Sugar Absorption Test Research Articles

Intestinal permeability and orocaecal transit time in elderly patients with Parkinson's disease.

The aetiology of weight loss in patients with Parkinson's disease is likely to be multifactorial. We studied 15 patients with Parkinson's disease and 15 age- and sex-matched controls and looked for evidence of malabsorption due to small bowel bacterial overgrowth or alteration of intestinal permeability. There was a marked increase in orocaecal transit time in the patients with Parkinson's disease, although lactulose hydrogen breath testing did not show evidence of small bowel bacterial contamination. Intestinal permeability measured by the differential sugar absorption test was also deranged. There was reduced absorption of mannitol in patients with Parkinson's disease while lactulose absorption was similar in both groups, suggesting decreased non-mediated uptake across the enterocyte brush border membrane in patients with Parkinson's disease.

Screening relatives of coeliacs with the sugar absorption test

Using AR4-2J rat pancreatic carcinoma cells, the effects of a novel bombesin (BN) receptor antagonist [d-F5Phe6, d-Ala11]BN(6–13)OMe(BIM26226) on BN- or GRP-stimulated amylase release and binding of radio-labeled bombesin-like peptides to these cells were examined and compared to [d-Phe6,Leu13Ψ(CH2NH)Leu14]BN(6–14) (Psi Bn(6–14)), one of the most potent BN receptor antagonists presently known. BN and GRP both stimulated amylase release with EC50 values in the nanomolar range. Both antagonists were devoid of agonist activity when tested alone. BIM26226 was most potent, antagonizing BN- or GRP-stimulated amylase release with IC50 values in the nanomolar range, whereas Psi Bn(6–14) was approximately ten times less potent. With 125I-[Tyr15]GRP bound to these cells, the binding affinities were BIM26226 > GRP > Psi Bn(6–14) ⪢ neuromedin B. BIM 22626 was not able to inhibit binding of radio-labeled CCK-33, gastrin-17 or VIP. These results suggest that BIM26226 is one of the most potent and specific bombesin receptor antagonists in vitro and seems to be a useful tool to define the physiologic role of GRP in vivo.

The effect of different osmolarities of the solution of sugar absorption tests on intestinal permeability

The effect of different osmolarities of the solution of sugar absorption tests on intestinal permeability

Intestinal permeability testing in dogs with diet-responsive intestinal disease.

Fifteen dogs with signs of small and, or, large bowel disease that responded clinically to an exclusion diet were studied, using differential sugar absorption as an objective parameter of the mucosal response to the diet. Intestinal permeability and function were assessed by determining the urinary excretion ratios of lactulose/rhamnose and xylose/3-O-methylglucose, respectively, following oral administration of a mixture of these four sugars. Five dogs, all retrievers, were tentatively diagnosed as having dietary hypersensitivity, based upon resolution of clinical signs and normalisation of high intestinal permeability following an exclusion diet and recurrence of signs (in four of five dogs) upon challenge with the original diet. The fifth dog did not become symptomatic when challenged, but intestinal permeability increased. The remaining 10 dogs were diagnosed as having food intolerance, based upon clinical improvement on an exclusion diet, relapse on challenge with their original diet, but lack of improvement in intestinal permeability. These findings suggest that a differential sugar absorption test may be useful to determine the reasons for clinical response to exclusion diets. Demonstration of increased intestinal permeability with subsequent normalisation following an exclusion diet may be useful in the diagnosis of dietary hypersensitivity, while persistent abnormalities in intestinal permeability are suggestive of underlying intestinal disease and food intolerance.

Repeatability of the sugar-absorption test, using lactulose and mannitol, for measuring intestinal permeability for sugars.

Differential sugar-absorption tests for measuring intestinal permeability for sugars have been studied in a variety of gastrointestinal diseases. Their use in general practice has been hampered by a lack of data on reference values and repeatability of the test and the laboratory assay. In this study, we determined the reference values of the sugar-absorption test, using lactulose and mannitol as probe molecules, for children and adults. The repeatability of the test is good; linear relationship: slope, 0.825 [95% confidence interval (CI), 0.571, 1.152); intercept, 0.005 (95% CI, -0.004, 0.010). The repeatability of the laboratory assay for the sugar-absorption test is excellent; linear relationship: slope, 1.014 (95% CI, 0.870, 1.094); intercept, 0.002 (95% CI, -0.005, 0.010). The validation of the sugar-absorption test makes the test useful as a simple, noninvasive, reliable intestinal permeability test for sugars, which can be of use for clinical practice. Taking possible interfering factors into account, the sugar-absorption test can be used as a diagnostic test for enteropathy of different etiologies and evaluation of therapeutic interventions in both children and adults. Studies with the sugar-absorption test may clarify the role of intestinal permeability in the pathophysiology of a variety of gastrointestinal diseases.

Antigenaemia during acute graft versus host disease.

Animal studies have shown that antigens present within the gut play an important role in the development of acute graft versus host disease (GvHD) following allogeneic bone marrow transplantation (BMT). In previous studies, inert sugars have been found to penetrate the small bowel mucosa after conditioning therapy for BMT; endotoxaemia can also occur during acute GvHD. Data on absorption of antigenic proteins across the gut following BMT in humans have not been presented as yet. Six patients undergoing allogeneic BMT were studied to determine whether enteric ovalbumin absorption increased or endotoxaemia developed during acute GvHD. Three patients had minimal antigenaemia and no detectable endotoxaemia before receiving conditioning therapy. At the onset of acute GvHD, however, much higher ovalbumin concentrations were detected in those patients with severe antigenaemia. Serum concentrations of specific antiovalbumin IgG and IgA, or antiendotoxin IgM or IgG had no bearing on detectable IgG or IgM ovalbumin or endotoxin concentrations. In five of six patients, small bowel permeability increased, as tested by the lactulose/mannitol sugar absorption test, but detectable ovalbumin absorption increased in only three of these and only two developed endotoxaemia. Antigens present within the gut can cross the mucosal epithelium during acute GvHD, probably resulting in an enhanced immune response.

Diarrhoea and increased intestinal permeability in laboratory beagles associated with proximal small intestinal bacterial overgrowth.

Repeated episodes of diarrhoea were seen in 4 laboratory beagles after experimental renal surgery and feeding a modified diet. Small intestinal bacterial overgrowth (SIBO) was suspected by exclusion of other causes and measurement of plasma folate. SIBO was confirmed by quantitative duodenal bacteriology. Beagles with SIBO can show no clinical signs, experimental stress and dietary change may have been reasons why these 4 beagles exhibited clinical signs with SIBO. Despite normal gut histology an increase in gut permeability was found using sugar absorption tests. This increased permeability had the potential to cause variations in drug absorption during experimental studies.

Effect of disodiumcromoglycate on intestinal permeability changes and clinical response during cow's milk challenge

Oral disodiumcromoglycate (DSCG) has been used for many years in the prevention of food allergic reactions. The reported effectiveness varies widely and little is known about the mode of action. The aim of this study was to evaluate the effect of DSCG pretreatment (2 x 100 mg) on intestinal permeability (IP), as measured with a sugar absorption test (SAT), in relation to the clinical response during food challenge in 30 children suspected of cow's milk allergy. In the SAT the urinary Lactulose/Mannitol (L/M) ratio was measured after oral administration of these compounds. DSCG pretreatment did not alter the number of clinically positive challenges. Children with clinically positive challenges showed a significant increase in the L/M ratio with placebo pretreatment as compared to children with clinically negative challenges (p = 0.0008). This difference was reduced to nonsignificant levels after DSCG pretreatment (p = 0.07). We conclude that DSCG in this dosage probably reduces the local intestinal response but does not prevent the extraintestinal reactions.

Intestinal permeability is increased after major vascular surgery

Purpose: In experimental animals increased intestinal permeability has been demonstrated after ischemia and reperfusion injury. In this study we determined intestinal permeability in patients after elective or emergency aortic aneurysm repair the latter patients were in severe shock on hospital admission.Methods: A dual sugar absorption test, with lactulose and mannitol as markers, was used to measure intestinal permeability on the second day between 24 and 30 hours after hospital admission.Results: The lactulose/mannitol excretion ration was 0.012 ± 0.005 in seven healthy control subjects, 0.118 ± 0.116 in seven patients having elective operation, and 0.098 ± 0.093 in eight patients having emergency operation, indicating a significant increase of intestinal permeability in both patient groups (p < 0.01). No significant difference was found in intestinal permeability between patients of the elective and emergency groups.Conclusions: A significant increase in intestinal permeability commonly occurs in patients after elective and emergency major vascular surgery. It is suggested that this is mainly due to reperfusion injury rather than the ischemic period of the intestine itself.

Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease.

The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease.

Intestinal permeability in pediatric gastroenterology.

The role of the physiologic barrier function of the small bowel and its possible role in health and disease has attracted much attention over the past decade. The intestinal mucosal barrier for luminal macromolecules and microorganism is the result of non-immunologic and immunologic defense mechanisms. The non-immunologic mechanisms consist of intraluminal factors such as gastric acid, proteolytic activity, and motility and of mucosal surface factors like mucin and the microvillous membrane. The immunologic mechanisms include secretary IgA and cell-mediated immunity. Both types of mechanism are not completely mature at birth. Maturation of this barrier is not finished before the 2nd year of life. One of the aspects of the mucosal barrier function can be estimated by the intestinal permeability (IP) for macromolecules. We use the differential sugar absorption test (SAT), in which the ratio of urinary excretion of a relatively large molecule, lactulose, is compared with that of a relatively small molecule, mannitol, after oral ingestion. Although the small intestine is permeable to certain macromolecules in normal developmental conditions, an increased IP could be involved in the pathophysiology of several diseases, including infectious diarrhea, food allergy, celiac disease, and Crohn's disease. It can be concluded that IP, as measured with the SAT, reflects the state of the mucosal barrier and is altered in several gastrointestinal diseases. The SAT is a non-invasive IP test that can be of diagnostic help to demonstrate alterations in the small-mucosal barrier function and may be useful to evaluate therapeutic interventions.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal permeability in the critically ill.

Alterations in intestinal permeability reflect one component of intestinal epithelial barrier function. The objective of this study was to assess the degree of derangement of intestinal permeability in critically ill patients and to investigate the relationship of this to markers of disease severity and sepsis. Sixteen patients admitted to the intensive care unit for a variety of problems were studied with the severity of illness and degree of sepsis recorded daily. A differential sugar absorption test, using lactulose and mannitol as markers, was performed, and in 10 patients this was repeated after an interval of between 4-11 days. The use of the lactulose/mannitol (L/M) ratio corrects for variables unrelated to permeability such as gastric emptying. The L/M ratio was significantly higher in patients (median 0.98) compared to normal controls (median 0.008). The ratios showed no relation to disease severity or sepsis. These results establish that increased intestinal permeability occurs in the general ICU patient but that it is not uniquely related to sepsis. The extent of this abnormality suggests that further study is required to show the various influences on this process.

Aggressive chemotherapy for acute leukaemia frequently causes intestinal protein leakage

Cytostatic drugs are known to produce disturbances in intestinal absorption of carbohydrates. To further explore the gastrointestinal (GI) toxicity of cytostatic therapy, 37 patients with acute leukaemia were investigated during and/or after remission induction courses by the use of the differential sugar absorption test (DSAT) and the intestinal clearance of alpha-1-antitrypsin (ClAAT). The ratio of the lactulose to the mannitol excretion in the urine was found abnormal in 44% of the tests. The ClAAT was increased in 74% of tests. The test results differed considerably from patient to patient and depended on the chemotherapy course; correlation between the tests was low, probably indicating that unrelated pathophysiological processes were measured. After haematological regeneration, abnormal test results normalised. It is concluded that aggressive chemotherapy not only causes a reduction in the absorption of sugars, but commonly also protein leakage. These GI side-effects are reversible, and the application of both tests in combination provides a practical and reproducible method for investigation of GI toxicity in patients treated with cytostatic drugs.

Simultaneous Assessment of Intestinal Permeability and Lactose Tolerance with Orally Administered Raffinose, Lactose and 1-Arabinose

1. In order to develop an improved differential sugar absorption test for simultaneously assessing intestinal permeability and lactose intolerance, methods were established for determining raffinose, lactose and L-arabinose in human urine. Using NAD(P)H-coupled enzymatic assays and fluorimetry, each sugar was measurable over a concentration range of approximately 3-300 mumol/l in diluted urine specimens. 2. After an overnight fast, 40 normal volunteers drank an iso-osmotic solution containing raffinose, lactose and L-arabinose. The median 5 h urinary sugar excretion was 0.26% of the ingested raffinose, 0.05% of lactose and 17.5% of L-arabinose. 3. In 143 patients with gastrointestinal disease, excretion of both ingested raffinose and lactose was significantly increased in coeliac disease in relapse or in partial remission and in Crohn's disease, but not in the irritable bowel syndrome, coeliac disease in remission or ulcerative colitis. Excretion of lactose, but not raffinose, was increased in patients with mucosal lactase deficiency, whereas excretion of L-arabinose was reduced in all disease groups except ulcerative colitis. 4. Discrimination between diseases was poor when based on individual sugar recoveries, but improved dramatically when excretion was expressed relative to that of L-arabinose. The raffinose/L-arabinose excretion ratio, an index of intestinal permeability, was greater than 0.08 in 15/15 untreated coeliac patients but less than 0.06 in all normal subjects and in 9/9 lactase-deficient patients, 15/16 recovered coeliac patients, 5/6 patients with ulcerative colitis, 13/16 patients with Crohn's disease and 61/62 patients with irritable bowel syndrome.

Combined assessment of intestinal disaccharidases in congenital asucrasia by differential urinary disaccharide excretion.

Investigation of intestinal disaccharide hydrolysis and permeability by means of a non-invasive differential sugar absorption test was performed in a family containing two siblings with primary sucrase-isomaltase deficiency. The procedure, which depends on measurement of urinary excretion ratios after the oral administration of lactose, sucrose, palatinose, lactulose and L-rhamnose, is capable of simultaneous determination of intestinal lactase, sucrase, and isomaltase activity and lactulose:rhamnose permeability. The results corresponded well with those of disaccharidase assay and histological findings in jejunal biopsy tissue obtained from the patients. Palatinose proved a satisfactory substrate for in vivo assessment of intestinal isomaltase activity. The method described provides a reliable and comprehensive assessment of intestinal disaccharide hydrolysis, and simultaneous estimation of permeability assists discrimination of primary from secondary disaccharidase deficiency. The ability to assess three different disaccharidase activities in addition to intestinal permeability by means of a single test, and the simplicity of preservation and transport of urine samples for sugar analysis, makes this a convenient, definitive method for the investigation of defective sugar absorption in both patients and population groups.

Rapid and simultaneous determination of lactulose and mannitol in urine, by HPLC with pulsed amperometric detection, for use in studies of intestinal permeability

The lactulose/mannitol dual sugar absorption test is a non-invasive test of intestinal permeability. Its widespread use has been limited by the difficulties of analysis for carbohydrates in urine at low concentrations. We describe a "high-pressure" liquid-chromatographic method for determining lactulose and mannitol in urine, in which anion-exchange chromatography and pulsed amperometric detection are used. Sample preparation is simple and fast, and lactulose and mannitol and the internal standards arabinose and cellobiose are well resolved within 15 min. Analytical response of the method is linear with concentrations to 3 g/L, and one can detect as little as 0.3 mg of lactulose per liter of urine. Analytical recovery was between 90% and 107% for all sugars analyzed, and there was good agreement with results by a gas-chromatographic method (r = 0.993 lactulose, 0.984 mannitol). The method may potentially be applied to the study of other carbohydrates present in biological fluids at low concentrations.

Small intestinal permeability in pediatric clinical practice.

Passive permeability of small intestine to lactulose and mannitol was studied in children suspected of having intestinal disease, using a hypertonic differential sugar absorption test. Children with coeliac disease and cows' milk intolerance were shown to have an elevated urinary lactulose/mannitol recovery ratio when compared with controls, children with normal jejunal biopsy, or children in whom alternative explanations for failure to thrive had been demonstrated. The abnormality in permeability ratio principally reflects a reduced urinary recovery of mannitol following oral administration. This study demonstrates that a hypertonic sugar absorption test is well tolerated even by young children, is practicable in routine clinical pediatric practice, and is capable of demonstrating abnormal intestinal function in children with small intestinal disease.

Small Intestinal Permeability in Pediatric Clinical Practice

SummaryPassive permeability of small intestine to lactulose and mannitol was studied in children suspected of having intestinal disease, using a hypertonic differential sugar absorption test. Children with coeliac disease and cows' milk intolerance were shown to have an elevated urinary lactulose/mannitol recovery ratio when compared with controls, children with normal jejunal biopsy, or children in whom alternative explanations for failure to thrive had been demonstrated. The abnormality in permeability ratio principally reflects a reduced urinary recovery of mannitol following oral administration. This study demonstrates that a hypertonic sugar absorption test is well tolerated even by young children, is practicable in routine clinical pediatric practice, and is capable of demonstrating abnormal intestinal function in children with small intestinal disease.

Small Intestinal Permeability in Dermatological Disease

Passive small intestinal permeability was investigated in 62 patients with atopic eczema, 29 with psoriasis and 18 with dermatitis herpetiformis, using the cellobiose/mannitol differential sugar absorption test. Urinary recovery of cellobiose and mannitol in patients with both psoriasis and eczema were similar to values in a control population, and were not affected by the extent or activity of skin disease. The cellobiose/mannitol recovery ratio was abnormally high in seven patients with eczema, six of whom underwent jejunal biopsy. Jejunal mucosal morphology was normal in five, and one patient was found to have coeliac disease. Cellobiose/mannitol recovery ratio was also abnormal in seven patients with psoriasis, and in 11 with dermatitis herpetiformis, seven of whom had a normal jejunal biopsy. These findings demonstrate that the passive permeability of the small intestine is normal in the majority of patients with atopic eczema and psoriasis. Increased absorption of macromolecules from the gut lumen cannot be ascribed to defective intestinal integrity, and is unlikely to be relevant to the pathogenesis of eczema. Abnormal intestinal permeability may be a more sensitive manifestation of gluten-sensitive enteropathy than jejunal biopsy in dermatitis herpetiformis.

Assessment of intestinal permeability in the experimental rat with [3H]cellobiotol and [14C]mannitol.

1. The intestinal absorption of a mixture of [3H]cellobiotol and [14C]mannitol was determined by measuring the 3H/14C ratio in urine after oral administration of the labelled sugars to rats. This index of intestinal permeability was used to identify cellular dysfunction in experimental enteropathy in rats. 2. Rats with mucosal damage induced with ethanol showed an increased uptake of [3H]cellobiotol and a decreased uptake of [14C]mannitol compared with normal controls. The increased 3H/14C ratio in urine reflected the abnormal cell function known to be caused by ethanol. 3. Methotrexate treatment reduced the absorption of the two sugars whereas cetrimide treatment enhanced their absorption. However, in both methotrexate-induced and cetrimide-induced enteropathy the 3H/14C ratio in urine was unaffected by the mucosal damage. Here the permeability change was not related to absorptive dysfunction of the mucosal cells. 4. It is concluded that this labelled sugar absorption test enables the rapid and accurate identification of malfunction of intestinal mucosal cells in the rat. Moreover, the test distinguishes between changes in permeability caused by abnormal cell function and changes caused by gross disturbance of the structure of the mucosal surface.