Objective:The lactulose H 2 -breath test is the most widely used non-invasive approach for evaluation of orocoecal transit time (OCTT). In the present study, doubly-labelled lactose-[ 13 C, 15 N]ureide (DLLU) was synthesized to investigate the OCTT in comparison to the conventional lactulose H 2 -breath test. Additionally, the bacterial breakdown rate (BBR) and rate of elimination and the metabolic pathways of the cleavage products of DLLU ( 13 CO 2 , [ 15 N]urea, and 15 NH 3 ) were investigated. Design and subjects: In a first study, DLLU was administered as a single oral-pulse-labelling (dosage: one gram) either without and after pretreatment of five grams of unlabelled lactoseureide (LU) on the day prior to the study to twelve healthy adult volunteers after breakfast. Breath and urine were collected in one and two hourintervals, respectively, over a one-day period. 13 C-enrichment in breath as well as 15 N-enrichment in urine fractions were measured by continuous flow-isotope ratio mass spectrometry (CF-IRMS). In a second study, lactulose was administered to the same subjects (dosage: ten grams). Breath was collected in quarter, half and one hour-intervals over a ten hour-period. Hydrogen concentration in breath was analysed using an electrochemical detector.
Results:The comparison of the lactose-[ 13 C]ureide 13 CO 2 -breath test and the lactulose H 2 -breath test showed that the mean increase of the 13 C-enrichment in CO 2 occurred 1.18 h later than the mean increase of H 2 in breath. The resulting OCTTs derived from the two methods were 3.02 1.7 h (P < 0.01), respectively. The 15 N-enrichment of urinary urea and ammonia without and after pretreatment with LU started between two and three hours after DLLUadministration. The cumulative percentage urinary excretion of the 15 N-and 13 C-tracer was 29.9% and 13.6% respectively, and was slightly increased after LU-pretreatment to 32.1% and 14.6% of the dose administered. A total of 35.2% of the 13 C was found to be exhaled and remained approximately constant after LU-pretreatment (36.2%). Conclusions: The use of the lactulose H 2 -breath test for evaluation of the OCTT showed a statistically significant shortening of 1.18 h in comparison to the lactose-[ 13 C]ureide 13 CO 2 -breath test in healthy adults. The most important limitations of the lactulose H 2 -breath test are its low specificity and sensitivity due to dosedependent accelerations of OCTT, interfering H 2 -rise from malabsorbed dietary fibre and H 2 -non-producers. In contrast, our lactose-[ 13 C]ureide 13 CO 2 -breath test was confirmed to avoid these disadvantages and to yield reliable results. This test is recommended especially if higher sensitivity and specificity is required, if IRMStechnique is available and if lactulose H 2 -tests lead to insufficient results.
IntroductionColoPulse tablets are an innovative development in the field of oral dosage forms characterized by a distal ileum and colon-specific release. Previous studies in humans showed release in the ileo-colonic region, but the relationship between gastrointestinal pH and release was not experimentally proven in vivo. This information will complete the in vivo release-profile of ColoPulse tablets.Materials and MethodsRelease from ColoPulse tablets was studied in 16 healthy volunteers using the dual label isotope strategy. To determine gastrointestinal pH profiles and transit times the IntelliCap system was used. A ColoPulse tablet containing 13C-urea and an uncoated, immediate release tablet containing 15N2-urea were taken simultaneously followed by a standardized breakfast after three hours. Five minutes after intake of the tablets the IntelliCap capsule was swallowed and pH was measured until excretion in the feces. Breath and urine samples were collected for isotope analysis.ResultsFull analysis could be performed in 12 subjects. Median bioavailability of 13C -urea was 82% (95% CI 74–94%, range 61–114%). The median lag time (5% release of 13C) was 5:42 h (95% CI 5:18–6:18 h, range 2:36–6:36 h,) There was no statistically significant difference between lag time based on isotope signal and colon arrival time (CAT) based on pH (median 5:42 vs 5:31 h p = 0.903). In all subjects an intestinal pH value of 7.0 was reached before release of 13C from the ColoPulse tablet occurred.Discussion and ConclusionsFrom the combined data from the IntelliCap system and the 13C -isotope signal it can be concluded that release from a ColoPulse tablet in vivo is not related to transit times but occurs in the ileo-colonic region after pH 7.0 is reached. This supports our earlier findings and confirms that the ColoPulse system is a promising delivery system for targeting the distal ileum and colon.Trial RegistrationISRCTN Registry 18301880
Tryptophan (TRP) is the limiting amino acid in low-protein infant formulas. This is mainly due to lower alpha-lactalbumin (alpha LA) content in cow's milk whey as compared with human milk protein. To study the effect of alpha LA-enrichment on the TRP supply, cross-over studies were carried out in 20 healthy infants up to 3 months of age. In this study, two protein-reduced (1.3%) infant formulas (moderate TRP content of 1.88% and higher TRP content of 2.10%) were alternately fed over a 2 week period in two groups of infants. Serum TRP levels of the formula-fed infants with the higher TRP content did not differ significantly from an exclusively breastfed control group of 11 infants (10.5 +/- 4.8 versus 10.9 +/- 4.7 mg l-1, p = 0.841), whereas levels of the formula-fed infants with the moderate TRP content were significantly lower (7.4 +/- 3.9, p = 0.038). The supplementation of alpha LA resulting in a higher TRP supply to low-protein diets is a further step towards the production of infant formulas more closely adapted to human breast milk.
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