Research Centre for Healthy and Sustainable Living

[EN] The Research Centre for Healthy and Sustainable Living of the University of Applied Sciences Utrecht aims to enable healthy urban living. According to the latest concept, health entails the capacity to respond resiliently to stressors that disturb homeostasis. In addition, an individual’s health benefits from the ability to self-manage and is determined by personalized conditions. One of the derived research challenges is to obtain know-how (biomarkers) and tools (e.g. point-of-care, wearables) to monitor an individual’s health condition in daily life. The well-known quotes “you are what you eat” and “sitting is the new smoking” indicate that condition of the oro-gastrointestinal tract and physical activity are pivotal to health. With this popular knowledge, we set out to identify biomarkers to monitor health benefits from nutrition and physical activity. Our first studies with human volunteers indicated that immune and intestinal parameters are responsive to physical stress (performed on a bicycle ergometer) in a clear kinetic manner, related to extent of physical activity and influenced by an unhealthy condition (deprivation of water intake during exercise). Our next research goals are to: -evaluate the initial selection of biomarkers in specific patient-groups and; -how these biomarkers are influenced by the condition of the oro-gastrointestinal tract, e.g. via nutrition.Pieters, R.; Bleijenberg, N.; Jerkovic, K.; Krul, C.; Veenhof, C.; Wittink, H. (2020). Research Centre for Healthy and Sustainable Living. Editorial Universitat Politècnica de València. http://hdl.handle.net/10251/156433OC

Prediction of carcinogenic potential of chemicals using repeated-dose (13-week) toxicity data

AbstractSub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in order to predict the tumour outcome of 24-month rat carcinogenicity studies obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals that did not induce putative preneoplastic lesions in the sub-chronic study also did not induce tumours in the carcinogenicity study (True Negatives). Cellular hypertrophy appeared to be an unreliable predictor of carcinogenicity. The negative predictivity, the measure of the compounds evaluated that did not show any putative preneoplastic lesion in de sub-chronic studies and were negative in the carcinogenicity studies, was 75%, whereas the sensitivity, a measure of the sub-chronic study to predict a positive carcinogenicity outcome was only 5%. The specificity, the accuracy of the sub-chronic study to correctly identify non-carcinogens was 90%. When the chemicals which induced tumours generally considered not relevant for humans (33 out of 37 False Negatives) are classified as True Negatives, the negative predictivity amounts to 97%. Overall, the results of this retrospective study support the concept that chemicals showing no histopathological risk factors for neoplasia in a sub-chronic study in rats may be considered non-carcinogenic and do not require further testing in a carcinogenicity study

DARTpaths, an in silico platform to investigate molecular mechanisms of compounds

SUMMARY: Xpaths is a collection of algorithms that allow for the prediction of compound-induced molecular mechanisms of action by integrating phenotypic endpoints of different species; and proposes follow-up tests for model organisms to validate these pathway predictions. The Xpaths algorithms are applied to predict developmental and reproductive toxicity (DART) and implemented into an in silico platform, called DARTpaths. AVAILABILITY AND IMPLEMENTATION: All code is available on GitHub https://github.com/Xpaths/dartpaths-app under Apache license 2.0, detailed overview with demo is available at https://www.vivaltes.com/dartpaths/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Symposium end report, SLIM; Faster from innovations to humans

This article describes the final meeting for the program SLiM (Sneller van innovatie naar mens). In cooperation with the Netherlands Knowledge Centre on Alternatives to animal use (NKCA) an overview was given of the results on accelerated acceptance of Replacement, Refinement and Reduction (3R) of animals in research

Innovative testing. Grenzen verleggen & bruggen bouwen; Veilig en verantwoord vernieuwen: Openbare les 13 februari 2009

In de openbare les van mijn collega lector Raymond Pieters, is het domein van het lectoraat ‘Innovative Testing in Life Sciences & Chemistry’ toegelicht. Kort samengevat richt dit lectoraat zich op de ontwikkeling en toepassing van innovatieve teststrategieën om geneesmiddelen, voedingsmiddelen of chemicaliën (stoffen) te beoordelen op hun werkzaamheid (effectiviteit) en veiligheid. De nadruk ligt op de ontwikkeling van snelle, kosteneffectieve testmethoden die een relevante voorspelling van effecten op de gezondheid van de mens en het milieu opleveren én waarbij geen of minder proefdieren worden gebruikt. In mijn les zal ik u laten zien waar proefdieren voor gebruikt worden. Hierbij zal ik mij voornamelijk richten op de Nederlandse situatie. Ik zal ingaan op de wetenschappelijke en maatschappelijke wens om minder proefdieren te gebruiken en op de vraag wat we verstaan onder ‘alternatieven voor dierproeven’. Daarna zal ik bespreken waarom er in Nederland en Europa recentelijk meer aandacht is voor dit onderwerp. Het overzicht zal niet uitputtend zijn, maar zal u een goede indruk geven van het landschap. Ook zal ik stil staan bij de vraag: Waarom zijn we tot nog toe zo weinig succesvol geweest op het gebied van alternatieven voor dierproeven? Wat zijn de obstakels en wat kunnen we hier van leren? Hoe zouden we in de praktijk de toepassing van alternatieven kunnen stimuleren? Wat moet er beter, en hoe gaan we dat doen? Als we slimmer willen testen moeten we de huidige grenzen verleggen, of beter over de grenzen van ons vakgebied heen kijken. Ik zal aangeven waar prioriteiten liggen en hoe we de meeste ‘winst’ kunnen behalen in termen van proefdiervermindering in relatie tot productinnovatie. Tot slot zal ik aangeven welke bruggen we moeten bouwen en wat de rol is van de Hogeschool Utrech

Mutagenic and antimutagenic activity of food compounds : Application of a dynamic in vitro gastrointestinal model

Exposure of humans to potential mutagenic and carcinogenic food compounds through the diet is unavoidable. On the other hand, there is epidemiological evidence for antimutagenic and anticarcinogenic properties of food as well (such as vegetables and fruit). The assessment of carcinogenic and cancer preventive properties of food compounds is generally restricted to genotoxicity assays available for the evaluation of manmade chemicals. Specific processes related to the gastrointestinal tract, such as digestion and bioaccessibility and interactions between various food components received little attention in the assessment of (anti)mutagenic and (anti)carcinogenic dietary compounds. A dynamic in vitro gastrointestinal model (TIM system), which simulates the human physiological conditions in the digestive tract, was used to study these processes. The aim of the studies described in this thesis was to investigate whether this dynamic in vitro gastrointestinal model, in combination with in vitro genotoxicity assays, is a suitable tool for the assessment of (anti)mutagenic activity of food compounds. In this TIM system the availability for absorption of food mutagens, such as heterocyclic aromatic amines (HAA) present in prepared meat, was studied. Furthermore, the mechanisms involved in the antimutagenic activity of green tea and black tea and their interaction with HAA were investigated. The addition of a food matrix, such as meat, milk or breakfast, influenced the availability for absorption and (anti)mutagenic activity of HAA and tea. The antimutagenic activity of tea was also studied in a crossbreed dlb-1/lacZ transgenic mice model. However, a convincing antimutagenic effect of green and black tea in the small intestine could not consistently be demonstrated in vivo, in which B(a)P was used to induce mutations in the endogenous dlb-1 gene and in the lacZ transgene in the same animal. Besides the presence of mutagens in the diet, mutagens can also be formed in the human body, e.g. at a low pH present in the stomach. The intragastric formation of nitrosamines, by a reaction of amine (derived from various fish species) and nitrite (produced by salivary bacteria after consumption of nitrate), was investigated under various human physiological conditions in the gastric compartment of the TIM system. Higher levels of nitrosamines were formed than expected on the basis of other in vitro models, but lower amounts than based on urinary exretion of nitrosamines in human studies. The nitrosation reaction was effectively inhibited by the addition of ascorbic acid (vitamin C) or green or black tea, which corresponds to in vivo studies. In the large-intestinal-model it was demonstrated that inter individual differences were observed in the conversion of the glucosinolate into isothiocyanate, a metabolite which possibly has anticarcinogenic properties, by the human colonic microflora. In conclusion, the dynamic in vitro gastrointestinal model, in combination with in vitro genotoxicity assays, is a useful tool for the assessment of mutagenic and antimutagenic activities of food compounds and suitable for mechanistic studies. The use of this in vitro gastrointestinal model will contribute to the further reduction of the number of laboratory animal studies

"Met partners op zoek naar de beste 3V-alternatieven"

Interview met Cyrille Krul