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The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men.
Kresovich, JK, Bulka, CM, Joyce, BT, Vokonas, PS, Schwartz, J, Baccarelli, AA, Hibler, EA, Hou, L
Biological trace element research. 2018;(1):49-57
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Abstract
Manganese is an essential nutrient that may play a role in the production of inflammatory biomarkers. We examined associations between estimated dietary manganese intake from food/beverages and supplements with circulating biomarkers of inflammation. We further explored whether estimated dietary manganese intake affects DNA methylation of selected genes involved in the production of these biomarkers. We analyzed 1023 repeated measures of estimated dietary manganese intakes and circulating blood inflammatory biomarkers from 633 participants in the Normative Aging Study. Using mixed-effect linear regression models adjusted for covariates, we observed positive linear trends between estimated dietary manganese intakes and three circulating interleukin proteins. Relative to the lowest quartile of estimated intake, concentrations of IL-1β were 46% greater (95% CI - 5, 126), IL-6 52% greater (95% CI - 9, 156). and IL-8 32% greater (95% CI 2, 71) in the highest quartiles of estimated intake. Estimated dietary manganese intake was additionally associated with changes in DNA methylation of inflammatory biomarker-producing genes. Higher estimated intake was associated with higher methylation of NF-κβ member activator NKAP (Q4 vs Q1: β = 3.32, 95% CI - 0.6, 7.3). When stratified by regulatory function, higher manganese intake was associated with higher gene body methylation of NF-κβ member activators NKAP (Q4 vs Q1: β = 10.10, 95% CI - 0.8, 21) and NKAPP1 (Q4 vs Q1: β = 8.14, 95% CI 1.1, 15). While needed at trace amounts for various physiologic functions, our results suggest estimated dietary intakes of manganese at levels slightly above nutritional adequacy contribute to inflammatory biomarker production.
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Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children.
Michelet, R, Dossche, L, De Bruyne, P, Colin, P, Boussery, K, Vande Walle, J, Van Bocxlaer, J, Vermeulen, A
Clinical pharmacokinetics. 2016;(9):1159-70
Abstract
INTRODUCTION Desmopressin is used for treatment of nocturnal enuresis in children. In this study, we investigated the pharmacokinetics of two formulations-a tablet and a lyophilisate-in both fasted and fed children. METHODS Previously published data from two studies (one in 22 children aged 6-16 years, and the other in 25 children aged 6-13 years) were analyzed using population pharmacokinetic modeling. A one-compartment model with first-order absorption was fitted to the data. Covariates were selected using a forward selection procedure. The final model was evaluated, and sensitivity analysis was performed to improve future sampling designs. Simulations were subsequently performed to further explore the relative bioavailability of both formulations and the food effect. RESULTS The final model described the plasma desmopressin concentrations adequately. The formulation and the fed state were included as covariates on the relative bioavailability. The lyophilisate was, on average, 32.1 % more available than the tablet, and fasted children exhibited an average increase in the relative bioavailability of 101 % in comparison with fed children. Body weight was included as a covariate on distribution volume, using a power function with an exponent of 0.402. Simulations suggested that both the formulation and the food effect were clinically relevant. CONCLUSION Bioequivalence data on two formulations of the same drug in adults cannot be readily extrapolated to children. This was the first study in children suggesting that the two desmopressin formulations are not bioequivalent in children at the currently approved dose levels. Furthermore, the effect of food intake was found to be clinically relevant. Sampling times for a future study were suggested. This sampling design should result in more informative data and consequently generate a more robust model.
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Might gluten traces in wheat substitutes pose a risk in patients with celiac disease? A population-based probabilistic approach to risk estimation.
Gibert, A, Kruizinga, AG, Neuhold, S, Houben, GF, Canela, MA, Fasano, A, Catassi, C
The American journal of clinical nutrition. 2013;(1):109-16
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Abstract
BACKGROUND In patients with treated celiac disease (CD), the ingestion of gluten traces contained in gluten-free (GF) wheat substitutes (eg, GF bread, flour, and pasta) could cause persisting intestinal mucosal damage. OBJECTIVE The objective was to evaluate the proportion of CD patients at risk of mucosal damage due to the consumption of GF products in 4 European countries (Italy, Spain, Germany, and Norway). DESIGN A probabilistic modeling approach was used to assess the risk of gluten intake at the population level. The input variables were 1) consumption of GF products, 2) concentration of gluten traces in GF products determined by the sandwich R5 ELISA method, and 3) the gluten threshold for mucosal damage of 10 to 50 mg/d. Different population and product availability scenarios were examined for risk assessment. RESULTS The gluten content of 205 commercially available GF products ranged between <5 and 27.8 mg/kg. Overall, 99.5% of the analyzed samples had a gluten concentration <20 mg/kg. Most (94%) had a gluten concentration below the limit of quantification (5 mg/kg). The mean percentage of the CD European population at risk of mucosal damage resulting from consumption of GF products ranged between 0.01 (Germany) and 0.15 (Italy) and remained very low, even in the worst-case scenario (<1%). CONCLUSIONS The adoption of a single gluten threshold (20 mg/kg) for gluten contamination is suggested. GF products in Europe constitute a very safe option for patients with CD. The dietary follow-up of CD patients should focus on other potential sources of gluten contamination.
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Health, wellbeing and nutritional status of older people living in UK care homes: an exploratory evaluation of changes in food and drink provision.
Kenkmann, A, Price, GM, Bolton, J, Hooper, L
BMC geriatrics. 2010;:28
Abstract
BACKGROUND Food and drink are important determinants of physical and social health in care home residents. This study explored whether a pragmatic methodology including routinely collected data was feasible in UK care homes, to describe the health, wellbeing and nutritional status of care home residents and assess effects of changed provision of food and drink at three care homes on residents' falls (primary outcome), anaemia, weight, dehydration, cognitive status, depression, lipids and satisfaction with food and drink provision. METHODS We measured health, wellbeing and nutritional status of 120 of 213 residents of six care homes in Norfolk, UK. An intervention comprising improved dining atmosphere, greater food choice, extended restaurant hours, and readily available snacks and drinks machines was implemented in three care homes. Three control homes maintained their previous system. Outcomes were assessed in the year before and the year after the changes. RESULTS Use of routinely collected data was partially successful, but loss to follow up and levels of missing data were high, limiting power to identify trends in the data. This was a frail older population (mean age 87, 71% female) with multiple varied health problems. During the first year 60% of residents had one or more falls, 40% a wound care visit, and 40% a urinary tract infection. 45% were on diuretics, 24% antidepressants, and 43% on psychotropic medication. There was a slight increase in falls from year 1 to year 2 in the intervention homes, and a much bigger increase in control homes, leading to a statistically non-significant 24% relative reduction in residents' rate of falls in intervention homes compared with control homes (adjusted rate ratio 0.76, 95% CI 0.57 to 1.02, p = 0.06). CONCLUSIONS Care home residents are frail and experience multiple health risks. This intervention to improve food and drink provision was well received by residents, but effects on health indicators (despite the relative reduction in falls rate) were inconclusive, partly due to problems with routine data collection and loss to follow up. Further research with more homes is needed to understand which, if any, components of the intervention may be successful.