 1996

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Ca2+ strongly modulates the effect of vitamin A on benzo[a]pyrene-induced cell proliferation in hamster tracheal epithelium in organ culture

Wolterbeek, A.P.M. (author), Ciotti, M.A.L.T. (author), Schoevers, E.J. (author), Feron, V.J. (author), Rutten, A.A.J.J.L. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)

Chemicals/CAS: benzo[a]pyrene, 50-32-8; calcium ion, 14127-61-8; retinol, 68-26-8, 82445-97-4

article 1996

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Overexpression of transforming growth factor-α and epidermal growth factor receptor, but not epidermal growth factor, in exocrine pancreatic tumours in hamsters

Visser, C.J.T. (author), Bruggink, A.H. (author), Korc, M. (author), Kobrin, M.S. (author), de Weger, R.A. (author), Seifert-Bock, I. (author), van Blokland, W.T.M. (author), van Garderen Hoetmer, A. (author), Woutersen, R.A. (author), TNO Voeding (author)

Using immunohistochemistry, Northern blotting and a semi-quantitative PCR technique, epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and epidermal growth factor receptor (EGFR) expression were studied in the pancreas of N-nitrosobis(2-oxopropyl)-amine (BOP)-treated hamsters. After initiation pancreatic carcinogenesis was...

article 1996

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Relation between benzo[a]pyrene-DNA adducts, cell proliferation and p53 expression in tracheal epithelium of hamsters fed a high B-carotene diet

Wolterbeek, A.P.M. (author), Roggeband, R. (author), Baan, R.A. (author), Feron, V.J. (author), Rutten, A.A.J.J.L. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Vitamin A and β-carotene protect against respiratory tract cancer by inhibiting the formation of DNA damage and controlling cellular proliferation and differentiation, Recently, it has been shown that the p53 tumor-suppressor gene plays a crucial role in the etiology of respiratory tract cancer. In the present study, we investigated the...

article 1995

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Effects of aminoglutethimide alone and in combination with surgical castration, on pancreatic carcinogenesis in rats and hamsters

Visser, C.J.T. (author), Meijers, M. (author), van Garderen-Hoetmer, A. (author), Klijn, J.G.M. (author), Foekens, J.A. (author), Woutersen, R.A. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

The present 12-month study was carried out to investigate the effects of the aromatase inhibitor aminoglutethimide, alone and in combination with orchiectomy, on pancreatic carcinogenesis in azaserine-treated rats and N-nitrosobis(2-oxopropyl)amine-treated hamsters. Treatment of the animals started 4 months after the last injection with the...

article 1995

document

Effects of dietary fish oil (MaxEPA) on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinogenesis in hamsters

Appel, M.J. (author), Woutersen, R.A. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

In the present study the chemopreventive potential of 25% fat (HF) diets containing 2 wt% linoleic acid (LA) and including 0.0, 1.2, 2.4, 4.7, 7.1 or 9.4 wt% dietary fish oil (MaxEPA) has been investigated using the N-nitrosobis(2-oxopropyl)amine (BOP)-hamster model for pancreatic cancer. The number of pancreatic borderline lesions (BLL) was...

article 1995

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Safety evaluation of β-glucanase derived from Trichoderma reesei: Summary of toxicological data

Coenen, T.M.M. (author), Schoenmakers, A.C.M. (author), Verhagen, H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Barlican, a β-glucanase enzyme obtained from Trichoderma reesei, was produced by a fermentation process and subjected to a series of toxicological tests to document its safety for use as a feed additive. The enzyme product was examined for general oral toxicity, inhalation toxicity, irritation to eye and skin, skin sensitization and mutagenic...

article 1995

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Vitamin A and β-carotene influence the level of benzo[a]pyrene-induced DNA adducts and DNA-repair activities in hamster tracheal epithelium in organ culture

Wolterbeek, A.P.M. (author), Roggeband, R. (author), van Moorsel, C.J.A. (author), Baan, R.A. (author), Koeman, J.H. (author), Feron, V.J. (author), Rutten, A.A.J.J.L. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Although most studies concerning the effect of vitamin A and β-carotene on chemical carcinogenesis are focused on tumour promotion and progression, these compounds may affect initiation as well. In this study the influence of vitamin A and β-carotene on unscheduled DNA synthesis (UDS) was investigated in hamster tracheal epithelium in organ...

article 1995

document

Effects of thiourea and ammonium bicarbonate on the formation and stability of bifunctional cisplatin-DNA adducts: Consequences for the accurate quantification of adducts in (cellular) DNA

Fichtinger-Schepman, A.M.J. (author), van Dijk-Knijnenburg, H.C.M. (author), Dijt, F.J. (author), van der Velde-Visser, S.D. (author), Berends, F. (author), Baan, R.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Cisplatin reacts with DNA by forming mainly bifunctional adducts via reactive monofunctional intermediates. When freshly platinated DNA was postincubated with thiourea (10 mM, at 23 or 37°C) for periods of up to 24 h, followed by determination of mono- and diadducts, a rapid initial decrease was seen in the fraction of diadducts, followed by a...

article 1995

document

Purification and characterization of eight glutathione S-transferase isoenzymes of hamster: comparison of subunit composition of enzymes from liver, kidney, testis, pancreas and trachea

Instituut CIVO-Toxicologie en Voeding TNO (author), Bogaards, J.J.P. (author), van Ommen, B. (author), van Bladeren, P.J. (author)

Eight dimeric isoenzymes of glutathione S-transferase (GST) were purified from liver, kidney and testis of the Syrian golden hamster, using S-hexylglutathione affinity chromatography and chromatofocusing. The isoenzymes were characterized according to their substrate selectivity, physical properties and amino acid sequence analysis. Thus a...

article 1992

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Effects of all-trans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. I. A cell proliferation study

Rutten, A.A.J.J.L. (author), Wilmer, J.W.G.M. (author), Beems, R.B. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The effects of cigarette smoke condensate (CSC) and all-trans retinol on the cell proliferative activity of vitamin A-deprived hamster tracheal epithelium have been studied in vitamin A-deficient, serum-free, hormone-supplemented medium in organ culture. In the absence of retinol, CSC induced a dose-dependent increase in labelig index (LI)...

article 1988

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Effects of all-trans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. II. A histomorphological study

Rutten, A.A.J.J.L. (author), Beems, R.B. (author), Wilmer, J.W.G.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The effects of all-trans retinol and cigarette smoke condensate (CSC) on tissue morphology and cellular differentiation were investigated in vitamin A-deprived tracheal epithelium cultured in vitamin A- and serum-free hormone-supplemented medium. Physiological retinol concentrations prevented the development of hyperplasia and squamous...

article 1988

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Effect of retinol and cigarette-smoke and condensate on dye-coupled intercellular communication between hamster tracheal epithelial cells

Rutten, A.A.J.J.L. (author), Jongen, W.M.F. (author), de Haan, L.H.J. (author), Hendriksen, E.G.J. (author), Koeman, J.H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The dye-coupled intercellular communication across gap junctions in primary hamster tracheal epithelial cells has been studied in serum-free, hormone-supplemented medium. In the absence of vitamin A, non-cytotoxic concentrations of cigarette-smoke condensate (CSC) inhibited intercellular communication between tracheal epithelial cells in a...

article 1988