Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Field-level model approach to assess water and nutrient use efficiencies : WaterFARMING project. Report for deliverable 2.1
Silva, J.V. ; Reidsma, P. ; Jomaa, S. ; Ghaley, B.B. ; Ittersum, M.K. van; Anten, N.P.R. - \ 2018
- 25 p.
- Two models have been chosen for field-level assessment of crop yields and water- and nutrient use efficiencies: WOFOST and DAISY.
- For WOFOST a post-doc (João Vasco Silva), who is an expert in this modelling approach has been added to the team. He is also the lead author of this report.
- For DAISY, a brief description of the model and data requirements are provided as a guide for the consortium on data needs.
- For WOFOST calibration and evaluation protocols and associated data needs have been worked out. Detailed templates have been developed and distributed in the team.
- For sites in Germany and the Netherlands detailed experiments have been chosen that are ideally suited for model calibration and evaluation. The quality and detail of the data available is very high. In Denmark, data are available from a combined food and energy system for the modelling task.
- Finding suitable experimental data for the other countries is ongoing, there being some challenges in this regard. In view of this we aim to find experimental data for at least one site in South Europe and one in North Africa.
Upscaling water and nutrient use efficiencies from field to catchment scale : a case study in the Selke catchment, Germany
Silva, J.V. ; Jomaa, S. ; Chukalla, A.D. ; Yang, X. ; Merbach, I. ; Rode, M. ; Anten, N.P.R. ; Ittersum, M.K. van; Reidsma, P. - \ 2018
In: Proceedings of the 20th Nitrogen Workshop. - INRA - p. 60 - 61.
Thyroid in a jar: towards an integrated in vitro testing strategy for thyroid-active compounds
Jomaa, B. - \ 2015
Wageningen University. Promotor(en): Ivonne Rietjens, co-promotor(en): Jac Aarts; Ad Peijnenburg. - Wageningen : Wageningen University - ISBN 9789090290089 - 187
schildklierziekten - schildklierhormonen - hormoonverstoorders - in vitro - assays - celgroei - thyroid diseases - thyroid hormones - endocrine disruptors - in vitro - assays - cell growth

Jomaa, B. (2015). Thyroid in a Jar: Towards an Integrated In Vitro Testing Strategy for Thyroid-Active Compounds. PhD thesis, Wageningen University, the Netherlands

Abstract

The aim of this thesis was to find in vitro and toxicogenomics-based alternatives to in vivo thyroid hormone disruption tests. In vitro alternatives can help reduce the amount of animal testing required under the European Union regulation for the registration, evaluation, authorization and restriction of chemicals (REACH). Moreover, with the use of human cell lines and human-identical synthetic proteins, interspecies differences can be reduced and in some cases eliminated. This thesis has shed light on the relevance of current in vitro assays for thyroid and pituitary cell proliferation, has led to the development of the TSH screen, a luminol-based thyroid peroxidase inhibition assay and the zebrafish-based general development score (GDS) for the detection of developmental toxicants, including those that act through the thyroid hormone system. Moreover, the microarray assay for real-time coregulator-nuclear receptor interaction (MARCoNI) assay was used to reveal the modulating effects of thyroid-active compounds on TRα and TRβ interactions with a peptide array representing 66 different coregulators. These developments along with an in-depth analysis of the thyroid hormone system and the presentation of the state of the art in thyroid disruption testing have highlighted the progress made and at the same time have underlined the challenges that lay ahead.

Simple and rapid in vitro assay for detecting human thyroid peroxidase disruption
Jomaa, B. ; Haan, L.H.J. de; Peijnenburg, A.A.C.M. ; Bovee, T.F.H. ; Aarts, J.M.M.J.G. ; Rietjens, I.M.C.M. - \ 2015
Altex 32 (2015)3. - ISSN 0946-7785 - p. 191 - 200.
A simple and rapid luminometric assay for the detection of chemical inhibitors of human thyroid peroxidase (hTPO) activity was developed and validated with 10 model compounds. hTPO was derived from the human thyroid follicular cell line Nthy-ori 3-1 and its activity was quantified by measuring the oxidation of luminol in the presence of hydrogen peroxide (H2O2), which results in the emission of light at 428 nm. In this assay,hTPO activity was shown to be inhibited by 5 known TPO inhibitors and not inhibited by 5 non-inhibitors. Similar results were obtained with porcine TPO (pTPO).The inhibition of hTPO by the model compounds was also tested with guaiacol and Ampliflu Red as alternative indicator substrates. While all substrates allowed the detection ofpTPO activity and its inhibition, only the Ampliflu Red and luminol-based methods were sensitive enough to allow the quantification of hTPO activity from Nthy-ori 3-1 cell lysates. Moreover, luminol gave results with a narrower 95% confidence interval and therefore more reliable data.Whole extracts of fast-growing Nthy-ori 3-1 cells circumvent the need for animal-derived thyroid organs,thereby reducing costs, eliminating potential contamination and providing the possibility to study human instead of porcine TPO. Overall, the application of luminoland Nthy-ori 3-1 cell lysate for the detection of the disruption of hTPO activity was found to represent a valuable in vitro alternative and a possible candidate for inclusion within a high throughput integrated testing strategy for the detection of compounds that potentially interfere with normal thyroid function in vivo.
Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test
Jomaa, B. ; Hermsen, S.A.B. ; Kessels, M.Y. ; Berg, J.H.J. van den; Peijenburg, A.C.M. ; Aarts, J.M.M.J.G. ; Piersma, A.H. ; Rietjens, I. - \ 2014
Altex 31 (2014)3. - ISSN 0946-7785 - p. 303 - 317.
Zebrafish embryos were exposed to concentration ranges of selected thyroid-active model compounds in order to assess the applicability of zebrafish-based developmental scoring systems within an alternative testing strategy to detect the developmental toxicity of thyroid-active compounds. Model compounds tested included triiodothyronine (T3), propylthiouracil (PTU), methimazole (MMI), sodium perchlorate (NaClO4) and amiodarone hydrochloride (AMI), selected to represent different modes of action affecting thyroid activity. Tested time windows included 48-120 hours post fertilization (hpf), 0-72 hpf and 0-120 hpf. All tested compounds resulted in developmental changes, with T3 being the most potent. The developmental parameters affected included reflective iridophores, beat and glide swimming, inflated swim bladders, as well as resorbed yolk sacs. These effects are only evident by 120 hpf and therefore an existing General Morphology Score (GMS) system was extended to create a General Developmental Score (GDS) that extends beyond the 72 hpf scoring limit of GMS and includes additional parameters that are affected by exposure to model thyroid-active compounds. Moreover, the GDS is cumulative as it includes not only the scoring of developmental morphologies but also integrates developmental dysmorphologies. Exposures from 48-120 hpf did not provide additional information to exposures from 0-120 hpf. The results indicate that the zebrafish GDS can detect the developmental toxicity of thyroid toxicants and may be of use in an integrated testing strategy to reduce, refine and, in certain cases, replace animal testing.
In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing
Jomaa, B. ; Aarts, M.M.J.G. ; Haan, L.H.J. de; Peijnenburg, A.A.C.M. ; Bovee, T.F.H. ; Murk, A.J. ; Rietjens, I.M.C.M. - \ 2013
In: Book of Abstracts of the 49th Congress of the European Societies of Toxicology (EUROTOX). - - p. S151 - S151.
This study investigates the in vitro effect of eleven thyroid-active compounds, known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called “T-screen,” and of FRTL-5 rat thyroid cells in a newly developed test denoted “TSH-screen” to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point at the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro, and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.
In Vitro Pituitary and Thyroid Cell Proliferation Assays and Their Relevance as Alternatives to Animal Testing
Jomaa, B. ; Aarts, M.M.J.G. ; Haan, L.H.J. de; Peijnenburg, A.A.C.M. ; Bovee, T.F.H. ; Murk, A.J. ; Rietjens, I.M.C.M. - \ 2013
Altex 30 (2013)3. - ISSN 0946-7785 - p. 293 - 307.
This study investigates the in vitro effect of eleven thyroid-active compounds known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid cells in a newly developed test denoted "TSH-screen" to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point to the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.
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