How is small bowel permeability in endometriosis patients? a case control pilot study.

Endometriosis is a chronic inflammatory disease of women of reproductive age. Small bowel (SB) permeability and lipopolysaccharides (LPS) could play a role in the perduration of low grade inflammation status and the pathogenesis of endometriosis. To clarify this hypothesis, we measured SB permeability through plasma values of LPS and urinary secretion of lactulose (La), mannitol (Ma) and their ratio (L/M) in patients with endometriosis compared with healthy controls (HC). Eight patients and 14 HC entered the study. SB permeability was evaluated by high-performance liquid chromatography of urine concentrations of La and Ma. Plasma levels of LPS were measured in the blood. Moreover, a nutritional, gastroenterological, quality of life evaluation was performed through validates questionnaires and complete gynaecological evaluations. The statistical analysis of the obtained data did not show differences in anthropometric and nutritional characteristics and gastrointestinal functional disease in the two groups. Patients reported higher levels of pelvic chronic pain (3.87 ± 2.99 vs 0.15 ± 0.55; pe = 0.001) and significantly higher LPS plasma levels (0.529 ± 0.11 vs 0.427 ± 0.08; p value = .027) than HC. Our results indicate that intestinal permeability is abnormal in endometriosis patients, and it might play a role in the pathogenesis of this chronic disease.

[Physiological effects, mechanisms of action and application of lactulose].

The discovery of lactulose as a bifidogenic factor became the background for the appearance of the prebiotics concept. Currently, lactulose is the most studied in terms of medical use oligosaccharide with a high prebiotic index. The exact mechanisms of action of lactulose remain largely unknown despite a number of new researches based on modern methods of molecular biology, genetics, and bioinformatics. The aim of this review to summarize and analyze the actual information about biological activity, probable mechanisms of action, and possible uses of lactulose in human nutrition. Results. The structure of lactulose, methods for its determination and preparation are briefly described. Promising methods for producing lactulose include enzymatic synthesis from lactose using ß-galactosidase or epimerase. Information on the physiological effects of lactulose and the mechanisms of its action on the human organism is presented. The works confirming the ability of lactulose to stimulate the growth of bifidobacteria and to influence the metabolism of the intestinal microbiota are summarized. The results of studies of the ability of lactulose to have antitoxic and anticarcinogenic effects are presented. The mechanisms of the positive effect of the prebiotic on the absorption of minerals, increased absorption of Ca and Mg in the human organism are described. The effect of lactulose on immunity and the possibility of its use to reduce the glucose blood level in patients with type 2 diabetes mellitus are shown. The main directions of the use of lactulose in food production are systematized. The data confirming the possibility of using lactulose as a growth factor for probiotics, as well as a protective agent to increase the survival of some starter cultures, are presented. Brief information on the doses and forms of lactulose apply in medicine is presented. The dependence of the effects of lactulose on the dose, health condition and age of patients has been established. Conclusion. Perspective directions of lactulose using in combination with probiotics, other prebiotics, and as an encapsulating ingredient for vitamins and other functional nutrition ingredients are determined. In this regard, the study of lactulose interaction with the components of complex products is relevant.

Additional Common Bean in the Diet of Malawian Children Does Not Affect Linear Growth, but Reduces Intestinal Permeability.

Background: Chronic malnutrition, as manifested by linear growth faltering, is pervasive among rural African children. Improvements in complementary feeding may decrease the burden of environmental enteric dysfunction (EED) and thus improve growth in children during the critical first 1000 d of development. Objective: We tested the hypothesis that systematically including common bean or cowpea into complementary feeding would reduce EED and growth faltering among children in rural Malawi. Methods: This was a double-blind clinical trial in which children 12-23 mo of age were randomly assigned to receive complementary feeding with 1 of 3 foods: roasted cowpea or common bean flour, or an isoenergetic amount of corn-soy blend as a control food for 48 wk. Children aged 12-23 mo received 155 kcal/d and thereafter until 35 mo received 200 kcal/d. The primary outcomes were change in length-for-age z score (LAZ) and improvements in a biomarker of EED, the percentage of lactulose (%L) excreted as part of the lactulose:mannitol dual-sugar absorption test. Anthropometric measurements and urinary %L excretion were compared between the 2 intervention groups and the control group separately with the use of linear mixed model analyses for repeated measures. Results: A total of 331 children completed the clinical trial. Compliance with the study interventions was excellent, with >90% of the intervention flour consumed as intended. No significant effects on LAZ, change in LAZ, or weight-for-length z score were observed due to either intervention legume, compared to the control. %L was reduced with common bean consumption (effect estimate was -0.07 percentage points of lactulose, P = 0.0007). The lactulose:mannitol test was not affected by the legume intervention. Conclusion: The addition of common bean to complementary feeding of rural Malawian children during the second year of life led to an improvement in a biomarker of gut health, although this did not directly translate into improved linear growth. This trial was registered at clinicaltrials.gov as NCT02472301.

Randomized Clinical Trial of Preoperative Feeding to Evaluate Intestinal Barrier Function in Neonates Requiring Cardiac Surgery.

OBJECTIVES: To evaluate intestinal barrier function in neonates undergoing cardiac surgery using lactulose/mannitol (L/M) ratio measurements, and to determine correlations with early breast milk feeding. STUDY DESIGN: This was a single-center, prospective, randomized pilot study of 27 term-born neonates (≥ 37 weeks gestation) requiring cardiac surgery who were randomized to 1 of 2 preoperative feeding groups: nil per os (NPO) or trophic (10 mL/kg/day) breast milk feeds. At 3 time points (preoperative [preop], postoperative [postop] day 7, and postop day 14), subjects were administered an oral L/M solution, after which urine L/M ratios were measured using gas chromatography, with higher ratios indicative of increased intestinal permeability. Trends over time in the mean urine L/M ratios for each group were estimated using a general linear mixed model. RESULTS: There were no adverse events related to preoperative trophic feeding. In the NPO group (n = 13), the mean urine L/M ratio was 0.06 at preop, 0.12 at postop day 7, and 0.17 at postop day 14. In the trophic breast milk feeds group (n = 14), the mean urine L/M ratio was 0.09 at preop, 0.19 at postop day 7, and 0.15 at postop day 14. In both groups, L/M ratios were significantly higher at postop day 7 and postop day 14 compared with preop (P < .05). CONCLUSION: Neonates have increased intestinal permeability after cardiac surgery extending to at least postop day 14. This pilot study was not powered to detect differences in benefit or adverse events comparing the NPO and trophic breast milk feeds groups. Further studies to identify mechanisms of intestinal injury and therapeutic interventions are warranted. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT01475357.

Differential trafficking of saccharidic probes following aspirin in clinical tests of intestinal permeability in young healthy women.

The effects of inflammatory changes on the absorption of different-sized probes and their permeability ratios are poorly understood. The aim of the present study was to determine the effects of a pharmacological agent on the permeability of the gut mucosa to saccharidic probes of larger and smaller molecular weight. Permeability was assessed by half-hourly urinary excretion of a combined dose of d-mannitol, l-rhamnose and lactulose following consumption of a single 600 mg dose of aspirin and compared with a placebo in a cross-over study in 20 healthy female volunteers. The temporal patterns of excretion of all probes were bimodal, being best fitted by polynomial functions. The relatively small early peak was evident for at least 4 h for smaller sugars, but was less evident with lactulose, being overshadowed by a larger second peak. These conclusions were further supported by separate analyses of the segments of the temporal plots between 2.5 and 4 h and between 4.5 and 6 h. The forms of these curves did not change significantly following dosing with aspirin. A greater proportion of the total dose of mannitol than rhamnose was excreted over the collection period. Following the consumption of aspirin, the cumulative rate of excretion of the smaller sugars (i.e. mannitol and rhamnose) was significantly reduced whereas that of lactulose was increased over the 6 h collection period. Aspirin has opposite effects on the absorption of larger and smaller probes, influencing the outcome of the test. These results have important consequences for the design and comparison of clinical tests of permeability.

Meta-analysis of oro-cecal transit time in fasting subjects.

PURPOSE: Computer simulations are utilized during pharmaceutical development in order to design appropriate formulation based on the absorption, distribution, metabolism, and excretion (ADME) and physicochemical properties of target compounds, so that adequate prescriptions are offered to patients. Oro-cecal transit time (OCTT) is an important factor affecting these simulations because the absorption of drug that administered orally and the resultant pharmacokinetic profile are expressed as a function of time. Given the large intra- and inter-individual variance in OCTT, it is unsurprising that an accurate model has not yet been proposed. METHODS: We conducted a meta-analysis using subject-level data to construct a statistical model that predicted OCTT. Literature that utilized lactulose to measure OCTT was identified and analyzed using a mixed-effects model. RESULTS: The OCTTs of fasting healthy subjects were expressed using a linear model, with the amount of lactulose as the single significant explanatory factor. We found that this model could statistically distinguish the OCTTs of subjects with altered physical status from those of healthy people. Specifically, cystic fibrosis and celiac disease most significantly affected OCTT. CONCLUSION: The OCTT models developed herein incorporate inter-subject variations and can contribute to providing more accurate predictions of drug pharmacokinetic profiles.

Semiquantitative assessment of breath hydrogen testing.

BACKGROUND AND AIM: A major use of breath hydrogen testing is to assess absorptive capacity for sugars to assist dietary design for management of gut symptoms. Qualitative reporting takes no account of the vigor of hydrogen response and provides little insight into degrees of malabsorption. This study aimed to describe a semiquantitative reporting method and to compare results with those reported qualitatively. METHODS: In consecutive Caucasian patients with Crohn's disease (n = 87), ulcerative colitis (59), functional gastrointestinal disorders (FGID) (162), and healthy controls (76), area under the curve was calculated for lactulose (15 g). This was compared with that for lactose (50 g) and fructose (35 g). Degree of malabsorption was categorized into arbitrary groups. RESULTS: Semiquantitative results for ≥ 30% (designated "convincing") malabsorption was most similar to those using a qualitative cutoff value of 20 ppm, but in 38% and 21% of patients, the classification of malabsorption (nil or clinically significant) changed for fructose and lactose, respectively. Using a cutoff of 10 ppm, 49% and 5% were classified differently. Crohn's disease had a higher prevalence (42%) of convincing fructose malabsorption than controls (24%) or patients with FGID (33%) (P < 0.02). Highest prevalence of convincing lactose malabsorption (38%) was in ulcerative colitis, greater than controls (18%) and FGID (18%) (P < 0.02). CONCLUSIONS: Semiquantitative assessment provides different results with different clinical implications in more than one third of patients, but disease-related alterations in prevalence are similar to those defined qualitatively. This method may be preferable because it lessens the confounding influence of the vigor of the hydrogen response.

Correlation of lactulose-to-mannitol ratios in plasma and urine for intestinal permeability assessment in pigs.

OBJECTIVE: The lactulose-to-mannitol ratio test is a test to assess the disorders associated with gut permeability. The test requires an oral administration of the mixture of lactulose and mannitol and urine collection. The urinary ratio of lactulose to mannitol is an indicator of intestinal permeability. Due to the complexity of urine collection in animal studies, plasma exposure ratios of lactulose to mannitol compared to their urinary concentration ratios were evaluated following an oral administration of the sugar mixture in pigs. ANIMALS: 10 pigs were orally dosed with a solution of lactulose and mannitol mixture. PROCEDURES: Plasma samples were collected at predose, 10 and 30 minutes and 2, 4, and 6 hours postdosing, and cumulated urinary samples were collected at 6 hours for liquid chromatography-mass spectrometry analysis. The ratios of pharmacokinetic parameters of lactulose to mannitol and the plasma sugar ratios at a single time point or the mean values of several time points were compared to their urinary sugar ratios. RESULTS: The results revealed that the lactulose-to-mannitol ratios of AUC0-6h, AUCextrap, and Cmax were correlated to the urinary sugar ratios, and the plasma sugar ratios of a single time point at 2, 4, or 6 hours and the mean values of those time points were also appropriate to replace their urinary ratios in pigs. CLINICAL RELEVANCE: Following an oral administration of lactulose and mannitol mixture, blood collection, and assay can be an option for assessing intestinal permeability, especially in animal studies.

Assessment of intestinal permeability using sugar probes: influence of urinary volume.

BACKGROUND: As the accuracy of the "Sugar Test" is currently debated, this study was conducted to focus on how urine volumes may impact the test results. METHODS: Fifty-five subjects, 23 healthy and 32 with Irritable Bowel Syndrome (IBS), were enrolled. Lactulose and D-mannitol dissolved in water were administered to all the participating subjects; the urine excreted was collected and the total urine volume was measured. The urine samples were analyzed by High Performance Liquid Chromatography (HPLC). The results were expressed as percentage of urine recovery of lactulose and D-mannitol and lactulose/D-mannitol ratio (LMR). RESULTS: All subjects were divided into two groups: subjects with urine volume < 500 mL and subjects with urine volume > or = 500 mL. Urine analysis showed that the mean LMR was significantly lower in subjects with urine volume > or = 500 mL than in subjects with urine volume < 500 mL (0.02 +/- 0.02 vs 0.04 +/- 0.04; p < 0.05). A significant increase in D-mannitol recovery was found to be associated with greater urine volumes (p < 0.001). CONCLUSIONS: The urine volume may influence urinary excretion of sugar probes. Intake of liquids should therefore be carefully monitored before and during the test and the volume of urine produced over the period of collection should be precisely measured.

Effects of timing, sex, and age on site-specific gastrointestinal permeability testing in children and adults.

OBJECTIVES: Measurement of gastrointestinal (GI) permeability is commonly used in research and often used clinically. Despite its utility, little is known about sugar excretion timeframes or the potential effects of age and sex on GI permeability testing. We seek to determine the timeframes of sugar excretion and the potential effects of age and sex on urinary recovery of the sugars. SUBJECTS AND METHODS: Healthy adults (n = 17) and children (n = 15) fasted 4 hours after the evening meal and then ingested a solution of sucrose, lactulose, mannitol, and sucralose. Urine was collected at 30, 60, and 90 minutes after ingestion and then each time the subjects voided during the next 24 hours. Each urine void was collected separately. RESULTS: Median age for the adults was 47.5 years (range 21-57 years) and for children 10 years (range 5-17 years). There were no differences between children and adults in mean percent dose of sugar recovered. The time of peak urinary recovery of the sugars was generally similar between children and adults. Sucrose urinary recovery declined with age (P = 0.008; r2 = 0.19) unrelated to sex. Lactulose and sucralose urinary recovery declined with age in females (P = 0.05, r2 = 0.24 and P = 0.011, r2 = 0.41; respectively) but not in males. CONCLUSIONS: Overall, sugar urinary recovery is comparable in children and adults. Specific sugar urinary recovery may change as a function of age and/or sex. These results need to be taken into account when planning and interpreting gastrointestinal permeability studies.

Does intestinal permeability lead to organ failure in experimental necrotizing enterocolitis?

PURPOSE: The rat gavage model is used to explore the pathogenesis and treatment of necrotizing enterocolitis (NEC). Although intestinal histological damage is seen in this model, intestinal perforation is rarely observed. Whether organ failure occurs in this model is largely unknown. We hypothesised that increased intestinal permeability leads to organ failure in experimental NEC. METHODS: NEC was induced in neonatal rats by gavage feeding of hypertonic formula plus exposure to hypoxia plus oral lipopolysaccharide (4 mg/kg per day daily). Breast-fed rats were used for comparison. At 92 h, lactulose (3 mg) and mannitol (2 mg) were administered orally in 0.1 ml water. Four hours later, rats were killed and blood samples collected. Lactulose and mannitol were measured by gas chromatography-mass spectrometry and lactulose/mannitol ratio calculated as index of intestinal permeability. Plasma cardiac troponin-I was measured by ELISA as a marker of cardiac damage and plasma creatinine measured spectrophotometrically as a marker of renal failure. RESULTS: Experimental NEC induced an increase in intestinal permeability (P = 0.0002). This was associated with cardiac damage (P < 0.0001), and renal failure (P = 0.004). CONCLUSION: Intestinal permeability is increased in experimental NEC in association with increased cardiac damage. Rat mortality may be due to cardiac failure secondary to an inflammatory response caused by increased intestinal permeability.

Measurement of intestinal permeability using lactulose and mannitol with conventional five hours and shortened two hours urine collection by two different methods: HPAE-PAD and LC-MSMS.

Urinary excretion of two orally-administered non-metabolizable sugars, lactulose and mannitol, is a valuable marker for evaluating intestinal permeability. Usually this test involves a time consuming procedure of about 5 hour's urine collection, which makes the test incompatible to some extent. As the results are expressed as the ratio of lactulose and mannitol recovered in urine within certain time, it may be possible to get similar result despite the reduced urine collection time of 2 hours. Moreover, different laboratories do the test by different methods, which make the results incomparable between laboratories. Here, we are also trying to find the correlation between results from most commonly used methods: HPAE-PAD and LC-MSMS. The lactulose: mannitol (LM) test was performed in a cohort of Bangladeshi infants considered at-risk for environmental enteropathy. 208 urine specimens from 104 (52 male and 52 female) infants were collected at 2 and 5 hours after LM solution administration and were tested for lactulose and mannitol by two different methods, one HPAE-PAD platform and another LC-MSMS platform. Median age of the children was 15.0 months (range 6.9 to 25.8 months) and their mean weight-for-age z-score was -0.92. A higher percentage of lactulose and mannitol recovery was found in 5 hours urine collection than in the corresponding 2 hours by both HPAE-PAD and LC-MSMS method, but when results were expressed as lactulose to mannitol ratio (LMR) there was no significant difference between 2 and 5 hours urine collection in both HPAE-PAD (P = 0.138) and LC-MSMS (P = 0.099) method. LMR based on 2 hours urine collection correlated well with LMR based on traditional 5 hours urine collection (Spearman's correlation coefficient 0.578 and 0.604 respectively for HPAE-PAD and LC-MSMS). In future, LM test to assess intestinal permeability in children can be simplified by shortening the urine collection time from 5 hours to 2 hours.

Effects of oral adenosine 5'-triphosphate and adenosine in enteric-coated capsules on indomethacin-induced permeability changes in the human small intestine: a randomized cross-over study.

BACKGROUND: It is well-known that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause damage to the small bowel associated with disruption of mucosal barrier function. In healthy human volunteers, we showed previously that topical administration of adenosine 5'-triphosphate (ATP) by naso-intestinal tube attenuated a rise in small intestinal permeability induced by short-term challenge with the NSAID indomethacin. This finding suggested that ATP may be involved in the preservation of intestinal barrier function. Our current objective was to corroborate the favourable effect of ATP on indomethacin-induced permeability changes in healthy human volunteers when ATP is administered via enteric-coated capsules, which is a more practically feasible mode of administration. Since ATP effects may have been partly mediated through its breakdown to adenosine, effects of encapsulated adenosine were tested also. METHODS: By ingesting a test drink containing 5 g lactulose and 0.5 g L-rhamnose followed by five-hour collection of total urine, small intestinal permeability was assessed in 33 healthy human volunteers by measuring the urinary lactulose/rhamnose excretion ratio. Urinary excretion of lactulose and L-rhamnose was determined by fluorescent detection high-pressure liquid chromatography (HPLC). Basal permeability of the small intestine was assessed as a control condition (no indomethacin, no ATP/adenosine). As a model of increased small intestinal permeability, two dosages of indomethacin were ingested at 10 h (75 mg) and 1 h (50 mg) before ingesting the lactulose/rhamnose test drink. At 1.5 h before indomethacin ingestion, two dosages of placebo, ATP (2 g per dosage) or adenosine (1 g per dosage) were administered via enteric-coated hydroxypropyl methylcellulose (HPMC) capsules with Eudragit L30D-55. RESULTS: Median urinary lactulose/rhamnose excretion ratio (g/g) in the control condition was 0.032 (interquartile range: 0.022-0.044). Compared to the control condition, lactulose/rhamnose ratio after ingestion of indomethacin plus placebo was significantly increased to 0.039 (0.035-0.068); P < 0.01). The indomethacin-induced increase was neither affected by administration of encapsulated ATP (0.047 (0.033-0.065)) nor adenosine (0.050 (0.030-0.067)). Differences in L/R ratios between the conditions with indomethacin plus placebo, ATP or adenosine were not significant. CONCLUSION: In this study, either ATP or adenosine administered via enteric-coated capsules had no effect on indomethacin-induced small intestinal permeability changes in healthy human volunteers. The observed lack of effect of encapsulated ATP/adenosine may have been caused by opening of the enteric-coated supplement at a site distal from the indomethacin-inflicted site. Further studies on site-specific effectiveness of ATP/adenosine on intestinal permeability changes are warranted.

Measurement of intestinal mucosal permeability in dogs with lymphocytic-plasmacytic enteritis.

Lymphocytic-plasmacytic enteritis (LPE) is a type of canine inflammatory bowel disease (IBD). One of its most probable causes is a defect in the mucosal permeability barrier. In the present study, intestinal permeability in LPE dogs was examinated to evaluate its clinical value. Twenty-nine dogs with LPE diagnosed by clinical and histological examinations were included in this study. Intestinal permeability was evaluated by measuring the ratio of the concentrations of two sugars (lactulose (L) and rhamnose (R)) with different molecular weights in urine samples after oral administration of a solution containing them. Biopsy specimens of duodenum were evaluated according to histological criteria. The urinary L:R ratio in the 29 LPE dogs (1.68 +/- 1.17, mean +/- SD) was significantly higher than that in the 10 healthy control dogs (0.75 +/- 0.38, P<0.01). In the LPE dogs, a weak correlation was observed between the histopathological grading score of the duodenum and the urinary L:R ratio (r=0.408, P<0.05). The urinary L:R ratio in the 20 dogs showing hypoalbuminemia (< 2.5 g/dl) was significantly higher than that in the 9 dogs with normal serum albumin levels > 2.5 g/dl (P<0.01). In conclusion, permeability of the intestinal mucosa as determined by the urinary L:R ratio could be a useful laboratory parameter for evaluating intestinal damage in LPE dogs.

Human small intestine is capable of restoring barrier function after short ischemic periods.

AIM: To assess intestinal barrier function during human intestinal ischemia and reperfusion (IR). METHODS: In a human experimental model, 6 cm of jejunum was selectively exposed to 30 min of ischemia (I) followed by 30 and 120 min of reperfusion (R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose (L) and rhamnose (R). Plasma concentrations of citrulline, an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions (TJs), by plasma marker for enterocytes damage (I-FABP) and analyzed by electron microscopy (EM) using lanthanum nitrate as an electrondense marker. RESULTS: Plasma L/R ratio's were significantly increased after 30 min of ischemia (30I) followed by 30 min of reperfusion (30R) compared to control (0.75 ± 0.10 vs 0.20 ± 0.09, P < 0.05). At 120 min of reperfusion (120R), ratio's normalized (0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points (correlation: 0.467, P < 0.01). TJs staining shows distortion of staining at 30I. An intact lining of TJs was again observed at 30I120R. Electron microscopy analysis revealed disrupted TJs after 30I with paracellular leakage of lanthanum nitrate, which restored after 30I120R. Furthermore, citrulline concentrations closely paralleled the histological perturbations during intestinal IR. CONCLUSION: This study directly correlates histological data with intestinal permeability tests, revealing that the human gut has the ability of to withstand short episodes of ischemia, with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.

Endurance Exercise Increases Intestinal Uptake of the Peanut Allergen Ara h 6 after Peanut Consumption in Humans.

Controlled studies on the effect of exercise on intestinal uptake of protein are scarce and underlying mechanisms largely unclear. We studied the uptake of the major allergen Ara h 6 following peanut consumption in an exercise model and compared this with changes in markers of intestinal permeability and integrity. Ten overnight-fasted healthy non-allergic men (n = 4) and women (n = 6) (23 ± 4 years) ingested 100 g of peanuts together with a lactulose/rhamnose (L/R) solution, followed by rest or by 60 min cycling at 70% of their maximal workload. Significantly higher, though variable, levels of Ara h 6 in serum were found during exercise compared to rest (Peak p = 0.03; area under the curve p = 0.006), with individual fold changes ranging from no increase to an increase of over 150-fold in the uptake of Ara h 6. Similarly, uptake of lactulose (2-18 fold change, p = 0.0009) and L/R ratios (0.4-7.9 fold change, p = 0.04) were significantly increased which indicates an increase in intestinal permeability. Intestinal permeability and uptake of Ara h 6 were strongly correlated (r = 0.77, p < 0.0001 for lactulose and Ara h 6). Endurance exercise after consumption may lead to increased paracellular intestinal uptake of food proteins.

Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease.

BACKGROUND: Abnormal barrier function may be genetically determined in Crohn's disease. AIM: To examine the role of abnormal intestinal permeability in genetic predisposition in multiplex vs. sporadic Crohn's disease families. METHODS: Intestinal permeability was measured in patients, relatives and partners by means of lactulose/mannitol test. Healthy subjects from the hospital staff served as controls. CARD15 mutations were investigated in sporadic and familial Crohn's disease patients and in a group of blood donors. RESULTS: The median lactulose/mannitol ratio was increased significantly in Crohn's disease patients vs. their relatives [0.03 (0.01-0.24) vs. 0.01 (0.003-0.19), P=0.005]. The percentage of abnormal tests was significantly higher in familial vs. sporadic first-degree relatives of Crohn's disease patients (29% vs. 11%, P=0.0281). Abnormal permeability occurred significantly more frequent in patients with familial Crohn's disease carrying the frameshift mutation. The frameshift mutation 3020 insC was associated with increased permeability in 75% in the multiplex and in 61% of the sporadic CD patients. One partner had abnormal lactulose/mannitol ratio. Conclusion Intestinal permeability is raised in Crohn's disease patients and relatives, with higher rates in familial vs. sporadic healthy relatives. CARD15 mutations are associated with abnormal permeability in ileal Crohn's disease.

Evaluation of intestinal mucosal permeability function in patients with acute pancreatitis.

This study aims to evaluate the intestinal mucosal permeability in patients with acute pancreatitis. The lactulose:mannitol (L:M) ratio was used to assess permeability. It is an inexpensive and quite reliable method. The intestinal permeability was increased in patients with acute pancreatitis compared with the controls. In addition, patients with severe pancreatitis had higher intestinal barrier dysfunction compared with patients with mild pancreatitis, the L:M ratio being .2 and .029, respectively. It was also concluded that the permeability increased gradually over the course of pancreatitis and was maximum at day 7 (P < .01). This provides a window of opportunity for therapeutic intervention to prevent the late observed increase in intestinal permeability.

Lactulose and mannitol intestinal permeability detected by capillary electrophoresis.

Aim of this study was to set up a method by capillary electrophoresis to detect lactulose and mannitol in urine after an oral load, and to estimate the intestinal permeability in controls and in type I diabetes patients. The underivatized carbohydrates were monitored by indirect UV detection using sorbate, cetyltrimethylammonium bromide and LiOH as background electrolyte. Urines were purified by solid phase extraction, shaken with cation exchange resin, filtered and analysed. Carbohydrates migrated in <10 min in relation to their pK(a) and M(r). Controls (n = 33) and patients (n = 23) had an excretion ratio lactulose/mannitol 0.025 (0.018-0.051) and 0.067 (0.050-0.127), respectively (p < 0.01, median, interquartile range).

Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis.

Low antimycobacterial drug concentrations have been observed in tuberculosis (TB) patients under treatment. The lactulose/mannitol urinary excretion test (L/M), normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R) and isoniazid (H) were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL) or H (3-6 mcg/mL) in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.