Biomedical subjects

F Stellaard

Publications and source records attributed to F Stellaard.

At least 19 recordsLinked to original sources

PubMed2006

Combined LDI/SAT test to evaluate intestinal lactose digestion and mucosa permeability.

BACKGROUND: Intestinal mucosal damage causes impaired digestive capacity and increased mucosal permeability. Quantification of damage can be used to improve treatment options. Currently, the Lactose Digestion Index (LDI) and the Sugar Absorption Test (SAT) are used for evaluation. The investigation studied whether both tests could be combined to provide a useful multifunctional test and whether measurements in blood (LDI) could be replaced by measurements in urine. MATERIALS AND METHODS: The LDI (25 g 13C-lactose, 0.5 g 2H-glucose), the SAT (5 g lactulose, 1 g L-rhamnose) and the LDI/SAT combination test were performed in seven lactose-digesting and eight lactose-maldigesting adults. Plasma glucose 13C-enrichment was determined by gas-chromatography/combustion/isotope ratio mass-spectrometry (GC/C/IRMS), 2H enrichment determined by gas-chromatography/mass-spectrometry (GC/MS) and urinary sugars by gas-chromatography (GC). RESULTS: The results of the separate LDI test were not different from those of the LDI/SAT in the lactose-digester group (0.82 +/- 0.06 vs. 0.81 +/- 0.09), nor in the lactose-maldigester group (0.36 +/- 0.12 vs. 0.35 +/- 0.06). A significant correlation was found between the 10-h urinary-lactose/lactulose ratio and the LDI (R2 = 0.71, P < 0.01). There were no differences in the lactulose/L-rhamnose ratio between lactose-digesters and lactose-maldigesters using both the SAT and LDI/SAT tests. CONCLUSION: The LDI/SAT test is a reliable method of measuring digestion and permeability simultaneously. The 10-h period urinary lactose/lactulose excretion ratio following lactose consumption reflects lactose digestive capacity.

Adult↗

PubMed2004

Oro-cecal transit time: influence of a subsequent meal.

BACKGROUND: Small intestinal and oro-cecal transit time (OCTT) is determined for clinical diagnostics and research purposes. Experimental protocols used vary with respect to the inclusion of a subsequent meal during the test period. This study was conducted to elucidate whether the ingestion of a subsequent meal during the test period influences the OCTT of the test meal. MATERIALS AND METHODS: The OCTT of a liquid test meal, measured with the lactose-[(13)C]ureide breath test, was compared between four groups of healthy volunteers (n = 36) who consumed the subsequent meal at different time points. Also, the OCTT was determined twice in eight subjects; a subsequent meal was ingested after 180 min (test A) and after 360 min (test B). RESULTS: An apparently meal-related increase in median OCTT was observed. The OCTT of the eight volunteers measured in test A (210; 210-349 median; quartiles) was significantly shorter than that found in test B (345; 300-375 min, P = 0.016). As result of the ingestion of the subsequent meal at 180 min the OCTT was shortened by 90; 64-116 min in 7/8 subjects. CONCLUSION: These data indicate that the ingestion of a subsequent meal affects the OCTT of a liquid test meal. This phenomenon could be explained by the increased intestinal motility in response to a meal, and should be taken into account when designing protocols for measurements of the OCTT and in the interpretation of small intestinal absorption studies.

Adult↗

PubMed2004

Lysine kinetics in preterm infants: the importance of enteral feeding.

INTRODUCTION: Lysine is the first limiting essential amino acid in the diet of newborns. First pass metabolism by the intestine of dietary lysine has a direct effect on systemic availability. We investigated whether first pass lysine metabolism in the intestine is high in preterm infants, particularly at a low enteral intake. PATIENTS AND METHODS: Six preterm infants (birth weight 0.9 (0.1) kg) were studied during two different periods: period A (n = 6): 40% of intake administered enterally, 60% parenterally; lysine intake 92 (6) micromol/(kg x h); and period B (n = 4): 100% enteral feeding; lysine intake 100 (3) micromol/(kg x h). Dual stable isotope tracer techniques were used to assess splanchnic and whole body lysine kinetics. RESULTS: Fractional first pass lysine uptake by the intestine was significantly higher during partial enteral feeding (period A 32 (10)% v period B 18 (7)%; p<0.05). Absolute uptake was not significantly different. Whole body lysine oxidation was significantly decreased during full enteral feeding (period A 44 (9) v period B 17 (3) micromol/(kg x h); p<0.05) so that whole body lysine balance was significantly higher during full enteral feeding (period A 52 (25) v period B 83 (3) micromol/(kg x h); p<0.05). CONCLUSIONS: Fractional first pass lysine uptake was much higher during partial enteral feeding. Preterm infants receiving full enteral feeding have lower whole body lysine oxidation, resulting in a higher net lysine balance, compared with preterm infants receiving partial enteral feeding. Hence parenterally administered lysine is not as effective as dietary lysine in promoting protein deposition in preterm infants.

Dietary Proteins↗

PubMed2003

Lactose intolerance: analysis of underlying factors.

BACKGROUND: We studied the degree of lactose digestion and orocecal transit time (OCTT) as possible causes for the variability of symptoms of lactose intolerance (LI) in a sample of a population with genetically determined low lactase activity. METHODS: Lactose digestion index (LDI) was measured by the recently developed 13C-lactose/2H-glucose test. The OCTT was determined using the breath hydrogen test. Based on a 6-h symptom score (SSC) after a challenge dose of 25 g of lactose the subjects were divided into a tolerant group (T: n= 15; SSC = 0) and an intolerant group (IT: n= 28; SSC 1-40). The intolerant group was subdivided according to the severity of symptoms: group ITa (n = 17; mild symptoms without diarrhoea) and group ITb (n = 11; with diarrhoea). RESULTS: The LDI was lower in the intolerant group (0.34 +/- 0.14) (mean +/- SD) than in the tolerant group (0.47 +/- 0.14) (P = 0.008). The OCTT of group IT (60, 30-90 min) (median, quartiles) was significantly shorter than that of group T (105, 60-120 min) (P = 0.003) and was positively correlated with the LDI (P = 0.050). In groups ITa and ITb the OCTT (60, 30-90 min; 60, 26-83 min) and LDI (0.30 +/- 0.14; 0.39 +/- 0.14) were similar. CONCLUSIONS: Lactose digestion capacity, which is determined by small intestinal lactase activity as well as by OCTT, affects the occurrence of lactose intolerance. However, the major difference in intolerance symptoms is caused by differences in the colonic processing of maldigested lactose.

Adult↗

PubMed2003

Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil.

BACKGROUND AND AIM: The aim of this study was to unravel the mechanisms responsible for the increased risk of gall stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride lowering therapy by bezafibrate and fish oil on determinants of cholelithiasis (biliary lipid composition and gall bladder motility) in HTG patients. PATIENTS AND METHODS: Gall bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between nine HTG patients and 10 age, sex, and body mass index matched normolipidaemic controls. The effects of bezafibrate and fish oil in HTG patients were studied in a randomised cross over trial. RESULTS: HTG patients showed 14-fold higher serum triglyceride (TG) levels than controls. Biliary lipid composition, fasting gall bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p<0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68% and -51% v baseline, respectively; both p<0.01). Fasting CCK levels were not affected whereas CCK induced gall bladder emptying increased during bezafibrate (+29%; p<0.001) and tended to increase on fish oil therapy (+13%; p=0.07). Postprandial gall bladder motility improved on bezafibrate and fish oil (+47 and +25% v baseline, respectively; both p<0.02) at least partly due to increased gall bladder sensitivity to CCK (both p<0.05 v baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p</=0.05) but no effects on cholesterol saturation index were seen with either treatment. CONCLUSIONS: We suggest that impaired gall bladder motility occurs in HTG patients due to decreased sensitivity to CCK, which may add to the enhanced risk of gall stone disease in HTG patients. Triglyceride lowering therapy by both fish oil and bezafibrate improve gall bladder dysmotility without adversely affecting biliary cholesterol saturation.

Analysis of Variance↗

PubMed2003

Dietary carbohydrate deprivation increases 24-hour nitrogen excretion without affecting postabsorptive hepatic or whole body protein metabolism in healthy men.

Because insulin is an important regulator of protein metabolism, we hypothesized that physiological modulation of insulin secretion, by means of extreme variations in dietary carbohydrate content, affects postabsorptive protein metabolism. Therefore, we studied the effects of three isocaloric diets with identical protein content and low-carbohydrate/high-fat (2% and 83% of total energy, respectively), intermediate-carbohydrate/intermediate-fat (44% and 41% of total energy, respectively), and high-carbohydrate/low-fat (85% and 0% of total energy, respectively) content in six healthy men. Whole body protein metabolism was assessed by 24-h urinary nitrogen excretion, postabsorptive leucine kinetics, and fibrinogen and albumin synthesis by infusion of [1-(13)C]leucine and [1-(13)C]valine. The low-carbohydrate/high-fat diet resulted in lower absorptive and postabsorptive plasma insulin concentrations, and higher rates of nitrogen excretion compared with the other two diets: 15.3 +/- 0.9 vs. 12.1 +/- 1.1 (P = 0.03) and 10.8 +/- 0.5 g/24 h (P = 0.005), respectively. Postabsorptive rates of appearance of leucine and of leucine oxidation were not different among the three diets. In addition, dietary carbohydrate content did not affect the synthesis rates of fibrinogen and albumin. In conclusion, eucaloric carbohydrate deprivation increases 24-h nitrogen loss but does not affect postabsorptive protein metabolism at the hepatic and whole body level. By deduction, dietary carbohydrate is required for an optimal regulation of absorptive, rather than postabsorptive, protein metabolism.

Adult↗

PubMed2002

Extracorporal albumin dialysis (MARS) improves cholestasis and normalizes low apo A-I levels in a patient with benign recurrent intrahepatic cholestasis (BRIC).

The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile salt levels, therapy-resistant extreme pruritus and peculiar biochemical abnormalities including low apolipoprotein apo A-I. Previously, symptomatic improvement has been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS). We hypothesized that MARS improves cholestasis, induces changes in the bile salt profile and normalizes apo A-I serum levels in BRIC. A 17-year-old-female patient with BRIC experienced an episode of cholestasis lasting for more than 6 months with extreme pruritus and diarrhoea not responding to standard therapy. During a period of five days the patient was treated 3 x 8 h with MARS. The procedures were well tolerated and resulted in reduction of plasma bile salts by 58%. The plasma bile salt profile changed into a more hydrophilic composition after MARS. Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a subjective scale. These effects lasted 4 months until a relapse occurred. Low plasma apo A-I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures were well tolerated. Fatigue was noted as the only transient side-effect. In conclusion, MARS may induce a long-term symptomatic improvement and decrease of cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of MARS in patients with BRIC are needed.

Adolescent↗

PubMed2001

The 13C/2H-glucose test for determination of small intestinal lactase activity.

To diagnose hypolactasia, determination of lactase enzyme activity in small intestinal biopsy material is considered to be the golden standard. Because of its strongly invasive character and the sampling problems, alternative methods have been looked for. We analysed the 13C-glucose response in serum after consumption of 25 g of naturally enriched 13C-lactose. As an internal standard, 0.5 g of 2H-glucose was added and the 2H-glucose response in serum was measured simultaneously. The studies were performed in healthy volunteers with a background of genetically determined lactase nonpersistence (n = 12; low lactase activity) and lactase persistence (n = 27; high lactase activity). The results were compared with those of the lactose hydrogen breath test, the lactose 13CO2 breath test and the previously described 13C-lactose digestion test. After consumption of 13C-lactose and 2H-glucose, the mean ratio 13C-glucose/2H-glucose concentration in serum at 45-75 min was 0.26 +/- 0.09 in the low lactase activity group and 0.93 +/- 0.17 in the high lactase activity group (P < 0.01). Threshold of the ratio between digesters and maldigesters was calculated as 0.46. Accuracy of the new test was superior to all other tests. We conclude that the 13C/2H-glucose test has the potential of determining the small intestinal lactase activity in vivo and of estimating the amount of lactose which is digested in the small intestine.

Adult↗

PubMed2001

Postprandial chylomicron clearance rate in late teenagers with diabetes mellitus type 1.

A delayed chylomicron (CM) clearance rate, a known risk factor for atherosclerosis, has been described in adults with diabetes type 1 (DM1). We determined the CM clearance rate in late teenagers with DM1, and the relationship between CM clearance rate and elevated plasma lipid concentrations in DM1 teenagers in poor metabolic control (as characterized by HbA(1c) percentage). Plasma lipids and CM clearance were determined in nine patients with DM1 (mean age +/- SD: 17.5 +/- 0.6 y) and four healthy controls (mean age +/- SD: 20.1 +/- 0.8 y), by measuring breath (13)CO(2), plasma triglyceride, retinyl palmitate, and (13)C-labeled oleic acid concentrations, after oral administration of a fat-rich meal together with vitamin A and (13)C-oleic acid. In patients with DM1, fasting triglyceride and cholesterol concentrations were positively correlated with HbA(1c) percentage (p < 0.05). Neither in DM1 patients, nor in controls, was an elevated triglyceride concentration (above 1.7 mmol/L) found. Yet, in 22% of DM1 patients, cholesterol concentration was above 5.2 mmol/L, but not in any of the controls. CM clearance rate in DM1 patients was similar to that in controls and did not significantly correlate with HbA(1c) percentage. Fasting lipid concentrations in DM1 patients were not significantly correlated with CM clearance rate. Present data indicate that elevated lipid concentrations in late teenagers with DM1 are not attributable to a delay in CM clearance rate. A delayed CM clearance rate at late teenager age is not a risk factor contributing to the increased risk for atherosclerosis in DM1.

Adolescent↗

PubMed2001

Measurement of parameters of cholic acid kinetics in plasma using a microscale stable isotope dilution technique: application to rodents and humans.

A stable isotope dilution method is described that allows measurement of cholic acid (CA) kinetics, that is, pool size, fractional turnover rate (FTR), and synthesis rate in mice, rats, and humans. Decay of administered [2,2,4,4-2H4]CA enrichment was measured in time in 50-microl plasma samples by gas-liquid chromatography/electron capture negative chemical ionization-mass spectrometry, applying the pentafluorobenzyl-trimethylsilyl derivative. The kinetic data expressed species-dependent differences. The CA pool sizes were 16.8 +/- 2.1, 10.6 +/- 1.2, and 2.4 +/- 0.7 micromol/100 g body weight for mice, rats, and humans, respectively. The FTR values were 0.44 +/- 0.03, 0.88 +/- 0.10, and 0.46 +/- 0.14 per day for mice, rats, and humans. The corresponding synthesis rates were 7.3 +/- 1.6, 9.3 +/- 0.1, and 1.0 +/- 0.2 micromol/100 g body weight per day. The human data agreed well with literature data obtained by conventional isotope dilution techniques. For rats and mice these are the first reported isotope dilution data. The method was validated by confirmation of isotopic equilibrium between biliary CA and plasma CA in the rat. Its applicability was demonstrated by the observation of increased CA FTR and CA synthesis rate in rats fed cholestyramine, which is known to increase fecal bile acid excretion. The presented stable isotope dilution method enables the determination of CA kinetic parameters in small plasma samples. The method can be applied in unanesthetized rodents with an intact enterohepatic circulation and may also be valuable when studying the development of human neonatal bile acid kinetics.

Adult↗

PubMed2000

The contribution of newly synthesized cholesterol to bile salt synthesis in rats quantified by mass isotopomer distribution analysis.

A new stable isotope procedure has been developed and validated in rats, applying [1-(13)C]acetate infusion to quantify the production of bile salts from de novo synthesized cholesterol making use of the mass isotopomer distribution analysis (MIDA) principle. Ions (m/z) 458-461, 370-373 and 285-288 were monitored by GC/MS (EI-mode) for the methyl trimethylsilylether derivatives of cholate, chenodeoxycholate and beta-muricholate, respectively. Rats with intact exteriorized enterohepatic circulation and rats with chronic bile diversion were infused with [1-(13)C]acetate for up to 14 h. After 10 h of infusion the enterohepatic circulation of the intact group was interrupted to deplete the existing bile salt pool (acute bile diversion). The fractions of biliary cholesterol and individual bile salts derived from newly synthesized cholesterol were determined by MIDA at t=14 h. In rats with acute bile diversion, these fractions were 20, 25, 27 and 23% for biliary cholesterol, cholate, chenodeoxycholate and beta-muricholate, respectively. After bile diversion for 8 days to induce hepatic cholesterol and bile salt synthesis, these fractions increased significantly to 32, 47, 41 and 47%, respectively. Calculated enrichments of the acetyl-CoA precursor pools were similar for all bile salts and biliary cholesterol within the two rat groups. However, chronic enterohepatic interruption decreased the acetyl-CoA pool size almost two-fold. We conclude that MIDA is a validated new stable isotope technique for studying the synthetic pathway from acetyl-CoA to bile salts. This technique provides an important new tool for studying bile salt metabolism in humans using stable isotopes.

Animals↗

PubMed2000

Lactose (mal)digestion evaluated by the 13C-lactose digestion test.

BACKGROUND: The prevalence of genetically determined lactase nonpersistence is based on the results of the lactose H2 breath test. This test, however, is an indirect test, which might lead to misinterpretation. DESIGN: We determined lactase activity in healthy Chinese and Dutch students using a novel 13C-lactose digestion test. The cut-off value of this test was established in a Chinese population with a homogenous genetic background of lactase nonpersistence and was compared with the results obtained in a Caucasian population. Twenty-five grams of a 13C-lactose solution was consumed by 12 known H2-positive and 5 H2-negative Chinese students and 48 Dutch students and, subsequently, 13C-glucose concentration in plasma and H2 excretion in breath were measured. RESULTS: A similar 13C-glucose response curve was found in all Chinese students. The mean response curve in the Dutch students was more pronounced (P < 0.01). The 1 h (peak) plasma 13C-glucose concentration was the best discriminator between lactose digesting and maldigesting subjects. The cut-off level of 2 mmol L-1 13C-glucose in plasma was defined in the H2-positive Chinese students group. Based on the 13C-glucose response the prevalence of lactose maldigestion in the Dutch subjects was 25%; based on the lactose H2 breath test 17%. CONCLUSIONS: Using the 13C-lactose digestion test the results demonstrate a higher prevalence of lactose maldigestion in a Caucasian population than indicated by the results of the H2 breath test. A moderate increase in the plasma 13C-glucose concentration after consumption of 13C-lactose in the young adult Chinese subjects indicates a residual lactase activity in that age group, even when a positive H2 breath test result is obtained. These results indicate that the 13C-glucose concentration in plasma more accurately reflects the small intestinal lactose digestion capacity than the lactose H2 breath test.

Adult↗

PubMed2000

13C-carbohydrate breath tests: impact of physical activity on the rate-limiting step in lactose utilization.

BACKGROUND: 13CO2 breath tests can be used to monitor carbohydrate digestion in the small intestine. However, after ingestion of 13C-substrates, 13CO2 excretion in breath originates from two sources: a digestive/oxidative fraction, derived from the small intestine, and a fermentation fraction, derived from undigested substrate spill-over in the colon. In this study, the determinants of the digestive/oxidative fraction were analysed in order to improve the sensitivity/specificity of the 13C-carbohydrate breath tests. METHODS: 13C-carbohydrate breath tests were performed in healthy adults using 13C-lactose, pre-digested 13C-lactose, 13C-glucose, and 13C-galactose as substrates. The effect of exercise (bicycling, 50 W), increasing the metabolism of digested/absorbed substrate, on the outcome of the test was analysed. RESULTS: In rest, no difference was observed in the 4-h cumulative percentage dose recovered in breath (4-h cPDR) after administration of glucose, pre-digested lactose, and lactose, which were 20.3 +/- 4.5%, 19.2 +/- 5.5%, and 19.9 +/- 4.9%, respectively. The 13CO2 excretion rate after 13C-galactose consumption was significantly slower than after 13C-glucose consumption. Exercise increased 4-h cPDR of 13C-glucose significantly: 76.0 +/- 1.0% vs. 22.7 +/- 2.3%. This effect was also observed using 13C-lactose as substrate: 66.1 +/- 6.2% vs. 19.6 +/- 3.9%. One subject had non-symptomatic lactose maldigestion indicated by a positive H2 breath test. The 13CO2 breath test of this subject in rest was indistinguishable from that of the others (4-h cPDR 16.6 vs. 19.6 +/- 3.9%), whereas the test was clearly indicative during exercise (4-h cPDR 20.5 vs. 66.1 +/- 6.2%). CONCLUSION: In healthy volunteers in rest, glucose oxidation is the rate-limiting step in lactose conversion into 13CO2. Increase of metabolism (for instance, by exercise) can shift this step to intestinal hydrolysis of lactose, making the 13C-lactose breath test more sensitive.

Adult↗

PubMed2000

Variations in colonic H2 and CO2 production as a cause of inadequate diagnosis of carbohydrate maldigestion in breath tests.

BACKGROUND: Lactose maldigestion is usually diagnosed by means of the H2 breath test. When 13C-lactose is used as substrate, a 13CO2 breath test can be performed simultaneously. In an earlier publication we described the relation between both the H2 and 13CO2 exhalation in breath and the measured intestinal lactase activity after consumption of 13C-lactose. We found a discrepancy between both breath test results in 36% of the cases. To investigate the possible cause of these incongruous breath test results, we studied gas production from carbohydrate in the colon, using 13C-lactulose as a non-absorbable substrate. METHODS: Experiments were performed in 21 subjects, by applying 5 different doses of 13C-lactulose. Repeatability studies were performed in six of these subjects, using 10 g substrate (three tests with 1-week intervals). RESULTS: Both the H2 and the 13CO2 excretion in breath varied strongly interindividually and intraindividually after consumption of 13C-lactulose. In both cases no dose-response relation was observed. A significant positive linear relationship was found between H2 and 13CO exhalation (r = 0.45, P < 0.005). Extrapolation of these results to 13C-lactose breath tests indicates that the colonic contribution of 13CO2 production to the total 13CO2 excretion in breath varies but is on the average large enough to cause false-negative 13CO2 breath test results. CONCLUSIONS: Excretion in breath of 13CO2 produced in the colon during a 13C-lactulose breath test correlates with the breath H2 excretion. This could explain the occurrence of false-negative 13CO2 lactose breath tests when colonic gas production is high and false-negative lactose H2 breath test results when gas production is low. It can also explain the improved sensitivity of the combined H2/13CO2 lactose breath test compared with both breath tests alone.

Adult↗

PubMed2000

Detection of impaired intestinal absorption of long-chain fatty acids: validation studies of a novel test in a rat model of fat malabsorption.

BACKGROUND: Classic fat balance studies detect fat malabsorption but do not discriminate between the potential causes of malabsorption, such as impaired intestinal lipolysis or reduced uptake of fatty acids. OBJECTIVE: We aimed to validate a novel test for the specific, sensitive detection of impaired intestinal uptake of long-chain unesterified fatty acids in an appropriate rat model of fat malabsorption. DESIGN: The absorption and appearance in plasma of [(13)C]palmitic acid were determined in control rats and in rats with fat malabsorption due either to chronic bile deficiency (permanent bile diversion) or to oral administration of the lipase inhibitor orlistat (200 mg/kg diet). [(13)C]Palmitic acid results were compared with the percentage absorption of ingested dietary fat determined by fat balance. RESULTS: Between 1 and 6 h after intraduodenal administration, plasma [(13)C]palmitate concentrations in control rats were 4-10-fold higher than in bile-deficient rats (P < 0.05) but were not significantly different between orlistat-supplemented rats and their controls. In control and bile-deficient rats, plasma [(13)C]palmitate concentrations allowed complete discrimination between normal (>92%) and reduced (<92%) fat absorption, whereas the percentage absorption of [(13)C]palmitate over 48 h appeared to be highly correlated with the percentage absorption of ingested dietary fat (r = 0.89, P < 0.001). CONCLUSIONS: The [(13)C]palmitic acid absorption test detects impaired intestinal absorption of long-chain fatty acids selectively and sensitively in a rat model of fat malabsorption due to bile deficiency. Our data strongly support the use of the [(13)C]palmitic acid absorption test for the diagnosis of clinical fat malabsorption syndromes.

Animals↗

PubMed2000

Digestion of so-called resistant starch sources in the human small intestine.

BACKGROUND: Resistant starch sources, which are only partially digested in the small intestine, can be used to increase colonic availability of short-chain fatty acids. OBJECTIVE: To study the characteristics of the fermentation of resistant starch, the digestion of resistant starch in the small intestine has to be quantified. We compared the metabolic fates of highly digestible cornstarch (DCS), Hylon VII (type 2 resistant starch), and Novelose 330 (type 3 resistant starch), which are of corn origin and, therefore, naturally enriched in (13)C. DESIGN: After administration of 40 g starch or glucose to 7 healthy volunteers, glucose and exogenous glucose concentrations in serum and (13)CO(2) excretion in breath were analyzed for 6 h. (13)C abundance in carbon dioxide was analyzed by isotope ratio mass spectrometry (IRMS) and (13)C abundance in glucose by gas chromatography-combustion IRMS. RESULTS: By comparing the area under the curve (2 h) of exogenous glucose concentration in serum ((13)C glycemic index) after intake of starch or glucose, (13)C glycemic indexes for DCS, Hylon VII, and Novelose 330 were calculated to be 82 +/- 23%, 44 +/- 16%, and 43 +/- 15%, respectively. Comparison of 6-h cumulative percentage dose recovery in breath showed that 119 +/- 28% of DCS, 55 +/- 23% of Hylon VII, and 50 +/- 26% of Novelose 330 was digested in the small intestine. CONCLUSION: The exogenous glucose response in serum and the (13)CO(2) excretion in breath can be used to estimate small intestinal digestion of resistant starch, which amounts to approximately 50%.

Adult↗

PubMed2000

Intestinal absorption and postabsorptive metabolism of linoleic acid in rats with short-term bile duct ligation.

We investigated in bile duct-ligated (BDL) and sham-operated control rats whether the frequent presence of essential fatty acid deficiency in cholestatic liver disease could be related to linoleic acid malabsorption, altered linoleic acid metabolism, or both. In plasma of BDL rats, the triene-to-tetraene ratio, a biochemical marker for essential fatty acid deficiency, was increased compared with controls (0.024 +/- 0.004 vs. 0.013 +/- 0.001; P < 0.05). Net and percentage of dietary linoleic acid absorbed were decreased in BDL rats compared with control rats (1.50 +/- 0.16 mmol/day and 81.3 +/- 3.3% vs. 2.08 +/- 0.07 mmol/day and 99.2 +/- 0.1%, respectively; each P < 0.001). At 24 h after [(13)C]linoleic acid administration, BDL rats had a similar ratio of plasma [(13)C]arachidonic acid to plasma [(13)C]linoleic acid concentration compared with control rats. Delta(6)-Desaturase activity was not significantly different in hepatic microsomes from control or BDL rats. At 3 h after [(13)C]linoleic acid administration, plasma appearance of [(13)C]linoleic acid and cumulative expiration of (13)CO(2) were decreased in BDL rats, compared with controls (by 54% and 80%, respectively). The present data indicate that the impaired linoleic acid status in cholestatic liver disease is mainly due to decreased net absorption and not to quantitative alterations in postabsorptive metabolism.

Animals↗

PubMed2000

Cafestol increases serum cholesterol levels in apolipoprotein E*3-Leiden transgenic mice by suppression of bile acid synthesis.

Cafestol, a diterpene present in unfiltered coffee, potently increases serum cholesterol levels in humans. So far, no suitable animal model has been found to study the biochemical background of this effect. We determined the effect of cafestol on serum cholesterol and triglycerides in different mouse strains and subsequently studied its mechanism of action in apolipoprotein (apo) E*3-Leiden transgenic mice. ApoE*3-Leiden, heterozygous low density lipoprotein-receptor (LDLR+/-) knockout, or wild-type (WT) C57BL/6 mice were fed a high- (0.05% wt/wt) or a low- (0.01% wt/wt) cafestol diet or a placebo diet for 8 weeks. Standardized to energy intake, these amounts are equal to 40, 8, or 0 cups of unfiltered coffee per 10 MJ per day in humans. In apoE*3-Leiden mice, serum cholesterol was statistically significantly increased by 33% on the low- and by 61% on the high-cafestol diet. In LDLR+/- and WT mice, the increases were 20% and 24%, respectively, on the low-cafestol diet and 55% and 46%, respectively, on the high-cafestol diet. These increases were mainly due to a rise in very low density lipoprotein (VLDL) and intermediate density lipoprotein cholesterol in all 3 mouse strains. To investigate the mechanism of this effect, apoE*3-Leiden mice were fed a high-cafestol or a placebo diet for 3 weeks. Cafestol suppressed enzyme activity and mRNA levels of cholesterol 7alpha-hydroxylase by 57% and 58%, respectively. mRNA levels of enzymes involved in the alternate pathway of bile acid synthesis, ie, sterol 27-hydroxylase and oxysterol 7alpha-hydroxylase, were reduced by 32% and 48%, respectively. The total fecal bile acid output was decreased by 41%. Cafestol did not affect hepatic free and esterified cholesterol, but it decreased LDLR mRNA levels by 37%. The VLDL apoB and triglyceride production rates, as measured after Triton injection, were 2-fold decreased by cafestol, indicating that the number of particles secreted had declined and that there was no change in the amount of triglycerides present in the VLDL particle during cafestol treatment. However, the VLDL particles contained a 4-times higher amount of cholesteryl esters, resulting in a net 2-fold increased secretion of cholesteryl esters. The decrease in triglyceride production was the result of a reduction in hepatic triglyceride content by 52%. In conclusion, cafestol increases serum cholesterol levels in apoE*3-Leiden mice by suppression of the major regulatory enzymes in the bile acid synthesis pathways, leading to decreased LDLR mRNA levels and increased secretion of hepatic cholesterol esters. We suggest that suppression of bile acid synthesis may provide an explanation for the cholesterol-raising effect of cafestol in humans.

Animals↗