New approaches to uncertainty analysis for use in aggregate and cumulative risk assessment of pesticides
Kennedy, M.C. ; Voet, H. van der; Roelofs, V.J. ; Roelofs, W. ; Glass, C.R. ; Boer, W.J. de; Kruisselbrink, J.W. ; Hart, A.D.M. - \ 2015
Food and Chemical Toxicology 79 (2015). - ISSN 0278-6915 - p. 54 - 64.
residential exposure - modeling framework - dietary
Risk assessments for human exposures to plant protection products (PPPs) have traditionally focussed on single routes of exposure and single compounds. Extensions to estimate aggregate (multi-source) and cumulative (multi-compound) exposure from PPPs present many new challenges and additional uncertainties that should be addressed as part of risk analysis and decision-making. A general approach is outlined for identifying and classifying the relevant uncertainties and variabilities. The implementation of uncertainty analysis within the MCRA software, developed as part of the EU-funded ACROPOLIS project to address some of these uncertainties, is demonstrated. An example is presented for dietary and non-dietary exposures to the triazole class of compounds. This demonstrates the chaining of models, linking variability and uncertainty generated from an external model for bystander exposure with variability and uncertainty in MCRA dietary exposure assessments. A new method is also presented for combining pesticide usage survey information with limited residue monitoring data, to address non-detect uncertainty. The results show that incorporating usage information reduces uncertainty in parameters of the residue distribution but that in this case quantifying uncertainty is not a priority, at least for UK grown crops. A general discussion of alternative approaches to treat uncertainty, either quantitatively or qualitatively, is included.
Prediction of nitrogen use in dairy cattle: a multivariate Bayesian approach
Reed, K.F. ; Moraes, L.E. ; Fadel, J.G. ; Casper, D.P. ; Dijkstra, J. ; France, J. ; Kebreab, E. - \ 2014
Animal Production Science 54 (2014)12. - ISSN 1836-0939 - p. 1918 - 1926.
cows - excretion - protein - management - metabolism - efficiency - ruminants - pollution - dietary - manure
Quantification of dairy cattle nitrogen (N) excretion and secretion is necessary to improve the efficiency with which feed N is converted to milk N (ENU). Faecal and urinary N excretion and milk N secretion are correlated with each other and thus are more accurately described by a multivariate model that can accommodate the covariance between the three observations than by three separate univariate models. Further, by simultaneously predicting the three routes of excretion and taking advantage of the mass balance relationships between them, covariate effects on N partitioning from feed to faeces and absorbed N and from absorbed N to milk and urine N and animal ENU can be estimated. A database containing 1094 lactating dairy cow observations collated from indirect calorimetry experiments was used for model development. Dietary metabolisable energy content (ME, MJ/kg DM) increased ENU at a decreasing rate, increased the efficiency with which feed N was converted to absorbed N and decreased the efficiency with which absorbed N was converted to milk N. However, the parameter estimate of the effect of ME on post-absorption efficiency was not different from zero when the model was fitted to a data subset in which net energy and metabolisable protein were at or above requirement. This suggests the effect of ME on post-absorption N use is dependent on the energy status of the animal.
Different in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study
Forouhi, N.G. ; Koulman, A. ; Sharp, S.J. ; Groenendijk-van Woudenbergh, G.J. ; Feskens, E.J.M. - \ 2014
The Lancet Diabetes & Endocrinology 2 (2014)10. - ISSN 2213-8587 - p. 810 - 818.
dairy product intake - de-novo lipogenesis - risk-factors - dietary - humans - cancer - biomarker - mellitus - disease - project
Background Conflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants. Methods The EPIC-InterAct case-cohort study includes 12¿403 people with incident type 2 diabetes and a representative subcohort of 16¿154 individuals who were selected from a cohort of 340¿234 European participants with 3·99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis. Findings SFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14:0 [myristic acid], 16:0 [palmitic acid], and 18:0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1·15 [95% CI 1·09–1·22], palmitic acid 1·26 [1·15–1·37], and stearic acid 1·06 [1·00–1·13]). By contrast, measured odd-chain SFAs (15:0 [pentadecanoic acid] and 17:0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0·79 [0·73–0·85] for pentadecanoic acid and 0·67 [0·63–0·71] for heptadecanoic acid), as were measured longer-chain SFAs (20:0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0·72 to 0·81 (95% CIs ranging between 0·61 and 0·92). Our findings were robust to a range of sensitivity analyses. Interpretation Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed. Funding EU FP6 programme, Medical Research Council Epidemiology Unit, Medical Research Council Human Nutrition Research, and Cambridge Lipidomics Biomarker Research Initiative.
Investigating the Transport Dynamics of Anthocyanins from Unprocessed Fruit and Processed Fruit Juice from Sour Cherry (Prunus cerasus L.) across Intestinal Epithelial Cells
Toydemir, G. ; Boyacioglu, D. ; Capanoglu, E. ; Meer, I.M. van der; Tomassen, M.M.M. ; Hall, R.D. ; Mes, J.J. ; Beekwilder, J. - \ 2013
Journal of Agricultural and Food Chemistry 61 (2013)47. - ISSN 0021-8561 - p. 11434 - 11441.
red grape juice - protein interactions - cellular uptake - absorption - quercetin - dietary - caco-2 - bioavailability - consumption - glucosides
Anthocyanins can contribute to human health through preventing a variety of diseases. The uptake of these compounds from food and the parameters determining uptake efficiency within the human body are still poorly understood. Here we have employed a Caco-2 cell based system to investigate the transport of key antioxidant food components from sour cherry (Prunus cerasus L.) across the intestinal epithelial barrier. Anthocyanins and (-)-epicatechin were supplied in three contrasting matrices: fruit, processed fruit cherry juice, and polyphenolic fractions obtained by solid-phase extraction. Results show that both compound types behave differently. Fruit or juice matrices display comparable transport across the epithelial cell layer. The juice supplements sucrose and citric acid, which are regularly added to processed foods, have a positive effect on stability and transport. Polyphenolic fractions display a lower transport efficiency, relative to that of the fruit or juice, indicating the importance of food matrix components for intestinal absorption of polyphenols
A high-fat SFA, MUFA, or n3 PUFA challenge affects the vascular response and initiates an activated state of cellular adherence in lean and obese middle-aged men
Esser, D. ; Dijk, S.J. van; Oosterink, E. ; Müller, M.R. ; Afman, L.A. - \ 2013
The Journal of Nutrition 143 (2013)6. - ISSN 0022-3166 - p. 843 - 851.
triglyceride-rich lipoproteins - postprandial lipemia - nonfasting triglycerides - cardiovascular-disease - arterial stiffness - oxidative stress - healthy-men - young men - dietary - women
BMI and fatty acid type affect postprandial metabolic TG responses, but whether these factors also affect vascular, inflammatory, and leukocyte adherence responses remains unclear. We therefore compared those postprandial responses between lean and obese men after 3 high-fat challenges differing in fatty acid composition. In a crossover double-blind study, 18 lean (BMI: 18–25 kg/m2) and 18 obese (BMI >29 kg/m2) middle-aged men received 3 isocaloric high-fat milkshakes containing 95 g fat (88% of energy), either high in SFAs (54% of energy/total fat), MUFAs (83% of energy/total fat), or n3 (omega-3) PUFAs (40% of energy/total fat). Hemodynamics, augmentation index (AIX), leukocyte cell surface adhesion markers, and plasma cytokines involved in vascular adherence, coagulation, and inflammation were measured before and after consumption of the milkshakes. In both groups and after all shakes were consumed, AIX decreased; plasma soluble intercellular adhesion molecule (sICAM) 1, sICAM3, soluble vascular cell adhesion molecule (sVCAM) 1, and interleukin-8 increased; monocyte CD11a, CD11b, and CD621 expression increased; neutrophil CD11a, CD11b, and CD621 expression increased; and lymphocyte CD62l expression increased (P <0.05). Lymphocyte CD11a and CD11b expression decreased in lean participants after consumption of all shakes but did not change in obese participants (P <0.05). Obese participants had a less pronounced decrease in heart rate after the consumption of all shakes (P <0.05). MUFA consumption induced a more pronounced decrease in blood pressure and AIX compared with the other milkshakes in both lean and obese participants (P <0.05). High-fat consumption initiates an activated state of cellular adherence and an atherogenic milieu. This response was independent of fatty acid type consumed or of being lean or obese, despite the clear differences in postprandial TG responses between the groups and different milkshakes. These findings suggest that in addition to increased TGs, other mechanisms are involved in the high-fat consumption–induced activated state of cellular adherence.
Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct
Romaguera, D. ; Norat, T. ; Wark, P.A. ; Vergnaud, A.C. ; Schulze, M.B. ; Woudenbergh, G.J. van; Beulens, J.W.J. ; Feskens, E.J.M. ; The InterAct Consortium, A. - \ 2013
Diabetologia 56 (2013)7. - ISSN 0012-186X - p. 1520 - 1530.
weight-gain - metabolic syndrome - body-weight - risk - project - obesity - cancer - cohort - dietary - women
Aims/hypothesis Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. Methods We established a case–cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case–cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. Results In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. Conclusions/interpretation This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults
Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice
Hoek-van den Hil, E.F. ; Keijer, J. ; Bunschoten, A. ; Vervoort, Jacques ; Stankova, B. ; Bekkenkamp-Grovestein, M. ; Herreman, L. ; Venema, D.P. ; Hollman, P.C.H. ; Tvrzicka, E. ; Rietjens, I. ; Schothorst, E.M. van - \ 2013
PLoS ONE 8 (2013)1. - ISSN 1932-6203 - 10 p.
fatty-acid oxidation - cytochrome-p450 reductase - liver-disease - receptor car - metabolism - dietary - rat - flavonoids - risk - hydroxylases
Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to quantitatively measure serum lipid profiles. Whole genome microarray analysis of liver tissue was used to identify possible mechanisms underlying altered circulating lipid levels. Body weight, energy intake and hepatic lipid accumulation did not differ significantly between the quercetin and the control group. In serum of quercetin-fed mice, triglycerides (TG) were decreased with 14% (p
Short communication: Urinary oxalate and calcium excretion by dogs and cats diagnosed with calcium oxalate urolithiasis
Dijcker, J.C. ; Kummeling, A. ; Hagen-Plantinga, E.A. ; Hendriks, W.H. - \ 2012
Veterinary Record 171 (2012)25. - ISSN 0042-4900 - p. 646 - 646.
Introduction Urine concentrations of oxalate and calcium play an important role in calcium oxalate (CaOx) urolith formation in dogs and cats, with high excretions of both substances increasing the chance of CaOx urolithiasis. In 17 CaOx-forming dogs, urine calcium:creatinine ratio (Ca:Cr) was found to be increased compared with healthy control dogs, whereas urine oxalate:creatinine ratio (Ox:Cr) did not differ (Stevenson and others 2004). In six CaOx-forming miniature schnauzers, urinary calcium excretion (in mg/kg/24 hours) was increased compared with healthy controls, while urinary oxalate excretion was not affected (Lulich and others 1991). However, in these studies, the urine samples were not always collected at the time CaOx uroliths were actually present in the urinary tract. Moreover, in these studies, individual urinary oxalate and calcium excretions were mostly not provided. The objective of this study was to determine the urinary oxalate and calcium excretion rates, and the urinary calcium to oxalate ratio (Ca:oxalate), at the time CaOx uroliths were present in the urinary tract of dogs and cats. Materials and Methods Data for this observational study were collected through urine sampling and questionnaires from May 2010 to January 2012. Participation in this study was voluntary, and informed consent was obtained from dog and cat owners who consulted the University Clinic for Companion Animals of the Utrecht University because of urolithiasis. Dogs and …
Biomarker-based evaluation of two 24-h recalls for comparing usual fish, fruit and vegetable intakes across European centers in the EFCOVAL Study
Vries, J.H.M. de; Crispim, S.P. ; Souverein, O.W. ; Hulshof, P.J.M. ; Ruprich, J. ; Dofkova, M. ; Huybrechts, I. ; Keyzer, W. de; Lillegaard, I.T.L. ; Lafay, L. ; Rousseau, A.S. ; Ocke, M.C. ; Slimani, N. ; Veer, P. van 't - \ 2011
European Journal of Clinical Nutrition 65 (2011). - ISSN 0954-3007 - p. S38 - S47.
serum cholesteryl esters - life-style factors - n-3 fatty-acids - food-consumption - plasma carotenoids - alcohol-consumption - level correlations - adipose-tissue - lipid classes - dietary
Background/Objectives: A standardized methodology is important to enable consistent monitoring of dietary intake across European countries. For this reason, we evaluated the comparability of the assessment of usual food intake collected with two non-consecutive computerized 24-h dietary recalls (24-HDRs) and a food propensity questionnaire (FPQ) among five European centers. Subjects/Methods: Two 24-HDRs using EPIC-Soft (the software developed to conduct 24-HDRs in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study) were performed to determine fish, fruit and vegetable (FV) consumed by 600 adults in Belgium (BE), the Czech Republic (CZ), France (FR), the Netherlands (NL) and Norway (NO) in a validation study. An FPQ was used to identify non-consumers. Information from the 24-HDRs and FPQ were used to estimate individual usual food intake by the Multiple Source Method (MSM). Blood samples were drawn to determine fatty acids in phospholipids and serum carotenoids as biomarkers of fish, and FV intake, respectively. Results: The pooled correlation between usual fish intake and eicosapentaenoic acid plus docosahexaenoic acid in phospholipids was 0.19 in men and 0.31 in women (P for heterogeneity >0.50) and center-specific correlations ranged between 0.08 (CZ) and 0.28 (BE and NO) in men, and between 0.19 (BE) and 0.55 (FR) in women. For usual FV intake, the pooled correlation with serum carotenoids was 0.31 in men and 0.40 in women (P for heterogeneity >0.10); the center-specific correlations varied between 0.07 (NO) and 0.52 (FR) in men, and between 0.25 (NL) and 0.45 (NO) in women. Conclusion: Two standardized 24-HDRs using EPIC-Soft and an FPQ appeared to be appropriate to rank individuals according to their fish and FV intake in a comparable way among five European centers.
Deconjugation Kinetics of Glucuronidated Phase II Flavonoid Metabolites by B-glucuronidase from Neutrophils
Bartholomé, R. ; Haenen, G. ; Hollman, P.C.H. ; Bast, A. ; Dagnelie, P.C. ; Roos, D. ; Keijer, J. ; Kroon, P.A. ; Needs, P.W. ; Arts, I.C.W. - \ 2010
Drug Metabolism and Pharmacokinetics 25 (2010)4. - ISSN 1347-4367 - p. 379 - 387.
quercetin glucuronides - grain dust - inflammation - dietary - ph - tissue - cells - fluid - quercetin-4'-glucoside - quercetin-3-glucoside
Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. Mammalian ß-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. We have studied deconjugation kinetics and pH optimum for four sources of ß-glucuronidase (human neutrophil, human recombinant, myeloid PLB-985 cells, Helix pomatia) with five flavonoid glucuronides (quercetin-3-glucuronide, quercetin-3'-glucuronide, quercetin-4'-glucuronide, quercetin-7-glucuronide, 3'-methylquercetin-3-glucuronide), 4-methylumbelliferyl-ß-D-glucuronide, and para-nitrophenol-glucuronide. All substrate-enzyme combinations tested exhibited first order kinetics. The optimum pH for hydrolysis was between 3.5-5, with appreciable hydrolysis activities up to pH 5.5. At pH 4, the Km ranged 44-fold from 22 µM for quercetin-4'-glucuronide with Helix pomatia ß-glucuronidase, to 981 µM for para-nitrophenol-glucuronide with recombinant ß-glucuronidase. Vmax (range: 0.735-24.012 µmol·min-1·unit-1 [1 unit is defined as the release of 1 µM 4-methylumbelliferyl-ß-D-glucuronide per min]) and the reaction rate constants at low substrate concentrations (k) (range: 0.002-0.062 min-1·(unit/L)-1 were similar for all substrates-enzyme combinations tested. In conclusion, we show that ß-glucuronidase from four different sources, including human neutrophils, is able to deconjugate flavonoid glucuronides and non-flavonoid substrates at fairly similar kinetic rates. At inflammatory sites in vivo the pH, neutrophil and flavonoid glucuronide concentrations seem favorable for deconjugation. However, it remains to be confirmed whether this is actually the case.
Increasing fish consumption does not affect genotozicity markers in the colon in an intervention study
Pot, G.K. ; Habermann, N. ; Majsak-Newman, G. ; Harvey, L.J. ; Geelen, A. ; Witteman, B.J.M. ; Meeberg, P.C. van de; Hart, A.R. ; Schaafsma, G. ; Hooiveld, G.J.E.J. ; Glei, M. ; Lund, E.K. ; Pool-Zobel, B.L. ; Kampman, E. - \ 2010
Carcinogenesis 31 (2010)6. - ISSN 0143-3334 - p. 1087 - 1091.
polyunsaturated fatty-acids - rectal cell-proliferation - fecal water genotoxicity - colorectal-cancer risk - induced dna-damage - comet assay - oxidative stress - eicosapentaenoic acid - dietary - carcinogenesis
Observational studies suggest that fish consumption is associated with a decreased colorectal cancer (CRC) risk. A possible mechanism by which fish could reduce CRC risk is by decreasing colonic genotoxicity. However, concerns have also been raised over the levels of toxic compounds found in mainly oil-rich fish, which could increase genotoxicity. Therefore, the objective was to investigate the effects of fish on genotoxicity markers in the colon in a randomized controlled parallel intervention study. For a period of 6 months, subjects were randomly allocated to receive two extra weekly portions of (i) oil-rich fish (salmon), (ii) lean fish (cod) or (iii) just dietary advice (DA). The Comet Assay was used to measure the DNA damage-inducing potential of fecal water (n = 89) and DNA damage in colonocytes (n = 70) collected pre- and post-intervention as markers of genotoxicity. Genotoxicity of fecal water was not markedly changed after fish consumption: 1.0% increase in tail intensity (TI) [95% confidence interval (CI) -5.1; 7.0] in the salmon group and 0.4% increase in TI (95% CI -5.3; 6.1) in the cod group compared with the DA group. DNA damage in colonocytes was also not significantly changed after fish consumption, in either the salmon group (-0.5% TI, 95% CI -6.9; 6.0) or cod group (-3.3% TI, 95% CI -10.8; 4.3) compared with the DA group. Measurements of genotoxicity of fecal water and DNA damage in colonocytes did not correlate (r = 0.06, n = 34). In conclusion, increasing consumption of either oil-rich or lean fish did not affect genotoxicity markers in the colon.
Determination of the neurotoxins BMAA (ß-N-methylamino-L-alanine) and DAB (a-,¿-diaminobutyric acid) by LC-MSMS in Dutch urban waters with cyanobacterial blooms
Faassen, E.J. ; Gillissen, F. ; Zweers, H. ; Lürling, M.F.L.L.W. - \ 2009
Amyotrophic Lateral Sclerosis 10 (2009)Suppl. 2. - ISSN 1748-2968 - p. 79 - 84.
amino-acid - neurodegenerative disease - chamorro people - flying foxes - guam - cycas - biomagnification - als/pdc - dietary - produce
We aimed to determine concentrations of the neurotoxic amino acids ß-N-methylamino-L-alanine (BMAA) and -,¿-diaminobutyric acid (DAB) in mixed species scum material from Dutch urban waters that suffer from cyanobacterial blooms. BMAA and DAB were analysed in scum material without derivatization by LC-MSMS (liquid chromatography coupled to tandem mass spectrometry) using hydrophilic interaction chromatography (HILIC). Our method showed high selectivity, good recovery of added compounds after sample extraction (86% for BMAA and 85% for DAB), acceptable recovery after sample hydrolysation (70% for BMAA and 56% for DAB) and acceptable precision. BMAA and DAB could be detected at an injected amount of 0.34 pmol. Free BMAA was detected in nine of the 21 sampled locations with a maximum concentration of 42 µg/g DW. Free DAB was detected in two locations with a maximum concentration of 4 µg/g DW. No protein-associated forms were detected. This study is the first to detect underivatized BMAA in cyanobacterial scum material using LC-MSMS. Ubiquity of BMAA in cyanobacteria scums of Dutch urban waters could not be confirmed, where BMAA and DAB concentrations were relatively low; however, co-occurrence with other cyanobacterial neurotoxins might pose a serious health risk including chronic effects from low-level doses
Lycopene supplementation elevates circulating insulin-like growth factor-binding protein-1 and-2 concentrations in persons at greater risk of colorectal cancer
Vrieling, A. ; Voskuil, D.W. ; Bonfrer, J.M. ; Korse, C.M. ; Doorn, J. ; Cats, A. ; Depla, A.C. ; Timmer, R. ; Witteman, B.J.M. ; Leeuwen, F.E. van; van't Veer, L.J. ; Rookus, M.A. ; Kampman, E. - \ 2007
American Journal of Clinical Nutrition 86 (2007)5. - ISSN 0002-9165 - p. 1456 - 1462.
factor-i - factor (igf)-i - factor system - igf-i - alpha-tocopherol - clinical-trial - human serum - c-peptide - dietary - carotenoids
Background: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding proteins (IGFBPs). Objective: The objective of our study was to investigate the effect of an 8-wk supplementation with tomato-derived lycopene (30 mg/d) on serum concentrations of total IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3. Design: We conducted a randomized, placebo-controlled, double-blinded crossover study in 40 men and 31 postmenopausal women with a family history of colorectal cancer, a personal history of colorectal adenoma, or both. Results: Lycopene supplementation significantly (P = 0.01) increased serum IGFBP-1 concentrations in women (median relative difference between serum IGFBP-1 concentrations after lycopene supplementation and after placebo, 21.7%). Serum IGFBP-2 concentrations were higher in both men and women after lycopene supplementation than after placebo, but to a lesser extent (mean relative difference 8.2%; 95% CI: 0.7%, 15.6% in men and 7.8%; 95% CI: ¿5.0%, 20.6% in women). Total IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly altered by lycopene supplementation. Conclusions: This is the first study known to show that lycopene supplementation may increase circulating IGFBP-1 and IGFBP-2 concentrations. Because of high interindividual variations in IGFBP-1 and IGFBP-2 effects, these results should be confirmed in larger randomized intervention studies
Parenteral long-acting amoxicillin reduces intestinal bacterial community diversity in piglets even 5 weeks after the administration
Janzcyk, P. ; Pieper, R. ; Souffrant, W.B. ; Bimczok, D. ; Rothkotter, H.J. ; Smidt, H. - \ 2007
ISME Journal 1 (2007). - ISSN 1751-7362 - p. 180 - 183.
gradient gel-electrophoresis - weaning piglets - human feces - sp nov. - microbiota - antibiotics - butyrate - abundant - dietary - pigs
We investigated the long-term effects of a single intramuscular administration of amoxicillin (15 mg kg-1) 1 day after birth, on piglet intestinal microbiota. Animals received no creep feed before weaning on day 28 of age. For the next 11 days, the piglets received a wheat¿barley-based diet. Colon digesta samples were collected on day 39 and subjected to denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA gene fragments. DGGE fingerprint diversity indices differed between the group treated with amoxicillin and the untreated group (0.80.19 and 1.030.17, respectively, P=0.012). Reamplification and sequencing of two bands present in all samples revealed that a Roseburia faecalis-related population was strongly reduced in relative abundance (98% identity) in the treated group, while an enterobacterial population with 100% identity to Shigella spp., Escherichia coli and Salmonella enterica serovar Typhi was enriched. A band corresponding to Lactobacillus sobrius was present only in the control group. The protective effect of prophylactic antibiotic administration may be outweighed by the long-lasting disturbance of the gut ecosystem.
Changes in the diversity of pig ileal lactobacilli around weaning determined by means of 16S rRNA gene amplification and denaturing gradient gel electrophoresis
Janzcyk, P. ; Pieper, R. ; Smidt, H. ; Souffrant, W.B. - \ 2007
FEMS microbiology ecology 61 (2007)1. - ISSN 0168-6496 - p. 132 - 140.
lactic-acid bacteria - molecular ecological analysis - human fecal samples - intestinal microbiota - caco-2 cells - piglets - pcr - dietary - dna - quantification
Our study aimed to provide a comprehensive characterization of changes in porcine intestinal Lactobacillus populations around the time of weaning based on 16S rRNA gene amplification and denaturing gradient gel electrophoresis (DGGE). DNA was extracted from the ileal contents of piglets at weaning (28 days of age) and after 1, 2, 5 and 11 days. PCR amplicons (V2-V3 fragments of 16S rRNA genes) were separated using DGGE. Predominant bands were excised and sequenced after reamplification. A band corresponding to Lactobacillus salivarius was present 1 and 2 days post-weaning (pw), while Lactobacillus crispatus was detected only 1 and 11 days pw. Lactobacillus sobrius gave the most dominant band in all animals. The number of bands decreased from 13±3 at weaning to 9±1 at 5 days pw, but the species richness had recovered by 11 days pw. The similarity of profiles between sampling days was high for 1 and 2 days pw (>91%), but was low for 5 and 11 days pw (
Preliminary Investigation into the Absorption of Genistein and Daidzein by Domestic Cats (Felis catus)1-3
Bell, K.M. ; Pearce, P.D. ; Ugarte, C.E. ; Hendriks, W.H. - \ 2006
The Journal of Nutrition 136 (2006)7. - ISSN 0022-3166 - p. 2004S - 2006S.
soy isoflavones - adult cats - dietary - bioavailability - estrogens - urine
Differential induction of electrophile-responsive element-regulated genes by n-3 and n-6 polyunsaturated fatty acids
Beelen, V.A. van; Aarts, M.G.M. ; Reus, A. ; Mooibroek, H. ; Sijtsma, L. ; Bosch, H.J. ; Rietjens, I.M.C.M. ; Alink, G.M. - \ 2006
FEBS Letters 580 (2006)19. - ISSN 0014-5793 - p. 4587 - 4590.
antioxidant response - fish-oil - dietary - carcinogenesis - mechanisms - protection - oxidation - reductase - pathway - cancer
In this study the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid and docosahexaenoic acid appear to be effective inducers of electrophile-responsive element (EpRE) regulated genes, whereas the n-6 PUFA arachidonic acid is not. These n-3 PUFAs need to be oxidized to induce EpRE-regulated gene expression, as the antioxidant vitamin E can partially inhibit the PUFA induced dose-dependent effect. Results were obtained using a reporter gene assay, real-time RT-PCR and enzyme activity assays. The induction of EpRE-regulated phase II genes by n-3 PUFAs may be a major pathway by which n-3 PUFAs, in contrast to n-6 PUFAs, are chemopreventive and anticarcinogenic.
Low toenail chromium concentration and increased risk of nonfatal myocardial infarction
Guallar, E. ; Jimenez, J. ; Veer, P. van 't; Bode, P. ; Riemersma, R.A. ; Gomez-Aracena, J. ; Kark, J.D. ; Arab, L. ; Kok, F.J. ; Martin-Moreno, J.M. - \ 2005
American Journal of Epidemiology 162 (2005)2. - ISSN 0002-9262 - p. 157 - 164.
cardiovascular-disease - coronary-artery - dietary - metaanalysis - weight - atherosclerosis - supplements - picolinate - nutrition - glucose
Chromium intake may increase insulin sensitivity, glucose tolerance, and the ratio of high density lipoprotein cholesterol to low density lipoprotein cholesterol. However, the epidemiologic evidence on the association between chromium and cardiovascular disease is very limited. To determine whether low toenail chromium concentrations were associated with risk of nonfatal myocardial infarction, the authors conducted an incident, population-based, case-control study in eight European countries and Israel in 1991-1992. Cases (n = 684) were men with a first diagnosis of myocardial infarction recruited from the coronary units of participating hospitals. Controls (n = 724) were men selected randomly from population registers (five study centers) or through other sources, such as hospitalized patients (three centers), general practitioners' practices (one center), or relatives or friends of cases (one center). Toenail chromium concentration was assessed by neutron activation analysis. Average toenail chromium concentrations were 1.10 ¿g/g in cases (95% confidence interval: 1.01, 1.18) and 1.30 ¿g/g in controls (95% CI: 1.21, 1.40). Multivariate odds ratios for quintiles 2-5 were 0.82 (95% CI: 0.52, 1.31), 0.68 (95% CI: 0.43, 1.08), 0.60 (95% CI: 0.37, 0.97), and 0.59 (95% CI: 0.37, 0.95). Toenail chromium concentration was inversely associated with the risk of a first myocardial infarction in men. These results add to an increasing body of evidence that points to the importance of chromium for cardiovascular health
Effects of Nitrogen fertilisation and regrowth period on fatty acid concentrations in perennial ryegrass (Lolium perenne L.)
Elgersma, A. ; Maudet, P. ; Witkowska, I.M. ; Wever, A.C. - \ 2005
Annals of Applied Biology 147 (2005)2. - ISSN 0003-4746 - p. 145 - 152.
conjugated linoleic-acid - reduces cancer-risk - cutting date - fresh grass - dairy-cows - dietary - digestibility - performance - cultivars - interval
Information on lipids in forages is scarce, and effects of nitrogen (N) application level and regrowth period on the fatty acid (FA) concentration and composition of perennial ryegrass (Lolium perenne L.) were studied. N was applied at 0, 45 and 100 kg ha1, and swards were cut after various regrowth periods, resulting in six treatments designed as randomised blocks with three replicates. The stages of development ranged from vegetative to elongating swards, with herbage yield levels from 1.9 to 4.2 t dry matter (DM) ha1. Concentrations of individual FA were determined by gas chromatography, and canopy characteristics and herbage quality were assessed. The treatments resulted in canopies with contrasting DM yields and protein concentrations. Five FAs, representing 98% of total FAs, were studied in detail. On an average, the concentration of these major FAs in fresh grass was 15.1 g kg1 DM, and 69% of the major FAs consisted of C18:3. Regrowth period affected (P <0.05) the total FA concentration, and significantly (P <0.01) lower concentrations of C18:3 and C16:1 were found after a longer period of regrowth. N application resulted in higher (P <0.001) concentrations of all FAs. The FA composition was not affected by N application, but a longer regrowth period significantly (P <0.001) decreased the proportion of C18:3 and increased those of C18:2 and C16:0. A strong, positive overall linear relation was found between the concentrations of total FAs and C18:3 with the crude protein concentration in the herbage. These studies demonstrate opportunities to affect the FA concentration and composition of FA in herbage through management strategies, which could affect milk FA composition.
Effect of Homocysteine-Lowering Nutrients on Blood Lipids: Result from Four Randomised, Placebo-Controlled Studies in Healthy Humans
Olthof, M.R. ; Vliet, T. van; Verhoef, P. ; Zock, P.L. ; Katan, M.B. - \ 2005
PLOS Medicine 2 (2005)5. - ISSN 1549-1676
coronary-heart-disease - density-lipoprotein cholesterol - folic-acid supplementation - plasma homocysteine - myocardial-infarction - s-methyltransferase - controlled-trial - betaine - choline - dietary
Background Betaine (trimethylglycine) lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals are lacking. Such an effect on cholesterol would counteract any favourable effect on homocysteine. We therefore investigated the effect of betaine, of its precursor choline in the form of phosphatidylcholine, and of the classical homocysteine-lowering vitamin folic acid on blood lipid concentrations in healthy humans. Methods and Findings We measured blood lipids in four placebo-controlled, randomised intervention studies that examined the effect of betaine (three studies, n = 151), folic acid (two studies, n = 75), and phosphatidylcholine (one study, n = 26) on plasma homocysteine concentrations. We combined blood lipid data from the individual studies and calculated a weighted mean change in blood lipid concentrations relative to placebo. Betaine supplementation (6 g/d) for 6 wk increased blood LDL cholesterol concentrations by 0.36 mmol/l (95% confidence interval: 0.25¿0.46), and triacylglycerol concentrations by 0.14 mmol/l (0.04¿0.23) relative to placebo. The ratio of total to HDL cholesterol increased by 0.23 (0.14¿0.32). Concentrations of HDL cholesterol were not affected. Doses of betaine lower than 6 g/d also raised LDL cholesterol, but these changes were not statistically significant. Further, the effect of betaine on LDL cholesterol was already evident after 2 wk of intervention. Phosphatidylcholine supplementation (providing approximately 2.6 g/d of choline) for 2 wk increased triacylglycerol concentrations by 0.14 mmol/l (0.06¿0.21), but did not affect cholesterol concentrations. Folic acid supplementation (0.8 mg/d) had no effect on lipid concentrations. Conclusions Betaine supplementation increased blood LDL cholesterol and triacylglycerol concentrations in healthy humans, which agrees with the limited previous data. The adverse effects on blood lipids may undo the potential benefits for cardiovascular health of betaine supplementation through homocysteine lowering. In our study phosphatidylcholine supplementation slightly increased triacylglycerol concentrations in healthy humans. Previous studies of phosphatidylcholine and blood lipids showed no clear effect. Thus the effect of phosphatidylcholine supplementation on blood lipids remains inconclusive, but is probably not large. Folic acid supplementation does not seem to affect blood lipids and therefore remains the preferred treatment for lowering of blood homocysteine concentrations