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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    Correction to: Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein
    Keating, Samuel T. ; Groh, Laszlo ; Thiem, Kathrin ; Bekkering, Siroon ; Li, Yang ; Matzaraki, Vasiliki ; Heijden, Charlotte D.C.C. van der; Puffelen, Jelmer H. van; Lachmandas, Ekta ; Jansen, Trees ; Oosting, Marije ; Bree, L.C.J. de; Koeken, Valerie A.C.M. ; Moorlag, Simone J.C.F.M. ; Mourits, Vera P. ; Diepen, Janna van; Stienstra, Rinke ; Novakovic, Boris ; Stunnenberg, Hendrik G. ; Crevel, Reinout van; Joosten, Leo A.B. ; Netea, Mihai G. ; Riksen, Niels P. - \ 2020
    Journal of Molecular Medicine 98 (2020). - ISSN 0946-2716

    The correct name of the 17th Author is presented in this paper. In the paragraph “Metabolic analysis” of the Method section “an XFp Analyzer” should be changed to “an XFe96 Analyzer”.

    Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein
    Keating, Samuel T. ; Groh, Laszlo ; Thiem, Kathrin ; Bekkering, Siroon ; Li, Yang ; Matzaraki, Vasiliki ; Heijden, Charlotte D.C.C. van der; Puffelen, Jelmer H. van; Lachmandas, Ekta ; Jansen, Trees ; Oosting, Marije ; Bree, L.C.J. de; Koeken, Valerie A.C.M. ; Moorlag, Simone J.C.F.M. ; Mourits, Vera P. ; Diepen, Janna van; Stienstra, Rinke ; Novakovic, Boris ; Stunnenberg, Hendrik G. ; Crevel, Reinout van; Joosten, Leo A.B. ; Netea, Mihai G. ; Riksen, Niels P. - \ 2020
    Journal of Molecular Medicine 98 (2020). - ISSN 0946-2716 - p. 819 - 831.
    Atherosclerosis - Cardiovascular disease - Diabetes complications - Glycolysis - Immunometabolism - Inflammation - Trained immunity

    Abstract: Stimulation of monocytes with microbial and non-microbial products, including oxidized low-density lipoprotein (oxLDL), induces a protracted pro-inflammatory, atherogenic phenotype sustained by metabolic and epigenetic reprogramming via a process called trained immunity. We investigated the intracellular metabolic mechanisms driving oxLDL-induced trained immunity in human primary monocytes and observed concomitant upregulation of glycolytic activity and oxygen consumption. In two separate cohorts of healthy volunteers, we assessed the impact of genetic variation in glycolytic genes on the training capacity of monocytes and found that variants mapped to glycolytic enzymes PFKFB3 and PFKP influenced trained immunity by oxLDL. Subsequent functional validation with inhibitors of glycolytic metabolism revealed dose-dependent inhibition of trained immunity in vitro. Furthermore, in vivo administration of the glucose metabolism modulator metformin abrogated the ability for human monocytes to mount a trained response to oxLDL. These findings underscore the importance of cellular metabolism for oxLDL-induced trained immunity and highlight potential immunomodulatory strategies for clinical management of atherosclerosis. Key messages: Brief stimulation of monocytes to oxLDL induces a prolonged inflammatory phenotype.This is due to upregulation of glycolytic metabolism.Genetic variation in glycolytic genes modulates oxLDL-induced trained immunity.Pharmacological inhibition of glycolysis prevents trained immunity.

    Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects
    Lachmandas, Ekta ; Eckold, Clare ; Böhme, Julia ; Koeken, Valerie A.C.M. ; Marzuki, Mardiana Binte ; Blok, Bastiaan ; Arts, Rob J.W. ; Chen, Jinmiao ; Teng, Karen W.W. ; Ratter, Jacqueline ; Smolders, Elise J. ; Heuvel, Corina Van den; Stienstra, Rinke ; Dockrell, Hazel M. ; Newell, Evan ; Netea, Mihai G. ; Singhal, Amit ; Cliff, Jacqueline M. ; Crevel, Reinout Van - \ 2019
    The Journal of Infectious Diseases 220 (2019)1. - ISSN 0022-1899 - p. 139 - 150.
    antimycobacterial mechanisms - gene transcription - host-directed therapy - Metformin - tuberculosis

    BACKGROUND: Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis. METHODS: We investigated in vitro and in vivo effects of metformin in humans. RESULTS: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to nonclassical monocytes. At a functional level, metformin lowered ex vivo production of tumor necrosis factor α, interferon γ, and interleukin 1β but increased phagocytosis activity and reactive oxygen species production. CONCLUSION: Metformin has a range of potentially beneficial effects on cellular metabolism, immune function, and gene transcription involved in innate host responses to M. tuberculosis.

    Tissue Metabolic Changes Drive Cytokine Responses to Mycobacterium tuberculosis
    Lachmandas, Ekta ; Rios-Miguel, Ana B. ; Koeken, Valerie A.C.M. ; Pasch, Eva van der; Kumar, Vinod ; Matzaraki, Vasiliki ; Li, Yang ; Oosting, Marije ; Joosten, Leo A.B. ; Notebaart, Richard A. ; Noursadeghi, Mahdad ; Netea, Mihai G. ; Crevel, Reinout van; Pollara, Gabriele - \ 2018
    The Journal of Infectious Diseases 218 (2018)1. - ISSN 0022-1899 - p. 165 - 170.
    cytokines - functional genomics - human challenge model - immune response - immunometabolism - metabolism - microarrays - transcriptomics - tuberculosis

    Cellular metabolism can influence host immune responses to Mycobacterium tuberculosis. Using a systems biology approach, differential expression of 292 metabolic genes involved in glycolysis, glutathione, pyrimidine, and inositol phosphate pathways was evident at the site of a human tuberculin skin test challenge in patients with active tuberculosis infection. For 28 metabolic genes, we identified single nucleotide polymorphisms that were trans-acting for in vitro cytokine responses to M. tuberculosis stimulation, including glutathione and pyrimidine metabolism genes that alter production of Th1 and Th17 cytokines. Our findings identify novel therapeutic targets in host metabolism that may shape protective immunity to tuberculosis.

    Cerebral tryptophan metabolism and outcome of tuberculous meningitis : An observational cohort study
    Laarhoven, Arjan van; Dian, Sofiati ; Aguirre-Gamboa, Raúl ; Avila-Pacheco, Julian ; Ricaño-Ponce, Isis ; Ruesen, Carolien ; Annisa, Jessi ; Koeken, Valerie A.C.M. ; Chaidir, Lidya ; Li, Yang ; Achmad, Tri Hanggono ; Joosten, Leo A.B. ; Notebaart, Richard A. ; Ruslami, Rovina ; Netea, Mihai G. ; Verbeek, Marcel M. ; Alisjahbana, Bachti ; Kumar, Vinod ; Clish, Clary B. ; Ganiem, A.R. ; Crevel, Reinout van - \ 2018
    The Lancet Infectious Diseases 18 (2018)5. - ISSN 1473-3099 - p. 526 - 535.
    Background: Immunopathology contributes to the high mortality of tuberculous meningitis, but the biological pathways involved are mostly unknown. We aimed to compare cerebrospinal fluid (CSF) and serum metabolomes of patients with tuberculous meningitis with that of controls without tuberculous meningitis, and assess the link between metabolite concentrations and mortality. Methods: In this observational cohort study at the Hasan Sadikin Hospital (Bandung, Indonesia) we measured 425 metabolites using liquid chromatography-mass spectrometry in CSF and serum from 33 HIV-negative Indonesian patients with confirmed or probable tuberculous meningitis and 22 control participants with complete clinical data between March 12, 2009, and Oct 27, 2013. Associations of metabolite concentrations with survival were validated in a second cohort of 101 patients from the same centre. Genome-wide single nucleotide polymorphism typing was used to identify tryptophan quantitative trait loci, which were used for survival analysis in a third cohort of 285 patients. Findings: Concentrations of 250 (70%) of 351 metabolites detected in CSF were higher in patients with tuberculous meningitis than in controls, especially in those who died during follow-up. Only five (1%) of the 390 metobolites detected in serum differed between patients with tuberculous meningitis and controls. CSF tryptophan concentrations showed a pattern different from most other CSF metabolites; concentrations were lower in patients who survived compared with patients who died (9-times) and to controls (31-times). The association of low CSF tryptophan with patient survival was confirmed in the validation cohort (hazard ratio 0·73; 95% CI 0·64-0·83; p<0·0001; per each halving). 11 genetic loci predictive for CSF tryptophan concentrations in tuberculous meningitis were identified (p<0·00001). These quantitative trait loci predicted survival in a third cohort of 285 HIV-negative patients in a prognostic index including age and sex, also after correction for possible confounders (p=0·0083). Interpretation: Cerebral tryptophan metabolism, which is known to affect Mycobacterium tuberculosis growth and CNS inflammation, is important for the outcome of tuberculous meningitis. CSF tryptophan concentrations in tuberculous meningitis are under strong genetic influence, probably contributing to the variable outcomes of tuberculous meningitis. Interventions targeting tryptophan metabolism could improve outcomes of tuberculous meningitis. Funding: Royal Dutch Academy of Arts and Sciences; Netherlands Foundation for Scientific Research; Radboud University; National Academy of Sciences; Ministry of Research, Technology, and Higher Education, Indonesia; European Research Council; and PEER-Health.
    Transmissible mycobacterium tuberculosis strains share genetic markers and immune phenotypes
    Nebenzahl-Guimaraes, Hanna ; Laarhoven, Arjan van; Farhat, Maha R. ; Koeken, Valerie A.C.M. ; Mandemakers, Jornt J. ; Zomer, Aldert ; Hijum, Sacha A.F.T. Van; Netea, Mihai G. ; Murray, Megan ; Crevel, Reinout van; Soolingen, Dick van - \ 2017
    American Journal of Respiratory and Critical Care Medicine 195 (2017)11. - ISSN 1073-449X - p. 1519 - 1527.
    Bacterial genomes - Immunology - Transmission - Tuberculosis

    Rationale: Successful transmission of tuberculosis depends on the interplay of human behavior, host immune responses, and Mycobacterium tuberculosis virulence factors. Previous studies have been focused on identifying host risk factors associated with increased transmission, but the contribution of specific genetic variations in mycobacterial strains themselves are still unknown. Objectives: To identify mycobacterial genetic markers associated with increased transmissibility and to examine whether these markers lead to altered in vitro immune responses. Methods: Using a comprehensive tuberculosis registry (n = 10,389) and strain collection in the Netherlands, we identified a set of 100 M. tuberculosis strains either least or most likely to be transmitted after controlling for host factors.Wesubjected these strains to wholegenome sequencing and evolutionary convergence analysis, and we repeated this analysis in an independent validation cohort. We then performed immunological experiments to measure in vitro cytokine production and neutrophil responses to a subset of the original strains with or without the identified mutations associated with increased transmissibility. Measurements and Main Results: We identified the loci espE, PE-PGRS56, Rv0197, Rv2813-2814c, and Rv2815-2816c as targets of convergent evolution among transmissible strains. We validated four of these regions in an independent set of strains, and we demonstrated that mutations in these targets affected in vitro monocyte and T-cell cytokine production, neutrophil reactive oxygen species release, and apoptosis. Conclusions: In this study, we identified genetic markers in convergent evolution of M. tuberculosis toward enhanced transmissibility in vivo that are associated with altered immune responses in vitro.

    Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity
    Arts, Rob J.W. ; Novakovic, Boris ; Horst, Rob ter; Carvalho, Agostinho ; Bekkering, Siroon ; Lachmandas, Ekta ; Rodrigues, Fernando ; Silvestre, Ricardo ; Cheng, Shih Chin ; Wang, Shuang Yin ; Habibi, Ehsan ; Gonçalves, Luís G. ; Mesquita, Inês ; Cunha, Cristina ; Laarhoven, Arjan van; Veerdonk, Frank L. van de; Williams, David L. ; Meer, Jos W.M. van der; Logie, Colin ; O'Neill, Luke A. ; Dinarello, Charles A. ; Riksen, Niels P. ; Crevel, Reinout van; Clish, Clary ; Notebaart, Richard A. ; Joosten, Leo A.B. ; Stunnenberg, Hendrik G. ; Xavier, Ramnik J. ; Netea, Mihai G. - \ 2016
    Cell Metabolism 24 (2016)6. - ISSN 1550-4131 - p. 807 - 819.
    cholesterol metabolism - epigenetics - glutamine metabolism - glycolysis - trained immunity

    Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by β-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to β-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by β-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.

    Different pathogenic stimuli induce specific metabolic rewiring in human monocytes
    Lachmandas, Ekta ; Boutens, Lily ; Ratter, Jacqueline ; Hijmans, Anneke ; Hooiveld, Guido ; Crevel, Reinout van; Netea, Mihai ; Stienstra, Rinke - \ 2016
    Wageningen University
    Homo sapiens - GSE78699 - Homo sapiens - GSE78699 - PRJNA313233
    Recent studies have demonstrated that upon encountering a pathogenic stimulus, robust metabolic rewiring of immune cells occurs. A switch away from oxidative phosphorylation to glycolysis, even in the presence of sufficient amounts of oxygen (akin the Warburg effect), is typically observed in activated innate and adaptive immune cells and is thought to accommodate adequate inflammatory responses. However, whether the Warburg effect is a general phenomenon applicable in human monocytes exposed to different pathogenic stimuli is unknown. Our results using human monocytes from healthy donors demonstrate that the Warburg effect only holds true for TLR4 activated cells. Although activation of other TLRs leads to an increase in glycolysis, no reduction or even an enhancement in oxidative phosphorylation is observed. Moreover, specific metabolic rewiring occurs in TLR4 vs. TLR2 stimulated cells characterized by altered gene expression profiles of pathways related to metabolism, changes in spare respiratory capacity of the cells and differential regulation of mitochondrial enzyme activity. Similarly, results from ex vivo and in vivo studies demonstrate metabolic rewiring of immune cells that is highly dependent on the type of pathogenic stimulus. Although the Warburg effect is observed in human monocytes after TLR4 activation, we propose that this typical metabolic response is not applicable to other inflammatory signalling routes including TLR2 in human monocytes. Instead, each pathogenic stimulus and subsequently activated inflammatory signalling cascade induces specific metabolic rewiring of the immune cell to accommodate an appropriate response.
    Microbial stimulation of different Toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes
    Lachmandas, Ekta ; Boutens, Lily ; Ratter, Jacqueline M. ; Hijmans, Anneke ; Hooiveld, Guido J. ; Joosten, Leo A.B. ; Rodenburg, Richard J. ; Fransen, Jack A.M. ; Houtkooper, Riekelt H. ; Crevel, R. van; Netea, Mihai G. ; Stienstra, R. - \ 2016
    Nature Microbiology 2 (2016). - ISSN 2058-5276

    Microbial stimuli such as lipopolysaccharide (LPS) induce robust metabolic rewiring in immune cells known as the Warburg effect. It is unknown whether this increase in glycolysis and decrease in oxidative phosphorylation (OXPHOS) is a general characteristic of monocytes that have encountered a pathogen. Using CD14+ monocytes from healthy donors, we demonstrated that most microbial stimuli increased glycolysis, but that only stimulation of Toll-like receptor (TLR) 4 with LPS led to a decrease in OXPHOS. Instead, activation of other TLRs, such as TLR2 activation by Pam3CysSK4 (P3C), increased oxygen consumption and mitochondrial enzyme activity. Transcriptome and metabolome analysis of monocytes stimulated with P3C versus LPS confirmed the divergent metabolic responses between both stimuli, and revealed significant differences in the tricarboxylic acid cycle, OXPHOS and lipid metabolism pathways following stimulation of monocytes with P3C versus LPS. At a functional level, pharmacological inhibition of complex I of the mitochondrial electron transport chain diminished cytokine production and phagocytosis in P3C- but not LPS-stimulated monocytes. Thus, unlike LPS, complex microbial stimuli and the TLR2 ligand P3C induce a specific pattern of metabolic rewiring that involves upregulation of both glycolysis and OXPHOS, which enables activation of host defence mechanisms such as cytokine production and phagocytosis.

    Cytokines related to nutritional status in patients with untreated pulmonary tuberculosis in Indonesia
    Karyadi, E. ; Dolmans, W.M.V. ; West, C.E. ; Crevel, R. ; Nelwan, R.H.H. ; Amin, Z. ; Gross, R. ; Ven-Jongekrijg, J. Van der; Meer, J.W.M. van der - \ 2007
    Asia Pacific Journal of Clinical Nutrition 16 (2007)2. - ISSN 0964-7058 - p. 218 - 226.
    necrosis-factor-alpha - vitamin-a - zinc-deficiency - mycobacterium-tuberculosis - interleukin-6 - supplementation - malnutrition - secretion - infection - children
    Although several studies have dealt with the patterns of cytokine production in tuberculosis, little is known about the association between nutrient deficiencies and cytokines in tuberculosis. The objective of this study was to assess the concentration of cytokines related to nutritional status during tuberculosis. In 41 untreated tuberculosis patients and matched healthy controls in an urban hospital in Indonesia, we measured: height and weight, parameters of iron, vitamin A and zinc; and cytokines concentrations in the circulation and production in whole blood cultures. Plasma interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were significantly higher in patients than in controls. Patients with cavities (n=26) had higher concentrations of IL-6 than patients without cavities (n=15). Body mass index
    The prevalence, cost and basis of food allergy across Europe
    Mills, E.N.C. ; Mackie, A.R. ; Burney, P. ; Beyer, K. ; Frewer, L.J. ; Madsen, C. ; Botjes, E. ; Crevel, R.W.R. ; Ree, R. van - \ 2007
    Allergy 62 (2007)7. - ISSN 0105-4538 - p. 717 - 722.
    Abstract The development of effective management strategies to optimize the quality of life for allergic patients is currently hampered by a lack of good quality information. Estimates of how many individuals suffer from food allergy and the major foods involved vary widely and inadequacies of in vitro diagnostics make food challenges the only reliable means of diagnosis in many instances. The EuroPrevall project brings together a multidisciplinary partnership to address these issues. Cohorts spanning the main climatic regions of Europe are being developed in infants through a birth cohort, community surveys in school-age children and adults and an outpatient clinic study. Confirmatory double-blind placebo-controlled food challenge diagnosis is being undertaken using foods as they are eaten with titrated doses to allow no-effect and lowest-observable effect levels for allergenic foods to be determined. The cohorts will also facilitate validation of novel in vitro diagnostics through the development of the EuroPrevall Serum Bank. Complementary studies in Ghana, western Siberia, India and China will allow us to gain insights into how different dietary patterns and exposure to microorganisms affect food allergies. New instruments to assess the socioeconomic impact of food allergy are being developed in the project and their application in the clinical cohorts will allow, for the first time, an assessment to be made of the burden this disease places on allergy sufferers and their communities. IgE-mediated food allergy is a disease affecting all age groups and because the only treatment is still avoidance (1), it changes quality of life in a profoundly negative way (2). Allergy sufferers have to deal with disbelief about their condition and face difficulties in managing their social life. Patients¿ (or allergic children¿s parents¿) anxiety about severe reactions can lead to social isolation and mental health problems (3). Everyday activities become complicated, requiring forethought and preparation, even extending to the need for special diets during hospitalization. Clear food labelling regarding food allergens is essential to help allergic consumers manage their condition, although precautionary labelling can lead to unnecessary restrictions (4). Such social problems are compounded by the fact that, whilst knowledge of the diagnosis and treatment of food allergy by health professionals and dieticians should be standard, it is frequently inadequate (5). The majority of food allergies are IgE-mediated, but sensitization to a specific food does not always lead to clinical reactivity. Consequently serological tests for food-specific IgE cannot be used alone for diagnosis. As a consequence of inadequate diagnostic procedures, food allergy is sometimes over-diagnosed (6). On the other hand, food allergy is also often not recognized or incorrectly treated. Therefore, patients still leave the hospital without either a prescription for self-injectable adrenaline or even referral to an allergy specialist after treatment for acute anaphylaxis (7). Within this context it is the objective of the EU-funded integrated project EuroPrevall ( to deliver the information and tools necessary for policy makers, regulators, clinicians and allergic consumers, together with the food industry, to effectively manage food allergies and the allergens that cause them. This is being undertaken in a pan-European manner with a view of improving the quality of life of food allergic consumers. The project includes 56 partners from 21 different countries (from 19 European countries, Ghana, India and China) with additional collaborating centres and partners from the USA, Australia and New Zealand.
    Communication needs and food allergy : an analysis of stakeholder views
    Miles, S. ; Crevel, R. ; Chryssochoidis, G. ; Frewer, L.J. ; Grimshaw, K. ; Guidonet Riera, A. ; Gowland, H. ; Knibb, R. ; Koch, P. ; Madson, C. ; Mills, C. ; Palkonen, S. ; Pfaff, S. ; Roccaldo, R. ; Scholderer, J. ; Ueland, O. ; Valovirta, E. ; Verbeke, W. - \ 2006
    In: Allergy Matters : new Approaches to Allergy Prevention and Management / Gilissen, L.J.E.J., Wichers, H.J., Savelkoul, H.F.J., Bogers, R.J., Wageningen, the Netherlands : Wageningen University Press (Wageningen UR Frontis Series 10) - ISBN 9781402038969 - p. 171 - 193.
    Abstract At present, the most useful approaches to communicating information about food allergy to different stakeholder groups are not understood. Stakeholders include allergic consumers, their carers, health professionals, public authorities (regulators and compliance authorities), retailers, manufacturers, caterers and the general public. Communication needs are reviewed both generally and specifically from the perspectives of different stakeholders. A stakeholder consultation was conducted to solicit the views of different stakeholders regarding what information is required. This indicated some common needs regarding, for example, causes and symptomology of food allergy. In addition, some specific information needs for different stakeholders were also identified. The industrial sector requires more information about clear guidelines for labelling practices, whereas the allergic consumers and health professionals require more information about symptomology, treatment and prevention. Regulators specifically need information from risk assessors regarding issues key to the implementation of an effective regulatory framework. This may need to be at a more detailed level of technicality than that required by other stakeholders (for example, consumers). The results therefore suggest that targeted information strategies may be the most resource-efficient way to communicate effectively to different stakeholders about food allergy. However, those information channels which are best suited to specific stakeholder needs remain to be established and exploited. Keywords: food allergy; communication; stakeholders
    Interleukin-6 and human immunodeficiency virus load, but not plasma leptin concentration, predict anorexia and wasting in adults with pulmonary tuberculosis in Malawi
    Lettow, M. van; Meer, J.W.M. van der; West, C.E. ; Crevel, R. ; Semba, R.D. - \ 2005
    Journal of Clinical Endocrinology and Metabolism 90 (2005)8. - ISSN 0021-972X - p. 4771 - 4776.
    immune-response - malnutrition - inflammation - cytokines - coinfection
    Background: Wasting is a prominent feature of tuberculosis and may be more severe among individuals with HIV coinfection. It is likely that several biological mechanisms, including the anorexia of infection, are contributing to wasting. Objective: The purpose of this study was to determine whether leptin concentrations, in relation to the inflammatory cytokine response and level of HIV infection, are contributing to loss of appetite and wasting in adults with pulmonary tuberculosis and HIV infection. Design: We characterized plasma leptin concentrations in relationship with self-reported loss of appetite, body mass index, fat mass (FM), IL-6, and HIV load in a cross-sectional study of 500 adults who presented with pulmonary tuberculosis in Zomba, Malawi. Results: Plasma leptin concentrations, associated with FM, significantly decreased by increasing tertile of plasma HIV load (P = 0.0001). Leptin concentrations were inversely associated with plasma IL-6 concentrations after adjusting for sex, age, FM, and HIV load. Plasma leptin concentrations were associated with neither loss of appetite nor wasting. Inflammation, reflected by increased IL-6 concentrations, was associated with loss of appetite (odds ratio, 3.41; 95% confidence interval, 1.91-6.09), when adjusted for sex, age, FM, leptin concentrations, and HIV load. A high plasma HIV load was associated with severe wasting, defined as body mass index less than 16.0 kg/m(2) ( odds ratio, 2.14; 95% confidence interval, 1.09-4.19) when adjusted for sex, age, IL-6, FM, and leptin concentrations. Conclusion: This study suggests that the anorexia and wasting seem primarily determined by the level of inflammation and the level of HIV infection in patients with tuberculosis and HIV coinfection.
    Information provision for allergic consumers : where are we going with food allergen labelling?
    Mills, E.N.C. ; Valovirta, E. ; Madsen, C. ; Taylor, S.L. ; Vieths, S. ; Anklam, E. ; Baumgartner, S. ; Koch, P. ; Crevel, R.W.R. ; Frewer, L.J. - \ 2004
    Allergy 59 (2004)12. - ISSN 0105-4538 - p. 1262 - 1268.
    peanut allergens - double-blind - challenge - protein - milk
    As the current treatment for food allergy involves dietary exclusion of the problem food, information for food-allergic consumers provided on food labels about the nature of allergenic ingredients is important to the management of their condition. The members of an EU-funded networking project, InformAll, focusing on developing strategies for the provision of credible, reliable sources of information for food allergy sufferers, regulators and the food industry, have been considering these matters with respect to food labelling. This paper presents an overview of the genesis of the new EU directive on food labelling, its relevance to food-allergic consumers and the problems that might arise if precautionary labelling becomes more widespread in response to concerns regarding inadvertent allergen contamination in foods. International efforts to define threshold levels of allergens able to trigger a reaction coupled with validated allergen detection methods are essential if the food industry is to implement effective hazard control procedures and address the problems of cross-contact allergens without devaluing the information provided to consumers on food labels.
    Assessment of the safety of foods derived from genetically modified (GM) crops
    König, A. ; Cockburn, A. ; Crevel, R.W.R. ; Debruyne, E. ; Grafstroem, R. ; Hammerling, U. ; Kimber, I. ; Knudsen, I. ; Kuiper, H.A. ; Peijnenburg, A.A.C.M. ; Penninks, A.H. ; Poulsen, M. ; Schauzu, M. ; Wal, J.M. - \ 2004
    Food and Chemical Toxicology 42 (2004)7. - ISSN 0278-6915 - p. 1047 - 1088.
    selectable marker genes - in-vitro toxicology - beta-lactoglobulin - rice genome - intrachromosomal recombination - potential allergenicity - conventional cottonseed - substantial equivalence - protein allergenicity - consumption surveys
    This paper provides guidance on how to assess the safety of foods derived from genetically modified crops (GM crops); it summarises conclusions and recommendations of Working Group 1 of the ENTRANSFOOD project. The paper provides an approach for adapting the test strategy to the characteristics of the modified crop and the introduced trait, and assessing potential unintended effects from the genetic modification. The proposed approach to safety assessment starts with the comparison of the new GM crop with a traditional counterpart that is generally accepted as safe based on a history of human food use (the concept of substantial equivalence). This case-focused approach ensures that foods derived from GM crops that have passed this extensive test-regime are as safe and nutritious as currently consumed plant-derived foods. The approach is suitable for current and future GM crops with more complex modifications. First, the paper reviews test methods developed for the risk assessment of chemicals, including food additives and pesticides, discussing which of these methods are suitable for the assessment of recombinant proteins and whole foods. Second, the paper presents a systematic approach to combine test methods for the safety assessment of foods derived from a specific GM crop. Third, the paper provides an overview on developments in this area that may prove of use in the safety assessment of GM crops, and recommendations for research priorities. It is concluded that the combination of existing test methods provides a sound test-regime to assess the safety of GM crops. Advances in our understanding of molecular biology, biochemistry, and nutrition may in future allow further improvement of test methods that will over time render the safety assessment of foods even more effective and informative.
    Plasma leptin, nutritional status and the acute phase response in patients with tuberculosis
    Crevel, R. van; Karyadi, E. ; West, C.E. ; Netea, M.G. ; Nelwan, R.H.H. ; Verhoef, H. ; Meer, J.W.M. van der - \ 2002
    The Netherlands Journal of Medicine 58A (2002). - ISSN 0300-2977 - p. 62 - 63.
    Decreased plasma leptin concentrations in tuberculosis patients are associated with wasting and inflammation
    Crevel, R. van; Karyadi, E. ; Netea, M.G. ; Verhoef, H. ; Nelwan, R.H.H. ; West, C.E. ; Meer, J.W.M. van der - \ 2002
    Journal of Clinical Endocrinology and Metabolism 87 (2002)2. - ISSN 0021-972X - p. 758 - 763.
    Tuberculosis patients often suffer from severe weight loss, which is considered to be immunosuppressive and a major determinant of severity and outcome of disease. Because leptin is involved in weight regulation and cellular immunity, its possible role in tuberculosis-associated wasting was investigated. In an urban clinic in Indonesia, plasma leptin concentrations, indicators of adipocyte mass, appetite, C-reactive protein (CRP), tuberculin reactivity, and cytokine response were measured in tuberculosis patients and healthy controls. Plasma leptin concentrations were lower in patients than in controls (615 vs. 2,550 ng/liter; P < 0.001). Multivariate regression analysis showed that body fat mass and inflammation were two independent factors determining plasma leptin concentrations; there was a positive correlation between fat and leptin, whereas, unexpectedly, leptin was inversely associated with CRP and tumor necrosis factor- production. Concentrations of both CRP and leptin were independently associated with loss of appetite. Our results do not support the concept that weight loss in tuberculosis is caused by enhanced production of leptin. Rather, loss of body fat leads to low plasma leptin concentrations, and prolonged inflammation may further suppress leptin production. Because leptin is important for cell-mediated immunity, low leptin production during active tuberculosis may contribute to increased disease severity, especially in cachectic patients
    Nutritional status and immune response of tuberculosis patients in Indonesia: vitamin A and zinc supplementation improves disease outcome
    Karyadi, E. ; West, C.E. ; Dolmans, W.M.V. ; Nelwan, R.H.H. ; Amin, Z. ; Schultink, W. ; Gross, R. ; Crevel, R. van; Meer, J.W.M. van der - \ 2001
    In: Annals of Nutrition & Metabolism : 17th International Congress of Nutrition, August 27-31, Vienna, Austria - p. 292 - 292.
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