The duration of enzyme induction in orocaecal transit time measurements

Abstract

Objective: In this study, the duration of enzyme induction provoked by unlabelled lactose ureide (LU) in orocaecal transit time (OCTT) measurements with lactose-[ 13 C]ureide ( 13 C-LU) was evaluated. Design: Experimental study. Setting: University of Rostock, Children's Hospital, Research Laboratory. Subjects: Fifteen healthy adults aged 19-54 years. Intervention: One-half gram of 13 C-LU was administered together with a continental breakfast. After 1 week, the test was repeated after pre-dosing of 5 Â 100 mg LU on the day before the study began. The 13 C-LU ingestion was repeated under identical conditions but without pre-dosing 1 and 3 weeks after pre-dosing. Expired air samples were taken over 14 h. 13 CO 2 -enrichment was measured by isotope ratio mass spectrometry (SerCon, Crewe, UK). The OCTT was calculated from the interval between 13 C-LU administration and the detection of a significant and sustained 13 C-rise of 2 delta over baseline in breath. Results: Without pre-dosing, an OCTT of 419782 min was measured. The pre-dosing resulted in higher 13 C-enrichments and caused a significant OCTT shortening of 311799 min (P ¼ 0.028). One and 3 weeks after pre-dosing, the measured OCTT again increased to 4047124 and 3797103 min, respectively. Conclusions: Pre-dosing with LU before pulse labelling with 13 C-LU led to an induction of enzyme activity and resulted in a definitive estimation of the OCTT when using a threshold of 2 delta over baseline. After 1 and 3 weeks, respectively, the OCTT was no longer significantly different to those without pre-dosing, indicating the disappearance of enzyme induction. Therefore, a pre-dosing with LU on the day before 13 C-LU ingestion is essential for OCTT measurements.

Simultaneous measurement of gastric emptying and gastrocecal transit times in conscious rats using a breath test after ingestion of [1-¹³C] acetic acid and lactose-[¹³C] ureide

“…It has been shown clinically that priming with lactose-ureide is necessary to investigate the orocecal transit time (Wutzke et al, 2007). We also confirmed that a priming dose of lactose-ureide is necessary in the breath testing of rats (Uchida et al, 2009a).…”

The metabolic fate of doubly labelled lactose-[13C, 15N]ureide after pre-dosing with different ureides

“…The increase of the 13 CO 2 -enrichment in the expired air reflected the microbial degradation of DLLU. These observations of an apparently shorter OCTT after pre-dosing with chemically different sugar ureides strongly suggest a preceding induction of the enzyme activity as already claimed earlier when pre-dosing with the same ureide in its unlabelled form (Wutzke et al, 1997;Wutzke and Glasenapp, 2004;Wutzke and Schütt, 2007). Furthermore, it could be demonstrated that pre-dosing with merely 3 Â 120 mg GU as well as the equimolar dosage of 3 Â 200 mg CU is high enough to induce the enzyme activity and to give reliable results.…”

“…The observed CPDR and CPE data were also in the same order of magnitude with the values published earlier (Wutzke and Glasenapp, 2004;Wutzke and Schütt, 2007). In contrast to the measurement of the OCTT along with the mandatory pre-treatment procedure, our findings demonstrate that (except for the GU pre-dosing with a high s.d., presumably caused by an incomplete homogenization of the faeces) neither the urinary nor the faecal total CPE are affected by pre-dosing with both unlabelled ureides ( Table 2).…”

“…In our previous studies, 13 C-LU, glucose-[ 13 C]ureide ( 13 C-GU) and cellobiose-[ 13 C]ureide ( 13 C-CU) were confirmed to yield reliable results when pre-dosing with the analogous unlabelled ureides, lactose ureide (LU), glucose ureide (GU) and cellobiose ureide (CU), respectively (Wutzke et al, 1997;Wutzke and Glasenapp, 2004). Furthermore, it could be demonstrated that the induced enzyme activity is short-lived and no longer exists after 1 week (Wutzke and Schütt, 2007). Therefore, a pre-treatment with LU on the day before 13 C-LU ingestion is essential for OCTT measurements.…”

“…It is commonly assumed that 13 C-GU and the corresponding glucose ureide hydrolase are the key substance and the key enzyme, respectively, of the enzymatic sugar ureide degradation process that is exclusively initiated by C. innocuum in the human caecum (Mohr et al, 1999;Wutzke and Glasenapp, 2004). Our previous studies revealed that the application of 13 C-LU, 13 C-GU and 13 C-CU lead to significantly shorter OCTT data of 419 vs 311 (P ¼ 0.028), 415 vs 287 (P ¼ 0.017) and 401 vs 266 (P ¼ 0.012) min, respectively, when pre-dosing with the respective unlabelled ureides LU, GU and CU (Wutzke and Glasenapp, 2004;Wutzke and Schütt, 2007). Therefore, we concluded that pre-dosing with the analogues substrate in its unlabelled form is essential for OCTT measurements to obtain reliable results.…”