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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Multimodal Tracking of Controlled Staphylococcus aureus Infections in Mice
Welling, Mick M. ; Korne, Clarize M. De; Spa, Silvia J. ; Willigen, Danny M. Van; Hensbergen, Albertus W. ; Bunschoten, Anton ; Duszenko, Nikolas ; Smits, Wiep Klaas ; Roestenberg, Meta ; Leeuwen, Fijs W.B. Van - \ 2019
Bmc Infectious Diseases 5 (2019)7. - ISSN 1471-2334 - p. 1160 - 1168.
bacterial infection - cell-tracking - fluorescence - multimodal - SPECT - ubiquicidin

There is a need to develop diagnostic and analytical tools that allow noninvasive monitoring of bacterial growth and dissemination in vivo. For such cell-tracking studies to hold translational value to controlled human infections, in which volunteers are experimentally colonized, they should not require genetic modification, and they should allow tracking over a number of replication cycles. To gauge if an antimicrobial peptide tracer, 99m Tc-UBI 29-41 -Cy5, which contains both a fluorescent and a radioactive moiety, could be used for such in vivo bacterial tracking, we performed longitudinal imaging of a thigh-muscle infection with 99m Tc-UBI 29-41 -Cy5-labeled Staphylococcus aureus. Mice were imaged using SPECT and fluorescence-imaging modalities at various intervals during a 28 h period. Biodistribution analyses were performed to quantitate radioactivity in the abscess and other tissues. SPECT and fluorescence imaging in mice showed clear retention of the 99m Tc-UBI 29-41 -Cy5-labeled bacteria following inoculation in the thigh muscle. Despite bacterial replication, the signal intensity in the abscess only modestly decreased within a 28 h period: 52% of the total injected radioactivity per gram of tissue (%ID/g) at 4 h postinfection (pi) versus 44%ID/g at 28 h pi (15% decrease). After inoculation, a portion of the bacteria disseminated from the abscess, and S. aureus cultures were obtained from radioactive urine samples. Bacterial staining with 99m Tc-UBI 29-41 -Cy5 allowed noninvasive bacterial-cell tracking during a 28 h period. Given the versatility of the presented bacterial-tracking method, we believe that this concept could pave the way for precise imaging capabilities during controlled-human-infection studies.

Fluorescent imaging of bacterial infections and recent advances made with multimodal radiopharmaceuticals
Welling, Mick M. ; Hensbergen, Albertus W. ; Bunschoten, Anton ; Velders, Aldrik H. ; Scheper, Henk ; Smits, Wiep Klaas ; Roestenberg, Meta ; Leeuwen, Fijs W.B. van - \ 2019
Clinical and Translational Imaging 7 (2019)2. - ISSN 2281-5872 - p. 125 - 138.
Bacterial infection - Fluorescence imaging - Infectious diseases - Molecular imaging - Radioactivity

Background: Today, both radioactive SPECT and PET imaging radiopharmaceuticals are used for clinical diagnosis of bacterial infections. Due to the possible applications in image-guided surgery, fluorescent imaging of infections has gained interest. We here present the highlights and recent developments in the use of fluorescence imaging for bacterial infections. In this overview, we also include the latest developments in multimodal bacterial imaging strategies that combine radioactive and fluorescent imaging. Based on this literature, we present our future perspectives for the field including the translational potential. Methods: In the current review, we complement earlier reports with the most recent fluorescent and multimodal radiopharmaceuticals for bacterial infection imaging. Where possible, in this review, the chemical structure of the compounds and clinical images were shown. Results: A total of 35 out of 77 original articles on pre-clinical and clinical imaging of bacterial infections with fluorescent tracers and multimodality radiopharmaceuticals were included for reviewing. Conclusion: In our view, the highest translational potential lies with compounds that are based on targeting vectors that are specific for bacteria: e.g., fluorescently labelled UBI 29–41 , polymyxin B, vancomycin, ZnDPA and a M. tuberculosis-specific β-lactamase-cleavable linker CNIP800. Multimodal concepts using dually labelled UBI 29–41 , vancomycin, and ZnDPA help connect optical imaging to the more traditional use of radiopharmaceuticals in infectious diseases. Multimodal bacterial imaging is a promising strategy not only to diagnose bacterial infections but also to evaluate the effectivity of surgical treatment for infections.

An update on radiotracer development for molecular imaging of bacterial infections
Welling, Mick M. ; Hensbergen, Albertus W. ; Bunschoten, Anton ; Velders, Aldrik H. ; Roestenberg, Meta ; Leeuwen, Fijs W.B. van - \ 2019
Clinical and Translational Imaging 7 (2019)2. - ISSN 2281-5872 - p. 105 - 124.
Infectious diseases - Molecular imaging - Nuclear medicine - Pathogens - Radiotracers

Background: Bacterial infections are still a major global healthcare problem. To combat the increasing antimicrobial resistance, early diagnosis of bacterial infections—including the identification of bacterial species—is needed to improve antibiotic stewardship and to help reduce the use of broad-spectrum antibiotics. To aid successful targeted antibiotic treatment, specific detection and localisation of infectious organisms is warranted. Nuclear medicine imaging approaches have been successfully used to diagnose bacterial infections and to differentiate between pathogen induced infections and sterile inflammatory processes. Aim: In this comprehensive review we present an overview of recent developments in radiolabelled bacterial imaging tracers. Methods: The PubMed/MEDLINE and Embase (OvidSP) literature databases were systematically searched for publications on SPECT and PET on specific imaging of bacterial using specific guidelines with MeSH-terms, truncations, and completion using cross-references. Tracers in literature that was extensively reviewed before 2016 were not included in this update. Where possible, the chemical structure of the radiolabelled compounds and clinical images were shown. Results: In 219 original articles pre-clinical and clinical imaging of bacterial infection with new tracers were included. In our view, the highest translational potential lies with tracers that are specific to target the pathogens: e.g., 99m Tc- and 68 Ga-labelled UBI 29–41 , 99m Tc-vancomycin, m-[ 18 F]-fluoro-PABA, [methyl- 11 C]-D-methionine, [ 18 F]-FDS, [ 18 F]-maltohexaose and [ 18 F]-maltotriose. An encouraging note is that some of these tracers have already been successfully evaluated in clinical settings. Conclusion: This review summarises updates in tracer development for specific (pre-clinical and clinical) imaging of bacterial infections. We propsed some promising tracers that are likely to become innovative standards in the clinical setting in the near feature.

In vivo stability of supramolecular host–guest complexes monitored by dual-isotope multiplexing in a pre-targeting model of experimental liver radioembolization
Welling, Mick M. ; Spa, Silvia J. ; Willigen, Danny M. van; Rietbergen, Daphne D.D. ; Roestenberg, Meta ; Buckle, Tessa ; Leeuwen, Fijs W.B. van - \ 2019
Journal of Controlled Release 293 (2019). - ISSN 0168-3659 - p. 126 - 134.
Dual-labeling - Interventional radiology - Pre-targeting - Radioembolization - Supramolecular chemistry - Theranostics

Introduction: Cyclodextrin (CD)-based supramolecular interactions have been proposed as nanocarriers for drug delivery. We previously explored the use of these supramolecular interactions to perform targeted hepatic radioembolization. In a two-step procedure the appropriate location of the diagnostic pre-targeting vector can first be confirmed, after which the therapeutic vector will be targeted through multivalent host–guest interactions. Such a procedure would prevent therapeutic errors that come from a mismatch between diagnostic and therapeutic procedures. In the current study we explored the use of dual-isotope imaging to assess the in vivo stability of the formed complex and individual components. Methods: Dual-isotope imaging of the host and guest vectors was performed after labeling of the pre-targeted guest vector, being adamantane (Ad) functionalized macro-aggregated albumin (MAA) particles, with technetium-99 m (99mTc-MAA-Ad). The host vector, Cy50.5CD9PIBMA39, was labeled with indium-111 (111In-Cy50.5CD9PIBMA39). The in situ stability of both the individual vectors and the resulting [MAA-Ad–111In-Cy50.5CD9PIBMA39] complexes was studied over 44 h at 37 °C in a serum protein-containing buffer. In vivo, the host vector 111In-Cy50.5CD9PIBMA39 was administered two hours after local deposition of 99mTc-MAA-Ad in mice. Dual-isotope SPECT imaging and quantitative biodistribution studies were performed between 2 and 44 h post intravenous host vector administration. Results: The individual vectors portrayed <5% dissociation of the radioisotope over the course of 20 h. Dissociation of [MAA-Ad–111In-Cy50.5CD9PIBMA39] complexes remained within a 10–20% range after incubation in serum. In vivo dual-isotope SPECT imaging of host–guest interactions revealed co-localization of the tracer components. Quantitative assessment of the biodistribution revealed that the hepatic accumulation of the host vector nearly doubled between 2 h and 44 h post-injection (from 14.9 ± 6.1%ID/g to 26.2 ± 2.1%ID/g). Conclusions: Assessment of intra-hepatic host–guest complexation was successfully achieved using dual isotope multiplexing, underlining the complex stability that was found in situ (up to 44 h in serum). Overall, the results obtained in this study highlight the potential of supramolecular chemistry as a versatile platform that could advance the field of nanomedicine.

A supramolecular approach for liver radioembolization
Spa, Silvia J. ; Welling, Mick M. ; Oosterom, Matthias N. van; Rietbergen, Daphne D.D. ; Burgmans, Mark C. ; Verboom, Willem ; Huskens, Jurriaan ; Buckle, Tessa ; Leeuwen, Fijs W.B. van - \ 2018
Theranostics 8 (2018)9. - ISSN 1838-7640 - p. 2377 - 2386.
Interventional radiology - Nanotechnology - Pre-targeting - Radioembolization - Supramolecular chemistry
Hepatic radioembolization therapies can suffer from discrepancies between diagnostic planning (scout-scan) and the therapeutic delivery itself, resulting in unwanted side-effects such as pulmonary shunting. We reasoned that a nanotechnology-based pre-targeting strategy could help overcome this shortcoming by directly linking pre-interventional diagnostics to the local delivery of therapy. Methods: The host-guest interaction between adamantane and cyclodextrin was employed in an in vivo pre-targeting set-up. Adamantane (guest)-functionalized macro albumin aggregates (MAA-Ad; d = 18 μm) and (radiolabeled) Cy5 and β-cyclodextrin (host)-containing PIBMA polymers (99mTc-Cy50.5CD10PIBMA39; MW ~ 18.8 kDa) functioned as the reactive pair. Following liver or lung embolization with (99mTc)-MAA-Ad or (99mTc)-MAA (controls), the utility of the pre-targeting concept was evaluated after intravenous administration of 99mTc-Cy50.5CD10PIBMA39. Results: Interactions between MAA-Ad and Cy50.5CD10PIBMA39 could be monitored in solution using confocal microscopy and were quantified by radioisotope-based binding experiments. In vivo the accumulation of the MAA-Ad particles in the liver or lungs yielded an approximate ten-fold increase in accumulation of 99mTc-Cy50.5CD10PIBMA39 in those organs (16.2 %ID/g and 10.5 %ID/g, respectively) compared to the control. Pre-targeting with MAA alone was shown to be only half as efficient. Uniquely, for the first time, this data demonstrates that the formation of supramolecular interactions between cyclodextrin and adamantane can be used to drive complex formation in the chemically challenging in vivo environment. Conclusion: The in vivo distribution pattern of the cyclodextrin host could be guided by the pre-administration of the adamantane guest, thereby creating a direct link between the scout-scan (MAA-Ad) and delivery of therapy.
Aberrant gut microbiota composition at the onset of type 1 diabetes in young children
Goffau, M.C. de; Fuentes, S. ; Bogert, B. van den; Honkanen, H. ; Vos, W.M. de; Welling, G.W. ; Hyöty, H. ; Harmsen, H.J. - \ 2014
Diabetologia 57 (2014)8. - ISSN 0012-186X - p. 1569 - 1577.
intestinal microbiota - storage-conditions - disease - butyrate - age - community - immunity - health - bacteria - differs
Aims/hypothesis Recent studies indicate that an aberrant gut microbiota is associated with the development of type 1 diabetes, yet little is known about the microbiota in children who have diabetes at an early age. To this end, the microbiota of children aged 1–5 years with new-onset type 1 diabetes was compared with the microbiota of age-matched healthy controls. Methods A deep global analysis of the gut microbiota composition was established by phylogenetic microarray analysis using a Human Intestinal Tract Chip (HITChip). Results Principal component analyses highlighted the importance of age when comparing age-matched pairs. In pairs younger than 2.9 years, the combined abundance of the class Bacilli (notably streptococci) and the phylum Bacteroidetes was higher in diabetic children, whereas the combined abundance of members of Clostridium clusters IV and XIVa was higher in the healthy controls. Controls older than 2.9 years were characterised by a higher fraction of butyrate-producing species within Clostridium clusters IV and XIVa than was seen in the corresponding diabetic children or in children from the younger age groups, while the diabetic children older than 2.9 years could be differentiated by having an increased microbial diversity. Conclusions/interpretation The results from both age groups suggest that non-diabetic children have a more balanced microbiota in which butyrate-producing species appear to hold a pivotal position.
Molecular biological methods for studying the gut microbiota : the EU human gut flora project
Blaut, M. ; Collins, M.D. ; Welling, G.W. ; Dore, J. ; Loo, J. van; Vos, W.M. de - \ 2002
The British journal of nutrition 87 (2002)2. - ISSN 0007-1145 - p. S203 - S211.
Seven European laboratories co-operated in a joint project (FAIR CT97-3035) to develop, refine and apply molecular methods towards facilitating elucidation of the complex composition of the human intestinal microflora and to devise robust methodologies for monitoring the gut flora in response to diet. An extensive database of 16S rRNA sequences for tracking intestinal bacteria was generated by sequencing the 16S rRNA genes of new faecal isolates and of clones obtained by amplification with polymerase chain reaction (PCR) on faecal DNA from subjects belonging to different age groups. The analyses indicated that the number of different species (diversity) present in the human gut increased with age. The sequence information generated, provided the basis for design of 16S rRNA-directed oligonucleotide probes to specifically detect bacteria at various levels of phylogenetic hierarchy. The probes were tested for their specificity and used in whole-cell and dot-blot hybridisations. The applicability of the developed methods was demonstrated in several studies and the major outcomes are described.
Hedgerows: suitable corridors for ground welling forest carabid beetles?
Plat, S. ; Kuivenhoven, P. ; Dijk, Th.S. van - \ 1995
Proceedings of the Section Experimental and Applied Entomology of the Netherlands Entomological Society 6 (1995). - ISSN 1388-8390 - p. 73 - 76.
Chimeric parvovirus B19 capsids for the presentation of foreign epitopes.
Brown, C.S. ; Welling-Wester, S. ; Feijlbrief, M. ; Lent, J.W.M. van; Spaan, W.J.M. - \ 1994
Virology 198 (1994). - ISSN 0042-6822 - p. 477 - 488.
Paardenpatienten in een veterinaire praktijk
Bruin, G. ; Elema, T. ; Nanne, D. ; Offereins, E. ; Hulshof, A.J.J. ; Welling, E.K. - \ 1990
Praktijkonderzoek / Praktijkonderzoek Rundvee, Schapen en Paarden (PR), Waiboerhoeve 3 (1990)5. - ISSN 0921-8874 - p. 32 - 34.
Bij het vragen van een prestatie van paarden treden er vaak problemen op. De oorzaak ligt dan in de aanleg van het paard of in de behandeling die het paard tot dat tijdstip heeft gekregen.
Stereoselectivity in the biotransformation of crop protectants.
Bladeren, P.J. van - \ 1988
In: Stereoselectivity of pesticides. Biological and chemical problems / Ariens, E.J., van Rensen, J.J.S., Welling, W., Amsterdam : - p. 357 - 374.
Stereoselective perception of antifeedants in insects.
Schoonhoven, L.M. - \ 1988
In: Stereoselectivity of pesticides; biological and chemical problems / Ariens, E.J., van Rensen, J.J.S., Welling, W., Amsterdam : Elsevier - p. 289 - 302.
Practical implications of pesticide stereoselectivity.
Welling, W. ; Ariens, E.J. ; Rensen, J.J.S. van - \ 1988
In: Stereoselectivity of pesticides: Biological and chemical problems / Ariens, E.J., van Rensen, J.J.S., Welling, W., Elsevier - p. 529 - 543.
The role of stereoselectivity in the action of herbicides and other pesticides.
Naber, J.D. ; Rensen, J.J.S. van - \ 1988
In: Stereoselectivity of pesticides: Biological and chemical problems / Ariens, E.J., van Rensen, J.J.S., Welling, W., Elsevier - p. 263 - 288.
Stereoselectivity of pesticides: Biological and chemical problems.
Ariens, E.J. ; Rensen, J.J.S. van; Welling, W. - \ 1988
Amsterdam : Elsevier Science Publishers - 544 p.
Immunoneutralisatie van somatostatine bij de geit in relatie tot geboortegewicht en melkproduktie, groei- en slachtkwaliteitsaspecten van de boklammeren = Immunoneutralization of somatostatin in goats in relation to birth weight and milk yield, performance of male kids and slaughter quality aspects
Garssen, G.J. ; Welling, A.M.A.W. ; Boxtel, H.L. van - \ 1987
Zeist : IVO (I.V.O.-rapport B-305) - 52
antilichamen - geiten - hormonen - immunoglobulinen - implantatie - reticulo-endotheliaal systeem - somatotropine - antibodies - goats - hormones - immunoglobulins - implantation - reticuloendothelial system - somatotropin
Doel van het onderzoek was na te gaan of immunoneutralisatie van somatostatine (een natuurlijke remmer op de afgifte van somatotropine uit de hypofyse) invloed heeft op de melkgift en prenatale groei bij de geit. 20 Nederlandse witte geiten werden hiervoor halverwege de dracht opgenomen in een proef, waarbij 2 groepen van 10 geiten werden geformeerd op basis van hun melkproduktie over de vorige (1e) lactatie, actueel lichaamsgewicht en dekdatum. Een groep geiten werd geimmuniseerd tegen somatostatine met een conjugaat van dit peptide en humaan serum alfa-globuline; de controlegroep werd geimmuniseerd tegen enkel het globuline. 18 weken na aflammen werd de immunisatie herhaald
Active immunisation against somatostatin increases milk yield in goats
Garssen, G.J. ; Welling, A.M.A.W. ; Spencer, G.S.G. - \ 1986
Zeist : I.V.O. (I.V.O.-rapport B-288) - 22
antilichamen - endocrinologie - geiten - hormonen - immunisatie - immunoglobulinen - immunotherapie - reticulo-endotheliaal systeem - somatotropine - vaccinatie - vaccins - diergeneeskunde - antibodies - endocrinology - goats - hormones - immunization - immunoglobulins - immunotherapy - reticuloendothelial system - somatotropin - vaccination - vaccines - veterinary science
In dit onderzoek is nagegaan wat het effect is van actieve immunisatie tegen somatostatine op de melkproduktie van de geit, door 6 geiten, halverwege de dracht geimmuniseerd met een conjugaat van somatostatine en humaan alfa-glubuline, te vergelijken met 6 andere geiten van dezelfde jaargang met een vergelijkbare melkproduktie en gewicht die alleen met globuline waren geimmuniseerd. Somatostatine, een 14 aminozuren tellend peptide, is o.a. betrokken bij de regeling van de groeihormoon-afgifte door de hypofyse, waarop het remmend werkt
Actieve immunisatie tegen somatostatine bij het slachtlam van de Texelaar x Flevolander kruising : een poging om groeisnelheid en voederconversie te beinvloeden = [Active immunization against somatostatin in slaughterlambs of the Texel x Flevolander crossbred : a trial to improve rate of gain and feed conversion]
Garssen, G.J. ; Welling, A.M.A.W. ; Spencer, G.S.G. - \ 1984
Zeist : I.V.O. (I.V.O.-rapport. Instituut voor Veeteeltkundig Onderzoek "Schoonoord" no. B-254) - 48
antilichamen - hormonen - immunoglobulinen - implantatie - reticulo-endotheliaal systeem - schapenrassen - somatotropine - antibodies - hormones - immunoglobulins - implantation - reticuloendothelial system - sheep breeds - somatotropin
Een van de stoffen die voor de groei zorgt is het groeihormoon. Deze werkt via groei-stimulatoren, de somatedinen, die weer geremd worden door een andere stof, het somatostatine. Getracht is om door immunisatie de werking van het somatostatine te verkleinen en zo de groei te bevorderen. Bij een proef met slachtlammeren van de kruising van Texelaar x Flevolander werd echter geen effect geconstateerd
Onderzoek naar het nitraatgehalte van het ondiepe grondwater in de omgeving van Achterberg
Tusveld, M.C.L. ; Welling, S.E. - \ 1984
Wageningen : L.H. - 44
grondwater - chemische eigenschappen - waterkwaliteit - verontreinigingsbeheersing - grondwaterverontreiniging - bescherming - bodem - uitspoelen - stalmest - nitraten - stikstofkringloop - bacteriën - nederland - utrecht - gelderland - gelderse vallei - groundwater - chemical properties - water quality - pollution control - groundwater pollution - protection - soil - leaching - farmyard manure - nitrates - nitrogen cycle - bacteria - netherlands
Een bestudering van het verloop van het nitraatgehalte van het ondiepe grondwater en bepaling van de menselijke invloed op de samenstelling van het ondiepe grondwater door het chloridegehalte hiervan te vergelijken met het nitraatgehalte; dit in verband met de eutrofiering van het grond- en oppervlaktewater door bemestingsgiten (in een gedeelte van de Gelderse Vallei)
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