Pharmacokinetics of alkylresorcinol metabolites in human urine.

Wholegrain cereals are reported to promote beneficial health effects. Wholegrain wheat and rye are almost exclusive sources of alkylresorcinols, and intact alkylresorcinols together with their plasma and urinary metabolites, 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA) and 3,5-dihydroxybenzoic acid (DHBA), have been proposed as biomarkers of the intake of these foods in humans. The pharmacokinetics of alkylresorcinols and their metabolites in plasma have been determined but not that of the urinary metabolites. We aimed to characterise the urinary pharmacokinetics of alkylresorcinol metabolites in humans to evaluate their potential as biomarkers of wholegrain wheat and rye. A group of fifteen volunteers followed a low-alkylresorcinol diet for 2 d before ingesting a single dose of rye bread, containing 100 mg alkylresorcinols. Urine was collected between baseline (0 h) and 25 h after administration. Thereafter alkylresorcinol metabolites were quantified by HPLC with coulometric electrode array detection. Maximum excretion rates were observed at 5-6 h for both metabolites, DHPPA being predominant over DHBA and also possessing a greater area under the curve0-25 h. Total urinary recovery between 0 and 25 h yielded 43 % of ingested alkylresorcinols, and at 25 h significant amounts of metabolites were still retained in the body, suggesting that even a spot urine sample may be sufficient to indicate whether or not wholegrain wheat or rye is a daily dietary component. These results support the use of urinary DHPPA and DHBA as biomarkers of wholegrain wheat and rye and enable new potential for studying the association between wholegrain intake and diseases, even in the absence of dietary data.

Plasma pharmacokinetics of alkylresorcinol metabolites: new candidate biomarkers for whole-grain rye and wheat intake.

BACKGROUND: Alkylresorcinols are phenolic compounds that are present almost exclusively in rye and wheat fiber. Alkylresorcinols are absorbed and thereafter metabolized to 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), which have been detected in human urine and plasma. OBJECTIVE: The objective was to determine the plasma pharmacokinetics of DHBA and DHPPA in human subjects to estimate whether they show potential as biomarkers for whole-grain rye and/or wheat intake. DESIGN: Fifteen human volunteers followed a low-alkylresorcinol diet for 2 d before ingesting a single dose of high-fiber rye bread containing 100 mg alkylresorcinols [corrected]. Plasma samples were collected for 25 h, and the alkylresorcinol metabolites were quantified by HPLC with coulometric electrode array detection. RESULTS: Maximum concentrations were reached at approximately 6 h for both metabolites, although interindividual variation was found. The half-life was significantly (P < 0.0002) longer for DHPPA (16.3 h) than for DHBA (10.1 h). No significant differences were discovered between women and men in the half-life of each metabolite, which, from a pharmacokinetic point of view, is the most important parameter. The area under the curve differed significantly between DHBA and DHPPA (P < 0.0001) and between women and men (P = 0.03 for DHBA and P = 0.01 for DHPPA). However, when corrected for body weight, the difference between sexes was no longer significant. CONCLUSIONS: Our results suggest that DHBA and DHPPA are both good candidate biomarkers for whole-grain rye and/or wheat intake; however, DHPPA is the better indicator because of its longer half-life. This could provide a practical tool when investigating the association between diet and diseases.

Predicting fatal outcome in the early phase of severe acute pancreatitis by using novel prognostic models.

BACKGROUND/AIMS: Survival in acute pancreatitis and particularly in severe acute and necrotizing pancreatitis is a combination of therapy-associated and patient-related factors. There are only few relevant methods for predicting fatal outcome in acute pancreatitis. Scores such as Ranson, Imrie, Blamey, and APACHE II are practical in assessing the severity of the disease, but are not sufficiently validated for predicting fatal outcome among patients with severe acute pancreatitis. The aim of this study was to construct a novel prediction model for predicting fatal outcome in the early phase of severe acute pancreatitis (SAP) and to compare this model with previously reported predictive systems. METHODS: Hospital records of 253 patients with SAP were retrospectively analyzed. 234 patients with adequate data were included to the test set to construct five logistic regression and three artificial neural network (ANN) models. Two models were tested in an independent prospective validation set of 60 consecutive patients with SAP and compared with previously reported predictive systems. RESULTS: The prediction model considered optimal was a logistic model with four variables: age, highest serum creatinine value within 60-72 h from primary admission, need for mechanical ventilation, and chronic health status. In the validation set, the predictive accuracy, determined by the area under the receiver operating characteristic curve value, was 0.862 for the chosen model, 0.847 for the ANN model using eight variables, 0.817 for APACHE II, 0.781 for multiple organ dysfunction score, 0.655 for Ranson, and 0.536 for Imrie scores. CONCLUSIONS: Ranson and Imrie scores are inaccurate indicators of the mortality in SAP. A novel predictive model based on four variables can reach at least the same predictive performance as the APACHE II system with 14 variables.