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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    Dermal absorption and toxicological risk assessment : pitfalls and promises
    Buist, H. - \ 2016
    Wageningen University. Promotor(en): Ruud Woutersen; Ivonne Rietjens, co-promotor(en): J.J.M. van de Sandt. - Wageningen : Wageningen University - ISBN 9789462577275 - 200
    skin - absorption - permeability - in vitro - experiments - exposure assessment - risk assessment - toxicology - biocides - rodenticides - preservatives - disinfection - huid - absorptie - permeabiliteit - in vitro - experimenten - blootstellingsbepaling - risicoschatting - toxicologie - biociden - rodenticiden - conserveermiddelen - desinfectie

    Absorption of toxic substances via the skin is an important phenomenon in the assessment of the risk of exposure to these substances. People are exposed to a variety of substances and products via the skin, either directly or indirectly, while at work, at home or in public space. Pesticides, organic solvents and metalworking fluids are seen to be important contributors to adverse health effects due to occupational exposure via the skin. In daily life, cosmetics, clothing and household products are the most relevant commodities with respect to exposure via the skin.

    Given the importance of skin exposure in the assessment of the risk of toxic substances, the objective of this thesis was to further develop, evaluate and improve methods for including skin absorption data this assessment.

    In this thesis, four factors influencing dermal absorption, namely dermal loading (chapters 3 and 6), irritative/corrosive potential (chapters 3 and 4), frequency of exposure (chapters 3, 4 and 5) and the vehicle used (chapter 5), were investigated in more detail. Furthermore, a model to extrapolate infinite dose absorption data to finite dose conditions, baptized Dermal Absorption Model for Extrapolation (DAME), was developed and tested.

    I

    n chapter 2 of this thesis, the relationship between relative dermal absorption and dermal loading was investigated. Hundred-and-thirty-eight dermal publicly available absorption experiments with 98 substances were evaluated. The results obtained revealed that dermal loading ranged mostly between 0.001 and 10 mg/cm2. In 87 experiments (63%), an inverse relationship was observed between relative dermal absorption and dermal loading. On average, relative absorption at high dermal loading was 33 times lower than at low dermal loading. Known skin irritating and volatile substances less frequently showed an inverse relationship between dermal loading and relative absorption. It was concluded that when using relative dermal absorption in regulatory risk assessment, its value should be determined at or extrapolated to dermal loadings relevant for the exposure conditions being evaluated.

    I

    n chapter 3 of this thesis, a literature search was presented with the aim to investigate whether neglecting the effects of repeated exposure may lead to an incorrect estimate of dermal absorption. The results demonstrated that the effect of repeated versus single exposure does not demonstrate a unique trend. Nevertheless, an increase in daily absorption was frequently observed upon repeated daily exposure. The little information available mostly concerned pharmaceuticals. However, consumers and workers may be repeatedly exposed to other types of chemicals, like disinfectants and cleaning products, which often contain biocidal active substances that may decrease the barrier function of the skin, especially after repeated exposure. These biocidal products, therefore, may present a safety risk that is not covered by the current risk assessment practice since absorption data are usually obtained by single exposure experiments. Consequently, it was decided to investigate the importance of this issue for biocide safety evaluation. As the literature search revealed that hardly any data on absorption upon repeated dermal exposure to biocides are available, it was concluded that data need to be generated by testing.

    To cover the entire range of biocidal products in such testing, a representative series of biocidal substances should be tested, making in vitro testing of dermal absorption the preferred choice over in vivo testing. Based on an inventory made, it appeared that the 16 product types represented among the biocidal products authorised in the Netherlands could be clustered into 6 more or less homogeneous categories based on similarity in active substances. This result could facilitate experimental testing by providing a basis for selection of a limited number of representative compounds to be evaluated.

    I

    n chapter 4 of this thesis, the importance of the effect of repeated dermal exposure on skin permeability for biocide safety evaluation was investigated, using a selection of nine representative biocides from the inventory made in chapter 3. The in vitro dermal penetration of tritiated water and [14C]propoxur was chosen as a measure of the permeability and integrity of human abdominal skin after single and repeated exposure. The results indicated that single and repeated exposure to specific biocidal products (e.g. the quaternary ammonium chlorides DDAC and ADBAC) may significantly increase skin permeability, especially when the compounds are applied at high concentrations, while a substance like formaldehyde may reduce skin permeability under specific conditions.

    I

    n chapter 5 of this thesis, the in vitro dermal absorption kinetics of the quaternary ammonium compound didecyldimethylammonium chloride (DDAC) during single and repeated exposure was studied in more detail. In addition, the influence of biocidal formulations on the absorption of DDAC was investigated, because it was expected that formulation characteristics may be another factor influencing its dermal absorption. The analysis of biocidal products on the Dutch market, reported in chapter 3, indicated that DDAC is often used in combination with other active ingredients. DDAC was most frequently combined with formaldehyde, glutaraldehyde and/or alkyldimethylbenzyl­ammo­nium chloride (ADBAC). Consequently, commercial formulations containing one or more of these additional active ingredients were selected, in addition to one formulation containing only DDAC as an active ingredient. The selected commercial formulations tended to reduce skin penetration of DDAC. This was most pronounced with the formulation containing the highest concentration of formaldehyde (196 mg/mL) and glutaraldehyde (106 mg/mL), which reduced the flux of DDAC across the skin by 95%. The reduction caused by the only tested formulation containing no other active ingredients than DDAC, and thus incorporating no aldehydes, was smallest, and did not reach statistical significance.

    I

    n chapter 6 of this thesis, a simple in silico model to predict finite dose dermal absorption from infinite dose data (kp and lag time) and the stratum corneum/water partition coefficient (KSC,W) was developed. This model was tentatively called Dermal Absorption Model for Extrapolation (DAME). As dermal exposure may occur under a large variety of conditions leading to quite different rates of absorption, such a predictive model using simple experimental or physicochemical inputs provides a cost-effective means to estimate dermal absorption under different conditions.

    To evaluate the DAME, a series of in vitro dermal absorption experiments was performed under both infinite and finite dose conditions using a variety of different substances. The kp’s and lag times determined in the infinite dose experiments were entered into DAME to predict relative dermal absorption value under finite dose conditions. For six substances, the predicted relative dermal absorption under finite dose conditions was not statistically different from the measured value. For all other substances, measured absorption was overpredicted by DAME, but most of the overpredicted values were still lower than 100%, the European default absorption value for the tested compounds.

    In conclusion, our finite dose prediction model (DAME) provides a useful and cost-effective estimate of in vitro dermal absorption, to be used in risk assessment for non-volatile substances dissolved in water at non-irritating concentrations.

    I

    n chapter 7 of this thesis, the results of the research reported in chapters 2 to 6 were put into perspective, the pitfalls and promises emanating from them discussed and general conclusions drawn. The possible influence of vehicles on absorption and the possible impact of irritative or corrosive vehicles or chemicals on the skin barrier have been demonstrated in this thesis. An in silico predictive model tentatively called DAME was developed, which enables the user to evaluate a variety of dermal exposure scenarios with limited experimental data (kp and lag time) and easy to obtain physicochemical properties (MW and log KOW). The predictions of our experiments reported in chapter 6 were compared to those of the Finite Dose Skin Permeation (FDSP) model published on the internet by the US Centers for Disease Control and Prevention (CDC). DAME outperformed FDSP (R2 of the correlation predicted/measured potential absorption 0.64 and 0.12, respectively). At present, the applicability domain of DAME is limited to non-volatile substances dissolved in aqueous solvents. However, in future the model will be adapted to include volatile substances as well.

    Altogether, it is concluded that dermal exposure can be an important factor in risks posed by chemicals and should be taken into account in risk assessment. The methods to actually do this are still open for further improvement to better account for the various factors influencing skin penetration and to develop adequate combinations of in vitro and in silico models that can accurately predict human dermal absorption.

    Oligosaccharides in Urine, Blood, and Feces of Piglets Fed Milk Replacer Containing Galacto-oligosaccharides
    Difilippo, Elisabetta ; Bettonvil, Monique ; Willems, Rianne ; Braber, Saskia ; Fink-Gremmels, Johanna ; Jeurink, Prescilla V. ; Schoterman, Margriet H.C. ; Gruppen, Harry ; Schols, Henk A. - \ 2015
    Journal of Agricultural and Food Chemistry 63 (2015)50. - ISSN 0021-8561 - p. 10862 - 10872.
    absorption - capillary electrophoresis - creatinine - fermentation - GOS - intestine - liquid chromatography - mass spectrometry - pig - prebiotics

    Human milk oligosaccharides (HMOs) are absorbed into the blood (about 1% of the HMO intake) and subsequently excreted in urine, where they may protect the infant from pathogen infection. As dietary galacto-oligosaccharides (GOS) have partial structural similarities with HMOs, this study investigated the presence of GOS and oligosaccharides originating from milk replacer in blood serum, urine, and cecal and fecal samples of piglets, as a model for human infants. Using liquid chromatography-mass spectrometry and capillary electrophoresis with fluorescence detection, oligosaccharides originating from piglet diet including 3′-sialyllactose and specific GOS ranging from degree of polymerization 3 to 6 were detected in blood serum and in urine of piglets. In blood serum, GOS levels ranged from 16 to 23 μg/mL, representing about 0.1% of the GOS daily intake. In urine, approximately 0.85 g of GOS/g of creatinine was found. Cecum digesta and feces contained low amounts of oligosaccharides, suggesting an extensive GOS intestinal fermentation in piglets.

    Interacties tussen ijzerchelaten en andere spoorelementen vaak onderschat : analysecijfers tonen niet altijd wat beschikbaar is voor plant
    Staalduinen, J. van; Voogt, W. - \ 2015
    Onder Glas 12 (2015)5. - p. 10 - 11.
    glastuinbouw - voedingsstoffen - bemesting - ijzerhoudende meststoffen - plantenvoeding - ijzerabsorptie - chelaten - meststoffen met sporenelementen - absorptie - zuurgraad - substraten - recirculatiesystemen - irrigatiewater - greenhouse horticulture - nutrients - fertilizer application - iron fertilizers - plant nutrition - iron absorption - chelates - trace element fertilizers - absorption - acidity - substrates - recirculating systems - irrigation water
    IJzer is onder normale wortelcondities vaak moeilijk opneembaar voor planten. Dat geldt ook en misschien wel juist voor substraatteelten. IJzerchelaten – organische moleculen die ijzerionen adsorberen en afstaan aan of in plantenwortels – bieden uitkomst. Bij de keuze van het juiste chelaat dient men niet alleen oog te hebben voor de pH van de voedingsoplossing of in de mat. Zij kunnen ook verbindingen aangaan met andere spoorelementen, waardoor drainwateranalyse soms een vertekend beeld geeft van wat er werkelijk beschikbaar is.
    Bioavailability and biodistribution of differently charged polystyrene nanoparticles upon oral exposure in rats
    Walczak, A.P. ; Hendriksen, P.J.M. ; Woutersen, R.A. ; Zande, M. van der; Undas, A.K. ; Helsdingen, J.R. ; Berg, J.H.J. van den; Rietjens, I.M.C.M. ; Bouwmeester, H. - \ 2015
    Journal of Nanoparticle Research : an Interdisciplinary Forum for Nanoscale Science and Technology 17 (2015). - ISSN 1388-0764 - 13 p.
    zinc-oxide nanoparticles - titanium-dioxide nanoparticles - tissue distribution - silver nanoparticles - particle-size - absorption - food - translocation - microspheres - elimination
    The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral, positive and negative) using a Caco-2/HT29-MTX in vitro intestinal translocation model. The NPs translocated in a surface charge-dependent manner. The present study aimed to validate this in vitro intestinal model by an in vivo study. For this, rats were orally exposed to a single dose of these polystyrene NPs and the uptake in organs was determined. A negatively charged NP was taken up more than other NPs, with the highest amounts in kidney (37.4 µg/g tissue), heart (52.8 µg/g tissue), stomach wall (98.3 µg/g tissue) and small intestinal wall (94.4 µg/g tissue). This partly confirms our in vitro findings, where the same NPs translocated to the highest extent. The estimated bioavailability of different types of NPs ranged from 0.2 to 1.7 % in vivo, which was much lower than in vitro (1.6–12.3 %). Therefore, the integrated in vitro model cannot be used for a direct prediction of the bioavailability of orally administered NPs. However, the model can be used for prioritizing NPs before further in vivo testing for risk assessment.
    In vitro selenium accessibility in pet foods is affected by diet composition and type
    Zelst, M. van; Hesta, M. ; Alexander, L.G. ; Gray, K. ; Bosch, G. ; Hendriks, W.H. ; Laing, G. Du; Meulenaer, B. de; Goethals, K. ; Janssens, G. - \ 2015
    The British journal of nutrition 113 (2015)12. - ISSN 0007-1145 - p. 1888 - 1894.
    nutrient digestion - organic selenium - bioavailability - absorption - dog - bioaccessibility - selenomethionine - metabolism - prediction - fiber
    Se bioavailability in commercial pet foods has been shown to be highly variable. The aim of the present study was to identify dietary factors associated with in vitro accessibility of Se (Se Aiv) in pet foods. Se Aiv is defined as the percentage of Se from the diet that is potentially available for absorption after in vitro digestion. Sixty-two diets (dog, n 52; cat, n 10) were in vitro enzymatically digested: fifty-four of them were commercially available (kibble, n 20; pellet, n 8; canned, n 17; raw meat, n 6; steamed meat, n 3) and eight were unprocessed (kibble, n 4; canned, n 4) from the same batch as the corresponding processed diets. The present investigation examined if Se Aiv was affected by diet type, dietary protein, methionine, cysteine, lysine and Se content, DM, organic matter and crude protein (CP) digestibility. Se Aiv differed significantly among diet types (P<0·001). Canned and steamed meat diets had a lower Se Aiv than pelleted and raw meat diets. Se Aiv correlated positively with CP digestibility in extruded diets (kibbles, n 19; r 0·540, P =0·017) and negatively in canned diets (n 16; r - 0·611, P =0·012). Moreover, the canning process (n 4) decreased Se Aiv (P =0·001), whereas extrusion (n 4) revealed no effect on Se Aiv (P =0·297). These differences in Se Aiv between diet types warrant quantification of diet type effects on in vivo Se bioavailability.
    Fat coating of Ca butyrate results in extended butyrate release in the gastrointestinal tract of broilers
    Borne, J.J.G.C. van den; Heetkamp, M.J.W. ; Buyse, J. ; Niewold, T.A. - \ 2015
    Livestock Science 175 (2015). - ISSN 1871-1413 - p. 96 - 100.
    acid breath test - c-13-octanoic acid - chickens - absorption - passage
    Based on its described beneficial effects on small and large intestinal epithelium, butyrate can be a very good alternative to antimicrobial growth promoters. Effective dietary application requires coating because the majority of uncoated butyrate is purportedly absorbed before reaching the proximal small intestine. Several studies using different protocols reported varying stomach passage times in chickens. In the present study, we compared feeding uncoated vs. fat coated [1-13C] labeled Ca butyrate, and compared the effect of butyrate coating with [1-13C] labeled octanoic acid which is an established indicator of stomach passage. By monitoring 13CO2 expiration continuously, we show that the majority (about 80%) of uncoated Ca butyrate is oxidized proximally of the small intestine, and that base line levels were reached after 6 h. Fat coating of Ca butyrate resulted in reduced proximal oxidation (from about 80% to about 45%), and in an extended release pattern of 13CO2 from butyrate similar to that of octanoic acid, and that the return to base line levels was extended to 12 h. This indicated that fat coating of butyrate results in absorption along the entire intestinal tract in broilers, offering an explanation for the described beneficial effects as a growth promoter.
    Factors contributing to the variation in feline urinary oxalate excretion
    Dijcker, J.C. ; Hagen-Plantinga, E.A. ; Everts, H. ; Queau, Y. ; Biourge, V.C. ; Hendriks, W.H. - \ 2014
    Journal of Animal Science 92 (2014)3. - ISSN 0021-8812 - p. 1029 - 1036.
    glycolate excretion - dietary-protein - ascorbic-acid - calcium - cats - hydroxyproline - vitamin-b-6 - fructose - requirement - absorption
    This study aimed to identify factors (season, animal, and diet) contributing to the variation in urinary oxalate (Uox) excretion rate, Uox concentration, and urine volume in healthy adult cats. A data set (1,940 observations) containing information on Uox excretion rate of 65 cats fed 252 diets (i.e., each diet was fed to a group of 6 to 8 cats), with known dietary oxalate concentrations, collected over a 6 yr period at a feline nutrition facility, were retrospectively analyzed. Data related to season, animal (i.e., age, gender, body weight, and breed), and diet (i.e., nutrient content) characteristics were subjected to stepwise multivariate regression analysis to identify factors significantly correlated to Uox excretion rate (µmol/(kg BW0.67·d)) and concentration (mmol/L) as well as urine volume (mL/(kg BW0.67·d)). Independent factors significantly (P <0.05) associated with lower Uox concentration (mmol/L) included greater ash, Ca, and Na intake and lower nitrogen-free extract, total dietary fiber, P, and oxalate intake, and a body weight
    A higher proportion of Iron-Rich leafy vegatables in a typical burkinabe maize meal does not increase the amount of iron absorbed in young women
    Cercamondi, C.I. ; Icard-Verniere, C. ; Egli, I. ; Vernay, M. ; Hama, F. ; Brouwer, I.D. - \ 2014
    The Journal of Nutrition 144 (2014)9. - ISSN 0022-3166 - p. 1394 - 1400.
    phenolic-compounds - stable-isotope - pearl-millet - fortification iron - ascorbic-acid - phytic acid - in-field - absorption - foods - sorghum
    Food-to-food fortification can be a promising approach to improve the low dietary iron intake and bioavailability from monotonous diets based on a small number of staple plant foods. In Burkina Faso, the common diet consists of a thick, cereal-based paste consumed with sauces composed of mainly green leaves, such as amaranth and jute leaves. Increasing the quantity of leaves in the sauces substantially increases their iron concentration. To evaluate whether increasing the quantity of leaves in sauces would provide additional bioavailable iron, an iron absorption study in 18 young women was conducted in Zurich, Switzerland. Burkinabe composite test meals consisting of the maize paste tô accompanied by an iron-improved amaranth sauce, an iron-improved jute sauce, or a traditional amaranth sauce were provided as multiple meals twice a day for 2 consecutive days. Iron absorption was measured as erythrocyte incorporation of stable iron isotopes. Mean fractional iron absorption from maize paste consumed with an iron-improved amaranth sauce (4.9%) did not differ from the same meal consumed with an iron-improved jute sauce (4.9%; P = 0.9), resulting in a similar quantity of total iron absorbed (679 vs. 578 µg; P = 0.3). Mean fractional iron absorption from maize paste accompanied by a traditional amaranth sauce (7.4%) was significantly higher than that from the other 2 meal types (P <0.05), but the quantity of total iron absorbed was similar (591 µg; P = 0.4 and 0.7, respectively). A food-to-food fortification approach based on an increase in leafy vegetables does not provide additional bioavailable iron, presumably due to the high phenolic compound concentration of the leaves tested. Alternative measures, such as adding iron absorption enhancers to the sauces, need to be investigated to improve iron nutrition from Burkinabe maize meals.
    Food matrix effects on bioaccessibility of B-Carotene can be measured in a vitro gastrointestinal model
    Loo-Bouwman, C.A. van; Naber, T.H.J. ; Minekus, M. ; Hulshof, P.J.M. ; Schaafsma, G. - \ 2014
    Journal of Agricultural and Food Chemistry 62 (2014)4. - ISSN 0021-8561 - p. 950 - 955.
    green leafy vegetables - digestion method - pro-vitamin - folic-acid - accessibility - serum - bioavailability - absorption - retinol - cassava
    Since the food matrix determines ß-carotene availability for intestinal absorption, food matrix effects on the bioaccessibility of ß-carotene from two diets were investigated in vitro and compared with in vivo data. The “mixed diet” consisted of ß-carotene-rich vegetables, and the “oil diet” contained ß-carotene-low vegetables with supplemental ß-carotene. The application of extrinsically labeled ß-carotene was also investigated. The bioaccessibility of ß-carotene was 28 µg/100 µg ß-carotene from the mixed diet and 53 µg/100 µg ß-carotene from the oil diet. This ratio of 1.9:1 was consistent with in vivo data, where the apparent absorption was 1.9-fold higher in the oil diet than in the mixed diet. The labeled ß-carotene was not equally distributed over time. In conclusion, the food matrix effects on bioaccessibility of ß-carotene could be measured using an in vitro model and were consistent with in vivo data. The application of extrinsically labeled ß-carotene was not confirmed.
    A physiologically based kinetic (PBK) model describing plasma concentrations of quercetin and its metabolites in rats
    Boonpawa, R. ; Spenkelink, A. ; Rietjens, I. ; Punt, A. - \ 2014
    Biochemical Pharmacology 89 (2014)2. - ISSN 0006-2952 - p. 287 - 299.
    flavonoid-mediated inhibition - blood partition-coefficients - oral bioavailability - biological-activity - biliary-excretion - intestinal uptake - glucuronidation - humans - absorption - tissues
    Biological activities of flavonoids in vivo are ultimately dependent on the systemic bioavailability of the aglycones as well as their metabolites. In the present study, a physiologically based kinetic (PBK) model was developed to predict plasma concentrations of the flavonoid quercetin and its metabolites and to tentatively identify the regiospecificity of the major circulating metabolites. The model was developed based on in vitro metabolic parameters and by fitting kinetic parameters to literature available in vivo data. Both exposure to quercetin aglycone and to quercetin-4'-O-glucoside, for which in vivo data were available, were simulated. The predicted plasma concentrations of different metabolites adequately matched literature reported plasma concentrations of these metabolites in rats exposed to 4'-O-glucoside. The bioavailability of aglycone was predicted to be very low ranging from 0.004%-0.1% at different oral doses of quercetin or quercetin-4'-O-glucoside. Glucuronidation was a crucial pathway that limited the bioavailability of the aglycone, with 95–99% of the dose being converted to monoglucuronides within 1.5–2.5 h at different dose levels ranging from 0.1 to 50 mg/kg bw quercetin or quercetin-4'-O-glucoside. The fast metabolic conversion to monoglucuronides allowed these metabolites to further conjugate to di- and tri-conjugates. The regiospecificity of major circulating metabolites was observed to be dose-dependent. As we still lack in vivo kinetic data for many flavonoids, the developed model has a great potential to be used as a platform to build PBK models for other flavonoids as well as to predict the kinetics of flavonoids in humans.
    Predicting individual responses to pravastatin using a physiologically based kinetic model for plasma cholesterol levels
    Pas, N.C.A. van de; Rullmann, J. ; Woutersen, R.A. ; Ommen, B. van; Rietjens, I. ; Graaf, A.A. de - \ 2014
    Journal of Pharmacokinetics and Pharmacodynamics 41 (2014)4. - ISSN 1567-567X - p. 351 - 362.
    coa reductase inhibitors - statin therapy - lowering-therapy - ldl cholesterol - hepg2 cells - atorvastatin - simvastatin - absorption - metabolism - trial
    We used a previously developed physiologically based kinetic (PBK) model to analyze the effect of individual variations in metabolism and transport of cholesterol on pravastatin response. The PBK model is based on kinetic expressions for 21 reactions that interconnect eight different body cholesterol pools including plasma HDL and non-HDL cholesterol. A pravastatin pharmacokinetic model was constructed and the simulated hepatic pravastatin concentration was used to modulate the reaction rate constant of hepatic free cholesterol synthesis in the PBK model. The integrated model was then used to predict plasma cholesterol concentrations as a function of pravastatin dose. Predicted versus observed values at 40 mg/d pravastatin were 15 versus 22 % reduction of total plasma cholesterol, and 10 versus 5.6 % increase of HDL cholesterol. A population of 7,609 virtual subjects was generated using a Monte Carlo approach, and the response to a 40 mg/d pravastatin dose was simulated for each subject. Linear regression analysis of the pravastatin response in this virtual population showed that hepatic and peripheral cholesterol synthesis had the largest regression coefficients for the non-HDL-C response. However, the modeling also showed that these processes alone did not suffice to predict non-HDL-C response to pravastatin, contradicting the hypothesis that people with high cholesterol synthesis rates are good statin responders. In conclusion, we have developed a PBK model that is able to accurately describe the effect of pravastatin treatment on plasma cholesterol concentrations and can be used to provide insight in the mechanisms behind individual variation in statin response.
    The effect of fibers on coagulation of casein-based enteral nutrition in an artificial gastric digestion model
    Luttikhold, J. ; Norren, K. van; Minor, M. ; Buijs, N. ; Braak, C.C.M. van den; Ludwig, T. ; Abrahamse, E. ; Rijna, H. ; Leeuwen, P.A.M. - \ 2014
    Food & Function 5 (2014). - ISSN 2042-6496 - p. 1866 - 1871.
    critically-ill patients - thermodynamic incompatibility - intestinal-obstruction - in-vitro - motility - proteins - absorption - guidelines - mixtures - feedings
    A serious complication seen in critically ill patients is the solidification of enteral nutrition causing gastrointestinal obstruction. It has been suggested that enteral nutrition enriched with insoluble fibers may increase the risk of this complication. Therefore, we investigate the effect of soluble and insoluble dietary fibers on the coagulation of a casein-based enteral nutrition in an artificial gastric digestion model. A 100% casein-based enteral nutrition was enriched with increasing concentrations of soluble fibers (acacia fiber, oligofructose and inulin) and insoluble fibers (soy polysaccharide, resistant starch and alpha cellulose). After digestion in an artificial gastric model, the chyme was poured over sequentially placed sieves, separating the coagulate into size fractions of larger than 2 mm, between 1 and 2 mm, and between 0.25 and 1 mm. Of these fractions we measured wet weight, dry weight and protein content. A significant effect on the fraction larger than 2 mm was considered to be clinically relevant. Addition of high concentrations soy polysaccharide and resistant starch to a casein-based enteral nutrition, did not alter the wet weight, whereas dry weight and protein content of the coagulate was significantly reduced. When high concentrations of soy polysaccharide and resistant starch are added to a 100% casein-based enteral nutrition, the coagulate consist of more water and less proteins, which may lead to an increased protein digestion and absorption in a clinical setting. The suggestion that insoluble fibers increase the risk of gastrointestinal obstruction in critically ill patients is not supported by these data.
    The effect of steam pelleting of a dry dog food on the Maillard reaction
    Rooijen, C. van; Bosch, G. ; Wierenga, P.A. ; Hendriks, W.H. ; Poel, A.F.B. van der - \ 2014
    Animal Feed Science and Technology 198 (2014). - ISSN 0377-8401 - p. 238 - 247.
    glycation end-products - physical quality - nutritive-value - animal feed - lysine - diet - digestibility - absorption - components - proteins
    During processing of pet foods, the Maillard reaction (MR) can occur, which reduces the bioavailability of essential amino acids like lysine and results in the formation of advanced Maillard reaction products (MRPs). This study examined the effect of conditioning temperature (65 and 90 °C) and die hole length (ø 5 × 45, 65, and 80 mm) during pelleting processing of a standard dry dog food on selected indicators of the MR (total lysine, reactive lysine, fructoselysine, ¿-N-carboxymethyllysine, (5-hydroxymethyl)-2-furfural, lysinoalanine), browning development and CIE-Lab color. Steam pelleting variables did not cause a significant loss of lysine or change in color and absorbance values. Analyzing the unprocessed ingredient mix suggests that the choice of the ingredients used in the ingredient mix, rather than the pelleting process applied, is responsible for the RL/TL ratio observed in the dry standard dog food used in this study. MRP content increased during steam pelleting (fructoselysine: 366.2 to 538.8 mg/kg DM; ¿-N-carboxymethyllysine: 12.6 to 14.8 mg/kg DM; lysinoalanine: 5.7 to 7.7 mg/kg DM; P <0.05). Increasing conditioning temperature from 65 to 90 °C increased fructoselysine (475.9 to 601.6 mg/kg DM; P <0.01) and ¿-N-carboxymethyllysine (14.3 to 15.1 mg/kg DM; P = 0.003). An increased die hole length of 80 mm decreased fructoselysine content compared to 45 and 65 mm (461.3 vs. 573.3 and 581.6 mg/kg DM; P <0.01) but increased lysinoalanine content (8.8 vs. 7.4 and 6.8 mg/kg DM; P = 0.002). Analyzing total and reactive lysine and absorbance values are not accurate enough to predict the MR and formation of MRPs during processing.
    Electroactive behavior assessment of poly(acrylic acid)-graphene oxide composite hydrogel in the detection of cadmium
    Bejarano-Jimenez, A. ; Escobar-Barrios, V.A. ; Kleijn, J.M. ; Oritz-Ledon, C.A. ; Chazaro-Ruiz, L.F. - \ 2014
    Journal of Applied Polymer Science 131 (2014)19. - ISSN 0021-8995 - 10 p.
    carbon-paste electrodes - swelling properties - metal-ions - acid) - polymerization - gels - complexation - absorption - water - ph
    Super absorbent polymers of acrylic acid-graphene oxide (PAA-GO) were synthesized with different percentage of chemical neutralization (0, 10, and 20%) of the acrylic acid monomer before its polymerization. The influence of their swelling and adsorption/desorption capacity of cadmium ions in aqueous solutions were studied and revealed that the GO enables greater mechanical stability in the materials. The PAA hydrogels, with the same degrees of neutralization, were also prepared without GO to compare with the composites. Additionally, carbon paste electrodes (CPE) modified with the composites PAA-GO were used to asses and compare their adsorption properties with cadmium(II). The anodic stripping voltammetry (ASV) peak, in the differential pulse voltammetry mode, for cadmium oxidation was found to be influenced by the presence of GO into the polymer, and also by their percentage of neutralization. The accumulation of cadmium(II) on the surface of the modified CPEs was performed under open-circuit conditions taking an account the preconcentration time of the metal cation. The presence of GO enhances the electrical signal of the electrodes in short times of immersion in cadmium(II) solutions. This property contributed to get linear responses of the CPEs modified with the composites, which were influenced by their degrees of neutralization. The PAA-GO 10N electrode with 10% of neutralization combined the influence of GO and the degree of neutralization in the same matrix, and also showed good performance in terms of its mechanical stability, it was chosen for preliminary studies on the selectivity of the electrode toward Zn(II) and Cu(II).
    Peripartal calcium homoeostasis of multiparous dairy cows fed rumen-protected rice bran or a lowered dietary cation/anion balance diet before calving
    Martin-Tereso, J. ; Wijlen, H. ter; Laar, H. van; Verstegen, M.W.A. - \ 2014
    Journal of Animal Physiology and Animal Nutrition 98 (2014)4. - ISSN 0931-2439 - p. 775 - 784.
    anion difference - milk fever - dry period - hypocalcemia - metaanalysis - absorption - disorders - nutrition - health - cattle
    Milk fever is one of the most important metabolic diseases in dairy cattle. Reducing the dietary cation/anion balance (DCAD) with anionic salts is a common prevention strategy. However, many small European farms cannot use total mixed rations (TMR) in the close-up period. Including anionic salts in compound feeds can result in feed refusals and moderate inclusions to preserve feed palatability results in insufficient DCAD reduction. Rumen-protected rice bran induces the adaptation of Ca metabolism in dairy cows by a reduction of Ca intake and by a reduction of the availability of dietary Ca. In the presence of a negative control, rumen-protected rice bran (2.8 kg/day) was compared with a lowered DCAD diet (from 269 to 4 meq/kg DM) in their effect to prevent milk fever. In a randomized block design, 45 multiparous Holstein cows joined the trial sequentially from 21 days before the expected calving date and were observed until the 8th week of lactation. Feed and nutrient intakes were recorded, and Ca, P, Mg in serum and urine, urine pH, serum NEFA and milk production in early lactation were compared. Feeding rumen-protected rice bran before calving improved the recovery of calcaemia after calving and had a positive effect on DMI after calving. The moderately low DCAD diet did not positively influence serum Ca at calving. Calcaemia recovered even later than in control, and cows showed reduced DMI post-calving and higher NEFA levels in the first 36 h after calving. This moderate reduction of DCAD did not provide an intermediate prevention level indicating that DCAD needs to be reduced to the recommended levels to prevent milk fever. Rumen-protected rice bran may be a suitable feed to reduce hypocalcaemia post-partum and can be included in pre-calving compound feeds representing a palatable alternative to anionic salts.
    Efficacy of dimethylglycine as a feed additive to improve broiler production
    Kalmar, I.D. ; Verstegen, M.W.A. ; Vanrompay, D. ; Maenner, K. ; Zentek, J. ; Iben, C. ; Leitgeb, R. ; Schiavone, A. ; Prola, L. ; Janssens, G. - \ 2014
    Livestock Science 164 (2014). - ISSN 1871-1413 - p. 81 - 86.
    amino-acids - n,n-dimethylglycine - supplementation - digestibility - performance - absorption - choline - betaine - diet
    Dimethylglycine (DMG) is a naturally occurring glycine derivative, which is useful as additive to broiler diets as it improves nutrient digestibility and reduces the development of broiler ascites syndrome. This study evaluated the efficacy of dietary DMG to enhance performance of broiler chickens. Three trials were conducted to evaluate the effect of dietary supplementation with 1 g Na DMG/kg on growth performance and carcass characteristics. In Trial 1, the effect of sex was also assessed in a 2×2 factorial arrangement of treatments. In Trials 1 (Germany), 2 (Austria), and 3 (Italy), each treatment consisted of 6, 12, and 11 replicate pens with 20, 15, and 16 one-day-old broiler chickens per pen, respectively. Dietary DMG supplementation resulted in improved feed conversion ratio (FCR) in the starter phase by 8.8% (P=0.004), 6.4% (P=0.001), and 4.8% (P=0.006) compared with the control diet in Trials 1, 2, and 3, respectively. The overall FCR improved in broiler chickens fed the diets supplemented with DMG by 3.8% and 4.1% in Trials 1 (P=0.007) and 3 (P=0.006), respectively. In addition, final body weight increased by 5.5% (P=0.001) in Trial 2 and production value improved by 6.8% (P=0.015) in Trial 1 by dietary DMG supplementation. Mortality in all trials was similar between dietary treatments. In all 3 trials, cold carcass weight and total meat yield were as well similar between broiler chickens fed the control and DMG diets. In Trial 1, dietary DMG had no effect on breast meat yield in male broiler chickens, but it increased breast meat yield in female broiler chickens (diet×sex, P=0.004). Organoleptic quality of roasted breast meat assessed only in Trial 2 was not affected by dietary treatments. In conclusion, dietary supplementation of DMG at 1 g Na DMG/kg can considerably improve s production performance in broiler chickens.
    Conversion of major soy isoflavone glucosides and aglycones in in vitro intestinal models
    Islam, M.A. ; Punt, A. ; Spenkelink, A. ; Murk, A.J. ; Leeuwen, F.X.R. ; Rietjens, I. - \ 2014
    Molecular Nutrition & Food Research 58 (2014)3. - ISSN 1613-4125 - p. 503 - 515.
    rat small-intestine - lactase-phlorhizin hydrolase - caco-2 cell monolayers - beta-glucosidase - 1st-pass metabolism - phyto-estrogens - human plasma - absorption - bioavailability - glycosides
    ScopeThis study compares conversion of three major soy isoflavone glucosides and their aglycones in a series of in vitro intestinal models. Methods and resultsIn an in vitro human digestion model isoflavone glucosides were not deconjugated, whereas studies in a Caco-2 transwell model confirmed that deconjugation is essential to facilitate transport across the intestinal barrier. Deconjugation was shown upon incubation of the isoflavone glucosides with rat as well as human intestinal S9. In incubations with rat intestinal S9 lactase phlorizin hydrolase, glucocerebrosidase, and cytosolic broad-specific -glucosidase all contribute significantly to deconjugation, whereas in incubations with human intestinal S9 deconjugation appeared to occur mainly through the activity of broad-specific -glucosidase. Species differences in glucuronidation and sulfation were limited and generally within an order of magnitude with 7-O-glucuronides being the major metabolites for all three isoflavone aglycones and the glucuronidation during first pass metabolism being more efficient in rats than in humans. Comparison of the catalytic efficiencies reveals that deconjugation is less efficient than conjugation confirming that aglycones are unlikely to enter the systemic circulation. ConclusionAltogether, the data point at possible differences in the characteristics for intestinal conversion of the major soy isoflavones between rat and human, especially with respect to their deconjugation.
    Quantum Chemical Studies on Solvents for Post-Combustion Carbon Dioxide Capture: Calculation of pKa and Carbamate Stability of Disubtituted Piperazines
    Gangarapu, S. ; Wierda, G.J. ; Marcelis, A.T.M. ; Zuilhof, H. - \ 2014
    ChemPhysChem 15 (2014). - ISSN 1439-4235 - p. 1880 - 1886.
    sterically hindered amines - co2 capture - aqueous piperazine - pilot-plant - absorption - performance - technology - basicities - parameters - constants
    Piperazine is a widely studied solvent for post-combustion carbon dioxide capture. To investigate the possibilities of further improving this process, the electronic and steric effects of CH3, CH2F, CH2OH, CH2NH2, COCH3, and CN groups of 2,5-disubstituted piperazines on the pKa and carbamate stability towards hydrolysis are investigated by quantum chemical methods. For the calculations, B3LYP, M11L, and spin-component-scaled MP2 (SCS-MP2) methods are used and coupled with the SMD solvation model. The experimental pKa values of piperazine, 2-methylpiperazine, and 2,5-dimethylpiperazine agree well with the calculated values. The present study indicates that substitution of CH3, CH2NH2, and CH2OH groups on the 2- and 5-positions of piperazine has a positive impact on the CO2 absorption capacity by reducing the carbamate stability towards hydrolysis. Furthermore, their higher boiling points, relative to piperazine itself, will lead to a reduction of volatility-related losses.
    Theory of ion transport with fast acid-base equilibrations in bioelectrochemical systems
    Dykstra, J.E. ; Biesheuvel, P.M. ; Bruning, H. ; Heijne, A. ter - \ 2014
    Physical Review. E, Statistical nonlinear, and soft matter physics 90 (2014). - ISSN 1539-3755 - 10 p.
    microbial electrolysis cell - hydrogen-production - fuel-cells - quantitative approach - mathematical-model - ammonium recovery - chemical-reaction - inorganic carbon - urine - absorption
    Bioelectrochemical systems recover valuable components and energy in the form of hydrogen or electricity from aqueous organic streams. We derive a one-dimensional steady-state model for ion transport in a bioelectrochemical system, with the ions subject to diffusional and electrical forces. Since most of the ionic species can undergo acid-base reactions, ion transport is combined in our model with infinitely fast ion acid-base equilibrations. The model describes the current-induced ammonia evaporation and recovery at the cathode side of a bioelectrochemical system that runs on an organic stream containing ammonium ions. We identify that the rate of ammonia evaporation depends not only on the current but also on the flow rate of gas in the cathode chamber, the diffusion of ammonia from the cathode back into the anode chamber, through the ion exchange membrane placed in between, and the membrane charge density.
    In Silico Prediction and Automatic LC–MSn Annotation of Green Tea Metabolites in Urine
    Ridder, L.O. ; Hooft, J.J.J. van der; Verhoeven, S. ; Vos, R.C.H. de; Vervoort, J.J.M. ; Bino, R.J. - \ 2014
    Analytical Chemistry 86 (2014)10. - ISSN 0003-2700 - p. 4767 - 4774.
    human fecal microbiota - mass-spectrometry - structural elucidation - human plasma - phenolic-compounds - spectral trees - polyphenols - identification - absorption - metabolomics
    The colonic breakdown and human biotransformation of small molecules present in food can give rise to a large variety of potentially bioactive metabolites in the human body. However, the absence of reference data for many of these components limits their identification in complex biological samples, such as plasma and urine. We present an in silico workflow for automatic chemical annotation of metabolite profiling data from liquid chromatography coupled with multistage accurate mass spectrometry (LC-MSn), which we used to systematically screen for the presence of tea-derived metabolites in human urine samples after green tea consumption. Reaction rules for intestinal degradation and human biotransformation were systematically applied to chemical structures of 75 green tea components, resulting in a virtual library of 27¿245 potential metabolites. All matching precursor ions in the urine LC–MSn data sets, as well as the corresponding fragment ions, were automatically annotated by in silico generated (sub)structures. The results were evaluated based on 74 previously identified urinary metabolites and lead to the putative identification of 26 additional green tea-derived metabolites. A total of 77% of all annotated metabolites were not present in the Pubchem database, demonstrating the benefit of in silico metabolite prediction for the automatic annotation of yet unknown metabolites in LC–MSn data from nutritional metabolite profiling experiments.
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