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.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Physiologically based kinetic modelling based prediction of oral systemic bioavailability of flavonoids, their metabolites, and their biological effects
Boonpawa, Rungnapa - \ 2017
University. Promotor(en): Ivonne Rietjens, co-promotor(en): Arjen Punt. - Wageningen : Wageningen University - ISBN 9789463430371 - 180
flavonoids - bioavailability - modeling - metabolites - quercetin - physiology - hesperidin - flavonoïden - biologische beschikbaarheid - modelleren - metabolieten - quercetine - fysiologie - hesperidine

Flavonoids, abundantly present in fruits and vegetables, have been reported to exert various positive health effects based on in vitro bioassays. However, effects detected in in vitro models cannot be directly correlated to human health as most in vitro studies have been performed using flavonoid aglycones at high concentration ignoring extensive metabolism of flavonoids in the human body. To better understand positive health effects of flavonoids in humans, it is of importance to gain insight in at which form and concentration flavonoids are present in the systemic circulation after consumption. This insight can be obtained using physiologically based kinetic (PBK) computer modeling. The results obtained show that PBK modeling provides a useful additional research tool for studies on the fate of flavonoids in the human body and can reveal at what oral dose levels of flavonoids in vitro positive health effects can be expected to occur in vivo, presenting opportunities that are not easily provided by other methods.

Akkermansia species : phylogeny, physiology and comparative genomics
Ouwerkerk, J.P. - \ 2016
University. Promotor(en): Willem de Vos, co-promotor(en): Clara Belzer. - Wageningen : Wageningen University - ISBN 9789462577411 - 178 p.
akkermansia - akkermansia muciniphila - gastrointestinal microbiota - phylogeny - physiology - genomics - dna sequencing - nucleotide sequences - transcriptomes - antibiotic resistance - genome annotation - microbiota van het spijsverteringskanaal - fylogenie - fysiologie - genomica - dna-sequencing - nucleotidenvolgordes - transcriptomen - antibioticaresistentie - genoomannotatie

The gastrointestinal tract is lined with a mucus layer, which is colonized by a distinct mucosal microbial population. The anaerobic gut bacterium Akkermansia muciniphila is a well-described member of the mucosal microbiota and has been shown to be a human gut symbiont. In the mucus layer this gut symbiont is likely exposed to the oxygen that diffuses from mucosal epithelial cells. We showed that A. muciniphila has an active detoxification system to cope with reactive oxygen species and can use oxygen for respiration at nanomolar oxygen concentrations, with cytochrome bd as terminal oxidase.

Until now, the type strain A. muciniphila MucT was the only cultured representative of this species. We isolated and characterized six new A. muciniphila strains from faecal samples of four different human subjects. These A. muciniphila strains showed minimal genomic and physiologic divergence while retaining their mucin degrading and utilisation capacities. Apart from the human gastrointestinal tract, we detected Akkermansia species in intestinal samples of numerous mammals. An additional ten new A. muciniphila strains were isolated from seven different mammalian species and showed high genomic and physiologic similarity to type strain A. muciniphila MucT. Apart from Akkermansia species, other Verrucomicrobia were identified within the gastrointestinal tract of non-human mammals. Furthermore, we obtained an Akkermansia isolate from the reticulated python, which had a similar mucin degrading capacity as the human strain A. muciniphila MucT but showed more efficient galactose utilization. On the basis of further phylogenetic, physiological, and genomic characterisations, strain PytT was found to represent a novel species within the genus Akkermansia, for which the name Akkermansia glycaniphilus sp. nov. is proposed.

Overall, A. muciniphila strains isolated from intestinal samples of human and other mammals show very limited genomic and physiologic divergence. This together with the widely-spread global presence of A. muciniphila and the dependence on mucin for optimal growth, points towards a conserved symbiosis. This conserved symbiosis might be indicative for the beneficial role of this organism in respect to the host metabolic health. This is in line with the observation that A. muciniphila has been negatively associated with obesity and its associated metabolic disorders.

In mice, treatment with viable A. muciniphila cells reversed high-fat diet-induced obesity. We described a scalable workflow for the preparation and preservation of high numbers of viable cells of A. muciniphila under strict anaerobic conditions for therapeutic interventions. Moreover, we developed various quality assessment and control procedures aimed to ensure the use of viable cells of A. muciniphila at any location in the world. These viable cells were used in a pilot study in humans in which no adverse events were observed. This is promising for future applications of A. muciniphila as a new therapeutic, leading towards the potential treatment of unhealthy states of the microbiota.

Waarom kun je door blijven eten terwijl je eigenlijk al vol zit?
Witkamp, R.F. - \ 2015
Universiteit van Nederland
voedselconsumptie - overeten - voedingsgedrag - fysiologie - neurofysiologie - verslaving - biologie - food consumption - overeating - feeding behaviour - physiology - neurophysiology - addiction - biology
Je hebt al een amuse, voorgerecht, hoofdgerecht en toetje op, en dan is-ie daar ineens: de kaasplank. Hoe is het mogelijk dat je door kunt blijven eten terwijl je al vol zit? Renger Witkamp, hoogleraar Voeding en Farmacologie (Wageningen UR), legt je uit wat hier de verklaring voor is en waarom dat ooit nuttig was.
Hoe kan je je eetlust remmen?
Witkamp, R.F. - \ 2015
Universiteit van Nederland
eetlust - eetlustremmers - cannabis - voeding en gezondheid - voedingsfysiologie - fysiologie - voedselonderzoek - appetite - anorexiants - nutrition and health - nutrition physiology - physiology - food research
Denk je bij cannabis aan het krijgen van een vreetkick? Na dit college van Renger Witkamp (Wageningen UR) snap je wat het verband tussen die twee is en hoe we die kennis kunnen gebruiken om je eetlust te remmen. Klinkt goed, toch? Er is alleen één groot probleem. Welk? Dat hoor je in dit college.
Hoe kun je te dik en toch gezond zijn?
Witkamp, R.F. - \ 2015
Universiteit van Nederland
overgewicht - lichaamsgewicht - quetelet index - obesitas - gezondheid - volksgezondheid - buikvet - lichaamsvet - fysiologie - overweight - body weight - body mass index - obesity - health - public health - abdominal fat - body fat - physiology
Je kijkt naar beneden en ziet dat er zich in de loop der jaren wat vet is gaan ophopen rondom je middel. Waarom is het gevaarlijk om juist daar teveel vet te hebben? Renger Witkamp (Wageningen UR) legt uit hoe het nu precies zit met de gevaren van die extra kilootjes en of het per definitie ongezond is om wat dikker te zijn.
Wat moet je doen en laten als je gezonder wilt
Witkamp, R.F. - \ 2015
Universiteit van Nederland
diëten - voeding en gezondheid - voedselwetenschappen - fysiologie - voedselproducten - gezondheidsvoedsel - gezondheidsbevordering - voedingsonderzoek - diets - nutrition and health - food sciences - physiology - food products - health foods - health promotion - nutrition research
Slik jij de praatjes van afslankguru's als zoete koek? Ken jij alle diëten uit je hoofd? Renger Witkamp, hoogleraar Voeding en Farmacologie (Wageningen UR) bekijkt al deze hypes met een nuchtere en wetenschappelijke blik. Na dit praatje kun je alles wat je voorgeschoteld krijgt in de media over je gezondheid beter in perspectief plaatsen.
The Impact of Food Bioactives on Health: in vitro and ex vivo models
Verhoeckx, K. ; Cotter, P. ; Lopez-Exposito, I. ; Lea, T. ; Mackie, A. ; Requena, T. ; Swiatecka, D. ; Wichers, H.J. - \ 2015
Zeist : Springer International Publishing - ISBN 9783319157917 - 338
bioactieve verbindingen - voedselwetenschappen - fysiologie - voedselmicrobiologie - voedsel - gezondheid - bioactive compounds - food sciences - physiology - food microbiology - food - health
“Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists…). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.
Molecular and physiological assessment of metabolic health : adipose tissue, transcriptome analysis and challenge tests
Duivenvoorde, L.P.M. - \ 2015
University. Promotor(en): Jaap Keijer, co-promotor(en): Evert van Schothorst. - Wageningen : Wageningen University - ISBN 9789462573017 - 186
muizen - metabolisme - gezondheid - vetweefsel - transcriptomen - stofwisselingsstoornissen - fysiologie - laboratoriumdieren - mice - metabolism - health - adipose tissue - transcriptomes - metabolic disorders - physiology - laboratory animals

Summary of main findings

Maintenance of metabolic health not only ensures that energy is made available in times of need and stored in times of excess, but also prevents resistance to nutritional cues, ectopic lipid accumulation and dysfunction of metabolic organs. The proportion of humans that is at risk for reduced metabolic health increases worldwide due to the current epidemic of obesity and the increase in both mean and maximum life span. Better understanding of the various factors that influence metabolic health may offer opportunities to fight this threat to human health. This thesis aims to assess metabolic health using transcriptome analysis and non-invasive challenge tests. Special focus is on the development and validation of InCa-based non-invasive challenge tests. In most chapters of this thesis white adipose tissue (WAT) formed the major organ of interest because of its key role in whole-body energy homeostasis. WAT function was, among others, studied with whole-genome gene expression analysis, which, compared to single parameter analysis, extends the scale and depth of understanding biological processes.

Metabolic health was also quantified as metabolic flexibility, with the use of non-invasive, indirect calorimetry (InCa) based challenge tests. One of the InCa based challenge tests described in this thesis, the oxygen restriction (OxR) challenge, is a novel approach to investigate metabolic flexibility in mice. In each study, OxR was applied acute ([O2] reduction within 30 minutes) and for a short period of 6 hours in fasted mice. The other two InCa-based challenge tests: fasting and re-feeding and fasting and glucose consumption are nutrient-based and were described previously, although in different formats and settings.

In chapter 2 we demonstrate that dietary restriction on a high-fat diet (HF-DR) improves metabolic health of mice compared with mice receiving the same diet on an ad libitum basis (HF-AL). Already after five weeks of restriction, the serum levels of cholesterol and leptin were significantly decreased in HF-DR mice, whereas their glucose tolerance and serum adiponectin levels were increased. The body weight and measured serum parameters remained stable in the following 7 weeks of restriction, implying metabolic adaptation. To understand the molecular events associated with this adaptation, we analysed gene expression in WAT with whole genome microarrays. HF-DR strongly influenced gene expression in WAT; in total, 8643 genes were differentially expressed between both groups of mice, with a major role for genes involved in lipid metabolism and mitochondrial functioning. DR also increases mitochondrial density in WAT. These results show that WAT, indeed, has an important role in the improvement of metabolic health of dietary restricted mice and suggest that the development of substrate efficiency plays an important role in the observed changes in health status. Finally, mitochondrial density might be used as a marker for WAT health status.

Chapter 3 shows how indirect calorimetry can be used to noninvasively assess metabolic and age-related flexibility in mice. In this study, we tested the sensitivity and response stability over time of three InCa-based treatments in old versus adult mice. For the first treatment, diurnal patterns of respiratory exchange ratio were followed for 24 hours under standard conditions. For the second and third treatment, which were both based on a challenge approach, mice were fasted and either received a glucose bolus to test switch-effectiveness from fat to glucose oxidation (Treatment 2), or were exposed to oxygen restriction (OxR, Treatment 3) in the InCa system, which was introduced as a novel approach to asses metabolic flexibility. Opposite to the mice that were dietary restricted (chapter 2), aging appeared to increase adiposity and decrease WAT mitochondrial density, which further suggests that WAT mitochondrial density might be used as a marker for WAT health. We observed that the test results of the first treatment were not stable between test periods, possibly because of behavioural differences within the group of old mice between both measurements. For the second treatment, no differences between groups were observed. With Treatment 3, however, stable significant differences could be detected: old mice did not maintain reduced oxygen consumption under OxR during both measurements, whereas adult mice did. Further biochemical and gene expression analyses showed that OxR affected glucose and lactate homeostasis in liver and WAT of adult mice, supporting the observed differences in oxygen consumption. This was the first study to show that InCa analysis of the response to OxR is a sensitive and reproducible treatment to noninvasively measure age-impaired metabolic health in mice. Evaluation of metabolic health under non-challenged conditions may be confounded by behavioural-induced variation between animals

The study described in chapter 4 followed up on the promising results that were obtained with the OxR challenge in chapter 3. In this study we tested whether OxR can also be used to reveal diet-induced health effects in an early stage. Early detection of diet-induced health effects might shorten animal experiments and reduce costs and age-related variation. Timely identification may increase options for reversal. Mice were exposed to a low-fat (LF) or high-fat (HF) diet for only 5 days, after which they were exposed to OxR or remained under normoxic conditions. The response to OxR was assessed by calorimetric measurements, followed by analysis of gene expression in liver and WAT. A novelty described in this chapter was the analysis of serum markers for protein glycation and oxidation, to detect differences in the response to OxR between LF and HF mice. Although HF feeding increased body weight, HF and LF mice did not differ in indirect calorimetric values under normoxic conditions and in a fasting state. Exposure to OxR however, increased oxygen consumption and lipid oxidation in HF mice versus LF mice. Furthermore, OxR induced gluconeogenesis and an antioxidant response in the liver of HF mice, whereas it induced de novo lipogenesis and an antioxidant response in eWAT of LF mice, indicating that HF and LF mice differed in their adaptation to OxR. OxR also increased serum markers of protein glycation and oxidation in HF mice, whereas these changes were absent in LF mice. From this study we concluded that OxR is a promising new method to test food products on potential beneficial effects for metabolic health.

The study described in chapter 5 aimed to assess differences in metabolic health of mice on iso-caloric diets differing in fatty acid composition using the OxR challenge. We also implemented a fasting and re-feeding challenge. One diet, the HFpu diet, predominantly contained poly-unsaturated fatty acids (PUFAs), which are considered to be healthier than saturated fatty acids (SFAs) that mainly made up the fat component of the second diet, the HFs diet. Since health effects of fatty acids also depend on the ratio of dietary omega-6 to omega-3 PUFAs (n6/n3 ratio), this ratio was kept similar between both diets. Mice received the isocaloric high-fat diets for six months, during and after which several biomarkers for health were measured. We found that HFpu and HFs diets only induce minor differences in static health markers: HFpu and HFs mice did not differ in body weight, total adiposity, adipose tissue health, serum adipokines, whole body energy balance, or circadian rhythm. HFpu and HFs mice also had a similar glucose tolerance, even though HFs mice had more triglycerides in liver and skeletal muscle and larger adipocytes in the eWAT depot. Interestingly, HFs mice were less flexible in their response to both fasting and re-feeding and OxR, which shows the relevance and sensitivity of InCa-based challenge tests. We concluded that InCa-based challenge tests are a valuable contribution to the analysis of metabolic health in mice. Challenge tests in the InCa system may, furthermore, reveal relevant consequences of small changes in metabolic health status, such as adipocyte hypertrophy or ectopic lipid storage.

Chapter 6 describes an in-depth study to the response to OxR both at whole body level using InCa and serum metabolomics (amino acids and (acyl)carnitines) and at WAT level using transcriptomics and the analysis of amino acid and (acyl)carnitine levels. Serum and tissue amino acids levels indicate the level of protein catabolism and certain amino acids are, typically, increased in obese individuals. Serum and tissue (acyl)carnitine levels indicate the rate and completeness of mitochondrial fatty acid oxidation; serum acylcarnitine levels are significantly increased in individuals that suffer from ambient oxygen restriction. The metabolic adaptation to OxR was studied in diet-induced moderately obese mice that received a high-fat diet (HFpu diet, as in chapter 5) for 6 weeks, which is expected to lead to WAT expansion and possibly to reduce oxygen availability in WAT. We found that OxR reduced mitochondrial oxidation at whole-body level, as shown by a reduction in whole-body oxygen consumption and an increase in serum long-chain acylcarnitine levels. WAT did not seem to contribute to this serum profile, since only short-chain acylcarnitines were increased in WAT and gene expression analysis indicated an increase in mitochondrial oxidation, based on coordinate down-regulation of Sirt4, Gpam and Chchd3/Minos3. In addition, OxR did not induce oxidative stress in WAT, but increased molecular pathways involved in cell growth and proliferation. OxR increased levels of tyrosine, lysine and ornithine in serum and of leucine/isoleucine in WAT. This study shows that OxR limits oxidative phosphorylation at whole-body level, but in WAT compensatory mechanisms seem to operate. The down-regulation of the mitochondria-related genes Sirt4, Gpam, and Chchd3 may be considered as a biomarker profile for WAT mitochondrial reprogramming in response to acute exposure to limited oxygen availability.

To conclude, the work presented in this thesis provides more insight in the analysis of metabolic health in mice with the use of transcriptome analysis and InCa-based challenge tests. We show that non-invasive tests using the InCa-system are more likely to reveal differences in metabolic flexibility than invasive challenge tests, such as the oral glucose tolerance test. Furthermore, we show that the challenge approach is more sensitive than analysis of metabolic health under non-challenged (free-feeding) conditions. Transcriptome analysis proved to be very valuable to provide in-depth molecular understanding of the mechanisms underlying reduced or improved metabolic health. Ideally, transciptomic or metabolomic approaches should be integrated with InCa-based challenge tests to further extent physiological understanding of diet-induced health effects.

Physiologically based in silico modelling to examine DNA adduct formation by different food-borne a,ß-unsaturated aldehydes at realistic low dietary exposure levels
Kiwamoto, R. - \ 2015
University. Promotor(en): Ivonne Rietjens, co-promotor(en): Ans Punt. - Wageningen : Wageningen University - ISBN 9789462572843 - 200
aldehyden - dna - ontgifting - voedseladditieven - aromatische stoffen - genotoxiciteit - carcinogenen - modellen - wiskundige modellen - fysiologie - simulatiemodellen - toxicologie - aldehydes - detoxification - food additives - flavourings - genotoxicity - carcinogens - models - mathematical models - physiology - simulation models - toxicology

Abstract (R.Kiwamoto ISBN 978-94-6257-284-3)

Various α,β-unsaturated aldehydes are present in fruits, vegetables, spices, or processed products containing these items as natural constituents or as added food flavouring agents. Because of the α,β-unsaturated aldehyde moiety the β carbon in the molecule becomes electron deficient and the aldehydes react with electron rich molecules including DNA via Michael addition. The formation of DNA adducts raises a concern for genotoxicity, although formation of DNA adducts may not be significant at low doses relevant for dietary exposure in vivo because of adequate detoxification. This thesis therefore aimed at determining dose-dependent detoxification and DNA adduct formation of food-borne α,β-unsaturated aldehydes by using a physiologically based in silico modelling approach in order to contribute to the safety assessment of these aldehydes used as food flavourings instead of performing animal experiments.

Physiologically based in silico models were developed for 18 α,β-unsaturated aldehydes. The model outcomes indicated that the DNA adduct formation by the 18 α,β-unsaturated aldehydes as food flavourings is negligible and does not raise a safety concern at their levels of intake resulting from their use as food flavourings. The application of QSAR models strongly accelerated the development process of the PBK/D models of the group of 18 compounds. Also, it was illustrated that physiologically based in silico models provide a very useful and powerful tool to facilitate a group evaluation and read-across for food-borne DNA reactive agents. PBK/D models developed for the group of compounds supported read-across from cinnamaldehyde which is known not to be genotoxic or carcinogenic in vivo to other aldehydes, by allowing comparison of dose-dependent DNA adduct formations. Altogether this thesis presented physiologically based in silico modelling as an approach to test relevance of positive in vitro genotoxicity results by DNA reactive compounds in vivo without using animal experiments.

Physiology and biochemistry of aromatic hydrocarbon-degrading bacteria that use chlorate and/or nitrate as electron acceptor
Oosterkamp, M.J. - \ 2013
University. Promotor(en): Fons Stams, co-promotor(en): Caroline Plugge; Peter Schaap. - Wageningen : Wageningen University - ISBN 9789461737779 - 191
bacteriën - aromatische koolwaterstoffen - fysiologie - biochemie - elektronen - genomen - nitraten - chloraten - microbiologie - bacteria - aromatic hydrocarbons - physiology - biochemistry - electrons - genomes - nitrates - chlorates - microbiology
Physiologically based biokinetic (PBBK) modeling and validation of dose-, species-, interindividual- and matrix dependent effects on the bioactivation and detoxification of safrole
Martati, E. - \ 2013
University. Promotor(en): Ivonne Rietjens; Peter van Bladeren, co-promotor(en): Ans Punt. - S.l. : s.n. - ISBN 9789461737458 - 202
safrol - biologische activiteit - ontgifting - modelleren - fysiologie - wiskundige modellen - safrole - biological activity - detoxification - modeling - physiology - mathematical models

Keywords: safrole, PBBK model, DNA adduct, mace

Safrole has been demonstrated to be carcinogenic in rodent studies at high doses of the pure compound. The use of pure safrole in foodshas already been prohibited. As a result, the main exposure to safrole occurs through the use of herbs and spices containing low levels of safrole, such as nutmeg, mace, star anise, pimento, cinnamon, and black pepper, and food products containing these herbs and spices or their essential oils.

The Scientific Committee on Food of the European Union concluded in their evaluation that safrole is genotoxic and carcinogenic and that reductions in the exposure and restriction in the use levels are indicated. This opinion is based on carcinogenicity data from rodent studies as adequate human data were not available. Therefore, translation from animal bioassays at high dose levels of the pure compound to the risk for the human population exposed to safrole at relatively low levels via dietary intake within the complex food matrix is obviously needed. The aim of this thesis was to obtain insight into the dose-, species-, interindividual- and matrix dependent effects on the bioactivation and detoxification of safrole using physiologically based biokinetic (PBBK) modeling.

PBBK models for safrole in male rats and humans were developed based on in vitro metabolic parameters determined, in silico derived partition coefficients, and physiological parameter values taken from literature. The performance of the PBBK model for rats was evaluated by comparison of predicted levels of 1,2-dihydroxy-4-allylbenzene, 1′-hydroxysafrole glucuronide and total urinary safrole metabolites to the reported levels of these metabolites in urine of rats exposed to safrole. This evaluation revealed that the predictions adequately matched observed experimental values. The PBBK model for humans was evaluated by comparison of the PBBK predicted and the reported experimental data on the level of total safrole metabolites detected in the urine of human volunteers exposed to safrole whichshowed an adequately match. The comparison of the PBBK model for rats and humans revealed that the predicted level of formation of 1ʹ-hydroxysafrole in human liver is fourfold higher than that for rat liver and the predicted formation of 1ʹ-sulfooxysafrole is about fivefold higher than that for rat liver. This indicates that the interspecies differences in toxicokinetics for bioactivation of safrole between rat an human are in line with the uncertainty factor normally taken into account for interspecies differences in toxicokinetics of 4. Species differences between humans and rats in the nature of the detoxification pathways of 1ʹ-hydroxysafrole were larger, with the formation of 1ʹ-oxosafrole being the main detoxification pathway in humans but a minor pathway in rats and glucuronidation of 1ʹ-hydroxysafrole being less important in humans than in rats. Monte Carlo simulations revealed that the formation of 1′-sulfooxysafrole was predicted to vary 4- to 17-fold in the population (fold-difference between the 95th and median, and 95th and 5th percentile, respectively).

Risk assessment of safrole resulting from consumption of herbs and spices containing safrole should be performed taking into account the possible modulating effect of other compounds present in these herbs or spices. In this study, mace was chosen as the model spice of interest because it contains significant levels of safrole. Mace fraction with the highest SULT inhibiting activity was identified as malabaricone C. Studies using human HepG2 cells exposed to 1ʹ-hydroxysafrole and in the presence of mace extract showed that formation of the DNA adduct N2-(trans-isosafrol-3′-yl)-2′-deoxyguanosine was inhibited. To investigate the possible effects on safrole bioactivation to 1′-sulfooxysafrole by malabaricone C-containing mace extract could also be expected in vivo, the SULT inhibition was integrated into the PBBK model. The PBBK models predicted that at a dose of 50 mg/kg bw safrole and a ratio of malabaricone C-containing mace extract to safrole similar to the level of these constituents in mace, inhibition of 1′-sulfooxysafrole formation by malabaricone C-containing mace extract for rats and humans amounts to 90 and 100%, respectively. To see whether the inhibition of safrole DNA adduct formation by malabaricone C-containing mace extract is also observed in in vivo, to the end, Sprague-Dawley rats were orally exposed to mace extract and safrole. The results demonstrated that safrole DNA adduct formation in the liver of Sprague-Dawley rats by the mace extract was reduced by 55%.

The results of the in vitro and in vivo studies that demonstrated inhibition of the formation of safrole DNA adducts by mace extract, support that combination effects should be taken into account in the risk assessment when safrole is tested in the presence of a relevant food matrix. To integrate thefood matrix dependent modulation of safrole bioactivation in the risk assessment of safrole, the so-called Margin of Exposure (MOE) approach can be used. This revealed that when safrole would be tested in rodent bioassays in the presence of a matrix containing SULT inhibitors the MOE values would be higher and the need for risk management actions would be lower.

Relying on satiety cues in food consumption : studies on the role of social context, appearance focus, and mindfulness
Veer, E. van de - \ 2013
University. Promotor(en): Hans van Trijp, co-promotor(en): Erica van Herpen. - S.l. : s.n. - ISBN 9789461736895 - 240
voedselconsumptie - sociale psychologie - consumenten - voedselopname - verzadigdheid - eetlust - eetlustcontrole - honger - fysiologie - bewustzijn (consciousness) - eten - maaltijden - snacks - food consumption - social psychology - consumers - food intake - satiety - appetite - appetite control - hunger - physiology - consciousness - eating - meals
Consumers eat at various sequential occasions throughout the day. The current thesis addresses the question of how one consumption episode can affect the amount of consumption at a subsequent episode. The thesis focuses specifically on how the social context during a consumption episode affects subsequent consumption, and on when consumers rely on hunger and satiety cues in sequential consumption episodes.
De baard van Koning Winter - ijshaar of haarijs
Vossestein, M. ; Mulder, S. - \ 2009
Nature Today 2009 (2009)29-1-2009.
dood hout - fysiologie - schimmels - natuurverschijnselen - dead wood - physiology - fungi - natural phenomena
IJshaar of haarijs is soms in beuken- of gemengde bossen met beuken of eiken te vinden. Tot nu toe is dit zeer zeldzame fenomeen alleen aangetroffen op dode takken van eik en beuk, waarvan de schors net is losgeraakt
Energie- en eiwitbehoefte van biologisch gehouden pluimvee = Energy and protein requirements of organic housed poultry
Knegsel, A.T.M. van; Krimpen, M.M. van - \ 2008
Lelystad : Animal Sciences Group (Rapport / Animal Sciences Group 122) - 21
pluimveehouderij - biologische landbouw - pluimvee - pluimveevoeding - energiebehoeften - eiwitbehoefte - fysiologie - voederconversievermogen - dierhouderij - poultry farming - organic farming - poultry - poultry feeding - energy requirements - protein requirement - physiology - feed conversion efficiency - animal husbandry
In this literature review, the physiological basis for possible differences in energy and protein requirements of organic versus conventional poultry is investigated. Energy need for maintenance of organic housed poultry seems to be increased, whereas protein requirements might not differ between the two systems. This might result in an increased energy to protein ration in organic diets.
Nog steeds schildklier
Heide, D. van der - \ 2005
Wageningen : Wageningen Universiteit - 18
schildklier - schildklierhormonen - schildklierziekten - jodium - fysiologie - thyroid gland - thyroid hormones - thyroid diseases - iodine - physiology
Plants and lactation: from tradition to the mechanism of action
Lompo, Z. - \ 2003
University. Promotor(en): D. van der Heide; L. Sawadogo, co-promotor(en): E.M. van der Beek. - [S.I.] : S.n. - ISBN 9058089118 - 104
zogende vrouwen - lactatie - melkproductie - plantextracten - stimulatie - etnobotanie - dierproeven - farmacologie - fysiologie - geneeskunde - burkina faso - lactating women - lactation - milk production - plant extracts - stimulation - ethnobotany - animal experiments - pharmacology - physiology - medicine
Insemination strategies in swine: physiological backgrounds and practical consequences
Soede, N.M. ; Langendijk, P. ; Kemp, B. - \ 2003
In: Perspectives in Pig Science / Wiseman, J., Varley, M.A., Kemp, B., Nottingham UK : Nottingham University Press - ISBN 1897676190 - p. 257 - 278.
varkens - kunstmatige inseminatie - dierfysiologie - voortplanting - fysiologie - pigs - artificial insemination - animal physiology - reproduction - physiology
Stress and stress disorders in a teleost fish, the common carp Cyprinus carpio L.
Ruane, N.M. - \ 2002
University. Promotor(en): E.A. Huisman; Hans Komen. - S.l. : S.n. - ISBN 9789058087485 - 160
karper - zoetwatervissen - stressreactie - stress - hydrocortison - fysiologie - dierenwelzijn - visteelt - afwijkingen - psychologische fysiologie - carp - freshwater fishes - stress response - hydrocortisone - physiology - animal welfare - fish culture - abnormalities - psychological physiology
<p>Unlike research using mammalian animal models such as rats or mice, experimental fish often come from wild or commercial sources, leading to a lack of well defined experimental animal models. Isogenic carp offer us a well defined fish model for physiological research. The aim of this thesis was to, therefore, investigate the physiological stress response of isogenic strains of carp. Increased levels of stress in intensively reared animals results in large economical losses (due to disease mortalities, poor growth) and an increased understanding of the stress response is therefore relevant to the fish farming industry. Using a standard stressor, we aimed to examine the influence of environmental disturbances (e.g. high densities, restricted feeding levels) on the physiological response of the carp to this stressor. Fish showed a mild response to the period of crowding, although they appeared to recover physiologically, fish reared at a high density were more sensitive to an additional disturbance as seen by the higher levels of stress-hormones in the circulation. In addition, alternate periods of optimal or maintenance feeding levels were also found to affect the response to stress. An alternative method for measuring chronic stress in fish was also established through hormonal measurements in the water. A stress disorder was noted in one strain, these fish appear to suffer from a disorder similar to the 'chronic adrenal hyperplasia' which occurs in mammals. As this has never been described in a lower vertebrate, these fish may prove to be an important model for future studies on fish endocrinology.
Verspreiding van organisch stof rond de mengvoederbedrijven in Doetinchem : oriëntatiemeting organisch stof
Doekes, G. ; Loon, J. van; Spithoven, J. - \ 2001
Wageningen : Wetenschapswinkel (Adviesbrief / Wetenschapswinkel 164) - 35
verontreiniging - geluidshinder - luchtverontreiniging - stof - meelindustrie - nederland - ademhaling - fysiologie - gelderland - pollution - noise pollution - air pollution - dust - milling industry - netherlands - respiration - physiology
Biochemistry and physiology of halorespiration by Desulfitobacterium dehalogenans
Pas, B.A. van de - \ 2000
Agricultural University. Promotor(en): W.M. de Vos; Fons Stams. - S.l. : S.n. - ISBN 9789058083494 - 141
biodegradatie - biologische behandeling - organische halogeenverbindingen - microbiële fysiologie - biochemie - fysiologie - biodegradation - biological treatment - organic halogen compounds - microbial physiology - biochemistry - physiology
<p>Halorespiration is a novel respiratory pathway, which has been discovered as a result of the search for microorganisms that can be used in bioremediation of chlorinated compounds. Halorespiring bacteria are able to use these compounds as terminal electron acceptor for growth in anaerobic environments. These bacteria have developed enzyme systems with high dechlorination rates and low threshold values. These characteristics are important for the application of dechlorinating bacteria in bioremediation.</p><div align="center"><img src="/wda/abstracts/i2903_1.gif" width="564" height="402" alt="Figure 1" border="0"/><br/>Figure 1. A 16S rRNA based phylogenetic tree reflecting the relationships of halorespiring bacteria (marked *) with other bacteria.</div><p>The diversity of bacteria capable of using chlorinated compounds as terminal electron acceptor indicates that halorespiration is widespread throughout the bacterial domain (Fig 1). Insight in the physiology and biochemistry of these bacteria is currently lacking. This study aimed to get a better comprehension of the biochemistry of halorespiration. The research has focused on three topics:</p><ol type="i"><li>elucidation of the coupling of reductive dechlorination to ATP formation in <em>Desulfitobacterium dehalogenans,</em></li><li>isolation and characterization of dehalogenases from different <em>Desulfitobacterium</em> species, and</li><li>isolation and characterization of a novel <em>Desulfitobacterium</em> strain from human feces.</li></ol><p>In <strong>Chapter 1</strong> , an overview is given of microbial dehalogenation mechanisms with emphasis on halorespiration. The halorespiring bacteria that have been obtained in pure culture, the current models for 3-chlorobenzoate and tetrachloroethene (PCE) respiration, and the characteristics of reductive dehalogenases, are also reviewed.</p><p><em>Desulfitobacterium dehalogenans</em> is an anaerobic Gram-positive bacterium that uses <em>ortho</em> -chlorinated phenolic compounds as terminal electron acceptor for growth. In <strong>Chapter 2,</strong> the growth yields of <em>D. dehalogenans</em> grown with hydrogen, formate, pyruvate, or lactate as electron donor and Cl-OHPA as electron acceptor have been compared. In addition, the activities of the different electron donating and electron accepting enzymes were localized. These results indicate that the oxidation of lactate and pyruvate coupled to the reduction of Cl-OHPA yields 1 ATP per mole of acetate produced by substrate level phosphorylation. When formate or hydrogen is used as electron donor for reductive dechlorination, the growth yield is approximately 1/3 of the growth yield with pyruvate as electron donor. Under these growth conditions, energy cannot be conserved via substrate-level phosphorylation.</p><p>However, a proton motive force (PMF) may be established, which can be used by a proton-driven ATPase for ATP-formation. A model has been postulated in which the localization of the electron-donating enzyme (e.g. hydrogenase, formate dehydrogenase, lactase dehydrogenase, or pyruvate ferredoxin oxidoreductase) determines whether a PMF is established. In contrast to the electron transport by the electron transport chain (ETC) and the reduction of the chlorinated compound by the reductive dehalogenase, which do not contribute to the PMF. We have investigated the composition of the ETC, which is involved in electron transport from formate to Cl-OHPA in cell suspensions and have compared it with the ETC involved in fumarate respiration with formate as electron donor ( <strong>Chapter 3</strong> ). Menaquinone, cytochrome c, and b were components that were found to be present in cells grown with formate and either Cl-OHPA or fumarate. We have demonstrated that these components could be reduced by formate and oxidized upon addition of the induced electron acceptor. This suggests that (a part of) the halorespiratory chain is shared with fumarate respiration. However, the ETCs involved in halorespiration and fumarate respiration are not identical. The involvement of cytochrome b in fumarate respiration could be demonstrated while this was not possible for halorespiration. The results suggest that cytochrome b is the direct electron donor for fumarate reductase.</p><p>The electron transport chain from formate to Cl-OHPA has been investigated in more detail by electron paramagnetic resonance spectroscopy. In these experiments, we have shown that molybdenum, iron-sulfur clusters, cobalamin, a high spin heme and an unknown iron-sulfur cluster are components that were reduced by formate and oxidized by Cl-OHPA. This may indicate that the formate dehydrogenase which is active in halorespiration is a molybdenum and iron-sulfur containing formate dehydrogenase. This enzyme donates its electrons either to cytochrome c, or the electrons are transferred to cytochrome b. The electrons may then be transferred to menaquinone which takes 2 protons from the cytoplasm and, depending on the localization of the reductive dehalogenase, the protons are released at the outside or inside of the cell, as is shown in figure 2 model A and B, respectively. In addition, oxidation of cobalamin, a cofactor of chlorophenol reductive dehalogenase, was observed in cell suspensions upon addition of Cl-OHPA. This observation strongly suggests that the dehalogenase, which we have characterized, is involved in in vivo halorespiration.</p><div align="center"><img src="/wda/abstracts/i2903_2.gif" width="330" height="300" alt="Figure 2 Model A" border="0"/><img src="/wda/abstracts/i2903_3.gif" width="330" height="300" alt="Figure 2 Model B" border="0"/><br/>Figure 2: The electron transport system of <em>D. dehalogenans</em> catalyzing the oxidation of formate coupled to reductive dechlorination of 3-chloro-4-hydroxyphenyl acetate. It shows two tentative models for the generation of a proton gradient based on the localization of the <em>ortho</em> -chlorophenol reductive dehalogenase at the outer (model A) or the inner aspect (model B) of the cytoplasmic membrane.</div><p>The isolation and characterization of a chlorophenol reductive dehalogenase is described in <strong>Chapter 4</strong> . This enzyme was purified anaerobically from a Triton X-100 extract of the membrane fraction. The purified enzyme catalyzed the dechlorination of Cl-OHPA with a V <sub>max</sub> of 28 units/mg protein and a K <sub>m</sub> of 20 mM. In addition, the purified dehalogenase catalyzed the reductive dehalogenation of several <em>ortho</em> -chlorinated phenols and 2-bromo-4-chlorophenol with reduced methyl viologen as electron donor. The EPR analysis indicated one [4Fe-4S] cluster (midpoint redox potential <em>(E <sub>m</em></sub> = -440 mV), one [3Fe-4S] cluster <em>(E <sub>m</sub></em> = 170 mV), and one cobalamin per 48-kDa monomer. The Co <sup>+</sup> /Co <sup>2+</sup> transition had an <em>E <sub>m</sub></em> of -370 mV. The corresponding gene has been isolated, cloned, and sequenced, and revealed the presence of two closely linked genes: (i) <em>cpr</em> A, encoding the o-chlorophenol reductive dehalogenase, (ii) <em>cpr</em> B, coding for an integral membrane protein that could act as a membrane anchor of the dehalogenase. Moreover, <em>cprA</em> contains a twin-arginine type signal sequence that is processed in the purified enzyme.</p><p>Besides <em>ortho</em> -chlorinated phenols, <em>D. dehalogenans</em> is able to use other electron acceptors. In <strong>Chapter 5</strong> , the influence of other electron acceptors on the induction of dechlorinating activity and on the dechlorinating activity in cell suspensions and cell extracts is described. The results indicate that <em>D. dehalogenans</em> does not have a preferred electron acceptor in batch cultures, but it utilizes several electron acceptors simultaneously. This could be relevant for in situ bioremediation techniques because the presence of multiple electron acceptors in polluted sediments is not unusual.</p><p>While <em>D. dehalogenans</em> is able use <em>ortho</em> -chlorinated phenols as terminal electron acceptors for growth, <em>Desulfitobacterium</em> sp. <em></em> strain PCE1 is able to use both chlorophenols and PCE and <em>Desulfitobacterium frappieri</em> strain TCE1 can use PCE and TCE. We compared the substrate spectrum of the enzymes in cell extracts of these strains grown with Cl-OHPA or PCE as electron acceptors ( <strong>Chapter 6</strong> ). The results indicate that strain PCE1 contains separate enzymes for PCE and chlorophenol dechlorination. This was studied in more detail by the isolation of the chlorophenol reductive dehalogenase and the PCE reductive dehalogenase of strain PCE1 and the PCE/TCE reductive dehalogenase from strain TCE1. Based on the N-terminal sequence, size and substrate spectrum, the chlorophenol reductive dehalogenase of strain PCE1 was found to be very similar to the dehalogenase of <em>D. dehalogenans.</em> The PCE/TCE reductive dehalogenase of strain TCE1 has similar characteristics as have been described for PCE reductive dehalogenase of strain PCE-S. The PCE reductive dehalogenase from strain PCE1 was found to be a novel type of reductive dehalogenase. The enzyme catalyzed the reduction of PCE, and had a low activity with TCE. The purified enzyme had a subunit size of 45 kDa on SDS-PAGE. The activity of this enzyme as well as of the chlorophenol reductive dehalogenase of strain PCE1 was found to be inhibited upon addition of the cobalamin inhibitors 1-iodopropane and NO to cell extracts.</p><p>In <strong>Chapter 7</strong> , the isolation and characterization of a new strain of <em>Desulfitobacterium frappieri</em> is described. This isolate is the first <em>Desulfitobacterium</em> strain described that is not able to use chlorinated ethenes or phenols as terminal electron acceptor.</p><p><strong>Keywords</strong> :Halorespiration, <em>Desulfitobacterium dehalogenans</em> , anaerobic dechlorination, bioremediation, PCE, chlorophenol.</p>
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