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Nauwynck H.J.,Ghent University | Sanchez R.,University of the Philippines at Los Baños | Meerts P.,Ablynx | Lefebvre D.J.,CODA CERVA | And 3 more authors.
Virus Research | Year: 2012

Porcine circovirus 2 (PCV2) may induce reproductive failure (return to oestrus, embryonic death, mummification, weak- and stillborn piglets) and postweaning multisystemic wasting syndrome (PMWS). Furthermore, it may modulate the immunity in such a way that it aggravates the outcome of many bacterial and viral infections. In the present paper, the cellular tropism and entry of PCV2 are described and linked with the pathological and clinical consequences. © 2011 Elsevier B.V.


PubMed | Vrije Universiteit Brussel, CODA CERVA, University of Antwerp, Scientific Institute of Public Health WIV ISP and University of Liège
Type: | Journal: Toxicology in vitro : an international journal published in association with BIBRA | Year: 2016

Endocrine activity of 65 compounds migrating from polycarbonate replacement plastic baby bottles was assessed using in vitro cell based assays (reporter gene assays) involving 7 nuclear receptors, i.e. human steroid hormones receptors (oestrogen, androgen, progesterone and glucocorticoid receptors), human thyroid beta and peroxisome proliferator-activated gamma receptors, and the mouse aryl hydrocarbon receptor. The chemicals were tested at 4 concentrations ranging from 0.001mM to 1mM. Only twelve chemicals did not show any activity towards any of the nuclear receptors, while fifty three compounds showed a possible endocrine activity. Most of the agonistic activities were observed towards the oestrogen receptor while the PPAR was the target for most of the recorded antagonistic activities. Agonistic activities were recorded for several phthalates, benzophenones, aromatic hydrocarbons and phenols, while compounds such as benzaldehydes, ketones and esters of fatty acid showed antagonistic activities. Thirty five chemicals were able of agonistic activities on 1 to 4 receptors and antagonistic activities were recorded for 35 compounds as well, towards 1 to 7 receptors. Sixteen compounds were able of both agonistic and antagonistic activities, but not on the same receptors, except in 2 cases for the oestrogen receptor and 4 cases for the PPAR.


Versilovskis A.,Coda Research | Versilovskis A.,Ghent University | Geys J.,Coda Research | Huybrechts B.,Coda Research | And 3 more authors.
World Mycotoxin Journal | Year: 2012

In vivo metabolism of masked or conjugated mycotoxins is poorly documented as standards are not commercially available and indirect analysis using hydrolytic enzymes is difficult to validate and cumbersome. We synthesised zearalenone-14-glucoside (ZEA-14G) chemically. Deoxynivalenol-3-glucuronide (DON-3GlcA) and glucuronides of 3- and 15-acetyl-deoxynivalenol (3- and 15-ADON-GlcAs), de-epoxydeoxynivalenol, zearalenone (ZEA), α- and β-zearalenol (α- and β-ZOL) were synthesised using rat microsomes. For the first time three ADON-GlcAs were synthesised: two 3-ADON-GlcAs and one 15-ADON-GlcA. After purification, the masked mycotoxin and the metabolites were characterised by NMR (DON-3GlcA, ZEA-14G) or by full scan MS, MS/MS fragmentation, UV-spectra, β-glucosidase and β-glucuronidase treatment. In a first experiment, rats were fed orally DON-3-glucoside (DON-3G) and ZEA-14G, together with 13C-DON and 13C-ZEA and were sacrificed after 55 minutes. A total of 21 masked metabolites, metabolites and parent mycotoxins were quantified in rat organs. Whereas DON-3G was hardly hydrolysed in the stomach, ZEA was clearly formed from ZEA-14G. In a second experiment, 3- and 15-ADON were given orally to rats. The acetylated forms of DON were hydrolysed in the stomach, in contrast to DON-3G. Rats can directly glucuronidate ADONs without deacetylation. Neither DOM, α- or β-ZOL nor their glucuronides could be quantified. Glucuronidated 3-ADON accumulated in the small intestines, together with DON-3GlcA in rats fed orally with 3- and 15-ADON. These differences in masked mycotoxins metabolism can be important in risk analysis of masked mycotoxins in food and feed. © 2012 Wageningen Academic Publishers.


Verleysen E.,CODA CERVA | De Temmerman P.-J.,CODA CERVA | De Temmerman P.-J.,Catholic University of Leuven | Van Doren E.,CODA CERVA | And 3 more authors.
Powder Technology | Year: 2014

The physical properties of TiO2 nanomaterials are determined quantitatively using a method that combines imaging by transmission electron microscopy (TEM) with semi-automatic particle detection and analysis. The method is applied on four powdered TiO2 nanomaterials, NM-102, NM-103, NM-104 and NM-105, dispersed in distilled water. Qualitative analysis shows that the stability and polydispersity of the dispersed nanomaterials are influenced by the material from which the vial used for dispersion, is made. In glass vials, the uncoated nanomaterials, NM-102 and NM-105, precipitate immediately after sonication, while the coated nanomaterials, NM-103 and NM-104, remain stable in dispersion. In polypropylene vials, stable dispersions are obtained for all nanomaterials. It is shown that the vial material alters the pH of the dispersions, which in turn influences the agglomeration state of the nanomaterials. Quantitative analysis of stable dispersions, based on TEM imaging combined with semi-automatic image analysis, results in number-based distributions of characteristic parameters, measuring the size, shape and surface topology of the unbound, aggregated and agglomerated TiO2 particles. Iterative curve fitting is applied to the number-based distributions of selected parameters and allows objective comparison of the distributions based on the properties of the fitted curves. Using this method, it is shown that the size, the shape and the surface properties of NM-102 and NM-105 and of the coated nanomaterials, NM-103 and NM-104, are significantly different. The physical characteristics of NM-103 and NM-104 are similar. This supports the validity of the method as these are in fact the same material with a different coating. © 2014 Elsevier B.V.


Ferreira H.L.,University of Sao Paulo | Pirlot J.F.,CODA CERVA | Reynard F.,R and D MERIAL S. A.S | Van Den Berg T.,CODA CERVA | And 2 more authors.
Avian Diseases | Year: 2012

Ducks play an important role in the epidemiology of avian influenza, and there is a need for new avian influenza vaccines that are suitable for mass vaccination in ducks. The immune responses as well as highly pathogenic avian influenza (HPAI) H5N1 protection induced by a Newcastle disease virus (NDV) vector expressing an H5N1 hemagglutinin (rNDV-H5) were investigated in mule ducks, a hybrid between Muscovy (Cairina moschata domesticus) males and Pekin (Anas platyrhynchos domesticus) females. Immunological tools to measure NDV and H5-specific serum antibody, mucosal, and cell-mediated immune (CMI) responses in ducks have been validated after infection with the vector NDV and an H5N1 low pathogenic avian influenza virus. The effect of maternally-derived antibodies (MDAs) to NDV on the humoral and CMI responses after NDV-H5 vaccination was also investigated. Our results showed the rNDV-H5 vaccine elicits satisfactory humoral and cellular responses in 11-day-old ducks correlating with a complete clinical and virological protection against the H5N1 strain. However, vaccination with rNDV-H5 in the presence of NDV MDA induced lower NDV-specific serum antibody, mucosal, and CMI responses than in ducks with no MDA, while interestingly the H5-specific serum antibody and duodenal IgY response were higher in ducks with NDV MDA. To our knowledge, this is the first report of the use of an NDV vector in ducks and of an HPAI H5N1 challenge in mule ducks, which appeared to be as resistant as Pekin ducks.


Rangelova D.,Technical University of Denmark | Nielsen J.,Technical University of Denmark | Strandbygaard B.,Technical University of Denmark | Koenen F.,CODA CERVA | And 2 more authors.
Vaccine | Year: 2012

Marker vaccines offer the possibility to differentiate classical swine fever (CSF) infected from CSF vaccinated animals based on serology and their implementation will ensure free trade with pigs. Therefore, new generations of promising marker vaccines have been developed, among them the chimeric vaccine CP7_E2alf. However, in populations previously vaccinated with live attenuated vaccines like the C-strain, passive immunity through maternal antibodies can interfere with efficacy of CP7_E2alf vaccination. Therefore, the efficacy of CP7_E2alf was examined in piglets from sows vaccinated once intramuscularly with C-strain vaccine 4. weeks before farrowing. Thus, these piglets were vaccinated intramuscularly with CP7_E2alf at the age of 5 or 8. weeks. Subsequently, the piglets and their mock-vaccinated littermate controls were challenged 2. weeks post vaccination with highly virulent Classical swine fever virus (CSFV) strain "Koslov"CP7_E2alf provided clinical protection upon challenge as no severe clinical signs or mortality was observed in the vaccinated piglets. Post mortem examination revealed pathological changes associated to CSFV only in the mock-vaccinated piglets. No infectious CSFV could be isolated from the tonsils of the vaccinated piglets. Two weeks after vaccination at the time of challenge, the vaccinated piglets only, had an increase in the ELISA antibody titer. Interestingly, the maternally derived immunity in the mock-vaccinated control piglets seems to neutralize the challenge virus. Thus, the previously observed 100% mortality in naïve (negative for antibodies to CSFV) piglets infected with CSFV Koslov was reduced in the control piglets of this study to 30% for challenge at the age of 7. weeks and 50% at the age of 10. weeks, respectively. In conclusion, CP7_E2alf proved to be effective in preventing mortality, severe clinical signs and pathological lesions in 5 or 8. weeks old piglets positive for maternal antibodies derived from sows vaccinated intramuscularly 4. weeks before farrowing with one dose of C-strain vaccine. © 2012 Elsevier Ltd.


PubMed | Vrije Universiteit Brussel, CODA CERVA, University of Antwerp, Scientific Institute of Public Health Site Elsene and University of Liège
Type: | Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association | Year: 2016

Since the European Commission prohibited the use of bisphenol A in the production of polycarbonate (PC) baby bottles, many other materials have replaced PC for the manufacture of this type of food contact materials. In the present study, the potential migration risks associated with these alternative materials were investigated. First, all substances were evaluated for endocrine disruptive (ED) activity by using different existing lists of (suspected) ED chemicals. Next, the potential non-ED risks were assessed. A distinction was made between migrants listed in Annex I of European Regulation 10/2011 and the unlisted substances (e.g. non-intentionally added substances). For the listed substances, concentrations in the migration solutions were compared to their respective specific migration limits (SML) (when applicable). Migration of all substances was shown to be below their SML. The unlisted substances were evaluated using toxicological information from previous evaluations, or if not available, by applying the Threshold of Toxicological Concern (TTC) approach. In case the estimated exposure to the unlisted substance exceeded the human exposure TTC value, a more indepth risk assessment was performed. Based on the results of both parts of the study, four baby bottles were considered of high concern because of the potential toxicity of migrating compounds.


PubMed | Vrije Universiteit Brussel, CODA CERVA, University of Antwerp, Scientific Institute of Public Health Site Elsene and University of Liège
Type: | Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association | Year: 2016

Due to the worldwide concern that bisphenol A might act as an endocrine disruptor, alternative materials for polycarbonate (PC) have been introduced on the European market. However, PC-replacement products might also release substances of which the toxicological profile--including their genotoxic effects--has not yet been characterized. Because a thorough characterization of the genotoxic profile of all these substances is impossible in the short term, a strategy was developed in order to prioritize those substances for which additional data are urgently needed. The strategy consisted of a decision tree using hazard information related to genotoxicity. The relevant information was obtained from the database of the European Chemicals Agency (ECHA), in silico prediction tools (ToxTree and Derek Nexus(TM)) and the in vitro Vitotox() test for detecting DNA damage. By applying the decision tree, substances could be classified into different groups, each characterized by a different probability to induce genotoxic effects. Although none of the investigated substances could be unequivocally identified as genotoxic, the presence of genotoxic effects could neither be excluded for any of them. Consequently, all substances require more data to investigate the genotoxic potential. However, the type and the urge for these data differs among the substances.


PubMed | CODA CERVA, Agentschap Natuur en Bos and University of Liège
Type: | Journal: Veterinary microbiology | Year: 2016

Schmallenberg virus (SBV) emerged across Europe in 2011 and Belgium was among the first countries affected. In this study, published findings are combined with new data from veterinary surveillance networks and the Belgian reference laboratory for SBV at the Veterinary and Agrochemical Research centre (CODA-CERVA) to reconstruct the epidemic in Belgium. First retrospective cases of SBV were reported by veterinarians that observed decreased milk yield and fever in dairy cattle in May 2011. The number of SBV suspicions subsequently increased in adult cattle in August 2011. That month, first SBV positive pools of Culicoides were detected and extensive virus circulation occurred in Belgium during late summer and autumn 2011. As a consequence, most pregnant ruminants were infected and their fetuses exposed to the virus. This resulted in an outbreak of abortions, still-births and malformed new-borns observed between January and April 2012. The number of cases drastically diminished in 2012-2013, although multiple lines of evidence obtained from cross-sectional serological surveys, analyses on aborted foetuses, sentinel herd surveillance and surveillance of SBV in vectors prove that SBV was still circulating in Belgium at that time. Virus circulation was then probably strongly reduced in 2013-2014, while increasing evidence indicates its recirculation in 2014-2015 in Belgium. Based on the experience gathered with the closely related Akabane virus, recurrent outbreaks of congenital events can be expected for a long period. Vaccination of seronegative animals before the first mating could be used to prevent the deleterious effects of SBV. During this epidemic, different surveillance approaches including syndromic surveillance, sentinel herd surveillance, cross-sectional seroprevalence studies and pathogen surveillance in vectors have proven their utility and should be considered to continue in the future.


PubMed | CODA CERVA and University of Liège
Type: | Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association | Year: 2016

Reporter gene assays incorporating nuclear receptors (estrogen, androgen, thyroid and PPAR2) have been implemented to assess the endocrine activity of 13 mycotoxins and their mixtures. As expected, zearalenone and its metabolites -zearalenol and - zearalenol turned out to have the strongest estrogenic potency (EC50 8,7 10-100,8; 3,1 10-110,5 and 1,3 10-80,3M respectively). The metabolite of deoxynivalenol, 3-acetyl-deoxynivalenol also had estrogenic activity (EC50 3,8 10-71,1M). Furthermore, most of the mycotoxins (and their mixtures) showed anti-androgenic effects (15-acetyldeoxynivalenol, 3-acetyl-deoxynivalenol and -zearalenol with potencies within one order of magnitude of that of the reference compound flutamide). In particular, deoxynivalenol and 15-acetyl-deoxynivalenol acted as antagonists for the PPARy2 receptor. When testing mixtures of mycotoxins on the same cell systems, we showed that most of the mixtures reacted as predicted by the concentration addition (CA) theory. Generally, the CA was within the 95% confidence interval of the observed ones, only minor deviations were detected. Although these reporter gene tests cannot be directly extrapolated invivo, they can be the basis for further research. Especially the additive effects of ZEN and its metabolites are of importance and could have repercussions invivo.

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