Metabolic Alterations in Aging Macrophages: Ingredients for Inflammaging?
Beek, Adriaan A. Van; Bossche, Jan Van den; Mastroberardino, Pier G. ; Winther, Menno P.J. De; Leenen, Pieter J.M. - \ 2019
Trends in Immunology 40 (2019)2. - ISSN 1471-4906 - p. 113 - 127.
Aging is a complex process with an impact on essentially all organs. Declined cellular repair causes increased damage at genomic and proteomic levels upon aging. This can lead to systemic changes in metabolism and pro-inflammatory cytokine production, resulting in low-grade inflammation, or ‘inflammaging’. Tissue macrophages, gatekeepers of parenchymal homeostasis and integrity, are prime inflammatory cytokine producers, as well as initiators and regulators of inflammation. In this opinion piece, we summarize intrinsic alterations in macrophage phenotype and function with age. We propose that alternatively activated macrophages (M2-like), which are yet pro-inflammatory, can accumulate in tissues and promote inflammaging. Age-related increases in endoplasmic reticulum stress and mitochondrial dysfunction might be cell-intrinsic forces driving this unusual phenotype.
Tryptophan restriction arrests B cell development and enhances microbial diversity in WT and prematurely aging Ercc1−/Δ7 mice
Beek, A.A. van; Hugenholtz, F. ; Meijer, B. ; Sovran, B. ; Perdijk, O.I.J. ; Vermeij, W. ; Brandt, R.M. ; Barnhoorn, R. ; Hoeijmakers, Jan H.J. ; Vos, P. de; Leenen, P.J. ; Hendriks, R.W. ; Savelkoul, H.F.J. - \ 2017
Journal of Leukocyte Biology 101 (2017)4. - ISSN 0741-5400 - p. 811 - 821.
With aging, tryptophan metabolism is affected. Tryptophan has a crucial role in the induction of immune tolerance and the maintenance of gut microbiota. We, therefore, studied the effect of dietary tryptophan restriction in young wild-type (WT) mice (118-wk life span) and in DNA-repair deficient, premature-aged (Ercc1−/Δ7) mice (20-wk life span). First, we found that the effect of aging on the distribution of B and T cells in bone marrow (BM) and in the periphery of 16-wk-old Ercc1−/Δ7 mice was comparable to that in 18-mo-old WT mice. Dietary tryptophan restriction caused an arrest of B cell development in the BM, accompanied by diminished B cell frequencies in the periphery. In general, old Ercc1−/Δ7 mice showed similar responses to tryptophan restriction compared with young WT mice, indicative of age-independent effects. Dietary tryptophan restriction increased microbial diversity and made the gut microbiota composition of old Ercc1−/Δ7 mice more similar to that of young WT mice. The decreased abundances of Alistipes and Akkermansia spp. after dietary tryptophan restriction correlated significantly with decreased B cell precursor numbers. In conclusion, we report that dietary tryptophan restriction arrests B cell development and concomitantly changes gut microbiota composition. Our study suggests a beneficial interplay between dietary tryptophan, B cell development, and gut microbial composition on several aspects of age-induced changes.
The aging immune system and nutritional interventions
Beek, Adriaan A. - \ 2017
Wageningen University. Promotor(en): Huub Savelkoul; R.W. Hendriks, co-promotor(en): P.J.M. Leenen; Harry Wichers. - Wageningen : Wageningen University - ISBN 9789462579552 - 250
immune system - senescence - gastrointestinal microbiota - basophils - macrophages - dna - nutritional intervention - immuunsysteem - veroudering - microbiota van het spijsverteringskanaal - basofielen - macrofagen - dna - maatregel op voedingsgebied
The increased numbers of elderly people pose a major burden to public health care and society. DNA damage is considered to be the major origin of age-related changes in the body. With aging, the immune system becomes deregulated and is characterized by a low-grade inflammation (inflammaging). In this thesis, we investigate the effects of nutritional and microbial interventions on the aging immune system.
In chapter 2, we elaborate on the role of basophils in the immune system, particularly in the initiation and perpetuation of allergic immune responses. We found that basophils and dendritic cells interact in vitro, which reciprocally affects their surface markers and cytokine production. Thus, by modulating cytokine production and surface marker expression on dendritic cells, basophils may act as accessory cells in immune responses. Because little is known about the effects of aging on basophils, we investigated in chapter 3 whether basophils are affected with aging. We found that frequencies of basophils in the spleen of aging mice are increasing, while their phenotype in bone marrow and spleen changes. Moreover, to investigate the role of microbiota in the aging process, we studied the effects of microbiota transfer from young or aged mice into germfree mice. Aging, and microbiota from aged mice, in particular affect differentiation and function of basophil precursors. These findings warrant further studies on the role of basophils in T helper-2 immune responses with aging.
The contribution of macrophages to inflammaging is described in chapter 4. Important aspects for macrophage polarization and function, like autophagy and cellular metabolism, are discussed. Targeting of aged macrophages by (nutritional) interventions may open up new therapeutic opportunities for elderly.
In chapter 5, we studied the in vitro interaction between bacterial supplementations and immune cells (whole spleen cells and macrophages). We noticed that aged immune cells mount a different response to bacterial strains than young immune cells. Based on these outcomes, we selected three bacterial strains (Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, Bifidobacterium breve DSM20213) for in vivo application in chapter 6. We used Ercc1-/Δ7 mice, which lack fully functional ERCC1 protein. As a consequence, DNA repair is compromised, which results in accelerated aging features in all organs, including the immune system. We supplemented Ercc1-/Δ7 mice, as well as control Ercc1+/+ mice with the three selected bacterial strains. We observed that L. plantarum prevented the age-related decline in mucus barrier function of Ercc1-/Δ7 mice, whereas B. breve exacerbated the age-related decline in mucus barrier. L. casei supplementation elevated multiple systemic inflammatory markers in Ercc1-/Δ7 mice, including Ly6Chi monocytes, neutrophils, and Th17 cells in spleen. Strikingly, we found major changes in the mucus barrier and immune system after supplementation of Ercc1-/Δ7 mice with L. plantarum and L. casei, but not after supplementation of Ercc1+/+ mice. Therefore, we conclude that caution is needed in the selection of candidate probiotic strains for supplementation of aging individuals.
In chapter 7, we took a different approach to modulate the aging immune system by applying dietary tryptophan restriction in Ercc1+/+ and Ercc1-/Δ7 mice. We observed that in both mouse models dietary tryptophan restriction modulated B cell development and microbiota composition. In particular, we found a near-complete absence of B cell precursors in the bone marrow after dietary tryptophan restriction. The decline in B cell precursors was correlated with decreased abundance of the Akkermansia and Alistipes bacterial strains in the intestine. Thus, our results show that dietary tryptophan restriction is a powerful intervention to shape immunity and gut microbiota, also in aging. In chapter 8, we assessed the role of microbiota in the aging gut and immune system. Microbiota from young and aged mice were transferred to germfree mice. Aged microbiota induced higher T helper-1 cell and regulatory T cell frequencies in the spleen. In the ileum, the expression of inflammatory markers was increased after transferring aged microbiota, accompanied by differences in the abundance of microbial species. We conclude that senescent microbiota contribute to the inflammaging observed in aging mice.
In chapter 9, we discuss the findings presented in this thesis, concluding with directions for future research. In summary, our studies show that the aging gut and immune system of mice can be modulated by nutritional and/or microbial interventions. Interestingly, our mouse models clearly provide evidence that age-related effects could be reverted or prevented by these interventions. Nevertheless, our studies at the same time show the need for translational research in order to apply the presented dietary and microbial interventions in elderly.
Supplementation with Lactobacillus plantarum WCFS1 prevents Decline of Mucus Barrier in Colon of Accelerated Aging Ercc1-/Δ7 Mice
Beek, A.A. van; Sovran, B. ; Hugenholtz, F. ; Meijer, B. ; Hoogerland, Joanne ; Mihailova, Violeta ; Ploeg, Corine van der; Belzer, C. ; Boekschoten, M.V. ; Hoeijmakers, Jan H.J. ; Vermeij, W.P. ; Vos, P. de; Wells, J.M. ; Leenen, P.M. ; Nicoletti, C. ; Hendriks, R.W. ; Savelkoul, H.F.J. - \ 2016
Mus musculus - GSE87368 - PRJNA344500
Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-wk bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1-/Δ7 mice, which have a median lifespan of ~20wk, and their wild-type littermates. The colonic barrier in Ercc1-/Δ7 mice was characterized by a thin (<10µm) mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1-/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1-/Δ7 mice. L. plantarum- and L. casei-treated Ercc1-/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum – but not with L. casei and B. breve – prevented the decline in the mucus barrier in Ercc1-/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly.
Interaction of mouse splenocytes and macrophages with bacterial strains in vitro: the effect of age in the immune response
Beek, A.A. van; Hoogerland, Joanne ; Belzer, C. ; Vos, P. de; Vos, W.M. de; Savelkoul, H.F.J. ; Leenen, P.J. - \ 2016
Beneficial Microbes 7 (2016)2. - ISSN 1876-2883 - p. 275 - 287.
Probiotics influence the immune system, both at the local and systemic level. Recent findings suggest the relation between microbiota and the immune system alters with age. Our objective was to address direct effects of six bacterial strains on immune cells from young and aged mice: Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, Lactococcus lactis MG1363, Bifidobacterium breve ATCC15700, Bifidobacterium infantis ATCC15697, and Akkermansia muciniphila ATCC BAA-835. We used splenocytes and naïve or interferon-γ-stimulated bone marrow-derived macrophages (BMDM) as responder populations. All tested bacterial strains induced phenotypic and cytokine responses in splenocytes and BMDM. Based on magnitude of the cellular inflammatory response and cytokine profiles, two subgroups of bacteria were identified, i.e. L. plantarum and L. casei versus B. breve, B. infantis, and A. muciniphila. The latter group of bacteria induced high levels of cytokines produced under inflammatory conditions, including tumour necrosis factor (TNF), interleukin (IL)-6 and IL-10. Responses to L. lactis showed features of both subgroups. In addition, we compared responses by splenocytes and BMDM derived from young mice to those of aged mice, and found that splenocytes and BMDM derived from aged mice had an increased IL-10 production and dysregulated IL-6 and TNF production compared to young immune cells. Overall, our study shows differential inflammatory responses to distinct bacterial strains, and profound age-dependent effects. These findings, moreover, support the view that immune environment importantly influences bacterial immune effects.
|The effect of long-term probiotic intervention in fast-aging Ercc1-/Δ7
Beek, A.A. van; Sovran, B. ; Boekschoten, M.V. ; Vos, Paul de; Wells, J.M. ; Hoeijmakers, J.J.H. ; Leenen, P.J. ; Hendriks, R.W. - \ 2015
Prevalence and Risk Factors for Colonization With Extended-Spectrum Cephalosporin-Resistant Escherichia coli in Children Attending Daycare Centers: A Cohort Study in the Netherlands
Koningstein, M. ; Leenen, M.A. ; Mughini-Gras, L. ; Scholts, R.M.C. ; Huisstede-Vlaanderen, K.W. van; Enserink, R. ; Zuidema, R. ; Kooistra-Smid, M.A.M.D. ; Veldman, K.T. ; Mevius, D.J. ; Pelt, W. van - \ 2015
Journal of the Pediatric Infectious Diseases Society 4 (2015)4. - ISSN 2048-7193 - p. e93 - e99.
Background The purpose of this study was to determine the prevalence and risk factors for colonization with extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli in daycare center (DCC)-attending children. Methods This is a prospective cohort study including 44 DCCs in the Netherlands, combining DCC characteristics and monthly collected stool samples from their attendees, and was performed in 2010–2012. During a 22-month study period, 852 stool samples were collected and screened for ESC-R E coli. Risk factors were studied using logistic regression analysis. Results In DCC-attending children (<4 years old), the overall prevalence of ESC-R E coli was 4.5%, and it was 8% in <1-year-old attendees. Among the 38 children carrying ESC-R E coli, the most common types were blaCMY-2 (26%), blaCTX-M-1 (16%), and chromosomal AmpC type 3 promoter mutants (13%). Extended-spectrum cephalosporin-resistant E coli was less common in DCCs where stricter hygiene protocols were enforced, eg, not allowing ill children to enter the DCC (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.14–0.84), performing extra checks on handwashing of ill children (OR, 0.42; 95% CI, 0.20–0.87), and reporting suspected outbreaks to local health authorities (OR, 0.27; 95% CI, 0.11–0.69). Conclusions The distribution of ESC-R E coli types in DCCs differs from that of the general population. Extended-spectrum cephalosporin-resistant E coli carriage in DCC-attending children is associated with the hygiene policies enforced in the DCC. Although our results are not conclusive enough to change current DCC practice beyond ensuring compliance with standing policies, they generated hypotheses and defined the degree of ESC resistance among DCC attendees, which may influence empiric antibiotic therapy choices, and tracked the increasing trend in ESC resistance.
Beleving van water in de stad: een literatuurstudie
Hunen, S.E. van; Kruining, M. van; Leenen, I. ; Maessen, M. - \ 2015
H2O : tijdschrift voor watervoorziening en afvalwaterbehandeling 43 (2015)19. - ISSN 0166-8439 - p. 34 - 35.
waterbeheer - stedelijke bevolking - stedelijke samenleving - watersystemen - ontwerp - participatie - stadsontwikkeling - landschapsbouw - literatuuroverzichten - water management - urban population - urban society - water systems - design - participation - urban development - landscaping - literature reviews
Mensen wonen en werken bij water in de stad en willen ook steeds meer betrokken raken bij het waterbeheer in de stad. Uit onderzoek blijkt dat een leefomgeving, die plezierig overkomt op mensen, leidt tot sterke tevredenheid en geluk. Die positieve beleving van burgers draagt bij tot meer acceptatie, medewerking en begrip bij ingrepen in en aanpassingen van het watersysteem. Het is daarom belangrijk om na te gaan hoe water door de burger wordt beleefd en dit mee te nemen in het ontwerp van watersystemen. Land en water zijn allebei bepalend voor de kwaliteit van het landschap en moeten op elkaar worden afgestemd. Het water moet passen in het beeld dat mensen van de omgeving hebben
|Long-term probiotic intervention alters immune competence and gut barrier in fast ageing Ercc1-/ ¿7 mice
Beek, A.A. van; Sovran, B. ; Meijer, B. ; Hugenholtz, F. ; Vos, P. de; Boekschoten, M.V. ; Hoeijmakers, J.J.H. ; Leenen, P.J. ; Hendriks, R.W. ; Savelkoul, H.F.J. - \ 2014
|Probiotic intervention in fast ageing Ercc1-/ 7 mice affects mucosal and systemic immunity
Beek, A.A. van; Sovran, B. ; Meijer, B. ; Vos, P. de; Dekker, J. ; Wells, J.M. ; Wichers, H.J. ; Leenen, P.J. ; Savelkoul, H.F.J. - \ 2014
|Nutritional intervention study in fast ageing Ercc1- 7mice
Beek, A.A. van; Sovran, B. ; Meijer, B. ; Leenen, P.J. ; Wichers, H.J. ; Savelkoul, H.F.J. - \ 2014
|Long-term probiotic intervention affects B cell differentiation in bone marrow of fast ageing Ercc1-/¿7 mice
Beek, A.A. van; Sovran, B. ; Meijer, B. ; Vos, P. de; Hoeijmakers, J.J.H. ; Leenen, P.J. ; Hendriks, R.W. ; Savelkoul, H.F.J. - \ 2014
Gut microbiota and immunity are related and alter upon ageing. Therefore, we investigated the effects of probiotics on maturation and function of ageing B cells. We used fast ageing Ercc1-/¿7 mice (median lifespan 20 weeks) and wild-type mice to study the effect of probiotics on the ageing immune system. Mice were supplemented the probiotic strains L. plantarum WCFS1, L. casei BL23 and B. breve DSM20213 by gavage for 10 weeks. At 16 weeks of age, the B cell composition of various organs was measured by multicolour flow cytometry. Immune competence was evaluated by stimulating spleen and bone marrow (BM) cells with several ligands (e.g. LPS). B cell frequencies in particular decreased in the BM after L. casei treatment in Ercc1-/¿7 (15 vs. 27%; p
|Ercc1-/¿7 mice are a suitable model for ageing of mucosal immunity and microbiota
Beek, A.A. van; Meijer, B. ; Sovran, B. ; Vos, P. de; Hoeijmakers, J.J.H. ; Leenen, P.J. ; Hugenholtz, F. ; Boekschoten, M.V. ; Savelkoul, H.F.J. - \ 2014
As ageing profoundly affects the immune system, we investigated the effects of ageing on systemic and mucosal immunity, gut barrier and physiology, and microbiota composition. We compared the intestinal physiology and the mucosal immune system of young and old fast ageing Ercc1-/¿7 and wild-type (WT) mice. Multicolour flow cytometry was performed on several immune organs, and histology and FISH were performed on jejunum, ileum and colon of both Ercc1-/¿7 and WT mice. Gene expression arrays on ileum and colon and MIT-Chips were performed in Ercc1-/¿7 mice. In aged Ercc1-/¿7 and WT mice, a decrease in mucus thickness with bacteria touching the epithelium and leukocyte infiltration was observed both in ileum and colon. Multicolour flow cytometry showed several changes in immune status, including increased neutrophil and decreased lymphocyte frequencies in bone marrow and spleen. Gene expression arrays revealed upregulation of immune pathways in the ileum and colon of aged mice, such as pathways of granulocyte adhesion and diapedesis, and leukocyte extravastion. TGF-ß1, IFN-¿ and TNF were predicted to be more active (p
Balancing of Histone H3K4 Methylation States by the Kdm5c/SMCX Histone Demethylase Modulates Promoter and Enhancer Function
Outchkourov, N.S. ; Muino Acuna, J.M. ; Kaufmann, K. ; IJken, W.F.J. ; Groot Koerkamp, M.J. ; Leenen, D. van; Graaf, P. de; Holstege, F.C.P. ; Grosveld, F. ; Timmers, H.T.M. - \ 2013
Cell Reports 3 (2013)4. - ISSN 2211-1247 - p. 1071 - 1079.
little-imaginal-discs - embryonic stem-cells - binding-protein 2 - gene-expression - distinct functions - self-renewal - human genome - transcription - differentiation - reveals
The functional organization of eukaryotic genomes correlates with specific patterns of histone methylations. Regulatory regions in genomes such as enhancers and promoters differ in their extent of methylation of histone H3 at lysine-4 (H3K4), but it is largely unknown how the different methylation states are specified and controlled. Here, we show that the Kdm5c/Jarid1c/SMCX member of the Kdm5 family of H3K4 demethylases can be recruited to both enhancer and promoter elements in mouse embryonic stem cells and in neuronal progenitor cells. Knockdown of Kdm5c deregulates transcription via local increases in H3K4me3. Our data indicate that by restricting H3K4me3 modification at core promoters, Kdm5c dampens transcription, but at enhancers Kdm5c stimulates their activity. Remarkably, an impaired enhancer function activates the intrinsic promoter activity of Kdm5c-bound distal elements. Our results demonstrate that the Kdm5c demethylase plays a crucial and dynamic role in the functional discrimination between enhancers and core promoters
|The roles of floodplains from a socio-economic perspective
Penning, E. ; Gerritsen, A.L. ; Querner, E.P. ; Swart, E. de; Haasnoot, M. ; Leenen, I. - \ 2006
In: How to use floodplains for flood risk reduction; Ecoflood guidelines / Blackwell, M.S.A., Maltby, E., Luxembourg : EC (Project Report EUR 22001) - ISBN 9789279009624 - p. 71 - 82.
Ecoflood guidelines : how to use floodplains for flood risk reduction
Blackwell, M.S.A. ; Maltby, E. ; Gerritsen, A.L. ; Haasnoot, M. ; Hoffmann, C.C. ; Kotowski, W. ; Leenen, E.J.T.M. ; Okruszko, T. ; Penning, W.E. ; Piorkowski, H. ; Platteeuw, M. ; Querner, E.P. ; Siedlecki, T. ; Swart, E.O.A.M. de - \ 2005
[S.l.] : Ecoflood Project - 144
stroomvlakten - hoogwaterbeheersing - overstromingen - risicovermindering - richtlijnen (guidelines) - rivieren - europa - risicobeheersing - floodplains - flood control - floods - risk reduction - guidelines - rivers - europe - risk management
The main objective of these guidelines is to promote the use of floodplains as natural flood defence measures, while at the same time optimising other compatible functions and values through conservation and restoration. It is intended that these guidelines will be used as a tool primarily by policy-makers and decision-makers who are aware of the potential advantages of floodplain restoration and management in the role of flood control, but may benefit from comprehensive guidance on assessing, initiating, funding and carrying-out such schemes as well as information on the other functions floodplains can perform. It is also intended that they will be an accessible source of information for a wide range of stakeholders with an interest in floodplain management. Case studies are provided to illustrate the wide range of schemes that can be carried out and the degrees of success that have been achieved. Case studies from the Netherlands are: 1. Meinerswijk, Rhine; 2. Zandmaas and Grensmaas, Meuse; 3. Gamerensche Waard, Lower Rhine; 4. Afferdensche en Deestsche Waarden, Lower Rhine
Campylobacter in zwemwater en mogelijke emissiebronnen
Ruiter, H. ; Rijs, G. ; Jacobs-Reitsma, W.F. ; Leenen, I. - \ 2004
H2O : tijdschrift voor watervoorziening en afvalwaterbehandeling 37 (2004)12. - ISSN 0166-8439 - p. 19 - 21.
campylobacter - zwemmen - waterverontreiniging - humane ziekten - waterkwaliteit - besmetting - oppervlaktewater - afvoerwater - volksgezondheid - campylobacter - swimming - water pollution - human diseases - water quality - contamination - surface water - effluents - public health
Campylobacter vormt samen met Salmonella en Shigella één van de belangrijkste bacteriële ziekteverwekkers van het maagdarmkanaal bij de mens. De bacterie Campylobacter komt voor bij eenden, meeuwen, kippen en kalkoenen, maar is ook aanwezig in koeien, varkens en schapen. Al deze dieren zijn drager, maar worden er zelf niet ziek van. Infecties met Campylobacter leiden in Nederland jaarlijks tot circa honderdduizend gevallen van maagdarmstoornissen en enkele duizenden gevallen van reactieve artritis (spierontsteking). De infectieuze dosis is laag en de besmetting vindt doorgaans plaats via de fecaal-orale route. Uit een inventariserend onderzoek blijkt dat naast de algemeen bekende besmettingsroute via voedsel (voornamelijk pluimveevlees) ook verontreinigd zwemwater een besmettingsbron kan vormen
Kennisintegratie via (inter)nationale samenwerking; "standaard raamwerk" maakt koppeling rekenmodellen mogelijk
Leenen, J. ; Blind, M. ; Giessen, A. van der; Groenendijk, P. ; Melger, E. - \ 2004
H2O : tijdschrift voor watervoorziening en afvalwaterbehandeling 37 (2004)10. - ISSN 0166-8439 - p. 38 - 39.
waterbeheer - waterbeleid - simulatiemodellen - informatietechnologie - informatiesystemen - kennis - samenwerking - computer software - water management - water policy - simulation models - information technology - information systems - knowledge - cooperation - computer software
Maatschappelijke afwegingen in het waterbeleid en -beheer zijn veelomvattend. Ze vragen om steeds meer samenwerking tussen diverse organisaties, ook voor uitwisseling van informatie. Zes Nederlandse kennisinstituten (Alterra, TNO, RIVM, Rijkswaterstaat, STOWA en WL/Delft Hydraulics) hebben daarom gezamenlijk het 'Standaard Raamwerk' ontwikkeld: een soort van infrastructuur voor ICT die het mogelijk maakt om verschillende rekenmodellen en bijbehorende gegevens aan elkaar te koppelen tot een samenhangend modelinstrumentarium voor integrale analyses van water en milieu. Zo kan de kennis van verschillende kennisinstellingen optimaal worden benut. Met enkele veel toegepaste modellen is de praktische bruikbaarheid van het raamwerk inmiddels aangetoond. Het is intussen overgenomen op Europese schaal. Uiteindelijk moet het leiden tot een moderne IT-architectuur die het beleid en beheer op watergebied op een snelle, flexibele en geharmoniseerde wijze ondersteunt.
Supplementation of plasma with olive oil phenols and extracts: Influence on LDL oxidation
Leenen, R. ; Roodenburg, A.J.C. ; Vissers, M.N. ; Schuurbiers, J.A.E. ; Putte, K.P.A.M. van; Wiseman, S.A. ; Put, F.H.M.M. van de - \ 2002
Journal of Agricultural and Food Chemistry 50 (2002)5. - ISSN 0021-8561 - p. 1290 - 1297.
low-density-lipoprotein - in-vitro oxidation - lipid-peroxidation - heart-disease - vitamin-e - dietary oils - antioxidants - oleuropein - humans - susceptibility
Phenols present in olive oil may contribute to the health effects of the Mediterranean lifestyle. Olive oil antioxidants increase the resistance of low-density lipoproteins (LDL) against oxidation in vitro, but human intervention studies have failed to demonstrate similar consistent effects. To better mimic the in vivo situation, plasma was incubated with either individual olive oil phenols or olive oil extracts with different phenolic compositions, and LDL was subsequently isolated and challenged for its resistance to oxidation. The results show that the ortho-dihydroxy phenols (hydroxytyrosol and oleuropein-aglycone) are more efficient than their mono-hydroxy counterparts (tyrosol and ligstroside-aglycone) in increasing the resistance of LDL to oxidation. However, the concentration of antioxidants required to inhibit LDL oxidation when added to whole plasma was substantially higher as compared to previous data where antioxidants are directly added to isolated LDL. In conclusion, this study supports the hypothesis that extra virgin olive oil phenols protect LDL in plasma against oxidation. The explanation that in vitro studies show protective effects in contrast to the lack of effect in the majority of human studies may be that the dose of the phenols and thus their plasma concentration in humans was too low to influence ex vivo LDL oxidizability. Further studies are required to gain a better understanding of the potential health benefits that extra virgin olive oil may provide
Olive oil phenols are absorbed in humans
Vissers, M.N. ; Zock, P.L. ; Roodenburg, A.J.C. ; Leenen, R. ; Katan, M.B. - \ 2002
The Journal of Nutrition 132 (2002)3. - ISSN 0022-3166 - p. 409 - 417.
Animal and in vitro studies suggest that olive oil phenols are effective antioxidants. The most abundant phenols in olive oil are the nonpolar oleuropein- and ligstroside-aglycones and the polar hydroxytyrosol and tyrosol. The aim of this study was to gain more insight into the metabolism of those phenols in humans. We measured their absorption in eight healthy ileostomy subjects. We also measured urinary excretion in the ileostomy subjects and in 12 volunteers with a colon. Subjects consumed three different supplements containing 100 mg of olive oil phenols on separate days in random order. Ileostomy subjects consumed a supplement with mainly nonpolar phenols, one with mainly polar phenols and one with the parent compound oleuropein-glycoside. Subjects with a colon consumed a supplement without phenols (placebo) instead of the supplement with oleuropein-glycoside. Ileostomy effluent and urine were collected for 24 h after supplement intake. Tyrosol and hydroxytyrosol concentrations were low (< 4 mol/100 mol of intake) in the ileostomy effluent, and no aglycones were detected. We estimated that the apparent absorption of phenols was at least 55–66% of the ingested dose. Absorption was confirmed by the excretion of tyrosol and hydroxytyrosol in urine. In ileostomy subjects, 12 mol/100 mol and in subjects with a colon, 6 mol/100 mol of the phenols from the nonpolar supplement were recovered in urine as tyrosol or hydroxytyrosol. In both subject groups, 5–6 mol/100 mol of the phenols was recovered from the polar supplement. When ileostomy subjects were given oleuropein-glycoside, 16 mol/100 mol was recovered in 24-h urine, mainly in the form of hydroxytyrosol. Thus, humans absorb a large part of ingested olive oil phenols and absorbed olive oil phenols are extensively modified in the body. -------------------------------------------------------------------------------- KEY WORDS: … phenols … olive oil … absorption … ileostomy … humans