Significant differences exist in the composition of current milk replacers (MR) and bovine whole milk. This study investigated how the macronutrient profile of 3 different MR formulations containing varying amounts of fat, lactose, and protein, and a whole milk powder (WP), affect postprandial metabolism and gut permeability in male Holstein calves. Sixty-four calves (45.4 ± 4.19 kg [mean ± SD] and 1.8 ± 0.62 d of age) were blocked in order of arrival to the facility and within each block, calves were randomly assigned to 1 of 4 treatments. Treatments included a high-fat MR (HF: 25.0% dry matter [DM] fat, 22.5% protein, 38.6% lactose; n = 14), a high-lactose MR (HL: 44.6% lactose, 22.5% protein, 18.0% fat; n = 17), a high-protein MR (HP: 26.0% protein, 18.0% fat, 41.5% lactose; n = 17), and WP (26.0% fat, 24.5% protein, 38.0% lactose; n = 16). Calves were fed 3.0 L (135 g/L) 3 times daily at 0600, 1200, and 1800 h with a teat bucket. Milk intake was recorded daily for the first 28 d after arrival, and blood sampling and body weight measurements were performed at arrival and on d 7, 14, 21, and 27. Gut permeability was estimated from fractional urinary excretion of indigestible markers (Cr-EDTA, lactulose, and d-mannitol) administered as a single dose on d 21 instead of the morning milk meal. Digestibility was determined simultaneously from a total collection of feces over 24 h. Postprandial dynamics were measured on d 28 by sequential blood sampling over 7.5 h. Dry matter intake of MR over 28 d was slightly greater in calves fed HL and HP than in WP. Recovery of Cr-EDTA and d-mannitol over a 24-h urine collection was greater in calves fed WP and HP than HL calves. Apparent total-tract digestibility of crude ash, protein, and fat did not differ among treatments; however, DM digestibility was lower in calves fed WP than in other treatment groups. In addition, abomasal emptying, as indicated by the area under the curve (AUC) for acetaminophen, was slower in calves fed WP than in calves fed HF and HL. The AUC for postprandial plasma glucose was lower in calves fed HL than WP and HF and lower in calves fed HP than WP. The AUC for postprandial serum insulin was greater in calves fed HP than WP and HF, whereas calves fed HL did not differ from the other treatments. Postprandial triglycerides were greater in calves fed WP, and postprandial adiponectin was higher in calves fed HL than other treatments. The high content of lactose and protein in MR had a major effect on postprandial metabolism. This raises the possibility of optimizing MR formulations to maintain metabolic homeostasis and influence development.

Insufficient nutrient intake is a strong independent predictor of mortality in elderly patients with heart failure. However, it is unclear to what extent energy intake affects their prognosis. This study investigated the association between patient outcomes and actual measured energy intake in elderly patients (≥65 years) with heart failure.

This study enrolled 139 elderly patients who were hospitalized with worsening heart failure at Shingu Municipal Medical Center, Shingu, Japan, between May 2017 and April 2018. Energy intake was evaluated for three days (from three days prior to the day of discharge until the day of discharge). Based on basal energy expenditure calculated using the Harris-Benedict equation, the patients were classified into a low-energy group (n = 38) and a high-energy group (n = 101). We assessed the prognosis in terms of both all-cause mortality and readmission due to worsening heart failure as a primary outcome.

Compared to the patients in the high-energy group, the patients in the low-energy group were predominantly female, less frequently had smoking habits and ischemic heart diseases, and had a higher left ventricular ejection fraction. The low-energy group had higher mortality than the high-energy group (p = 0.028), although the two groups showed equivalent event rates of the primary outcome (p = 0.569).

Calculations based on the Harris-Benedict equation revealed no significant difference in the primary outcome between the two groups, with a secondary outcome that showed worse mortality in the low-energy group. Given this result, energy requirement-based assessments using the Harris-Benedict equation might help in the management of elderly heart failure patients in terms of improved life outcomes.

An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised "normal" body weight and individually optimal weight. To this end, the basic principle of personalised medicine "one size does not fit all" has to be applied. Contextually, "normal" but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters-all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice.

Increased gut permeability might contribute to the pathogenesis of irritable bowel syndrome or functional abdominal pain (IBS or FAP). We investigated whether siblings and parents of children with IBS or FAP have increased gut permeability.

We performed permeability tests (using sucrose, lactulose, mannitol, and sucralose) on 29 siblings and 43 parents of children with IBS or FAP, and 43 children (controls) and 42 parents of controls, from primary and secondary care. Permeability studies were repeated in 7 siblings and 37 parents of children with IBS or FAP and 23 controls and 36 parents of controls following ingestion of 400 mg of ibuprofen. Percent recovery of sucrose was calculated based on analyses of urine collected overnight; the lactulose/mannitol ratio and percent recovery of sucralose were based on analyses of urine samples collected over a 24-hour period.

When we controlled for age, sex, and family membership, siblings of children with IBS or FAP had increased small bowel permeability (urinary lactulose/mannitol ratio) vs controls (P = .004). There was no difference in gastroduodenal (percent sucrose recovery) or colonic (percent sucralose recovery) permeability between groups. Similarly, parents of children with IBS or FAP also had increased small bowel permeability, compared with parents of controls (P = .015), with no differences in gastric or colonic permeability. After administration of ibuprofen, gastroduodenal and small bowel permeability tended to be greater in IBS or FAP siblings (P = .08) and gastroduodenal permeability tended to be greater in IBS or FAP parents (P = .086).

Siblings and parents of children with IBS or FAP have increased baseline small intestinal permeability compared with control children and their parents. These results indicate that there are familial influences on gastrointestinal permeability in patients with IBS or FAP.

The dual sugar absorption test, specifically the lactulose:mannitol test, is used to assess gut health. Lactulose absorption is said to represent gut damage and mannitol absorption is used as a measure of normal small bowel function and serves as normalizing factor for lactulose. A underappreciated limitation of this common understanding of the lactulose:mannitol test is that mannitol is not absorbed to any substantial extent by a transcellular process. Additionally, this interpretation of lactulose:mannitol is not consistent with current understanding of paracellular pathways, where three pathway types exist: pore, leak, and unrestricted. Pore and leak pathways are regulated biological constructions of the small bowel barrier, and unrestricted pathways represent micropathological damage. We analyzed 2334 lactulose:mannitol measurements rigorously collected from 622 young rural Malawian children at high risk for poor gut health in light of the pathway model. An alternative method of normalizing for gut length utilizing autopsy data is described. In our population, absorbed lactulose and mannitol are strongly correlated, r = 0.68 P <0.0001, suggesting lactulose and mannitol are traversing the gut barrier via the same pathways. Considering measurements where pore pathways predominate, mannitol flux is about 14 times that of lactulose. As more leak pathways are present, this differential flux mannitol:lactulose falls to 8:1 and when increased numbers of unrestricted pathways are present, the differential flux of mannitol:lactulose is 6:1. There was no substantial correlation between the lactulose:mannitol and linear growth. Given that mannitol will always pass through a given pathway at a rate at least equal to that of lactulose, and lactulose absorption is a composite measure of flux through both physiologic and pathologic pathways, we question the utility of the lactulose:mannitol test. We suggest using lactulose alone is as informative as lactulose:mannitol in a sugar absorption testing in subclinical gut inflammation. Impact statement Our work integrates the standard interpretation of the lactulose:mannitol test (L:M), with mechanistic insight of intestinal permeability. There are three paracellular pathways in the gut epithelium; pore, leak, and unrestricted. Using thousands of L:M measurements from rural Malawian children at risk for increased intestinal permeability, we predict the differential flux of L and M through the pathways. Our findings challenge the traditional notions that little L is absorbed through a normal epithelial barrier and that M is a normalizing factor for L. Our observations are consistent with pore pathways allowing only M to pass. And that substantial amounts of L and M pass through leak pathways which are normal, regulated, cell-junctional adaptations. So M is a composite measure of all pathways, and L is not a measure solely of pathologic gut damage. Using L alone as a probe will yield more information about gut health than L:M.

Anorexia nervosa (AN) is one of the most common chronic illnesses in female adolescents and exhibits the highest mortality risk of all psychiatric disorders. Evidence for the effectiveness of psychotherapeutic or psychopharmacological interventions is weak. Mounting data indicate that the gut microbiome interacts with the central nervous system and the immune system by neuroendocrine, neurotransmitter, neurotrophic and neuroinflammatory afferent and efferent pathways. There is growing evidence that the gut microbiota influences weight regulation and psychopathology, such as anxiety and depression. This article reviews how the gut-brain interaction may impact the development and course of AN. A "leaky gut", characterized by antigens traversing the intestinal wall, was demonstrated in an animal model of AN, and could underlie the low-grade inflammation and increased risk of autoimmune diseases found in AN. Moreover, starvation has a substantial impact on the gut microbiome, and diets used for re-nutrition based on animal products may support the growth of bacteria capable of triggering inflammation. As there is currently no empirically derived agreement on therapeutic re-nourishment in AN, this review discusses how consideration of gut-brain interactions may be important for treatment regarding the determination of target weight, rapidity of weight gain, refeeding methods and composition of the diet which might all be of importance to improve long-term outcome of one of the most chronic psychiatric disorders of adolescence.

Increasing evidence shows that gut microbiota composition is related to changes of gut barrier function including gut permeability and immune function. Gut microbiota is different in obese compared to lean subjects, suggesting that gut microbes are also involved in energy metabolism and subsequent nutritional state. While research on gut microbiota and gut barrier has presently mostly focused on intestinal inflammatory bowel diseases and more recently on obesity and type 2 diabetes, this review aims at summarizing the present knowledge regarding the impact, in vivo, of depleted nutritional states on structure and function of the gut epithelium, the gut-associated lymphoid tissue (GALT), the gut microbiota and the enteric nervous system. It highlights the complex interactions between the components of gut barrier in depleted states due to food deprivation, food restriction and protein energy wasting and shows that these interactions are multidirectional, implying the existence of feedbacks.

Water-soluble nutrients are absorbed by the small intestine via transcellular and paracellular mechanisms. Based on a few previous studies, the capacity for paracellular nutrient absorption seems greater in flying mammals than in nonflying mammals, but there has been little investigation of the mechanisms driving this difference. Therefore, we studied three species each of bats (Artibeus lituratus, Sturnira lilium and Carollia perspicillata) and nonflying mammals (Akodon montensis, Mus musculus and Rattus norvegicus). Using standard pharmacokinetic techniques in intact animals, we confirmed the greater paracellular nutrient absorption in the fliers, comparing one species in each group. Then we conducted in situ intestinal perfusions on individuals of all species. In both approaches, we measured the absorption of 3OMD-glucose, a nonmetabolizable glucose analog absorbed both paracellularly and transcellularly, as well as L-arabinose, which has no mediated transport. Fractional absorption of L-arabinose was three times higher in the bat (S. lilium: 1.2±0.24) than in the rodent (A. montensis: 0.35±0.04), whereas fractional absorption of 3OMD-glucose was complete in both species (1.46±0.4 and 0.97±0.12, respectively). In agreement, bats exhibited two to 12 times higher l-arabinose clearance per square centimeter nominal surface area than rodents in intestinal perfusions. Using L-arabinose, we estimated that the contribution of the paracellular pathway to total glucose absorption was higher in all three bats (109-137%) than in the rodents (13-39%). These findings contribute to an emerging picture that reliance on the paracellular pathway for nutrient absorption is much greater in bats relative to nonflying mammals and that this difference is driven by differences in intestinal permeability to nutrient-sized molecules.

Although the serum sickness-like reaction (SSLR) in children after the administration of cefaclor has long been recognized, the exact mechanism of cefaclor-associated SSLR remains unclear. This study aims to investigate the association between intestinal mucosal permeability and cefaclor-associated SSLR in children. A total of 82 pediatric patients with upper respiratory tract infection following the cefaclor therapy was divided into cefaclor-associated SSLR positive group and negative group based on the presence or absence of SSLR after taking cefaclor, and 30 healthy volunteers served as control group. Urinary lactulose/mannitol (L/M) ratios and serum diamine oxidase (DAO) levels were determined in all cases on days 7, 9, 11, 13, and 15 after oral administration of cefaclor. The children in the control group were given the same measurements after enrollment in this study. From days 7 to 13, the urinary L/M ratio of children with cefaclor SSLR gradually increased and reached to the highest level of 0.38 ± 0.14 on day 13. Compared with the cefaclor-associated SSLR negative group and control group, urinary L/M ratios increased significantly in the cefaclor SSLR positive group on days 7, 9, 11, 13, and 15 after taking cefaclor, and serum levels of DAO following the treatment of cefaclor increased significantly in children with cefaclor SSLR on days 9, 11, 13, and 15. No significant difference in urinary L/M ratios and serum levels of DAO between SSLR negative group and control group through the entire experiment was observed. In conclusion, administration of cefaclor may induce SSLR in children by increasing the intestinal mucosal permeability and/or affecting the integrity of the intestinal mucosa. Determinations of urinary L/M ratios and serum DAO levels may be helpful for observing or predicting the occurrence of SSLR after administration of cefaclor, which will encourage physicians to proceed with extreme caution when prescribing cefaclor for pediatric patients.

Physical exercise places high demands on the adaptive capacity of the human body. Strenuous physical performance increases the blood supply to active muscles, cardiopulmonary system, and skin to meet the altered demands for oxygen and nutrients. The redistribution of blood flow, necessary for such an increased blood supply to the periphery, significantly reduces blood flow to the gut, leading to hypoperfusion and gastrointestinal (GI) compromise. A compromised GI system can have a negative impact on exercise performance and subsequent postexercise recovery due to abdominal distress and impairments in the uptake of fluid, electrolytes, and nutrients. In addition, strenuous physical exercise leads to loss of epithelial integrity, which may give rise to increased intestinal permeability with bacterial translocation and inflammation. Ultimately, these effects can deteriorate postexercise recovery and disrupt exercise training routine. This review provides an overview on the recent advances in our understanding of GI physiology and pathophysiology in relation to strenuous exercise. Various approaches to determine the impact of exercise on the individual athlete's GI tract are discussed. In addition, we elaborate on several promising components that could be exploited for preventive interventions.

Studying the role of the human microbiome as it relates to human health status has revolutionized our view of microbial community contributions to a large number of diseases, particularly chronic inflammatory disorders. The lower gastrointestinal (GI) tract houses trillions of microbial cells representing a large diversity of species in relatively well-defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is not surprising, therefore, that many GI inflammatory diseases, including inflammatory bowel disease (IBD), are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response. Here we review current knowledge in the emerging field of human microbiome research as it relates to IBD, specifically focusing on Crohn's disease (CD) and ulcerative colitis (UC). We discuss bacteriotherapeutic efforts to restore GI microbial assemblage integrity via probiotic supplementation of IBD patients, and speculate on future directions for the field.

Fed the same dry diet, large dogs show poorer fecal quality than small ones. A high colonic permeability could explain a low water and electrolyte net balance leading to high fecal water content. This experiment was conducted to evaluate colonic permeability in dogs varying in body size and to determine whether colonic permeability is related to fecal sodium concentration and fecal quality. Four breeds of dogs were used: six Miniature Poodles (MP), six Standard Schnauzers (SS), six Giant Schnauzers (GS) and six Great Danes (GD). Colonic permeability was evaluated using the ratio of urinary lactulose to sucralose (L:S) after oral administration. Fecal sodium concentration was measured by flame photometry. The urinary L:S ratio was significantly lower in GD, indicating a higher colonic permeability, than in the three other breeds (0.35 ± 0.12 for GD and 0.51 ± 0.05 for MP). GD also presented the higher fecal sodium concentrations and the poorest fecal quality. The higher fecal sodium concentration observed in GD could be explained by the higher colonic permeability and both these variables could be important explanations for higher fecal moisture in large dogs.

Lactulose/mannitol (L/M) intestinal permeability tests were completed to compare the intestinal function of severely underweight children recovering from diarrhea and other illnesses and of nonmalnourished children from the same communities, and to evaluate the effects of food supplementation, with or without psychosocial stimulation, on the changes in intestinal function among the underweight children.

Seventy-seven malnourished children completed intestinal permeability studies at baseline and 3 months after receiving 1 of the following randomly assigned treatment regimens: group-C--fortnightly follow-up at community-based follow-up units, including growth monitoring and promotion, health education, and micronutrient supplementation, n = 17; group-SF--same as group-C plus supplementary food (SF) to provide 150 to 300 kcal/day, n = 23; group-PS--same as group-C plus psychosocial stimulation (PS), n = 17; or group-SF + PS--same as group-C plus SF and PS, n = 20. Seventeen nonmalnourished children were included as comparison subjects.

The malnourished children's mean ± SD initial age was 13.1 ± 4.0 months, their mean weight-for-age z score was -3.82 ± 0.61, and their median (interquartile range) urinary L/M recovery ratio was 0.16 (0.10-0.28). Eighty-four percent of the children had L/M ≥ 0.07, suggestive of impaired intestinal function. The median L/M of the malnourished children was significantly greater than that of 17 relatively well-nourished children (median 0.09; interquartile range 0.05-0.12; P = 0.001). There were no significant differences in baseline characteristics of the severely malnourished children by treatment group. Following treatment, the L/M ratio improved in all of the groups (P < 0.001), but there were no significant differences in these changes by treatment group. There was a significant positive association between weight gain and the magnitude of improvement in L/M ratio (r = 0.30, P = 0.012).

Intestinal mucosal function, as measured by sugar permeability, is impaired among severely underweight children. Intestinal permeability improves in relation to weight gain, but intestinal mucosal recovery is not specifically related to the types or amount of food supplementation or PS provided in this trial.

The present study was carried out to evaluate the pharmacological effect of Zn in diarrhoea in relation to intestinal permeability. Seventy-two weaning piglets, aged 24 d, were allocated to three dietary treatments: (1) control diet without supplemental Zn; (2) control diet supplemented with 2000 mg Zn/kg from ZnO; (3) control diet supplemented with 2000 mg Zn/kg from tetrabasic zinc chloride (TBZC). At the end of a 14 d experiment period, piglets were weighed, feed consumption was measured, and mucosal barrier function was determined using the lactulose/mannitol test. Expression of mucosal tight junction protein was measured at RNA and protein level. Inclusion of TBZC or ZnO in the diet significantly increased average daily gain (P < 0.01) and average daily feed intake (P < 0.05), while leading to reduced feed conversion ratio (P < 0.05) and faecal scores (P < 0.01). TBZC reduced urinary lactulose:mannitol ratios of weaning piglets (P < 0.05), while dietary supplementation with ZnO tended to reduce urinary lactulose:mannitol ratios (P = 0.061). ZnO or TBZC significantly enhanced the mRNA and protein expression of occludin (P < 0.05) and zonula occludens protein-1 (ZO-1) (P < 0.05) in the ileal mucosa. Piglets fed the TBZC-supplemented diet had a higher level of occludin than pigs fed the ZnO-supplemented diet (P < 0.05). The results indicate that Zn supplementation decreased faecal scores and the reduction was accompanied by reduced intestinal permeability, which was evident from the reduced urinary lactulose:mannitol ratios and increased expression of occludin and ZO-1. Therefore, the protective effect of pharmacological levels of dietary Zn in reducing diarrhoea might, at least partly, be associated with reduced intestinal permeability.

The prevalence of lactose malabsorption (LM) is increased in the elderly, although the mechanisms responsible are still a matter of speculation. The objective of this study was to investigate the possible roles of reduced functional small intestinal absorptive area, lactase deficiency and small intestinal bacterial overgrowth (SIBO).

Twenty Caucasian (Anglo-Celtic), asymptomatic, well-nourished, elderly volunteers (median age 79 years, range 70-94 years) with no clinically apparent predisposition to SIBO underwent a 50 g lactose breath hydrogen test (LBHT) and mannitol absorption test, the latter as an index of functional small intestinal absorptive area. Those with LM additionally underwent bacteriological assessment of small intestinal secretions and mucosal biopsy, to assess the contribution of SIBO and lactase deficiency, respectively, to the pathogenesis of LM in individual cases. The prevalence of SIBO was also determined in elderly subjects without LM. Twenty asymptomatic younger subjects (median age 29 years, age range 18-35 years) served as controls. All subjects were "hydrogen producers" in response to lactulose.

LM was evident in 10/20 (50%) elderly subjects and 1/20 (5%) younger subjects (p=0.003). Mannitol absorption did not differ significantly in elderly and younger subjects or in elderly subjects with and without LM. SIBO was documented in 9/10 (90%) elderly subjects with LM; eradication was associated with resolution of LM. Lactase deficiency was evident in only one elderly subject with LM. SIBO was evident in 2/10 (20%) elderly subjects without LM (p=0.005 compared to those with LM). Lactulose breath hydrogen test identified only 2/11 (18%) elderly subjects with SIBO.

Increased prevalence of LM in the elderly is mostly due to clinically non-apparent SIBO, rather than mucosal factors. The lactulose breath hydrogen test cannot be relied upon to identify elderly subjects with SIBO, even in those without an anatomical predisposition.

Anecdotal evidence suggests that birds have smaller intestines than mammals. In the present analysis, we show that small birds and bats have significantly shorter small intestines and less small intestine nominal (smooth bore tube) surface area than similarly sized nonflying mammals. The corresponding >50% reduction in intestinal volume and hence mass of digesta carried is advantageous because the energetic costs of flight increase with load carried. But, a central dilemma is how birds and bats satisfy relatively high energy needs with less absorptive surface area. Here, we further show that an enhanced paracellular pathway for intestinal absorption of water-soluble nutrients such as glucose and amino acids may compensate for reduced small intestines in volant vertebrates. The evidence is that l-rhamnose and other similarly sized, metabolically inert, nonactively transported monosaccharides are absorbed significantly more in small birds and bats than in nonflying mammals. To broaden our comparison and test the veracity of our finding we surveyed the literature for other similar studies of paracellular absorption. The patterns found in our focal species held up when we included other species surveyed in our analysis. Significantly greater amplification of digestive surface area by villi in small birds, also uncovered by our analysis, may provide one mechanistic explanation for the observation of higher paracellular absorption relative to nonflying mammals. It appears that reduced intestinal size and relatively enhanced intestinal paracellular absorption can be added to the suite of adaptations that have evolved in actively flying vertebrates.

Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies, indicating that CC is a pan-intestinal disease. In small-intestinal disease, the intestinal barrier function may be impaired, and the permeability of the small intestine altered. The purpose of this research was to study small-bowel function in patients with CC as expressed by intestinal permeability.

Ten patients with CC and chronic diarrhoea participated in the study. Coeliac disease was excluded by small-bowel biopsy and/or serology. Intestinal permeability was assessed as urinary excretion (ratios) 2, 4 and 6 h after ingestion of 14C-labelled mannitol (14C-mannitol) and 99mTc-labelled diethylenetriamine-pentaacetic acid (99mTc-DTPA). Data were compared with the results from healthy controls.

No difference was found between groups in urinary excretion of 14C-mannitol and 99mTc-DTPA after 2, 4 or 6 h, respectively. Likewise, no significant differences in the 99mTc-DTPA/14C-mannitol ratios between patients and controls were detected after 2 h: 0.030 (0.008-0.130) versus 0.020 (0.007-0.030), p = 0.19, after 4 h: 0.040 (0.009-0.180) versus 0.020 (0.008-0.040), p = 0.14 or after 6 h: 0.040 (0.012-0.180) versus 0.020 (0.010-0.040), p = 0.17.

No alterations in intestinal permeability in patients with CC could be demonstrated. Impairment of the integrity of the mucosa of the small bowel and the presence of a general dysfunction of the small intestine in patients with CC seem unlikely.

Irritable bowel syndrome (IBS) is a heterogeneous condition and defined according to symptoms. Low-grade inflammation has been associated with IBS, particularly that following infection, but whether altered intestinal permeability profiles relate to irritable bowel subtype or onset is uncertain. Our aim was to compare small and large intestinal permeability in various subtypes of IBS to healthy controls.

Intestinal permeability was measured using 1.8 MBq of 51Cr-EDTA and collecting urine over 24 h; Study 1: patients with diarrhea-predominant postinfectious IBS (N=15), constipation-predominant IBS (N=15), and healthy controls (N=15); Study 2: two groups of diarrhea-predominant IBS (D-IBS), one with a history of onset after acute gastroenteritis (postinfectious) (N=15) and the other without such a history (nonpostinfectious) (N=15) both compared with healthy controls (N=12).

Permeability expressed as percentage of total dose excreted in urine (median [inter-quartile range]). Study 1: Proximal small intestinal permeability was increased in postinfectious IBS (0.19 [0.12-0.23]) in contrast to constipated IBS (0.085 [0.043-0.13]) and controls (0.07 [0.035-0.19]) (p=0.02). IBS patients with eczema, asthma, or hayfever had increased proximal small intestinal permeability compared with IBS patients without atopy (p=0.02). Study 2: Small intestinal permeability was greater in nonpostinfectious diarrhea-predominant IBS (0.84 [0.69-1.49]) compared with postinfectious IBS (0.43 [0.29-0.63], p=0.028) or controls (0.27 [0.2-0.39]), p=0.001).

Small intestinal permeability is frequently abnormal in diarrhea-predominant IBS. Those without a history of infectious onset appear to have a more severe defect.

The effects of surgery on gastric emptying have been documented for a considerable time, but less is known about the effects in the small intestine. It is thought that there is minimal diminution in the absorptive capacity of the small intestine after operation, although there is no literature on drug absorption in the early period after surgery. This study investigated drug absorption from the small bowel in patients undergoing abdominal surgery.

A prospective study of patients undergoing major abdominal surgery in which patients acted as their own preoperative controls was carried out. Patients were administered the test substances, acetaminophen and (99m)TcDTPA, before operation and 2 days after operation. Small intestine transit times, plasma concentrations and other pharmacokinetic variables were compared using Student's paired t-test. Two complementary studies were carried out to establish pharmacokinetic parameters.

There were no significant differences in the pre- and postoperative values of t(max), area under the curve, and area under the moment curve (AUMC) before and after operation (P>0.05). There were significant differences between the pre- and postoperative values of C(max) [C(max (preop))>C(max (postop)); P<0.05] and the pre- and postoperative values of mean residence time (MRT) [MRT((preop))<MRT((postop)); P<0.01].

Drug absorption from the small bowel in the postoperative patient does not differ significantly from its preoperative absorptive capacity.

Patients with cirrhosis are at increased risk of developing infections due to bacterial translocation. This process depends on three principal factors: bacterial overgrowth, immunodepression, and altered intestinal permeability. Intestinal barrier functions may be disturbed in cirrhosis, related to the toxic effects of alcohol (on mucosa and biological membranes) and portal hypertensive enteropathy. Few studies on the assessment of intestinal permeability in cirrhotic patients are available, and contradictory results may be explained by methodological differences. However, four studies using a differential sugar absorption test (lactulose-mannitol test, a combination of an oligosaccharide and a monosaccharide) showed an increased intestinal permeability in cirrhotic patients. The recurrence of spontaneous bacterial peritonitis can be appreciated only by one similar case history, a low rate of protides in ascites (<10 g/L), bilirubinemia > 55 micromol/L, and thrombocytopenia<98.000/mm3. These results suggest that primary antibiotherapy prophylaxis should be recommended, but this recommendation is limited by the risk of bacterial resistant selection and by the fact that no patient survival benefits was shown. Intestinal permeability could be another predictive factor to justify preventive antibiotherapy; but more studies are needed and methods should be standardized (technique used to measure permeability, patient groups involved).

This article provides a critical review of the evidence indicating that an increase in intestinal permeability is associated with the installation of bacteremia, sepsis, and the multiple organ failure syndrome and that glutamine in pharmacologic doses reduces the acute increase of intestinal permeability and the infection frequency in critically ill patients.

All studies published until December 2004 about intestinal permeability, bacterial translocation, and glutamine were located by search of PubMed and Web of Science. The reference lists of review articles and primary publications were also examined to identify references not detected in the computer search.

Clinical and experimental studies investigating the correlation between intestinal permeability, bacterial translocation, and frequency of infections, associated or not with the effect of glutamine administration.

Information regarding patient population, experimental design, glutamine doses and routes of administration, nutritional therapy prescribed, methods used to assess intestinal permeability, metabolic variables, and the frequency of infections were obtained from the primary literature.

Intestinal permeability is increased in critically ill patients. The results have not always been consistent, but the studies whose results support the association between intestinal permeability and systemic infections have had better design and more appropriate controls. The administration of glutamine by the intravenous or oral route and at the doses recommended before or immediately after surgery, burns, or the administration of parenteral nutrition has a protective effect that prevents or reduces the intensity of the increase in intestinal permeability. Glutamine reduces the frequency of systemic infections and may also reduce the translocation of intestinal bacteria and toxins, but this has not been demonstrated.

Glutamine administration improves the prognosis of critically ill patients presumably by maintaining the physiologic intestinal barrier and by reducing the frequency of infections.

Conventional dual sugar tests of intestinal permeability assess only the stomach and small intestine. A novel triple sugar method of assessing colonic permeability has recently been described in animals. This utilizes the non-fermented sweetener sucralose, in addition to conventional sugars. It has been postulated that this test enables the simultaneous assessment of small-intestinal and colonic barrier function in humans. The aim of this study was to evaluate the triple sugar test using healthy volunteers and ileostomists.

Twenty-one healthy volunteers and 18 ileostomists underwent the triple sugar test. After an overnight fast, subjects drank a solution containing lactulose (5 g), rhamnose (1 g) and sucralose (5 g). Urine was collected for 0-5 h and 5-19 h. Urinary sugars were quantified using HPLC, and 5 and 24-h excretion calculated. Nineteen control subjects and 16 ileostomists also underwent a 51Cr-EDTA permeability test. Permeability data were presented as medians (IQR), and differences between groups analysed with Mann-Whitney U-tests.

Lactulose excretion and the 5-h lactulose/rhamnose (L/R) ratio were similar in controls and ileostomists [L/R ratio 0.024 (0.022-0.034) vs. 0.025 (0.022-0.035), P = 0.955]. Twenty-four hours excretion of sucralose was significantly higher in control subjects compared with ileostomists [1.41% (1.17-1.68) vs. 0.96% (0.64-1.2), P = 0.003]. The same pattern was seen with 51Cr-EDTA [2.73% (2.06-3.76) vs. 2.06% (1.55-2.71), P = 0.037] and with lactulose [0.52% (0.42-0.60) vs. 0.25% (0.16-0.35), P = 0.002].

Both sucralose and 51Cr-EDTA underwent significant colonic absorption. A significant amount of lactulose also appeared to be absorbed in the colon. This unexpected finding requires further study.

Cardiopulmonary bypass provokes a systemic inflammatory reaction that, in 1% to 2% of all cases, leads to multiorgan disfunction. The aim of this study was to evaluate the possible role of the intestine in the pathogenesis and development of this reaction.

Eleven selected patients scheduled for elective coronary artery bypass graft surgery were enrolled in a open, prospective clinical study. Gastric tonometry, chromium-labeled test and double sugar intestinal absorption tests, polymerase chain reaction microbial DNA test, and measurement of cytokines and transcriptional factor (nuclear factor kappaB) activation were performed.

During the postoperative period, gastric pH remained stable (range,7.2 to 7.3). The partial pressure for carbon dioxide gradient between the gastric mucosa and arterial blood increased significantly (from 1 to 23 mm Hg), peaking in the sixth postoperative hour. Interleukin 6 increased significantly over basal levels, peaking 3 hours after cardiopulmonary bypass (96.3 versus 24 pg/mL). Nuclear factor kappaB never reached levels higher than those observed after lipopolysaccharide stimulation. Escherichia coli translocation was documented in 10 patients: in eight cases from removal of aortic cross-clamps and in two cases from the first postoperative hour. With respect to basal value (6.4%), the urine collection revealed a significant increase in excretion of the radioisotope during the first 24 hours after surgery (39.1%), although there were no significant variations with the double sugar test.

The results obtained showed a correlation between the damage of the gastrointestinal mucosa, subsequent increased permeability, E coli bacteremia, and the activation of a self-limited inflammatory response in the absence of significant macrocirculatory changes and postoperative complications.

Malnutrition and absence of exogenous luminal nutrients in the gastrointestinal tract affect intestinal permeability (IP) leading to an increased penetration of substances that passively cross intestinal epithelium via intercellular pathways. We hypothesised that an increase in IP could occur in patients with anorexia nervosa because of their prolonged fasting and chronic malnutrition. Therefore, we assessed IP in 14 drug-free anorexic women and 19 drug-free age-matched healthy women by means of the lactulose/mannitol (LA/MA) test. To this purpose, after an overnight fast, subjects ingested an oral solution containing 5 g lactulose and 2 g mannitol in 100 ml water. Urine specimens were collected immediately before and 30, 60, 120, 180, 240 and 300 min after the ingestion of the sugar solution. Urinary lactulose and mannitol were determined by high-performance anion exchange chromatography coupled with pulsed amperometric detection. We found that IP, as expressed by the 5-h LA/MA excretion ratio, was significantly decreased in anorexic women because of a lower urinary recovery of lactulose. Moreover, in patients, the time course of lactulose excretion significantly differs from healthy controls. These results do not confirm our hypothesis of increased IP in anorexia nervosa. Since IP reflects the anatomo-functional status of intestinal mucosa, the present findings support the idea that changes in the anatomo-physiology of intestinal mucosa occur in anorexia nervosa.

The pharmacokinetics of extracellular solutes is determined by the blood-tissue exchange kinetics and the volume of distribution in the interstitial space in the different organs. This information can be used to develop a general physiologically based pharmacokinetic (PBPK) model applicable to most extracellular solutes.

The human pharmacokinetic literature was surveyed to tabulate the steady state and equilibrium volume of distribution of the solutes mannitol, EDTA, morphine-6-glucuronide, morphine-3-glucuronide, inulin and beta-lactam antibiotics with a range of protein binding (amoxicillin, piperacillin, cefatrizine, ceforanide, flucloxacillin, dicloxacillin). A PBPK data set was developed for extracellular solutes based on the literature for interstitial organ volumes. The program PKQuest was used to generate the PBPK model predictions. The pharmacokinetics of the protein (albumin) bound beta-lactam antibiotics were characterized by two parameters: 1) the free fraction of the solute in plasma; 2) the interstitial albumin concentration. A new approach to estimating the capillary permeability is described, based on the pharmacokinetics of the highly protein bound antibiotics.

About 42% of the total body water is extracellular. There is a large variation in the organ distribution of this water - varying from about 13% of total tissue water for skeletal muscle, up to 70% for skin and connective tissue. The weakly bound antibiotics have flow limited capillary-tissue exchange kinetics. The highly protein bound antibiotics have a significant capillary permeability limitation. The experimental pharmacokinetics of the 11 solutes is well described using the new PBPK data set and PKQuest.

Only one adjustable parameter (systemic clearance) is required to completely characterize the PBPK for these extracellular solutes. Knowledge of just this systemic clearance allows one to predict the complete time course of the absolute drug concentrations in the major organs. PKQuest is freely available http://www.pkquest.com.

We tested predictions that: (1) absorption of water-soluble probes decreases with increasing molecular size, consistent with movement through effective pores in epithelia, and (2) absorption of probes is enhanced when measured in the presence of luminal nutrients, as predicted for paracellular solvent drag. Probes (L-arabinose, L-rhamnose, perseitol, lactulose; MW 150.1-342.3 Da) were gavaged in nonanesthetized House sparrows ( Passer domesticus), or injected into the pectoralis, and serially measured in plasma. Bioavailability was calculated as F=AUC by gavage/AUC by injection, where AUC is the area under the curve of plasma probe concentration vs. time. Consistent with predictions, F declined with probe size by 75% from the smallest to the largest probe, and absorption of probes increased by 40% in the presence of luminal glucose or food compared to a mannitol control. Absorption of water-soluble probes by sparrows is much higher than in humans, which is much higher than in rats. These differences seem mainly attributable to differences in paracellular solvent flux and less to differences in effective paracellular pore size.

Orally administered (51)Cr-labelled ethylenediaminetetraacetic acid ((51)CrEDTA) has been used to evaluate intestinal permeability in inflammatory bowel disease, especially Crohn's disease. However, information about colonic permeability in ulcerative colitis (UC) is relatively scarce. The aim of this study was to investigate the urinary excretion of orally administered (51)CrEDTA, its relation to disease activity and its response to medical therapy in patients with UC. Forty-three patients with UC and 19 controls were examined. Disease activity was evaluated by endoscopy. In 19 patients with active UC, the (51)CrEDTA permeability test was repeated after medical therapy. (51)CrEDTA (95 microCi; 26 MBq) was given orally after an overnight fast and urine was collected over a 24 h period. The first urine samples were taken 5 h and the second 24 h after the oral administration of (51)CrEDTA. Urine samples were counted in a gamma counter. In controls, the median 5 h and 24 h excretions were 0.10% and 0.93%, respectively. Patients with UC showed significantly increased urine (51)CrEDTA excretion at both time intervals (5 h: 2.41%, P<0.0002; 24 h: 6.72%, P<0.0001). There was also a significant correlation between intestinal permeability and disease activity (5 h: r=0.45, P=0.0025; 24 h: r=0.51 P=0.0006). After medical therapy, (51)CrEDTA urinary excretion was significantly decreased (pre-treatment UC: 7.87%; post-treatment UC: 2.50%; P<0.0002). Briefly, the (51)CrEDTA test reflected colonic permeability in UC and might be useful as an indicator of disease severity. Moreover, this study suggested that, in patients with UC, medical therapy not only leads to the recovery of acute inflammation but also restores mucosal barrier integrity and function.

To evaluate intestinal permeability and absorption in healthy cats in association with diet and normal intestinal microflora.

6 healthy domestic shorthair cats.

A sugar solution containing D-xylose, 30-methyl-D-glucose, L-rhamnose, lactulose, and 51Cr-EDTA was administered intragastrically to healthy cats, and urinary excretion of ingested sugars was determined 5 hours after administration. After the same cats had received metronidazole for 1 month, the study was repeated. A final study was performed while cats were maintained on a new diet differing in composition and processing.

Lactulose-to-rhamnose ratios, reflecting intestinal permeability, were higher in cats, compared with values for humans or dogs, and values obtained before and after metronidazole administration (mean +/- SEM; before, 0.40 +/- 0.08; after, 0.45 +/- 0.09) were not significantly different. Intestinal absorption also was unaltered after antibiotic administration, and the xylose-to-glucose ratio was 0.70 +/- 0.03 before and 0.71 +/- 0.06 after metronidazole administration. Sugar recovery did not differ significantly while cats were maintained on canned or dry food.

Reference ranges were established for the percentage urinary recovery of orally administered D-xylose, 3-0-methyl-D-glucose, L-rhamnose, lactulose, and 51Cr-EDTA obtained after 5 hours in healthy cats. The intestines of cats appear to be more permeable than those of other species, although the normal bacterial microflora does not appear to influence the integrity or function of the feline intestine, because values obtained for the measured variables before or after antibiotic administration were not significantly different. In addition, differences were not detected when the diet was completely altered.

The effect of helminth infestation on the nutrition, growth, and physiology of the host is still poorly understood. Anthelmintic treatment of children in developing countries has had varying success in terms of growth improvements.

The objective of this study was to assess the effect of regular deworming on child growth, physiology, and biochemical status.

The study was a 12-mo longitudinal intervention in 123 Bangladeshi children aged 2-5 y. Treatment (mebendazole) or placebo tablets were administered every 2 mo for 8 mo and again at 12 mo. Weight, height, midupper arm circumference, intestinal permeability, plasma albumin, alpha(1)-antichymotrypsin, and total protein concentration were assessed every 2 mo.

Treatment with mebendazole reduced the prevalence of Ascaris lumbricoides from 78% to 8%, of Trichuris trichiura from 65% to 9%, and of hookworm from 4% to 0%. There was no significant difference in the growth of treated children compared with those given placebo tablets. No changes in intestinal permeability or plasma albumin were observed after deworming. Significant decreases in total protein (P<0.001) and alpha(1)-antichymotrypsin (P<0.001) were observed in the treatment group, indicating possible reductions in inflammation and immunoglobulin concentration after deworming. A significant increase in the prevalence of Giardia intestinalis (from 4% to 49%) in the treatment group was associated with a short-term reduction in weight (P = 0.02) and higher intestinal permeability (P <0.001) in infected subjects. No long-term effects of G. intestinalis on growth were observed.

Low-intensity helminth infections, predominantly of A. lumbricoides and T. trichiura, do not contribute significantly to the poor growth and biochemical status of rural Bangladeshi children.

Gut integrity, which can be measured by the urinary lactulose:mannitol excretion test, deteriorates with the introduction of weaning foods. In The Gambia, gut integrity measured monthly over 15 months in 119 infants (aged 2-15 months) was least impaired from April to June. This coincides with the time of year of maximum vitamin A (VA) intake-the mango season. Subsequently, two VA intervention studies were done in infants in India. Eighty infants attending a community health center received 16,700 IU weekly or placebo. In another study, 94 hospitalized infants were given 200, 000 IU VA or placebo: 31 received VA on admission, while the rest (32 VA, 31 placebo) received treatment on discharge. All VA-treated groups had more rapid improvement in gut integrity than the placebo groups, but no group had gut integrity normalized by Western standards. The data suggest that VA status may influence gut integrity.

Reliability of differential sugar absorption tests is hampered by a lack of standardization of the content and osmolarity of the test solutions. We evaluated the effect of osmolarity of the test solution of the sugar absorption test on the 5 hour urine excretion of orally administered lactulose and mannitol. A group of 28 controls and 14 coeliacs, with villous atrophy grade II to IV, ingested a hyperosmolar sugar absorption test solution and a "low"-osmolar solution, respectively. After an overnight fast, each subject ingested hyperosmolar sugar absorption test solution (2 g mannitol, 5 g lactulose and 40 g sucrose/100 ml (around 1,560 mmol/l)). After two days, this procedure was repeated with low-osmolar solution (2 g mannitol and 5 g lactulose/100 ml (around 375 mmol/l). The influence of the sequence of the tests on the results had previously been excluded. All urine from the 5 h-period following ingestion of the test solution was collected. To calculate the low-osmolar solution ratio, samples were analysed for lactulose and mannitol concentrations by gas chromatography The sensitivity of hyperosmolar SAT solution and low-osmolar solution for the detection of mucosal abnormalities in coeliacs was 64% and 43%, respectively. In conclusion, a hyperosmolar solution discriminates better between normal and damaged mucosa of the small bowel such as villous atrophy due to a relative increase in permeability for lactulose.

Poor growth performance during infancy and early childhood is a frequent fact of life in most developing countries. Work in The Gambia has demonstrated that more than 43 % of observed growth faltering during the first 15 months of life can be explained by the presence of a mucosal enteropathy in the small intestine. Within communities the illness is very common: in the area investigated more than 95 % of infants above 8 months of age were affected, and on average they suffered a growth-limiting enteropathy for more than 75 % of their first year of life. Two mechanisms of weight loss have been defined. First, partial villus atrophy reduces absorption and digestion of lactose and probably other nutrients. Second, and more importantly, damage to the mucosal barrier allows translocation of macromolecules into the mucosa and blood, triggering both local and systemic immune and inflammatory mechanisms. Given the severity of the enteropathy it is not surprising that infants fail to grow at a normal rate. Recent findings suggest that these lesions continue throughout childhood and into adulthood. Thus, a persistence of chronic, local and systemic inflammation throughout childhood may be responsible for continued poor growth during this period. Although the nature of the enteropathy and the mechanisms of growth failure have been defined, the factors involved in the initiation and persistence of the intestinal lesion remain uncertain, making clinical management difficult. More work is clearly required to elucidate these factors and to define interventions to prevent or treat the enteropathy.

To assess the validity of the use of a blood specimen for the sugar permeability test because of the high failure rate of 5-hour urine collection in young children with diarrhea.

Simultaneous 5-hour urine collections and timed blood tests were taken after ingestion of an isotonic solution of lactulose (L) and L-rhamnose (R) in 24 children with acute gastroenteritis and 25 children without diarrhea in a control group. Sugars were measured with high performance liquid chromatography, and the percent of recovered sugars was expressed as an L-R ratio.

With acute gastroenteritis the geometric mean L-R ratios (95% confidence intervals) were 12.4 (9.3 to 16.3) in urine and 9.4 (6.7 to 13.1) in blood compared with 6.7 (5.0 to 8.8) and 5.9 (4.4 to 7.8), respectively, in the control group. The level of agreement (kappa) among normal, intermediate, and high ratios for blood and urine was 0.71 (0.51 to 0.92). The failure rate of L-R tests was significantly reduced with a blood specimen (urine 37% vs blood 10%; P <.0001).

Intestinal permeability testing on a blood specimen is a valid alternative to urine collection in young children and has a significantly lower test failure rate.

Noninvasive assessment of intestinal permeability in vivo is based on the measurement of urinary excretion of orally administered sugar probes. It is expressed as a ratio, usually lactulose/rhamnose or 3-O-methyl-D-glucose (3-OMG)/rhamnose. In both endotoxemic and control rats that were receiving fluid, we observed an increase in the recovery of lactulose and 3-OMG but not rhamnose in both groups, suggesting an enhancement of intestinal permeability. In the measurement of intestinal permeability, all pre- and postmucosal factors are considered equal for all sugars. We hypothesized that postmucosal factors and not changes in intestinal permeability caused the increased urinary lactulose and 3-OMG recoveries observed during fluid loading. Therefore, the effects of fluid loading on urinary excretion of the sugar probes were studied in healthy rats receiving the sugars intravenously. After intravenous injection, fluid loading increased urinary lactulose recovery threefold but not that of 3-OMG and rhamnose. In conclusion, fluid loading increases the lactulose/rhamnose ratio independent of changes in intestinal permeability. The 3-OMG/rhamnose ratio is not influenced by fluid loading.

Northern Territory Aboriginal children hospitalised with acute gastroenteritis have high rates of acidosis, hypokalaemia, and dehydration.

To determine whether Aboriginal children with and without diarrhoea have greater impairment in intestinal function than non-Aboriginal children, as assessed by increased permeability ratios.

A descriptive study of 124 children (96 Aboriginal and 28 non-Aboriginal) hospitalised with and without diarrhoea. Intestinal permeability was assessed by the lactulose to rhamnose (L-R) ratio from a five hour urine collection.

In Aboriginal children, mean L-R ratios (95% confidence intervals) were 18.3 (17.1 to 19.6) with diarrhoea and 9.0 (7.3 to 11.0) without diarrhoea, and in non-Aboriginal children they were 5.9 (2.8 to 12. 3) and 4.2 (3.3 to 5.2), respectively. In patients with diarrhoea, L-R ratios were significantly raised when accompanied by acidosis (mean, 22.8; 95% CI, 17.0 to 30.5), hypokalaemia (mean, 20.7; 95% CI, 15.4 to 27.9), and >/= 5% dehydration (mean, 24.3; 95% CI, 19.0 to 29.6) compared with none of these complications (mean, 7.0; 95% CI, 3.5 to 13.8).

The high incidence of acidosis, hypokalaemia, and dehydration in Aboriginal children admitted with diarrhoeal disease is related to underlying small intestinal mucosal damage.

By varying stool water content using lactulose and codeine, we investigated the influence of luminal water content on the absorption of quinine, a transcellular probe, and 51Cr-EDTA, a paracellular probe, from the distal gut.

Sixteen volunteers entered a three-way cross-over trial in which absorption of probe markers from a timed-release delivery system was determined following treatment with lactulose 20 mls tds (increasing water content), or codeine 30 gms qds (decreasing water content), and compared with control untreated values. Stool water content was assessed by freeze drying stool samples. Site of release was determined by gamma scintigraphy, and absorption was measured by plasma levels and urinary recovery of the marker probes.

Lactulose accelerated ascending colon transit (3.7 +/- 0.8 vs 4.5 +/- 1.4 hrs, p < 0.05), increased stool water content (75 +/- 2 vs 71 +/- 2%, p < 0.01), caused greater dispersion of released material (dispersion score 3.4 +/- 0.3 vs 1.8 +/- 0.2, p < 0.01), and enhanced absorption of the transcellular probe quinine (4.66 +/- 0.78 vs 3.02 +/- 0.63%, p < 0.05) compared to control. Conversely codeine slowed ascending colon transit (8.9 +/- 1.8 hrs), reduced stool water content (61 +/- 2 vs 71.2%, p < 0.05), and tended to diminish absorption (2.60 +/- 0.77 vs 3.02 +/- 0.63%, p = 0.20). Within the ascending colon specifically, there was a significant trend for treatments increasing luminal water content to enhance quinine absorption (medians: codeine = 1.2%, [n = 81 < control = 2.3%, [n = 5] < lactulose = 3.2%, [n = 71, p < 0.01). Delivery site also had an important influence on absorption, with more distal release resulting in less absorption in the control arm (medians: small intestine = 4.4% [n = 5] > ascending colon = 2.3% [n = 5] > transverse colon = 1.5% [n = 6], p < 0.005).

Lactulose accelerates transit, increases stool water content, and enhances drug absorption from the distal gut whilst codeine slows transit, decreases stool water content, and tends to diminish absorption, compared to controls. We conclude that water content may be an important determinant in colonic drug absorption.

Vitamin A is the generic term for a variety of fat-soluble substances including retinol, retinyl palmitate and the provitamin A carotenoids such as all-trans-beta-carotene. Vitamin A is commonly known as the anti-infective vitamin and has an essential role in vision and cellular differentiation, the latter providing a unique core mechanism helping to explain the influence of vitamin A on epithelial barriers. Alterations in the epithelial lining of vital organs occur early in deficiency, suggesting a potentially important role for the barrier function. Vitamin A deficiency (VAD) is most commonly recognized in the eye. The conjunctival-impression cytology test detects the presence of larger irregular keratinized cells and the absence of mucous-secreting goblet cells, indicative of VAD. The method is simple, quick and sensitive in populations where VAD is present. In the respiratory tract, observational studies all show an association with VAD, although vitamin A supplementation studies appear to have little effect on respiratory disease. Organ-specific targeting may improve success rates. The dual-sugar intestinal-permeability test allows the effect of vitamin A supplementation to be monitored on the gastrointestinal tract. Two vitamin A supplementation studies were carried out recently in Orissa State, India. Healthy infants of weaning age were administered orally eight weekly doses of 5.0 mg retinol equivalents and hospitalized infants received one large oral dose 60 mg retinol equivalents in the form of retinyl palmitate. Improvements in gut integrity and haematological status were observed in both studies. In summary, the response of the eye to vitamin A supplementation is well established; the present review highlights some of the more recent observations examining the effects of vitamin A.

Subclinical alterations of small intestinal function have been reported frequently in tropical countries. Studies of small intestinal permeability to lactulose and mannitol were therefore completed in Guatemalan infants from a low-income, periurban community to assess the prevalence of altered intestinal function and the factors associated with this condition.

Two hundred studies were successfully completed in 158 infants who had been free of diarrhea for at least 1 week before the day of study. Urinary concentrations of lactulose and mannitol during the 5-hour period after ingestion of 400 mg/kg body weight of lactulose and 100 mg/kg body weight of mannitol were measured by gas-liquid chromatography and compared by age group, feeding practices, anthropometric indexes, and serum iron and zinc concentrations.

The overall prevalence of altered intestinal permeability (defined as a ratio of urinary recovery of lactulose to mannitol [L/M] > or =0.07) was 30%. The urinary L/M recovery ratio was positively associated with age; low weight for age; and, in infants less than 6 months of age, non-breast-feeding. Children with serum iron concentrations less than 7.16 microM/l (40 [microg/dl) had higher median L/M ratios (L/M = 0.068; 95% confidence interval [CI], 0.054, 0.085) than those with iron levels higher than this cutoff (L/M = 0.052; CI = 0.046, 0.058; p = 0.038). The median urinary L/M recovery ratio in 10 currently asymptomatic infants who had diarrhea during the week before testing (0.087; CI = 0.49, 0.154) was higher than that in children who had been free from diarrhea for at least 1 week (0.052; CI = 0.048, 0.056; p = 0.01).

Age, feeding practices, low weight-for-age, low serum iron concentration, and recent diarrhea were all associated with altered intestinal function in this group of Guatemalan infants.

Non-steroidal anti-inflammatory drugs induce damage throughout the entire gastrointestinal tract. Administration of site-specific permeability probes is a non-invasive technique for assessing the functional integrity of the gastrointestinal mucosa. A systematic search tor NSAID-induced permeability studies using MEDLINE and EMBASE, and an analysis of the literature on NSAID-induced gastrointestinal permeability, were carried out. The advantages and disadvantages of the various probes and study protocols are discussed. Identification of the underlying mechanisms of regulatory control of the epithelial tight junction is still needed. A greater appreciation of the pharmacokinetics and distribution of NSAIDs, coupled with gastrointestinal permeability studies, may help delineate the pathogenesis of NSAID-induced gastrointestinal toxicity. Non-invasive tests of gastric, intestinal and colonic permeability have shown promise in both basic research and in clinical practice. While such tests could not replace endoscopy, they may represent clinically useful techniques for identifying patients who would benefit from endoscopy, to assess the response to treatment, and perhaps to predict the clinical course of disease.

Specially collected, spray-dried bovine and porcine blood plasma have been incorporated previously in feeds of weanling farm animals, resulting in increased dietary intakes and greater rates of weight gain than observed in control animals. Before conducting similar trials in human populations, preliminary studies have been completed to assess the acceptability, safety, and digestibility of processed animal plasma in young children.

Masked study diets were provided sequentially to each of ten young, Peruvian children recovering from severe protein-energy malnutrition during three randomly ordered 7-day dietary periods. The control diet was prepared from rice, milk, vegetable oil, and sugar; the two study diets included spray-dried, bovine serum concentrate to replace either 25% or 50% of the milk protein of the control diet. Urine and feces were collected quantitatively during the last four days of each diet period to assess stool weight, apparent absorption of macronutrients, and retention of nitrogen.

All children consumed the entire amounts offered of each of the diets. The mean number of daily bowel movements and mean apparent absorption and retention of nitrogen and mean apparent absorption of carbohydrate were similar for each diet. Fractional absorption of dietary lipid and of total energy increased significantly in relation to the amount of bovine serum concentrate in the diet, although this might be explained by the simultaneous replacement of milk fat with additional vegetable oil.

Each of the diets was well accepted by the study children, and there was no evidence of any adverse effects of bovine serum concentrate.