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Sample records for abnormal intestinal permeability

  1. Abnormal intestinal permeability in primary biliary cirrhosis.

    Science.gov (United States)

    Feld, Jordan J; Meddings, Jonathan; Heathcote, E Jenny

    2006-09-01

    Antimitochondrial antibodies (AMAs) found in patients with primary biliary cirrhosis (PBC) cross-react with bacterial proteins and hence molecular mimicry has been proposed as a mechanism for AMA development. Alterations in gastrointestinal permeability would provide a potential route for increased exposure of gut flora to the immune system. In this study we aimed to compare the measured gastrointestinal permeability in patients with PBC to that in patients with liver disease (hepatitis C) and healthy control populations. Subjects drank a mixture of sucrose, lactulose, and mannitol dissolved in water. Eight-hour urinary excretion of the sugars was measured to assess intestinal permeability. Antiendomysial antibody testing was performed to exclude subclinical celiac disease. Eighty-six patients with PBC were evaluated and compared to 69 hepatitis C patients and 155 healthy controls. The mean urinary excretion of sucrose in the PBC patients (133.89 +/- 72.56 mg) was significantly higher than that in hepatitis C patients (101.07+/-63.35) or healthy controls (89.46+/-41.76) (P=0.0001), suggesting abnormal gastric or proximal small intestinal permeability. Sucrose excretion was not increased among patients with hepatitis C compared to healthy controls. The ratio of lactulose:mannitol excretion, reflecting small bowel permeability, was also elevated in the PBC group (0.017+/-0.012) compared to healthy controls (0.012+/-0.007) (P=0.0001) but was equal to that found among patients with hepatitis C (0.016+/-0.011) (P=NS). We conclude that the permeability of both the stomach and the small bowel is increased in patients with PBC, however, it is unclear if it is a cause, consequence, or manifestation of the disease.

  2. Alterations in Intestinal Permeability After Thermal Injury,

    Science.gov (United States)

    1992-01-01

    circulation, remain un- intestinal mucosal blood flow is markedly decreased after metabolized , and are excreted by the kidney. Mannitol is thermal...is a positive correlation between burn 6. Menzles IS, Pounder R, Laker MP, et al. Abnormal Intes- size and endotoxemia , not every burned patient...develops tinal permeability to sugars In villous atrophy. Lancet. 1979; endotoxemia during the postburn course. It is possible 2:1107-1109. that a

  3. INTESTINAL PERMEABILITY IN PEDIATRIC GASTROENTEROLOGY

    NARCIS (Netherlands)

    VANELBURG, RM; UIL, JJ; DEMONCHY, JGR; HEYMANS, HSA

    1992-01-01

    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

  4. Quantitation of small intestinal permeability during normal human drug absorption

    OpenAIRE

    Levitt, David G

    2013-01-01

    Background Understanding the quantitative relationship between a drug?s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorpti...

  5. Intestinal permeability - a new target for disease prevention and therapy

    NARCIS (Netherlands)

    Bischoff, S.C.; Barbara, G.; Buurman, W.; Ockhuizen, T.; Schulzke, J.D.; Serino, M.; Tilg, H.; Watson, A.; Wells, J.M.

    2014-01-01

    Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review,

  6. Intestinal permeability in exocrine pancreatic insufficiency due to cystic fibrosis or chronic pancreatitis

    NARCIS (Netherlands)

    vanElburg, RM; Uil, JJ; vanAalderen, WMC; Mulder, CJJ; Heymans, HSA

    Disturbances of the intestinal integrity, reflected by an increased intestinal permeability, are reported in cystic fibrosis (CF). Controversy exists whether the increased intestinal permeability is due to CF itself or a consequence of the concomitant exocrine pancreatic insufficiency (PI). We

  7. Bovine Colostrum Supplementation During Running Training Increases Intestinal Permeability

    Directory of Open Access Journals (Sweden)

    Grant D. Brinkworth

    2009-12-01

    Full Text Available Endurance exercise training can increase intestinal permeability which may contribute to the development of gastrointestinal symptoms in some athletes. Bovine colostrum (BC supplementation reduces intestinal permeability induced by non-steroidal anti-inflammatory drugs. This study aimed to determine whether BC could also reduce intestinal permeability induced by endurance exercise. Thirty healthy adult males (25.0 ± 4.7 yr; mean ± SD completed eight weeks of running three times per week for 45 minutes at their lactate threshold while consuming 60 g/day of BC, whey protein (WP or control (CON. Intestinal permeability was assessed at baseline and after eight weeks by measuring the ratio of urinary lactulose (L and rhamnose (R excretion. After eight weeks the L/R ratio increased significantly more in volunteers consuming BC (251 ± 140% compared with WP (21 ± 35%, P < 0.05 and CON (−7 ± 13%, P < 0.02. The increase in intestinal permeability with BC may have been due to BC inducing greater leakiness of tight junctions between enterocytes or by increasing macromolecular transport as it does in neonatal gut. Further research should investigate the potential for BC to increase intestinal macromolecular transport in adults.

  8. Quantitation of small intestinal permeability during normal human drug absorption

    Science.gov (United States)

    2013-01-01

    Background Understanding the quantitative relationship between a drug’s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorption in humans was determined by deconvolution and related to the intestinal permeability by the use of a new 3 parameter model function (“Averaged Model” (AM)). The theoretical validity of this AM model was evaluated by comparing it to the standard diffusion-convection model (DC). This analysis was applied to 90 drugs using previously published data. Only drugs that were administered in oral solution form to fasting subjects were considered so that the rate of gastric emptying was approximately known. All the calculations are carried out using the freely available routine PKQuest Java (http://www.pkquest.com) which has an easy to use, simple interface. Results Theoretically, the AM permeability provides an accurate estimate of the intestinal DC permeability for solutes whose absorption ranges from 1% to 99%. The experimental human AM permeabilities determined by deconvolution are similar to those determined by direct human jejunal perfusion. The small intestinal pH varies with position and the results are interpreted in terms of the pH dependent octanol partition. The permeability versus partition relations are presented separately for the uncharged, basic, acidic and charged solutes. The small uncharged solutes caffeine, acetaminophen and antipyrine have very high permeabilities (about 20 x 10-4 cm/sec) corresponding to an unstirred layer of only 45 μm. The weak acid aspirin also has a large AM permeability despite its low octanol partition at pH 7.4, suggesting

  9. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Christopher B Forsyth

    Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress, and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP. Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD, as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for earlier

  10. Regulation of intestinal permeability: The role of proteases.

    Science.gov (United States)

    Van Spaendonk, Hanne; Ceuleers, Hannah; Witters, Leonie; Patteet, Eveline; Joossens, Jurgen; Augustyns, Koen; Lambeir, Anne-Marie; De Meester, Ingrid; De Man, Joris G; De Winter, Benedicte Y

    2017-03-28

    The gastrointestinal barrier is - with approximately 400 m 2 - the human body's largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extra-intestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases.

  11. Pathogenesis of the permeability barrier abnormality in epidermolytic hyperkeratosis.

    Science.gov (United States)

    Schmuth, M; Yosipovitch, G; Williams, M L; Weber, F; Hintner, H; Ortiz-Urda, S; Rappersberger, K; Crumrine, D; Feingold, K R; Elias, P M

    2001-10-01

    Epidermolytic hyperkeratosis is a dominantly inherited ichthyosis, frequently associated with mutations in keratin 1 or 10 that result in disruption of the keratin filament cytoskeleton leading to keratinocyte fragility. In addition to blistering and a severe disorder of cornification, patients typically display an abnormality in permeability barrier function. The nature and pathogenesis of the barrier abnormality in epidermolytic hyperkeratosis are unknown, however. We assessed here, first, baseline transepidermal water loss and barrier recovery kinetics in patients with epidermolytic hyperkeratosis. Whereas baseline transepidermal water loss rates were elevated by approximately 3-fold, recovery rates were faster in epidermolytic hyperkeratosis than in age-matched controls. Electron microscopy showed no defect in either the cornified envelope or the adjacent cornified-bound lipid envelope, i.e., a corneocyte scaffold abnormality does not explain the barrier abnormality. Using the water-soluble tracer, colloidal lanthanum, there was no evidence of tracer accumulation in corneocytes, despite the fragility of nucleated keratinocytes. Instead, tracer, which was excluded in normal skin, moved through the extracellular stratum corneum domains. Increasing intercellular permeability correlated with decreased quantities and defective organization of extracellular lamellar bilayers. The decreased lamellar material, in turn, could be attributed to incompletely secreted lamellar bodies within granular cells, demonstrable not only by several morphologic findings, but also by decreased delivery of a lamellar body content marker, acid lipase, to the stratum corneum interstices. Yet, after acute barrier disruption a rapid release of preformed lamellar body contents was observed together with increased organelle contents in the extracellular spaces, accounting for the accelerated recovery kinetics in epidermolytic hyperkeratosis. Accelerated recovery, in turn, correlated with a

  12. Intestinal permeability and glucagon-like peptide-2 in children with autism

    DEFF Research Database (Denmark)

    Robertson, Marli A; Sigalet, David L; Holst, Jens Juul

    2008-01-01

    We measured small intestinal permeability using a lactulose:mannitol sugar permeability test in a group of children with autism, with current or previous gastrointestinal complaints. Secondly, we examined whether children with autism had an abnormal glucagon-like peptide-2 (GLP-2) response...... to feeding. Results were compared with sibling controls and children without developmental disabilities. We enrolled 14 children with autism, 7 developmentally normal siblings of these children and 8 healthy, developmentally normal, unrelated children. Our study did not detect differences in these measures...... of gastrointestinal function in a group of children with autism....

  13. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease.

    Science.gov (United States)

    Schwiertz, Andreas; Spiegel, Jörg; Dillmann, Ulrich; Grundmann, David; Bürmann, Jan; Faßbender, Klaus; Schäfer, Karl-Herbert; Unger, Marcus M

    2018-02-12

    Intestinal inflammation and increased intestinal permeability (both possibly fueled by dysbiosis) have been suggested to be implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The objective of the current study was to investigate whether fecal markers of inflammation and impaired intestinal barrier function corroborate this pathogenic aspect of PD. In a case-control study, we quantitatively analyzed established fecal markers of intestinal inflammation (calprotectin and lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age) by enzyme-linked immunosorbent assay. The study design controlled for potential confounding factors. Calprotectin, a fecal marker of intestinal inflammation, and two fecal markers of increased intestinal permeability (alpha-1-antitrypsin and zonulin) were significantly elevated in PD patients compared to age-matched controls. Lactoferrin, as a second fecal marker of intestinal inflammation, showed a non-significant trend towards elevated concentrations in PD patients. None of the four fecal markers correlated with disease severity, PD subtype, dopaminergic therapy, or presence of constipation. Fecal markers reflecting intestinal inflammation and increased intestinal permeability have been primarily investigated in inflammatory bowel disease so far. Our data indicate that calprotectin, alpha-1-antitrypsin and zonulin could be useful non-invasive markers in PD as well. Even though these markers are not disease-specific, they corroborate the hypothesis of an intestinal inflammation as contributing factor in the pathogenesis of PD. Further investigations are needed to determine whether calprotectin, alpha-1-antitrypsin and zonulin can be used to define PD subgroups and to monitor the effect of interventions in PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Increasing dietary oat fibre decreases the permeability of intestinal mucus.

    Science.gov (United States)

    Mackie, Alan; Rigby, Neil; Harvey, Pascale; Bajka, Balazs

    2016-10-01

    This study investigates the influence of the dietary fibre β-glucan on nutrient composition and mucus permeability. Pigs were fed a standard diet or a diet containing twice the β-glucan content for 3 days (n = 5 per group), followed by the collection of small intestinal mucus and tissue samples. Samples of the consumed diets were subjected to in vitro digestion to determine β-glucan release, nutrient profile and assessment of mucus permeability. In vitro digestion of the diets indicated that 90% of the β-glucan was released in the proximal small intestine. Measurements of intestinal mucus showed a reduction in permeability to 100 nm latex beads and also lipid from the digested enhanced β-glucan diet. The data from this study show for the first time that reducing mass transfer of bile and lipid through the intestinal mucus layer may be one way in which this decrease in bile reabsorption by soluble fibre is enabled.

  15. Intestinal permeability and carrier-mediated monosaccharide absorption in preterm neonates during the early postnatal period

    NARCIS (Netherlands)

    Rouwet, Ellen V.; Heineman, Erik; Buurman, Wim A.; ter Riet, Gerben; Ramsay, Graham; Blanco, Carlos E.

    2002-01-01

    Immaturity of intestinal epithelial barrier function and absorptive capacity may play a role in the pathophysiology of intestinal complications in preterm neonates during the early postnatal period. We determined the intestinal permeability and carrier-mediated absorption of monosaccharides in

  16. Fructokinase, Fructans, Intestinal Permeability, and Metabolic Syndrome: An Equine Connection?

    Science.gov (United States)

    Johnson, Richard J; Rivard, Chris; Lanaspa, Miguel A.; Otabachian-Smith, Silvia; Ishimoto, Takuji; Cicerchi, Christina; Cheeke, Peter R.; MacIntosh, Bridgett; Hess, Tanja

    2012-01-01

    Fructose is a simple sugar present in honey and fruit, but can also exist as a polymer (fructans) in pasture grasses. Mammals are unable to metabolize fructans, but certain gram positive bacteria contain fructanases and can convert fructans to fructose in the gut. Recent studies suggest that fructose generated from bacteria, or directly obtained from the diet, can induce both increased intestinal permeability and features of metabolic syndrome, especially the development of insulin resistance. The development of insulin resistance is driven in part by the metabolism of fructose by fructokinase C in the liver, which results in oxidative stress in the hepatocyte. Similarly, the metabolism of fructose in the small bowel by intestinal fructokinase may lead to increased intestinal permeability and endotoxemia. While speculative, these observations raise the possibility that the mechanism by which fructans induce laminitis could involve intestinal and hepatic fructokinase. Further studies are indicated to determine the role of fructanases, fructose and fructokinase in equine metabolic syndrome and laminitis. PMID:23439477

  17. Intestinal permeability study of minoxidil: assessment of minoxidil as a high permeability reference drug for biopharmaceutics classification.

    Science.gov (United States)

    Ozawa, Makoto; Tsume, Yasuhiro; Zur, Moran; Dahan, Arik; Amidon, Gordon L

    2015-01-05

    The purpose of this study was to evaluate minoxidil as a high permeability reference drug for Biopharmaceutics Classification System (BCS). The permeability of minoxidil was determined in in situ intestinal perfusion studies in rodents and permeability studies across Caco-2 cell monolayers. The permeability of minoxidil was compared with that of metoprolol, an FDA reference drug for BCS classification. In rat perfusion studies, the permeability of minoxidil was somewhat higher than that of metoprolol in the jejunum, while minoxidil showed lower permeability than metoprolol in the ileum. The permeability of minoxidil was independent of intestinal segment, while the permeability of metoprolol was region-dependent. Similarly, in mouse perfusion study, the jejunal permeability of minoxidil was 2.5-fold higher than that of metoprolol. Minoxidil and metoprolol showed similar permeability in Caco-2 study at apical pH of 6.5 and basolateral pH of 7.4. The permeability of minoxidil was independent of pH, while metoprolol showed pH-dependent transport in Caco-2 study. Minoxidil exhibited similar permeability in the absorptive direction (AP-BL) in comparison with secretory direction (BL-AP), while metoprolol had higher efflux ratio (ER > 2) at apical pH of 6.5 and basolateral pH of 7.4. No concentration-dependent transport was observed for either minoxidil or metoprolol transport in Caco-2 study. Verapamil did not alter the transport of either compounds across Caco-2 cell monolayers. The permeability of minoxidil was independent of both pH and intestinal segment in intestinal perfusion studies and Caco-2 studies. Caco-2 studies also showed no involvement of carrier mediated transport in the absorption process of minoxidil. These results suggest that minoxidil may be an acceptable reference drug for BCS high permeability classification. However, minoxidil exhibited higher jejunal permeability than metoprolol and thus to use minoxidil as a reference drug would raise the

  18. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease.

    Science.gov (United States)

    Fasano, A; Not, T; Wang, W; Uzzau, S; Berti, I; Tommasini, A; Goldblum, S E

    2000-04-29

    We identified zonulin, a novel human protein analogue to the Vibrio cholerae derived Zonula occludens toxin, which induces tight junction disassembly and a subsequent increase in intestinal permeability in non-human primate intestinal epithelia. Zonulin expression was raised in intestinal tissues during the acute phase of coeliac disease, a clinical condition in which tight junctions are opened and permeability is increased.

  19. Pathophysiology of increased intestinal permeability in obstructive jaundice

    Science.gov (United States)

    Assimakopoulos, Stelios F; Scopa, Chrisoula D; Vagianos, Constantine E

    2007-01-01

    Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome. PMID:18161914

  20. Computational approaches for modeling human intestinal absorption and permeability.

    Science.gov (United States)

    Subramanian, Govindan; Kitchen, Douglas B

    2006-07-01

    Human intestinal absorption (HIA) is an important roadblock in the formulation of new drug substances. Computational models are needed for the rapid estimation of this property. The measurements are determined via in vivo experiments or in vitro permeability studies. We present several computational models that are able to predict the absorption of drugs by the human intestine and the permeability through human Caco-2 cells. The training and prediction sets were derived from literature sources and carefully examined to eliminate compounds that are actively transported. We compare our results to models derived by other methods and find that the statistical quality is similar. We believe that models derived from both sources of experimental data would provide greater consistency in predictions. The performance of several QSPR models that we investigated to predict outside the training set for either experimental property clearly indicates that caution should be exercised while applying any of the models for quantitative predictions. However, we are able to show that the qualitative predictions can be obtained with close to a 70% success rate.

  1. Intestinal permeability and nutritional status in developmental disorders.

    Science.gov (United States)

    Souza, Nilian Carla Silva; Mendonca, Jacqueline Nakau; Portari, Guilherme Vannucchi; Jordao Junior, Alceu Afonso; Marchini, Julio Sergio; Chiarello, Paula Garcia

    2012-01-01

    Autism is a developmental disorder with a possible connection between dietary components and triggering or worsening of symptoms. An altered intestinal permeability might allow absorption of incompletely digested peptides (gluten and casein) that could produce opioid-like activity on the brain, causing significant changes in behavior. To assess the intestinal permeability and nutritional status of participants with developmental disorders to determine if changes in the intestinal mucosal barrier and/or injury to the intercellular junctions have occurred that might justify application of further dietary modifications. To assess intestinal permeability, the research team analyzed participants urine under fasting conditions, using gas chromatography to determine chromatographic peaks. To assess nutritional status, the team determined participants heights and weights and performed a bioelectric bioimpedance examination at least 4 hours after their most recent meal. In addition, the team determined food intake using three diet diaries. They asked participants and caregivers to register each food consumed during 2 nonconsecutive weekdays and 1 weekend day. The study occurred at the Ribeirao Preto School of Medicine, Sao Paulo University. Seven participants aged 9 to 23 years with developmental disorders (the developmental group, DG) completed the study. The research team recruited them through the Association of Friends of the Autistic Persons of Ribeirao Preto in Ribeirao Preto, Brazil. The control group (CG) consisted of nonsmoking healthy volunteers in the general population who were similar in age to the experimental group and did not suffer from diseases that potentially could influence nutritional status and intestinal function. To assess intestinal permeability, participants ingested 150 mL of an isosmolar solution of the sugars mannitol (2 g) and lactulose (7.5 g) under fasting conditions and the researchers collected all voided urine over a period of 5 hours

  2. Clinical implications of the sugar absorption test: intestinal permeability test to assess mucosal barrier function

    NARCIS (Netherlands)

    Uil, J. J.; van Elburg, R. M.; van Overbeek, F. M.; Mulder, C. J.; vanBerge-Henegouwen, G. P.; Heymans, H. S.

    1997-01-01

    Functional integrity as an aspect of the mucosal barrier function of the small bowel can be estimated by the intestinal permeability for macromolecules. In the first part of this paper, an overview of intestinal permeability and its measurement is given. In the second part of the paper our own

  3. Increased intestinal marker absorption due to regional permeability changes and decreased intestinal transit during sepsis in the rat

    International Nuclear Information System (INIS)

    Wang, Q.; Pantzar, N.; Jeppson, B.; Westroem, B.R.; Karlsson, B.W.

    1994-01-01

    The intestinal barrier properties are impaired during inflammation and sepsis, but the mechanisms behind this are unknown and were therefore investigated during experimental sepsis in rats. The different-sized intestinal absorption markers 51 Cr-labeled ethylenediaminetetraacetic acid (EDTA) and ovalbumin were gavaged to rats made septic by intra-abdominal bacterial implantation and to sham-operated rats. Regional tissue permeability was measured in diffusion chambers, and intestinal transit was evaluated by intestinal accumulation of gavaged 51 Cr-EDTA. In comparison with the sham-operated rats, septic rats had higher 51 Cr-EDTA levels in blood and urine and showed a prolonged intestinal transit. Septic rats also had a lower tissue permeability to both markers in the small intestines but higher permeability to ovalbumin in the colon. Rats receiving morphine to decrease intestinal motility showed similar changes, with a decreased intestinal transit and increased marker absorption. Thr results suggest that the increased intestinal absorption during sepsis was due to regional permeability changes and prolonged intestinal transit. 38 refs., 4 figs., 2 tabs

  4. Intestinal permeability to 99mTc-diethylenetriaminopentaacetic acid in inflammatory bowel disease

    International Nuclear Information System (INIS)

    Casellas, F.; Aguade, S.; Soriano, B.; Accarino, A.; Molero, J.; Guarner, L.

    1986-01-01

    Intestinal permeability in inflammatory bowel disease and its relation to periods of disease activity has been investigated by measuring the urinary excretion of DTPA labeled with 99mTc. Urine excretion in 10 control subjects was 2.7 +/- 1% of the test dose. Twelve patients with ulcerative colitis excreted 5.08 +/- 1.6% in remission, 10.61 +/- 2% during periods of mild activity, 19.41 +/- 0.9% during moderate activity, and 15.41 +/- 6.3% with severe activity. Sixteen patients with Crohn's disease excreted 5.7 +/- 1.9% in remission, 8.47 +/- 2.8% during mild activity of the disease, and 14.29 +/- 5.8% during moderate activity. No differences were observed between ulcerative colitis and Crohn's disease, or between ileal and colonic forms of Crohn's disease. Excretion in remission was significantly greater than in control subjects and there was a correlation between excretion and disease activity. In serial determinations done in seven patients we found that urine excretion of the test substance correlated with disease activity. We also studied DTPA excretion in 10 cases with gastric or duodenal ulcer (2.28 +/- 1.4%), six cases of acute gastroenteritis (4.87 +/- 3.1%) and nine cases with other intestinal diseases (3.6 +/- 1.1%). In all these cases, DTPA excretion was lower than in inflammatory bowel disease. Our results show that the urinary excretion of DTPA is a simple test that measures accurately the degree of activity of inflammatory bowel disease. The test is useful in Crohn's disease as well as in ulcerative colitis, and detects intestinal permeability abnormalities even in clinical remission. Significantly lower excretions are found in other intestinal diseases. The test may be recommended as a screening test for use in clinical practice

  5. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.

    Science.gov (United States)

    Drago, Sandro; El Asmar, Ramzi; Di Pierro, Mariarosaria; Grazia Clemente, Maria; Tripathi, Amit; Sapone, Anna; Thakar, Manjusha; Iacono, Giuseppe; Carroccio, Antonio; D'Agate, Cinzia; Not, Tarcisio; Zampini, Lucia; Catassi, Carlo; Fasano, Alessio

    2006-04-01

    Little is known about the interaction of gliadin with intestinal epithelial cells and the mechanism(s) through which gliadin crosses the intestinal epithelial barrier. We investigated whether gliadin has any immediate effect on zonulin release and signaling. Both ex vivo human small intestines and intestinal cell monolayers were exposed to gliadin, and zonulin release and changes in paracellular permeability were monitored in the presence and absence of zonulin antagonism. Zonulin binding, cytoskeletal rearrangement, and zonula occludens-1 (ZO-1) redistribution were evaluated by immunofluorescence microscopy. Tight junction occludin and ZO-1 gene expression was evaluated by real-time polymerase chain reaction (PCR). When exposed to gliadin, zonulin receptor-positive IEC6 and Caco2 cells released zonulin in the cell medium with subsequent zonulin binding to the cell surface, rearrangement of the cell cytoskeleton, loss of occludin-ZO1 protein-protein interaction, and increased monolayer permeability. Pretreatment with the zonulin antagonist FZI/0 blocked these changes without affecting zonulin release. When exposed to luminal gliadin, intestinal biopsies from celiac patients in remission expressed a sustained luminal zonulin release and increase in intestinal permeability that was blocked by FZI/0 pretreatment. Conversely, biopsies from non-celiac patients demonstrated a limited, transient zonulin release which was paralleled by an increase in intestinal permeability that never reached the level of permeability seen in celiac disease (CD) tissues. Chronic gliadin exposure caused down-regulation of both ZO-1 and occludin gene expression. Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.

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

    NARCIS (Netherlands)

    Koetse, H. A.; Klaassen, D.; van der Molen, A. R. H.; Elzinga, H.; Bijsterveld, K.; Boverhof, R.; Stellaard, F.

    2006-01-01

    Background Intestinal mucosal damage causes impaired digestive capacity and increased mucosal permeability. Quantification of damage can be used to improve treatment options. Currently, the Lactose Digestion Index (LDI) and the Sugar Absorption Test (SAT) are used for evaluation. The investigation

  7. Intestinal and gastric permeability in children with eosinophilic esophagitis and reflux esophagitis.

    Science.gov (United States)

    Leung, Aldrich J T; Persad, Sujata; Slae, Mordechai; Abdelradi, Amr; Kluthe, Cheryl; Shirton, Leanne; Danchuk, Ronda; Persad, Rabin; Meddings, Jon; Huynh, Hien Q

    2015-02-01

    Eosinophilic esophagitis (EoE) is an allergic and immune-mediated entity that leads to a characteristic inflammation of esophageal mucosa. Patients complain of dysphagia and reflux-like symptoms. As many as 80% of patients with EoE may also have a history of atopy, and patients with asthma and eczema have previously been shown to have increased intestinal permeability. This study was designed to assess small intestinal and gastric permeability in patients with EoE and to see whether it differed from healthy individuals and patients with reflux esophagitis (RE). Gastric and small intestinal permeability was measured using sugar probe tests containing lactulose, mannitol, and sucrose. Lactulose-to-mannitol (L/M) ratios in the patient's urine were a measure for intestinal permeability, and total sucrose was a measure for gastric permeability. We analyzed samples from 23 patients with EoE, 20 RE, 14 normal upper endoscopy with gastrointestinal symptoms, and 26 healthy controls. All of the 4 groups had L/M ratios less than the upper limit of normal (<0.025). There was no statistically significant difference in gastric permeability between the 4 groups (L/M P = 0.26, sucrose P = 0.46). Our data suggest that an alteration in gastric and intestinal permeability does not play a role in EoE or RE pathogenesis.

  8. Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice.

    Science.gov (United States)

    Diao, Lei; Mei, Qiao; Xu, Jian-Ming; Liu, Xiao-Chang; Hu, Jing; Jin, Juan; Yao, Qiang; Chen, Mo-Li

    2012-03-14

    To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

  9. Transmural intestinal wall permeability in severe ischemia after enteral protease inhibition.

    Directory of Open Access Journals (Sweden)

    Angelina E Altshuler

    Full Text Available In intestinal ischemia, inflammatory mediators in the small intestine's lumen such as food byproducts, bacteria, and digestive enzymes leak into the peritoneal space, lymph, and circulation, but the mechanisms by which the intestinal wall permeability initially increases are not well defined. We hypothesize that wall protease activity (independent of luminal proteases and apoptosis contribute to the increased transmural permeability of the intestine's wall in an acutely ischemic small intestine. To model intestinal ischemia, the proximal jejunum to the distal ileum in the rat was excised, the lumen was rapidly flushed with saline to remove luminal contents, sectioned into equal length segments, and filled with a tracer (fluorescein in saline, glucose, or protease inhibitors. The transmural fluorescein transport was determined over 2 hours. Villi structure and epithelial junctional proteins were analyzed. After ischemia, there was increased transmural permeability, loss of villi structure, and destruction of epithelial proteins. Supplementation with luminal glucose preserved the epithelium and significantly attenuated permeability and villi damage. Matrix metalloproteinase (MMP inhibitors (doxycycline, GM 6001, and serine protease inhibitor (tranexamic acid in the lumen, significantly reduced the fluorescein transport compared to saline for 90 min of ischemia. Based on these results, we tested in an in-vivo model of hemorrhagic shock (90 min 30 mmHg, 3 hours observation for intestinal lesion formation. Single enteral interventions (saline, glucose, tranexamic acid did not prevent intestinal lesions, while the combination of enteral glucose and tranexamic acid prevented lesion formation after hemorrhagic shock. The results suggest that apoptotic and protease mediated breakdown cause increased permeability and damage to the intestinal wall. Metabolic support in the lumen of an ischemic intestine with glucose reduces the transport from the lumen

  10. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress.

    Science.gov (United States)

    Karl, J Philip; Margolis, Lee M; Madslien, Elisabeth H; Murphy, Nancy E; Castellani, John W; Gundersen, Yngvar; Hoke, Allison V; Levangie, Michael W; Kumar, Raina; Chakraborty, Nabarun; Gautam, Aarti; Hammamieh, Rasha; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

    2017-06-01

    The magnitude, temporal dynamics, and physiological effects of intestinal microbiome responses to physiological stress are poorly characterized. This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers ( n = 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ± 57% (mean ± SD, P Intestinal microbiota responses were characterized by increased α-diversity and changes in the relative abundance of >50% of identified genera, including increased abundance of less dominant taxa at the expense of more dominant taxa such as Bacteroides Changes in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Together, pre-STRESS Actinobacteria relative abundance and changes in serum IL-6 and stool cysteine concentrations accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation and with intestinal microbiota composition and metabolism. Associations between IP, the pre-STRESS microbiota, and microbiota metabolites suggest that targeting the intestinal microbiota could provide novel strategies for preserving IP during physiological stress. NEW & NOTEWORTHY Military training, a unique model for studying temporal dynamics of intestinal barrier and intestinal microbiota responses to stress, resulted in increased intestinal permeability concomitant with

  11. /sup 51/Cr-EDTA//sup 14/C-mannitol intestinal permeability test. Clinical use in screening for coeliac disease

    Energy Technology Data Exchange (ETDEWEB)

    Fotherby, K.J.; Wraight, E.P.; Neale, G.

    1988-01-01

    An intestinal permeability test with a combination of /sup 51/Cr-EDTA and /sup 14/C-mannitol was performed under routine conditions on 176 occasions in 161 adult patients. Of these patients, 116 were under investigation for possible coeliac disease, 33 were known to have coeliac disease, and 12 had inflammatory bowel disease. Small-bowel biopsies were performed in 61 patients. Expressing the results as the ratio of the 6-h urinary recoveries of the two probes was as sensitive as 95%, but more specific for histological mucosal abnormality (62% versus 46%) than measuring the urinary recovery of /sup 51/Cr-EDTA alone. All but two of the patients with active inflammatory bowel disease, whether Crohn's disease or ulcerative colitis, had an abnormal ratio. The /sup 51/Cr-EDTA//sup 14/C-mannitol intestinal permeablity test with a 6-h urine collection is a rapid and simple test of small-intestinal function suitable for routine use. 19 refs.

  12. Oral Supplementation with Bovine Colostrum Decreases Intestinal Permeability and Stool Concentrations of Zonulin in Athletes

    Directory of Open Access Journals (Sweden)

    Maciej Hałasa

    2017-04-01

    Full Text Available Increased intestinal permeability has been implicated in various pathologies, has various causes, and can develop during vigorous athletic training. Colostrum bovinum is a natural supplement with a wide range of supposed positive health effects, including reduction of intestine permeability. We assessed influence of colostrum supplementation on intestinal permeability related parameters in a group of 16 athletes during peak training for competition. This double-blind placebo-controlled study compared supplementation for 20 days with 500 mg of colostrum bovinum or placebo (whey. Gut permeability status was assayed by differential absorption of lactulose and mannitol (L/M test and stool zonulin concentration. Baseline L/M tests found that six of the participants (75% in the colostrum group had increased intestinal permeability. After supplementation, the test values were within the normal range and were significantly lower than at baseline. The colostrum group Δ values produced by comparing the post-intervention and baseline results were also significantly lower than the placebo group Δ values. The differences in stool zonulin concentration were smaller than those in the L/M test, but were significant when the Δ values due to intervention were compared between the colostrum group and the placebo group. Colostrum bovinum supplementation was safe and effective in decreasing of intestinal permeability in this series of athletes at increased risk of its elevation.

  13. Oral Supplementation with Bovine Colostrum Decreases Intestinal Permeability and Stool Concentrations of Zonulin in Athletes.

    Science.gov (United States)

    Hałasa, Maciej; Maciejewska, Dominika; Baśkiewicz-Hałasa, Magdalena; Machaliński, Bogusław; Safranow, Krzysztof; Stachowska, Ewa

    2017-04-08

    Increased intestinal permeability has been implicated in various pathologies, has various causes, and can develop during vigorous athletic training. Colostrum bovinum is a natural supplement with a wide range of supposed positive health effects, including reduction of intestine permeability. We assessed influence of colostrum supplementation on intestinal permeability related parameters in a group of 16 athletes during peak training for competition. This double-blind placebo-controlled study compared supplementation for 20 days with 500 mg of colostrum bovinum or placebo (whey). Gut permeability status was assayed by differential absorption of lactulose and mannitol (L/M test) and stool zonulin concentration. Baseline L/M tests found that six of the participants (75%) in the colostrum group had increased intestinal permeability. After supplementation, the test values were within the normal range and were significantly lower than at baseline. The colostrum group Δ values produced by comparing the post-intervention and baseline results were also significantly lower than the placebo group Δ values. The differences in stool zonulin concentration were smaller than those in the L/M test, but were significant when the Δ values due to intervention were compared between the colostrum group and the placebo group. Colostrum bovinum supplementation was safe and effective in decreasing of intestinal permeability in this series of athletes at increased risk of its elevation.

  14. Artificial neural network models for prediction of intestinal permeability of oligopeptides

    Directory of Open Access Journals (Sweden)

    Kim Min-Kook

    2007-07-01

    Full Text Available Abstract Background Oral delivery is a highly desirable property for candidate drugs under development. Computational modeling could provide a quick and inexpensive way to assess the intestinal permeability of a molecule. Although there have been several studies aimed at predicting the intestinal absorption of chemical compounds, there have been no attempts to predict intestinal permeability on the basis of peptide sequence information. To develop models for predicting the intestinal permeability of peptides, we adopted an artificial neural network as a machine-learning algorithm. The positive control data consisted of intestinal barrier-permeable peptides obtained by the peroral phage display technique, and the negative control data were prepared from random sequences. Results The capacity of our models to make appropriate predictions was validated by statistical indicators including sensitivity, specificity, enrichment curve, and the area under the receiver operating characteristic (ROC curve (the ROC score. The training and test set statistics indicated that our models were of strikingly good quality and could discriminate between permeable and random sequences with a high level of confidence. Conclusion We developed artificial neural network models to predict the intestinal permeabilities of oligopeptides on the basis of peptide sequence information. Both binary and VHSE (principal components score Vectors of Hydrophobic, Steric and Electronic properties descriptors produced statistically significant training models; the models with simple neural network architectures showed slightly greater predictive power than those with complex ones. We anticipate that our models will be applicable to the selection of intestinal barrier-permeable peptides for generating peptide drugs or peptidomimetics.

  15. Human in vivo regional intestinal permeability: quantitation using site-specific drug absorption data.

    Science.gov (United States)

    Sjögren, Erik; Dahlgren, David; Roos, Carl; Lennernäs, Hans

    2015-06-01

    Application of information on regional intestinal permeability has been identified as a key aspect of successful pharmaceutical product development. This study presents the results and evaluation of an approach for the indirect estimation of site-specific in vivo intestinal effective permeability (Peff) in humans. Plasma concentration-time profiles from 15 clinical studies that administered drug solutions to specific intestinal regions were collected and analyzed. The intestinal absorption rate for each drug was acquired by deconvolution, using historical intravenous data as reference, and used with the intestinal surface area and the dose remaining in the lumen to estimate the Peff. Forty-three new Peff values were estimated (15 from the proximal small intestine, 11 from the distal small intestine, and 17 from the large intestine) for 14 active pharmaceutical ingredients representing a wide range of biopharmaceutical properties. A good correlation (r(2) = 0.96, slope = 1.24, intercept = 0.030) was established between these indirect jejunal Peff estimates and jejunal Peff measurements determined directly using the single-pass perfusion double balloon technique. On average, Peff estimates from the distal small intestine and large intestine were 90% and 40%, respectively, of those from the proximal small intestine. These results support the use of the evaluated deconvolution method for indirectly estimating regional intestinal Peff in humans. This study presents the first comprehensive data set of estimated human regional intestinal permeability values for a range of drugs. These biopharmaceutical data can be used to improve the accuracy of gastrointestinal absorption predictions used in drug development decision-making.

  16. Comparison of Mass Transfer Models for Determination of the Intestinal Permeability

    Directory of Open Access Journals (Sweden)

    P Zakeri-Milani

    2008-09-01

    Full Text Available Background and the purpose of the study: In determination of the permeability of the intestinal wall by external perfusion techniques, several models have been proposed. In the present study three models were used for experimental results that differ in their convection and diffusion assumptions. Material and Methods: Permeability coefficients for 13 compounds (metoprolol, propranolol, naproxen, ketoprofen, furosemide, hydrochlorothiazide, cimetidine, ranitidine, atenolol, piroxicam, antipyrine, ibuprofen and carbamazepine with known human intestinal permeability values were determined in anaesthetized rats by different mass transfer models and plotted versus the observed human intestinal permeabilities. Results: The calculated dimensionless wall permeability values were in the range of 0.37 - 4.85, 0.38-6.54 and 0.41-16.59 for complete radial mixing, mixing tank and laminar flow models respectively. The results indicated that all of the models work relatively well for our data despite fundamentally different assumptions. The wall permeabilities were in the order laminar flow > mixing tank > complete radial mixing. Conclusion: Although laminar flow model provides the most direct measure of the intrinsic wall permeability, it has limitations for highly permeable drugs such as ibuprofen. The normal physiological hydrodynamics is more complex and more investigation is required to find out the real hydrodynamics.

  17. Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability.

    Science.gov (United States)

    Zakeri-Milani, Parvin; Fasihi, Zohreh; Akbari, Jafar; Jannatabadi, Ensieh; Barzegar-Jalali, Mohammad; Loebenberg, Raimar; Valizadeh, Hadi

    We assessed the feasibility of using crystal-liquid fugacity ratio (CLFR) as an alternative parameter for intestinal permeability in the biopharmaceutical classification (BCS) of passively absorbed drugs. Dose number, fraction of dose absorbed, intestinal permeability, and intrinsic dissolution rate were used as the input parameters. CLFR was determined using thermodynamic parameters i.e., melting point, molar fusion enthalpy, and entropy of drug molecules obtained using differential scanning calorimetry. The CLFR values were in the range of 0.06-41.76 mole percent. There was a close relationship between CLFR and in vivo intestinal permeability (r > 0.8). CLFR values of greater than 2 mole percent corresponded to complete intestinal absorption. Applying CLFR versus dose number or intrinsic dissolution rate, more than 92% of tested drugs were correctly classified with respect to the reported classification system on the basis of human intestinal permeability and solubility. This investigation revealed that the CLFR might be an appropriate parameter for quantitative biopharmaceutical classification. This could be attributed to the fact that CLFR could be a measure of solubility of compounds in lipid bilayer which was found in this study to be directly proportional to the intestinal permeability of compounds. This classification enables researchers to define characteristics for intestinal absorption of all four BCS drug classes using suitable cutoff points for both intrinsic dissolution rate and crystal-liquid fugacity ratio. Therefore, it may be used as a surrogate for permeability studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  18. Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse

    Science.gov (United States)

    Arrieta, M C; Madsen, K; Doyle, J; Meddings, J

    2008-01-01

    Background: Defects in the small intestinal epithelial barrier have been associated with inflammatory bowel disease but their role in the causation of disease is still a matter of debate. In some models of disease increased permeability appears to be a very early event. The interleukin 10 (IL10) gene-deficient mouse spontaneously develops colitis after 12 weeks of age. These mice have been shown to have increased small intestinal permeability that appears early in life. Furthermore, the development of colitis is dependent upon luminal agents, as animals do not develop disease if raised under germ-free conditions. Aims: To determine if the elevated small bowel permeability can be prevented, and if by doing so colonic disease is prevented or attenuated. Methods: IL10 gene-deficient (IL10−/−) mice) were treated with AT-1001 (a zonulin peptide inhibitor), a small peptide previously demonstrated to reduce small intestinal permeability. Small intestinal permeability was measured, in vivo, weekly from 4 to 17 weeks of age. Colonic disease was assessed at 8 weeks in Ussing chambers, and at 17 weeks of age inflammatory cytokines and myeloperoxidase were measured in the colon. Colonic permeability and histology were also endpoints. Results: Treated animals showed a marked reduction in small intestinal permeability. Average area under the lactulose/mannitol time curve: 5.36 (SE 0.08) in controls vs 3.97 (SE 0.07) in the high-dose AT-1001 group, p<0.05. At 8 weeks of age there was a significant reduction of colonic mucosal permeability and increased electrical resistance. By 17 weeks of age, secretion of tumour necrosis factor α (TNFα) from a colonic explant was significantly lower in the treated group (25.33 (SE 4.30) pg/mg vs 106.93 (SE 17.51) pg/ml in controls, p<0.01). All other markers also demonstrated a clear reduction of colitis in the treated animals. Additional experiments were performed which demonstrated that AT-1001 was functionally active only in the small

  19. Do intestinal hyperpermeability and the related food antigens play a role in the progression of IgA nephropathy? I. Study of intestinal permeability

    NARCIS (Netherlands)

    Kovács, T.; Kun, L.; Schmelczer, M.; Wagner, L.; Davin, J. C.; Nagy, J.

    1996-01-01

    Intestinal permeability was investigated by using 51Cr-EDTA as a probe molecule in 29 patients with immunoglobulin A nephropathy (IgA NP) and 20 healthy controls in 1990. Intestinal permeability was significantly higher in the IgA NP patients than in the controls (IgA NP, 3.86 +/- 0.29%; controls,

  20. High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids.

    Science.gov (United States)

    Stenman, Lotta K; Holma, Reetta; Korpela, Riitta

    2012-03-07

    To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism. Male C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF). Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls, P fat feeding also increased jejunal FXR expression, as well as TNF expression along the intestine, especially in the colon. High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.

  1. Zonulin Regulates Intestinal Permeability and Facilitates Enteric Bacteria Permeation in Coronary Artery Disease

    OpenAIRE

    Li, Chuanwei; Gao, Min; Zhang, Wen; Chen, Caiyu; Zhou, Faying; Hu, Zhangxu; Zeng, Chunyu

    2016-01-01

    Several studies have reported an association between enteric bacteria and atherosclerosis. Bacterial 16S ribosomal RNA (rRNA) gene belong to Enterobacteriaceae have been detected in atherosclerotic plaques. How intestinal bacteria go into blood is not known. Zonulin reversibly modulate intestinal permeability (IP), the circulating zonulin levels were increased in diabetes, obesity, all of which are risk factors for atherosclerosis. It is unclear whether the circulating zonulin levels were cha...

  2. Involvement of intestinal permeability in the oral absorption of clarithromycin and telithromycin.

    Science.gov (United States)

    Togami, Kohei; Hayashi, Yoshiaki; Chono, Sumio; Morimoto, Kazuhiro

    2014-09-01

    The involvement of intestinal permeability in the oral absorption of clarithromycin (CAM), a macrolide antibiotic, and telithromycin (TEL), a ketolide antibiotic, in the presence of efflux transporters was examined. In order independently to examine the intestinal and hepatic availability, CAM and TEL (10 mg/kg) were administered orally, intraportally and intravenously to rats. The intestinal and hepatic availability was calculated from the area under the plasma concentration-time curve (AUC) after administration of CAM and TEL via different routes. The intestinal availabilities of CAM and TEL were lower than their hepatic availabilities. The intestinal availability after oral administration of CAM and TEL increased by 1.3- and 1.6-fold, respectively, after concomitant oral administration of verapamil as a P-glycoprotein (P-gp) inhibitor. Further, an in vitro transport experiment was performed using Caco-2 cell monolayers as a model of intestinal epithelial cells. The apical-to-basolateral transport of CAM and TEL through the Caco-2 cell monolayers was lower than their basolateral-to-apical transport. Verapamil and bromosulfophthalein as a multidrug resistance-associated proteins (MRPs) inhibitor significantly increased the apical-to-basolateral transport of CAM and TEL. Thus, the results suggest that oral absorption of CAM and TEL is dependent on intestinal permeability that may be limited by P-gp and MRPs on the intestinal epithelial cells. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Determination of Regional Intestinal Permeability of Diclofenac and ...

    African Journals Online (AJOL)

    Purpose: To develop a simple and rapid reversed-phase high performance liquid chromatographic (HPLC) method with UV detection for the simultaneous determination of diclofenac, metoprolol tartrate, phenol red and propyl paraben in intestinal segments. Methods: The mobile phase consisted of 55 % methanol, 45 % of ...

  4. The biopharmaceutics of successful controlled release drug product: Segmental-dependent permeability of glipizide vs. metoprolol throughout the intestinal tract.

    Science.gov (United States)

    Zur, Moran; Cohen, Noa; Agbaria, Riad; Dahan, Arik

    2015-07-15

    The purpose of this work was to study the challenges and prospects of regional-dependent absorption in a controlled-release scenario, through the oral biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS solubility class of glipizide was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability class boundary marker. Glipizide was found to be a low-solubility compound. All intestinal permeability experimental methods revealed similar trend; a mirror image small intestinal permeability with opposite regional/pH-dependency was obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet the lowest permeability of glipizide (terminal Ileum) was comparable to the lowest permeability of metoprolol (proximal jejunum). At the colon, similar permeability was evident for glipizide and metoprolol, that was higher than metoprolol's jejunal permeability. We present an analysis that identifies metoprolol's jejunal permeability as the low/high permeability class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form. This represents a key biopharmaceutical characteristic for a successful controlled-release dosage form. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro

    NARCIS (Netherlands)

    Bijlsma, P. B.; van Raaij, M. T.; Dobbe, C. J.; Timmerman, A.; Kiliaan, A. J.; Taminiau, J. A.; Groot, J. A.

    2001-01-01

    Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to

  6. INTESTINAL PERMEABILITY IN PATIENTS WITH CELIAC-DISEASE AND RELATIVES OF PATIENTS WITH CELIAC-DISEASE

    NARCIS (Netherlands)

    VANELBURG, RM; UIL, JJ; MULDER, CJJ; HEYMANS, HSA

    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

  7. The effects of a multispecies probiotic on migraine and markers of intestinal permeability-results of a randomized placebo-controlled study

    NARCIS (Netherlands)

    Roos, De N.M.; Hemert, Van S.; Rovers, J.M.P.; Smits, M.G.; Witteman, B.J.M.

    2017-01-01

    Background/Objectives:Migraine, associated with several gastrointestinal disorders, may result from increased intestinal permeability, allowing endotoxins to enter the bloodstream. We tested whether probiotics could reduce migraine through an effect on intestinal permeability and

  8. Intestinal fatty acid-binding protein and gut permeability responses to exercise.

    Science.gov (United States)

    March, Daniel S; Marchbank, Tania; Playford, Raymond J; Jones, Arwel W; Thatcher, Rhys; Davison, Glen

    2017-05-01

    Intestinal cell damage due to physiological stressors (e.g. heat, oxidative, hypoperfusion/ischaemic) may contribute to increased intestinal permeability. The aim of this study was to assess changes in plasma intestinal fatty acid-binding protein (I-FABP) in response to exercise (with bovine colostrum supplementation, Col, positive control) and compare this to intestinal barrier integrity/permeability (5 h urinary lactulose/rhamnose ratio, L/R). In a double-blind, placebo-controlled, crossover design, 18 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac). For each arm participants performed two baseline (resting) intestinal permeability assessments (L/R) pre-supplementation and one post-exercise following supplementation. Blood samples were collected pre- and post-exercise to determine I-FABP concentration. Two-way repeated measures ANOVA revealed an arm × time interaction for L/R and I-FABP (P exercise in Plac (273% of pre, P exercise values significantly lower with Col (P exercise in Plac (191% of pre-exercise, P = 0.002) but not in the Col arm (107%, P = 0.862) with post-exercise values significantly lower with Col (P = 0.013). Correlations between the increase in I-FABP and L/R were evident for visit one (P = 0.044) but not visit two (P = 0.200) although overall plots/patterns do appear similar for each. These findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute.

  9. Permeability of plumbagin across human intestinal cell in vitro.

    Science.gov (United States)

    Sumsakul, Wiriyaporn; Na-Bangchang, Kesara

    2016-03-01

    Plumbagin is the active compound isolated from plants used in traditional medicine for treatment of various diseases such as activities malaria, leishmaniasis, viral infections and cancers. The aim of the study was to investigate the permeability of plumbagin across Caco-2 (human epithelial colorectal adenocarcinoma) cell monolayer and its effects on the expression and function of P-glycoprotein. The integrity of Caco-2 cell monolayer was evaluated by measuring trans-epithelial electrical resistance and permeation (Papp) of Lucifer yellow across the cell monolayer. The effect of plumbagin on P-glycoprotein was detected by measuring its interference with the transport of the P-glycoprotein substrate (R123) and the effect on MDR-1 mRNA expression was detected by RT-PCR. The Papp of plumbagin (2-8 µM) for the apical to basolateral and basolateral to apical directions were 10.29-15.96 × 10(-6) and 7.40-9.02 × 10(-6) cm/s, respectively, with the efflux ratios of 0.57-0.73. Plumbagin is not either a substrate or inhibitor of P-glycoprotein. It did not interfere with the P-glycoprotein-mediated R123 transport across Caco-2 cell monolayer, as well as the function of P-glycoprotein and the expression of MDR-1 mRNA. Results suggest moderate permeability of plumbagin across the Caco-2 cell monolayer in both directions. The transport mechanism is likely to be a passive transport.

  10. Enhancing the intestinal membrane permeability of zanamivir: a carrier mediated prodrug approach.

    Science.gov (United States)

    Gupta, Sheeba Varghese; Gupta, Deepak; Sun, Jing; Dahan, Arik; Tsume, Yasuhiro; Hilfinger, John; Lee, Kyung-Dall; Amidon, Gordon L

    2011-12-05

    The purpose of this study was to improve the membrane permeability and oral absorption of the poorly permeable anti-influenza agent, zanamivir. The poor oral bioavailability is attributed to the high polarity (cLogP ∼ -5) resulting from the polar and zwitterionic nature of zanamivir. In order to improve the permeability of zanamivir, prodrugs with amino acids were developed to target the intestinal membrane transporter, hPepT1. Several acyloxy ester prodrugs of zanamivir conjugated with amino acids were synthesized and characterized. The prodrugs were evaluated for their chemical stability in buffers at various pHs and for their transport and tissue activation by enzymes. The acyloxy ester prodrugs of zanamivir were shown to competitively inhibit [(3)H]Gly-Sar uptake in Caco-2 cells (IC(50): 1.19 ± 0.33 mM for L-valyl prodrug of zanamivir). The L-valyl prodrug of zanamivir exhibited ∼3-fold higher uptake in transfected HeLa/hPepT1 cells compared to wild type HeLa cells, suggesting, at least in part, carrier mediated transport by the hPepT1 transporter. Further, enhanced transcellular permeability of prodrugs across Caco-2 monolayer compared to the parent drug (P(app) = 2.24 × 10(-6) ± 1.33 × 10(-7) cm/s for L-valyl prodrug of zanamivir), with only parent zanamivir appearing in the receiver compartment, indicates that the prodrugs exhibited both enhanced transport and activation in intestinal mucosal cells. Most significantly, several of these prodrugs exhibited high intestinal jejunal membrane permeability, similar to metoprolol, in the in situ rat intestinal perfusion system, a system highly correlated with human jejunal permeability. In summary, this mechanistic targeted prodrug strategy, to enhance oral absorption via intestinal membrane carriers such as hPepT1, followed by activation to parent drug (active pharmaceutical ingredient or API) in the mucosal cell, significantly improves the intestinal epithelial cell permeability of zanamivir and has the

  11. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression

    International Nuclear Information System (INIS)

    Pinton, Philippe; Nougayrede, Jean-Philippe; Del Rio, Juan-Carlos; Moreno, Carolina; Marin, Daniela E.; Ferrier, Laurent; Bracarense, Ana-Paula; Kolf-Clauw, Martine; Oswald, Isabelle P.

    2009-01-01

    'The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health.

  12. Epithelial Cell Damage Activates Bactericidal/Permeability Increasing-Protein (BPI Expression in Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Arjun Balakrishnan

    2017-08-01

    Full Text Available As the first line of defense against invading pathogen, intestinal epithelium produces various antimicrobial proteins (AMP that help in clearance of pathogen. Bactericidal/permeability-increasing protein (BPI is a 55 kDa AMP that is expressed in intestinal epithelium. Dysregulation of BPI in intestinal epithelium is associated with various inflammatory diseases like Crohn’s Disease, Ulcerative colitis, and Infectious enteritis’s. In this paper, we report a direct correlation between intestinal damage and BPI expression. In Caco-2 cells, we see a significant increase in BPI levels upon membrane damage mediated by S. aureus infection and pore-forming toxins (Streptolysin and Listeriolysin. Cells detect changes in potassium level as a Danger-associated molecular pattern associated with cell damage and induce BPI expression in a p38 dependent manner. These results are further supported by in vivo findings that the BPI expression in murine intestinal epithelium is induced upon infection with bacteria which cause intestinal damage (Salmonella Typhimurium and Shigella flexneri whereas mutants that do not cause intestinal damage (STM ΔfliC and STM ΔinvC did not induce BPI expression. Our results suggest that epithelial damage associated with infection act as a signal to induce BPI expression.

  13. Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects.

    Science.gov (United States)

    Esnafoglu, Erman; Cırrık, Selma; Ayyıldız, Sema Nur; Erdil, Abdullah; Ertürk, Emine Yurdakul; Daglı, Abdullah; Noyan, Tevfik

    2017-09-01

    To evaluate the serum levels of zonulin, which regulates tight junctions between enterocytes and is a physiological modulator controlling intestinal permeability, in patients with autism spectrum disorders (ASDs). Serum zonulin levels were determined in 32 patients with ASD and 33 healthy controls using an enzyme-linked immunosorbent assay. The severity of ASD symptoms was assessed with the Childhood Autism Rating Scale. Serum zonulin levels were significantly higher in the patients with ASD (122.3 ± 98.46 ng/mL) compared with the healthy controls (41.89 ± 45.83 ng/mL). There was a positive correlation between zonulin levels and Childhood Autism Rating Scale score when all subjects were assessed (r = 0.523; P zonulin, which regulates intestinal permeability, plays a role in the development of symptoms of ASD. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Intestinal Permeability Biomarker Zonulin is Elevated in Healthy Aging.

    Science.gov (United States)

    Qi, YanFei; Goel, Ruby; Kim, Seungbum; Richards, Elaine M; Carter, Christy S; Pepine, Carl J; Raizada, Mohan K; Buford, Thomas W

    2017-09-01

    Increased gut permeability ("leaky gut") has been proposed as a potential contributor to age-related inflammation and gut dysbiosis. However, information on the relationship between a leaky gut and inflammation and physical frailty during aging are limited. To investigate the hypothesis that an aging-associated leaky gut is linked to the age-related inflammation and frailty. Two cohorts of healthy adults were studied: young (18-30 years old, n = 19) and older (≥70 years old, n = 18). Serum concentrations of the tumor necrosis factor (TNF)-α and interleukin (IL)-6, zonulin (a marker for leaky gut), and high-mobility group box protein (HMGB1, a nuclear protein triggering inflammation) were measured. Correlations of serum levels of zonulin and HMGB1 with strength of plantar flexor muscles and number of steps taken per day were analyzed. Serum concentration of zonulin and HMGB1 were 22% (P = .005) and 16% (P = .010) higher in the older versus young adults. Serum zonulin was positively associated with concentrations of TNF-α (r = 0.357, P = .032) and IL-6 (r = 0.345, P = .043). Importantly, both zonulin and HMGB1 were negatively correlated with skeletal muscle strength (zonulin: r = -0.332, P = .048; HMGB1: r = -0.383, P = .023), and habitual physical activity (zonulin: r = -0.410, P = .016; HMGB1: r = -0.483, P = .004). Serum zonulin was associated with both systemic inflammation and 2 key indices of physical frailty. These data suggest that a leaky gut may play a critical role in the development of age-related inflammation and frailty. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  15. Acylation of salmon calcitonin modulates in vitro intestinal peptide flux through membrane permeability enhancement

    DEFF Research Database (Denmark)

    Trier, Sofie; Linderoth, Lars; Bjerregaard, Simon

    2015-01-01

    Acylation of peptide drugs with fatty acid chains has proven beneficial for prolonging systemic circulation, as well as increasing enzymatic stability and interactions with lipid cell membranes. Thus, acylation offers several potential benefits for oral delivery of therapeutic peptides, and we hy...... on Caco-2 cells, indicating that acylation of sCT may represent a promising tool to increase intestinal permeability without adding oral permeation enhancers....

  16. Segmental-dependent membrane permeability along the intestine following oral drug administration: Evaluation of a triple single-pass intestinal perfusion (TSPIP) approach in the rat.

    Science.gov (United States)

    Dahan, Arik; West, Brady T; Amidon, Gordon L

    2009-02-15

    In this paper we evaluate a modified approach to the traditional single-pass intestinal perfusion (SPIP) rat model in investigating segmental-dependent permeability along the intestine following oral drug administration. Whereas in the traditional model one single segment of the intestine is perfused, we have simultaneously perfused three individual segments of each rat intestine: proximal jejunum, mid-small intestine and distal ileum, enabling to obtain tripled data from each rat compared to the traditional model. Three drugs, with different permeabilities, were utilized to evaluate the model: metoprolol, propranolol and cimetidine. Data was evaluated in comparison to the traditional method. Metoprolol and propranolol showed similar P(eff) values in the modified model in all segments. Segmental-dependent permeability was obtained for cimetidine, with lower P(eff) in the distal parts. Similar P(eff) values for all drugs were obtained in the traditional method, illustrating that the modified model is as accurate as the traditional, throughout a wide range of permeability characteristics, whether the permeability is constant or segment-dependent along the intestine. Three-fold higher statistical power to detect segmental-dependency was obtained in the modified approach, as each subject serves as his own control. In conclusion, the Triple SPIP model can reduce the number of animals utilized in segmental-dependent permeability research without compromising the quality of the data obtained.

  17. Assessment of Passive Intestinal Permeability Using an Artificial Membrane Insert System.

    Science.gov (United States)

    Berben, Philippe; Brouwers, Joachim; Augustijns, Patrick

    2018-01-01

    Despite reasonable predictive power of current cell-based and cell-free absorption models for the assessment of intestinal drug permeability, high costs and lengthy preparation steps hamper their use. The use of a simple artificial membrane (without any lipids present) as intestinal barrier substitute would overcome these hurdles. In the present study, a set of 14 poorly water-soluble drugs, dissolved in 2 different media (fasted state simulated/human intestinal fluids [FaSSIF/FaHIF]), were applied to the donor compartment of an artificial membrane insert system (AMI-system) containing a regenerated cellulose membrane. Furthermore, to investigate the predictive capacity of the AMI-system as substitute for the well-established Caco-2 system to assess intestinal permeability, the same set of 14 drugs dissolved in FaHIF were applied to the donor compartment of a Caco-2 system. For 14 drugs, covering a broad range of physicochemical parameters, a reasonable correlation between both absorption systems was observed, characterized by a Pearson correlation coefficient r of 0.95 (FaHIF). Using the AMI-system, an excellent predictive capacity of FaSSIF as surrogate medium for FaHIF was demonstrated (r = 0.96). Based on the acquired data, the AMI-system appears to be a time- and cost-effective tool for the early-stage estimation of passive intestinal permeability for poorly water-soluble drugs. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. [51Cr]EDTA intestinal permeability in children with cow's milk intolerance

    International Nuclear Information System (INIS)

    Schrander, J.J.; Unsalan-Hooyen, R.W.; Forget, P.P.; Jansen, J.

    1990-01-01

    Making use of [ 51 Cr]EDTA as a permeability marker, we measured intestinal permeability in a group of 20 children with proven cow's milk intolerance (CMI), a group of 17 children with similar complaints where CMI was excluded (sick controls), and a group of 12 control children. [ 51 Cr]EDTA test results (mean +/- SD) were 6.85 +/- 3.64%, 3.42 +/- 0.94%, and 2.61 +/- 0.67% in the group with CMI, the sick control, and the control group, respectively. When compared to both control groups, patients with cow's milk intolerance (CMI) showed a significantly increased small bowel permeability. We conclude that the [ 51 Cr]EDTA test can be helpful for the diagnosis of cow's milk intolerance

  19. (51Cr)EDTA intestinal permeability in children with cow's milk intolerance

    Energy Technology Data Exchange (ETDEWEB)

    Schrander, J.J.; Unsalan-Hooyen, R.W.; Forget, P.P.; Jansen, J. (Academic Hospital Maastricht (Netherlands))

    1990-02-01

    Making use of ({sup 51}Cr)EDTA as a permeability marker, we measured intestinal permeability in a group of 20 children with proven cow's milk intolerance (CMI), a group of 17 children with similar complaints where CMI was excluded (sick controls), and a group of 12 control children. ({sup 51}Cr)EDTA test results (mean +/- SD) were 6.85 +/- 3.64%, 3.42 +/- 0.94%, and 2.61 +/- 0.67% in the group with CMI, the sick control, and the control group, respectively. When compared to both control groups, patients with cow's milk intolerance (CMI) showed a significantly increased small bowel permeability. We conclude that the ({sup 51}Cr)EDTA test can be helpful for the diagnosis of cow's milk intolerance.

  20. Chlorogenic acid decreases intestinal permeability and increases expression of intestinal tight junction proteins in weaned rats challenged with LPS.

    Directory of Open Access Journals (Sweden)

    Zheng Ruan

    Full Text Available Chlorogenic acid, a natural phenolic acid present in fruits and plants, provides beneficial effects for human health. The objectives of this study were to investigate whether chlorogenic acid (CHA could improve the intestinal barrier integrity for weaned rats with lipopolysaccharide (LPS challenge. Thirty-two weaned male Sprague Dawley rats (21 ± 1 d of age; 62.26 ± 2.73 g were selected and randomly allotted to four treatments, including weaned rat control, LPS-challenged and chlorogenic acid (CHA supplemented group (orally 20 mg/kg and 50 mg/kg body. Dietary supplementation with CHA decreased (P<0.05 the concentrations of urea and albumin in the serum, compared to the LPS-challenged group. The levels of IFN-γ and TNF-α were lower (P<0.05 in the jejunal and colon of weaned rats receiving CHA supplementation, in comparison with the control group. CHA supplementation increased (P<0.05 villus height and the ratio of villus height to crypt depth in the jejunal and ileal mucosae under condictions of LPS challenge. CHA supplementation decreased (P<0.05 intestinal permeability, which was indicated by the ratio of lactulose to mannitol and serum DAO activity, when compared to weaned rats with LPS challenge. Immunohistochemical analysis of tight junction proteins revealed that ZO-1 and occludin protein abundances in the jejunum and colon were increased (P<0.05 by CHA supplementation. Additionally, results of immunoblot analysis revealed that the amount of occludin in the colon was also increased (P<0.05 in CHA-supplemented rats. In conclusion, CHA decreases intestinal permeability and increases intestinal expression of tight junction proteins in weaned rats challenged with LPS.

  1. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

    Science.gov (United States)

    Kelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.

    2015-01-01

    The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function. PMID:26528128

  2. Circulating Zonulin, a Marker of Intestinal Permeability, Is Increased in Association with Obesity-Associated Insulin Resistance

    OpenAIRE

    Moreno-Navarrete, José María; Sabater, Mònica; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

    2012-01-01

    Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measure...

  3. Assessment of intestinal permeability and bacterial translocation employing nuclear methods in murine mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Pessoa, Rafaela M.; Takenaka, Isabella K.T.M.; Barros, Patricia A.V.; Moura, Livia P.; Contarini, Sara M.L.; Amorim, Juliana M.; Castilho, Raquel O.; Leite, Camila M.A.; Cardoso, Valbert N.; Diniz, Simone Odilia F. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Mg (Brazil)

    2017-07-01

    Full text: Introduction: Mucositis affects approximately 80% of patients who receive chemotherapy combinations. The lesions are painful, restrict food intake and make patients more susceptible to systemic infections. Some agents and strategies are being studied for controlling mucositis, none of them is used in clinical practice. In Minas Gerais, many studies have addressed the popular use of the plant Arrabidaea chica in the form of tea, to treat intestinal cramps and diarrhea, the main symptoms of mucositis. Objective: To evaluate the potential of Arrabidaea chica extract in the management of the integrity of the intestinal mucosa, using the experimental model of gut mucositis induced by 5-Fluorouracila (5-FU). Methods: The UFMG Ethics Committee for Animal Experimentation (CETEA/UFMG) approved this study (nº 411/2015). Male BALB/c mice between 6-8 weeks of age were randomly divided into four groups (n=9) as follows: 1. Control (CTL) - oral administration of saline solution (10 days); 2. A. chica (AC) - oral administration of A. chica extract (10 days); 3. Mucositis (MUC) - underwent mucositis (5-FU) (10 days); 4. Mucositis + A. chica (MUC+ AC) - underwent mucositis and received oral administration of A. chica extract (10 days). At the 7{sup th} day, mice in the MUC and MUC + AC groups received an intraperitoneal (IP) injection containing 300 mg/kg 5-FU, whereas the animals of the CTL and AC groups received a saline IP injection. After 72 hours (10{sup th} experimental day), intestinal permeability was determined by measuring the radioactivity diffusion in the blood after oral administration of diethylenetriaminepentaacetic acid (DTPA) labelled with technetium-99m ({sup 99m}Tc) and bacterial translocation was determined by measuring the radioactivity diffusion in the blood after oral administration of E. coli labelled with technetium-99m ({sup 99m}Tc). After 4 hours, the mice were euthanized and assessed for intestinal permeability, bacterial translocation and

  4. Intestinal permeability to [51Cr]EDTA in children with Crohn's disease and celiac disease

    International Nuclear Information System (INIS)

    Turck, D.; Ythier, H.; Maquet, E.; Deveaux, M.; Marchandise, X.; Farriaux, J.P.; Fontaine, G.

    1987-01-01

    [ 51 Cr]EDTA was used as a probe molecule to assess intestinal permeability in 7 healthy control adults, 11 control children, 17 children with Crohn's disease, and 6 children with untreated celiac disease. After subjects fasted overnight, 75 kBq/kg (= 2 microCi/kg) 51 Cr-labeled EDTA was given by mouth; 24-h urinary excretion of [ 51 Cr]EDTA was measured and expressed as a percentage of the total oral dose. Mean and SD were as follows: control adults 1.47 +/- 0.62, control children 1.59 +/- 0.55, and patients with Crohn's disease or celiac disease 5.35 +/- 1.94. The difference between control children and patients was statistically significant (p less than 0.001). These results show that intestinal permeability to [ 51 Cr]EDTA is increased among children with active or inactive Crohn's disease affecting small bowel only or small bowel and colon, and with untreated celiac disease. The [ 51 Cr]EDTA permeability test could facilitate the decision to perform more extensive investigations in children suspected of small bowel disease who have atypical or poor clinical and biological symptomatology

  5. Intestinal permeability to [51Cr]EDTA in children with cystic fibrosis

    International Nuclear Information System (INIS)

    Leclercq-Foucart, J.; Forget, P.; Sodoyez-Goffaux, F.; Zappitelli, A.

    1986-01-01

    Intestinal permeability was investigated in 14 children with cystic fibrosis making use of [ 51 Cr]EDTA as probe molecule. Ten normal young adults and 11 children served as controls. After oral administration of [ 51 Cr]EDTA, 24 h urine was collected. Urinary radioactivity was calculated and results expressed as percentage of oral dose excreted in 24 h urine. Mean and SEM were as follows: 2.51 +/- 0.21, 2.35 +/- 0.24, and 13.19 +/- 1.72 for control children, normal adults, and cystic fibrosis patients, respectively. The permeability differences between cystic fibrosis patients and either control children or control adults are significant (p less than 0.001)

  6. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3.

    Science.gov (United States)

    Lammers, Karen M; Lu, Ruliang; Brownley, Julie; Lu, Bao; Gerard, Craig; Thomas, Karen; Rallabhandi, Prasad; Shea-Donohue, Terez; Tamiz, Amir; Alkan, Sefik; Netzel-Arnett, Sarah; Antalis, Toni; Vogel, Stefanie N; Fasano, Alessio

    2008-07-01

    Celiac disease is an immune-mediated enteropathy triggered by gliadin, a component of the grain protein gluten. Gliadin induces an MyD88-dependent zonulin release that leads to increased intestinal permeability, a postulated early element in the pathogenesis of celiac disease. We aimed to establish the molecular basis of gliadin interaction with intestinal mucosa leading to intestinal barrier impairment. Alpha-gliadin affinity column was loaded with intestinal mucosal membrane lysates to identify the putative gliadin-binding moiety. In vitro experiments with chemokine receptor CXCR3 transfectants were performed to confirm binding of gliadin and/or 26 overlapping 20mer alpha-gliadin synthetic peptides to the receptor. CXCR3 protein and gene expression were studied in intestinal epithelial cell lines and human biopsy specimens. Gliadin-CXCR3 interaction was further analyzed by immunofluorescence microscopy, laser capture microscopy, real-time reverse-transcription polymerase chain reaction, and immunoprecipitation/Western blot analysis. Ex vivo experiments were performed using C57BL/6 wild-type and CXCR3(-/-) mouse small intestines to measure intestinal permeability and zonulin release. Affinity column and colocalization experiments showed that gliadin binds to CXCR3 and that at least 2 alpha-gliadin 20mer synthetic peptides are involved in this binding. CXCR3 is expressed in mouse and human intestinal epithelia and lamina propria. Mucosal CXCR3 expression was elevated in active celiac disease but returned to baseline levels following implementation of a gluten-free diet. Gliadin induced physical association between CXCR3 and MyD88 in enterocytes. Gliadin increased zonulin release and intestinal permeability in wild-type but not CXCR3(-/-) mouse small intestine. Gliadin binds to CXCR3 and leads to MyD88-dependent zonulin release and increased intestinal permeability.

  7. Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class.

    Directory of Open Access Journals (Sweden)

    Monica Vera-Lise Tulstrup

    Full Text Available Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group were dosed by oral gavage with either amoxicillin (AMX, cefotaxime (CTX, vancomycin (VAN, metronidazole (MTZ, or water (CON daily for 10-11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in

  8. Morphological abnormalities and apoptosis in lamellar tissue of equines after intestinal obstruction and treatment with hydrocortisone

    Directory of Open Access Journals (Sweden)

    L.M Laskoski

    2010-12-01

    Full Text Available Four experimental groups of equines were used in order to study morphological abnormalities and apoptosis in lamellar tissue. Group Cg (control was composed of animals without any surgical procedure; group Ig (instrumented, animals that underwent enterotomy; group Tg (treated, animals that were subjected to intestinal obstruction and were treated with hydrocortisone; and group Ug (untreated, animals that were subjected to intestinal obstruction without treatment. The lamellar tissue was analyzed regarding the presence of tissue abnormalities and apoptosis. No morphological abnormalities were observed in animals of surgical groups, and no difference in apoptosis was observed between groups. It was concluded that intestinal obstruction allowed laminitis to develop, probably by systemic activation, and that the maneuvers performed in the enterotomy aggravated the process. Hydrocortisone did not aggravate the lesions of the lamellar tissue

  9. [Effect of multicomponent environment on intestinal permeability of puerarin in biopharmaceutics classification system of Chinese materia medica].

    Science.gov (United States)

    Liu, Yang; Wang, Gang; Dong, Ling; Tang, Ming-Min; Zhu, Mei-Ling; Dong, Hong-Huant; Hou, Cheng-Bo

    2014-12-01

    The evaluation of permeability in biopharmaceutics classification system of Chinese materia medica (CMMBCS) requires multicomponent as a whole in order to conduct research, even in the study of a specific component, should also be put in the multicomponent environment. Based on this principle, the high content components in Gegen Qinlian decoction were used as multicomponent environmental impact factors in the experiment, and the relevant parameters of intestinal permeability about puerarin were measured with using in situ single-pass intestinal perfusion model, to investigate and evaluate the intestinal permeability of puerarin with other high content components. The experimental results showed that different proportions of baicalin, glycyrrhizic acid and berberine had certain influence on intestinal permeability of puerarin, and glycyrrhizic acid could significantly inhibit the intestinal absorption of puerarin, moreover, high concentration of berberine could promote the absorption of puerarin. The research results indicated that the important research ideas of permeability evaluation in biopharmaceutics classification system of Chinese materia medica with fully considering the effects of other ingredients in multicomponent environment.

  10. Intestinal permeability of 51Cr-labelled ethylenediaminetetraacetic acid in patients with Crohn's disease and their healthy relatives

    International Nuclear Information System (INIS)

    Ainsworth, M.; Eriksen, J.; Rasmussen, J.W.; Muckadell, O.B.S. de

    1989-01-01

    An increased intestinal permeability has been proposed as an aetiologic factor in Crohn's disease. The 24-h urinary excretion of 100 μCi 51 Cr-labelled ethylenediaminetetraacetic acid (EDTA) was used to test the permeability in 15 patients with Crohn's disease and in 20 healthy first-degree relatives, who were known to have a genetic predisposition to inflammatory bowel disease. Twenty-eight healthy persons not related to patients with inflammatory bowel disease served as control material. The 51 Cr-EDTA excretion of the relatives was not significantly higher than that of the controls, whereas patients with Crohn's disease had a significantly higher excretion than both the relatives and the controls. Among patients the increased excretion was found only if the small intestine was involved. It is concluded that 1) as a group, patient with Crohn's disease in the small intestine have an increased intestinal permeability, in contrast to their healthy relatives, who have a normal permeability; 2) a considerable overlap of the results of the 51 Cr-EDTA test was found between the groups studied, and the test is not suitable for evaluating individual patients; 3) the results do not support the hypothesis of an increase in intestinal permeability as an aetiologic factor in Crohn's disease. 29 refs

  11. POSTOPERATIVE ABNORMALITIES OF INTESTINE AND FACILITIES OF IT'S CORRECTION IN CHILDREN WITH ANORECTAL MALFORMATION

    Directory of Open Access Journals (Sweden)

    U.Sh. Karimov

    2007-01-01

    Full Text Available In abstract the authors represent the observation after 114 patients in age from 1 till 14 years passing the treatment last 15 years. All of them were been operated in cause of an rectal abnormality and suffering by dysfunction of terminal part of intestine and unsuccessful treatment of medics of different specification. Authors developed the principles of treatment accounting peculiarity and type of dysfunction, which noticeably improve the results of treatment.Key words: congenital abnormality of an rectal zone, motility disturbances of large intestine, children.

  12. Enhanced Permeability of Etoposide across Everted Sacs of Rat Small Intestine by Vitamin E-TPGS.

    Science.gov (United States)

    Parsa, Abdolhamid; Saadati, Roonak; Abbasian, Zahra; Azad Aramaki, Saeed; Dadashzadeh, Simin

    2013-01-01

    Etoposide, a widely used anticancer drug, exhibits low and variable oral bioavailability mainly because of being substrate for the efflux transporter, P-glycoprotein (P-gp). Therefore, the present study was aimed to investigate the effect of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and PEG 400 as P-gp inhibitors on the intestinal absorption of etoposide. Everted sacs of rat small intestine were incubated in Krebs buffer solution which contained etoposide in the absence or presence of various concentrations of TPGS or PEG 400. The effect of verapamil as a known P-gp inhibitor on the absorption of drug was also studied. The absorptive transport of etoposide was significantly enhanced (p effect on the etoposide transport. No significant difference was found between the permeability values in the absence and presence of the maximum concentration of TPGS for two transport markers, lucifer yellow and imipramine, indicating that the enhancement in etoposide permeability in the presence of TPGS was not due to the compromise in tight junctions or membrane integrity of epithelial cells. The results of the study suggest that the use of TPGS as a safe excipient in etoposide formulations may enhance the oral bioavailability of etoposide and result in a predictable oral absorption.

  13. Low Dosage of Chitosan Supplementation Improves Intestinal Permeability and Impairs Barrier Function in Mice

    Directory of Open Access Journals (Sweden)

    Guiping Guan

    2016-01-01

    Full Text Available The purpose of this study was to explore relationships between low dose dietary supplementation with chitosan (COS and body weight, feed intake, intestinal barrier function, and permeability in mice. Twenty mice were randomly assigned to receive an unadulterated control diet (control group or a dietary supplementation with 30 mg/kg dose of chitosan (COS group for two weeks. Whilst no significant differences were found between the conditions for body weight or food and water intake, mice in the COS group had an increased serum D-lactate content (P<0.05 and a decreased jejunal diamine oxidase (DAO activity (P<0.05. Furthermore, mice in COS group displayed a reduced expression of occludin and ZO-1 (P<0.05 and a reduced expression of occludin in the ileum (P<0.05. The conclusion drawn from these findings showed that although 30 mg/kg COS-supplemented diet had no effect on body weight or feed intake in mice, this dosage may compromise intestinal barrier function and permeability. This research will contribute to the guidance on COS supplements.

  14. Physicochemical properties and in vitro intestinal permeability properties and intestinal cell toxicity of silica particles, performed in simulated gastrointestinal fluids.

    Science.gov (United States)

    Sakai-Kato, Kumiko; Hidaka, Masayuki; Un, Keita; Kawanishi, Toru; Okuda, Haruhiro

    2014-03-01

    Amorphous silica particles with the primary dimensions of a few tens of nm, have been widely applied as additives in various fields including medicine and food. Especially, they have been widely applied in powders for making tablets and to coat tablets. However, their behavior and biological effects in the gastrointestinal tracts associated with oral administration remains unknown. Amorphous silica particles with diameters of 50, 100, and 200nm were incubated in the fasted-state and fed-state simulated gastric and intestinal fluids. The sizes, intracellular transport into Caco-2 cells (model cells for intestinal absorption), the Caco-2 monolayer membrane permeability, and the cytotoxicity against Caco-2 cells were then evaluated for the silica particles. Silica particles agglomerated in fed-state simultaneous intestinal fluids. The agglomeration and increased particles size inhibited the particles' absorption into the Caco-2 cells or particles' transport through the Caco-2 cells. The in vitro cytotoxicity of silica particles was not observed when the average size was larger than 100nm, independent of the fluid and the concentration. Our study indicated the effect of diet on the agglomeration of silica particles. The sizes of silica particles affected the particles' absorption into or transport through the Caco-2 cells, and cytotoxicity in vitro, depending on the various biological fluids. The findings obtained from our study may offer valuable information to evaluate the behavior of silica particles in the gastrointestinal tracts or safety of medicines or foods containing these materials as additives. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Plasma endocannabinoid levels in lean, overweight and obese humans: relationships with intestinal permeability markers, inflammation and incretin secretion.

    Science.gov (United States)

    Little, Tanya J; Cvijanovic, Nada; DiPatrizio, Nicholas V; Argueta, Donovan A; Rayner, Christopher K; Feinle-Bisset, Christine; Young, Richard L

    2018-02-13

    Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion. 20 lean, 18 overweight and 19 obese participants underwent intraduodenal Intralipid® infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumour necrosis factor-α (TNF-α), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and toll-like receptor-4 (TLR4) (RT-PCR), were assessed. Fasting plasma AEA was increased in obese, compared with lean and overweight (Plean (Plean and overweight. The relationships between plasma AEA with duodenal ZO-1 and IAP, and GIP, suggest that altered endocannabinoid signalling may contribute to changes in intestinal permeability, inflammation and incretin release in human obesity.

  16. Expressions of tight junction proteins Occludin and Claudin-1 are under the circadian control in the mouse large intestine: implications in intestinal permeability and susceptibility to colitis.

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    Oh-oka Kyoko

    Full Text Available BACKGROUND & AIMS: The circadian clock drives daily rhythms in behavior and physiology. A recent study suggests that intestinal permeability is also under control of the circadian clock. However, the precise mechanisms remain largely unknown. Because intestinal permeability depends on tight junction (TJ that regulates the epithelial paracellular pathway, this study investigated whether the circadian clock regulates the expression levels of TJ proteins in the intestine. METHODS: The expression levels of TJ proteins in the large intestinal epithelium and colonic permeability were analyzed every 4, 6, or 12 hours between wild-type mice and mice with a mutation of a key clock gene Period2 (Per2; mPer2(m/m. In addition, the susceptibility to dextran sodium sulfate (DSS-induced colitis was compared between wild-type mice and mPer2(m/m mice. RESULTS: The mRNA and protein expression levels of Occludin and Claudin-1 exhibited daily variations in the colonic epithelium in wild-type mice, whereas they were constitutively high in mPer2(m/m mice. Colonic permeability in wild-type mice exhibited daily variations, which was inversely associated with the expression levels of Occludin and Claudin-1 proteins, whereas it was constitutively low in mPer2(m/m mice. mPer2(m/m mice were more resistant to the colonic injury induced by DSS than wild-type mice. CONCLUSIONS: Occludin and Claudin-1 expressions in the large intestine are under the circadian control, which is associated with temporal regulation of colonic permeability and also susceptibility to colitis.

  17. Pseudomonas fluorescens alters epithelial permeability and translocates across Caco-2/TC7 intestinal cells

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    Madi Amar

    2010-11-01

    Full Text Available Abstract Background Pseudomonas fluorescens has long been considered as a psychrotrophic microorganism. Recently, we have shown that clinical strains of P. fluorescens (biovar 1 are able to adapt at a growth temperature of 37°C or above and induce a specific inflammatory response. Interestingly, a highly specific antigen of P. fluorescens, I2, is detected in the serum of patients with Crohn's disease but the possible role of this bacterium in the disease has not yet been explored. In the present study, we examined the ability of a psychrotrophic and a clinical strain of P. fluorescens to modulate the permeability of a Caco-2/TC7 intestinal epithelial model, reorganize the actin cytoskeleton, invade the target cells and translocate across the epithelium. The behaviour of these two strains was compared to that of the well known opportunistic pathogen P. aeruginosa PAO1. Results Both strains of P. fluorescens were found to decrease the transepithelial resistance (TER of Caco-2/TC7 differentiated monolayers. This was associated with an increase in paracellular permeability and F-actin microfilaments rearrangements. Moreover, the invasion and translocation tests demonstrated that the two strains used in this study can invade and translocate across the differentiated Caco-2/TC7 cell monolayers. Conclusions The present work shows for the first time, that P. fluorescens is able to alter the intestinal epithelial barrier function by disorganizing the F-actin microfilament network. Moreover, we reveal that independently of their origins, the two P. fluorescens strains can translocate across differentiated Caco-2/TC7 cell monolayers by using the transcellular pathway. These findings could, at least in part, explain the presence of the P. fluorescens specific I2 antigen in the serum of patients with Crohn's disease.

  18. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells

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    Artursson, P.; Karlsson, J. (Uppsala Univ., (Sweden))

    1991-03-29

    Monolayers of a well differentiated human intestinal epithelial cell line, Caco-2, were used as a model to study passive drug absorption across the intestinal epithelium. Absorption rate constants (expressed as apparent permeability coefficients) were determined for 20 drugs and peptides with different structural properties. The permeability coefficients ranged from approximately 5 x 10{sup {minus} 8} to 5 x 10{sup {minus} 5} cm/s. A good correlation was obtained between data on oral absorption in humans and the results in the Caco-2 model. Drugs that are completely absorbed in humans had permeability coefficients greater than 1 x 10{sup {minus} 6} cm/s. Drugs that are absorbed to greater than 1% but less than 100% had permeability coefficients of 0.1-1.0 x 10{sup {minus} 6} cm/s while drugs and peptides that are absorbed to less than 1% had permeability coefficients of less than or equal to 1 x 10{sup {minus} 7} cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption.

  19. Ascorbic Acid may Exacerbate Aspirin-Induced Increase in Intestinal Permeability.

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    Sequeira, Ivana R; Kruger, Marlena C; Hurst, Roger D; Lentle, Roger G

    2015-09-01

    Ascorbic acid in combination with aspirin has been used to prevent aspirin-induced oxidative GI damage. We aimed to determine whether ascorbic acid reduces or prevents aspirin-induced changes in intestinal permeability over a 6-hr period using saccharidic probes mannitol and lactulose. The effects of administration of 600 mg aspirin alone, 500 mg ascorbic acid alone and simultaneous dosage of both agents were compared in a cross-over study in 28 healthy female volunteers. These effects were also compared with that of a placebo. The ability of ascorbic acid to mitigate the effects of aspirin when administered either half an hour before or after dosage with aspirin was also assessed in 19 healthy female volunteers. The excretion of lactulose over the 6-hr period was augmented after consumption of either aspirin or ascorbic acid compared with that after consumption of placebo. Dosage with ascorbic acid alone augmented the excretion of lactulose more than did aspirin alone. Simultaneous dosage with both agents augmented the excretion of lactulose in an additive manner. The timing of dosage with ascorbic acid in relation to that with aspirin had no significant effect on the excretion of the two sugars. These findings indicate that ascorbic acid does not prevent aspirin-induced increase in gut permeability rather that both agents augment it to a similar extent. The additive effect on simultaneous dosage with both agents in augmenting the absorption of lactulose suggests that each influences paracellular permeability by different pathways. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  20. Protection against increased intestinal permeability and bacterial translocation induced by intestinal obstruction in mice treated with viable and heat-killed Saccharomyces boulardii.

    Science.gov (United States)

    Generoso, Simone V; Viana, Mirelle L; Santos, Rosana G; Arantes, Rosa M E; Martins, Flaviano S; Nicoli, Jacques R; Machado, José A N; Correia, Maria Isabel T D; Cardoso, Valbert N

    2011-06-01

    There are substantial evidences suggesting that probiotics can protect the gastrointestinal tract against inflammatory or infectious episodes. The effects of oral treatment with viable or heat-killed cells of Saccharomyces boulardii (Sb) on bacterial translocation, intestinal permeability, histological aspect of the ileum, and some immunological parameters were evaluated in a murine intestinal obstruction (IO) model. Bacterial translocation and intestinal permeability in the IO group were significantly higher when compared to a Sham group (p viable and heat-killed S. boulardii prevented these increases, and the data obtained for IO + Sb and IO + heat-killed Sb groups were similar to those observed in the Sham group (p > 0.05). Histological analysis showed preservation of the ileum mucosa in mice that received both forms of the yeast when compared to the lesions observed in the IO group. The levels of serum interleukin (IL)-10 and intestinal secretory immunoglobulin A (sIgA) were higher in the animals that received both yeast treatments when compared to those from IO and Sham groups. Oral treatment with viable or heat-killed cells of S. boulardii maintained intestinal integrity and modulated the immune system in a murine IO model, preventing bacterial translocation and intestinal lesions.

  1. The effect of salt adaptation on the permeability and cation selectivity of the goldfish intestinal epithelium.

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    Ellory, J C; Nibelle, J; Smith, M W

    1973-05-01

    1. The short-term uptake of Na by the goldfish mucosa was compared using both inulin and choline as markers of extracellular space. The results were virtually identical, the distribution of both choline and inulin increasing rapidly to measure a space at 1 min which then remained nearly constant during a following 4 min incubation.2. Using inulin as space marker, the uptake of various alkali metal cations was determined from a 1 min contact with the mucosa. The relative rates of uptake were Tl > K > Rb > Cs > Na > Li, with a low selectivity ratio, the range of permeabilities being no greater than 5.3. The selectivity sequence was the same in both salt and fresh-water adapted fish. Of the alkali metal cations tested, only Na showed a significantly decreased uptake on adaptation to salt.4. Isolated intestinal preparations from salt-adapted fish showed a reduced short-circuit current compared with fish adapted to fresh water, the values being 12.3 +/- 1.2 and 35.7 +/- 1.5 muA cm(-2) respectively. In both cases the short-circuit current was equivalent to the net transport of Na measured isotopically.5. In Krebs-Henseleit medium, the measured tissue resistance was approximately 100 Omega cm(-2) for both salt and fresh-water adapted fish.6. It is concluded that regulation of cation transport in goldfish intestinal epithelium is specific for Na and mediated primarily through cellular rather than extracellular pathways.

  2. Zonulin Regulates Intestinal Permeability and Facilitates Enteric Bacteria Permeation in Coronary Artery Disease.

    Science.gov (United States)

    Li, Chuanwei; Gao, Min; Zhang, Wen; Chen, Caiyu; Zhou, Faying; Hu, Zhangxu; Zeng, Chunyu

    2016-06-29

    Several studies have reported an association between enteric bacteria and atherosclerosis. Bacterial 16S ribosomal RNA (rRNA) gene belong to Enterobacteriaceae have been detected in atherosclerotic plaques. How intestinal bacteria go into blood is not known. Zonulin reversibly modulate intestinal permeability (IP), the circulating zonulin levels were increased in diabetes, obesity, all of which are risk factors for atherosclerosis. It is unclear whether the circulating zonulin levels were changed in coronary artery disease (CAD) patients and modulate IP. The 16S rRNA gene of bacteria in blood sample was checked by 454 pyrosequencing. The zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA) methods. The distribution of zonulin was detected by confocal immunofluorescence microscopy. Bacteria and Caco-2 cell surface micro-structure were checked by transmission electron microscopy. A high diversity of bacterial 16S rRNA gene can be detected in samples from CAD patients, most of them (99.4%) belong to Enterobacteriaceaes, eg. Rahnella. The plasma zonulin levels were significantly higher in CAD patients. Pseudomonas fluorescens exposure significantly increased zonulin expression and decreased IP in a time dependent manner. The elevated zonulin increase IP and may facilitate enteric translocation by disassembling the tight junctions, which might explain the observed high diversity of bacterial 16S rRNA genes in blood samples.

  3. Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms

    Science.gov (United States)

    Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio

    2010-01-01

    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type 1 diabetes (T1D), a hyperglycosaemia caused by a destructive autoimmune process targeting the insulin-producing pancreatic islet cells. Even if environmental factors and genetic susceptibility are clearly involved in the pathogenesis of autoimmunity, for most autoimmune disorders there is no or little knowledge about the causing agent or genetic makeup underlying the disease. In this respect, CD represents a unique autoimmune disorder because a close genetic association with HLA-DQ2 or HLA-DQ8 haplotypes and, more importantly, the environmental trigger (the gliadin fraction of gluten-containing grains wheat, barley, and rye) are known. Conversely, the trigger for autoimmune destruction of pancreatic ß cells in T1D is unclear. Interestingly, recent data suggest that gliadin is also involved in the pathogenesis of T1D. There is growing evidence that increased intestinal permeability plays a pathogenic role in various autoimmune diseases including CD and T1D. Therefore, we hypothesize that besides genetic and environmental factors, loss of intestinal barrier function is necessary to develop autoimmunity. In this review, each of these components will be briefly reviewed. PMID:19538307

  4. Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2009-08-01

    Sulfasalazine is characterized by low intestinal absorption, which essentially enables its colonic targeting and therapeutic action. The mechanisms behind this low absorption have not yet been elucidated. The purpose of this study was to investigate the role of efflux transporters in the intestinal absorption of sulfasalazine as a potential mechanism for its low small-intestinal absorption and colonic targeting following oral administration. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on sulfasalazine bidirectional permeability were studied across Caco-2 cell monolayers, including dose-response analysis. Sulfasalazine in vivo permeability was then investigated in the rat jejunum by single-pass perfusion, in the presence vs. absence of inhibitors. Sulfasalazine exhibited 19-fold higher basolateral-to-apical (BL-AP) than apical-to-basolateral (AP-BL) Caco-2 permeability, indicative of net mucosal secretion. MRP2 inhibitors (MK-571 and indomethacin) and BCRP inhibitors [fumitremorgin C (FTC) and pantoprazole] significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport in a concentration-dependent manner. No effect was observed with the P-gp inhibitors verapamil and quinidine. The IC50 values of the specific MRP2 and BCRP inhibitors MK-571 and FTC on sulfasalazine secretion were 21.5 and 2.0 microM, respectively. Simultaneous inhibition of MRP2 and BCRP completely abolished sulfasalazine Caco-2 efflux. Without inhibitors, sulfasalazine displayed low (vs. metoprolol) in vivo intestinal permeability in the rat model. MK-571 or FTC significantly increased sulfasalazine permeability, bringing it to the low-high permeability boundary. With both MK-571 and FTC present, sulfasalazine displayed high permeability. In conclusion, efflux transport mediated by MRP2 and BCRP, but not P-gp, shifts sulfasalazine permeability from high to low, thereby enabling its

  5. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

    Science.gov (United States)

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-11-01

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

  6. FROG INTESTINAL PERFUSION TO EVALUATE DRUG PERMEABILITY: APPLICATION TO P-gp AND CYP3A4 SUBSTRATES

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    Neelima eYerasi

    2015-07-01

    Full Text Available AbstractTo evaluate the reliability of using in situ frog intestinal perfusion technique for permeability assessment of carrier transported drugs which are also substrates for CYP enzymes. Single Pass Intestinal Perfusion (SPIP studies were performed in frogs of the species Rana tigrina using established method for rats with some modifications after inducing anesthesia. Effective permeability coefficient (Peff of losartan and midazolam was calculated in the presence and absence of inhibitors using the parallel-tube model. Peff of losartan when perfused alone was found to be 0.427 ± 0.27×10-4cm/s and when it was co-perfused with inhibitors, significant change in Peff was observed. Peff of midazolam when perfused alone was found to be 2.03 ± 0.07 × 10-4cm/s and when it was co-perfused with inhibitors, no significant change in Peff was observed. Comparison of Peff calculated in frog with that of other available models and also humans suggested that the Peff values are comparable and reflected well with human intestinal permeability. It is possible to determine the Peff value for compounds which are dual substrates of P-gp and CYP3A4 using in situ frog intestinal perfusion technique. The calculated Peff values correlated well with reported Peff values of probe drugs. comparison of the Peff value of losartan obtained with that of reported human’s Peff and Caco 2 cell data, and comparison of the Peff value of midazolam with that of reported rat’s Peff, we could conclude that SPIP from model can be reliably used in preclinical studies for permeability estimation. This model may represent a valuable alternative to the low speed and high cost of conventional animal models (typically rodents for the assessment of intestinal permeability.

  7. Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities

    Science.gov (United States)

    Valentin-Vega, Yasmine A.; Box, Neil; Terzian, Tamara; Lozano, Guillermina

    2014-01-01

    Mdm4 is a critical inhibitor of the p53 tumor suppressor. Mdm4 null mice die early during embryogenesis due to increased p53 activity. In this study, we explore the role that Mdm4 plays in the intestinal epithelium by crossing mice carrying the Mdm4 floxed allele to mice with the Villin Cre transgene. Our data show that loss of Mdm4 (Mdm4intΔ) in this tissue resulted in viable animals with no obvious morphological abnormalities. However, these mutants displayed increased p53 levels and apoptosis exclusively in the proliferative compartment of the intestinal epithelium. This phenotype was completely rescued in a p53 null background. Notably, the observed compartmentalized apoptosis in proliferative intestinal epithelial cells was not due to restricted Mdm4 expression in this region. Thus, in this specific cellular context, p53 is negatively regulated by Mdm4 exclusively in highly proliferative cells. PMID:19371999

  8. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease.

    Science.gov (United States)

    Lerner, Aaron; Matthias, Torsten

    2015-06-01

    The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression. Copyright © 2015. Published by Elsevier B.V.

  9. Increased intestinal permeability, measured by serum zonulin, is associated with metabolic risk markers in overweight pregnant women.

    Science.gov (United States)

    Mokkala, Kati; Pellonperä, Outi; Röytiö, Henna; Pussinen, Pirkko; Rönnemaa, Tapani; Laitinen, Kirsi

    2017-04-01

    Increased intestinal permeability with subsequent metabolic endotoxemia, i.e., elevated circulating levels of bacterial lipopolysaccharide, LPS, has been introduced as a novel initiator of obesity related metabolic disturbances in non-pregnant individuals. The objective was to investigate the extent to which intestinal permeability, measured by serum zonulin concentration, is related to metabolic endotoxemia and metabolic risk markers in overweight pregnant women. This was a cross-sectional study including 100 pregnant overweight women in early pregnancy. Serum zonulin was analyzed using ELISA, and markers for metabolic endotoxemia (LPS), inflammation (high-sensitive C-reactive protein and glycoprotein acetylation GlyA), glucose metabolism (fasting glucose and insulin), and lipid metabolism were measured. Higher serum zonulin concentration associated positively with LPS (P=0.02), inflammatory markers (Pzonulin quartiles). All the observed associations were confirmed (Pzonulin concentration, i.e., increased intestinal permeability, contributes to metabolic endotoxemia, systemic inflammation, and insulin resistance in overweight pregnant women. By reinforcing intestinal barrier, it may be possible to manipulate maternal metabolism during pregnancy with subsequent health benefits. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?

    Science.gov (United States)

    Ganda Mall, John-Peter; Östlund-Lagerström, Lina; Lindqvist, Carl Mårten; Algilani, Samal; Rasoal, Dara; Repsilber, Dirk; Brummer, Robert J; V Keita, Åsa; Schoultz, Ida

    2018-03-20

    Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults. Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA). Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin. Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.

  11. Intestinal permeability induced by lipopolysaccharide and measured by lactulose, rhamnose and mannitol sugars in chickens.

    Science.gov (United States)

    Gilani, S; Howarth, G S; Kitessa, S M; Tran, C D; Forder, R E A; Hughes, R J

    2017-07-01

    Increased intestinal permeability (IP) can lead to compromised health. Limited in vivo IP research has been conducted in chickens. The objectives of the current study were to develop a model of increased IP utilizing lipopolysaccharide (LPS Escherichia coli O55:B5) and to evaluate IP changes using the lactulose, mannitol and rhamnose (LMR) sugar permeability test. In addition, fluorescein isothiocyanate dextran (FITC-d), d-lactate, zonula occludens (ZO-1) and diamine oxidase (DAO) permeability tests were employed. Male Ross chickens were reared until day 14 on the floor in an animal care facility and then transferred to individual cages in three separate experiments. In each of experiments 1 and 2, 36 chicks were randomly allocated to receive either saline (control) or LPS (n=18/group). Lactulose, mannitol and rhamnose sugar concentration in blood was measured at 0, 30, 60, 90, 120 and 180 min in experiment 1, at 60, 90 and 120 min in experiment 2 and at 90 min in experiment 3 (n=16/group). Lipopolysaccharide was injected intraperitoneally at doses of 0.5, 1 and 1 mg/kg BW in experiments 1, 2 and 3, respectively, on days 16, 18 and 20, whereas control received sterile saline. On day 21, only birds in experiments 1 and 2 were fasted for 19.5 h. Chicks were orally gavaged with the LMR sugars (0.25 gL, 0.05 gM, 0.05 gR/bird) followed by blood collection (from the brachial vein) as per time point for each experiment. Only in experiment 3, were birds given an additional oral gavage of FITC-d (2.2 mg/ml per bird) 60 min after the first gavage. Plasma d-lactate, ZO-1 and DAO concentrations were also determined by ELISA in experiment 3 (n=10). Administration of LPS did not affect IP as measured by the LMR sugar test compared with control. This was also confirmed by FITC-d and DAO levels in experiment 3 (P>0.05). The plasma levels of d-lactate were decreased (Psugar can be detected in blood 90 min after the oral gavage. Further studies are needed for the applicability of

  12. Fecal lactoferrin and intestinal permeability are effective non-invasive markers in the diagnostic work-up of chronic diarrhea.

    Science.gov (United States)

    Caccaro, Roberta; D'Incà, Renata; Martinato, Matteo; Pont, Elisabetta Dal; Pathak, Surajit; Frigo, Anna Chiara; Sturniolo, Giacomo Carlo

    2014-10-01

    Non-invasive markers able to identify patients with chronic diarrhea at risk of organic disease are missing. Aim of the study was to assess the diagnostic ability of intestinal permeability (IP) test and fecal lactoferrin (FL) in distinguishing functional from organic disease in patients with chronic diarrhea. We retrospectively enrolled patients referring to the gastroenterology outpatient clinic for chronic diarrhea. Among the 103 patients included, 40 % had an organic disease, with IP and FL levels significantly higher compared to those with a functional disorder (p chronic diarrhea patients. Together these tests could recognize both the presence of intestinal damage and its site.

  13. Liquid chromatography-tandem mass spectrometry for analysis of intestinal permeability of loperamide in physiological buffer.

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    Miriam S Rubelt

    Full Text Available Analysis of in vitro samples with high salt concentrations represents a major challenge for fast and specific quantification with liquid chromatography-tandem mass spectrometry (LC-MS/MS. To investigate the intestinal permeability of opioids in vitro employing the Ussing chamber technique, we developed and validated a fast, sensitive and selective method based on LC-MS/MS for the determination of loperamide in HEPES-buffered Ringer's solution. Chromatographic separation was achieved with an Atlantis dC18 column, 2.1 mm×20 mm, 3 µm particle size and a gradient consisting of methanol/0.1% formic acid and ammonium acetate. The flow rate was 0.7 ml/min, and the total run time was 3 min. For quantification, two mass transitions for loperamide and a deuterated internal standard (methadone-d(3 were used. The lower limit of loperamide quantification was 0.2 ng/ml. This new LC-MS/MS method can be used for the detection of loperamide in any experimental setup using HEPES-buffered Ringer's solution as a matrix compound.

  14. Effect of acute, slightly increased intra-abdominal pressure on intestinal permeability and oxidative stress in a rat model.

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    Yuxin Leng

    Full Text Available INTRODUCTION: Intra-abdominal hypertension (IAH is known as a common, serious complication in critically ill patients. Bacterial translocation and permeability changes are considered the pathophysiological bases for IAH-induced enterogenic endotoxemia and subsequent multiorgan failure. Nevertheless, the effects of slightly elevated intra-abdominal pressures (IAPs on the intestinal mucosa and the associated mechanisms remain unclear. METHODS: To investigate the acute effects of different nitrogen pneumoperitoneum grades on colonic mucosa, male Sprague-Dawley rats were assigned to six groups with different IAPs (0 [control], 4, 8, 12, 16, and 20 mmHg, n = 6/group. During 90 min of exposure, we dynamically monitored the heart rate and noninvasive hemodynamic parameters. After gradual decompression, arterial blood gas analyses were conducted. Thereafter, structural injuries to the colonic mucosa were identified using light microscopy. Colon permeability was determined using the expression of tight junction proteins, combined with fluorescein isothiocyanate dextran (FD-4 absorption. The pro-oxidant-antioxidant balance was determined based on the levels of malondialdehyde (MDA and antioxidant enzymes. RESULTS: IAH significantly affected the histological scores of the colonic mucosa, tight junction protein expression, mucosal permeability, and pro-oxidant-antioxidant balance. Interestingly, elevations of IAP that were lower than the threshold for IAH also showed a similar, undesirable effect. In the 8 mmHg group, mild hyponatremia, hypocalcemia, and hypoxemia occurred, accompanied by reduced blood and abdominal perfusion pressures. Mild microscopic inflammatory infiltration and increased MDA levels were also detected. Moreover, an 8-mm Hg IAP markedly inhibited the expression of tight junction proteins, although no significant differences in FD-4 permeability were observed between the 0- and 8-mmHg groups. CONCLUSIONS: Acute exposure to slightly

  15. Effect of early enteral nutrition (EN) on endotoxin in serum and intestinal permeability in patients with severe acute pancreatitis.

    Science.gov (United States)

    Shen, Q-X; Xu, G-X; Shen, M-H

    2017-06-01

    This work aimed at studying the effect of early enteral nutrition (EN) on serum endotoxin and intestinal permeability in patients with severe acute pancreatitis. 70 cases of patients with severe acute pancreatitis were cured in our hospital from April 2015 to January 2016. Patients selected were randomly divided into two groups including a group of patients having parenteral nutrition (group PN) and that had enteral nutrition (group EN). The results were assessed by: 1) the differences of serum endotoxin level; 2) the differences of the lactulose/mannitol ratio of urine, before intervention and one and two weeks after the intervention. Before the intervention, both groups had similar levels of serum endotoxin and the same lactulose/mannitol excretion rate of urine (p>0.05). One and two weeks after the intervention, the serum endotoxin level and the lactulose/mannitol excretion rate of urine of the group PN were significantly higher than the group EN (pEN has a bigger effect on serum endotoxin and intestinal permeability in patients with severe acute pancreatitis. EN can better promote the elimination of serum endotoxin and reduce intestinal permeability. Therefore, EN deserves clinical expansion.

  16. Rapid small intestinal permeability assay based on riboflavin and lactulose detected by bis-boronic acid appended benzyl viologens.

    Science.gov (United States)

    Resendez, Angel; Abdul Halim, Md; Landhage, Caroline M; Hellström, Per M; Singaram, Bakthan; Webb, Dominic-Luc

    2015-01-15

    Although organoboronic acids are efficient high-throughput sugar sensors, they have not been pursued for gut permeability studies. A modification of the lactulose/mannitol assay is described by which small intestinal permeability is assessed at the time of urine collection using a lactulose/riboflavin ratio. Volunteers ingested 50mg riboflavin and either 5 g mannitol or 10 g lactulose. Urine was collected for 6 hrs. Riboflavin was assayed by autofluorescence. Riboflavin was removed by C18 solid phase extraction. Lactulose and mannitol were then assayed using 1,1'-bis(2-boronobenzyl)-4,4'-bipyridinium (4,4'oBBV) coupled to the fluorophore HPTS. The temporal profile over 6 hrs for riboflavin paralleled mannitol. Riboflavin recovery in urine was 11.1 ± 1.9 % (mean ± SEM, n=7), similar to mannitol. There was selective binding of 4,4'oBBV to lactulose, likely involving cooperativity between the fructose and galactose moieties. Lower limits of detection and quantification were 90 and 364 μM. The lactulose assay was insensitive to other permeability probes (e.g., sucrose, sucralose) while tolerating glucose or lactose. This assay can be adapted to automated systems. Stability of 4,4'oBBV exceeds 4 years. Riboflavin measured by autofluorescence combined with lactulose measured with 4,4'oBBV represents a useful new chemistry for rapid measurement of intestinal permeability with excellent stability, cost and throughput benefits. Copyright © 2014. Published by Elsevier B.V.

  17. Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation.

    Directory of Open Access Journals (Sweden)

    Keith C Summa

    Full Text Available The circadian clock orchestrates temporal patterns of physiology and behavior relative to the environmental light:dark cycle by generating and organizing transcriptional and biochemical rhythms in cells and tissues throughout the body. Circadian clock genes have been shown to regulate the physiology and function of the gastrointestinal tract. Disruption of the intestinal epithelial barrier enables the translocation of proinflammatory bacterial products, such as endotoxin, across the intestinal wall and into systemic circulation; a process that has been linked to pathologic inflammatory states associated with metabolic, hepatic, cardiovascular and neurodegenerative diseases - many of which are commonly reported in shift workers. Here we report, for the first time, that circadian disorganization, using independent genetic and environmental strategies, increases permeability of the intestinal epithelial barrier (i.e., gut leakiness in mice. Utilizing chronic alcohol consumption as a well-established model of induced intestinal hyperpermeability, we also found that both genetic and environmental circadian disruption promote alcohol-induced gut leakiness, endotoxemia and steatohepatitis, possibly through a mechanism involving the tight junction protein occludin. Circadian organization thus appears critical for the maintenance of intestinal barrier integrity, especially in the context of injurious agents, such as alcohol. Circadian disruption may therefore represent a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease, as well as other conditions associated with intestinal hyperpermeability and an endotoxin-triggered inflammatory state.

  18. Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Utzeri, Erika; Usai, Paolo

    2017-06-14

    The use of non-steroidal anti-inflammatory drugs (NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of non-alcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.

  19. Ex vivo permeability experiments in excised rat intestinal tissue and in vitro solubility measurements in aspirated human intestinal fluids support age-dependent oral drug absorption.

    Science.gov (United States)

    Annaert, Pieter; Brouwers, Joachim; Bijnens, Ann; Lammert, Frank; Tack, Jan; Augustijns, Patrick

    2010-01-31

    The possible influence of advanced age on intestinal drug absorption was investigated by determining the effects of aging on (i) solubility of model drugs in human intestinal fluids (HIF) obtained from two age groups (18-25 years; 62-72 years); and (ii) transepithelial permeation of model drugs across intestinal tissue excised from young, adult and old rats. Average equilibrium solubility values for 10 poorly soluble compounds in HIF aspirated from both age groups showed high interindividual variability, but did not reveal significant differences. Characterization of the HIF from both age groups demonstrated comparable pH profiles, while concentrations of individual bile salts showed pronounced variability between individuals, however without statistical differences between age groups. Transepithelial permeation of the transcellular probe metoprolol was significantly increased in old rats (38 weeks) compared to the younger age groups, while the modulatory role of P-glycoprotein in transepithelial talinolol transport was observed in adult and old rats but not in young rats. In conclusion, age-dependent permeability of intestinal tissue (rather than age-dependent luminal drug solubility) may contribute to altered intestinal drug absorption in older patients compared to young adults. Copyright 2009 Elsevier B.V. All rights reserved.

  20. In vitro studies of intestinal permeability and hepatic and intestinal metabolism of 8-prenylnaringenin, a potent phytoestrogen from hops (Humulus lupulus L.).

    Science.gov (United States)

    Nikolic, Dejan; Li, Yongmei; Chadwick, Lucas R; van Breemen, Richard B

    2006-05-01

    The absorption potential and metabolism of 8-prenylnaringenin (8-PN) from hops (Humulus lupulus L.) were investigated. 8-PN is a potent estrogen with the potential to be used for the relief of menopausal symptoms in women. Monolayers of the human intestinal epithelial cancer cell line Caco-2 and human hepatocytes were incubated with 8-PN to model its intestinal absorption and hepatic metabolism, respectively. The apparent permeability coefficients for 8-PN in the apical-to-basolateral and basolateral-to-apical directions of a Caco-2 monolayer were 5.2 +/- 0.7 x 10(-5) and 4.9 +/- 0.5 x 10(-5) cm/s, respectively, indicating good intestinal absorption via passive diffusion. Both glucuronide and sulfate conjugates of 8-PN were detected in the Caco-2 cell incubations. The 4'-O-glucuronide was the predominant Caco-2 cell metabolite, followed by 7-O-sulfate and 4'-O-sulfate. Both phase I and phase II metabolites of 8-PN were formed by human hepatocytes. The 7-O-glucuronide was the most abundant hepatocyte metabolite, and no sulfate conjugates were detected. Incubations with various cDNA-expressed UDP-glucuronosyltransferases indicated that the isozymes UGT1A1, UGT1A6, UGT1A8, and UGT1A9 were responsible for glucuronidation of 8-PN. Although orally administered 8-PN should be readily absorbed from the intestine, its bioavailability should be reduced significantly by intestinal and hepatic metabolism.

  1. Water absorption enhances the uptake of mannitol and decreases Cr-EDTA/mannitol permeability ratios in cat small intestine in situ

    NARCIS (Netherlands)

    Bijlsma, P. B.; Fihn, B. M.; Sjöqvist, A.; Groot, J. A.; Taminiau, J. A. J. M.; Jodal, M.

    2002-01-01

    Background: Recently, we hypothesized that mannitol absorption in human intestinal permeability tests is a reflection of small intestinal water absorption and is dependent mainly on the efficiency of the countercurrent multiplier in the villi. This may affect the outcome of clinical double-sugar

  2. Knockout of MIMP protein in lactobacillus plantarum lost its regulation of intestinal permeability on NCM460 epithelial cells through the zonulin pathway.

    Science.gov (United States)

    Liu, Zhihua; Kang, Liang; Li, Chao; Tong, Chao; Huang, Meijin; Zhang, Xingwei; Huang, Nanqi; Moyer, Mary Pat; Qin, Huanlong; Wang, Jianping

    2014-10-03

    Previous studies indicated that the micro integral membrane protein located within the media place of the integral membrane protein of Lactobacillus plantarum CGMCC 1258 had protective effects against the intestinal epithelial injury. In our study, we mean to establish micro integral membrane protein -knockout Lactobacillus plantarum (LPKM) to investigate the change of its protective effects and verify the role of micro integral membrane protein on protection of normal intestinal barrier function. Binding assay and intestinal permeability were performed to verify the protective effects of micro integral membrane protein on intestinal permeability in vitro and in vivo. Molecular mechanism was also determined as the zonulin pathway. Clinical data were also collected for further verification of relationship between zonulin level and postoperative septicemia. LPKM got decreased inhibition of EPEC adhesion to NCM460 cells. LPKM had lower ability to alleviate the decrease of intestinal permeability induced by enteropathogenic-e.coli, and prevent enteropathogenic-e.coli -induced increase of zonulin expression. Overexpression of zonulin lowered the intestinal permeability regulated by Lactobacillus plantarum. There was a positive correlation between zonulin level and postoperative septicemia. Therefore, micro integral membrane protein could be necessary for the protective effects of Lactobacillus plantarum on intestinal barrier. MIMP might be a positive factor for Lactobacillus plantarum to protect the intestinal epithelial cells from injury, which could be related to the zonulin pathway.

  3. Abnormal Wnt and PI3Kinase signaling in the malformed intestine of lama5 deficient mice.

    Directory of Open Access Journals (Sweden)

    Léa Ritié

    Full Text Available Laminins are major constituents of basement membranes and are essential for tissue homeostasis. Laminin-511 is highly expressed in the intestine and its absence causes severe malformation of the intestine and embryonic lethality. To understand the mechanistic role of laminin-511 in tissue homeostasis, we used RNA profiling of embryonic intestinal tissue of lama5 knockout mice and identified a lama5 specific gene expression signature. By combining cell culture experiments with mediated knockdown approaches, we provide a mechanistic link between laminin α5 gene deficiency and the physiological phenotype. We show that laminin α5 plays a crucial role in both epithelial and mesenchymal cell behavior by inhibiting Wnt and activating PI3K signaling. We conclude that conflicting signals are elicited in the absence of lama5, which alter cell adhesion, migration as well as epithelial and muscle differentiation. Conversely, adhesion to laminin-511 may serve as a potent regulator of known interconnected PI3K/Akt and Wnt signaling pathways. Thus deregulated adhesion to laminin-511 may be instrumental in diseases such as human pathologies of the gut where laminin-511 is abnormally expressed as it is shown here.

  4. Intestinal permeability to (/sup 51/Cr)EDTA in children with Crohn's disease and celiac disease

    Energy Technology Data Exchange (ETDEWEB)

    Turck, D.; Ythier, H.; Maquet, E.; Deveaux, M.; Marchandise, X.; Farriaux, J.P.; Fontaine, G.

    1987-07-01

    (/sup 51/Cr)EDTA was used as a probe molecule to assess intestinal permeability in 7 healthy control adults, 11 control children, 17 children with Crohn's disease, and 6 children with untreated celiac disease. After subjects fasted overnight, 75 kBq/kg (= 2 microCi/kg) /sup 51/Cr-labeled EDTA was given by mouth; 24-h urinary excretion of (/sup 51/Cr)EDTA was measured and expressed as a percentage of the total oral dose. Mean and SD were as follows: control adults 1.47 +/- 0.62, control children 1.59 +/- 0.55, and patients with Crohn's disease or celiac disease 5.35 +/- 1.94. The difference between control children and patients was statistically significant (p less than 0.001). These results show that intestinal permeability to (/sup 51/Cr)EDTA is increased among children with active or inactive Crohn's disease affecting small bowel only or small bowel and colon, and with untreated celiac disease. The (/sup 51/Cr)EDTA permeability test could facilitate the decision to perform more extensive investigations in children suspected of small bowel disease who have atypical or poor clinical and biological symptomatology.

  5. Autoimmune gastritis and parietal cell reactivity in two children with abnormal intestinal permeability

    NARCIS (Netherlands)

    Greenwood, Deanne L. V.; Crock, Patricia; Braye, Stephen; Davidson, Patricia; Sentry, John W.

    Autoimmune gastritis is characterised by lymphocytic infiltration of the gastric submucosa, with loss of parietal and chief cells and achlorhydria. Often, gastritis is expressed clinically as cobalamin deficiency with megaloblastic anaemia, which is generally described as a disease of the elderly.

  6. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease.

    Science.gov (United States)

    Thomas, Karen E; Sapone, Anna; Fasano, Alessio; Vogel, Stefanie N

    2006-02-15

    Recent studies have demonstrated the importance of TLR signaling in intestinal homeostasis. Celiac disease (CD) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. In this study, we sought to test the hypothesis that gliadin initiates this response by stimulating the innate immune response to increase intestinal permeability and by up-regulating macrophage proinflammatory gene expression and cytokine production. To this end, intestinal permeability and the release of zonulin (an endogenous mediator of gut permeability) in vitro, as well as proinflammatory gene expression and cytokine release by primary murine macrophage cultures, were measured. Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be potent inducers of both a zonulin-dependent increase in intestinal permeability and macrophage proinflammatory gene expression and cytokine secretion. Gliadin-induced zonulin release, increased intestinal permeability, and cytokine production were dependent on myeloid differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data support the following model for the innate immune response to gliadin in the initiation of CD. Gliadin interaction with the intestinal epithelium increases intestinal permeability through the MyD88-dependent release of zonulin that, in turn, enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa. There, the interaction of gliadin with macrophages elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive immune response seen in patients with CD.

  7. Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA).

    Science.gov (United States)

    Petit, Charlotte; Bujard, Alban; Skalicka-Woźniak, Krystyna; Cretton, Sylvian; Houriet, Joëlle; Christen, Philippe; Carrupt, Pierre-Alain; Wolfender, Jean-Luc

    2016-03-01

    At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay is one of the most frequently used in vitro models to predict transcellular passive absorption. While thousands of new chemical entities have been screened with the parallel artificial membrane permeability assay, in general, permeation properties of natural products have been scarcely evaluated. In this study, the parallel artificial membrane permeability assay through a hexadecane membrane was used to predict the passive intestinal absorption of a representative set of frequently occurring natural products. Since natural products are usually ingested for medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of such an assay to study the constituents directly in medicinal crude plant extracts was further investigated. Three representative crude plant extracts with different natural product compositions were chosen for this study. The first extract was composed of furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica), and the third extract contained flavonoid glycosides (Pueraria montana var. lobata). For each medicinal plant, the effective passive permeability values Pe (cm/s) of the main natural products of interest were rapidly calculated thanks to a generic ultrahigh-pressure liquid chromatography-UV detection method and because Pe calculations do not require knowing precisely the concentration of each natural product within the extracts. The original parallel artificial membrane permeability assay through a hexadecane membrane was found to keep its predictive power when applied to constituents directly in crude plant extracts provided that higher quantities of the extract were initially loaded in the assay in order to ensure suitable detection of the individual constituents of the extracts. Such an approach is thus valuable for the high

  8. Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity

    Science.gov (United States)

    Hollon, Justin; Leonard Puppa, Elaine; Greenwald, Bruce; Goldberg, Eric; Guerrerio, Anthony; Fasano, Alessio

    2015-01-01

    Background: Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). Methods: Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. Results: Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. Conclusions: Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity. PMID:25734566

  9. Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity

    Directory of Open Access Journals (Sweden)

    Justin Hollon

    2015-02-01

    Full Text Available Background: Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD, celiac patients in remission (RCD, non-celiac patients with gluten sensitivity (GS and non-celiac controls (NC. Methods: Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. Results: Intestinal explants from all groups (ACD (n = 6, RCD (n = 6, GS (n = 6, and NC (n = 5 demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. Conclusions: Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity.

  10. Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

    Science.gov (United States)

    Chen, Wei-Yang; Wang, Min; Zhang, Jingwen; Barve, Shirish S; McClain, Craig J; Joshi-Barve, Swati

    2017-12-01

    Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

    Directory of Open Access Journals (Sweden)

    José María Moreno-Navarrete

    Full Text Available Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity. Circulating zonulin increased with body mass index (BMI, waist to hip ratio (WHR, fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002 contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01 contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

  12. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

    Science.gov (United States)

    Moreno-Navarrete, José María; Sabater, Mònica; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

    2012-01-01

    Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

  13. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Schütz, Tanja

    2000-01-01

    BACKGROUND/AIMS: No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (Mr>1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse...... and mild to more advanced stages of liver disease, and to measure the concentration of endotoxins in the plasma, as these compounds derive from the intestinal flora and are suspected to contribute to the development of alcoholic liver disease (ALD). METHODS: The permeability to polyethylene glycol Mr 400......, Mr 1500, Mr 4000, and Mr 10,000 and endotoxin plasma concentrations were measured in 54 patients with alcoholic liver disease, 19 of them with cirrhosis, and in 30 non-alcoholic healthy controls. RESULTS: Permeability to polyethylene glycol Mr 400 was found to be unchanged in patients with ALD...

  14. TNF-α Modulation of Intestinal Tight Junction Permeability Is Mediated by NIK/IKK-α Axis Activation of the Canonical NF-κB Pathway

    Science.gov (United States)

    Al-Sadi, Rana; Guo, Shuhong; Ye, Dongmei; Rawat, Manmeet; Ma, Thomas Y.

    2017-01-01

    Tumor necrosis factor (TNF)-α, a key mediator of intestinal inflammation, causes an increase in intestinal epithelial tight junction (TJ) permeability by activating myosin light chain kinase (MLCK; official name MYLK3) gene. However, the precise signaling cascades that mediate the TNF-α–induced activation of MLCK gene and increase in TJ permeability remain unclear. Our aims were to delineate the upstream signaling mechanisms that regulate the TNF-α modulation of intestinal TJ barrier function with the use of in vitro and in vivo intestinal epithelial model systems. TNF-α caused a rapid activation of both canonical and noncanonical NF-κB pathway. NF-κB–inducing kinase (NIK) and mitogen-activated protein kinase kinase-1 (MEKK-1) were activated in response to TNF-α. NIK mediated the TNF-α activation of inhibitory κB kinase (IKK)-α, and MEKK1 mediated the activation of IKK complex, including IKK-β. NIK/IKK-α axis regulated the activation of both NF-κB p50/p65 and RelB/p52 pathways. Surprisingly, the siRNA induced knockdown of NIK, but not MEKK-1, prevented the TNF-α activation of both NF-κB p50/p65 and RelB/p52 and the increase in intestinal TJ permeability. Moreover, NIK/IKK-α/NF-κB p50/p65 axis mediated the TNF-α–induced MLCK gene activation and the subsequent MLCK increase in intestinal TJ permeability. In conclusion, our data show that NIK/IKK-α/regulates the activation of NF-κB p50/p65 and plays an integral role in the TNF-α–induced activation of MLCK gene and increase in intestinal TJ permeability. PMID:26948423

  15. High paracellular nutrient absorption in intact bats is associated with high paracellular permeability in perfused intestinal segments.

    Science.gov (United States)

    Brun, Antonio; Price, Edwin R; Gontero-Fourcade, Manuel N; Fernandez-Marinone, Guido; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

    2014-09-15

    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. © 2014. Published by The Company of Biologists Ltd.

  16. Association between intestinal permeability and faecal microbiota composition in Italian children with beta cell autoimmunity at risk for type 1 diabetes.

    Science.gov (United States)

    Maffeis, Claudio; Martina, Alessia; Corradi, Massimiliano; Quarella, Sara; Nori, Nicole; Torriani, Sandra; Plebani, Mario; Contreas, Giovanna; Felis, Giovanna E

    2016-10-01

    Pancreatic organ-specific autoimmunity in subjects at risk for type 1 diabetes (T1D) is associated with increased intestinal permeability and an aberrant gut microbiota, but these factors have not yet been simultaneously investigated in the same subjects. Thus, the aim of this study was to assess both intestinal permeability and gut microbiota composition in an Italian sample of children at risk for T1D. Ten Italian children with beta cell autoimmunity at risk for T1D and 10 healthy children were involved in a case-control study. The lactulose/mannitol test was used to assess intestinal permeability. Analysis of microbiota composition was performed using polymerase chain reaction followed by denaturing gradient gel electrophoresis, based on the 16S rRNA gene. Intestinal permeability was significantly higher in children at risk for T1D than in healthy controls. Moreover, the gut microbiota of the former differed from that of the latter group: Three microorganisms were detected - Dialister invisus, Gemella sanguinis and Bifidobacterium longum - in association with the pre-pathologic state. The results of this study validated the hypothesis that increased intestinal permeability together with differences in microbiota composition are contemporaneously associated with the pre-pathological condition of T1D in a sample of Italian children. Further studies are necessary to confirm the microbial markers identified in this sample of children as well as to clarify the involvement of microbiota modifications in the mechanisms leading to increased permeability and the autoimmune mechanisms that promote diabetes onset. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Review article: Associations between immune activation, intestinal permeability and the irritable bowel syndrome.

    Science.gov (United States)

    Matricon, J; Meleine, M; Gelot, A; Piche, T; Dapoigny, M; Muller, E; Ardid, D

    2012-12-01

    Irritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, markedly impairing patients' quality of life. Drug development for IBS treatment has been hampered by the lack of understanding of IBS aetiology. In recent years, numerous data have emerged that suggest the involvement of immune activation in IBS, at least in a subset of patients. To determine whether immune activation and intestinal permeabilisation are more frequently observed in IBS patients compared with healthy controls. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, inflammation, immune activation, permeabilisation, intestine, assay, histology and human. The retrieved studies, including blood, faecal and histological studies, were analysed to provide a comprehensive and structured overview of the available data including the type of assay, type of inflammatory marker investigated or intestinal segment studied. Immune activation was more frequently observed in IBS patients than in healthy controls. An increase in the number of mast cells and lymphocytes, an alteration in cytokine levels and intestinal permeabilisation were reported in IBS patients. No consistent changes in the numbers of B cells or enterochromaffin cells or in mucosal serotonin production were demonstrated. The changes observed were modest and often heterogeneous among the studied population. Only appropriate interventions improving irritable bowel syndrome symptoms could highlight and confirm the role of immune activation in this pathophysiology. © 2012 Blackwell Publishing Ltd.

  18. Psychological stress exacerbates NSAID-induced small bowel injury by inducing changes in intestinal microbiota and permeability via glucocorticoid receptor signaling.

    Science.gov (United States)

    Yoshikawa, Kenichi; Kurihara, Chie; Furuhashi, Hirotaka; Takajo, Takeshi; Maruta, Koji; Yasutake, Yuichi; Sato, Hirokazu; Narimatsu, Kazuyuki; Okada, Yoshikiyo; Higashiyama, Masaaki; Watanabe, Chikako; Komoto, Shunsuke; Tomita, Kengo; Nagao, Shigeaki; Miura, Soichiro; Tajiri, Hisao; Hokari, Ryota

    2017-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are popular painkillers, but they have serious side effects, not only in the upper gastrointestinal tract but also in the small intestine. It is well known that psychological stress may exacerbate various gastrointestinal diseases. The aim of this study was to determine whether psychological stress exacerbates NSAID enteropathy and to determine the possible underlying mechanisms for this. Experiment 1: mice were exposed to water avoidance stress (WAS) or sham stress for 1 h per day for 8 consecutive days, and then enteropathy was induced by indomethacin. Experiment 2: cecal contents from stress (-) or (+) mice were transplanted into mice that had received antibiotics and in which NSAID enteropathy had been induced without WAS. Experiment 3: mifepristone, a glucocorticoid receptor antagonist, was injected before WAS for 8 days. Small intestinal injury, mRNA expression of TNFα, intestinal permeability, and the microbial community were assessed. Psychological stress exacerbated NSAID enteropathy and increased intestinal permeability. Psychological stress induced changes in the ileal microbiota that were characterized by increases in the total number of bacteria and the proportion of Gram-negative bacteria. The increased susceptibility to NSAIDs and intestinal permeability due to WAS was transferable via cecal microbiota transplantation. The increased permeability and aggravation of NSAID enteropathy caused by WAS were blocked by the administration of mifepristone. This study demonstrated a relationship between NSAID enteropathy and psychological stress, and showed the utility of studying the intestinal microbiota in order to elucidate the pathophysiology of NSAID enteropathy. It also showed the impact of stress on the intestinal microbiota and the mucosal barrier in gastrointestinal diseases.

  19. Mast cells and histamine alter intestinal permeability during malaria parasite infection.

    Science.gov (United States)

    Potts, Rashaun A; Tiffany, Caitlin M; Pakpour, Nazzy; Lokken, Kristen L; Tiffany, Connor R; Cheung, Kong; Tsolis, Renée M; Luckhart, Shirley

    2016-03-01

    Co-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can present as life-threatening bacteremia, in contrast to self-resolving NTS diarrhea in healthy individuals. In previous work with our mouse model of malaria/NTS co-infection, we showed increased gut mastocytosis and increased ileal and plasma histamine levels that were temporally associated with increased gut permeability and bacterial translocation. Here, we report that gut mastocytosis and elevated plasma histamine are also associated with malaria in an animal model of falciparum malaria, suggesting a broader host distribution of this biology. In support of mast cell function in this phenotype, malaria/NTS co-infection in mast cell-deficient mice was associated with a reduction in gut permeability and bacteremia. Further, antihistamine treatment reduced bacterial translocation and gut permeability in mice with malaria, suggesting a contribution of mast cell-derived histamine to GI pathology and enhanced risk of bacteremia during malaria/NTS co-infection. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Intestinal Permeability and Cellular Antioxidant Activity of Phenolic Compounds from Mango (Mangifera indica cv. Ataulfo) Peels.

    Science.gov (United States)

    Pacheco-Ordaz, Ramón; Antunes-Ricardo, Marilena; Gutiérrez-Uribe, Janet A; González-Aguilar, Gustavo A

    2018-02-08

    Mango ( Mangifera indica cv. Ataulfo) peel contains bound phenolics that may be released by alkaline or acid hydrolysis and may be converted into less complex molecules. Free phenolics from mango cv. Ataulfo peel were obtained using a methanolic extraction, and their cellular antioxidant activity (CAA) and permeability were compared to those obtained for bound phenolics released by alkaline or acid hydrolysis. Gallic acid was found as a simple phenolic acid after alkaline hydrolysis along with mangiferin isomers and quercetin as aglycone and glycosides. Only gallic acid, ethyl gallate, mangiferin, and quercetin were identified in the acid fraction. The acid and alkaline fractions showed the highest CAA (60.5% and 51.5%) when tested at 125 µg/mL. The value of the apparent permeability coefficient (Papp) across the Caco-2/HT-29 monolayer of gallic acid from the alkaline fraction was higher (2.61 × 10 -6 cm/s) than in the other fractions and similar to that obtained when tested pure (2.48 × 10 -6 cm/s). In conclusion, mango peels contain bound phenolic compounds that, after their release, have permeability similar to pure compounds and exert an important CAA. This finding can be applied in the development of nutraceuticals using this important by-product from the mango processing industry.

  1. Enhanced Intestinal Permeability of Bufalin by a Novel Bufalin-Peptide-Dendrimer Inclusion through Caco-2 Cell Monolayer.

    Science.gov (United States)

    Chan, Chi-On; Jing, Jing; Xiao, Wei; Tan, Zhexu; Lv, Qiuyue; Yang, Jingyu; Chen, Sibao

    2017-11-29

    Bufalin (BFL) has excellent physiological activities such as defending tumors, improving cardiac function, and so on. However, due to its poor water-solubility and bioavailability, the clinical application of BFL remains limited. In order to improve bioavailability of BFL, in our previous research, a novel peptide-dendrimer (PD) was synthesized and applied to encapsulate BFL. In the present study, we investigate the absorption property and mechanism of BFL in free form and BFL-peptide-dendrimer inclusion (BPDI) delivery system by using the Caco-2 cell monolayer model in vitro. The apparent permeability coefficient ( P app ) values of BFL in free or BPDI form were over 1.0 × 10 -6 cm/s. Meanwhile, their almost equal bi-directional transport and linear transport percentage with time and concentration course indicated that BFL in both forms was absorbed mainly through passive diffusion. The most important result is that the P app values of BFL increased about three-fold more BPDI than those of its free form, which indicated the intestinal permeability of BFL could be improved while BFL was encapsulated in BPDI form. Therefore, PD encapsulation may be a potential delivery system to increase the bioavailability of BFL.

  2. Conjugated primary bile salts reduce permeability of endotoxin through bacteria-stimulated intestinal epithelial cells and synergize with lecithin in suppression of inflammatory cytokine production

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schaeckeler, Simone; Moser, Lydia

    2007-01-01

    Objective: Endotoxemia was shown to be integral in the pathophysiology of obstructive jaundice. In the current study, the role of conjugated primary bile salts (CPBS) and phosphatidylcholine on the permeability of endotoxin through a layer of intestinal epithelial cells and the consequent...

  3. Brief Report: Normal Intestinal Permeability at Elevated Platelet Serotonin Levels in a Subgroup of Children with Pervasive Developmental Disorders in Curacao (The Netherlands Antilles)

    Science.gov (United States)

    Kemperman, Ramses F. J.; Muskiet, Fred D.; Boutier, A. Inge; Kema, Ido P.; Muskiet, Frits A. J.

    2008-01-01

    This study investigated the relationship between platelet (PLT) serotonin (5-HT) and intestinal permeability in children with pervasive developmental disorders (PDD). Differential sugar absorption and PLT 5-HT were determined in 23 children with PDD. PLT 5-HT (2.0-7.1 nmol/10[to the ninth power] PLT) was elevated in 4/23 patients. None exhibited…

  4. Conjugated primary bile salts reduce permeability of endotoxin through intestinal epithelial cells and synergize with phosphatidylcholine in suppression of inflammatory cytokine production

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schaeckeler, S.; Moser, L.

    2007-01-01

    OBJECTIVE: Endotoxemia was shown to be integral in the pathophysiology of obstructive jaundice. In the current study, the role of conjugated primary bile salts (CPBS) and phosphatidylcholine on the permeability of endotoxin through a layer of intestinal epithelial cells and the consequent...

  5. Antibiotic treatment affects intestinal permeability and gut microbial composition in Wistar rats dependent on antibiotic class

    DEFF Research Database (Denmark)

    Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera

    2015-01-01

    Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, by disrupting the intricate balance between specific bacterial groups within this ecosystem...... potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (n=12 per group) were dosed by oral gavage with either amoxicillin...

  6. Persistent abnormal liver fibrosis after weaning off parenteral nutrition in pediatric intestinal failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Koivusalo, Antti I; Rintala, Risto J; Pakarinen, Mikko P

    2013-08-01

    The aim of this study was to evaluate the long-term effects of pediatric intestinal failure (IF) on liver histology. Altogether, 38 IF patients (median age: 7.2 years; range, 0.2-27) underwent liver biopsy, gastroscopy, abdominal ultrasound, and laboratory tests. Sixteen patients were on parenteral nutrition (PN) after 74 PN months (range, 2.5-204). Twenty-two had weaned off PN 8.8 years (range, 0.3-27) earlier, after 35 PN months (range, 0.7-250). Fifteen transplant donor livers served as controls. Abnormal liver histology was found in 94% of patients on PN and 77% of patients weaned off PN (P = 0.370). During PN, liver histology weighted with cholestasis (38% of patients on PN versus 0% of patients weaned off PN; P = 0.003) and portal inflammation (38% versus 9%; P = 0.050) were found. Fibrosis (88% versus 64%; P = 0.143; Metavir stage: 1.6 [range, 0-4] versus 1.1 [range, 0-2]; P = 0.089) and steatosis (50% versus 45%; P = 1.000) were equally common during and after weaning off PN. Plasma alanine aminotransferase (78 U/L [range, 19-204] versus 34 [range, 9-129]; P = 0.009) and conjugated bilirubin (43 μmol/L [range, 1-215] versus 4 [range, 1-23]; P = 0.037) were significantly higher during than after weaning off PN. Esophageal varices were encountered in 1 patient after weaning off PN. Metavir stage was associated with small bowel length (r = -0.486; P = 0.002) and number of septic episodes (r = 0.480; P = 0.002). In a multivariate analysis, age-adjusted small bowel length (ß = -0.533; P = 0.001), portal inflammation (ß = 0.291; P = 0.030), and absence of an ileocecal valve (ß = 0.267; P = 0.048) were predictive for fibrosis stage. Despite resolution of cholestasis and portal inflammation, significant liver fibrosis and steatosis persist after weaning off PN. Extensive small intestinal resection was the major predictor for liver fibrosis stage. Copyright © 2013 American Association for the Study of Liver Diseases.

  7. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications.

    Science.gov (United States)

    Fasano, Alessio

    2012-10-01

    One of the most important and overlooked functions of the gastrointestinal tract is to provide a dynamic barrier to tightly controlled antigen trafficking through both the transcellular and paracellular pathways. Intercellular tight junctions (TJ) are the key structures regulating paracellular trafficking of macromolecules. Although steady progress has been made in understanding TJ ultrastructure, relatively little is known about their pathophysiological regulation. Our discovery of zonulin, the only known physiological modulator of intercellular TJ described so far, increased understanding of the intricate mechanisms that regulate gut permeability and led us to appreciate that its up-regulation in genetically susceptible individuals may lead to immune-mediated diseases. This information has translational implications, because the zonulin pathway is currently exploited to develop both diagnostic and therapeutic applications pertinent to a variety of immune-mediated diseases. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. Intestinal Fluid Permeability in Atlantic Salmon (Salmo salar L. Is Affected by Dietary Protein Source.

    Directory of Open Access Journals (Sweden)

    Haibin Hu

    Full Text Available In Atlantic salmon (Salmo salar L., and also in other fish species, certain plant protein ingredients can increase fecal water content creating a diarrhea-like condition which may impair gut function and reduce fish growth. The present study aimed to strengthen understanding of the underlying mechanisms by observing effects of various alternative plant protein sources when replacing fish meal on expression of genes encoding proteins playing key roles in regulation of water transport across the mucosa of the distal intestine (DI. A 48-day feeding trial was conducted with five diets: A reference diet (FM in which fish meal (72% was the only protein source; Diet SBMWG with a mix of soybean meal (30% and wheat gluten (22%; Diet SPCPM with a mix of soy protein concentrate (30% and poultry meal (6%; Diet GMWG with guar meal (30% and wheat gluten (14.5%; Diet PM with 58% poultry meal. Compared to fish fed the FM reference diet, fish fed the soybean meal containing diet (SBMWG showed signs of enteritis in the DI, increased fecal water content of DI chyme and higher plasma osmolality. Altered DI expression of a battery of genes encoding aquaporins, ion transporters, tight junction and adherens junction proteins suggested reduced transcellular transport of water as well as a tightening of the junction barrier in fish fed the SBMWG diet, which may explain the observed higher fecal water content and plasma osmolality. DI structure was not altered for fish fed the other experimental diets but alterations in target gene expression and fecal water content were observed, indicating that alterations in water transport components may take place without clear effects on intestinal structure.

  9. The effects of a multispecies probiotic on migraine and markers of intestinal permeability-results of a randomized placebo-controlled study.

    Science.gov (United States)

    de Roos, N M; van Hemert, S; Rovers, J M P; Smits, M G; Witteman, B J M

    2017-12-01

    Migraine, associated with several gastrointestinal disorders, may result from increased intestinal permeability, allowing endotoxins to enter the bloodstream. We tested whether probiotics could reduce migraine through an effect on intestinal permeability and inflammation. In total, 63 patients were randomly allocated to the probiotic (n=31) or the placebo group (n=32). Participants ingested a multispecies probiotic (5x10 9 colony-forming units) or placebo daily for 12 weeks. Migraine was assessed with the Migraine Disability Assessment Scale (MIDAS), the Headache Disability Inventory (HDI) and headache diaries. At baseline and 12 weeks, intestinal permeability was measured with the urinary lactulose/mannitol test and fecal and serum zonulin; inflammation was measured from interleukin (IL) -6, IL-10, tumor necrosis factor-α and C-reactive protein in serum. The MIDAS migraine intensity score significantly decreased in both groups (P<0.001) and the HDI score significantly decreased in the probiotic group (P=0.032) and borderline in the placebo group (P=0.053). In the probiotics group, patients had a median of 6 migraine days in the first month, 4 in the second month (P=0.002) and 5 in the last month, which was not significantly different from the 5, 4, and 4 days in the placebo group. A ⩾2day reduction in migraine days was seen in 12/31 patients in the probiotics group versus 7/29 in the placebo group (ns). Probiotic use did not significantly affect medication use, intestinal permeability or inflammation compared to placebo. In this study, we could not confirm significant benefit from a multispecies probiotic compared to a placebo on the outcome parameters of migraine and intestinal integrity.

  10. The Microbiome Activates CD4 T-cell–mediated Immunity to Compensate for Increased Intestinal PermeabilitySummary

    Directory of Open Access Journals (Sweden)

    Karen L. Edelblum

    2017-09-01

    Full Text Available Background & Aims: Despite a prominent association, chronic intestinal barrier loss is insufficient to induce disease in human subjects or experimental animals. We hypothesized that compensatory mucosal immune activation might protect individuals with increased intestinal permeability from disease. We used a model in which intestinal barrier loss is triggered by intestinal epithelial-specific expression of constitutively active myosin light chain kinase (CA-MLCK. Here we asked whether constitutive tight junction barrier loss impacts susceptibility to enteric pathogens. Methods: Acute or chronic Toxoplasma gondii or Salmonella typhimurium infection was assessed in CA-MLCK transgenic or wild-type mice. Germ-free mice or those lacking specific immune cell populations were used to investigate the effect of microbial-activated immunity on pathogen translocation in the context of increased intestinal permeability. Results: Acute T gondii and S typhimurium translocation across the epithelial barrier was reduced in CA-MLCK mice. This protection was due to enhanced mucosal immune activation that required CD4+ T cells and interleukin 17A but not immunoglobulin A. The protective mucosal immune activation in CA-MLCK mice depended on segmented filamentous bacteria (SFB, because protection against early S typhimurium invasion was lost in germ-free CA-MLCK mice but could be restored by conventionalization with SFB-containing, not SFB-deficient, microbiota. In contrast, chronic S typhimurium infection was more severe in CA-MLCK mice, suggesting that despite activation of protective mucosal immunity, barrier defects ultimately result in enhanced disease progression. Conclusions: Increased epithelial tight junction permeability synergizes with commensal bacteria to promote intestinal CD4+ T-cell expansion and interleukin 17A production that limits enteric pathogen invasion. Keywords: Barrier Function, Tight Junction, Microbiota, CD4 T Cell, Mucosal Immunity

  11. Intestinal epithelium in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet

    2014-01-01

    homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course......The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...

  12. Bile acid malabsorption or disturbed intestinal permeability in patients treated with enzyme substitution for exocrine pancreatic insufficiency is not caused by bacterial overgrowth

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Graff, Jesper; Philipsen, Else Kirstine

    2003-01-01

    permeability was assessed from urine excretion of ingested 14C-mannitol and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA), and these data were compared with results for 10 age-matched healthy men. RESULTS: No patients had abnormal breath hydrogen or methane concentrations after glucose intake...

  13. A win-win solution in oral delivery of lipophilic drugs: supersaturation via amorphous solid dispersions increases apparent solubility without sacrifice of intestinal membrane permeability.

    Science.gov (United States)

    Miller, Jonathan M; Beig, Avital; Carr, Robert A; Spence, Julie K; Dahan, Arik

    2012-07-02

    Recently, we have revealed a trade-off between solubility increase and permeability decrease when solubility-enabling oral formulations are employed. We have shown this trade-off phenomenon to be ubiquitous, and to exist whenever the aqueous solubility is increased via solubilizing excipients, regardless if the mechanism involves decreased free fraction (cyclodextrins complexation, surfactant micellization) or simple cosolvent solubilization. Discovering a way to increase drug solubility without concomitant decreased permeability represents a major advancement in oral delivery of lipophilic drugs and is the goal of this work. For this purpose, we sought to elucidate the solubility-permeability interplay when increased apparent solubility is obtained via supersaturation from an amorphous solid dispersion (ASD) formulation. A spray-dried ASD of the lipophilic drug progesterone was prepared in the hydrophilic polymer hydroxypropyl methylcellulose acetate succinate (HPMC-AS), which enabled supersaturation up to 4× the crystalline drug's aqueous solubility (8 μg/mL). The apparent permeability of progesterone from the ASD in HPMC-AS was then measured as a function of increasing apparent solubility (supersaturation) in the PAMPA and rat intestinal perfusion models. In contrast to previous cases in which apparent solubility increases via cyclodextrins, surfactants, and cosolvents resulted in decreased apparent permeability, supersaturation via ASD resulted in no decrease in apparent permeability with increasing apparent solubility. As a result, overall flux increased markedly with increasing apparent solubility via ASD as compared to the other formulation approaches. This work demonstrates that supersaturation via ASDs has a subtle yet powerful advantage over other solubility-enabling formulation approaches. That is, increased apparent solubility may be achieved without the expense of apparent intestinal membrane permeability. Thus, supersaturation via ASDs presents a

  14. Zonulin level, a marker of intestinal permeability, is increased in association with liver enzymes in young adolescents.

    Science.gov (United States)

    Kim, Ji Hee; Heo, Ju Sun; Baek, Kyung Suk; Kim, Soo-Yeon; Kim, Jung Hyun; Baek, Kwang-Hyun; Kim, Ki Eun; Sheen, Youn Ho

    2018-06-01

    Zonulin is acknowledged as the only physiological mediator established to reversibly regulate intestinal permeability through modulation of intercellular tight junctions. We aimed to determine whether there are differences in zonulin levels between 74 subjects with overweight or obesity and 76 with normal-weight and to assess correlations of circulating zonulin levels with anthropometric measures and obesity-related biomarkers. We assessed anthropometric and laboratory measures, including body mass index (BMI) z-score, blood pressure, liver enzymes, lipid profiles, and insulin resistance. Serum zonulin levels were measured using an enzyme-linked immunosorbent assay. The mean age of the participants was 12.8 ± 1.5 years. Circulating serum zonulin levels were significantly increased in subjects with overweight/obesity compared with those of normal-weight (P = 0.03). Zonulin levels were significantly and positively associated with BMI z-score, alanine aminotransferase levels, triglyceride, fasting insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P zonulin levels in adolescents with overweight or obesity (P zonulin levels in this subgroup analysis (P = 0.06). Serum zonulin is a biomarker associated with hepatic metabolic disturbances in young adolescents with overweight or obesity. The positive relationship suggests a potentially relevant pathophysiological mechanism linking zonulin to hepatic metabolism in this age group of young adolescents with overweight or obesity. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Abnormal Nuclear Pore Formation Triggers Apoptosis in the Intestinal Epithelium of elys-Deficient Zebrafish

    NARCIS (Netherlands)

    de Jong-Curtain, Tanya A.; Parslow, Adam C.; Trotter, Andrew J.; Hall, Nathan E.; Verkade, Heather; Tabone, Tania; Christie, Elizabeth L.; Crowhurst, Meredith O.; Layton, Judith E.; Shepherd, Iain T.; Nixon, Susan J.; Parton, Robert G.; Zon, Leonard I.; Stainier, Didier Y. R.; Lieschke, Graham J.; Heath, Joan K.

    Background & Aims: Zebrafish mutants generated by ethylnitrosourea-mutagenesis provide a powerful toot for dissecting the genetic regulation of developmental processes, including organogenesis. One zebrafish mutant, "flotte lotte" (flo), displays striking defects in intestinal, liver, pancreas, and

  16. Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow's milk allergy in toddlers.

    Science.gov (United States)

    Kalach, Nicolas; Kapel, Nathalie; Waligora-Dupriet, Anne-Judith; Castelain, Marie-Christine; Cousin, Marie Odile; Sauvage, Christine; Ba, Fatimata; Nicolis, Ioannis; Campeotto, Florence; Butel, Marie José; Dupont, Christophe

    2013-02-01

    Food allergy is a common problem in France involving 4%-6% of toddlers. As opposed to IgE-mediated cow's milk allergy (CMA), delayed-onset CMA, mostly, non-IgE-mediated, remains difficult to diagnose in toddlers. Our study assessed the diagnostic performances of intestinal permeability and of fecal markers, in comparison with the standard allergic work-up in children referred for CMA diagnosis. Twenty-five consecutive children, mean age (standard deviation) 6.3 months (4.8) with digestive and/or extra-digestive manifestations suggesting CMA, were prospectively studied based on a standardized allergic work-up (specific cow's protein IgE and IgG, skin prick test, atopy patch test and oral open cow's milk challenge) and digestive work-up including fecal microbiota analysis, intestinal permeability determination (urinary lactitol/mannitol ratio) and fecal markers measurement, i.e., α(1)-antitrypsin, tumor necrosis factor-α, calprotectin, β-defensin2, secretory IgA and eosinophil-derived neurotoxin (EDN). Receiver operating characteristic (ROC) curves were calculated for all markers in order to define cut-off levels. The cow's milk challenge was positive in 11 children and negative in 14. The global test performances, i.e., the number of true positive+negative cases/the total number of cases, were 76% for intestinal permeability; 72% for fecal EDN; contrasting with atopy patch test, 68%; IgE, 60%; skin prick test, 55% and IgG, 52%. In this routine diagnosis allergy work-up for CMA in toddlers, the best efficacy was seen for intestinal permeability compared to IgE, IgG, skin prick test and atopy patch test. Moreover, fecal EDN in a single spot sample displayed a similar performance.

  17. Gut Microbiota Richness and Composition and Dietary Intake of Overweight Pregnant Women Are Related to Serum Zonulin Concentration, a Marker for Intestinal Permeability.

    Science.gov (United States)

    Mokkala, Kati; Röytiö, Henna; Munukka, Eveliina; Pietilä, Sami; Ekblad, Ulla; Rönnemaa, Tapani; Eerola, Erkki; Laiho, Asta; Laitinen, Kirsi

    2016-09-01

    Increased intestinal permeability may precede adverse metabolic conditions. The extent to which the composition of the gut microbiota and diet contribute to intestinal permeability during pregnancy is unknown. The aim was to investigate whether the gut microbiota and diet differ according to serum zonulin concentration, a marker of intestinal permeability, in overweight pregnant women. This cross-sectional study included 100 overweight women [mean age: 29 y; median body mass index (in kg/m(2)): 30] in early pregnancy (zonulin (primary outcome) was determined by using ELISA, gut microbiota by 16S ribosomal RNA sequencing, and dietary intake of macro- and micronutrients from 3-d food diaries. The Mann-Whitney U test was used for pairwise comparisons and linear regression and Spearman's nonparametric correlations for relations between serum zonulin and other outcome variables. Women were divided into "low" (zonulin groups on the basis of the median concentration of zonulin (46.4 ng/mL). The richness of the gut microbiota (Chao 1, observed species and phylogenetic diversity) was higher in the low zonulin group than in the high zonulin group (P = 0.01). The abundances of Bacteroidaceae and Veillonellaceae, Bacteroides and Blautia, and Blautia sp. were lower and of Faecalibacterium and Faecalibacterium prausnitzii higher (P zonulin group than in the high zonulin group. Dietary quantitative intakes of n-3 (ω-3) polyunsaturated fatty acids (PUFAs), fiber, and a range of vitamins and minerals were higher (P zonulin group than those in the high zonulin group. The richness and composition of the gut microbiota and the intake of n-3 PUFAs, fiber, and a range of vitamins and minerals in overweight pregnant women are associated with serum zonulin concentration. Modification of the gut microbiota and diet may beneficially affect intestinal permeability, leading to improved metabolic health of both the mother and fetus. This trial was registered at clinicaltrials.gov as NCT

  18. Development of novel amisulpride-loaded liquid self-nanoemulsifying drug delivery systems via dual tackling of its solubility and intestinal permeability.

    Science.gov (United States)

    Gamal, Wael; Fahmy, Rania H; Mohamed, Magdy I

    2017-09-01

    The aim of the current investigation was at enhancing the oral biopharmaceutical behavior; solubility and intestinal permeability of amisulpride (AMS) via development of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) containing bioenhancing excipients. The components of L-SNEDDS were identified via solubility studies and emulsification efficiency tests, and ternary phase diagrams were constructed to identify the efficient self-emulsification regions. The formulated systems were assessed for their thermodynamic stability, globule size, self-emulsification time, optical clarity and in vitro drug release. Ex vivo evaluation using non-everted gut sac technique was adopted for uncovering the permeability enhancing effect of the formulated systems. The optimum formulations were composed of different ratios of Capryol™ 90 as an oil phase, Cremophor ® RH40 as a surfactant, and Transcutol ® HP as a co-surfactant. All tested formulations were thermodynamically stable with globule sizes ranging from 13.74 to 29.19 nm and emulsification time not exceeding 1 min, indicating the formation of homogenous stable nanoemulsions. In vitro drug release showed significant enhancement from L-SNEDDS formulations compared to aqueous drug suspension. Optimized L-SNEDDS showed significantly higher intestinal permeation compared to plain drug solution with nearly 1.6-2.9 folds increase in the apparent permeability coefficient as demonstrated by the ex vivo studies. The present study proved that AMS could be successfully incorporated into L-SNEDDS for improved dissolution and intestinal permeation leading to enhanced oral delivery.

  19. Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI

    DEFF Research Database (Denmark)

    Cramer, Stig Præstekær; Simonsen, Helle Juhl; Frederiksen, Jette Lautrup Battistini

    2013-01-01

    To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics.......To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics....

  20. Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

    Science.gov (United States)

    Liu, Bo; Gulati, Ajay S; Cantillana, Viviana; Henry, Stanley C; Schmidt, Elyse A; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A; Sartor, R Balfour; Taylor, Gregory A

    2013-10-15

    Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

  1. Permeability, zonulin production, and enteropathy in dermatitis herpetiformis.

    Science.gov (United States)

    Smecuol, Edgardo; Sugai, Emilia; Niveloni, Sonia; Vázquez, Horacio; Pedreira, Silvia; Mazure, Roberto; Moreno, María Laura; Label, Marcelo; Mauriño, Eduardo; Fasano, Alessio; Meddings, Jon; Bai, Julio César

    2005-04-01

    Dermatitis herpetiformis (DH) is characterized by variable degrees of enteropathy and increased intestinal permeability. Zonulin, a regulator of tight junctions, seems to play a key role in the altered intestinal permeability that characterizes the early phase of celiac disease. Our aim was to assess both intestinal permeability and serum zonulin levels in a group of patients with DH having variable grades of enteropathy. We studied 18 DH patients diagnosed on the basis of characteristic immunoglobulin (Ig)A granular deposits in the dermal papillae of noninvolved skin. Results were compared with those of classic celiac patients, patients with linear IgA dermatosis, and healthy controls. According to Marsh's classification, 5 patients had no evidence of enteropathy (type 0), 4 patients had type II, 2 patients had type IIIb damage, and 7 patients had a more severe lesion (type IIIc). Intestinal permeability (lactulose/mannitol ratio [lac/man]) was abnormal in all patients with DH. Patients with more severe enteropathy had significantly greater permeability ( P zonulin concentration (enzyme-linked immunosorbent assay) for patients with DH was 2.1 +/- .3 ng/mg with 14 of 16 (87.5%) patients having abnormally increased values. In contrast, patients with linear IgA dermatosis had normal histology, normal intestinal permeability, and negative celiac serology. Increased intestinal permeability and zonulin up-regulation are common and concomitant findings among patients with DH, likely involved in pathogenesis. Increased permeability can be observed even in patients with no evidence of histologic damage in biopsy specimens. Patients with linear IgA dermatosis appear to be a distinct population with no evidence of gluten sensitivity.

  2. Flos Lonicera ameliorates obesity and associated endotoxemia in rats through modulation of gut permeability and intestinal microbiota.

    Science.gov (United States)

    Wang, Jing-Hua; Bose, Shambhunath; Kim, Gi-Cheol; Hong, Seung-Ug; Kim, Ji-Hun; Kim, Jai-Eun; Kim, Hojun

    2014-01-01

    Increasing evidence has indicated a close association of host-gut flora metabolic interaction with obesity. Flos Lonicera, a traditional herbal medicine, is used widely in eastern Asia for the treatment of various disorders. The aim of this study was to evaluate whether unfermented or fermented formulations of Flos Lonicera could exert a beneficial impact to combat obesity and related metabolic endotoxemia. Obesity and metabolic endotoxemia were induced separately or together in rats through feeding a eight-week high fat diet either alone (HFD control group) or in combination with a single LPS stimulation (intraperitoneal injection, 0.75 mg/kg) (LPS control group). While, the mechanism of action of the Lonicera formulations was explored in vitro using RAW 264.7 and HCT 116 cell lines as models. In cell-based studies, treatment with both unfermented Flos Lonicera (UFL) and fermented Flos Lonicera (FFL) formulations resulted in suppression of LPS-induced NO production and gene expression of vital proinflammatory cytokines (TNF-α, COX-2, and IL-6) in RAW 264.7 cells, reduced the gene expression of zonula occludens (ZO)-1 and claudin-1, and normalized trans epithelial electric resistance (TEER) and horseradish peroxidase (HRP) flux in LPS-treated HCT-116 cells. In an animal study, treatment of HFD as well as HFD+LPS groups with UFL or FFL resulted in a notable decrease in body and adipose tissue weights, ameliorated total cholesterol, HDL, triglyceride, aspartate transaminase and endotoxin levels in serum, reduced the urinary lactulose/mannitol ratio, and markedly alleviated lipid accumulation in liver. In addition, exposure of HFD as well as HFD+LPS groups with UFL or FFL resulted in significant alteration of the distribution of intestinal flora, especially affecting the population of Akkermansia spp. and ratio of Bacteroidetes and Firmicutes. This evidence collectively demonstrates that Flos Lonicera ameliorates obesity and related metabolic endotoxemia via

  3. Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene.

    Science.gov (United States)

    Oshima, M; Oshima, H; Kitagawa, K; Kobayashi, M; Itakura, C; Taketo, M

    1995-05-09

    Mutations in the APC (adenomatous polyposis coli) gene appear to be responsible for not only familial adenomatous polyposis but also many sporadic cases of gastrointestinal cancers. Using homologous recombination in mouse embryonic stem cells, we constructed mice that contained a mutant gene encoding a product truncated at a 716 (Apc delta 716). Mendelian transmission of the gene caused most homozygous mice to die in utero before day 8 of gestation. The heterozygotes developed multiple polyps throughout the intestinal tract, mostly in the small intestine. The earliest polyps arose multifocally during the third week after birth, and new polyps continued to appear thereafter. Surprisingly, every nascent polyp consisted of a microadenoma covered with a layer of the normal villous epithelium. These microadenomas originated from single crypts by forming abnormal outpockets into the inner (lacteal) side of the neighboring villi. We carefully dissected such microadenomas from nascent polyps by peeling off the normal epithelium and determined their genotype by PCR: all microadenomas had already lost the wild-type Apc allele, whereas the mutant allele remained unchanged. These results indicate that loss of heterozygosity followed by formation of intravillous microadenomas is responsible for polyposis in Apc delta 716 intestinal mucosa. It is therefore unlikely that the truncated product interacts directly with the wild-type protein and causes the microadenomas by a dominant negative mechanism.

  4. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    ), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol–water partition coefficients (Do:w) were...

  5. Effect of prebiotic intake on gut microbiota, intestinal permeability and glycemic control in children with type 1 diabetes: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Ho, Josephine; Reimer, Raylene A; Doulla, Manpreet; Huang, Carol

    2016-07-26

    The gut microbiome is increasingly recognized as a contributor to disease states. Patients with type 1 diabetes (DM1) have distinct gut microbiota in comparison to non-diabetic individuals, and it has been linked to changes in intestinal permeability, inflammation and insulin resistance. Prebiotics are non-digestible carbohydrates that alter gut microbiota and could potentially improve glycemic control in children with DM1. This pilot study aims to determine the feasibility of a 12-week dietary intervention with prebiotics in children with DM1. This pilot study is a single-centre, randomized, double-blind, placebo-controlled trial in children aged 8 to 17 years with DM1 for at least one year. Participants will be randomized to receive either placebo (maltodextrin 3.3 g orally/day) or prebiotics (oligofructose-enriched inulin 8 g orally/day; Synergy1, Beneo, Mannheim, Germany). Measures to be assessed at baseline, 3 months and 6 months include: anthropometric measures, insulin doses/regimens, frequency of diabetic ketoacidosis, frequency of severe hypoglycemia, average number of episodes of hypoglycemia per week, serum C-peptide, HbA1c, serum inflammatory markers (IL-6, IFN-gamma, TNF-alpha, and IL-10), GLP-1 and GLP-2, intestinal permeability using urine assessment after ingestion of lactulose, mannitol and 3-O-methylglucose, and stool sample collection for gut microbiota profiling. This is a novel pilot study designed to test feasibility for a fully powered study. We hypothesize that consumption of prebiotics will alter gut microbiota and intestinal permeability, leading to improved glycemic control. Prebiotics are a potentially novel, inexpensive, low-risk treatment addition for DM1 that may improve glycemic control by changes in gut microbiota, gut permeability and inflammation. ClinicalTrials.gov: NCT02442544 . Registered on 10 March 2015.

  6. Flos Lonicera ameliorates obesity and associated endotoxemia in rats through modulation of gut permeability and intestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Jing-Hua Wang

    Full Text Available BACKGROUND AND AIM: Increasing evidence has indicated a close association of host-gut flora metabolic interaction with obesity. Flos Lonicera, a traditional herbal medicine, is used widely in eastern Asia for the treatment of various disorders. The aim of this study was to evaluate whether unfermented or fermented formulations of Flos Lonicera could exert a beneficial impact to combat obesity and related metabolic endotoxemia. METHODS: Obesity and metabolic endotoxemia were induced separately or together in rats through feeding a eight-week high fat diet either alone (HFD control group or in combination with a single LPS stimulation (intraperitoneal injection, 0.75 mg/kg (LPS control group. While, the mechanism of action of the Lonicera formulations was explored in vitro using RAW 264.7 and HCT 116 cell lines as models. RESULTS: In cell-based studies, treatment with both unfermented Flos Lonicera (UFL and fermented Flos Lonicera (FFL formulations resulted in suppression of LPS-induced NO production and gene expression of vital proinflammatory cytokines (TNF-α, COX-2, and IL-6 in RAW 264.7 cells, reduced the gene expression of zonula occludens (ZO-1 and claudin-1, and normalized trans epithelial electric resistance (TEER and horseradish peroxidase (HRP flux in LPS-treated HCT-116 cells. In an animal study, treatment of HFD as well as HFD+LPS groups with UFL or FFL resulted in a notable decrease in body and adipose tissue weights, ameliorated total cholesterol, HDL, triglyceride, aspartate transaminase and endotoxin levels in serum, reduced the urinary lactulose/mannitol ratio, and markedly alleviated lipid accumulation in liver. In addition, exposure of HFD as well as HFD+LPS groups with UFL or FFL resulted in significant alteration of the distribution of intestinal flora, especially affecting the population of Akkermansia spp. and ratio of Bacteroidetes and Firmicutes. CONCLUSION: This evidence collectively demonstrates that Flos Lonicera

  7. IMPROVEMENT OF INTESTINAL PERMEABILITY WITH ALANYL-GLUTAMINE IN HIV PATIENTS: a randomized, double blinded, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Robério Dias LEITE

    2013-03-01

    Full Text Available Context Glutamine is the main source of energy of the enterocyte and diarrhea and weight loss are frequent in HIV infected patients. Objective To determine the effect of alanyl-glutamine supplementation on intestinal permeability and absorption in these patients. Methods Randomized double-blinded, placebo-controlled study using isonitrogenous doses of alanyl-glutamine (24 g/day and placebo (glycine, 25 g/day during 10 days. Before and after this nutritional supplementation lactulose and mannitol urinary excretion were determined by high performance liquid chromatography. Results Forty six patients with HIV/AIDS, 36 of whom were male, with 37.28 ± 3 (mean ± standard error years were enrolled. Twenty two and 24 subjects were treated with alanyl-glutamine and with glycine respectively. In nine patients among all in the study protocol that reported diarrhea in the 14 days preceding the beginning of the study, mannitol urinary excretion was significantly lower than patients who did not report this symptom [median (range: 10.51 (3.01–19.75 vs. 15.37 (3.93–46.73; P = 0.0281] and lactulose/mannitol ratio was significantly higher [median (range: 0.04 (0.00–2.89 vs. 0.02 (0.00–0.19; P = 0.0317]. There was also a significant increase in mannitol urinary excretion in the group treated with alanyl-glutamine [median (range: 14.38 (8.25–23.98 before vs 21.24 (6.27–32.99 after treatment; n = 14, P = 0.0382]. Conclusion Our results suggest that the integrity and intestinal absorption are more intensely affected in patients with HIV/AIDS who recently have had diarrhea. Additionally, nutritional supplementation with alanyl-glutamine was associated with an improvement in intestinal absorption. Contexto A glutamina é a principal fonte de energia do enterócito e diarreia e perda de peso são frequentes em pacientes infectados pelo HIV. Objetivo Determinar o efeito da alanil-glutamina sobre a permeabilidade e a absorção intestinais nesses

  8. L-arginine supplementation prevents increases in intestinal permeability and bacterial translocation in male Swiss mice subjected to physical exercise under environmental heat stress.

    Science.gov (United States)

    Costa, Kátia Anunciação; Soares, Anne Danieli Nascimento; Wanner, Samuel Penna; Santos, Rosana das Graças Carvalho dos; Fernandes, Simone Odília Antunes; Martins, Flaviano dos Santos; Nicoli, Jacques Robert; Coimbra, Cândido Celso; Cardoso, Valbert Nascimento

    2014-02-01

    Dietary supplementation with l-arginine has been shown to improve the intestinal barrier in many experimental models. This study investigated the effects of arginine supplementation on the intestinal permeability and bacterial translocation (BT) induced by prolonged physical exercise under heat stress. Under anesthesia, male Swiss mice (5-wk-old) were implanted with an abdominal sensor to record their core body temperature (T(core)). After recovering from surgery, the mice were divided into 3 groups: a non-supplemented group that was fed the standard diet formulated by the American Institute of Nutrition (AIN-93G; control), a non-supplemented group that was fed the AIN-93G diet and subjected to exertional hyperthermia (H-NS), and a group supplemented with l-arginine at 2% and subjected to exertional hyperthermia (H-Arg). After 7 d of treatment, the H-NS and H-Arg mice were forced to run on a treadmill (60 min, 8 m/min) in a warm environment (34°C). The control mice remained at 24°C. Thirty min before the exercise or control trials, the mice received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with technetium-99m ((99m)Tc-DTPA) or (99m)Tc-Escherichia coli by gavage to assess intestinal permeability and BT, respectively. The H-NS mice terminated the exercise with T(core) values of ∼40°C, and, 4 h later, presented a 12-fold increase in the blood uptake of (99m)Tc-DTPA and higher bacterial contents in the blood and liver than the control mice. Although supplementation with arginine did not change the exercise-induced increase in T(core), it prevented the increases in intestinal permeability and BT caused by exertional hyperthermia. Our results indicate that dietary l-arginine supplementation preserves the integrity of the intestinal epithelium during exercise under heat stress, acting through mechanisms that are independent of T(core) regulation.

  9. Inulin-enriched pasta improves intestinal permeability and modifies the circulating levels of zonulin and glucagon-like peptide 2 in healthy young volunteers.

    Science.gov (United States)

    Russo, Francesco; Linsalata, Michele; Clemente, Caterina; Chiloiro, Marisa; Orlando, Antonella; Marconi, Emanuele; Chimienti, Guglielmina; Riezzo, Giuseppe

    2012-12-01

    Apart from the intestinal environment, inulin induces physiological effects, which includes a reduction in glucose and lipid concentrations and modulation of gastrointestinal motility through the release of different peptides. We hypothesized that inulin-enriched pasta may also improve small intestine permeability in relation to zonulin and glucagon-like peptide 2 (GLP-2) levels in healthy young subjects. Twenty healthy, young male volunteers completed a randomized, double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched or control pasta), with an 8-week washout period in between. The intestinal barrier function was assessed by lactulose-mannitol excretion in urine. Zonulin values and GLP-2 release were evaluated by enzyme-linked immunosorbent assay. In the inulin group, the urinary lactulose recovery was significantly lower than the other 2 groups. There were no significant differences in urinary mannitol levels between groups. Accordingly, the lactulose-mannitol excretion ratio was significantly decreased in the inulin-enriched pasta group compared with the other 2 groups. The inulin-enriched pasta group had significantly lower zonulin serum values and significantly higher GLP-2 basal values when compared with the baseline and control pasta groups. The dietary use of inulin-enriched pasta preserves intestinal mucosal barrier functioning and modulates circulating levels of zonulin and GLP-2, suggesting that prebiotics could be used in the prevention of gastrointestinal diseases and metabolic disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Morphological abnormalities in the innervation of the atretic segment of bowel in neonates with intestinal atresia.

    Science.gov (United States)

    Ramachandran, P; Vincent, P; Ganesh, S; Sridharan, S

    2007-12-01

    The aim of this study was to examine precisely the morphological abnormalities in the myenteric plexus at the atretic end of the bowel in jejunoileal atresia (JIA). Although changes in the myenteric plexus has been examined in the proximal and distal segments of bowel in JIA, a histochemical analysis of the atretic segment is lacking. Specimens from the atretic end of bowel were obtained from six neonates with JIA. Whole-mount preparations were made of the myenteric plexus, and the cholinergic and nitrergic components were studied by staining with acetylcholine esterase (Ach E) and NADPH diaphorase, respectively. Controls were obtained from two neonates undergoing small bowel resection for Meckel's diverticulum. At the blind end of bowel in type 3a atresia (5 neonates), the intensity of NADPH staining was comparable with controls. However, there was distortion of polygonal architecture of the primary and secondary plexuses at the blind end arranged in concentric fashion parallel to the circular muscle fibres. The ganglia were large and irregularly shaped and contained round neuronal cells. In the sausage shaped segment of bowel in multiple atresia, there was total loss of polygonal architecture with abnormal ganglia, and whorls of nerve fibers. Neuronal cells could not be made out in the ganglia. In specimens stained with Ach E, the findings were similar except that the staining intensity was markedly reduced compared with controls. The morphological abnormalities in the atretic bowel in type 3a were restricted to the architecture of the plexuses and ganglia. The neuronal cells were normal. However, the total loss of polygonal architecture and absence of neuronal cells in the ganglia in multiple atresia probably indicate a different etiology for this type of atresia.

  11. Segmental dependent transport of low permeability compounds along the small intestine due to P-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2009-01-01

    The purpose of this study was to investigate the role of P-gp efflux in the in vivo intestinal absorption process of BCS class III P-gp substrates, i.e. high-solubility low-permeability drugs. The in vivo permeability of two H (2)-antagonists, cimetidine and famotidine, was determined by the single-pass intestinal perfusion model in different regions of the rat small intestine, in the presence or absence of the P-gp inhibitor verapamil. The apical to basolateral (AP-BL) and the BL-AP transport of the compounds in the presence or absence of various efflux transporters inhibitors (verapamil, erythromycin, quinidine, MK-571 and fumitremorgin C) was investigated across Caco-2 cell monolayers. P-gp expression levels in the different intestinal segments were confirmed by immunoblotting. Cimetidine and famotidine exhibited segmental dependent permeability through the gut wall, with decreased P(eff) in the distal ileum in comparison to the proximal regions of the intestine. Coperfusion of verapamil with the drugs significantly increased the permeability in the ileum, while no significant change in the jejunal permeability was observed. Both drugs exhibited significantly greater BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Concentration dependent decrease of this secretion was obtained by the P-gp inhibitors verapamil, erythromycin and quinidine, while no effect was evident by the MRP2 inhibitor MK-571 and the BCRP inhibitor FTC, indicating that P-gp is the transporter mediates the intestinal efflux of cimetidine and famotidine. P-gp levels throughout the intestine were inversely related to the in vivo permeability of the drugs from the different segments. The data demonstrate that for these high-solubility low-permeability P-gp substrates, P-gp limits in vivo intestinal absorption in the distal segments of the small intestine; however P-gp plays a minimal role in the proximal intestinal segments due to significant lower P-gp expression levels

  12. [Small intestine atresia and abnormal insertion of the umbilicus in a child with fetal alcohol syndrome].

    Science.gov (United States)

    Tourtet, S; Michaud, L; Gottrand, F; Boute, O; Bonnevalle, M; Meyer, N; Turck, D

    1997-07-01

    Fetal alcohol syndrome is quite common in our region (incidence: 1/700 live births). It usually associates facial dysmorphism, intra-uterine growth retardation and mental delay. Jonathan, born to an alcoholic mother, presented a typical dysmorphy of fetal alcohol syndrome and a low inserted umbilicus. A small bowel atresia was discovered at the third day of life and operated on. Although never been previously described, this association suggests a common embryological origin between fetal alcohol syndrome, small bowel atresia, and umbilical abnormality.

  13. Evaluation of a selected lactic acid bacteria-based probiotic on Salmonella enterica serovar Enteritidis colonization and intestinal permeability in broiler chickens.

    Science.gov (United States)

    Prado-Rebolledo, Omar F; Delgado-Machuca, Jaime de Jesus; Macedo-Barragan, Rafael J; Garcia-Márquez, Luis J; Morales-Barrera, Jesus E; Latorre, Juan D; Hernandez-Velasco, Xochitl; Tellez, Guillermo

    2017-02-01

    Two experiments were conducted to evaluate the effect of a lactic acid bacteria-based probiotic (FloraMax-B11 ® ) against Salmonella enterica serovar Enteritidis intestinal colonization and intestinal permeability in broiler chickens. Experiment 1 consisted of two independent trials. In each trial, day-old broiler chicks were assigned to one of two groups: control + S. Enteritidis or probiotic + S. Enteritidis. At 72 h post-S. Enteritidis challenge, haematology and caecal content were evaluated for S. Enteritidis colonization. In Experiment 2, day-old broiler chicks were assigned to one of four groups: negative control; probiotic; control + S. Enteritidis; or probiotic + S. Enteritidis. At 72 h post-S. Enteritidis challenge, chickens in all groups were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). In both trials of Experiment 1, a significant reduction (P < 0.05) in colony-forming units/gram of S. Enteritidis in caecal content and a reduction in the incidence of S. Enteritidis enriched caecal samples were observed in probiotic + S. Enteritidis chickens. In addition, significant heterophilia and lymphopaenia were observed in control + S. Enteritidis chickens. In Experiment 2, a decrease in numbers of S. Enteritidis in caeca were observed in probiotic + S. Enteritidis chickens when compared to control + S. Enteritidis. Also, an increase in serum FITC-d concentration was detected in control + S. Enteritidis. These results suggest that early infection with S. Enteritidis can increase intestinal permeability, but the adverse effects can be prevented by the administration of the probiotic tested.

  14. Bovine colostrum increases pore-forming claudin-2 protein expression but paradoxically not ion permeability possibly by a change of the intestinal cytokine milieu.

    Directory of Open Access Journals (Sweden)

    Peggy Bodammer

    Full Text Available An impaired intestinal barrier function is involved in the pathogenesis of inflammatory bowel disease (IBD. Several nutritional factors are supposed to be effective in IBD treatment but scientific data about the effects on the intestinal integrity remain scarce. Bovine colostrum was shown to exert beneficial effects in DSS-induced murine colitis, and the present study was undertaken to explore the underlying molecular mechanisms. Western blot revealed increased claudin-2 expression in the distal ileum of healthy mice after feeding with colostrum for 14 days, whereas other tight junction proteins (claudin-3, 4, 10, 15 remained unchanged. The colostrum-induced claudin-2 induction was confirmed in differentiated Caco-2 cells after culture with colostrum for 48 h. Paradoxically, the elevation of claudin-2, which forms a cation-selective pore, was neither accompanied by increased ion permeability nor impaired barrier function. In an in situ perfusion model, 1 h exposure of the colonic mucosa to colostrum induced significantly increased mRNA levels of barrier-strengthening cytokine transforming growth factor-β, while interleukine-2, interleukine-6, interleukine-10, interleukine-13, and tumor-necrosis factor-α remained unchanged. Thus, modulation of the intestinal transforming growth factor-β expression might have compensated the claudin-2 increase and contributed to the observed barrier strengthening effects of colostrum in vivo and in vitro.

  15. Evaluation of the intestinal permeability of rosemary (Rosmarinus officinalis L. extract polyphenols and terpenoids in Caco-2 cell monolayers.

    Directory of Open Access Journals (Sweden)

    Almudena Pérez-Sánchez

    Full Text Available Rosemary (Rosmarinus officinalis is grown throughout the world and is widely used as a medicinal herb and to season and preserve food. Rosemary polyphenols and terpenoids have attracted great interest due to their potential health benefits. However, complete information regarding their absorption and bioavailability in Caco-2 cell model is scarce. The permeation properties of the bioactive compounds (flavonoids, diterpenes, triterpenes and phenylpropanoids of a rosemary extract (RE, obtained by supercritical fluid extraction, was studied in Caco-2 cell monolayer model, both in a free form or liposomed. Compounds were identified and quantitated by liquid chromatography coupled to quadrupole time-of-flight with electrospray ionization mass spectrometry analysis (HPLC-ESI-QTOF-MS, and the apparent permeability values (Papp were determined, for the first time in the extract, for 24 compounds in both directions across cell monolayer. For some compounds, such as triterpenoids and some flavonoids, Papp values found were reported for the first time in Caco-2 cells.Our results indicate that most compounds are scarcely absorbed, and passive diffusion is suggested to be the primary mechanism of absorption. The use of liposomes to vehiculize the extract resulted in reduced permeability for most compounds. Finally, the biopharmaceutical classification (BCS of all the compounds was achieved according to their permeability and solubility data for bioequivalence purposes. BCS study reveal that most of the RE compounds could be classified as classes III and IV (low permeability; therefore, RE itself should also be classified into this category.

  16. Evaluation of the intestinal permeability of rosemary (Rosmarinus officinalis L.) extract polyphenols and terpenoids in Caco-2 cell monolayers

    Science.gov (United States)

    Arráez-Román, David; González-Álvarez, Isabel; Ibáñez, Elena; Segura-Carretero, Antonio; Bermejo, Marival; Micol, Vicente

    2017-01-01

    Rosemary (Rosmarinus officinalis) is grown throughout the world and is widely used as a medicinal herb and to season and preserve food. Rosemary polyphenols and terpenoids have attracted great interest due to their potential health benefits. However, complete information regarding their absorption and bioavailability in Caco-2 cell model is scarce. The permeation properties of the bioactive compounds (flavonoids, diterpenes, triterpenes and phenylpropanoids) of a rosemary extract (RE), obtained by supercritical fluid extraction, was studied in Caco-2 cell monolayer model, both in a free form or liposomed. Compounds were identified and quantitated by liquid chromatography coupled to quadrupole time-of-flight with electrospray ionization mass spectrometry analysis (HPLC-ESI-QTOF-MS), and the apparent permeability values (Papp) were determined, for the first time in the extract, for 24 compounds in both directions across cell monolayer. For some compounds, such as triterpenoids and some flavonoids, Papp values found were reported for the first time in Caco-2 cells.Our results indicate that most compounds are scarcely absorbed, and passive diffusion is suggested to be the primary mechanism of absorption. The use of liposomes to vehiculize the extract resulted in reduced permeability for most compounds. Finally, the biopharmaceutical classification (BCS) of all the compounds was achieved according to their permeability and solubility data for bioequivalence purposes. BCS study reveal that most of the RE compounds could be classified as classes III and IV (low permeability); therefore, RE itself should also be classified into this category. PMID:28234919

  17. Effect of Cryptosporidium parvum infection on the absorptive capacity and paracellular permeability of the small intestine in neonatal calves

    Czech Academy of Sciences Publication Activity Database

    Klein, P.; Kleinová, T.; Volek, Z.; Šimůnek, Jiří

    2008-01-01

    Roč. 152, 1-2 (2008), s. 53-59 ISSN 0304-4017 Institutional research plan: CEZ:AV0Z50450515 Keywords : calves * cryptosporidium parvum * intestinal absorption Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.039, year: 2008

  18. Intestinal epithelium in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mehmet eCoskun

    2014-08-01

    Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

  19. The Occurrence of Antibodies Against Gluten in Children with Autism Spectrum Disorders Does Not Correlate with Serological Markers of Impaired Intestinal Permeability.

    Science.gov (United States)

    Józefczuk, Jan; Konopka, Ewa; Bierła, Joanna Beata; Trojanowska, Ilona; Sowińska, Agnieszka; Czarnecki, Rafał; Sobol, Lucjan; Józefczuk, Paweł; Surdy, Weronika; Cukrowska, Bożena

    2018-02-01

    There is evidence that children with autism spectrum disorders (ASDs) display an increased immune reactivity against gluten, which is supposed to be the effect of intestinal barrier abnormalities. The aim of study was to evaluate the relation of antibody induced by gluten to zonulin and intestinal fatty acid binding proteins (I-FABP), that is, serological markers of an impaired gut barrier. The study included 77 patients with ASDs. Zonulin, I-FABP, celiac-specific antibodies, anti-gliadin antibodies (AGA), and antibodies against neural transglutaminase 6 (TG6) of immunoglobulin (Ig) A and IgG classes were detected in sera. Celiac-specific antibodies were negative in all ASD children, four children (5.2%) had positive anti-TG6 antibodies, and increased AGA-IgG production was found in 21 patients (27.3%). Mean levels of zonulin and I-FABP in ASD patients were similar to those found in healthy controls and revealed a negative correlation with age, whereas regression analysis revealed a significant positive relationship between antibody production and the age. Serum concentrations of zonulin and I-FABP showed no statistically significant association with antibody positivity. An increased production of antibodies related to gliadin and neural TG6 in ASD children is not related to serological markers of an impaired intestinal barrier.

  20. Propylene glycol-linked amino acid/dipeptide diester prodrugs of oleanolic acid for PepT1-mediated transport: synthesis, intestinal permeability, and pharmacokinetics.

    Science.gov (United States)

    Cao, Feng; Gao, Yahan; Wang, Meng; Fang, Lei; Ping, Qineng

    2013-04-01

    In our previous studies, ethylene glycol-linked amino acid diester prodrugs of oleanolic acid (OA), a Biopharmaceutics Classification System (BCS) class IV drug, designed to target peptide transporter 1 (PepT1) have been synthesized and evaluated. Unlike ethylene glycol, propylene glycol is of very low toxicity in vivo. In this study, propylene glycol was used as a linker to further compare the effect of the type of linker on the stability, permeability, affinity, and bioavailability of the prodrugs of OA. Seven diester prodrugs with amino acid/dipeptide promoieties containing L-Val ester (7a), L-Phe ester (7b), L-Ile ester (7c), D-Val-L-Val ester (9a), L-Val-L-Val ester (9b), L-Ala-L-Val ester (9c), and L-Ala-L-Ile ester (9d) were designed and successfully synthesized. In situ rat single-pass intestinal perfusion (SPIP) model was performed to screen the effective permeability (P(eff)) of the prodrugs. P(eff) of 7a, 7b, 7c, 9a, 9b, 9c, and 9d (6.7-fold, 2.4-fold, 1.24-fold, 1.22-fold, 4.15-fold, 2.2-fold, and 1.4-fold, respectively) in 2-(N-morpholino)ethanesulfonic acid buffer (MES) with pH 6.0 showed significant increase compared to that of OA (p propylene glycol-linked amino acid/dipeptide diester prodrugs showed better stability, permeability, affinity, and bioavailability. In conclusion, propylene glycol-linked amino acid/dipeptide diester prodrugs of OA may be suitable for PepT1-targeted prodrugs of OA to improve the oral bioavailability of OA.

  1. Fecal Markers of Intestinal Inflammation and Permeability Associated with the Subsequent Acquisition of Linear Growth Deficits in Infants

    Science.gov (United States)

    Kosek, Margaret; Haque, Rashidul; Lima, Aldo; Babji, Sudhir; Shrestha, Sanjaya; Qureshi, Shahida; Amidou, Samie; Mduma, Estomih; Lee, Gwenyth; Yori, Pablo Peñataro; Guerrant, Richard L.; Bhutta, Zulfiqar; Mason, Carl; Kang, Gagandeep; Kabir, Mamun; Amour, Caroline; Bessong, Pascal; Turab, Ali; Seidman, Jessica; Olortegui, Maribel Paredes; Quetz, Josiane; Lang, Dennis; Gratz, Jean; Miller, Mark; Gottlieb, Michael

    2013-01-01

    Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrheal illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood. PMID:23185075

  2. The impact of probiotics and n-3 long-chain polyunsaturated fatty acids on intestinal permeability in pregnancy: a randomised clinical trial.

    Science.gov (United States)

    Mokkala, K; Pussinen, P; Houttu, N; Koivuniemi, E; Vahlberg, T; Laitinen, K

    2018-02-27

    A disruption in intestinal barrier integrity may predispose individuals to metabolic aberrations, particularly during the vulnerable period of pregnancy. We investigated whether intestinal permeability, as measured by serum zonulin concentration, changes over the duration of pregnancy and whether this change is reflected in lipopolysaccharide (LPS) activity. Second, we tested in a randomised double-blind placebo controlled clinical trial the impact of consuming dietary probiotics and/or long chain polyunsaturated fatty acid (LC-PUFA) supplements in lowering serum zonulin concentration and LPS activity. The probiotic supplement was a combination of two bacteria, Bifidobacterium animalis ssp. lactis 420 and Lactobacillus rhamnosus HN001. This study included 200 overweight pregnant women participating in an on-going study; participants were randomised to consume either (1) probiotics, (2) LC-PUFA, (3) probiotics and LC-PUFA, or (4) placebo for each supplement. Blood samples were obtained at early, the baseline, and late pregnancy (mean 14 and 35 weeks of gestation, respectively). Serum zonulin concentration increased from early (mean (standard deviation): 62.7 (12.9) ng/ml) to late pregnancy by 5.3 (95%CI 3.7-6.9) ng/ml, and LPS activity increased from (0.16 (0.04) EU/ml) by 0.04 (95%CI 0.03-0.05) EU/ml. No differences among the intervention groups were detected in the change from early to late pregnancy in serum zonulin concentration (P=0.8) or LPS activity (P=0.2). The change in serum zonulin concentration during the pregnancy was associated with the weeks of follow up (r=0.25, Pzonulin concentration or LPS activity.

  3. Enhanced intestinal permeability and oral bioavailability of enalapril maleate upon complexation with the cationic polymethacrylate Eudragit E100.

    Science.gov (United States)

    Ramírez-Rigo, María V; Olivera, María E; Rubio, Modesto; Manzo, Ruben H

    2014-05-13

    The low bioavailability of enalapril maleate associated to its instability in solid state motivated the development of a polyelectrolyte-drug complex between enalapril maleate and the cationic polymethacrylate Eudragit E100. The solid complexes were characterized by DSC-TG, FT-IR and X-ray diffraction. Their aqueous dispersions were evaluated for drug delivery in bicompartimental Franz cells and electrokinetic potentials. Stability in solid state was also evaluated using an HPLC-UV stability indicating method. Absorption of enalapril maleate was assessed thorough the rat everted gut sac model. In addition, urinary recovery after oral administration in rats was used as an indicator of systemic exposition. The solid materials are stable amorphous solids in which both moieties of enalapril maleate are ionically bonded to the polymer. Their aqueous dispersions exhibited controlled release over more than 7h in physiologic saline solution, being ionic exchange the fundamental mechanism that modified the extent and rate of drug release. Intestinal permeation of enalapril maleate was 1.7 times higher in the presence of the cationic polymer. This increase can be related with the capacity to adhere the mucosa due to the positive zeta potential of the complexes. As a consequence bioavailability was significantly improved (1.39 times) after oral administration of the complexes. In addition, no signs of chemical decomposition were observed after a 14months period. The results indicated that the products are new chemical entities that improve unfavorable properties of a useful drug. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth.

    Science.gov (United States)

    Nucera, G; Gabrielli, M; Lupascu, A; Lauritano, E C; Santoliquido, A; Cremonini, F; Cammarota, G; Tondi, P; Pola, P; Gasbarrini, G; Gasbarrini, A

    2005-06-01

    Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non-invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption. To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients. We enrolled 98 consecutive irritable bowel syndrome patients. All subjects underwent hydrogen lactulose, lactose, fructose and sorbitol hydrogen breath tests. Small intestinal bacterial overgrowth patients were treated with 1-week course of antibiotics. All tests were repeated 1 month after the end of therapy. A positive lactulose breath test was found in 64 of 98 (65%) subjects; these small intestinal bacterial overgrowth patients showed a significantly higher prevalence of positivity to the lactose breath test (P fructose breath test (P fructose and sorbitol breath tests positivity (17% vs. 100%, 3% vs. 62%, and 10% vs. 71% respectively: P malabsorption misdiagnosis.

  5. Protective effect of intestinal trefoil factor on injury of intestinal epithelial tight junction induced by platelet activating factor.

    Science.gov (United States)

    Xu, Ling-fen; Teng, Xu; Guo, Jing; Sun, Mei

    2012-02-01

    Intestinal barrier dysfunction plays an important role in the pathogenesis of inflammatory bowel disease (IBD). To evaluate the effect of intestinal trefoil factor (ITF) on increased intestinal permeability and its association with tight junction proteins, an in vitro intestinal epithelia barrier model was established with Caco-2 cells and treated with platelet-activating factor (PAF). We found that exposing cells to 0.3 M ITF (30 min before or 30 min after PAF treatment) attenuated the PAF-induced changes in transepithelial electrical resistance and Lucifer yellow flux. A quantitative RT-PCR and western blot analysis revealed that ITF suppressed PAF-induced downregulation of tight junction proteins claudin-1 and ZO-1 expression; furthermore, an abnormal localization and distribution of these proteins was inhibited, as assessed by immunofluorescence staining. These results suggest that ITF decreases mucosal permeability and shows potential as a therapy for treating IBD.

  6. MEK/ERK pathway activation by insulin receptor isoform alteration is associated with the abnormal proliferation and differentiation of intestinal epithelial cells in diabetic mice.

    Science.gov (United States)

    Ouyang, Hui; Yang, Hong-Sheng; Yu, Tao; Shan, Ti-Dong; Li, Jie-Yao; Huang, Can-Ze; Zhong, Wa; Xia, Zhong-Sheng; Chen, Qi-Kui

    2016-02-01

    In previous studies, we have reported the abnormal proliferation and differentiation of intestinal epithelial cells (IECs) in diabetes mellitus (DM) mice. The insulin receptor (IR) and its downstream mitogen-activated protein kinase kinase (MAPKK also known as MEK)/extracellular-regulated protein kinase (ERK) pathway is a classic pathway associated with cell proliferation and differentiation. The purpose of the present study is to investigate the role of the MEK/ERK pathway in abnormal proliferation and differentiation of IECs in DM mice. DM mouse models were induced by intraperitoneal injection of streptozotocin. The expression levels of the IR and its isoforms in IECs of DM mice and in IEC-6 cells were investigated. To ensure that the downstream pathways were monitored, QPCR and Western blotting were performed to detect the expression levels of MEK1/2, ERK1/2, PI3K, and Akt. Moreover, siRNA for IR-A and U0126, a specific inhibitor of MEK, were used to further investigate the relationship between the IR/MEK/ERK pathway and abnormal proliferation and differentiation of IECs in DM mice. In DM mice, excessive proliferation, disturbed differentiation, and a high ratio of IR-A/IR-B were detected in IECs. The expression levels of MEK1, MEK2, and ERK1/2 and their phosphorylated proteins in DM mice were significantly higher than those in the control group (P < 0.05), which could be offset by using siRNA for IR-A. The abnormal proliferation and differentiation of IECs in DM mice were normalized after the in vivo administration of U0126. The abnormal proliferation and differentiation of IECs in DM mice are associated with high IR-A/IR-B ratio and increased IR/MEK/ERK pathway activity.

  7. Abnormal accumulation of intestinal fluid following ingestion of an unabsorbable carbohydrate in patients with irritable bowel syndrome: an MRI study.

    Science.gov (United States)

    Undseth, R; Berstad, A; Kløw, N-E; Arnljot, K; Moi, K S; Valeur, J

    2014-12-01

    Postprandial discomfort following intake of poorly absorbable, but fermentable carbohydrates is a common complaint in patients with irritable bowel syndrome (IBS). We used lactulose as a model substance for this group of symptom triggering carbohydrates, aiming to visualize the intestinal response in IBS patients compared to healthy controls. Patients with IBS according to Rome III criteria (n = 52) and healthy controls (n = 16) underwent a lactulose challenge test. By using magnetic resonance imaging, we measured small bowel water content (SBWC), and distension (diameter) of the distal ileum and the colon, both in fasting state and 1 h after ingestion of 10 g lactulose. We recorded symptoms after lactulose ingestion. Lactulose provoked significantly more symptoms in IBS patients than in healthy controls (p intestine or impaired function of the ileocecal segment. © 2014 John Wiley & Sons Ltd.

  8. Assessment of the Effect of Intestinal Permeability Probes (Lactulose And Mannitol and Other Liquids on Digesta Residence Times in Various Segments of the Gut Determined by Wireless Motility Capsule: A Randomised Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Ivana R Sequeira

    Full Text Available Whilst the use of the mannitol/lactulose test for intestinal permeability has been long established it is not known whether the doses of these sugars modify transit time Similarly it is not known whether substances such as aspirin that are known to increase intestinal permeability to lactulose and mannitol and those such as ascorbic acid which are stated to be beneficial to gastrointestinal health also influence intestinal transit time.Gastric and intestinal transit times were determined with a SmartPill following consumption of either a lactulose mannitol solution, a solution containing 600 mg aspirin, a solution containing 500 mg of ascorbic acid or an extract of blackcurrant, and compared by doubly repeated measures ANOVA with those following consumption of the same volume of a control in a cross-over study in six healthy female volunteers. The dominant frequencies of cyclic variations in gastric pressure recorded by the Smartpill were determined by fast Fourier transforms.The gastric transit times of lactulose mannitol solutions, of aspirin solutions and of blackcurrant juice did not differ from those of the control. The gastric transit times of the ascorbic acid solutions were significantly shorter than those of the other solutions. There were no significant differences between the various solutions either in the total small intestinal or colonic transit times. The intraluminal pHs during the initial quartiles of the small intestinal transit times were lower than those in the succeeding quartiles. This pattern did not vary with the solution that was consumed. The power of the frequencies of cyclic variation in intragastric pressure recorded by the Smartpill declined exponentially with increase in frequency and did not peak at the reported physiological frequencies of gastric contractile activity.Whilst the segmental residence times were broadly similar to those using other methods, the high degree of variation between subjects generally

  9. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives.

    Science.gov (United States)

    Sapone, Anna; de Magistris, Laura; Pietzak, Michelle; Clemente, Maria G; Tripathi, Amit; Cucca, Francesco; Lampis, Rosanna; Kryszak, Deborah; Cartenì, Maria; Generoso, Maddalena; Iafusco, Dario; Prisco, Francesco; Laghi, Francesca; Riegler, Gabriele; Carratu, Romano; Counts, Debra; Fasano, Alessio

    2006-05-01

    Zonulin, a protein that modulates intestinal permeability, is upregulated in several autoimmune diseases and is involved in the pathogenesis of autoimmune diabetes in the BB/Wor animal model of the disease. To verify the association between serum zonulin levels and in vivo intestinal permeability in patients with type 1 diabetes, both parameters were investigated in different stages of the autoimmune process. Forty-two percent (141 of 339) of the patients had abnormal serum zonulin levels, as compared with age-matched control subjects. The increased zonulin levels correlated with increased intestinal permeability in vivo and changes in claudin-1, claudin-2, and myosin IXB genes expression, while no changes were detected in ZO1 and occludin genes expression. When tested in serum samples collected during the pre-type 1 diabetes phase, elevated serum zonulin was detected in 70% of subjects and preceded by 3.5 +/- 0.9 years the onset of the disease in those patients who went on to develop type 1 diabetes. Combined, these results suggest that zonulin upregulation is associated with increased intestinal permeability in a subgroup of type 1 diabetic patients. Zonulin upregulation seems to precede the onset of the disease, providing a possible link between increased intestinal permeability, environmental exposure to non-self antigens, and the development of autoimmunity in genetically susceptible individuals.

  10. Undernutrition, Vitamin A and Iron Deficiency Are Associated with Impaired Intestinal Mucosal Permeability in Young Bangladeshi Children Assessed by Lactulose/Mannitol Test.

    Directory of Open Access Journals (Sweden)

    Md Iqbal Hossain

    Full Text Available Lactulose/mannitol (L:M test has been used as a non-invasive marker of intestinal mucosal -integrity and -permeability (enteropathy. We investigated the association of enteropathy with anthropometrics, micronutrient- status, and morbidity in children.The urine and blood samples were collected from 925 children aged 6-24 months residing in Mirpur slum of Dhaka, Bangladesh during November 2009 to April 2013. L:M test and micronutrient status were assessed in the laboratory of International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b following standard procedure.Mean±SD age of the children was 13.2±5.2 months and 47.8% were female. Urinary- lactulose recovery was 0.264±0.236, mannitol recovery was 3.423±3.952, and L:M was 0.109±0.158. An overall negative correlation (Spearman's-rho of L:M was found with age (rs = -0.087; p = 0.004, weight-for-age (rs = -0.077; p = 0.010, weight-for-length (rs = -0.060; p = 0.034, mid-upper-arm-circumference (rs = -0.098; p = 0.001 and plasma-retinol (rs = -0.105; p = 0.002; and a positive correlation with plasma α-1-acid glycoprotein (rs = 0.066; p = 0.027. However, most of the correlations were not very strong. Approximately 44% of children had enteropathy as reflected by L:M of ≥0.09. Logistic regression analysis revealed that younger age (infancy (adjusted odds ratio (AOR = 1.35; p = 0.027, diarrhea (AOR = 4.00; p = 0.039 or fever (AOR = 2.18; p = 0.003 within previous three days of L:M test were the risk factors of enteropathy (L:M of ≥0.09.Enteropathy (high L:M is associated with younger age, undernutrition, low vitamin A and iron status, and infection particularly diarrhea and fever.

  11. Catalase and superoxide dismutase conjugated with platelet-endothelial cell adhesion molecule antibody distinctly alleviate abnormal endothelial permeability caused by exogenous reactive oxygen species and vascular endothelial growth factor.

    Science.gov (United States)

    Han, Jingyan; Shuvaev, Vladimir V; Muzykantov, Vladimir R

    2011-07-01

    Reactive oxygen species (ROS) superoxide anion (O(2)()) and hydrogen peroxide (H(2)O(2)) produced by activated leukocytes and endothelial cells in sites of inflammation or ischemia cause endothelial barrier dysfunction that may lead to tissue edema. Antioxidant enzymes (AOEs) catalase and superoxide dismutase (SOD) conjugated with antibodies to platelet-endothelial cell adhesion molecule-1 (PECAM-1) specifically bind to endothelium, quench the corresponding ROS, and alleviate vascular oxidative stress and inflammation. In the present work, we studied the effects of anti-PECAM/catalase and anti-PECAM/SOD conjugates on the abnormal permeability manifested by transendothelial electrical resistance decline, increased fluorescein isothiocyanate-dextran influx, and redistribution of vascular endothelial-cadherin in human umbilical vein endothelial cell (HUVEC) monolayers. Anti-PECAM/catalase protected HUVEC monolayers against H(2)O(2)-induced endothelial barrier dysfunction. Polyethylene glycol-conjugated catalase exerted orders of magnitude lower endothelial uptake and no protective effect, similarly to IgG/catalase. Anti-PECAM/catalase, but not anti-PECAM/SOD, alleviated endothelial hyperpermeability caused by exposure to hypoxanthine/xanthine oxidase, implicating primarily H(2)O(2) in the disruption of the endothelial barrier in this model. Thrombin-induced endothelial permeability was not affected by treatment with anti-PECAM/AOEs or the NADPH oxidase inhibitor apocynin or overexpression of AOEs, indicating that the endogenous ROS play no key role in thrombin-mediated endothelial barrier dysfunction. In contrast, anti-PECAM/SOD, but not anti-PECAM/catalase, inhibited a vascular endothelial growth factor (VEGF)-induced increase in endothelial permeability, identifying a key role of endogenous O(2)() in the VEGF-mediated regulation of endothelial barrier function. Therefore, AOEs targeted to endothelial cells provide versatile molecular tools for testing the roles of

  12. The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants : A randomized controlled trial

    NARCIS (Netherlands)

    van den Berg, Anemone; Fetter, Willem P. F.; Westerbeek, Elisabeth A. M.; van der Vegt, Ina M.; van der Molen, Hilda R. A.; van Elburg, Ruurd M.

    2006-01-01

    Background: Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion. Glutamine depletion has negative effects on intestinal integrity. The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity, as

  13. The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants: A randomized controlled trial

    NARCIS (Netherlands)

    van den Berg, Anemone; Fetter, Willem P. F.; Westerbeek, Elisabeth A. M.; van der Vegt, Ina M.; van der Molen, Hilda R. A.; van Elburg, Ruurd M.

    2006-01-01

    Background: Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion. Glutamine depletion has negative effects on intestinal integrity. The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity, as

  14. Surgical intervention of intestinal malrotations in paediatric patients without other congenital anatomical abnormalities: Overview from a single center

    International Nuclear Information System (INIS)

    Berge, F. ten; Tolboom, J.J.M.; Boetes, C.; Severijnen, R.S.V.M.; Draaisma, J.M.Th.

    2006-01-01

    The subject of malrotation in infants and children without other congenital anatomical abnormalities is reviewed from the perspective of experience with 97 patients operated in 11 years. Fifty-five patients were younger than 6 weeks at operation. They often presented with bilious vomiting, in contrast to older children who presented with non-bilious vomiting or feeding problems. Patients younger than 6 weeks were operated more often acutely than older patients. Volvulus was more common in infants younger than 6 weeks. Two patients with a resulting short bowel syndrome died. In 73 of the surviving 95 (76.8%) children their symptoms disappeared. In the children younger than 6 weeks persisting abdominal problems were significantly less frequent than in older children. In the children presenting with proven gastro-esophageal reflux disease before the malrotation operation, abdominal problems persisted significantly more often. Although there remains considerable controversy over how older children without signs of vascular problems should be managed, failure to respond to radiographic evidence of malrotation could be considered malpractice if volvulus was to occur subsequently. For this reason, every patient with a radiological proven malrotation merits diagnostic laparoscopy

  15. Surgical intervention of intestinal malrotations in paediatric patients without other congenital anatomical abnormalities: Overview from a single center

    Energy Technology Data Exchange (ETDEWEB)

    Berge, F. ten [Department of Paediatrics, University Medical Center St Radboud, Postbus 9101, 6500 HB Nijmegen (Netherlands); Tolboom, J.J.M. [Department of Paediatrics, University Medical Center St Radboud, Postbus 9101, 6500 HB Nijmegen (Netherlands); Boetes, C. [Department of Radiology, University Medical Center St Radboud, Postbus 9101, 6500 HB Nijmegen (Netherlands); Severijnen, R.S.V.M. [Department of Paediatric Surgery, University Medical Center St Radboud, Postbus 9101, 6500 HB Nijmegen (Netherlands); Draaisma, J.M.Th. [Department of Paediatrics, University Medical Center St Radboud, Postbus 9101, 6500 HB Nijmegen (Netherlands)]. E-mail: j.draaisma@cukz.umcn.nl

    2006-07-15

    The subject of malrotation in infants and children without other congenital anatomical abnormalities is reviewed from the perspective of experience with 97 patients operated in 11 years. Fifty-five patients were younger than 6 weeks at operation. They often presented with bilious vomiting, in contrast to older children who presented with non-bilious vomiting or feeding problems. Patients younger than 6 weeks were operated more often acutely than older patients. Volvulus was more common in infants younger than 6 weeks. Two patients with a resulting short bowel syndrome died. In 73 of the surviving 95 (76.8%) children their symptoms disappeared. In the children younger than 6 weeks persisting abdominal problems were significantly less frequent than in older children. In the children presenting with proven gastro-esophageal reflux disease before the malrotation operation, abdominal problems persisted significantly more often. Although there remains considerable controversy over how older children without signs of vascular problems should be managed, failure to respond to radiographic evidence of malrotation could be considered malpractice if volvulus was to occur subsequently. For this reason, every patient with a radiological proven malrotation merits diagnostic laparoscopy.

  16. A comparison of antibody testing, permeability testing, and zonulin levels with small-bowel biopsy in celiac disease patients on a gluten-free diet.

    Science.gov (United States)

    Duerksen, D R; Wilhelm-Boyles, C; Veitch, R; Kryszak, D; Parry, D M

    2010-04-01

    Active celiac disease is associated with positive endomysial (EMA) and tissue transglutaminase (TTG) antibodies, elevated zonulin levels, and increased intestinal permeability. There is little known about what happens to these immunologic and structural abnormalities in patients on a gluten-free diet and their correlation with small-bowel biopsy changes. Adult patients previously diagnosed with celiac disease and on a gluten-free diet for greater than 1 year were considered for the study. All patients underwent the following: measurement of EMA and TTG antibodies, serum zonulin levels, intestinal permeability (IP) testing with lactulose/mannitol ratios, food diary analysis for gluten ingestion and small- bowel biopsy. A total of 21 patients on a gluten-free diet for a mean of 9.7 years completed the study. There were ten patients who had normalization of intestinal biopsies, IP and TTG, and EM antibodies. Six patients had Marsh type 2 or 3 lesions and all had either abnormal IP (5/6) or TTG antibody (4/6). In patients with Marsh type 3 lesions, there was a correlation between IP and zonulin levels. A subgroup of patients with celiac disease on a gluten-free diet has complete normalization of intestinal biopsies, intestinal permeability defects, and antibody levels. Patients with Marsh type 3 lesions have abnormal TTG antibodies and intestinal permeability with zonulin levels that correlate with IP. These abnormalities may be due to continued gluten ingestion. Further study is needed to determine the clinical utility of TTG antibodies and IP testing in following patients with celiac disease.

  17. Crustal permeability

    Science.gov (United States)

    Gleeson, Tom; Ingebritsen, Steven E.

    2016-01-01

    Permeability is the primary control on fluid flow in the Earth’s crust and is key to a surprisingly wide range of geological processes, because it controls the advection of heat and solutes and the generation of anomalous pore pressures.  The practical importance of permeability – and the potential for large, dynamic changes in permeability – is highlighted by ongoing issues associated with hydraulic fracturing for hydrocarbon production (“fracking”), enhanced geothermal systems, and geologic carbon sequestration.  Although there are thousands of research papers on crustal permeability, this is the first book-length treatment.  This book bridges the historical dichotomy between the hydrogeologic perspective of permeability as a static material property and the perspective of other Earth scientists who have long recognized permeability as a dynamic parameter that changes in response to tectonism, fluid production, and geochemical reactions. 

  18. Notional Permeability

    NARCIS (Netherlands)

    Kik, R.; Van den Bos, J.P.; Maertens, J.; Verhagen, H.J.; Van der Meer, J.W.

    2012-01-01

    Different layer design of a rock slope and under layers has a large effect on the strengths on the rock slope itself. In the stability formula developed of VAN DER MEER [1988] this effect is represented by the term Notional Permeability with symbol P. A more open, or permeable, structure underneath

  19. Combined effect of rifampicin-induced P-glycoprotein expression and lipopolysaccharide-induced intestinal sepsis on the effective permeability and pharmacokinetics of an anti-malarial candidate CDRI 97/78 in rats.

    Science.gov (United States)

    Singh, Yeshwant; Hidau, Mahendra Kumar; Krishna, Jampala; Singh, Shio Kumar

    2015-01-01

    1. The study aimed to investigate the influences on the pharmacokinetics (PK) of an anti-malarial drug 97/78 in rats pretreated with orally administered rifampicin and bacterial endotoxin lipopolysaccharide (LPS). 2. In-situ intestinal absorption studies were conducted on rats pretreated with rifampicin and LPS or both to estimate effective permeability (Peff) of 97/78. In-vivo studies were then conducted to explore 97/78 PK profile under these conditions. In-situ studies revealed that Peff value decreased to 64% (2.7 ± 0.6) × 10(-4 )cm/s in rats pretreated with rifampicin. This decrease was further enhanced very significantly to 4.5% (0.19 ± 0.03) × 10(-4 )cm/s in rats pretreated both with rifampicin and LPS (p97/78 in rifampicin-pretreated rats. This decrease was further augmented to 12-fold upon rifampicin and LPS pretreatment. 3. Orally administered rifampicin decreased the concentration of 97/78 in circulation. This decrease was further enhanced significantly to a very low level by LPS-induced intestinal sepsis.

  20. Mucin phenotypic expression and p53 gene abnormality of gastric super-minute well-differentiated adenocarcinoma: re-evaluation with relationship between histogenesis of well-differentiated adenocarcinoma and intestinal metaplasia in distal stomach.

    Science.gov (United States)

    Wada, Ryo; Yamaguchi, Toshikazu; Tanizaki, Takayuki

    2005-09-01

    gastric and intestinal phenotypic mucin, are considered to develop from the tubular proliferative zone with the incomplete type of the intestinal metaplasia and p53 gene abnormality, while a part of them, which had only gastric phenotypic mucin, may derive from the gastric native tubules (non-metaplastic epithelium) with p53 gene abnormality.

  1. Mucin phenotypic expression and p53 gene abnormality of gastric super-minute well-differentiated adenocarcinoma: Re-evaluation with relationship between histogenesis of well-differentiated adenocarcinoma and intestinal metaplasia in distal stomach

    Directory of Open Access Journals (Sweden)

    Yamaguchi Toshikazu

    2005-01-01

    lesions in the distal stomach, which had both gastric and intestinal phenotypic mucin, are considered to develop from the tubular proliferative zone with the incomplete type of the intestinal metaplasia and p53 gene abnormality, while a part of them, which had only gastric phenotypic mucin, may derive from the gastric native tubules (non-metaplastic epithelium with p53 gene abnormality.

  2. Crosstalk between Inflammation and ROCK/MLCK Signaling Pathways in Gastrointestinal Disorders with Intestinal Hyperpermeability

    Directory of Open Access Journals (Sweden)

    Lijun Du

    2016-01-01

    Full Text Available The barrier function of the intestine is essential for maintaining the normal homeostasis of the gut and mucosal immune system. Abnormalities in intestinal barrier function expressed by increased intestinal permeability have long been observed in various gastrointestinal disorders such as Crohn’s disease (CD, ulcerative colitis (UC, celiac disease, and irritable bowel syndrome (IBS. Imbalance of metabolizing junction proteins and mucosal inflammation contributes to intestinal hyperpermeability. Emerging studies exploring in vitro and in vivo model system demonstrate that Rho-associated coiled-coil containing protein kinase- (ROCK- and myosin light chain kinase- (MLCK- mediated pathways are involved in the regulation of intestinal permeability. With this perspective, we aim to summarize the current state of knowledge regarding the role of inflammation and ROCK-/MLCK-mediated pathways leading to intestinal hyperpermeability in gastrointestinal disorders. In the near future, it may be possible to specifically target these specific pathways to develop novel therapies for gastrointestinal disorders associated with increased gut permeability.

  3. Intestinal Barrier and Behavior.

    Science.gov (United States)

    Julio-Pieper, M; Bravo, J A

    2016-01-01

    The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses. © 2016 Elsevier Inc. All rights reserved.

  4. [Digestion of pea and soya proteins in the preruminant calf. I. Circulating levels of nutrients, antibody formation and intestinal permeability to macromolecules].

    Science.gov (United States)

    Nunes do Prado, I; Toullec, R; Lallès, J P; Guéguen, J; Hingand, J; Guilloteau, P

    1989-01-01

    Three milk-substitutes (control, pea and soya-bean)were given to 6 preruminant calves. In the control diet protein was almost entirely provided by skim milk powder. In the pea diet a pregelatinized dehulled pea flour provided 33.5% of the protein, the remainder being supplied by skim milk powder. In the soya-bean diet, 73.2% of the protein were provided by a soya-bean isolate and the remainder by whey powder. The concentrations of plasma triglycerides and the free alpha-amino nitrogen in the peripheral blood were lower with the pea and soya-bean diets than with the control diet before the morning meal, but became higher after feeding. That suggested a faster abomasal emptying of fat and protein with the pea and especially the soya-bean diet. Systemic antibody responses were induced against pea protein but not against soya-bean protein. No effect of the diet on the plasma concentration of immunoreactive beta-lactoglobulin was apparent after 6 days, suggesting there was no important change in gut permeability at least at that time.

  5. Mucosal pathobiology and molecular signature of epithelial barrier dysfunction in the small intestine in irritable bowel syndrome.

    Science.gov (United States)

    González-Castro, Ana M; Martínez, Cristina; Salvo-Romero, Eloísa; Fortea, Marina; Pardo-Camacho, Cristina; Pérez-Berezo, Teresa; Alonso-Cotoner, Carmen; Santos, Javier; Vicario, María

    2017-01-01

    Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders in developed countries. Its etiology remains unknown; however, a common finding, regardless of IBS subtype, is the presence of altered intestinal barrier. In fact, signaling and location of cell-to-cell adhesion proteins, in connection with increased immune activity, seem abnormal in the intestinal epithelium of IBS patients. Despite that most research is performed on distal segments of the intestine, altered permeability has been reported in both, the small and the large bowel of all IBS subtypes. The small intestine carries out digestion and nutrient absorption and is also the site where the majority of immune responses to luminal antigens takes place. In fact, the upper intestine is more exposed to environmental antigens than the colon and is also a site of symptom generation. Recent studies have revealed small intestinal structural alterations of the epithelial barrier and mucosal immune activation in association with intestinal dysfunction, suggesting the commitment of the intestine as a whole in the pathogenesis of IBS. This review summarizes the most recent findings on mucosal barrier alterations and its relationship to symptoms arising from the small intestine in IBS, including epithelial structural abnormalities, mucosal immune activation, and microbial dysbiosis, further supporting the hypothesis of an organic origin of IBS. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  6. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome.

    Science.gov (United States)

    Lee, Kang Nyeong; Lee, Oh Young

    2014-07-21

    Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10(14) cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.

  7. The utility of rat jejunal permeability for biopharmaceutics classification system.

    Science.gov (United States)

    Zakeri-Milani, Parvin; Valizadeh, Hadi; Tajerzadeh, Hosnieh; Islambulchilar, Ziba

    2009-12-01

    The biopharmaceutical classification system has been developed to provide a scientific approach for classifying drug compounds based on their dose/solubility ratio and human intestinal permeability. Therefore in this study a new classification is presented, which is based on a correlation between rat and human intestinal permeability values. In situ technique in rat jejunum was used to determine the effective intestinal permeability of tested drugs. Then three dimensionless parameters--dose number, absorption number, and dissolution number (D(o), A(n), and D(n))--were calculated for each drug. Four classes of drugs were defined, that is, class I, D(0) 5.09 x 10(-5) cm/s; class II, D(o) > 1, P(eff(rat)) > 5.09 x 10( -5) cm/s; class III, D(0) 1, P(eff(rat)) < 4.2 x 10(-5) cm/s. A region of borderline drugs (0.5 < D(o) < 1, 4.2 x 10(-5) < P(eff(rat)) < 5.09 x 10(-5) cm/s) was also defined. According to obtained results and proposed classification for drugs, it is concluded that drugs could be categorized correctly based on dose number and their intestinal permeability values in rat model using single-pass intestinal perfusion technique. This classification enables us to remark defined characteristics for intestinal absorption of all four classes using suitable cutoff points for both dose number and rat effective intestinal permeability values.

  8. Congenital Abnormalities

    Science.gov (United States)

    ... Stages Ages and Stages Prenatal Baby (0-12 mos.) Toddler 1-3yrs. Preschool 3-5yrs Grade School ... Categories of Congenital Abnormalities Chromosome Abnormalities Chromosomes are structures that carry genetic material inherited from one generation ...

  9. High-permeability criterion for BCS classification: segmental/pH dependent permeability considerations.

    Science.gov (United States)

    Dahan, Arik; Miller, Jonathan M; Hilfinger, John M; Yamashita, Shinji; Yu, Lawrence X; Lennernäs, Hans; Amidon, Gordon L

    2010-10-04

    The FDA classifies a drug substance as high-permeability when the fraction of dose absorbed (F(abs)) in humans is 90% or higher. This direct correlation between human permeability and F(abs) has been recently controversial, since the β-blocker sotalol showed high F(abs) (90%) and low Caco-2 permeability. The purpose of this study was to investigate the scientific basis for this disparity between permeability and F(abs). The effective permeabilities (P(eff)) of sotalol and metoprolol, a FDA standard for the low/high P(eff) class boundary, were investigated in the rat perfusion model, in three different intestinal segments with pHs corresponding to the physiological pH in each region: (1) proximal jejunum, pH 6.5; (2) mid small intestine, pH 7.0; and (3) distal ileum, pH 7.5. Both metoprolol and sotalol showed pH-dependent permeability, with higher P(eff) at higher pH. At any given pH, sotalol showed lower permeability than metoprolol; however, the permeability of sotalol determined at pH 7.5 exceeded/matched metoprolol's at pH 6.5 and 7.0, respectively. Physicochemical analysis based on ionization, pK(a) and partitioning of these drugs predicted the same trend and clarified the mechanism behind these observed results. Experimental octanol-buffer partitioning experiments confirmed the theoretical curves. An oral dose of metoprolol has been reported to be completely absorbed in the upper small intestine; it follows, hence, that metoprolol's P(eff) value at pH 7.5 is not likely physiologically relevant for an immediate release dosage form, and the permeability at pH 6.5 represents the actual relevant value for the low/high permeability class boundary. Although sotalol's permeability is low at pH 6.5 and 7.0, at pH 7.5 it exceeds/matches the threshold of metoprolol at pH 6.5 and 7.0, most likely responsible for its high F(abs). In conclusion, we have shown that, in fact, there is no discrepancy between P(eff) and F(abs) in sotalol's absorption; the data emphasize that

  10. Relationship between intestinal microflora imbalance and nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    MA Ruijuan

    2015-01-01

    Full Text Available The intestinal microecosystem is composed of natural microflora, intestinal epithelial cells, and intestinal mucosal immune system. Nonalcoholic fatty liver disease (NAFLD is a metabolic stress-induced liver injury associated with insulin resistance and genetic susceptibility. In recent years, there has been increasing evidence showing the involvement of imbalanced intestinal microflora in the pathogenesis of NAFLD. Overgrowth of intestinal microflora, increased permeability of intestinal mucosa, intestinal endotoxemia, and production of inflammatory cytokines play important roles in the development of NAFLD. Further studies on the relationship between intestinal microflora imbalance and the pathogenesis of NAFLD may shed light on the treatment and prevention of NAFLD.

  11. Developments in permeable and low permeability barriers

    International Nuclear Information System (INIS)

    Jefferis, S.A.; Norris, G.H.; Thomas, A.O.

    1997-01-01

    The concept of the reactive treatment zone whereby pollutants are attenuated as they move along a pathway in the ground has enabled a re-thinking of many of the concepts of containment. In particular it offers the potential for the control of the flux from a contaminated area by controlling the contaminant concentration in the pathway(s) as well as or instead of using a low permeability barrier. The paper outlines the basic concepts of the reactive treatment zone and the use of permeable and low permeability reactive systems. The paper then gives a case history of the installation of a permeable barrier using an in-situ reaction chamber

  12. Intestinal Cancer

    Science.gov (United States)

    ... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

  13. Meiotic abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  14. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity

    NARCIS (Netherlands)

    Verdam, F.J.; Fuentes Enriquez de Salamanca, S.; Jonge, de C.; Zoetendal, E.G.; Erbil, R.; Greve, J.W.; Buurman, W.A.; Vos, de W.M.; Rensen, S.S.

    2013-01-01

    OBJECTIVE: Intestinal microbiota have been suggested to contribute to the development of obesity, but the mechanism remains elusive. The relationship between microbiota composition, intestinal permeability, and inflammation in nonobese and obese subjects was investigated. DESIGN AND METHODS: Fecal

  15. Dietary non-digestible carbohydrates and the resistance to intestinal infections

    NARCIS (Netherlands)

    Bruggencate, ten S.J.M.

    2004-01-01

    Keywords: Non-digestible carbohydrates, prebiotics, inulin, FOS, calcium, microflora, short-chain fatty acids, mucin, intestinal permeability, salmonella, infection, rat, humanDietary non-digestible carbohydrates and the resistance to intestinal infectionsNon-digestible carbohydrates (NDC) stimulate

  16. Film Permeability Determination Using Static Permeability Cells

    Science.gov (United States)

    The permeability of tarps to soil fumigant pesticides varies depending on the active ingredient chemical: dimethyl disulfide (DMDS), methyl bromide, chloropicrin, or other. The diffusion rate can be represented by the mass transfer coefficient (MTC).

  17. Estimation of soil permeability

    Directory of Open Access Journals (Sweden)

    Amr F. Elhakim

    2016-09-01

    Full Text Available Soils are permeable materials because of the existence of interconnected voids that allow the flow of fluids when a difference in energy head exists. A good knowledge of soil permeability is needed for estimating the quantity of seepage under dams and dewatering to facilitate underground construction. Soil permeability, also termed hydraulic conductivity, is measured using several methods that include constant and falling head laboratory tests on intact or reconstituted specimens. Alternatively, permeability may be measured in the field using insitu borehole permeability testing (e.g. [2], and field pumping tests. A less attractive method is to empirically deduce the coefficient of permeability from the results of simple laboratory tests such as the grain size distribution. Otherwise, soil permeability has been assessed from the cone/piezocone penetration tests (e.g. [13,14]. In this paper, the coefficient of permeability was measured using field falling head at different depths. Furthermore, the field coefficient of permeability was measured using pumping tests at the same site. The measured permeability values are compared to the values empirically deduced from the cone penetration test for the same location. Likewise, the coefficients of permeability are empirically obtained using correlations based on the index soil properties of the tested sand for comparison with the measured values.

  18. Walking abnormalities

    Science.gov (United States)

    ... include: Arthritis of the leg or foot joints Conversion disorder (a mental disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  19. Ammonia and urea permeability of mammalian aquaporins

    DEFF Research Database (Denmark)

    Litman, Thomas; Søgaard, Rikke; Zeuthen, Thomas

    2009-01-01

    and 9 are found together with Rh proteins in cells exposed to portal blood coming from the intestine. In the kidney, AQP3 might participate in the excretion of NH(4) (+) in the collecting duct. The interplay between the ammonia-permeable aquaporins and the other types of ammonia- and urea......The human aquaporins,AQP3,AQP7, AQP8,AQP9, and possibly AQP10, are permeable to ammonia, and AQP7, AQP9, and possibly AQP3, are permeable to urea. In humans, these aquaporins supplement the ammonia transport of the Rhesus (Rh) proteins and the urea transporters (UTs). The mechanism by which...... ammonium is transported by aquaporins is not fully resolved. A comparison of transport equations, models, and experimental data shows that ammonia is transported in its neutral form, NH(3). In the presence of NH(3), the aquaporin stimulates H(+) transport. Consequently, this transport of H(+) is only...

  20. Intestinal Obstruction

    Science.gov (United States)

    ... the obstruction along the intestines. Treatment Suction via nasogastric tube Fluids given by vein Surgery for strangulation Sometimes ... nose and placed in the stomach (called a nasogastric tube) or into the intestine. Suction is applied to ...

  1. Permeability and relative permeability in rocks

    Energy Technology Data Exchange (ETDEWEB)

    Blair, S.C.; Berryman, J.G.

    1990-10-01

    Important features of the topology of the pore space of rocks can be usefully quantified by analyzing digitized images of rock cross sections. One approach computes statistical correlation functions using modern image processing techniques. These correlation functions contain information about porosity, specific surface area, tortuosity, formation factor, and elastic constants, as well as the fluid permeability and relative permeability. The physical basis of this approach is discussed and examples of the results for various sandstones are presented. The analysis shows that Kozeny-Carman relations and Archie's empirical laws must be modified to account for finite percolation thresholds in order to avoid unphysical behavior in the calculated relative permeabilities. 33 refs., 4 figs., 1 tab.

  2. DIAGNOSIS AND MANAGEMENT OF SUBACUTE INTESTINAL OBSTRUCTION: A PROSPECTIVE STUDY

    OpenAIRE

    Amit; Anjani; Shaleen; Vikram; Prasheel

    2014-01-01

    Intestinal obstruction can be defined as impairment to the abnormal passage of intestinal contents that may be due to either mechanical obstruction or failure of normal intestinal motility in the absence of an obstructing lesion. Intestinal obstruction is the most common surgical disorder of the small intestine. SAIO implies incomplete obstruction. It has been defined in a number of ways and there are many gray zones in the treatment protocols. It is characterized by conti...

  3. Herbal medicines that benefit epidermal permeability barrier function

    Directory of Open Access Journals (Sweden)

    Lizhi Hu

    2015-06-01

    Full Text Available Epidermal permeability barrier function plays a critical role in regulating cutaneous functions. Hence, researchers have been searching for effective and affordable regimens to enhance epidermal permeability barrier function. In addition to topical stratum corneum lipids, peroxisome proliferator-activated receptor, and liver X receptor ligands, herbal medicines have been proven to benefit epidermal permeability barrier function in both normal and diseased skin, including atopic dermatitis, glucocorticoid-induced skin damage, and UVB-damaged skin. The potential mechanisms by which herbal medicines improve the permeability barrier include stimulation of epidermal differentiation, lipid production, antimicrobial peptide expression, and antioxidation. Therefore, utilization of herbal medicines could be a valuable alternative approach to enhance epidermal permeability barrier function in order to prevent and/or treat skin disorders associated with permeability barrier abnormalities.

  4. Permeable Pavements at Purdue

    OpenAIRE

    Knapp, Jim

    2013-01-01

    Two case studies will be presented describing sustainable drainage alternatives. The processes used for the 2nd Street project in Seymour will provide a comparison of the design processes for conventional and green infrastructure solutions. Purdue University will discuss a number of permeable pavement installations on campus and provide a map for viewing. Asphalt, concrete, and permeable paver options will be discussed.

  5. Permeability prediction in chalks

    DEFF Research Database (Denmark)

    Alam, Mohammad Monzurul; Fabricius, Ida Lykke; Prasad, Manika

    2011-01-01

    The velocity of elastic waves is the primary datum available for acquiring information about subsurface characteristics such as lithology and porosity. Cheap and quick (spatial coverage, ease of measurement) information of permeability can be achieved, if sonic velocity is used for permeability...... prediction, so we have investigated the use of velocity data to predict permeability. The compressional velocity fromwireline logs and core plugs of the chalk reservoir in the South Arne field, North Sea, has been used for this study. We compared various methods of permeability prediction from velocities....... The relationships between permeability and porosity from core data were first examined using Kozeny’s equation. The data were analyzed for any correlations to the specific surface of the grain, Sg, and to the hydraulic property defined as the flow zone indicator (FZI). These two methods use two different approaches...

  6. Congenital central hypoventilation syndrome and intestinal ...

    African Journals Online (AJOL)

    ... hypoventilation syndrome (CCHS), also called 'Ondine's curse', is characterised by an abnormal ventilatory response to progressive hypercapnia and sustained hypoxaemia. Neonates with this condition experience hypoventilation or apnoea while asleep. Patients may also have congenital intestinal aganglionosis (CIA), ...

  7. Zidovudine-cyclodextrin inclusion complex and its permeability ...

    African Journals Online (AJOL)

    The permeability of zidovudine in zidovudine-cyclodextrin inclusion complex across stomach and intestinal compartments of rat was investigated spectrophotometrically. The absorption maximum ( ) for zidovudine in HCl max buffer (pH 1.2) and in phosphate buffer (pH 7.4) were 267 and 268 nm respectively. The inclusion ...

  8. Permeability of porour rhyolite

    Science.gov (United States)

    Cashman, K.; Rust, A.; Wright, H.; Roberge, J.

    2003-04-01

    The development of permeability in bubble-bearing magmas determines the efficiency of volatile escape during their ascent through volcanic conduits, which, in turn, controls their explosive potential. As permeability requires bubble connectivity, relationships between permeability and porosity in silicic magmas must be controlled by the formation, growth, deformation and coalescence of their constituent bubbles. Although permeability data on porous volcanic pyroclasts are limited, the database can be greatly extended by including data for ceramic and metallic foams1. Several studies indicate that a single number does not adequately describe the permeability of a foam because inertial effects, which predominate at high flow rates, cause deviations from Darcy's law. These studies suggest that permeability is best modeled using the Forschheimer equation to determine both the Darcy permeability (k1) and the non-Darcian (k2) permeability. Importantly, at the high porosities of ceramic foams (75-95%), both k1 and k2 are strongly dependent on pore size and geometry, suggesting that measurement of these parameters provides important information on foam structure. We determined both the connected porosity (by He-pycnometry) and the permeability (k1 and k2) of rhyolitic samples having a wide range in porosity (22-85%) and vesicle textures. In general, these data support previous observations of a power law relationship between connected porosity and Darcy permeability2. In detail, variations in k1 increase at higher porosities. Similarly, k2 generally increases in both mean and standard deviation with increasing porosity. Measurements made on three mutually perpendicular cores from individual pumice clasts suggest that some of the variability can be explained by anisotropy in the vesicle structure. By comparison with ceramic foams, we suggest that the remaining variability results from differences either in average vesicle size or, more likely, in the size of apertures

  9. Effect of pharmacologically induced smooth muscle activation on permeability in murine colitis

    NARCIS (Netherlands)

    F.J. Zijlstra (Freek); M.E. van Meeteren (Marieke); I.M. Garrelds (Ingrid); M.A.C. Meijssen (Maarten)

    2003-01-01

    textabstractBACKGROUND: Both intestinal permeability and contractility are altered in inflammatory bowel disease. Little is known about their mutual relation. Therefore, an in vitro organ bath technique was developed to investigate the simultaneous effects of inflammation on permeability and smooth

  10. Permeable pavement study (Edison)

    Data.gov (United States)

    U.S. Environmental Protection Agency — While permeable pavement is increasingly being used to control stormwater runoff, field-based, side-by-side investigations on the effects different pavement types...

  11. A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices.

    Science.gov (United States)

    Westerhout, Joost; van de Steeg, Evita; Grossouw, Dimitri; Zeijdner, Evelijn E; Krul, Cyrille A M; Verwei, Miriam; Wortelboer, Heleen M

    2014-10-15

    A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption, however, is often insufficient, especially when food-drug interactions are evaluated. Ideally, for this purpose healthy human intestinal tissue is used, but due to its limited availability there is a need for alternatives. The aim of this study was to evaluate the applicability of healthy porcine intestinal tissue mounted in a newly developed InTESTine™ system to predict human intestinal absorption of compounds with different chemical characteristics, and within biorelevant matrices. To that end, first, a representative set of compounds was chosen of which the apparent permeability (Papp) data in both Caco-2 cells and human intestinal tissue mounted in the Ussing chamber system, and absolute human oral bioavailability were reported. Thereafter, Papp values of the subset were determined in both porcine jejunal tissue and our own Caco-2 cells. In addition, the feasibility of this new approach to study regional differences (duodenum, jejunum, and ileum) in permeability of compounds and to study the effects of luminal factors on permeability was also investigated. For the latter, a comparison was made between the compatibility of porcine intestinal tissue, Caco-2 cells, and Caco-2 cells co-cultured with the mucin producing HT29-MTX cells with biorelevant samples as collected from an in vitro dynamic gastrointestinal model (TIM). The results demonstrated that for the paracellularly transported compounds atenolol, cimetidine, mannitol and ranitidine porcine Papp values are within 3-fold difference of human Papp values, whereas the Caco-2 Papp values are beyond 3-fold difference. Overall, the porcine intestinal tissue Papp values are more comparable to human Papp values (9 out

  12. Intestine transplantation

    Directory of Open Access Journals (Sweden)

    Tadeja Pintar

    2011-02-01

    Conclusion: Intestine transplantation is reserved for patients with irreversible intestinal failure due to short gut syndrome requiring total paranteral nutrition with no possibility of discontinuation and loss of venous access for patient maintenance. In these patients complications of underlying disease and long-term total parenteral nutrition are present.

  13. Permeable pavement study (Edison)

    Science.gov (United States)

    While permeable pavement is increasingly being used to control stormwater runoff, field-based, side-by-side investigations on the effects different pavement types have on nutrient concentrations present in stormwater runoff are limited. In 2009, the U.S. EPA constructed a 0.4-ha parking lot in Edison, New Jersey, that incorporated permeable interlocking concrete pavement (PICP), pervious concrete (PC), and porous asphalt (PA). Each permeable pavement type has four, 54.9-m2, lined sections that direct all infiltrate into 5.7-m3 tanks enabling complete volume collection and sampling. This paper highlights the results from a 12-month period when samples were collected from 13 rainfall/runoff events and analyzed for nitrogen species, orthophosphate, and organic carbon. Differences in infiltrate concentrations among the three permeable pavement types were assessed and compared with concentrations in rainwater samples and impervious asphalt runoff samples, which were collected as controls. Contrary to expectations based on the literature, the PA infiltrate had significantly larger total nitrogen (TN) concentrations than runoff and infiltrate from the other two permeable pavement types, indicating that nitrogen leached from materials in the PA strata. There was no significant difference in TN concentration between runoff and infiltrate from either PICP or PC, but TN in runoff was significantly larger than in the rainwater, suggesting meaningful inter-event dry de

  14. Acamprosate permeability across Caco-2 cell monolayer is predominantly paracellular

    DEFF Research Database (Denmark)

    Antonescu, Irina-Elena; Steffansen, Bente

    was mathematically accounting for the unstirred boundary layer permeability (PUBL), the filter permeability (Pf), the intrinsic passive transcellular permeability (Ptrans,0) and Ppara (1-3). The mathematical model thereby accounted for (i) the physical-chemical properties of acamprosate and mannitol (molecular...... role in acamprosate permeability, as only a very low fraction of acamprosate is in the neutral form at pH 7.4. The estimated acamprosate Ppara accounts for nearly 100% of the mathematically determined acamprosate Papp, calc (0.20 ± 0.10 x 10-6 cm/s), which matches well with the experimentally...... in the different regions of the rodent small intestine and colon. Biopharm Drug Dispos. 2017;38(2):94-114. 2. Avdeef A. Leakiness and size exclusion of paracellular channels in cultured epithelial cell monolayers-interlaboratory comparison. Pharm Res. 2010;27(3):480-9. 3. Avdeef A. Absorption and Drug Development...

  15. Effect of Lactobacilli on Paracellular Permeability in the Gut

    Directory of Open Access Journals (Sweden)

    Marie-Louise Johansson Hagslatt

    2011-01-01

    Full Text Available Paracellular permeability is determined by the complex structures of junctions that are located between the epithelial cells. Already in 1996, it was shown that the human probiotic strain Lactobacillus plantarum 299v and the rat-originating strain Lactobacillus reuteri R2LC could reduce this permeability in a methotrexate-induced colitis model in the rat. Subsequently, many animal models and cell culture systems have shown indications that lactobacilli are able to counteract increased paracellular permeability evoked by cytokines, chemicals, infections, or stress. There have been few human studies focusing on the effect of lactobacilli on intestinal paracellular permeability but recently it has been shown that they could influence the tight junctions. More precisely, short-term administration of L. plantarum WCSF1 to healthy volunteers increased the relocation of occludin and ZO-1 into the tight junction area between duodenal epithelial cells.

  16. Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis.

    Science.gov (United States)

    Taniguchi, Tomoyo; Miyauchi, Eiji; Nakamura, Shota; Hirai, Makoto; Suzue, Kazutomo; Imai, Takashi; Nomura, Takahiro; Handa, Tadashi; Okada, Hiroko; Shimokawa, Chikako; Onishi, Risa; Olia, Alex; Hirata, Jun; Tomita, Haruyoshi; Ohno, Hiroshi; Horii, Toshihiro; Hisaeda, Hajime

    2015-10-27

    Gastrointestinal symptoms, such as abdominal pain and diarrhea, are frequently observed in patients with Plasmodium falciparum malaria. However, the correlation between malaria intestinal pathology and intestinal microbiota has not been investigated. In the present study, infection of C57BL/6 mice with P. berghei ANKA (PbA) caused intestinal pathological changes, such as detachment of epithelia in the small intestines and increased intestinal permeability, which correlated with development with experimental cerebral malaria (ECM). Notably, an apparent dysbiosis occurred, characterized by a reduction of Firmicutes and an increase in Proteobacteria. Furthermore, some genera of microbiota correlated with parasite growth and/or ECM development. By contrast, BALB/c mice are resistant to ECM and exhibit milder intestinal pathology and dysbiosis. These results indicate that the severity of cerebral and intestinal pathology coincides with the degree of alteration in microbiota. This is the first report demonstrating that malaria affects intestinal microbiota and causes dysbiosis.

  17. Biopharmaceutics classification and intestinal absorption study of apigenin.

    Science.gov (United States)

    Zhang, Jianjun; Liu, Dapeng; Huang, Yanting; Gao, Yuan; Qian, Shuai

    2012-10-15

    The aim of the study was to characterize the biopharmaceutics classification system (BCS) category of apigenin (AP) using intrinsic dissolution rate (IDR) and rat intestinal permeability, and to investigate the intestinal absorption mechanism of AP in rats. In the present investigation, equilibrium solubility and intrinsic dissolution rate (IDR) of AP were estimated in phosphate buffers. Effective intestinal permeability (P(eff)) of AP was determined using single-pass intestinal perfusion (SPIP) technique in four segments (duodenum, jejunum, ileum and colon) of rat intestine at three concentrations (10, 50 and 100 μg/ml). The aqueous solubility of AP in tested phosphate buffers was very poor with maximum solubility of 2.16 μg/ml at pH 7.5. The IDR of AP was very low with a value of 0.006 mg/min/cm(2). The minimum and maximum P(eff)s determined by SPIP were 0.198×10(-4) and 0.713×10(-4) cm/s at jejunum and duodenum site, respectively. In addition, the concentration-dependent permeability behavior was observed in the duodenum and jejunum, which suggested that AP was transported by both passive and active carrier-mediated saturable mechanism in these two intestinal segments. However, the observed concentration-independent permeability behavior in ileum and colon indicated primarily passive transport mechanism of absorption of AP in the last two intestinal segments. AP was classified as class II drug of the BCS due to its low solubility and high intestinal permeability. AP could be well absorbed in the whole intestine with the main absorption site at duodenum. The absorption of AP in four intestinal segments exhibited different transport mechanisms. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Biostable glucose permeable polymer

    DEFF Research Database (Denmark)

    2017-01-01

    A new biostable glucose permeable polymer has been developed which is useful, for example, in implantable glucose sensors. This biostable glucose permeable polymer has a number of advantageous characteristics and, for example, does not undergo hydrolytic cleavage and degradation, thereby providing...... a composition that facilitates long term sensor stability in vivo. The versatile characteristics of this polymer allow it to be used in a variety of contexts, for example to form the body of an implantable glucose sensor. The invention includes the polymer composition, sensor systems formed from this polymer...

  19. Intestinal Ischemia

    Science.gov (United States)

    ... weight loss Intestinal ischemia Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  20. Exploring food effects on indinavir absorption with human intestinal fluids in the mouse intestine.

    Science.gov (United States)

    Holmstock, Nico; De Bruyn, Tom; Bevernage, Jan; Annaert, Pieter; Mols, Raf; Tack, Jan; Augustijns, Patrick

    2013-04-11

    Food can have a significant impact on the pharmacokinetics of orally administered drugs, as it may affect drug solubility as well as permeability. Since fed state conditions cannot easily be implemented in the presently available permeability tools, including the frequently used Caco-2 system, exploring food effects during drug development can be quite challenging. In this study, we investigated the effect of fasted and fed state conditions on the intestinal absorption of the HIV protease inhibitor indinavir using simulated and human intestinal fluids in the in situ intestinal perfusion technique in mice. Although the solubility of indinavir was 6-fold higher in fed state human intestinal fluids (FeHIF) as compared to fasted state HIF (FaHIF), the intestinal permeation of indinavir was 22-fold lower in FeHIF as compared to FaHIF. Dialysis experiments showed that only a small fraction of indinavir is accessible for absorption in FeHIF due to micellar entrapment, possibly explaining its low intestinal permeation. The presence of ritonavir, a known P-gp inhibitor, increased the intestinal permeation of indinavir by 2-fold in FaHIF, while there was no increase when using FeHIF. These data confirm that drug-food interactions form a complex interplay between solubility and permeability effects. The use of HIF in in situ intestinal perfusions holds great promise for biorelevant absorption evaluation as it allows to directly explore this complex solubility/permeability interplay on drug absorption. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Intestinal Coccidia

    OpenAIRE

    MJ Ggaravi

    2007-01-01

    Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycl...

  2. Biopharmaceutics permeability classification of lorcaserin, a selective 5-hydroxytryptamine 2C agonist: method suitability and permeability class membership.

    Science.gov (United States)

    Chen, Chuan; Ma, Michael G; Fullenwider, Cody L; Chen, Weichao G; Sadeque, Abu J M

    2013-12-02

    The objectives of the study were (1) to demonstrate that a Caco-2 cell-based permeability assay, developed in our laboratory, is suitable to identify the permeability classification according to the US Food and Drug Administration Biopharmaceutics Classification System guidance, and (2) to use the validated Caco-2 method to determine permeability class membership of lorcaserin. Lorcaserin, marketed in United States as Belviq, is a selective human 5-hydroxytryptamine 2C agonist used for weight management. First, the permeability of twenty commercially available drugs was determined in the apical-to-basolateral direction at a final concentration of 10 μM, with the pH of transporter buffer in the apical and basolateral compartments being 6.8 and 7.4, respectively. A rank-order relationship between in vitro permeability results and the extent of human intestinal absorption for the drugs tested was observed. Second, the apparent permeability coefficient values of lorcaserin at 2, 20, and 200 μM and apical pH values of 6.8 and 7.4 in the apical-to-basolateral direction were determined using the validated method and found to be comparable to those of the high-permeability internal standard metoprolol. Lorcaserin permeability across Caco-2 cell monolayers was not dependent on the variation of apical pH. Furthermore, lorcaserin was not a substrate for efflux transporters such as P-glycoprotein. In conclusion, using the validated Caco-2 permeability assay, it was shown that lorcaserin is a highly permeable compound.

  3. Small Intestine Disorders

    Science.gov (United States)

    ... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.

  4. Alternative Functional In Vitro Models of Human Intestinal Epithelia

    Directory of Open Access Journals (Sweden)

    Amanda L Kauffman

    2013-07-01

    Full Text Available Physiologically relevant sources of absorptive intestinal epithelial cells are crucial for human drug transport studies. Human adenocarcinoma-derived intestinal cell lines, such as Caco-2, offer conveniences of easy culture maintenance and scalability, but do not fully recapitulate in vivo intestinal phenotypes. Additional sources of renewable physiologically relevant human intestinal cells would provide a much needed tool for drug discovery and intestinal physiology. We sought to evaluate and compare two alternative sources of human intestinal cells, commercially available primary human intestinal epithelial cells (hInEpCs and induced pluripotent stem cell (iPSC-derived intestinal cells to Caco-2, for use in in vitro transwell monolayer intestinal transport assays. To achieve this for iPSC-derived cells, our previously described 3-dimensional intestinal organogenesis method was adapted to transwell differentiation. Intestinal cells were assessed by marker expression through immunocytochemical and mRNA expression analyses, monolayer integrity through Transepithelial Electrical Resistance (TEER measurements and molecule permeability, and functionality by taking advantage the well-characterized intestinal transport mechanisms. In most cases, marker expression for primary hInEpCs and iPSC-derived cells appeared to be as good as or better than Caco-2. Furthermore, transwell monolayers exhibited high TEER with low permeability. Primary hInEpCs showed molecule efflux indicative of P-glycoprotein transport. Primary hInEpCs and iPSC-derived cells also showed neonatal Fc receptor-dependent binding of immunoglobulin G variants. Primary hInEpCs and iPSC-derived intestinal cells exhibit expected marker expression and demonstrate basic functional monolayer formation, similar to or better than Caco-2. These cells could offer an alternative source of human intestinal cells for understanding normal intestinal epithelial physiology and drug transport.

  5. Acamprosate permeability across Caco-2 cell monolayer is predominantly paracellular

    DEFF Research Database (Denmark)

    Antonescu, Irina-Elena; Steffansen, Bente

    Background. The human oral bioavailability (BA) of acamprosate is 11% and its oral absorption is permeability limited (BCS class III). Acamprosate is not metabolized, therefore it’s BA has the same nominal value as its fraction absorbed (fa). It is however controversial whether the intestinal...... in the different regions of the rodent small intestine and colon. Biopharm Drug Dispos. 2017;38(2):94-114. 2. Avdeef A. Leakiness and size exclusion of paracellular channels in cultured epithelial cell monolayers-interlaboratory comparison. Pharm Res. 2010;27(3):480-9. 3. Avdeef A. Absorption and Drug Development...

  6. Simulating kinetic parameters in transporter mediated permeability across Caco-2 cells. A case study on estrange-3-sulphate

    DEFF Research Database (Denmark)

    Rolsted, Kamilla; Rapin, Nicolas; Steffansen, Bente

    2011-01-01

    Substances that compete for the same saturable intestinal transporters may when dosed together lead to altered permeability and hence influence bioavailability. The aim was to simulate kinetic parameters, i.e. K(m) and J(max), for transporter mediated E(1)S permeability across Caco-2 cells...

  7. The fraction dose absorbed, in humans, and high jejunal human permeability relationship.

    Science.gov (United States)

    Dahan, Arik; Lennernäs, Hans; Amidon, Gordon L

    2012-06-04

    The drug intestinal permeability (P(eff)) measure has been widely used as one of the main factors governing both the rate and/or extent of drug absorption (F(abs)) in humans following oral administration. In this communication we emphasize the complexity behind and the care that must be taken with this in vivo P(eff) measurement. Intestinal permeability, considering the whole of the human intestine, is more complex than generally recognized, and this can lead to misjudgment regarding F(abs) and P(eff) in various settings, e.g. drug discovery, formulation design, drug development and regulation. Setting the adequate standard for the low/high permeability class boundary, the different experimental methods for the permeability measurement, and segmental-dependent permeability throughout the human intestine due to different mechanisms are some of the main points that are discussed. Overall, the use of jejunal P(eff) as a surrogate for extent of absorption is sound and scientifically justified; a compound with high jejunal P(eff) will have high F(abs), eliminating the risk for misclassification as a BCS class I drug. Much more care should be taken, however, when jejunal P(eff) does not support a high-permeability classification; a thorough examination may reveal high-permeability after all, attributable to e.g. segmental-dependent permeability due to degree of ionization or transporter expression. In this situation, the use of multiple permeability experimental methods, including the use of metabolism, which except for luminal degradation requires absorption, is prudent and encouraged.

  8. The role of CDX2 in intestinal homeostasis and inflammation

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Troelsen, Jesper Thorvald; Nielsen, Ole Haagen

    2011-01-01

    a causal role in a large number of diseases and developmental disorders. Inflammatory bowel disease (IBD) is characterized by a chronically inflamed mucosa caused by dysregulation of the intestinal immune homeostasis. The aetiology of IBD is thought to be a combination of genetic and environmental factors......, including luminal bacteria. The Caudal-related homeobox transcription factor 2 (CDX2) is critical in early intestinal differentiation and has been implicated as a master regulator of the intestinal homeostasis and permeability in adults. When expressed, CDX2 modulates a diverse set of processes including...... of the intestinal homeostasis and further to reveal its potential role in inflammation....

  9. Abnormal Head Position

    Science.gov (United States)

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Abnormal Head Position En Español Read in Chinese What is an abnormal head posture? An abnormal or compensatory head posture occurs ...

  10. Determination of Regional Intestinal Permeability of Diclofenac and ...

    African Journals Online (AJOL)

    phosphate (KH2PO4) aqueous solution, adjusted to pH 7.0 using 0.2 N sodium hydroxide (NaOH) solution, and to .... The pH of buffer was adjusted to 7.4 by ortho-phosphoric acid. Perfusion medium was freshly prepared and then filtered through 0.45 µm membrane filter. ... exposed and cannulated with flexible PVC tubing.

  11. Chenodeoxycholic acid reduces intestinal permeability in newly weaned piglets

    NARCIS (Netherlands)

    Meer, van der Y.; Gerrits, W.J.J.; Bosch, van den M.; Holst, J.J.; Moreto, M.; Buurman, W.A.; Kulik, W.; Kempen, van T.A.T.G.

    2012-01-01

    Piglets are highly susceptible to gut health-related problems. Intravenously administered chenodeoxycholic acid (CDCA) affects gut health mediated through glucagon-like peptide 2 (GLP-2). To test whether CDCA is a suitable feed additive for improving gut health, a trial was performed with newly

  12. Chenodeoxycholic acid reduces intestinal permeability in newly weaned piglets

    DEFF Research Database (Denmark)

    van der Meer, Y; Gerrits, W J J; van den Bosch, M

    2012-01-01

    weaned (21 d) piglets offered a diet with or without 60 mg CDCA/kg feed (n = 24/treatment). Upon weaning, piglets were fasted for 16 h and then intragastrically dosed with 20 g test feed in 40 g water. Subsequently, a jugular blood sample was taken on 45, 90, 135, or 180 min for analysis of GLP-2......, and plasma GLP-2 and PYY. Serum cobalt and lactulose at day 10.5 tended to be lower in CDCA pigs compared with control pigs. Serum cobalt and lactulose concentrations were positively correlated (r = 0.67; P

  13. Drug Transporters in the Intestine

    DEFF Research Database (Denmark)

    Steffansen, Bente

    2016-01-01

    that may impact drug absorption. Thus absorptive transporters may facilitate BA of APIs that are substrates/victims for the transporters and have permeability-limited absorption, i.e. those that are classified in the biopharmaceutics classification system (BCS) Class 3 and 4. On the other hand, exsorptive...... transporters may restrict BA of APIs that are victims for these efflux transporters, especially those APIs classified to have solubility-limited absorption, i.e. compounds in BCS Class 2 and 4. The aim of the present Chapter is to review drug transporters (DTs) present within the intestine and to discuss...... and exemplify their roles in drug absorption/exsorption and in drug-drug interactions (DDIs). Although focus in the present Chapter is on DTs that are mentioned in American and European regulatory guidances, the intestinal transporters for nutrients and endogens (endogenous compounds) are also briefly...

  14. Biopharmaceutics classification of selected beta-blockers: solubility and permeability class membership.

    Science.gov (United States)

    Yang, Yongsheng; Faustino, Patrick J; Volpe, Donna A; Ellison, Christopher D; Lyon, Robbe C; Yu, Lawrence X

    2007-01-01

    The purpose of this study was to determine the permeability and solubility of seven beta-blockers (acebutolol, atenolol, labetalol, metoprolol, nadolol, sotalol, and timolol) and to classify them according to the Biopharmaceutics Classification System (BCS). Apparent permeability coefficients (Papp) were measured using the Caco-2 cell line, and the solubility was determined at 37 degrees C over a pH range of 1.0-7.5. The permeability coefficients ranged from 1.0x10(-7) to 4.8x10(-5) cm/s. On the basis of the in vitro permeability and solubility data observed in the study, labetolol, metoprolol, and timolol can be categorized as BCS Class I drugs, whereas acebutolol, atenolol, and nadolol belong to BCS Class III. The permeability coefficients in Caco-2 cells were consistent with the reported extent of intestinal absorption in humans for all drugs except sotalol. Sotalol displayed low permeability in the Caco-2 cell line, but the extent of intestinal absorption in humans is over 90%. The low permeability through the Caco-2 monolayers might be largely related to its low lipophilicity. In addition, the difference between the tightness of the intercellular junction in vivo and in vitro may partially contribute to this disparity in the sotalol permeability of in vivo and in vitro.

  15. Permeability measuremens of brazilian Eucalyptus

    Directory of Open Access Journals (Sweden)

    Marcio Rogério da Silva

    2010-09-01

    Full Text Available The permeability of Brazilian Eucalyptus grandis and Eucalyptus citriodora wood was measured in a custom build gas analysis chamber in order to determine which species could be successfully treated with preservatives. Liquid permeability was tested using an emulsion of Neen oil and a control of distillated water. Air was used to test the gas phase permeability. For both Eucalyptus grandis and Eucalyptus citriodora, the longitudinal permeability of gas was shown to be about twice as great as the liquid phase permeability. No radial permeability was observed for either wood. The permeability of air and water through the sapwood of Eucalyptus grandis was greater than that through the sapwood of Eucalyptus citriodora. The permeability of neen oil preservative through the sapwood of Eucalyptus grandis was also greater than through the sapwood of E. Citradora, but the difference was not statistically significant. Scanning Electron Microscopy images showed that the distribution and obstruction in the vessels could be correlated with observed permeability properties. Irrespective of the causes of differences in permeability between the species, the fluid phase flux through the sapwood of both species was significant, indicating that both Eucalyptus grandis and Eucalyptus citriodora could be successfully treated with wood preservative.

  16. FLLL32, a curcumin analog, ameliorates intestinal injury in necrotizing enterocolitis.

    Science.gov (United States)

    Eckert, Jeffrey; Scott, Brian; Lawrence, Shelley M; Ihnat, Michael; Chaaban, Hala

    2017-01-01

    Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease that primarily affects premature infants. It is characterized by inflammation and leukocyte infiltration that can progress to intestinal necrosis, perforation, systemic inflammatory response, and death. In this study, we examined the effect of FLLL32, a curcumin analog, on an NEC-like neonatal intestinal injury model. NEC was induced in CD-1 mice pups using the Paneth cell ablation and Klebsiella infection model. Pups were divided into sham, NEC, and NEC + FLLL32 groups. At the end of the experiment, pups were euthanized; whole blood and small intestines were harvested. Intestinal inflammatory cytokine profile, in vivo intestinal permeability using serum fluorescein isothiocyanate-dextran, and histological injury scores were compared between the groups. FLLL32-treated pups had lower intestinal injury, improved intestinal permeability, and lower proinflammatory cytokine profiles compared to those in untreated pups with NEC. These results suggest that FLLL32 plays a protective role in NEC.

  17. Regulation of Intestinal Homeostasis by Innate Immune Cells

    OpenAIRE

    Kayama, Hisako; Nishimura, Junichi; Takeda, Kiyoshi

    2013-01-01

    The intestinal immune system has an ability to distinguish between the microbiota and pathogenic bacteria, and then activate pro-inflammatory pathways against pathogens for host defense while remaining unresponsive to the microbiota and dietary antigens. In the intestine, abnormal activation of innate immunity causes development of several inflammatory disorders such as inflammatory bowel diseases (IBD). Thus, activity of innate immunity is finely regulated in the intestine. To date, multiple...

  18. Innovative Parenteral and Enteral Nutrition Therapy for Intestinal Failure

    OpenAIRE

    Le, Hau D.; Fallon, Erica M.; de Meijer, Vincent E.; Malkan, Alpin D.; Puder, Mark; Gura, Kathleen M.

    2010-01-01

    Children with intestinal failure suffer from insufficient intestinal length or function, making them dependent on parenteral nutrition (PN) for growth and survival. PN and its components are associated with many complications ranging from simple electrolyte abnormalities to life-threatening PN-associated liver disease, which is also called intestinal failure-associated liver disease (ILALD). From a nutrition perspective, the ultimate goal is to provide adequate caloric requirements and make t...

  19. Low Permeability Polyimide Insulation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Resodyn Technologies proposes a new technology that enables the application of polyimide based cryogenic insulation with low hydrogen permeability. This effort...

  20. Causality of small and large intestinal microbiota in weight regulation and insulin resistance.

    Science.gov (United States)

    Scheithauer, Torsten P M; Dallinga-Thie, Geesje M; de Vos, Willem M; Nieuwdorp, Max; van Raalte, Daniël H

    2016-09-01

    The twin pandemics of obesity and Type 2 diabetes (T2D) are a global challenge for health care systems. Changes in the environment, behavior, diet, and lifestyle during the last decades are considered the major causes. A Western diet, which is rich in saturated fat and simple sugars, may lead to changes in gut microbial composition and physiology, which have recently been linked to the development of metabolic diseases. We will discuss evidence that demonstrates the influence of the small and large intestinal microbiota on weight regulation and the development of insulin resistance, based on literature search. Altered large intestinal microbial composition may promote obesity by increasing energy harvest through specialized gut microbes. In both large and small intestine, microbial alterations may increase gut permeability that facilitates the translocation of whole bacteria or endotoxic bacterial components into metabolic active tissues. Moreover, changed microbial communities may affect the production of satiety-inducing signals. Finally, bacterial metabolic products, such as short chain fatty acids (SCFAs) and their relative ratios, may be causal in disturbed immune and metabolic signaling, notably in the small intestine where the surface is large. The function of these organs (adipose tissue, brain, liver, muscle, pancreas) may be disturbed by the induction of low-grade inflammation, contributing to insulin resistance. Interventions aimed to restoring gut microbial homeostasis, such as ingestion of specific fibers or therapeutic microbes, are promising strategies to reduce insulin resistance and the related metabolic abnormalities in obesity, metabolic syndrome, and type 2 diabetes. This article is part of a special issue on microbiota.

  1. Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

    Science.gov (United States)

    Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

    2016-07-01

    Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

  2. Harnessing the intestinal microbiome for optimal therapeutic immunomodulation

    OpenAIRE

    Viaud, S.; Daillere, R.; Boneca, I. G.; Lepage, Patricia; Pittet, M. J.; Ghiringhelli, F.; Trinchieri, G.; Goldszmid, R.; Zitvogel, L.

    2014-01-01

    Distinct cytotoxic agents currently used in the oncological armamentarium mediate their clinical benefit by influencing, directly or indirectly, the immune system in such a way that innate and adaptive immunity contributes to the tumoricidal activity. Now, we bring up evidence that both arms of anticancer immunity can be triggered through the intervention of the intestinal microbiota. Alkylating agents, such as cyclophosphamide, set up the stage for enhanced permeability of the small intestin...

  3. Autophagy and tight junction proteins in the intestine and intestinal diseases

    Directory of Open Access Journals (Sweden)

    Chien-An A. Hu

    2015-09-01

    Full Text Available The intestinal epithelium (IE forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus and antigens. The apical intercellular tight junctions (TJ are responsible for the paracellular barrier function and regulate trans-epithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease (IBD, necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy (self-eating mechanism is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis. Dysregulated autophagy has been shown to be directly associated with many pathological processes, including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2, a cation-selective, pore-forming, transmembrane TJ protein, for lysosome (autophagy-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines (for example, tumor necrosis factor-α, interleukin-6

  4. Transverse permeability of woven fabrics

    NARCIS (Netherlands)

    Grouve, Wouter Johannes Bernardus; Akkerman, Remko; Loendersloot, Richard; van den Berg, S.

    2008-01-01

    The transverse permeability is an essential input in describing the consolidation process of CETEX® laminates. A two-dimensional, finite difference based, Stokes flow solver has been developed to determine the mesoscopic permeability of arbitrary fabric structures. The use of a multigrid solver

  5. Intestinal pseudo-obstruction

    Science.gov (United States)

    Primary intestinal pseudo-obstruction; Acute colonic ileus; Colonic pseudo-obstruction; Idiopathic intestinal pseudo-obstruction; Ogilvie syndrome; Chronic intestinal pseudo-obstruction; Paralytic ileus - pseudo-obstruction

  6. Electrokinetic effects and fluid permeability

    International Nuclear Information System (INIS)

    Berryman, J.G.

    2003-01-01

    Fluid permeability of porous media depends mainly on connectivity of the pore space and two physical parameters: porosity and a pertinent length-scale parameter. Electrical imaging methods typically establish connectivity and directly measure electrical conductivity, which can then often be related to porosity by Archie's law. When electrical phase measurements are made in addition to the amplitude measurements, information about the pertinent length scale can then be obtained. Since fluid permeability controls the ability to flush unwanted fluid contaminants from the subsurface, inexpensive maps of permeability could improve planning strategies for remediation efforts. Detailed knowledge of fluid permeability is also important for oil field exploitation, where knowledge of permeability distribution in three dimensions is a common requirement for petroleum reservoir simulation and analysis, as well as for estimates on the economics of recovery

  7. Differential expression and novel permeability properties of three aquaporin 8 paralogs from seawater-challenged Atlantic salmon smolts

    DEFF Research Database (Denmark)

    Engelund, Morten Buch; Chauvigné, François; Christensen, Birgitte M

    2013-01-01

    paralog. Immunofluorescence microscopy localized Aqp8aa(1+2) to intracellular compartments of the liver and intestine, and Aqp8ab and Aqp8b to apical plasma membrane domains of the intestinal epithelium, with Aqp8b also in goblet cells. In a control experiment with rainbow trout, immunoelectron microscopy...... confirmed abundant labeling of Aqp8ab and -8b at apical plasma membranes of enterocytes in the middle intestine and also in subapical vesicular structures. During SW-challenge, Aqp8ab showed significantly increased levels of protein expression in plasma membrane enriched fractions of the intestine...... of SW challenged smolts. All three Aqp8 paralogs were permeable to water and urea, whereas Aqp8ab and -8b were, surprisingly, also permeable to glycerol. The mRNA tissue distribution of each paralog was distinct although some tissues, such as the intestine showed redundant expression of more than one...

  8. Regulation of intestinal homeostasis by innate immune cells.

    Science.gov (United States)

    Kayama, Hisako; Nishimura, Junichi; Takeda, Kiyoshi

    2013-12-01

    The intestinal immune system has an ability to distinguish between the microbiota and pathogenic bacteria, and then activate pro-inflammatory pathways against pathogens for host defense while remaining unresponsive to the microbiota and dietary antigens. In the intestine, abnormal activation of innate immunity causes development of several inflammatory disorders such as inflammatory bowel diseases (IBD). Thus, activity of innate immunity is finely regulated in the intestine. To date, multiple innate immune cells have been shown to maintain gut homeostasis by preventing inadequate adaptive immune responses in the murine intestine. Additionally, several innate immune subsets, which promote Th1 and Th17 responses and are implicated in the pathogenesis of IBD, have recently been identified in the human intestinal mucosa. The demonstration of both murine and human intestinal innate immune subsets contributing to regulation of adaptive immunity emphasizes the conserved innate immune functions across species and might promote development of the intestinal innate immunity-based clinical therapy.

  9. Intestinal myiasis

    Directory of Open Access Journals (Sweden)

    U S Udgaonkar

    2012-01-01

    Full Text Available Purpose: Intestinal myiasis is a condition when the fly larvae inhabit the gastrointestinal tract and are passed out in faeces. This type of infestation results when eggs or larvae of the fly, deposited on food are inadvertently taken by man. They survive the unfavourable conditions within the gastrointestinal tract and produce disturbances, which may vary from mild to severe. The condition is not uncommon and is often misdiagnosed as pinworm infestation. Correct diagnosis by the clinical microbiologist is important to avoid unnecessary treatment. Materials and Methods: We had 7 cases of intestinal myiasis. In 2 cases the larvae were reared to adult fly in modified meat and sand medium (developed by Udgaonkar. This medium is simple and can be easily prepared in the laboratory. Results: Of the 7 larvae, 5 were Sarcophaga haemorrhoidalis, 1 Megaselia species and 1 was identified as Muscina stabulans. Conclusions: S. haemorrhoidalis was the commonest maggot involved. A high index of suspicion is required for clinical diagnosis when the patient complains of passing wriggling worms in faeces for a long period without any response to antihelminthics. The reason for long duration of illness and recurrence of infestation is baffling. The nearest to cure was colonic wash. We feel prevention is of utmost importance, which is to avoid eating food articles with easy access to flies.

  10. Intestinal lymphangiectasia in dogs, challenging diagnosis: Four cases

    Directory of Open Access Journals (Sweden)

    Davitkov Darko

    2017-01-01

    Full Text Available Intestinal lymphangiectasia is an uncommon disease which can cause severe, chronic protein-losing enteropathy in dogs. Four dogs were presented at the Belgrade Clinic for Small Animals with clinical signs of chronic diarrhea, lethargy, anorexia, vomiting and weight loss. Abnormal physical examination findings included dehydration, signs of pain on abdominal palpation, and ascites. The most important clinicopathological findings were lymphopenia and hypoproteinemia with hypoalbuminemia. Abdominal ultrasound revealed intestinal abnormalities in all dogs. To establish an undoubted diagnosis of intestinal lymphangiectasia, endoscopy and histopathology were conducted. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III46002

  11. Tooth - abnormal colors

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003065.htm Tooth - abnormal colors To use the sharing features on this page, please enable JavaScript. Abnormal tooth color is any color other than white to yellowish- ...

  12. Urine - abnormal color

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  13. Abnormal uterine bleeding

    Science.gov (United States)

    Anovulatory bleeding; Abnormal uterine bleeding - hormonal; Polymenorrhea - dysfunctional uterine bleeding ... ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Reaffirmed 2015. ACOG. ...

  14. Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based on Caco-2.

    Science.gov (United States)

    Lozoya-Agullo, Isabel; Gonzalez-Alvarez, Isabel; Zur, Moran; Fine-Shamir, Noa; Cohen, Yael; Markovic, Milica; Garrigues, Teresa M; Dahan, Arik; Gonzalez-Alvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival; Avdeef, Alex

    2017-12-29

    The effective rat intestinal permeability (P eff ) was deconvolved using a biophysical model based on parameterized paracellular, aqueous boundary layer, transcellular permeabilities, and the villus-fold surface area expansion factor. Four types of rat intestinal perfusion data were considered: single-pass intestinal perfusion (SPIP) in the jejunum (n = 40), and colon (n = 15), closed-loop (Doluisio type) in the small intestine (n = 78), and colon (n = 74). Moreover, in vitro Caco-2 permeability values were used to predict rat in vivo values in the rat data studied. Comparable number of molecules permeate via paracellular water channels as by the lipoidal transcellular route in the SPIP method, although in the closed-loop method, the paracellular route appears dominant in the colon. The aqueous boundary layer thickness in the small intestine is comparable to that found in unstirred in vitro monolayer assays; it is thinner in the colon. The mucosal surface area in anaesthetized rats is 0.96-1.4 times the smooth cylinder calculated value in the colon, and it is 3.1-3.6 times in the small intestine. The paracellular permeability of the intestine appeared to be greater in rat than human, with the colon showing more leakiness (higher P para ) than the small intestine. Based on log intrinsic permeability values, the correlations between the in vitro and in vivo models ranged from r 2 0.82 to 0.92. The SPIP-Doluisio method comparison indicated identical log permeability selectivity trend with negligible bias.

  15. Permeability testing of biomaterial membranes

    Energy Technology Data Exchange (ETDEWEB)

    Dreesmann, L; Hajosch, R; Nuernberger, J Vaz; Schlosshauer, B [NMI Natural and Medical Sciences Institute at University Tuebingen, Markwiesenstr. 55, D-72770 Reutlingen (Germany); Ahlers, M [GELITA AG, Gammelsbacher Str. 2, D-69412 Eberbach (Germany)], E-mail: schlosshauer@nmi.de

    2008-09-01

    The permeability characteristics of biomaterials are critical parameters for a variety of implants. To analyse the permeability of membranes made from crosslinked ultrathin gelatin membranes and the transmigration of cells across the membranes, we combined three technical approaches: (1) a two-chamber-based permeability assay, (2) cell culturing with cytochemical analysis and (3) biochemical enzyme electrophoresis (zymography). Based on the diffusion of a coloured marker molecule in conjunction with photometric quantification, permeability data for a gelatin membrane were determined in the presence or absence of gelatin degrading fibroblasts. Cytochemical evaluation after cryosectioning of the membranes was used to ascertain whether fibroblasts had infiltrated the membrane inside. Zymography was used to investigate the potential release of proteases from fibroblasts, which are known to degrade collagen derivatives such as gelatin. Our data show that the diffusion equilibrium of a low molecular weight dye across the selected gelatin membrane is approached after about 6-8 h. Fibroblasts increase the permeability due to cavity formation in the membrane inside without penetrating the membrane for an extended time period (>21 days in vitro). Zymography indicates that cavity formation is most likely due to the secretion of matrix metalloproteinases. In summary, the combination of the depicted methods promises to facilitate a more rational development of biomaterials, because it provides a rapid means of determining permeability characteristics and bridges the gap between descriptive methodology and the mechanistic understanding of permeability alterations due to biological degradation.

  16. Permeability testing of biomaterial membranes

    International Nuclear Information System (INIS)

    Dreesmann, L; Hajosch, R; Nuernberger, J Vaz; Schlosshauer, B; Ahlers, M

    2008-01-01

    The permeability characteristics of biomaterials are critical parameters for a variety of implants. To analyse the permeability of membranes made from crosslinked ultrathin gelatin membranes and the transmigration of cells across the membranes, we combined three technical approaches: (1) a two-chamber-based permeability assay, (2) cell culturing with cytochemical analysis and (3) biochemical enzyme electrophoresis (zymography). Based on the diffusion of a coloured marker molecule in conjunction with photometric quantification, permeability data for a gelatin membrane were determined in the presence or absence of gelatin degrading fibroblasts. Cytochemical evaluation after cryosectioning of the membranes was used to ascertain whether fibroblasts had infiltrated the membrane inside. Zymography was used to investigate the potential release of proteases from fibroblasts, which are known to degrade collagen derivatives such as gelatin. Our data show that the diffusion equilibrium of a low molecular weight dye across the selected gelatin membrane is approached after about 6-8 h. Fibroblasts increase the permeability due to cavity formation in the membrane inside without penetrating the membrane for an extended time period (>21 days in vitro). Zymography indicates that cavity formation is most likely due to the secretion of matrix metalloproteinases. In summary, the combination of the depicted methods promises to facilitate a more rational development of biomaterials, because it provides a rapid means of determining permeability characteristics and bridges the gap between descriptive methodology and the mechanistic understanding of permeability alterations due to biological degradation

  17. Intestinal Failure (Short Bowel Syndrome)

    Science.gov (United States)

    Intestinal Failure (Short Bowel Syndrome) What is intestinal failure? Intestinal failure occurs when a significant portion of the small ... intestine does. Who is at risk for intestinal failure? N Babies (usually premature) who have had surgery ...

  18. Permeability of protective coatings to tritium

    International Nuclear Information System (INIS)

    Braun, J.M.

    1987-10-01

    The permeability of four protective coatings to tritium gas and tritiated water was investigated. The coatings, including two epoxies, one vinyl and one urethane, were selected for their suitability in CANDU plant service in Ontario Hydro. Sorption rates of tritium gas into the coatings were considerably larger than for tritiated water, by as much as three to four orders of magnitude. However, as a result of the very large solubility of tritiated water in the coatings, the overall permeability to tritium gas and tritiated water are comparable, being somewhat larger for HTO. Marked differences were also evident among the four coatings, the vinyl proving to be unique in behaviour and morphology. Because of a highly porous surface structure water condensation takes place at high relative humidities, leading to an abnormally high retention of free water. Desorption rates from the four coatings were otherwise quite similar. Of practical importance was the observation that more effective desorption of tritiated water could be carried out at relatively high humidities, in this case 60%. It was believed that isotopic exchange was responsible for this phenomenon. It appears that epoxy coatings having a high pigment-to-binder ratio are most suited for coating concrete in tritium handling facilities

  19. Evaluation of the membrane permeability (PAMPA and skin) of benzimidazoles with potential cannabinoid activity and their relation with the Biopharmaceutics Classification System (BCS).

    Science.gov (United States)

    Alvarez-Figueroa, M Javiera; Pessoa-Mahana, C David; Palavecino-González, M Elisa; Mella-Raipán, Jaime; Espinosa-Bustos, Cristián; Lagos-Muñoz, Manuel E

    2011-06-01

    The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P(oct) value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).

  20. Geothermal Permeability Enhancement - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Joe Beall; Mark Walters

    2009-06-30

    The overall objective is to apply known permeability enhancement techniques to reduce the number of wells needed and demonstrate the applicability of the techniques to other undeveloped or under-developed fields. The Enhanced Geothermal System (EGS) concept presented in this project enhances energy extraction from reduced permeability zones in the super-heated, vapor-dominated Aidlin Field of the The Geysers geothermal reservoir. Numerous geothermal reservoirs worldwide, over a wide temperature range, contain zones of low permeability which limit the development potential and the efficient recovery of heat from these reservoirs. Low permeability results from poorly connected fractures or the lack of fractures. The Enhanced Geothermal System concept presented here expands these technologies by applying and evaluating them in a systematic, integrated program.

  1. Membrane permeability in the gastrointestinal tract: the interplay between microclimate pH and transporters.

    Science.gov (United States)

    Kristl, Albin

    2009-11-01

    Some examples of pH- and transporter-dependent permeability, determined in side-by-side diffusion cells, are summarized. We investigated the polarized transport in the mucosal-to-serosal direction of monocarboxylic acid-type drugs through the excised rat jejunal tissue and an artificial membrane. We established that, in vitro, these substances are most probably not transported by monocarboxylate transporter 1, but by passive pH-dependent transport. We also studied various influences on the permeability of fluorescein, a low permeability marker, through isolated rat intestinal segments, Caco-2 cell monolayers, and an artificial membrane. Polarized transport of fluorescein in the serosal-to-mucosal direction through the rat jejunum by multidrug resistance-associated protein was triggered by the addition of D-glucose to the mucosal side, while the pH-dependent increase of fluorescein influx is presumably the consequence of a monocarboxylate transporter and a member of the organic-anion transporting polypeptide family. With permeability experiments through the excised segments of rat small intestine, we ascertained that ciprofloxacin is a low-permeability drug and has higher and pH-dependent transport in the mucosal-to-serosal direction than in the opposite direction. We also established that neither the permeability of fluoroquinolones nor their solubility in different buffers was influenced by the interactions with metal cations.

  2. The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis

    Science.gov (United States)

    Cipriani, Sabrina; Mencarelli, Andrea; Chini, Maria Giovanna; Distrutti, Eleonora; Renga, Barbara; Bifulco, Giuseppe; Baldelli, Franco; Donini, Annibale; Fiorucci, Stefano

    2011-01-01

    Background GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. Aims To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. Methods Colitis was induced in wild type and GP-BAR1−/− mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. Results GP-BAR1−/− mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. Conclusions GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand. PMID:22046243

  3. The bile acid receptor GPBAR-1 (TGR5 modulates integrity of intestinal barrier and immune response to experimental colitis.

    Directory of Open Access Journals (Sweden)

    Sabrina Cipriani

    Full Text Available BACKGROUND: GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. AIMS: To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. METHODS: Colitis was induced in wild type and GP-BAR1(-/- mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. RESULTS: GP-BAR1(-/- mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. CONCLUSIONS: GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand.

  4. Bacteria, bile salts, and intestinal monosaccharide malabsorption

    Science.gov (United States)

    Gracey, Michael; Burke, Valerie; Oshin, Ademola; Barker, Judith; Glasgow, Eric F.

    1971-01-01

    Intestinal monosaccharide transport was studied in a series of rats with a self-filling jejunal blind loop using 3mM arbutin (p-hydroxyphenyl-B-glucoside) or 1mM D-fructose as substrate in vitro and 10 mM arbutin or 5mM D-fructose in vivo. These results were compared with changes in the bacterial flora and state of conjugation of intraluminal bile salts in those animals. Observations were also made of the microscopic and ultrastructural appearances of the small-intestinal epithelium. In the small intestine of blind-loop rats intestinal monosaccharide transport is impaired, and in vitro is most marked in the blind loop, less so in the efferent jejunum, and not significantly altered in the afferent jejunum. A similar pattern of disturbed monosaccharide absorption was demonstrated by perfusions in vivo. The degree of the transport defect correlates closely with the luxuriance of the anaerobic flora, which averaged 108 per millilitre in the blind loop, 107 in the efferent jejunum, and 106 in the afferent jejunum. A similar pattern of abnormality of bile salt conjugation occurred. In the blind loop the ratio of free to conjugated bile salts was grossly abnormal; this disturbance was somewhat less marked in the efferent jejunum and considerably less in the intraluminal contents of the afferent jejunum. An irregularly distributed lesion, consisting of swelling and vacuolation of microvilli and intracellular organelles, was demonstrated in the small-intestinal epithelium of blind-loop animals. Impaired absorption of monosaccharides is a further consequence of bacterial contamination of the upper gut. It is suggested that this defect is caused by the presence of high levels of deconjugated bile salts produced by an abnormal anaerobic bacterial flora in the small intestine. ImagesFig. 3Fig. 4 PMID:4329096

  5. Clinical, clinicopathologic, radiographic, and ultrasonographic characteristics of intestinal lymphangiectasia in dogs: 17 cases (1996-1998).

    Science.gov (United States)

    Kull, P A; Hess, R S; Craig, L E; Saunders, H M; Washabau, R J

    2001-07-15

    To characterize the clinical, clinicopathologic, and imaging findings in dogs with intestinal lymphangiectasia and to compare the histologic grade of lymphangiectasia with clinicopathologic and imaging abnormalities. Retrospective study. 17 dogs with a histologic diagnosis of intestinal lymphangiectasia. Medical records of dogs with a histologic diagnosis of intestinal lymphangiectasia were reviewed for signalment, history, clinical signs, results of exploratory laparotomy, and clinicopathologic, radiographic, ultrasonographic, and histologic findings. Mean age of dogs was 8.3 years; the most common clinical signs were diarrhea, anorexia, lethargy, vomiting, and weight loss. Abnormal physical examination findings included dehydration, ascites, and signs of pain on palpation of the abdomen. The most notable clinicopathologic findings were low serum ionized calcium concentration and hypoalbuminemia. Abdominal ultrasonography was performed in 12 dogs and revealed intestinal abnormalities in 8 dogs and peritoneal effusion in 7 dogs. Exploratory laparotomy revealed abnormalities in 9 of 16 dogs including thickened small intestine, dilated lacteals, lymphadenopathy, and adhesions. On histologic examination of the small intestine, concurrent inflammation was observed in 15 of 17 dogs, crypt ectasia in 5 of 17, and lipogranulomas in 2 of 17. Intestinal lymphangiectasia in dogs appears to be a heterogeneous disorder characterized by various degrees of panhypoproteinemia, hypocholesterolemia, lymphocytopenia, and imaging abnormalities. In most dogs, the severity of hypoalbuminemia appears to offer the best correlation with severity of histologic lesions of lymphangiectasia. Imaging abnormalities are common in dogs with intestinal lymphangiectasia but are not specific enough to differentiate this disorder from other gastrointestinal disorders, nor are they predictive of histologic severity.

  6. Abnormalities of intestinal rotation and congenital intrinsic duodenal ...

    African Journals Online (AJOL)

    of further subsequent operative treatment. Ann Pediatr. Surg 9:61–64 c 2013 Annals of Pediatric Surgery. Annals of Pediatric Surgery 2013, 9:61–64. Keywords: congenital duodenal obstruction, duodenal diaphragm, malrotation, situs inversus. Department of Pediatric Surgery, Maternity and Children Hospital, Dammam,.

  7. Abnormal gastric and small intestinal motor function in diabetes mellitus

    NARCIS (Netherlands)

    Samsom, M.; Smout, A. J.

    1997-01-01

    It is now well recognized that the prevalence of delayed gastric emptying in both insulin-dependent as well as noninsulin-dependent diabetes mellitus is high. Recently performed studies have shown that motor disorders of several parts of the upper gastrointestinal tract contribute to this delay in

  8. Acute high-intensity interval running increases markers of gastrointestinal damage and permeability but not gastrointestinal symptoms.

    Science.gov (United States)

    Pugh, Jamie N; Impey, Samuel G; Doran, Dominic A; Fleming, Simon C; Morton, James P; Close, Graeme L

    2017-09-01

    The purpose of this study was to investigate the effects of high-intensity interval running on markers of gastrointestinal (GI) damage and permeability alongside subjective symptoms of GI discomfort. Eleven male runners completed an acute bout of high-intensity interval training (HIIT) (eighteen 400-m runs at 120% maximal oxygen uptake) where markers of GI permeability, intestinal damage, and GI discomfort symptoms were assessed and compared with resting conditions. Compared with rest, HIIT significantly increased serum lactulose/rhamnose ratio (0.051 ± 0.016 vs. 0.031 ± 0.021, p = 0.0047; 95% confidence interval (CI) = 0.006 to 0.036) and sucrose concentrations (0.388 ± 0.217 vs. 0.137 ± 0.148 mg·L -1 ; p HIIT and resting conditions. Plasma intestinal-fatty acid binding protein (I-FABP) was significantly increased (p HIIT whereas no changes were observed during rest. Mild symptoms of GI discomfort were reported immediately and at 24 h post-HIIT, although these symptoms did not correlate to GI permeability or I-FABP. In conclusion, acute HIIT increased GI permeability and intestinal I-FABP release, although these do not correlate with symptoms of GI discomfort. Furthermore, by using serum sampling, we provide data showing that it is possible to detect changes in intestinal permeability that is not observed using urinary sampling over a shorter time-period.

  9. Defining Abnormally Low Tenders

    DEFF Research Database (Denmark)

    Ølykke, Grith Skovgaard; Nyström, Johan

    2017-01-01

    The concept of an abnormally low tender is not defined in EU public procurement law. This article takes an interdisciplinary law and economics approach to examine a dataset consisting of Swedish and Danish judgments and verdicts concerning the concept of an abnormally low tender. The purpose...

  10. Biopharmaceutics classification system: validation and learnings of an in vitro permeability assay.

    Science.gov (United States)

    Thiel-Demby, Victoria E; Humphreys, Joan E; St John Williams, Lisa A; Ellens, Harma M; Shah, Nipa; Ayrton, Andrew D; Polli, Joseph W

    2009-01-01

    The Biopharmaceutics Classification System (BCS) is the scientific basis for classifying drugs based on their aqueous solubility and intestinal permeability that supports in vivo bioavailability and bioequivalence waivers for immediate-release solid dosage form drugs. One requirement of the BCS is that the permeability method must be validated. In order to accommodate the variety of in vitro/in situ permeability models, the BCS Guidance gives a general framework for the validation requirements, necessitating implemented experimental details to be selected by the applicant laboratory. The objective of this work was to define the parameters for a cell based in vitro permeability method (e.g., cell type, pH, transport direction, time, and concentration) and validate the method to support formal BCS classification of drugs. Twenty reference drugs were selected and permeability values determined using the Madin-Darby canine kidney type II cell line heterologously expressing the human P-glycoprotein transporter (MDCKII-MDR1). A rank order relationship was established between the in vitro permeability value and human intestinal absorption values. This relationship was as predicted and validates the MDCKII-MDR1 permeability method as defined by the BCS Guidance. The final validated in vitro permeability method employs the MDCKII-MDR1 cell line incubated with the Pgp inhibitor GF120918. It is a unidirectional apical-to-basolateral transport assay performed at apical pH values of 5.5 and 7.4 and a basolateral pH of 7.4. Four reference standards (metoprolol, pindolol, labetalol and ranitidine) dosed and analyzed as a single cassette are included in each experiment. A strategy on selection of drug concentrations and on how to deal with problematic compounds (i.e., those suffering from poor mass balance) is discussed.

  11. High-fat Diet-induced Intestinal Hyperpermeability is Associated with Increased Bile Acids in the Large Intestine of Mice.

    Science.gov (United States)

    Murakami, Yuki; Tanabe, Soichi; Suzuki, Takuya

    2016-01-01

    Metabolic syndrome is characterized by low-grade chronic systemic inflammation, which is associated with intestinal hyperpermeability. This study examined the effects of 3 high-fat diets (HFDs) composed of different fat sources (soybean oil and lard) on the intestinal permeability, tight junction (TJ) protein expression, and cecal bile acid (BA) concentrations in mice, and then analyzed their interrelations. C57/BL6 mice were fed the control diet, HFD (soybean oil), HFD (lard), and HFD (mix; containing equal concentrations of soybean oil and lard) for 8 wk. Glucose tolerance, intestinal permeability, TJ protein expression, and cecal BA concentration were evaluated. Feeding with the 3 HDFs similarly increased body weight, liver weight, and fat pad weight, and induced glucose intolerance and intestinal hyperpermeability. The expression of TJ proteins, zonula occludens-2 and junctional adhesion molecule-A, were lower in the colons of the 3 HFD groups than in the control group (P acid and ω-muricholic acids, were detected (P < 0.05). These results suggest that the HFD-induced intestinal hyperpermeability is associated with increased BA secretion. The abundance of SBAs in the large intestine may be responsible for the hyperpermeability. © 2015 Institute of Food Technologists®

  12. Plant abnormality diagnosis device

    International Nuclear Information System (INIS)

    Saeki, Akira.

    1992-01-01

    The device of the present invention diagnose an abnormal event occurred in a large-scaled plant, such as a nuclear power plant. The device comprises the following four functions. (1) Abnormality candidates are estimated based on an intelligence base storing characteristics established between the characteristics/functions and physical amounts of the plant components, and detected abnormality and measured values. Among the candidates, one which coincidents with the measured value such as an actual process amount is judged as a first cause. (2) In addition, a real time plant behavior is estimated based on parameters determining a plant operation mode. The candidate for the abnormality cause is estimated by the comparison between the result of the estimation and the measured value such as a process amount. (3) Characteristics established between the characteristics/functions and the physical amount of the plant components are structured stepwise thereby identifying the first abnormality cause. (4) Inactuated or failed portions of the components for restoring the abnormality to normal state are identified based on the intelligence base simultaneously with the estimation for the first abnormality cause. (I.S.)

  13. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability

    Directory of Open Access Journals (Sweden)

    Karin ede Punder

    2015-05-01

    Full Text Available Chronic non-communicable diseases (NCDs are the leading causes of work absence, disability and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here we hypothesize that stresses (defined as homeostatic disturbances can induce low-grade inflammation by increasing the availability of water, sodium and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases.

  14. Intestinal microbiome landscaping

    NARCIS (Netherlands)

    Shetty, Sudarshan A.; Hugenholtz, Floor; Lahti, Leo; Smidt, Hauke; Vos, de Willem M.

    2017-01-01

    High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for designing beneficial modulation strategies. Exemplified by the analysis of intestinal bacteria in a thousand Western adults, we discuss

  15. Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis.

    Science.gov (United States)

    Czaja, Albert J

    2016-11-14

    The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora (dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens (molecular mimicry). Activated gut-derived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as adjunctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies.

  16. Small Intestine Cancer Treatment

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  17. Chromosomal Abnormalities in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available The prevalence of fragile X syndrome, velocardiofacial syndrome (VCFS, and other cytogenetic abnormalities among 100 children (64 boys with combined type ADHD and normal intelligence was assessed at the NIMH and Georgetown University Medical Center.

  18. "Jeopardy" in Abnormal Psychology.

    Science.gov (United States)

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  19. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  20. Intestinal Epithelial Sirtuin 1 Regulates Intestinal Inflammation During Aging in Mice by Altering the Intestinal Microbiota.

    Science.gov (United States)

    Wellman, Alicia S; Metukuri, Mallikarjuna R; Kazgan, Nevzat; Xu, Xiaojiang; Xu, Qing; Ren, Natalie S X; Czopik, Agnieszka; Shanahan, Michael T; Kang, Ashley; Chen, Willa; Azcarate-Peril, M Andrea; Gulati, Ajay S; Fargo, David C; Guarente, Leonard; Li, Xiaoling

    2017-09-01

    Intestinal epithelial homeostasis is maintained by complex interactions among epithelial cells, commensal gut microorganisms, and immune cells. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD), but the mechanisms of this process are not clear. We investigated how Sirtuin 1 (SIRT1), a conserved mammalian NAD + -dependent protein deacetylase, senses environmental stress to alter intestinal integrity. We performed studies of mice with disruption of Sirt1 specifically in the intestinal epithelium (SIRT1 iKO, villin-Cre+, Sirt1 flox/flox mice) and control mice (villin-Cre-, Sirt1 flox/flox ) on a C57BL/6 background. Acute colitis was induced in some mice by addition of 2.5% dextran sodium sulfate to drinking water for 5-9 consecutive days. Some mice were given antibiotics via their drinking water for 4 weeks to deplete their microbiota. Some mice were fed with a cholestyramine-containing diet for 7 days to sequester their bile acids. Feces were collected and proportions of microbiota were analyzed by 16S rRNA amplicon sequencing and quantitative PCR. Intestines were collected from mice and gene expression profiles were compared by microarray and quantitative PCR analyses. We compared levels of specific mRNAs between colon tissues from age-matched patients with ulcerative colitis (n=10) vs without IBD (n=8, controls). Mice with intestinal deletion of SIRT1 (SIRT1 iKO) had abnormal activation of Paneth cells starting at the age of 5-8 months, with increased activation of NF-κB, stress pathways, and spontaneous inflammation at 22-24 months of age, compared with control mice. SIRT1 iKO mice also had altered fecal microbiota starting at 4-6 months of age compared with control mice, in part because of altered bile acid metabolism. Moreover, SIRT1 iKO mice with defective gut microbiota developed more severe colitis than control mice. Intestinal tissues from patients with ulcerative colitis expressed significantly lower

  1. Abnormal sound detection device

    International Nuclear Information System (INIS)

    Yamada, Izumi; Matsui, Yuji.

    1995-01-01

    Only components synchronized with rotation of pumps are sampled from detected acoustic sounds, to judge the presence or absence of abnormality based on the magnitude of the synchronized components. A synchronized component sampling means can remove resonance sounds and other acoustic sounds generated at a synchronously with the rotation based on the knowledge that generated acoustic components in a normal state are a sort of resonance sounds and are not precisely synchronized with the number of rotation. On the other hand, abnormal sounds of a rotating body are often caused by compulsory force accompanying the rotation as a generation source, and the abnormal sounds can be detected by extracting only the rotation-synchronized components. Since components of normal acoustic sounds generated at present are discriminated from the detected sounds, reduction of the abnormal sounds due to a signal processing can be avoided and, as a result, abnormal sound detection sensitivity can be improved. Further, since it is adapted to discriminate the occurrence of the abnormal sound from the actually detected sounds, the other frequency components which are forecast but not generated actually are not removed, so that it is further effective for the improvement of detection sensitivity. (N.H.)

  2. Claudins, dietary milk proteins, and intestinal barrier regulation.

    Science.gov (United States)

    Kotler, Belinda M; Kerstetter, Jane E; Insogna, Karl L

    2013-01-01

    The family of claudin proteins plays an important role in regulating the intestinal barrier by modulating the permeability of tight junctions. The impact of dietary protein on claudin biology has not been studied extensively. Whey proteins have been reported to improve intestinal barrier function, but their mechanism of action is not clear. Recent studies, however, have demonstrated increased intestinal claudin expression in response to milk protein components. Reviewed here are new findings suggesting that whey-protein-derived transforming growth factor β transcriptionally upregulates claudin-4 expression via a Smad-4-dependent pathway. These and other data, including limited clinical studies, are summarized below and, in the aggregate, suggest a therapeutic role for whey protein in diseases of intestinal barrier dysfunction, perhaps, in part, by regulating claudin expression. © 2013 International Life Sciences Institute.

  3. Hydrotropic solubilization of lipophilic drugs for oral delivery: The effects of urea and nicotinamide on carbamazepine solubility-permeability interplay

    Directory of Open Access Journals (Sweden)

    Avital Beig

    2016-10-01

    Full Text Available Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs' permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility-permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility-permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ~30-fold. A concomitant permeability decrease was evident both in-vitro and in-vivo (~17-fold for nicotinamide and ~9-fold for urea, revealing a solubility-permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility-permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility-permeability balance may promote the overall goal of the formulation to maximize oral drug exposure.

  4. Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility–Permeability Interplay

    Science.gov (United States)

    Beig, Avital; Lindley, David; Miller, Jonathan M.; Agbaria, Riad; Dahan, Arik

    2016-01-01

    Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs’ permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility–permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility–permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ∼30-fold). A concomitant permeability decrease was evident both in vitro and in vivo (∼17-fold for nicotinamide and ∼9-fold for urea), revealing a solubility–permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility–permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility–permeability balance may promote the overall goal of the formulation to maximize oral drug exposure. PMID:27826241

  5. Model prodrugs for the intestinal oligopeptide transporter

    DEFF Research Database (Denmark)

    Nielsen, C U; Andersen, R; Brodin, Birger

    2001-01-01

    The human intestinal di/tri-peptide carrier, hPepT1, has been suggested as a target for increasing intestinal transport of low permeability compounds by creating prodrugs designed for the transporter. Model ester prodrugs using the stabilized dipeptides D-Glu-Ala and D-Asp-Ala as pro...... with a pH of approximately 6.0, but still release the model drug at the intercellular and blood pH of approximately 7.4. Even though benzyl alcohol is not a low molecular weight drug molecule, these results indicate that the dipeptide prodrug principle is a promising drug delivery concept. However......, the physico-chemical properties such as electronegativity, solubility, and log P of the drug molecule may also have an influence on the potential of these kinds of prodrugs. The purpose of the present study is to investigate whether the model drug electronegativity, estimated as Taft substitution parameter...

  6. Ectopic intestinal glands after segmental small bowel irradiation in the cat

    International Nuclear Information System (INIS)

    Rubio, C.A.; Eriksson, B.; Johnsson, L.

    1983-01-01

    Following segmental irradiation of the small bowel, 5 of 64 cats demonstrated ectopic intestinal glands in the submucosal tissue. In addition, one of these 5 cats had foci of abnormal glands in the muscularis mucosae. In 2 of the 5 animals, cellular polymorphism, nucleolar irregularity and loss of cellular polarity were present in irradiation-induced ectopic intestinal glands. The review of the literature indicates that intestinal irradiation may induce intestinal adenocarcinomas with metastatic growth. The possibility that ectopic intestinal glands are precancerous lesions in the irradiated cat is discussed. (Auth.)

  7. Two Techniques of Intestinal Wall Suture in Surgical Treatment of Ileus in Dogs and the Importance of Omentalisation

    OpenAIRE

    M. Crha; J. Lorenzová; L. Urbanová; T. Fichtel; A. Nečas

    2008-01-01

    Model experimental studies focused on the intestinal suture techniques in relation to healing, postoperative narrowing of the intestinal lumen or adhesion formation can not comprise a number of clinical factors (foreign body presence in the intestine, haematological abnormalities, septic peritonitis, different age of patients, etc.) that under clinical practice conditions may have an effect on the healing of the intestinal suture. The aim of this clinical study was to confirm in a group of do...

  8. Comparison of two approaches of intestinal absorption by puerarin.

    Science.gov (United States)

    Li, Hewei; Dong, Ling; Liu, Yang; Wang, Gang; Zhang, Lei; Qiao, Yanjiang

    2014-01-01

    Everted gut sac (EGS) and in situ single-pass intestinal perfusion (SPIP) have been widely used in the study of drug absorption and biopharmaceutical classification systems (BCS). Furthermore, they could also be applied in the research of drug intestinal first-pass metabolism. Since most of Chinese herbal medicines (CHMs) are orally administrated, it is necessary to study the permeability of active ingredients of CHMs. Thus, we attempted to apply the EGS and SPIP models to study the permeability of puerarin, one of the active marker compounds (AMCs) of Puerariae Radix. In the present study, three rat models of ex vivo and in situ, EGS, SPIP, and in situ intestinal perfusion with venous sampling (IPVS), were established to determine the permeability coefficient of puerarin. The apparent permeability coefficient (Papp) was obtained by EGS. The SPIP model was used to determine the effective permeability coefficient (Peff) in different intestinal segments. The blood permeability coefficient (Pblood) was determined by IPVS. Puerarin concentration of perfusion and blood samples were measured by HPLC. Puerarin could filter into EGS incubated in aqueous extract of Puerariae Radix or puerarin solution. In the SPIP experiment, the concentration effect on Peff was observed in the ileum, but not in the other three intestinal segments. The Pblood was 0.068±0.002×10(-5)cm/s and was 16-fold lower than the Peff (1.114±0.153×10(-5)cm/s) in the IPVS experiment at 80μg/mL puerarin. As expected, the Peff (1.24±0.11×10(-5)cm/s) in SPIP did not differ from the Peff in IPVS. The Papp was 0.199×10(-5)cm/s at 1200μg/mL puerarin, 10-fold lower than Peff (2.047±0.116×10(-5)cm/s) in SPIP. Three models for permeability were successfully practiced in the study of puerarin absorption and our research strategy will be useful for herbal constituent absorption in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. DENTAL ABNORMALITIES OF EIGHT WILD QINLING GIANT PANDAS (AILUROPODA MELANOLEUCA QINLINGENSIS), SHAANXI PROVINCE, CHINA.

    Science.gov (United States)

    Jin, Yipeng; Chen, Si; Chao, Yanqiao; Pu, Tianchun; Xu, Hongqian; Liu, Xiaobin; Zhao, Kaihui; Nie, Yonggang; Wei, Wei; Lin, Degui

    2015-10-01

    Eight adult (six male and two female) wild Qinling giant pandas (Ailuropoda melanoleuca qinlingensis) from China National Foping Nature Reserve were tracked, and their dental data collected and recorded from October 2010 to April 2014. Each panda had dental abnormalities of varying severity. Dental wear and fracture were the most common conditions. Absent teeth were common, with premolars missing most often. Mild caries were present in five molar teeth between two animals. Different degrees of dental plaque and calculus occurred in all animals but without severe periodontal disease. Two animals with severe dental abnormalities died due to intestinal problems. Large segments of bamboo were found in their intestinal tracts, and intestinal perforation and ulcers were evident, indicating dental abnormalities can be an important factor in the health of wild giant pandas and may lead to death. Further research with larger sample sizes of wild and captive giant pandas will be required to substantiate the relationship between dental abnormalities and mortality in giant pandas.

  10. Permeable Pavement Research - Edison, New Jersey

    Science.gov (United States)

    This presentation provides the background and summary of results collected at the permeable pavement parking lot monitored at the EPA facility in Edison, NJ. This parking lot is surfaced with permeable interlocking concrete pavers (PICP), pervious concrete, and porous asphalt. ...

  11. Quantifying Evaporation in a Permeable Pavement System

    Science.gov (United States)

    Studies quantifying evaporation from permeable pavement systems are limited to a few laboratory studies and one field application. This research quantifies evaporation for a larger-scale field application by measuring the water balance from lined permeable pavement sections. Th...

  12. Loss of guanylyl cyclase C (GCC signaling leads to dysfunctional intestinal barrier.

    Directory of Open Access Journals (Sweden)

    Xiaonan Han

    2011-01-01

    Full Text Available Guanylyl Cyclase C (GCC signaling via uroguanylin (UGN and guanylin activation is a critical mediator of intestinal fluid homeostasis, intestinal cell proliferation/apoptosis, and tumorigenesis. As a mechanism for some of these effects, we hypothesized that GCC signaling mediates regulation of intestinal barrier function.Paracellular permeability of intestinal segments was assessed in wild type (WT and GCC deficient (GCC-/- mice with and without lipopolysaccharide (LPS challenge, as well as in UGN deficient (UGN-/- mice. IFNγ and myosin light chain kinase (MLCK levels were determined by real time PCR. Expression of tight junction proteins (TJPs, phosphorylation of myosin II regulatory light chain (MLC, and STAT1 activation were examined in intestinal epithelial cells (IECs and intestinal mucosa. The permeability of Caco-2 and HT-29 IEC monolayers, grown on Transwell filters was determined in the absence and presence of GCC RNA interference (RNAi. We found that intestinal permeability was increased in GCC-/- and UGN-/- mice compared to WT, accompanied by increased IFNγ levels, MLCK and STAT1 activation in IECs. LPS challenge promotes greater IFNγ and STAT1 activation in IECs of GCC-/- mice compared to WT mice. Claudin-2 and JAM-A expression were reduced in GCC deficient intestine; the level of phosphorylated MLC in IECs was significantly increased in GCC-/- and UGN-/- mice compared to WT. GCC knockdown induced MLC phosphorylation, increased permeability in IEC monolayers under basal conditions, and enhanced TNFα and IFNγ-induced monolayer hyperpermeability.GCC signaling plays a protective role in the integrity of the intestinal mucosal barrier by regulating MLCK activation and TJ disassembly. GCC signaling activation may therefore represent a novel mechanism in maintaining the small bowel barrier in response to injury.

  13. Clogging in permeable concrete: a review

    OpenAIRE

    Kia, A; Wong, HS; Cheeseman, CR

    2017-01-01

    Permeable concrete (or ??? pervious concrete ??? in North America) is used to reduce local flooding in urban areas and is an important sustainable urba n drainage system. However, permeable concrete exhibits reduction in permeability due to clogging by particulates, which severely limits service life. This paper reviews the clogging mechanism and current mitigating strategies in order to inform future research needs. The pore structure of permeable concrete and characteristics of flowing part...

  14. In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model.

    Science.gov (United States)

    Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

    2015-09-01

    Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. Mast Cell Tryptase Reduces Junctional Adhesion Molecule-A (JAM-A) Expression in Intestinal Epithelial Cells: Implications for the Mechanisms of Barrier Dysfunction in Irritable Bowel Syndrome.

    LENUS (Irish Health Repository)

    Wilcz-Villega, Ewa M

    2013-07-01

    The objective of this study was to investigate how mast cell tryptase may influence intestinal permeability and tight junction (TJ) proteins in vitro and explore translation to irritable bowel syndrome (IBS).

  16. Review of Hydrogen Isotope Permeability Through Materials

    Energy Technology Data Exchange (ETDEWEB)

    Steward, S. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    1983-08-15

    This report is the first part of a comprehensive summary of the literature on hydrogen isotope permeability through materials that do not readily form hydrides. While we mainly focus on pure metals with low permeabilities because of their importance to tritium containment, we also give data on higher-permeability materials such as iron, nickel, steels, and glasses.

  17. Variability of permeability with diameter of conduit

    Indian Academy of Sciences (India)

    Using some theoretical assumptions, it is demonstrated that permeability varies from zero at wall-fluid boundary to maximum at mid-stream, creating a permeability profile similar to the velocity profile. An equation was obtained to establish this. We also found that peak values of permeability increase with increasing porosity, ...

  18. Permeability of Non-Crimp Fabric Preforms

    NARCIS (Netherlands)

    Loendersloot, Richard; Lomov, Stepan V.

    2011-01-01

    Experimental permeability data of non-crimp fabrics (NCFs) is discussed in this chapter. The chapter starts with a general introduction on permeability, followed by a discussion on experimental permeability data. The infl uence of geometrical features of the textile architecture, in particular the

  19. Diabetes-induced mechanophysiological changes in the small intestine and colon

    DEFF Research Database (Denmark)

    Zhao, Mirabella; Liao, Donghua; Zhao, Jingbo

    2017-01-01

    they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut......The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities...... of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how...

  20. Intestinal endocrine cells in radiation enteritis

    International Nuclear Information System (INIS)

    Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis

  1. Experimental Volcanology: Fragmentation and Permeability

    Science.gov (United States)

    Spieler, O.

    2005-12-01

    An increasing number of scientists design new experiments to analyse processes that control the dynamics of explosive eruptions. There research is mostly coupled to numerical models and aims toward its controlling parameters. The fragmentation process, its threshold and the speed of the fragmentation wave as well as the energy consumed by the fragmentation are some hot spots of the experimental volcanology. Analysing the fragmentation behaviour of volcaniclastics as close to the natural system as possible, we found a number of physical constrains. Identifying the porosity as determining factor of the threshold, we realised that neither threshold nor the speed of the fragmentation process are solely controlled by the rock density. The later results of the shock tube type apparatus lead to the analysis of the specific surface area and permeability as direct links to textural features. Permeability analysis performed in a modified shock tube type apparatus, show two clear, distinct trends for dome rock and pyroclastic samples. The specific surface determined by Argon sorbtion (BET) as well as textural features of pumices from Campi Flegrei, Montserrat and Krakatoa (1883) give in contrary evidence of a more complex story. Large spherical, or ellipsoidal bubbles around fractured crystals prove that the high permeability of the pumice has partially developed after the fixing of the bubble size distribution. This puts up the question, if permeability measurements on pyroclastic samples reveal relevant numbers! The surface tension controlled 'self sealing' behaviour of surfaces from foaming obsidian hinders in situ measurements. Close textural investigations will have to clarify how the 'post process' samples deviate from the syneruptive conduit filling.

  2. Quantitative prediction of intestinal metabolism in humans from a simplified intestinal availability model and empirical scaling factor.

    Science.gov (United States)

    Kadono, Keitaro; Akabane, Takafumi; Tabata, Kenji; Gato, Katsuhiko; Terashita, Shigeyuki; Teramura, Toshio

    2010-07-01

    This study aimed to establish a practical and convenient method of predicting intestinal availability (F(g)) in humans for highly permeable compounds at the drug discovery stage, with a focus on CYP3A4-mediated metabolism. We constructed a "simplified F(g) model," described using only metabolic parameters, assuming that passive diffusion is dominant when permeability is high and that the effect of transporters in epithelial cells is negligible. Five substrates for CYP3A4 (alprazolam, amlodipine, clonazepam, midazolam, and nifedipine) and four for both CYP3A4 and P-glycoprotein (P-gp) (nicardipine, quinidine, tacrolimus, and verapamil) were used as model compounds. Observed fraction of drug absorbed (F(a)F(g)) values for these compounds were calculated from in vivo pharmacokinetic (PK) parameters, whereas in vitro intestinal intrinsic clearance (CL(int,intestine)) was determined using human intestinal microsomes. The CL(int,intestine) for the model compounds corrected with that of midazolam was defined as CL(m,index) and incorporated into a simplified F(g) model with empirical scaling factor. Regardless of whether the compound was a P-gp substrate, the F(a)F(g) could be reasonably fitted by the simplified F(g) model, and the value of the empirical scaling factor was well estimated. These results suggest that the effects of P-gp on F(a) and F(g) are substantially minor, at least in the case of highly permeable compounds. Furthermore, liver intrinsic clearance (CL(int,liver)) can be used as a surrogate index of intestinal metabolism based on the relationship between CL(int,liver) and CL(m,index). F(g) can be easily predicted using a simplified F(g) model with the empirical scaling factor, enabling more confident selection of drug candidates with desirable PK profiles in humans.

  3. New therapeutic approach in the management of intestinal disease: probiotics in intestinal disease in paediatric age.

    Science.gov (United States)

    Cucchiara, S; Falconieri, P; Di Nardo, G; Parcelii, M A; Dito, L; Grandinetti, A

    2002-09-01

    Current evidence supports the view that oral administration of probiotics may be of therapeutic usefulness in several clinical disorders by reestablishing normal flora in the gastrointestinal tract. These entities include inflammatory and infectious diseases of the gut as well as extraintestinal disorders (such as atopic eczema) in which a defective intestinal permeability plays a role. The probiotic effects are attributed to restoration to normal of increased intestinal permeability, unbalanced gut microecology, improved immunological gut barrier function, downregulation of the intestinal inflammatory responses with reduced generation of proinflammatory cytokines. Entities for which the impact of probiotic administration can be considered as proven are Rotavirus diarrhoea, Clostridium difficile diarrhoea, post-antibiotic diarrhoea, allergic diseases. On the other hand, entities for which administration of probiotics is considered under investigation are inflammatory bowel disease, necrotizing enterocolitis, cystic fibrosis, small bowel bacterial contamination, functional gastrointestinal disorders. The value of probiotics as therapy for a variety of gastrointestinal disorders in childhood still needs to be investigated in detail, through well controlled and rigorous studies, including a placebo group and strict criteria of randomisation. Much work needs to be done in this area by clearly defining indications, delivery system, costs, safety long-term effects.

  4. Intestinal metabolism of PAH: in vitro demonstration and study of its impact on PAH transfer through the intestinal epithelium

    International Nuclear Information System (INIS)

    Cavret, Severine; Feidt, Cyril

    2005-01-01

    Food would seem to be one of the main ways of animal and human contamination with polycyclic aromatic hydrocarbons (PAHs). In vivo studies suggest a transfer in intestinal epithelium by diffusion, which appears extensively governed by the physicochemical properties of PAHs, particularly lipophilicity. However, other mechanisms, such as metabolism, are considered to intervene. Our work aimed at testing in vitro intestinal metabolism and defining its impact on transepithelial transport of PAHs. Caco-2 cells were cultivated on permeable filters and incubated with 14 C-labeled benzo[a]pyrene (BaP), pyrene (Pyr), and phenanthrene (Phe), which differ in their physicochemical properties. The results showed that the cells were able to metabolize the compounds. In basal media, Phe appeared to be the least hydroxylated molecule (45% after a 6-h exposure), followed by Pyr (65%) and finally BaP (96%). Inhibition of PAH metabolism showed a determinant effect on kinetics profiles. Transfer in the basal compartment of BaP, Pyr, and Phe radioactivities was, respectively, 26, 4, and 2 times lower with inhibitors, corroborating that intestinal metabolism of PAHs would have a positive impact on their transfer, an impact that increased with their lipophilicity. Furthermore, after a 6-h incubation, metabolites were also detected in apical medium. These findings suggested that intestinal metabolism might play a key role in intestinal barrier permeability and thus in the bioavailability of tested micropollutants

  5. Intestinal barrier: A gentlemen's agreement between microbiota and immunity.

    Science.gov (United States)

    Caricilli, Andrea Moro; Castoldi, Angela; Câmara, Niels Olsen Saraiva

    2014-02-15

    Our body is colonized by more than a hundred trillion commensals, represented by viruses, bacteria and fungi. This complex interaction has shown that the microbiome system contributes to the host's adaptation to its environment, providing genes and functionality that give flexibility of diet and modulate the immune system in order not to reject these symbionts. In the intestine, specifically, the microbiota helps developing organ structures, participates of the metabolism of nutrients and induces immunity. Certain components of the microbiota have been shown to trigger inflammatory responses, whereas others, anti-inflammatory responses. The diversity and the composition of the microbiota, thus, play a key role in the maintenance of intestinal homeostasis and explain partially the link between intestinal microbiota changes and gut-related disorders in humans. Tight junction proteins are key molecules for determination of the paracellular permeability. In the context of intestinal inflammatory diseases, the intestinal barrier is compromised, and decreased expression and differential distribution of tight junction proteins is observed. It is still unclear what is the nature of the luminal or mucosal factors that affect the tight junction proteins function, but the modulation of the immune cells found in the intestinal lamina propria is hypothesized as having a role in this modulation. In this review, we provide an overview of the current understanding of the interaction of the gut microbiota with the immune system in the development and maintenance of the intestinal barrier.

  6. Interactions between the intestinal microbiome and helminth parasites.

    Science.gov (United States)

    Zaiss, M M; Harris, N L

    2016-01-01

    Throughout evolution, both helminths and bacteria have inhabited our intestines. As intestinal helminths and bacteria inhabit the same environmental niche, it is likely that these organisms interact with, and impact on, each other. In addition, intestinal helminths are well known to alter intestinal physiology, permeability, mucous secretion and the production of antimicrobial peptides - all of which may impact on bacterial survival and spatial organization. Yet despite rapid advances in our understanding of host-intestinal bacteria interactions, the impact of helminths on this relationship has remained largely unexplored. Moreover, although intestinal helminths are generally accepted to possess potent immuno-modulatory activity, it is unknown whether this capacity requires interactions with intestinal bacteria. We propose that this 'ménage à trois' situation is likely to have exerted a strong selective pressure on the development of our metabolic and immune systems. Whilst such pressures remain in developing countries, the eradication of helminths in industrialized countries has shifted this evolutionary balance, possibly underlying the increased development of chronic inflammatory diseases. Thus, helminth-bacteria interactions may represent a key determinant of healthy homoeostasis. © 2015 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

  7. Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays.

    Science.gov (United States)

    Lee, Jong Bong; Zgair, Atheer; Taha, Dhiaa A; Zang, Xiaowei; Kagan, Leonid; Kim, Tae Hwan; Kim, Min Gi; Yun, Hwi-Yeol; Fischer, Peter M; Gershkovich, Pavel

    2017-05-01

    In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (P app ) values reported in the literature were compared to experimental P app obtained in our laboratory. The differences were assessed by determining the root mean square error (RMSE) values between the datasets, which reached levels as high as 0.581 for the training set compounds, i.e. ten compounds with known effective human permeability (P eff ). The consequences of these differences in P app for prediction of oral drug absorption were demonstrated by introducing the P app into the absorption and pharmacokinetics simulation software application GastroPlus™ for prediction of the fraction absorbed (F a ) in humans using calibrated "user-defined permeability models". The RMSE were calculated to assess the differences between the simulated F a and experimental values reported in the literature. The RMSE for F a simulated with the permeability model calibrated using experimental P app from our laboratory was 0.128. When the calibration was performed using P app from literature datasets, the RMSE values for F a were higher in all cases except one. This study shows quantitative lab-to-lab variability of Caco-2 permeability results and the potential consequences this can have in the use of these results for predicting intestinal absorption of drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Glutathione metabolism in Bangladeshi children with increased small bowel permeability and impaired growth

    International Nuclear Information System (INIS)

    Kumar Roy, Swapan; Tomkins, A.; Johnson, A.

    2000-01-01

    Objectives: To determine whether intestinal permeability during diarrhoea is associated with increased requirement of Sulphur Containing Amino Acid (SCAA); Changes in SCAA metabolism are associated with decreased urinary sulphate and increased excretion of proline from collagen; Rates of turnover SCAA would change as intestinal permeability improves during different dietary levels of SCAA in nutritional regimes. Hypothesis: Supplementation of a standard diet with sulphur containing amino acids is necessary to meet requirements for sulphur under conditions of growth faltering, diarrhoea and increased intestinal permeability. Subjects: Children with persistent diarrhoea aged between 4 months to 18 months and height for age less than 95%. Study site: International Centre for Diarrhoeal Disease Research Bangladesh. Methods: At the baseline, children will be classified into low and normal ISE (Inorganic Sulphar excretion) then each group will be divided into two subgroups. A total of 40 children will be studied (20 in each group). One group will receive a dietary supplement of SCAA and another group will receive an isonitrogenous standard diet for six weeks. Children will be assessed for intestinal permeability at baseline and after two weeks of admission. Before and at six weeks of admission the children will receive a regular drink containing 15 N Glyceine at the rate of 2ml/kg/hr. Blood and urine samples will be collected at baseline and at the end of the supplementation i.e. at 6 weeks. Incorporation of 15 N Glyceine, plasma and red cell glutathione will be assessed by isotope rationing. Urine will be assessed for 15 N enrichment of urea and ammonia, which will used as an assessment of body protein turnover Folate status of these patients will be determined before and after supplementation with SCAA. Benefit of the study: The results of the study will provide specific information on the requirement of Sulphur containing amino acid during malnutrition and persistent

  9. [Design and analyze mathematical algorithms of intestinal absorption and metabolism of multicomponent drug].

    Science.gov (United States)

    Dong, Ling; Xiang, Jia-Mei; Wang, Yun; Wu, Rui-Guang; Tang, Ming-Min; Sun, Mo-Han

    2014-12-01

    Evaluation of the permeability mainly focuses on intestinal absorption in biopharmaceutics classification system (BCS). It is more complicated that the absorption and metabolism under multicomponent environment in biopharmaceutics classification system of Chinese materia medica (CMMBCS) compared with single component environment, which needs suitable mathematical models to be described. Therefore, with full consideration of existing single component mathematical algorithm combining with the characteristics of intestinal absorption and metabolism, we explored and designed a new mathematical algorithm of intestinal absorption and metabolism of multicomponent drug. Then we put forward a new coefficient, P (influence), the relative change rate of the single component's intestinal absorption and metabolism under multicomponent environment compared with single component environment, which described the influences of intestinal absorption and metabolism of the component under multicomponent environment. Moreover, P (influence) highlights the distinctive characteristics of multicomponent drug's intestinal absorption and metabolism, and lays the foundation for the construction of CMMBCS.

  10. Myosin light chain kinase mediates intestinal barrier disruption following burn injury.

    Directory of Open Access Journals (Sweden)

    Chuanli Chen

    Full Text Available BACKGROUND: Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC phosphorylation mediated by MLC kinase (MLCK is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. METHODOLOGY/PRINCIPAL FINDINGS: Male balb/c mice were assigned randomly to either sham burn (control or 30% total body surface area (TBSA full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg, an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. CONCLUSIONS/SIGNIFICANCE: The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury.

  11. Effect of aggregate grain size distribution on properties of permeable ...

    African Journals Online (AJOL)

    ) ratio on the mechanical properties of permeable concrete is investigated. The aim of this study is to prepare permeable concrete mixture with optimum properties in terms of strength and permeability. For this purpose, five different permeable ...

  12. Nitrofurantoin and congenital abnormalities

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Sørensen, Henrik Toft

    2001-01-01

    Objective: To study human teratogenic potential of oral nitrofurantoin treatment during pregnancy. Materials and Methods: Pair analysis of cases with congenital abnormalities and matched population controls in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital...

  13. CT of pleural abnormalities

    International Nuclear Information System (INIS)

    Webb, W.R.

    1995-01-01

    Briefly discussed were CT diagnosis of pleural thickening, CT technique for examining the pleura or pleuro-pulmonary disease, diagnosis of pleural collections, diagnosis of pleural fluid abnormalities in patients with pneumonia, pleural neoplasms, malignant (diffuse) mesothelioma, metastases, local fibrous tumor of the pleura (benign mesothelioma) (21 refs.)

  14. Chromosomal abnormalities and autism

    African Journals Online (AJOL)

    Farida El-Baz

    2015-06-19

    Jun 19, 2015 ... ORIGINAL ARTICLE. Chromosomal abnormalities and autism. Farida El-Baz a. , Mohamed Saad Zaghloul a. , Ezzat El Sobky a. ,. Reham M Elhossiny a,. *, Heba Salah a. , Neveen Ezy Abdelaziz b a Pediatric Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt b Children with Special ...

  15. Gastric and intestinal surgery.

    Science.gov (United States)

    Fossum, Theresa W; Hedlund, Cheryl S

    2003-09-01

    Gastric surgery is commonly performed to remove foreign bodies and correct gastric dilatation-volvulus and is less commonly performed to treat gastric ulceration or erosion, neoplasia, and benign gastric outflow obstruction. Intestinal surgery, although commonly performed by veterinarians, should never be considered routine. The most common procedures of the small intestinal tract performed in dogs and cats include enterotomy and resection/anastomosis. Surgery of the large intestine is indicated for lesions causing obstruction, perforations, colonic inertia, or chronic inflammation.

  16. Intestinal parasites and tuberculosis

    Directory of Open Access Journals (Sweden)

    Anuar Alonso Cedeño-Burbano

    2017-10-01

    Conclusions: The available evidence was insufficient to affirm that intestinal parasites predispose to developing tuberculous. The studies carried out so far have found statistically insignificant results.

  17. The effect of hyperosmosis on paracellular permeability in Caco-2 cell monolayers.

    Science.gov (United States)

    Inokuchi, Hitoshi; Takei, Takuto; Aikawa, Katsuyoshi; Shimizu, Makoto

    2009-02-01

    The intestinal epithelium is a significant barrier to oral absorption of hydrophilic compounds, and their passage through the intercellular space is restricted by the tight junctions. In this study we found that hyperosmosis is a significant factor altering paracellular transport in Caco-2 cell monolayers. Osmotic regulators, such as sodium chloride, mannitol, and raffinose, decreased transepithelial electrical resistance and enhanced lucifer yellow permeability. The effect of these osmotic regulators on Caco-2 cell monolayers was not likely to be caused by gross cytotoxicity. Although certain amino acids and oligosaccharides have been reported to have specific tight junction-modulating activity, we found that the increased paracellular permeability of Caco-2 monolayers induced by these compounds was at least partly due to the increased osmotic pressure of the test solutions. These findings provide a new potential precaution in the evaluation of paracellular permeability-modulating substances using the Caco-2 cell monolayer system.

  18. Effect of chitosan-coated alginate microspheres on the permeability of Caco-2 cell monolayers.

    Science.gov (United States)

    Silva, Catarina M; Veiga, Francisco; Ribeiro, António J; Zerrouk, Naïma; Arnaud, Philippe

    2006-10-01

    Alginate microspheres were prepared by emulsification/internal gelation and coated with chitosan. The ability of chitosan-coated alginate microspheres to increase the paracellular transport across Caco-2 cell monolayers was evaluated in comparison to uncoated microspheres and chitosan solutions. Transport studies were performed by using a permeability marker, Lucifer Yellow (LY), and by measuring the transepithelial electric resistance (TEER) variations. Furthermore, the occurrence of cytotoxic effects was assessed by evaluating neutral red uptake in viable cells and lactate dehydrogenase (LDH) release from damaged cells. A 3-fold increase on LY permeability was obtained for coated microspheres when compared to chitosan solutions. TEER variations were in agreement with permeability results. Chitosan solutions exhibited a dose-dependent toxicity, but coated microspheres did not decrease the viability of cells. Chitosan-coated alginate microspheres have potential to be used as carriers of poorly absorbable hydrophilic drugs to the intestinal epithelia and possibly increase their oral bioavailability.

  19. FLLL32, a curcumin analog, ameliorates intestinal injury in necrotizing enterocolitis

    Directory of Open Access Journals (Sweden)

    Eckert J

    2017-06-01

    Full Text Available Jeffrey Eckert,1 Brian Scott,1,2 Shelley M Lawrence,3 Michael Ihnat,4 Hala Chaaban1 1Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX, 3Department of Pediatrics, University of California San Diego, San Diego, CA, 4Department of Pharmaceutical Sciences, University of Oklahoma, College of Pharmacy, Oklahoma City, OK, USA Background: Necrotizing enterocolitis (NEC is a devastating gastrointestinal disease that primarily affects premature infants. It is characterized by inflammation and leukocyte infiltration that can progress to intestinal necrosis, perforation, systemic inflammatory response, and death. In this study, we examined the effect of FLLL32, a curcumin analog, on an NEC-like neonatal intestinal injury model. Methods: NEC was induced in CD-1 mice pups using the Paneth cell ablation and Klebsiella infection model. Pups were divided into sham, NEC, and NEC + FLLL32 groups. At the end of the experiment, pups were euthanized; whole blood and small intestines were harvested. Intestinal inflammatory cytokine profile, in vivo intestinal permeability using serum fluorescein isothiocyanate-dextran, and histological injury scores were compared between the groups. Results and conclusion: FLLL32-treated pups had lower intestinal injury, improved intestinal permeability, and lower proinflammatory cytokine profiles compared to those in untreated pups with NEC. These results suggest that FLLL32 plays a protective role in NEC. Keywords: necrotizing enterocolitis, neonatal intestinal inflammation, curcumin, FLLL32, STAT3 inhibitors

  20. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function.

    Science.gov (United States)

    Clemente, M G; De Virgiliis, S; Kang, J S; Macatagney, R; Musu, M P; Di Pierro, M R; Drago, S; Congia, M; Fasano, A

    2003-02-01

    Despite the progress made in understanding the immunological aspects of the pathogenesis of coeliac disease (CD), the early steps that allow gliadin to cross the intestinal barrier are still largely unknown. The aim of this study was to establish whether gliadin activates a zonulin dependent enterocyte intracellular signalling pathway(s) leading to increased intestinal permeability. The effect of gliadin on the enterocyte actin cytoskeleton was studied on rat intestinal epithelial (IEC-6) cell cultures by fluorescence microscopy and spectrofluorimetry. Zonulin concentration was measured on cell culture supernatants by enzyme linked immunosorbent assay. Transepithelial intestinal resistance (Rt) was measured on ex vivo intestinal tissues mounted in Ussing chambers. Incubation of cells with gliadin led to a reversible protein kinase C (PKC) mediated actin polymerisation temporarily coincident with zonulin release. A significant reduction in Rt was observed after gliadin addition on rabbit intestinal mucosa mounted in Ussing chambers. Pretreatment with the zonulin inhibitor FZI/0 abolished the gliadin induced actin polymerisation and Rt reduction but not zonulin release. Gliadin induces zonulin release in intestinal epithelial cells in vitro. Activation of the zonulin pathway by PKC mediated cytoskeleton reorganisation and tight junction opening leads to a rapid increase in intestinal permeability.

  1. Primary intestinal lymphangiectasia in adults - diagnostic and therapeutic challenge

    Directory of Open Access Journals (Sweden)

    Jocić Tatiana

    2018-01-01

    Full Text Available Introduction. Primary intestinal lymphangiectasia is a rare disorder, characterized by abnormal dilation of intestinal lymphatic vessels and extensive enteric loss of lymph rich in plasma proteins, lymphocytes and chylomicrons. The main characteristics of the disease are hypoalbuminemia, hypogammaglobulinemia, lymphocytopenia, and more rarely, the deficit of liposoluble vitamins and anemia. Except for primary, there are secondary lymphangiectasia, associated with celiac disease, malignant, infective and inflammatory diseases of the small intestine, fibrosis, liver and cardiovascular diseases. Case report. A male, 33 years of age, presented for his medical examination suffering from diarrhea and edema. The diagnosis was established upon the histological examination of a small intestine biopsy during double balloon enteroscopy, which revealed changes only in one segment of the intestine examined. Such a finding was later confirmed by the video endoscopy capsule. Conclusion. The diagnosis of intestinal lymphangiectasia is usually established before the age of 3, but it can also be diagnosed in adults. The diagnosis is based on the histological analysis of the intestinal mucosa biopsy, obtained by endoscopic procedures. The diagnosis of primary intestinal lymphangiectasia is also made upon the exclusion of secondary causes.

  2. A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients

    DEFF Research Database (Denmark)

    Sigalet, David L; Kravarusic, Dragan; Butzner, Decker

    2013-01-01

    and increased intestinal permeability. Healing of CD resulted in normalization of postprandial GLP-2 release and mucosal functioning (nutrient absorption and permeability), the latter due to an increase in mucosal surface area. These findings have implications for the use of GLP-2 and feeding strategies...

  3. Permeability of highly compacted bentonite

    International Nuclear Information System (INIS)

    Pusch, R.

    1980-12-01

    The object of the study was the water flow through the bentonite which is caused by hydraulic gradients. The study comprised laboratory tests and theoretical considerations. It was found that high bulk densities reduced the permeability to very low values. It was concluded that practically impervious conditions prevail when the gradients are low. Thus with a regional gradient of 10 -2 and a premeability of 10 -13 m/s the flow rate will not be higher than approximately 1 mm in 30 000 years. (G.B.)

  4. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure.

    Science.gov (United States)

    El Asmar, Ramzi; Panigrahi, Pinaki; Bamford, Penelope; Berti, Irene; Not, Tarcisio; Coppa, Giovanni V; Catassi, Carlo; Fasano, Alessio; El Asmar, Rahzi

    2002-11-01

    Enteric infections have been implicated in the pathogenesis of both food intolerance and autoimmune diseases secondary to the impairment of the intestinal barrier. On the basis of our recent discovery of zonulin, a modulator of small-intestinal tight junctions, we asked whether microorganisms might induce zonulin secretion and increased small-intestinal permeability. Both ex vivo mammalian small intestines and intestinal cell monolayers were exposed to either pathogenic or nonpathogenic enterobacteria. Zonulin production and changes in paracellular permeability were monitored in Ussing chambers and micro-snapwells. Zonula occludens 1 protein redistribution after bacteria colonization was evaluated on cell monolayers. Small intestines exposed to enteric bacteria secreted zonulin. This secretion was independent of either the species of the small intestines or the virulence of the microorganisms tested, occurred only on the luminal aspect of the bacteria-exposed small-intestinal mucosa, and was followed by a decrease in small-intestinal tissue resistance (transepithelial electrical resistance). The transepithelial electrical resistance decrement was secondary to the zonulin-induced tight junction disassembly, as also shown by the disengagement of the protein zonula occludens 1 protein from the tight junctional complex. This zonulin-driven opening of the paracellular pathway may represent a defensive mechanism, which flushes out microorganisms and contributes to the host response against bacterial colonization of the small intestine.

  5. Endoscopic biopsies in Ussing chambers evaluated for studies of macromolecular permeability in the human colon.

    Science.gov (United States)

    Wallon, Conny; Braaf, Ylva; Wolving, Mats; Olaison, Gunnar; Söderholm, Johan D

    2005-05-01

    Studies of mucosal permeability to protein antigens in humans are limited to in vitro techniques. The use of surgical specimens for such studies has major shortcomings. Endoscopic biopsies in Ussing chambers have been introduced as a means of studying secretion and transepithelial permeability, but have not been evaluated for studies of protein antigen uptake in human intestine. Standard forceps biopsies from the sigmoid colon of 24 healthy volunteers were mounted in Ussing chambers with an exposed tissue area of 1.76 mm2. 51Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP; 45 kDa protein antigen) were used as permeability markers. Mucosal permeability, electrophysiology, histology and energy contents of the biopsies were studied over time. To evaluate the ability of the technique to detect permeability changes, the mucosa was modulated with capric acid, a medium-chain fatty acid, known to affect tight junctions. In the Ussing chamber the mucosal biopsies were viable for 160 min with stable levels of ATP and lactate, and only minor changes in morphology. Steady-state permeability with low variability was seen for both markers during the 30-90 min period. Exposure to capric acid induced a rapid decrease in short-circuit current (Isc) and a slower reversible decrease in transepithelial resistance (TER), as well as an increased permeability to 51Cr-EDTA and HRP. Endoscopic biopsies of human colon are viable in Ussing chambers and are reliable tools for studies of mucosal permeability to protein antigens. The technique offers a broad potential for studies of mucosal function in the pathophysiology of human gastrointestinal diseases.

  6. Dopamine enhances duodenal epithelial permeability via the dopamine D5receptor in rodent.

    Science.gov (United States)

    Feng, X-Y; Zhang, D-N; Wang, Y-A; Fan, R-F; Hong, F; Zhang, Y; Li, Y; Zhu, J-X

    2017-05-01

    The intestinal barrier is made up of epithelial cells and intercellular junctional complexes to regulate epithelial ion transport and permeability. Dopamine (DA) is able to promote duodenal epithelial ion transport through D1-like receptors, which includes subtypes of D 1 (D 1 R) and D 5 (D 5 R), but whether D1-like receptors influence the duodenal permeability is unclear. FITC-dextran permeability, short-circuit current (I SC ), Western blot, immunohistochemistry and ELISA were used in human D 5 R transgenic mice and hyperendogenous enteric DA (HEnD) rats in this study. Dopamine induced a downward deflection in I SC and an increase in FITC-dextran permeability of control rat duodenum, which were inhibited by the D1-like receptor antagonist, SCH-23390. However, DA decreased duodenal transepithelial resistance (TER), an effect also reversed by SCH-23390. A strong immunofluorescence signal for D 5 R, but not D 1 R, was observed in the duodenum of control rat. In human D 5 R knock-in transgenic mice, duodenal mucosa displayed an increased basal I SC with high FITC-dextran permeability and decreased TER with a lowered expression of tight junction proteins, suggesting attenuated duodenal barrier function in these transgenic mice. D 5 R knock-down transgenic mice manifested a decreased basal I SC with lowered FITC-dextran permeability. Moreover, an increased FITC-dextran permeability combined with decreased TER and tight junction protein expression in duodenal mucosa were also observed in HEnD rats. This study demonstrates, for the first time, that DA enhances duodenal permeability of control rat via D 5 R, which provides new experimental and theoretical evidence for the influence of DA on duodenal epithelial barrier function. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  7. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity.

    Science.gov (United States)

    Verdam, Froukje J; Fuentes, Susana; de Jonge, Charlotte; Zoetendal, Erwin G; Erbil, Runi; Greve, Jan Willem; Buurman, Wim A; de Vos, Willem M; Rensen, Sander S

    2013-12-01

    Intestinal microbiota have been suggested to contribute to the development of obesity, but the mechanism remains elusive. The relationship between microbiota composition, intestinal permeability, and inflammation in nonobese and obese subjects was investigated. Fecal microbiota composition of 28 subjects (BMI 18.6-60.3 kg m(-2) ) was analyzed by a phylogenetic profiling microarray. Fecal calprotectin and plasma C-reactive protein levels were determined to evaluate intestinal and systemic inflammation. Furthermore, HbA1c , and plasma levels of transaminases and lipids were analyzed. Gastroduodenal, small intestinal, and colonic permeability were assessed by a multisaccharide test. Based on microbiota composition, the study population segregated into two clusters with predominantly obese (15/19) or exclusively nonobese (9/9) subjects. Whereas intestinal permeability did not differ between clusters, the obese cluster showed reduced bacterial diversity, a decreased Bacteroidetes/Firmicutes ratio, and an increased abundance of potential proinflammatory Proteobacteria. Interestingly, fecal calprotectin was only detectable in subjects within the obese microbiota cluster (n = 8/19, P = 0.02). Plasma C-reactive protein was also increased in these subjects (P = 0.0005), and correlated with the Bacteroidetes/Firmicutes ratio (rs = -0.41, P = 0.03). Intestinal microbiota alterations in obese subjects are associated with local and systemic inflammation, suggesting that the obesity-related microbiota composition has a proinflammatory effect. Copyright © 2013 The Obesity Society.

  8. A Sensitive Medium-Throughput Method to Predict Intestinal Absorption in Humans Using Rat Intestinal Tissue Segments.

    Science.gov (United States)

    Da Silva, Laís Cristina; Da Silva, Taynara Lourenço; Antunes, Alisson Henrique; Rezende, Kênnia Rocha

    2015-09-01

    A range of in vitro, ex vivo, and in vivo approaches are currently used for drug development. Highly predictive human intestinal absorption models remain lagging behind the times because of numerous variables concerning permeability through gastrointestinal tract in humans. However, there is a clear need for a drug permeability model early in the drug development process that can balance the requirements for high throughput and effective predictive potential. The present study developed a medium throughput screening Snapwell (MTS-Snapwell) ex vivo model to provide an alternative method to classify drug permeability. Rat small intestine tissue segments were mounted in commercial Snapwell™ inserts. Unidirectional drug transport (A-B) was measured by collecting samples at different time points. Viability of intestinal tissue segments was measured by examining transepithelial electric resistance (TEER) and phenol red and caffeine transport. As a result, the apparent permeability (Papp; ×10(-6) cm/s) was determined for atenolol (10.7 ± 1.2), caffeine (17.6 ± 3.1), cimetidine (6.9 ± 0.1), metoprolol (12.6 ± 0.7), theophylline (15.3 ± 1.6) and, ranitidine (3.8 ± 0.4). All drugs were classified in high/low permeability according to Biopharmaceutics Classification System showing high correlation with human data (r = 0.89). These findings showed a high correlation with human data (r = 0.89), suggesting that this model has potential predictive capacity for paracellular and transcellular passively absorbed molecules. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  9. Reduced mucin sulfonation and impaired intestinal barrier function in the hyposulfataemic NaS1 null mouse.

    Science.gov (United States)

    Dawson, P A; Huxley, S; Gardiner, B; Tran, T; McAuley, J L; Grimmond, S; McGuckin, M A; Markovich, D

    2009-07-01

    Sulfate (SO(4)(2-)) is an abundant component of intestinal mucins and its content is decreased in certain gastrointestinal diseases, including inflammatory bowel disease. In this study, the hyposulfataemic NaS1 sulfate transporter null (Nas1(-/-)) mice were used to investigate the physiological consequences of disturbed sulfate homeostasis on (1) intestinal sulfomucin content and mRNA expression; (2) intestinal permeability and proliferation; (3) dextran sulfate sodium (DSS)-induced colitis; and (4) intestinal barrier function against the bacterial pathogen, Campylobacter jejuni. Intestinal sulfomucins and sialomucins were detected by high iron diamine staining, permeability was assessed by fluorescein isothiocyanate (FITC)-dextran uptake, and proliferation was assessed by 5-bromodeoxyuridine (BrdU) incorporation. Nas1(-/-) and wild-type (Nas1(+/+)) mice received DSS in drinking water, and intestinal damage was assessed by histological, clinical and haematological measurements. Mice were orally inoculated with C jejuni, and intestinal and systemic infection was assessed. Ileal mRNA expression profiles of Nas1(-/-) and Nas1(+/+) mice were determined by cDNA microarrays and validated by quantitative real-time PCR. Nas1(-/-) mice exhibited reduced intestinal sulfomucin content, enhanced intestinal permeability and DSS-induced colitis, and developed systemic infections when challenged orally with C jejuni. The transcriptional profile of 41 genes was altered in Nas1(-/-) mice, with the most upregulated gene being pancreatic lipase-related protein 2 and the most downregulated gene being carbonic anhydrase 1 (Car1). Sulfate homeostasis is essential for maintaining a normal intestinal metabolic state, and hyposulfataemia leads to reduced intestinal sulfomucin content, enhanced susceptibility to toxin-induced colitis and impaired intestinal barrier to bacterial infection.

  10. Mango-bagasse functional-confectionery: vehicle for enhancing bioaccessibility and permeability of phenolic compounds.

    Science.gov (United States)

    Herrera-Cazares, Luz Abril; Hernández-Navarro, Fátima; Ramírez-Jiménez, Aurea K; Campos-Vega, Rocío; Reyes-Vega, María de la Luz; Loarca-Piña, Guadalupe; Morales-Sánchez, Eduardo; Wall-Medrano, Abraham; Gaytán-Martínez, Marcela

    2017-11-15

    Functional confectionery can be exploited as a vehicle for the protection of phenolic compounds (PCs) and for enhancing absorption during the gastrointestinal (GI) process. In this study, a confection containing 20% of mango bagasse (MB), gelatin and pectin was formulated. The PC profile, antioxidant capacity, in vitro bioaccessibility and apparent permeability (Papp) during mouth-stomach-intestine digestion (15, 30, 60, 120 min) and in vitro colonic fermentation (6, 12, 24 h) were evaluated for MB and the mango bagasse confection (MBC). HPLC-DAD analysis showed that mangiferin (830.69 μg g -1 ) was the most abundant compound in MBC. Total PCs (4.14 mg g -1 ), quercetin (244.83 μg g -1 ), and gallic acid (GA) (285.43 μg g -1 ) were highly bioaccessible mainly at the intestine at 60-120 min of digestion. GA was the most bioaccessible compound. Total flavonoids (TFs) and condensed tannins (CTs) had the maximum bioaccessibility in the mouth and stomach, respectively. For the permeability studies, PCs showed efflux rather than uptake in the intestine. Those compounds that exhibited intestinal absorption were mangiferin > GA > total PCs > TFs, whereas quercetin and CT absorption was negligible. The antioxidant capacity remained unchanged along the GI, mangiferin and quercetin being the most likely compounds to exert this activity. Overall results indicate that MBC has higher bioaccessibility, absorption and antioxidant capacity than MB, suggesting an effective protective role of gelatin and pectin, giving insight into the potential of MBC as a functional food.

  11. Neurological abnormalities predict disability

    DEFF Research Database (Denmark)

    Poggesi, Anna; Gouw, Alida; van der Flier, Wiesje

    2014-01-01

    To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed...... at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination.......0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological...

  12. adhesive intestinal obstruction

    African Journals Online (AJOL)

    2006-06-01

    Jun 1, 2006 ... ABSTRACT. Background: Adhesions after abdominal and pelvic surgery are a major cause of intestinal obstruction in the western world and the pathology is steadily gaining prominence in our practice. Objective: To determine the magnitude of adhesive intestinal obstruction; to determine the types.

  13. Equipment abnormality monitoring device

    International Nuclear Information System (INIS)

    Ando, Yasumasa

    1991-01-01

    When an operator hears sounds in a plantsite, the operator compares normal sounds of equipment which he previously heard and remembered with sounds he actually hears, to judge if they are normal or abnormal. According to the method, there is a worry that abnormal conditions can not be appropriately judged in a case where the number of objective equipments is increased and in a case that the sounds are changed gradually slightly. Then, the device of the present invention comprises a plurality of monitors for monitoring the operation sound of equipments, a recording/reproducing device for recording and reproducing the signals, a selection device for selecting the reproducing signals among the recorded signals, an acoustic device for converting the signals to sounds, a switching device for switching the signals to be transmitted to the acoustic device between to signals of the monitor and the recording/reproducing signals. The abnormality of the equipments can be determined easily by comparing the sounds representing the operation conditions of equipments for controlling the plant operation and the sounds recorded in their normal conditions. (N.H.)

  14. Steam-water relative permeability

    Energy Technology Data Exchange (ETDEWEB)

    Ambusso, W.; Satik, C.; Home, R.N. [Stanford Univ., CA (United States)

    1997-12-31

    A set of relative permeability relations for simultaneous flow of steam and water in porous media have been measured in steady state experiments conducted under the conditions that eliminate most errors associated with saturation and pressure measurements. These relations show that the relative permeabilities for steam-water flow in porous media vary approximately linearly with saturation. This departure from the nitrogen/water behavior indicates that there are fundamental differences between steam/water and nitrogen/water flows. The saturations in these experiments were measured by using a high resolution X-ray computer tomography (CT) scanner. In addition the pressure gradients were obtained from the measurements of liquid phase pressure over the portions with flat saturation profiles. These two aspects constitute a major improvement in the experimental method compared to those used in the past. Comparison of the saturation profiles measured by the X-ray CT scanner during the experiments shows a good agreement with those predicted by numerical simulations. To obtain results that are applicable to general flow of steam and water in porous media similar experiments will be conducted at higher temperature and with porous rocks of different wetting characteristics and porosity distribution.

  15. Experimental Study on Permeability of Concrete

    Science.gov (United States)

    Yang, Honglu; Liu, Rentai; Zheng, Zhuo; Liu, Haojie; Gao, Yan; Liu, Yankai

    2018-01-01

    To study the influencing factors on permeability of pervious concrete, by adding inorganic organic composite materials obtained experimental results show that different aggregate size, aggregate cement ratio of different, different water cement ratio on the permeability performance. The permeability of the concrete was tested by using the self - made permeable device. The experimental results showed that the permeation coefficient of the experiment was obtained and the factors influencing the permeability of the concrete were compared and analyzed. At the same time, the porosity of pervious concrete was measured, the influence of various variables on porosity was studied, and the influence of various factors on the permeability of voids was found. Finally, through comprehensive analysis of a variety of factors, the optimal water cement ratio is 0.28. At this time, the pervious performance of concrete is optimal.

  16. Air permeability of polyester nonwoven fabrics

    Directory of Open Access Journals (Sweden)

    Zhu Guocheng

    2015-03-01

    Full Text Available Air permeability is one of the most important properties of non-woven fabrics in many applications. This paper aims to investigate the effects of thickness, porosity and density on the air permeability of needle-punched non-woven fabrics and compare the experimental values with two models which are based on hydraulic radius theory and drag theory, respectively. The air permeability of the samples was measured by an air permeability tester FX3300. The results showed that the air permeability of non-woven fabrics decreased with the increase in thickness and density of samples, increased with the increase of porosity, and the air permeability was not directly proportional to the pressure gradient. Meanwhile, the prediction model based on hydraulic radius theory had a better agreement with experimental values than the model based on drag theory, but the values were much higher than the experimental results, especially for higher porosity and higher pressure gradient.

  17. Clogging in permeable concrete: A review.

    Science.gov (United States)

    Kia, Alalea; Wong, Hong S; Cheeseman, Christopher R

    2017-05-15

    Permeable concrete (or "pervious concrete" in North America) is used to reduce local flooding in urban areas and is an important sustainable urban drainage system. However, permeable concrete exhibits reduction in permeability due to clogging by particulates, which severely limits service life. This paper reviews the clogging mechanism and current mitigating strategies in order to inform future research needs. The pore structure of permeable concrete and characteristics of flowing particulates influence clogging, which occurs when particles build-up and block connected porosity. Permeable concrete requires regular maintenance by vacuum sweeping and pressure washing, but the effectiveness and viability of these methods is questionable. The potential for clogging is related to the tortuosity of the connected porosity, with greater tortuosity resulting in increased potential for clogging. Research is required to develop permeable concrete that can be poured on-site, which produces a pore structure with significantly reduced tortuosity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Human zonulin, a potential modulator of intestinal tight junctions.

    Science.gov (United States)

    Wang, W; Uzzau, S; Goldblum, S E; Fasano, A

    2000-12-01

    Intercellular tight junctions are dynamic structures involved in vectorial transport of water and electrolytes across the intestinal epithelium. Zonula occludens toxin derived from Vibrio cholerae interacts with a specific intestinal epithelial surface receptor, with subsequent activation of a complex intracellular cascade of events that regulate tight junction permeability. We postulated that this toxin may mimic the effect of a functionally and immunologically related endogenous modulator of intestinal tight junctions. Affinity-purified anti-zonula occludens toxin antibodies and the Ussing chamber assay were used to screen for one or more mammalian zonula occludens toxin analogues in both fetal and adult human intestine. A novel protein, zonulin, was identified that induces tight junction disassembly in non-human primate intestinal epithelia mounted in Ussing chambers. Comparison of amino acids in the active zonula occludens toxin fragment and zonulin permitted the identification of the putative receptor binding domain within the N-terminal region of the two proteins. Zonulin likely plays a pivotal role in tight junction regulation during developmental, physiological, and pathological processes, including tissue morphogenesis, movement of fluid, macromolecules and leukocytes between the intestinal lumen and the interstitium, and inflammatory/autoimmune disorders.

  19. Abnormal gastrointestinal accumulation of radiotracer by gastric bleeding during 99mTc-MDP bone scintigraphy

    International Nuclear Information System (INIS)

    Chun, Kyung A.; Lee, Sang Woo; Lee, Jae Tae; Lee, Kyu Bo

    1998-01-01

    We present a case in which a patient with acute hemorrhagic gastritis demonstrated abnormal gastrointestinal accumulation of radiotracer during 99m Tc-methylene diphosphonate (MDP) skeletal scintigraphy. A hemorrhagic gastritis was subsequently demonstrated by endoscopy. The mechanism for the intestinal localization of 99m Tc-MDP in this patients is not clear, but we guess that the extravasated blood containing the radiopharmaceutical cannot recirculate and stays at the bleeding site, so we can see the intestinal activity

  20. The Permeability of Boolean Sets of Cylinders

    Directory of Open Access Journals (Sweden)

    Willot F.

    2016-07-01

    Full Text Available Numerical and analytical results on the permeability of Boolean models of randomly-oriented cylinders with circular cross-section are reported. The present work investigates cylinders of prolate (highly-elongated and oblate (nearly flat types. The fluid flows either inside or outside of the cylinders. The Stokes flow is solved using full-fields Fourier-based computations on 3D binarized microstructures. The permeability is given for varying volume fractions of pores. A new upper-bound is derived for the permeability of the Boolean model of oblate cylinders. The behavior of the permeability in the dilute limit is discussed.

  1. Low Permeability Polyimide Insulation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Resodyn Technologies proposes a new technology that enables the application of polyimide based cryogenic insulation with low hydrogen permeability. This effort...

  2. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    Science.gov (United States)

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  3. Abnormal glucose tolerance and lipid abnormalities in Indian ...

    African Journals Online (AJOL)

    Discussion. Regardless of varying diagnostic classification, abnormal glucose tolerance is a well-documented risk factor. 16 Abnormalities in. Because ofthe small number offemale MI survivors, the effect of obesity and abnormal glucose tolerance on lipid levels was studied in the male patients only. There was no significant.

  4. Heat stress and reduced plane of nutrition decreases intestinal integrity and function in pigs.

    Science.gov (United States)

    Pearce, S C; Mani, V; Weber, T E; Rhoads, R P; Patience, J F; Baumgard, L H; Gabler, N K

    2013-11-01

    Heat stress can compromise intestinal integrity and induce leaky gut in a variety of species. Therefore, the objectives of this study were to determine if heat stress (HS) directly or indirectly (via reduced feed intake) increases intestinal permeability in growing pigs. We hypothesized that an increased heat-load causes physiological alterations to the intestinal epithelium, resulting in compromised barrier integrity and altered intestinal function that contributes to the overall severity of HS-related illness. Crossbred gilts (n=48, 43±4 kg BW) were housed in constant climate controlled rooms in individual pens and exposed to 1) thermal neutral (TN) conditions (20°C, 35-50% humidity) with ad libitum intake, 2) HS conditions (35°C, 20-35% humidity) with ad libitum feed intake, or 3) pair-fed in TN conditions (PFTN) to eliminate confounding effects of dissimilar feed intake. Pigs were sacrificed at 1, 3, or 7 d of environmental exposure and jejunum samples were mounted into modified Ussing chambers for assessment of transepithelial electrical resistance (TER) and intestinal fluorescein isothiocyanate (FITC)-labeled lipopolysaccharide (LPS) permeability (expressed as apparent permeability coefficient, APP). Further, gene and protein markers of intestinal integrity and stress were assessed. Irrespective of d of HS exposure, plasma endotoxin levels increased 45% (Palkaline phosphatase activity decreased (46 and 59%, respectively; P<0.05) over time in HS pigs, while the immune cell marker, myeloperoxidase activity, was increased (P<0.05) in the jejunum at d 3 and 7. These results indicate that both HS and reduced feed intake decrease intestinal integrity and increase endotoxin permeability. We hypothesize that these events may lead to increased inflammation, which might contribute to reduced pig performance during warm summer months.

  5. Exercises to Improve Gait Abnormalities

    Science.gov (United States)

    ... Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner of how a ...

  6. Mycotoxins and the intestine

    Directory of Open Access Journals (Sweden)

    Leon Broom

    2015-12-01

    Full Text Available Fungal biochemical pathways can yield various compounds that are not considered to be necessary for their growth and are thus referred to as secondary metabolites. These compounds have been found to have wide ranging biological effects and include potent poisons (mycotoxins. Mycotoxins invariably contaminate crops and (thus animal feeds. The intestine is the key link between ingested mycotoxins and their detrimental effects on the animal. Effects on the intestine, or intestinal environment, and immune system have been reported with various mycotoxins. These effects are almost certainly occurring across species. Most, if not all, of the reported effects of mycotoxins are negative in terms of intestinal health, for example, decreased intestinal cell viability, reductions in short chain fatty acid (SCFA concentrations and elimination of beneficial bacteria, increased expression of genes involved in promoting inflammation and counteracting oxidative stress. This challenge to intestinal health will predispose the animal to intestinal (and systemic infections and impair efficient digestion and absorption of nutrients, with the associated effect on animal productivity.

  7. Outcome of splanchnic blood flow determination in patients with suspected chronic intestinal ischaemia. A retrospective survey

    DEFF Research Database (Denmark)

    Møller, Søren; Madsen, Jan Lysgård

    2002-01-01

    flow: A, normal response (splanchnic blood flow > or = 200 ml/min); B, possible abnormal response (splanchnic blood flow 51-199 ml/min); and C, definitive abnormal response (splanchnic blood flow ... a normal meal-induced response, 23 patients had a possible abnormal response and 10 patients had a definitive abnormal response, which gave evidence of chronic intestinal ischaemia. In the total patient population, the increase in splanchnic blood flow was significantly correlated to an increase in hepatic...... oxygen uptake (r = 0.38, P abnormal meal-induced splanchnic blood flow and 30% of these patients...

  8. Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic sclerosis.

    Science.gov (United States)

    Marie, I; Antonietti, M; Houivet, E; Hachulla, E; Maunoury, V; Bienvenu, B; Viennot, S; Smail, A; Duhaut, P; Dupas, J-L; Dominique, S; Hatron, P-Y; Levesque, H; Benichou, J; Ducrotté, P

    2014-07-01

    To date, there are no large studies on videocapsule endoscopy in systemic sclerosis (SSc). Consequently, the prevalence and features of gastrointestinal mucosal abnormalities in SSc have not been determined. To determine both prevalence and characteristics of gastrointestinal mucosal abnormalities in unselected patients with SSc, using videocapsule endoscopy. To predict which SSc patients are at risk of developing potentially bleeding gastrointestinal vascular mucosal abnormalities. Videocapsule endoscopy was performed on 50 patients with SSc. Prevalence of gastrointestinal mucosal abnormalities was 52%. Potentially bleeding vascular mucosal lesions were predominant, including: watermelon stomach (34.6%), gastric and/or small intestinal telangiectasia (26.9%) and gastric and/or small intestinal angiodysplasia (38.5%). SSc patients with gastrointestinal vascular mucosal lesions more often exhibited: limited cutaneous SSc (P = 0.06), digital ulcers (P = 0.05), higher score of nailfold videocapillaroscopy (P = 0.0009), anaemia (P = 0.02), lower levels of ferritin (P correlation between gastrointestinal vascular mucosal lesions and presence of severe extra-digestive vasculopathy (digital ulcers and higher nailfold videocapillaroscopy scores). This latter supports the theory that SSc-related diffuse vasculopathy is responsible for both cutaneous and digestive vascular lesions. Therefore, we suggest that nailfold videocapillaroscopy may be a helpful test for managing SSc patients. In fact, nailfold videocapillaroscopy score should be calculated routinely, as it may result in identification of SSc patients at higher risk of developing potentially bleeding gastrointestinal vascular mucosal lesions. © 2014 John Wiley & Sons Ltd.

  9. Twist1 controls lung vascular permeability and endotoxin-induced pulmonary edema by altering Tie2 expression.

    Science.gov (United States)

    Mammoto, Tadanori; Jiang, Elisabeth; Jiang, Amanda; Lu, Yongbo; Juan, Aimee M; Chen, Jing; Mammoto, Akiko

    2013-01-01

    Tight regulation of vascular permeability is necessary for normal development and deregulated vascular barrier function contributes to the pathogenesis of various diseases, including acute respiratory distress syndrome, cancer and inflammation. The angiopoietin (Ang)-Tie2 pathway is known to control vascular permeability. However, the mechanism by which the expression of Tie2 is regulated to control vascular permeability has not been fully elucidated. Here we show that transcription factor Twist1 modulates pulmonary vascular leakage by altering the expression of Tie2 in a context-dependent way. Twist1 knockdown in cultured human lung microvascular endothelial cells decreases Tie2 expression and phosphorylation and increases RhoA activity, which disrupts cell-cell junctional integrity and increases vascular permeability in vitro. In physiological conditions, where Ang1 is dominant, pulmonary vascular permeability is elevated in the Tie2-specific Twist1 knockout mice. However, depletion of Twist1 and resultant suppression of Tie2 expression prevent increase in vascular permeability in an endotoxin-induced lung injury model, where the balance of Angs shifts toward Ang2. These results suggest that Twist1-Tie2-Angs signaling is important for controlling vascular permeability and modulation of this mechanism may lead to the development of new therapeutic approaches for pulmonary edema and other diseases caused by abnormal vascular permeability.

  10. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...... membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption...

  11. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption......A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...

  12. HDAC1 and HDAC2 restrain the intestinal inflammatory response by regulating intestinal epithelial cell differentiation.

    Directory of Open Access Journals (Sweden)

    Naomie Turgeon

    Full Text Available Acetylation and deacetylation of histones and other proteins depends on histone acetyltransferases and histone deacetylases (HDACs activities, leading to either positive or negative gene expression. HDAC inhibitors have uncovered a role for HDACs in proliferation, apoptosis and inflammation. However, little is known of the roles of specific HDACs in intestinal epithelial cells (IEC. We investigated the consequences of ablating both HDAC1 and HDAC2 in murine IECs. Floxed Hdac1 and Hdac2 homozygous mice were crossed with villin-Cre mice. Mice deficient in both IEC HDAC1 and HDAC2 weighed less and survived more than a year. Colon and small intestinal sections were stained with hematoxylin and eosin, or with Alcian blue and Periodic Acid Schiff for goblet cell identification. Tissue sections from mice injected with BrdU for 2 h, 14 h and 48 h were stained with anti-BrdU. To determine intestinal permeability, 4-kDa FITC-labeled dextran was given by gavage for 3 h. Microarray analysis was performed on total colon RNAs. Inflammatory and IEC-specific gene expression was assessed by Western blot or semi-quantitative RT-PCR and qPCR with respectively total colon protein and total colon RNAs. HDAC1 and HDAC2-deficient mice displayed: 1 increased migration and proliferation, with elevated cyclin D1 expression and phosphorylated S6 ribosomal protein, a downstream mTOR target; 2 tissue architecture defects with cell differentiation alterations, correlating with reduction of secretory Paneth and goblet cells in jejunum and goblet cells in colon, increased expression of enterocytic markers such as sucrase-isomaltase in the colon, increased expression of cleaved Notch1 and augmented intestinal permeability; 3 loss of tissue homeostasis, as evidenced by modifications of claudin 3 expression, caspase-3 cleavage and Stat3 phosphorylation; 4 chronic inflammation, as determined by inflammatory molecular expression signatures and altered inflammatory gene expression

  13. Bile acid receptor TGR5 overexpression is associated with decreased intestinal mucosal injury and epithelial cell proliferation in obstructive jaundice.

    Science.gov (United States)

    Ji, Chen-Guang; Xie, Xiao-Li; Yin, Jie; Qi, Wei; Chen, Lei; Bai, Yun; Wang, Na; Zhao, Dong-Qiang; Jiang, Xiao-Yu; Jiang, Hui-Qing

    2017-04-01

    Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS). Internal biliary drainage was superior to external biliary drainage in recovering intestinal permeability and mucosal histology in patients with obstructive jaundice. In BDL rats, feeding of chenodeoxycholic acid (CDCA) decreased intestinal mucosa injury. The levels of PCNA, a marker of proliferation, increased in response to CDCA feeding and were paralleled by elevated TGR5 expression. CDCA upregulated TGR5 expression and promoted proliferation in Caco-2 and FHs 74 Int cells pretreated with LPS. Overexpression of TGR5 resulted in increased PCNA, cell viability, EdU incorporation, and the proportion of cells in S phase, whereas knockdown of TGR5 had the opposite effect. Our data indicate that bile acids promote intestinal epithelial cell proliferation and decrease mucosal injury by upregulating TGR5 expression in obstructive jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Unraveling the ties between irritable bowel syndrome and intestinal microbiota.

    Science.gov (United States)

    Hong, Sung Noh; Rhee, Poong-Lyul

    2014-03-14

    Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder. It is a multifactorial disorder. Intestinal microbiota may cause the pathogenesis of IBS by contributing to abnormal gastrointestinal motility, low-grade inflammation, visceral hypersensitivity, communication in the gut-brain axis, and so on. Previous attempts to identify the intestinal microbiota composition in IBS patients have yielded inconsistent and occasionally contradictory results. This inconsistency may be due to the differences in the molecular techniques employed, the sample collection and handling methods, use of single samples that are not linked to fluctuating symptoms, or other factors such as patients' diets and phenotypic characterizations. Despite these difficulties, previous studies found that the intestinal microbiota in some IBS patients was completely different from that in healthy controls, and there does appear to be a consistent theme of Firmicutes enrichment and reduced abundance of Bacteroides. Based on the differences in intestinal microbiota composition, many studies have addressed the roles of microbiota-targeted treatments, such as antibiotics and probiotics, in alleviating certain symptoms of IBS. This review summarizes the current knowledge of the associations between intestinal microbiota and IBS as well as the possible modes of action of intestinal microbiota in the pathogenesis of IBS. Improving the current level of understanding of host-microbiota interactions in IBS is important not only for determining the role of intestinal microbiota in IBS pathogenesis but also for therapeutic modulation of the microbiota.

  15. [Penile congenital abnormalities].

    Science.gov (United States)

    Boillot, B; Teklali, Y; Moog, R; Droupy, S

    2013-07-01

    Congenital abnormalities of the penis are usually diagnosed at birth and pose aesthetic and functional problems sometimes requiring surgical management. A literature review was conducted on Medline considering the articles listed until January 2012. Hypospadias is the most common malformation (1 in 250 boys. Familial forms: 7%). The causes remain hypothetical but the doubling of the incidence in 30 years could be linked to fetal exposure to endocrine disruptors "estrogen-like" used in the food industry in particular. Surgical treatment is usually intended to improve the aesthetic appearance but sometimes, in case of significant curvature or posterior meatus, necessary for normal sexual life and fertility. Other malformations (epispades, buried penis, transpositions, twists and preputial abnormalities) as well as management for functional or aesthetic consequences of these malformations in adulthood require complex surgical care in a specialized environment. The improvement of surgical techniques and pediatric anesthesia allows an early and effective specialized surgical approach of penile malformations. Management of sequelae in adulthood must be discussed and requires experience of surgical techniques on pediatric and adult penis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Bioavailability of genistein, daidzein, and their glycosides in intestinal epithelial Caco-2 cells

    NARCIS (Netherlands)

    Steensma, A.; Noteborn, H.P.J.M.; Jagt, van der R.C.M.; Polman, Th.H.G.; Mengelers, M.J.B.; Kuiper, H.A.

    1999-01-01

    In this study information was obtained on bioavailability of genistein, daidzein and their glycosides in human intestinal epithelial Caco-2 cells grown on semi-permeable filters. The integrity of Caco-2 monolayers was confirmed by transepithelial electrical resistance measurements and by

  17. Development of microfluidic cell culture devices towards an in vitro human intestinal barrier model

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin

    Existing in vitro models of the human intestine such as the established epithelial cell line, Caco-2, cultured on porous membranes have been extensively used for assessing and predicting permeability and absorption of oral drugs in the pharmaceutical industries. However, such in vitro human intes...

  18. Incorporation of lipolysis in monolayer permeability studies of lipid-based oral drug delivery systems.

    Science.gov (United States)

    Sadhukha, Tanmoy; Layek, Buddhadev; Prabha, Swayam

    2018-04-01

    Lipid-based drug delivery systems, a well-tolerated class of formulations, have been evaluated extensively to enhance the bioavailability of poorly soluble drugs. However, it has been difficult to predict the in vivo performance of lipid dosage forms based on conventional in vitro techniques such as cell monolayer permeability studies because of the complexity of the gastrointestinal processing of lipid formulations. In the current study, we explored the feasibility of coupling Caco-2 and Madin-Darby canine kidney monolayer permeability studies with lipolysis, a promising in vitro technique to evaluate lipid systems. A self-emulsifying lipid delivery system was formulated using a blend of oil (castor oil), surfactant (Labrasol® or PL497), and co-surfactant (lecithin). Formulations demonstrating high drug solubility and rapid self-emulsification were selected to study the effect of lipolysis on in vitro cell permeability. Lipolysis of the formulations was carried out using pancreatin as the digestive enzyme. All the digested formulations compromised monolayer integrity as indicated by lowered trans-epithelial electrical resistance (TEER) and enhanced Lucifer yellow (LY) permeability. Further, the changes in TEER value and LY permeability were attributable to the digestion products of the formulation rather than the individual lipid excipients, drug, digestion enzyme, or the digestion buffer. The digested formulations were fractionated into pellet, oily phase, and aqueous phase, and the effect of each of these on cell viability was examined. Interestingly, the aqueous phase, which is considered important for in vivo drug absorption, was responsible for cytotoxicity. Because lipid digestion products lead to disruption of cell monolayer, it may not be appropriate to combine lipolysis with cell monolayer permeability studies. Additional in vivo studies are needed to determine any potential side effects of the lipolysis products on the intestinal permeability barrier

  19. Crustal permeability: Introduction to the special issue

    Science.gov (United States)

    Ingebritsen, Steven E.; Gleeson, Tom

    2015-01-01

    The topic of crustal permeability is of broad interest in light of the controlling effect of permeability on diverse geologic processes and also timely in light of the practical challenges associated with emerging technologies such as hydraulic fracturing for oil and gas production (‘fracking’), enhanced geothermal systems, and geologic carbon sequestration. This special issue of Geofluids is also motivated by the historical dichotomy between the hydrogeologic concept of permeability as a static material property that exerts control on fluid flow and the perspective of economic geologists, geophysicists, and crustal petrologists who have long recognized permeability as a dynamic parameter that changes in response to tectonism, fluid production, and geochemical reactions. Issues associated with fracking, enhanced geothermal systems, and geologic carbon sequestration have already begun to promote a constructive dialog between the static and dynamic views of permeability, and here we have made a conscious effort to include both viewpoints. This special issue also focuses on the quantification of permeability, encompassing both direct measurement of permeability in the uppermost crust and inferential permeability estimates, mainly for the deeper crust.

  20. A Negative Permeability Material at Red Light

    DEFF Research Database (Denmark)

    Yuan, Hsiao-Kuan; Chettiar, Uday K.; Cai, Wenshan

    2007-01-01

    A negative permeability in a periodic array of pairs of thin silver strips is demonstrated experimentally for two distinct samples. The effect of the strip surface roughness on negative permeability is evaluated. The first sample, Sample A, is fabricated of thinner strips with a root mean square ...

  1. Intercomparison on measurement of water vapour permeability

    DEFF Research Database (Denmark)

    Hansen, Kurt Kielsgaard

    Three different materials are tested - hard woodfibre board - damp proof course - underlay for roofing The water vapour permeability has been measured according to EN ISO 12572 (2001).......Three different materials are tested - hard woodfibre board - damp proof course - underlay for roofing The water vapour permeability has been measured according to EN ISO 12572 (2001)....

  2. Microorganism Removal in Permeable Pavement Parking Lots ...

    Science.gov (United States)

    Three types of permeable pavements (pervious concrete, permeable interlocking concrete pavers, and porous asphalt) were monitored at the Edison Environmental Center in Edison, New Jersey for indicator organisms such as fecal coliform, enterococci, and E. coli. Results showed that porous asphalt had much lower concentration in monitored infiltrate compared to pervious concrete and permeable interlocking concrete pavers. Concentrations of monitored organisms in infiltrate from porous asphalt were consistently below the bathing water quality standard. Fecal coliform and enterococci exceeded bathing water quality standards more than 72% and 34% of the time for permeable interlocking concrete pavers and pervious concrete, respectively. Purpose is to evaluate the performance of permeable pavement in removing indicator organisms from infiltrating stormwater runoff.

  3. Different Methods of Predicting Permeability in Shale

    DEFF Research Database (Denmark)

    Mbia, Ernest Ncha; Fabricius, Ida Lykke; Krogsbøll, Anette

    Permeability is often very difficult to measure or predict in shale lithology. In this work we are determining shale permeability from consolidation tests data using Wissa et al., (1971) approach and comparing the results with predicted permeability from Kozeny’s model. Core and cuttings materials...... were obtained from Fjerritslev shale Formation in Juassic interval of Stenlille and Vedsted on-shore wells of Danish basin. The calculated permeability from specific surface and porosity vary from 0.09 to 48.53 μD while that calculated from consolidation tests data vary from 1000 μD at a low vertical...... effective stress to 9 μD at high vertical effective stress of 100 MPa. The indirect permeability calculated from consolidation tests falls in the same magnitude at higher vertical effective stress, above 40 MPa, as that of the Kozeny model for shale samples with high non-clay content ≥ 70% but are higher...

  4. A prospective comparison of intestinal sonography and abdominal radiographs in a neonatal intensive care unit.

    Science.gov (United States)

    Silva, Cicero T; Daneman, Alan; Navarro, Oscar M; Moineddin, Rahim; Levine, Daniel; Moore, Aideen M

    2013-11-01

    No study reported in the literature comprehensively compares findings on neonatal abdominal radiographs with sonography. To compare the findings on abdominal radiographs and sonograms in infants in intensive care, to better understand how the various intestinal gas patterns on radiographs relate to the spectrum of appearances on sonography and, second, to evaluate the ability of sonography to differentiate necrotizing enterocolitis from other intestinal pathology. We prospectively evaluated sonograms and radiographs, blinded to the other modality and to clinical information. Patients' charts were reviewed by a third blinded reader and used as a reference standard for diagnosis. We made associations between sonographic findings, radiographic intestinal gas patterns and clinical diagnoses. We included 75 infants with gestational ages between 23 weeks and 41 weeks. Sonographic abnormalities were present in infants with all radiographic intestinal gas patterns, including normal patterns. We only saw absent intestinal perfusion and fluid collections on sonography (suggesting intestinal necrosis and sealed perforation) in infants with intestinal dilatation with elongation on radiographs. Separation of intestinal loops on radiographs was most commonly caused by reasons other than intestinal wall thickening. Increased intestinal echogenicity or free fluid with echoes on sonography correlated with a diagnosis of necrotizing enterocolitis, whereas anechoic free fluid correlated with absence of necrotizing enterocolitis. Sonography is complementary to radiographs in infants with suspected intestinal pathology, with a spectrum of appearances seen on each modality. Some sonographic findings either strongly suggest necrotizing enterocolitis or supply evidence against this diagnosis.

  5. Gas and Water Permeability of Concrete

    Energy Technology Data Exchange (ETDEWEB)

    Villar, M. V.; Martin, P. L.; Romero, F. J.; Gutierrez-Rodirgo, V.; Barcala, J. M.

    2012-11-01

    The gas pressure of concrete samples was measured in an unsteady-state equipment working under low injection pressures and in a newly fine tuned steady-state setup working under different pressures. These measurements allowed the estimation of the intrinsic and relative gas permeability of the concrete and of the effect of boundary conditions on them. Permeability decreased with water content, but it was also greatly affected by the hydraulic history of concrete, i.e. if it had been previously dried or wetted. In particular, and for a given degree of saturation, the gas permeability of concrete previously saturated was lower than if the concrete had been just air dried or saturated after air drying. In any case, the gas permeability was about two orders of magnitude higher than the liquid water permeability (10-16 vs. 10-18 m2), probably due to the chemical reactions taking place during saturation (carbonation). The relative gas permeability of concrete increased sharply for water degrees of saturation smaller than 50%. The boundary conditions also affected the gas permeability, which seemed to be mostly conditioned by the back pressure and the confining pressure, increasing as the former increased and decreasing as the latter increased, i.e. decreasing as the effective pressure increased. Overall the increase of pressure head or injection pressure implied a decrease in gas permeability. External,microcracking during air-drying could not be ruled out as responsible for the decrease of permeability with confining pressure. The apparent permeability obtained applying the Klinkenberg method for a given effective pressure was only slightly smaller than the average of all the values measured for the same confining pressure range. For this reason it is considered that the Klinkenberg effect was not relevant in the range of pressures applied. (Author) 37 refs.

  6. Farnesoid X Receptor Activation Attenuates Intestinal Ischemia Reperfusion Injury in Rats.

    Directory of Open Access Journals (Sweden)

    Laurens J Ceulemans

    Full Text Available The farnesoid X receptor (FXR is abundantly expressed in the ileum, where it exerts an enteroprotective role as a key regulator of intestinal innate immunity and homeostasis, as shown in pre-clinical models of inflammatory bowel disease. Since intestinal ischemia reperfusion injury (IRI is characterized by hyperpermeability, bacterial translocation and inflammation, we aimed to investigate, for the first time, if the FXR-agonist obeticholic acid (OCA could attenuate intestinal ischemia reperfusion injury.In a validated rat model of intestinal IRI (laparotomy + temporary mesenteric artery clamping, 3 conditions were tested (n = 16/group: laparotomy only (sham group; ischemia 60min+ reperfusion 60min + vehicle pretreatment (IR group; ischemia 60min + reperfusion 60min + OCA pretreatment (IR+OCA group. Vehicle or OCA (INT-747, 2*30mg/kg was administered by gavage 24h and 4h prior to IRI. The following end-points were analyzed: 7-day survival; biomarkers of enterocyte viability (L-lactate, I-FABP; histology (morphologic injury to villi/crypts and villus length; intestinal permeability (Ussing chamber; endotoxin translocation (Lipopolysaccharide assay; cytokines (IL-6, IL-1-β, TNFα, IFN-γ IL-10, IL-13; apoptosis (cleaved caspase-3; and autophagy (LC3, p62.It was found that intestinal IRI was associated with high mortality (90%; loss of intestinal integrity (structurally and functionally; increased endotoxin translocation and pro-inflammatory cytokine production; and inhibition of autophagy. Conversely, OCA-pretreatment improved 7-day survival up to 50% which was associated with prevention of epithelial injury, preserved intestinal architecture and permeability. Additionally, FXR-agonism led to decreased pro-inflammatory cytokine release and alleviated autophagy inhibition.Pretreatment with OCA, an FXR-agonist, improves survival in a rodent model of intestinal IRI, preserves the gut barrier function and suppresses inflammation. These results turn

  7. A Rare Stapes Abnormality

    Directory of Open Access Journals (Sweden)

    Hala Kanona

    2015-01-01

    Full Text Available The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50 dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively.

  8. Advantageous Solubility-Permeability Interplay When Using Amorphous Solid Dispersion (ASD) Formulation for the BCS Class IV P-gp Substrate Rifaximin: Simultaneous Increase of Both the Solubility and the Permeability.

    Science.gov (United States)

    Beig, Avital; Fine-Shamir, Noa; Lindley, David; Miller, Jonathan M; Dahan, Arik

    2017-05-01

    Rifaximin is a BCS class IV (low-solubility, low-permeability) drug and also a P-gp substrate. The aims of this work were to assess the efficiency of different rifaximin amorphous solid dispersion (ASDs) formulations in achieving and maintaining supersaturation and to investigate the consequent solubility-permeability interplay. Spray-dried rifaximin ASDs were prepared with different hydrophilic polymers and their ability to achieve and maintain supersaturation was assessed. Then, rifaximin's apparent intestinal permeability was investigated as a function of increasing supersaturation both in vitro using the parallel artificial membrane permeability assay (PAMPA) and in vivo using the single-pass rat intestinal perfusion (SPIP) model. The efficiency of the different ASDs to achieve and maintain supersaturation of rifaximin was found to be highly polymer dependent, and the copovidone/HPC-SL formulation was found to be superior to the other two, allowing supersaturation of 200× that of the crystalline solubility for 20 h. In vitro, rifaximin flux was increased and the apparent permeability was constant as a function of increasing supersaturation level. In vivo, on the other hand, absorption rate coefficient (k a ) was first constant as a function of increasing supersaturation, but at 250×, the crystalline solubility k a was doubled, similar to the k a in the presence of the strong P-gp inhibitor GF120918. In conclusion, a new and favorable nature of solubility-permeability interplay was revealed in this work: delivering high supersaturation level of the BCS class IV drug rifaximin via ASD, thereby saturating the drugs' P-gp-mediated efflux transport, led to the favorable unique win-win situation, where both the solubility and the permeability increased simultaneously.

  9. Long-term changes in corneal endothelial morphology after discontinuation of low gas-permeable contact lens wear

    NARCIS (Netherlands)

    Odenthal, M. T. P.; Gan, I. M.; Oosting, J.; Kijlstra, A.; Beekhuis, W. H.

    2005-01-01

    Purpose: Low gas-permeable contact lens wear of polymethyl methacrylate or hydroxyethyl methacrylate material is known to cause morphologic abnormalities in the corneal endothelial cell layer. These tenses were widely prescribed and successfully worn until their use was actively discouraged in the

  10. Long-term changes in corneal endothelial morphology after discontinuation of low gas-permeable contact lens wear

    NARCIS (Netherlands)

    Odenthal, M.T.; Gan, I.M.; Oosting, J.; Kijlstra, A.; Beekhuis, W.H.

    2005-01-01

    Low gas-permeable contact lens wear of polymethyl methacrylate or hydroxyethyl methacrylate material is known to cause morphologic abnormalities in the corneal endothelial cell layer. These lenses were widely prescribed and successfully worn until their use was actively discouraged in the late 1980s

  11. Hummingbirds rely on both paracellular and carrier-mediated intestinal glucose absorption to fuel high metabolism

    Science.gov (United States)

    McWhorter, Todd J; Bakken, Bradley Hartman; Karasov, William H; del Rio, Carlos Martínez

    2005-01-01

    Twenty years ago, the highest active glucose transport rate and lowest passive glucose permeability in vertebrates were reported in Rufous and Anna's hummingbirds (Selasphorus rufus, Calypte anna). These first measurements of intestinal nutrient absorption in nectarivores provided an unprecedented physiological foundation for understanding their foraging ecology. They showed that physiological processes are determinants of feeding behaviour. The conclusion that active, mediated transport accounts for essentially all glucose absorption in hummingbirds influenced two decades of subsequent research on the digestive physiology and nutritional ecology of nectarivores. Here, we report new findings demonstrating that the passive permeability of hummingbird intestines to glucose is much higher than previously reported, suggesting that not all sugar uptake is mediated. Even while possessing the highest active glucose transport rates measured in vertebrates, hummingbirds must rely partially on passive non-mediated intestinal nutrient absorption to meet their high mass-specific metabolic demands. PMID:17148346

  12. Standardising the lactulose mannitol test of gut permeability to minimise error and promote comparability.

    Directory of Open Access Journals (Sweden)

    Ivana R Sequeira

    Full Text Available BACKGROUND: Lactulose mannitol ratio tests are clinically useful for assessing disorders characterised by changes in gut permeability and for assessing mixing in the intestinal lumen. Variations between currently used test protocols preclude meaningful comparisons between studies. We determined the optimal sampling period and related this to intestinal residence. METHODS: Half-hourly lactulose and mannitol urinary excretions were determined over 6 hours in 40 healthy female volunteers after administration of either 600 mg aspirin or placebo, in randomised order at weekly intervals. Gastric and small intestinal transit times were assessed by the SmartPill in 6 subjects from the same population. Half-hourly percentage recoveries of lactulose and mannitol were grouped on a basis of compartment transit time. The rate of increase or decrease of each sugar within each group was explored by simple linear regression to assess the optimal period of sampling. KEY RESULTS: The between subject standard errors for each half-hourly lactulose and mannitol excretion were lowest, the correlation of the quantity of each sugar excreted with time was optimal and the difference between the two sugars in this temporal relationship maximal during the period from 2½-4 h after ingestion. Half-hourly lactulose excretions were generally increased after dosage with aspirin whilst those of mannitol were unchanged as was the temporal pattern and period of lowest between subject standard error for both sugars. CONCLUSION: The results indicate that between subject variation in the percentage excretion of the two sugars would be minimised and the differences in the temporal patterns of excretion would be maximised if the period of collection of urine used in clinical tests of small intestinal permeability were restricted to 2½-4 h post dosage. This period corresponds to a period when the column of digesta column containing the probes is passing from the small to the large

  13. Prenatal Intestinal Obstruction Affects the Myenteric Plexus and Causes Functional Bowel Impairment in Fetal Rat Experimental Model of Intestinal Atresia

    Science.gov (United States)

    Khen-Dunlop, Naziha; Sarnacki, Sabine; Victor, Anais; Grosos, Celine; Menard, Sandrine; Soret, Rodolphe; Goudin, Nicolas; Pousset, Maud; Sauvat, Frederique; Revillon, Yann; Cerf-Bensussan, Nadine; Neunlist, Michel

    2013-01-01

    Background Intestinal atresia is a rare congenital disorder with an incidence of 3/10 000 birth. About one-third of patients have severe intestinal dysfunction after surgical repair. We examined whether prenatal gastrointestinal obstruction might effect on the myenteric plexus and account for subsequent functional disorders. Methodology/Principal Findings We studied a rat model of surgically induced antenatal atresia, comparing intestinal samples from both sides of the obstruction and with healthy rat pups controls. Whole-mount preparations of the myenteric plexus were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (nNOS). Quantitative reverse transcription PCR was used to analyze mRNAs for inflammatory markers. Functional motility and permeability analyses were performed in vitro. Phenotypic studies were also performed in 8 newborns with intestinal atresia. In the experimental model, the proportion of nNOS-immunoreactive neurons was similar in proximal and distal segments (6.7±4.6% vs 5.6±4.2%, p = 0.25), but proximal segments contained a higher proportion of ChAT-immunoreactive neurons (13.2±6.2% vs 7.5±4.3%, p = 0.005). Phenotypic changes were associated with a 100-fold lower concentration-dependent contractile response to carbachol and a 1.6-fold higher EFS-induced contractile response in proximal compared to distal segments. Transcellular (p = 0.002) but not paracellular permeability was increased. Comparison with controls showed that modifications involved not only proximal but also distal segments. Phenotypic studies in human atresia confirmed the changes in ChAT expression. Conclusion Experimental atresia in fetal rat induces differential myenteric plexus phenotypical as well as functional changes (motility and permeability) between the two sides of the obstruction. Delineating these changes might help to identify markers predictive of motility dysfunction and to define guidelines for post-surgical care. PMID:23667464

  14. (--Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance

    Directory of Open Access Journals (Sweden)

    Eleonora Cremonini

    2018-04-01

    Full Text Available Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (--epicatechin (EC supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2–20 mg/kg body weight mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption. Keywords: Intestinal permeability, (--Epicatechin, Steatosis, Insulin resistance, Endotoxemia, NADPH oxidase

  15. Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells.

    Science.gov (United States)

    Cui, W; Li, L X; Sun, C M; Wen, Y; Zhou, Y; Dong, Y L; Liu, P

    2010-04-01

    The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-alpha) on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell microporous filters and treated with TNF-alpha (10 or 100 ng/mL) for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-alpha treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-alpha decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-alpha did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-alpha increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

  16. Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

    Directory of Open Access Journals (Sweden)

    W. Cui

    2010-04-01

    Full Text Available The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-α on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-α (10 or 100 ng/mL for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-α treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-α decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-α did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-α increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

  17. Study of Structure and Permeability Relationship of Flavonoids in Caco-2 Cells.

    Science.gov (United States)

    Fang, Yajing; Cao, Weiwei; Xia, Mengmeng; Pan, Siyi; Xu, Xiaoyun

    2017-11-29

    Flavonoids exhibit a broad range of biological activities. However, poor absorption of some flavonoids is a major limitation for use of flavonoids as nutraceuticals. To investigate the structure requirements for flavonoids intestinal absorption, transepithelial transport and cellular accumulation (CA) of 30 flavonoids were determined using the Caco-2 cell monolayer. The bilateral permeation of five types of flavonoids followed the order: flavanones ≥ isoflavones > flavones ≥ chalcones > flavonols. The concentration of flavonoids accumulated in cells did not correlate with cell penetration since the correlation coefficient between the apparent permeability coefficient ( P app ) and their corresponding CA was poor ( R ² < 0.3). Most flavonoids exhibited a ratio of 0.8-1.5 for P app A to B / P app B to A , suggesting passive diffusion pathways. However, luteolin, morin and taxifolin may involve the efflux mechanisms. The quantitative structure-permeability relationship (QSPR) study demonstrated that the intestinal absorption of flavonoids can be related to atomic charges on carbon 3' ( Q C3' ), molecule surface area ( S log P_V 3), balance between the center of mass and position of hydrophobic region ( vsurf_ID 1) and solvation energy of flavonoids ( E_sol ). These results provide useful information for initially screening of flavonoids with high intestinal absorption.

  18. Using magnetic permeability bits to store information

    Science.gov (United States)

    Timmerwilke, John; Petrie, J. R.; Wieland, K. A.; Mencia, Raymond; Liou, Sy-Hwang; Cress, C. D.; Newburgh, G. A.; Edelstein, A. S.

    2015-10-01

    Steps are described in the development of a new magnetic memory technology, based on states with different magnetic permeability, with the capability to reliably store large amounts of information in a high-density form for decades. The advantages of using the permeability to store information include an insensitivity to accidental exposure to magnetic fields or temperature changes, both of which are known to corrupt memory approaches that rely on remanent magnetization. The high permeability media investigated consists of either films of Metglas 2826 MB (Fe40Ni38Mo4B18) or bilayers of permalloy (Ni78Fe22)/Cu. Regions of films of the high permeability media were converted thermally to low permeability regions by laser or ohmic heating. The permeability of the bits was read by detecting changes of an external 32 Oe probe field using a magnetic tunnel junction 10 μm away from the media. Metglas bits were written with 100 μs laser pulses and arrays of 300 nm diameter bits were read. The high and low permeability bits written using bilayers of permalloy/Cu are not affected by 10 Mrad(Si) of gamma radiation from a 60Co source. An economical route for writing and reading bits as small at 20 nm using a variation of heat assisted magnetic recording is discussed.

  19. Anisotropy of permeability in faulted porous sandstones

    Science.gov (United States)

    Farrell, N. J. C.; Healy, D.; Taylor, C. W.

    2014-06-01

    Studies of fault rock permeabilities advance the understanding of fluid migration patterns around faults and contribute to predictions of fault stability. In this study a new model is proposed combining brittle deformation structures formed during faulting, with fluid flow through pores. It assesses the impact of faulting on the permeability anisotropy of porous sandstone, hypothesising that the formation of fault related micro-scale deformation structures will alter the host rock porosity organisation and create new permeability pathways. Core plugs and thin sections were sampled around a normal fault and oriented with respect to the fault plane. Anisotropy of permeability was determined in three orientations to the fault plane at ambient and confining pressures. Results show that permeabilities measured parallel to fault dip were up to 10 times higher than along fault strike permeability. Analysis of corresponding thin sections shows elongate pores oriented at a low angle to the maximum principal palaeo-stress (σ1) and parallel to fault dip, indicating that permeability anisotropy is produced by grain scale deformation mechanisms associated with faulting. Using a soil mechanics 'void cell model' this study shows how elongate pores could be produced in faulted porous sandstone by compaction and reorganisation of grains through shearing and cataclasis.

  20. Permeability Barrier Generation in the Martian Lithosphere

    Science.gov (United States)

    Schools, Joe; Montési, Laurent

    2015-11-01

    Permeability barriers develop when a magma produced in the interior of a planet rises into the cooler lithosphere and crystallizes more rapidly than the lithosphere can deform (Sparks and Parmentier, 1991). Crystallization products may then clog the porous network in which melt is propagating, reducing the permeability to almost zero, i.e., forming a permeability barrier. Subsequent melts cannot cross the barrier. Permeability barriers have been useful to explain variations in crustal thickness at mid-ocean ridges on Earth (Magde et al., 1997; Hebert and Montési, 2011; Montési et al., 2011). We explore here under what conditions permeability barriers may form on Mars.We use the MELTS thermodynamic calculator (Ghiorso and Sack, 1995; Ghiorso et al., 2002; Asimow et al., 2004) in conjunction with estimated Martian mantle compositions (Morgan and Anders, 1979; Wänke and Dreibus, 1994; Lodders and Fegley, 1997; Sanloup et al., 1999; Taylor 2013) to model the formation of permeability barriers in the lithosphere of Mars. In order to represent potential past and present conditions of Mars, we vary the lithospheric thickness, mantle potential temperature (heat flux), oxygen fugacity, and water content.Our results show that permeability layers can develop in the thermal boundary layer of the simulated Martian lithosphere if the mantle potential temperature is higher than ~1500°C. The various Martian mantle compositions yield barriers in the same locations, under matching variable conditions. There is no significant difference in barrier location over the range of accepted Martian oxygen fugacity values. Water content is the most significant influence on barrier development as it reduces the temperature of crystallization, allowing melt to rise further into the lithosphere. Our lower temperature and thicker lithosphere model runs, which are likely the most similar to modern Mars, show no permeability barrier generation. Losing the possibility of having a permeability

  1. In Situ Intestinal Perfusion in Rodents: Future Perspectives for Application on Absorption Studies and Classification of Drugs.

    Science.gov (United States)

    Dezani, Thaisa Marinho; Dezani, Andre Bersani; de Silva, Monica Maria Coquemala; Dos Reis Serra, Cristina Helena

    2017-01-01

    In 1995, the Biopharmaceutics Classification System (BCS) was proposed by Amidon and colleagues as a tool that considers two important parameters regarding drugs: solubility and permeability. Since then, several methods for solubility and permeability studies have been developed for drug delivery and absorption prediction. In recent years, permeability has gained a great highlight and the interaction between a molecule and a biological membrane is not enough to predict the in vivo behavior of a compound. Thus, different methods for permeability assessment are currently used for mechanistic studies including involvement of carriers and several transport pathways. Furthermore, the investigation regarding metabolism has been a focus in recent researches. Based on this idea, Wu and Benet proposed a new tool called Biopharmaceutics Drug Disposition Classification System (BDDCS), where drugs are classified into four classes considering their solubility and metabolism. Among several methods for permeability studies, the in situ intestinal perfusion is considered the closest to in vivo conditions due advantages as intact blood supply and innervation. This review presents the in situ intestinal perfusion model and its application for permeability/ transport studies of drugs and intestinal metabolism. Also, this paper discusses about how the in situ perfusion studies can be used for classification of drugs and the future perspectives for in vivo absorption prediction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. A new in vitro system for evaluation of passive intestinal drug absorption: establishment of a double artificial membrane permeation assay.

    Science.gov (United States)

    Kataoka, Makoto; Tsuneishi, Saki; Maeda, Yukako; Masaoka, Yoshie; Sakuma, Shinji; Yamashita, Shinji

    2014-11-01

    The aim of this present study was to establish a new in vitro assay, double artificial membrane permeation assay (DAMPA), to evaluate the human intestinal permeability of drugs. A double artificial membrane with an intracellular compartment was constructed in side-by-side chambers by sandwiching a filter containing buffer solution with impregnated lipophilic filters with dodecane containing 2w/v% phosphatidylcholine. Permeation data of ionic compounds clearly indicated that not only the pH value of the apical solution but also that of the intracellular compartment affected the permeability across the double artificial membrane. DAMPA was performed with 20 compounds at physiological pH (apical; 6.5, intracellular and basal; 7.4). Paracellular and transcellular permeabilities of compounds in human epithelium were estimated based on the characteristics of the paracellular pathway using physicochemical properties of compounds with the Renkin function and the area factor i.e. the difference in the effective surface area between human epithelium and the double artificial membrane, respectively. The human intestinal permeability of each compound was predicted by the sum of estimated transcellular and paracellular permeabilities. Predicted human intestinal permeability was significantly correlated with the fraction of absorbed dose in humans, indicating that DAMPA has the potential to predict oral absorption of drugs in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Permeability Tests on Silkeborg Sand No. 0000

    DEFF Research Database (Denmark)

    Lund, Willy; Jakobsen, Kim Parsberg

    on the characteristics of the soil matrix, the permeability is determined for different void ratios. All tests are performed on reconstituted specimens of Silkeborg Sand No. 0000. The permeability is determined by use of a falling head apparatus. The apparatus, test procedures and the analysis method are described......The flow through porous media plays an important role in various engineering disciplines, as for example in ground water hydrology and soil mechanics. In the present study the permeability is determined for a fine, saturated sand. As the flow through a porous media strongly depends...

  4. Permeability Tests on Eastern Scheldt Sand

    DEFF Research Database (Denmark)

    Jakobsen, Kim Parsberg

    on the characteristics of the soil matrix, the permeability is determined for different void ratios. All tests are performed on reconstituted specimens of Eastern Scheldt Sand. The permeability is determined by use of a falling head apparatus. Finally the test results are briefly summarised and a relationship between......The flow through porous media plays an important role in various engineering disciplines, as for example in ground water hydrology and soil mechanics. In the present study the permeability is determined for a fine, saturated sand. As the flow through a porous media strongly depends...

  5. Quantifying porosity, compressibility and permeability in Shale

    DEFF Research Database (Denmark)

    Mbia, Ernest Ncha; Fabricius, Ida Lykke; Frykman, Peter

    (XRD) of shale samples show about 50% silt and high content of kaolinite in the clay fraction when compared with offshore samples from the Central Graben. Porosity measurements from helium porosimetry-mercury immersion (HPMI), mercury injection capillary pressure (MICP) and nuclear magnetic resonance...... strain data. We found that Kozeny's modelled permeability fall in the same order of magnitude with measured permeability for shale rich in kaolinite but overestimates permeability by two to three orders of magnitudes for shale with high content of smectite. The empirical Yang and Aplin model gives good...

  6. Effect of temperature on sandstone permeability

    DEFF Research Database (Denmark)

    Rosenbrand, Esther; Kjøller, Claus

    of the salinity of the pore fluid can increase the electrical double layer repulsion between quartz grains and kaolinite particles in Berea sandstone, which could lead to kaolinite mobilisation and permeability reduction. Heating increases the magnitude of the mineral surface charge, whereas salinity reduction...... permeability to brine than to gas is often observed, which might be due to interaction between the mineral surface and the pore fluid. By modelling a layer of immobile fluid on the fluid-mineral interface permeability to brine was estimated, based on both the pore size distribution from NMR combined...

  7. Diagnosis of intestinal and extra intestinal amoebiasis

    International Nuclear Information System (INIS)

    Lopez, Myriam Consuelo; Quiroz, Damian Arnoldo; Pinilla, Analida Elizabeth

    2007-01-01

    The objective is to carry out a review of the national and international literature as of the XXth century in order to update the advances for the diagnosis of complex odd Entamoeba histolytic / Entamoeba dispar and that of intestinal and extra intestinal amoebiasis that may be of use to the scientific community. As well as to unify the diagnostic criteria of this parasitosis known as a public health problem, and as a consequence of that, optimize the quality of population care. Data source: there was a systematic search for the scientific literature Publisher in Spanish and English since 1960 until today, this selection started on the first semester of 2006 until 2007, in the development of the line on intestinal and extra-intestinal amoebiasis of the Medical School of the National University of Colombia. A retrospective search process was carried out, systematically reviewing the most relevant articles as well as the products of this research line. In deciding how to make this article, there was a continuous search in different data bases such as Medline, SciELO and other bases in the library of the National University of Colombia, as well as other classical books related to the subject. For that purpose the terms amoebiasis, odd Entamoeba histolytic, Entamoeba, diagnosis, epidemiology, dysentery, amoebic liver abscess, were used. Studies selection: titles and abstracts were reviewed to select the original publications and the most representative ones related to this article's subject. Data extraction: the articles were classified according to the subject, the chronology and the authors according to the scientific contribution to solve the problem. Synthesis of the data: in the fi rst instance, a chronological critical analysis was carried out to order and synthesize the progress made in the diagnosis until confirmation of the experts' agreements in the field of amoebiasis was obtained throughout the world. Conclusion: this article summarizes what has taken place

  8. Influence of fentanyl and morphine on intestinal circulation

    International Nuclear Information System (INIS)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of 86 Rb and 9-micron spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O 2 up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation

  9. Influence of fentanyl and morphine on intestinal circulation

    Energy Technology Data Exchange (ETDEWEB)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-06-01

    The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of /sup 86/Rb and 9-micron spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O/sub 2/up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation.

  10. Naturally occurring glycoalkaloids in potatoes aggravate intestinal inflammation in two mouse models of inflammatory bowel disease.

    Science.gov (United States)

    Iablokov, Vadim; Sydora, Beate C; Foshaug, Rae; Meddings, Jon; Driedger, Darcy; Churchill, Tom; Fedorak, Richard N

    2010-11-01

    Inflammatory bowel disease (IBD) may be initiated following disruption of the intestinal epithelial barrier. This disruption, in turn, permits luminal antigens unfettered access to the mucosal immune system and leads to an uncontrolled inflammatory response. Glycoalkaloids, which are found in potatoes, disrupt cholesterol-containing membranes such as those of the intestinal epithelium. Glycoalkaloid ingestion through potatoes may play a role in the initiation and/or perpetuation of IBD. To determine if commercial and high glycoalkaloids containing fried potato skins aggravate intestinal inflammation using two different animal models of IBD. Fried potato skins from commercial potatoes containing low/medium glycoalkaloid levels and high glycoalkaloids potatoes were fed for 20 days to interleukin 10 gene-deficient mice and dextran sodium sulfate-induced colitic mice. Intestinal permeability, mucosal cytokine and myeloperoxidase levels and body weight were determined to assess intestinal injury. Deep frying potato skins markedly increased glycoalkaloid content. Interleukin 10 gene-deficient mice fed fried commercial potato skins with medium glycoalkaloid content exhibited significantly elevated levels of ileal IFN-γ relative to controls. Mice in the dextran sodium sulfate colitis model that were fed the same strain of potatoes demonstrated significantly elevated levels of pro-inflammatory cytokines IFN-γ, TNF-α, and IL-17 in the colon in addition to an enhanced colonic permeability. Inflammatory response was intensified when the mice were fed potatoes with higher glycoalkaloid contents. Our results demonstrate that consumption of potato skins containing glycoalkaloids can significantly aggravate intestinal inflammation in predisposed individuals.

  11. Diagnostic accuracy of post mortem MRI for abdominal abnormalities in foetuses and children

    International Nuclear Information System (INIS)

    Arthurs, Owen J.; Thayyil, Sudhin; Owens, Catherine M.; Olsen, Oystein E.; Wade, Angie; Addison, Shea; Jones, Rod; Norman, Wendy; Scott, Rosemary J.

    2015-01-01

    Highlights: •Postmortem MR imaging (PMMR) has high overall accuracy for abdominal pathology in foetuses, newborns and children. •PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. •In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities. -- Abstract: Background: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for abdominal pathology in foetuses and children, compared to conventional autopsy. Methods: Institutional ethics approval and parental consent was obtained. 400 unselected foetuses and children underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data respectively. Results: Abdominal abnormalities were found in 70/400 (12%) autopsies. Overall sensitivity and specificity (95% confidence interval) of PMMR for abdominal pathology was 72.5% (61.0, 81.6) and 90.8% (87.0, 93.6), with positive (PPV) and negative predictive values (NPV) of 64.1% (53.0, 73.9) and 93.6% (90.2, 95.8) respectively. PMMR was good at detecting renal abnormalities (sensitivity 80%), particularly in foetuses, and relatively poor at detecting intestinal abnormalities (sensitivity 50%). Overall accuracy was 87.4% (83.6, 90.4). Conclusions: PMMR has high overall accuracy for abdominal pathology in foetuses, newborns and children. PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities

  12. Diagnostic accuracy of post mortem MRI for abdominal abnormalities in foetuses and children

    Energy Technology Data Exchange (ETDEWEB)

    Arthurs, Owen J., E-mail: owen.arthurs@gosh.nhs.uk [Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Institute of Child Health, UCL, London (United Kingdom); Thayyil, Sudhin, E-mail: s.thayyil@imperial.ac.uk [Perinatal Neurology and Neonatology, Imperial College London, London (United Kingdom); Owens, Catherine M., E-mail: Catherine.owens@gosh.nhs.uk [Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Cardiorespiratory Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Olsen, Oystein E., E-mail: oystein.olsen@gosh.nhs.uk [Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Institute of Child Health, UCL, London (United Kingdom); Wade, Angie, E-mail: a.wade@ucl.ac.uk [Clinical Epidemiology, Nutrition and Biostatistics Section, UCL Institute of Child health, London (United Kingdom); Addison, Shea, E-mail: shea.addison@imperial.ac.uk [Perinatal Neurology and Neonatology, Imperial College London, London (United Kingdom); Jones, Rod, E-mail: rod.jones@gosh.nhs.uk [Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Cardiorespiratory Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Norman, Wendy, E-mail: wendy.norman@gosh.nhs.uk [Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Cardiorespiratory Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Scott, Rosemary J., E-mail: rosemary.scott@uclh.nhs.uk [Department of Histopathology, University College London Hospital NHS Trust, London (United Kingdom); and others

    2015-03-15

    Highlights: •Postmortem MR imaging (PMMR) has high overall accuracy for abdominal pathology in foetuses, newborns and children. •PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. •In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities. -- Abstract: Background: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for abdominal pathology in foetuses and children, compared to conventional autopsy. Methods: Institutional ethics approval and parental consent was obtained. 400 unselected foetuses and children underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data respectively. Results: Abdominal abnormalities were found in 70/400 (12%) autopsies. Overall sensitivity and specificity (95% confidence interval) of PMMR for abdominal pathology was 72.5% (61.0, 81.6) and 90.8% (87.0, 93.6), with positive (PPV) and negative predictive values (NPV) of 64.1% (53.0, 73.9) and 93.6% (90.2, 95.8) respectively. PMMR was good at detecting renal abnormalities (sensitivity 80%), particularly in foetuses, and relatively poor at detecting intestinal abnormalities (sensitivity 50%). Overall accuracy was 87.4% (83.6, 90.4). Conclusions: PMMR has high overall accuracy for abdominal pathology in foetuses, newborns and children. PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities.

  13. Bifidobacterium animalis subsp lactis CNCM-I2494 restores gut barrier permeability in chronically low-grade inflamed mice

    Directory of Open Access Journals (Sweden)

    Rebeca eMartín

    2016-05-01

    Full Text Available Growing evidence supports the efficacy of many probiotic strains in the management of gastrointestinal disorders associated with deregulated intestinal barrier function and/or structure. In particular, bifidobacteria have been studied for their efficacy to both prevent and treat a broad spectrum of animal and/or human gut disorders. The aim of the current work was thus to evaluate effects on intestinal barrier function of Bifidobacterium animalis subsp lactis CNCM-I2494, a strain used in fermented dairy products. A chronic DNBS-induced low-grade inflammation model causing gut dysfunction in mice was used in order to study markers of inflammation, intestinal permeability and immune function in the presence of the bacterial strain. In this chronic low-grade inflammation mice model several parameters pointed out the absence of an over active inflammation process. However, gut permeability, lymphocyte populations and colonic cytokines were found to be altered. B. animalis subsp lactis CNCM-I2494 was able to protect barrier functions by restoring intestinal permeability, colonic goblet cell populations and cytokine levels. Furthermore, tight junction (TJ proteins levels were also measured by qRT-PCR showing the ability of this strain to specifically normalize the level of several TJ proteins, in particular for claudin-4. Finally, B. lactis strain counterbalanced CD4+ lymphocyte alterations in both spleen and mesenteric lymphoid nodes (MLN. It restores the Th1/Th2 ratio altered by the DNBS challenge (which locally augments CD4+ Th1 cells by increasing the Th2 response as measured by the increase in the production of major representative Th2 cytokines (IL-4, IL-5 and IL-10. Altogether, these data suggest that B. animalis subsp lactis CNCM-I2494 may efficiently prevent disorders associated with increased barrier permeability.

  14. Permeability of gypsum samples dehydrated in air

    Science.gov (United States)

    Milsch, Harald; Priegnitz, Mike; Blöcher, Guido

    2011-09-01

    We report on changes in rock permeability induced by devolatilization reactions using gypsum as a reference analog material. Cylindrical samples of natural alabaster were dehydrated in air (dry) for up to 800 h at ambient pressure and temperatures between 378 and 423 K. Subsequently, the reaction kinetics, so induced changes in porosity, and the concurrent evolution of sample permeability were constrained. Weighing the heated samples in predefined time intervals yielded the reaction progress where the stoichiometric mass balance indicated an ultimate and complete dehydration to anhydrite regardless of temperature. Porosity showed to continuously increase with reaction progress from approximately 2% to 30%, whilst the initial bulk volume remained unchanged. Within these limits permeability significantly increased with porosity by almost three orders of magnitude from approximately 7 × 10-19 m2 to 3 × 10-16 m2. We show that - when mechanical and hydraulic feedbacks can be excluded - permeability, reaction progress, and porosity are related unequivocally.

  15. Surface sedimentation at permeable pavement systems

    DEFF Research Database (Denmark)

    Støvring, Jan; Dam, Torben; Jensen, Marina Bergen

    2018-01-01

    of restorative cleaning (RC), nine recently built PP systems were tested for their infiltration capacity with and without restorative cleaning (RC) over an interval of 12–14.5 months. The results were related to each site’s unique history of sedimentation. RC significantly improved permeability, but when...... revisited after approximately one year, the permeability of cleaned surfaces was not significantly better for the RC spots than from their uncleaned neighbouring areas. Relating permeability to the contextual issues revealed that PP perimeter, adjacent bare soil and mismanagement strongly affected...... the sedimentation process. At two of the sites, sedimentation processes were so advanced that surface permeability was below the level of service (five-year design storm)....

  16. Intestinal anisakidosis (anisakiosis).

    Science.gov (United States)

    Takei, Hidehiro; Powell, Suzanne Z

    2007-10-01

    A case of intestinal anisakidosis in a 42-year-old man in Japan is presented. His chief complaint was an acute onset of severe abdominal pain. Approximately 12 hours before the onset of this symptom, he had eaten sliced raw mackerel ("sashimi"). Upper endoscopy was unremarkable. At exploratory laparotomy, an edematous, diffusely thickened segment of jejunum was observed, which was resected. The postoperative course was uneventful. The segment of small intestine showed a granular indurated area on the mucosal surface, and microscopically, a helminthic larva penetrating the intestinal wall, which was surrounded by a cuff of numerous neutrophils and eosinophils, as well as diffuse acute serositis. A cross section of the larva revealed the internal structures, pathognomonic of Anisakis simplex. Although anisakidosis is rare in the United States, with the increasing popularity of Japanese cuisine, the incidence is expected to increase, and pathologists should be familiar with this disease.

  17. Intestinal failure: a review

    Science.gov (United States)

    Allan, Philip; Lal, Simon

    2018-01-01

    Intestinal failure (IF) is the inability of the gut to absorb necessary water, macronutrients (carbohydrate, protein, and fat), micronutrients, and electrolytes sufficient to sustain life and requiring intravenous supplementation or replacement. Acute IF (types 1 and 2) is the initial phase of the illness and may last for weeks to a few months, and chronic IF (type 3) from months to years. The challenge of caring for patients with IF is not merely the management of the underlying condition leading to IF or the correct provision of appropriate nutrition or both but also the prevention of complications, whether thromboembolic phenomenon (for example, venous occlusion), central venous catheter-related bloodstream infection, IF-associated liver disease, or metabolic bone disease. This review looks at recent questions regarding chronic IF (type 3), its diagnosis and management, the role of the multidisciplinary team, and novel therapies, including hormonal treatment for short bowel syndrome but also surgical options for intestinal lengthening and intestinal transplant. PMID:29399329

  18. Small intestine diverticuli

    International Nuclear Information System (INIS)

    Pomakov, P.; Risov, A.

    1991-01-01

    The routine method of contrast matter passage applied to 850 patients with different gastrointestinal diseases proved inefficient to detect any small-intestinal diverticuli. The following modiffications of the method have been tested in order to improve the diagnostic possibilities of the X-ray: study at short intervals, assisted passage, enteroclysm, pharmacodynamic impact, retrograde filling of the ileum by irrigoscopy. Twelve diverticuli of the small-intestinal loops were identified: 5 Meckel's diverticuli, 2 solitary of which one of the therminal ileum, 2 double diverticuli and 1 multiple diverticulosis of the jejunum. The results show that the short interval X-ray examination of the small intestines is the method of choice for identifying local changes in them. The solitary diverticuli are not casuistic scarcity, its occurrence is about 0.5% at purposeful X-ray investigation. The assisted passage method is proposed as a method of choice for detection of the Meckel's diverticulum. 5 figs., 3 tabs. 18 refs

  19. Chronic intestinal pseudoobstruction syndrome

    International Nuclear Information System (INIS)

    Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok

    1992-01-01

    Chronic intestinal pseudoobstruction syndrome is a rare clinical condition in which impaired intestinal peristalsis causes recurrent symptoms of bowel obstruction in the absence of a mechanical occlusion. This syndrome may involve variable segments of small or large bowel, and may be associated with urinary bladder retention. This study included 6 children(3 boys and 3 girls) of chronic intestinal obstruction. Four were symptomatic at birth and two were of the ages of one month and one year. All had abdominal distension and deflection difficulty. Five had urinary bladder distension. Despite parenteral nutrition and surgical intervention(ileostomy or colostomy), bowel obstruction persisted and four patients expired from sepses within one year. All had gaseous distension of small and large bowel on abdominal films. In small bowel series, consistent findings were variable degree of dilatation, decreased peristalsis(prolonged transit time) and microcolon or microrectum. This disease entity must be differentiated from congenital megacolon, ileal atresia and megacystis syndrome

  20. Small Intestinal Infections.

    Science.gov (United States)

    Munot, Khushboo; Kotler, Donald P

    2016-06-01

    Small intestinal infections are extremely common worldwide. They may be bacterial, viral, or parasitic in etiology. Most are foodborne or waterborne, with specific etiologies differing by region and with diverse pathophysiologies. Very young, very old, and immune-deficient individuals are the most vulnerable to morbidity or mortality from small intestinal infections. There have been significant advances in diagnostic sophistication with the development and early application of molecular diagnostic assays, though these tests have not become mainstream. The lack of rapid diagnoses combined with the self-limited nature of small intestinal infections has hampered the development of specific and effective treatments other than oral rehydration. Antibiotics are not indicated in the absence of an etiologic diagnosis, and not at all in the case of some infections.

  1. The intestinal calcistat

    Directory of Open Access Journals (Sweden)

    M K Garg

    2013-01-01

    Full Text Available The main physiological function of vitamin D is maintenance of calcium homeostasis by its effect on calcium absorption, and bone health in association with parathyroid gland. Vitamin D deficiency (VDD is defined as serum 25-hydroxy vitamin D (25OHD levels <20 ng/ml. Do all subjects with VDD have clinical disease according to this definition? We hypothesize that there exist an intestinal calcistat, which controls the calcium absorption independent of PTH levels. It consists of calcium sensing receptor (CaSR on intestinal brush border, which senses calcium in intestinal cells and vitamin D system in intestinal cells. CaSR dampens the generation of active vitamin D metabolite in intestinal cells and decrease active transcellular calcium transport. It also facilitates passive paracellular diffusion of calcium in intestine. This local adaptation adjusts the fractional calcium absorption according the body requirement. Failure of local adaptation due to decreased calcium intake, decreased supply of 25OHD, mutation in CaSR or vitamin D system decreases systemic calcium levels and systemic adaptations comes into the play. Systemic adaptations consist of rise in PTH and increase in active vitamin D metabolites. These adaptations lead to bone resorption and maintenance of calcium homeostasis. Not all subjects with varying levels of VDD manifest with secondary hyperparathyroidism and decreased in bone mineral density. We suggest that rise in PTH is first indicator of VDD along with decrease in BMD depending on duration of VDD. Hence, subjects with any degree of VDD with normal PTH and BMD should not be labeled as vitamin D deficient. These subjects can be called subclinical VDD, and further studies are required to assess beneficial effect of vitamin D supplementation in this subset of population.

  2. Negative permeability from random particle composites

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Shahid, E-mail: shussain2@qinetiq.com

    2017-04-15

    Artificial media, such as those composed of periodically-spaced wires for negative permittivity and split ring resonators for negative permeability have been extensively investigated for negative refractive index (NRI) applications (Smith et al., 2004; Pendry et al., 1999) [1,2]. This paper presents an alternative method for producing negative permeability: granular (or particulate) composites incorporating magnetic fillers. Artificial media, such as split-ring resonators, are designed to produce a magnetic resonance feature, which results in negative permeability over a narrow frequency range about the resonance frequency. The position of the feature is dependent upon the size of the inclusion. The material in this case is anisotropic, such that the feature is only observable when the materials are orientated in a specific direction relative to the applied field. A similar resonance can be generated in magnetic granular (particulate) materials: ferromagnetic resonance from the natural spin resonance of particles. Although the theoretical resonance profiles in granular composites shows the permeability dipping to negative values, this is rarely observed experimentally due to resonance damping effects. Results are presented for iron in spherical form and in flake form, dispersed in insulating host matrices. The two particle shapes show different permeability performance, with the magnetic flakes producing a negative contribution. This is attributed to the stronger coupling with the magnetic field resulting from the high aspect ratio of the flakes. The accompanying ferromagnetic resonance is strong enough to overcome the effects of damping and produce negative permeability. The size of random particle composites is not dictated by the wavelength of the applied field, so the materials are potentially much thinner than other, more traditional artificial composites at microwave frequencies. - Highlights: • Negative permeability from random particle composites is

  3. Dietary soya saponins increase gut permeability and play a key role in the onset of soyabean-induced enteritis in Atlantic salmon (Salmo salar L.)

    DEFF Research Database (Denmark)

    Knudsen, Sven David Lausten; Jutfelt, Fredrik; Sundh, Henrik

    2008-01-01

    are naturally occurring amphiphilic molecules and have been associated with many biological activities. The aim of the present study was to investigate whether soya saponins trigger the onset of soyabean-induced enteritis in Atlantic salmon (Salmo salar L.), and to examine if dietary soya saponins...... increase the epithelial permeability of the distal intestine in Atlantic salmon. Seven experimental diets containing different levels of soya saponins were fed to seawater-adapted Atlantic salmon for 53 d. The diets included a fishmeal-based control diet, two fishmeal-based diets with different levels...... of added soya saponins, one diet containing 25 % lupin kernel meal, two diets based on 25 % lupin kernel meal with different levels of added soya saponins, and one diet containing 25 % defatted soyabean meal. The effect on intestinal morphology, intestinal epithelial permeability and faecal DM content...

  4. Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity.

    Science.gov (United States)

    Lucarini, Simone; Fagioli, Laura; Campana, Raffaella; Cole, Hannah; Duranti, Andrea; Baffone, Wally; Vllasaliu, Driton; Casettari, Luca

    2016-10-01

    Sugar based surfactants conjugated with fatty acid chains are an emerging broad group of highly biocompatible and biodegradable compounds with established and potential future applications in the pharmaceutical, cosmetic and food industries. In this work, we investigated absorption enhancing and antimicrobial properties of disaccharide lactose, monoesterified with unsaturated fatty acids through an enzymatic synthetic approach. After chemical and cytotoxicity characterizations, their permeability enhancing activity was demonstrated using intestinal Caco-2 monolayers through transepithelial electrical resistance (TEER) and permeability studies. The synthesized compounds, namely lactose palmitoleate (URB1076) and lactose nervonate (URB1077), were shown to exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram-negative microorganisms and fungi. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Charge Inversion in semi-permeable membranes

    Science.gov (United States)

    Das, Siddhartha; Sinha, Shayandev; Jing, Haoyuan

    Role of semi-permeable membranes like lipid bilayer is ubiquitous in a myriad of physiological and pathological phenomena. Typically, lipid membranes are impermeable to ions and solutes; however, protein channels embedded in the membrane allow the passage of selective, small ions across the membrane enabling the membrane to adopt a semi-permeable nature. This semi-permeability, in turn, leads to electrostatic potential jump across the membrane, leading to effects such as regulation of intracellular calcium, extracellular-vesicle-membrane interactions, etc. In this study, we theoretically demonstrate that this semi-permeable nature may trigger the most remarkable charge inversion (CI) phenomenon in the cytosol-side of the negatively-charged lipid bilayer membrane that are selectively permeable to only positive ions of a given salt. This CI is manifested as the changing of the sign of the electrostatic potential from negative to positive from the membrane-cytosol interface to deep within the cytosol. We study the impact of the parameters such as the concentration of this salt with selectively permeable ions as well as the concentration of an external salt in the development of this CI phenomenon. We anticipate such CI will profoundly influence the interaction of membrane and intra-cellular moieties (e.g., exosome or multi-cellular vesicles) having implications for a host of biophysical processes.

  6. Transformable ferroelectric control of dynamic magnetic permeability

    Science.gov (United States)

    Jiang, Changjun; Jia, Chenglong; Wang, Fenglong; Zhou, Cai; Xue, Desheng

    2018-02-01

    Magnetic permeability, which measures the response of a material to an applied magnetic field, is crucial to the performance of magnetic devices and related technologies. Its dynamic value is usually a complex number with real and imaginary parts that describe, respectively, how much magnetic power can be stored and lost in the material. Control of permeability is therefore closely related to energy redistribution within a magnetic system or energy exchange between magnetic and other degrees of freedom via certain spin-dependent interactions. To avoid a high power consumption, direct manipulation of the permeability with an electric field through magnetoelectric coupling leads to high efficiency and simple operation, but remains a big challenge in both the fundamental physics and material science. Here we report unambiguous evidence of ferroelectric control of dynamic magnetic permeability in a Co /Pb (Mg1/3Nb2/3) 0.7Ti0.3O3 (Co/PMN-PT) heterostructure, in which the ferroelectric PMN-PT acts as an energy source for the ferromagnetic Co film via an interfacial linear magnetoelectric interaction. The electric field tuning of the magnitude and line shape of the permeability offers a highly localized means of controlling magnetization with ultralow power consumption. Additionally, the emergence of negative permeability promises a new way of realizing functional nanoscale metamaterials with adjustable refraction index.

  7. The Permeability of an Artificial Membrane for Wide Range of pH in Human Gastrointestinal Tract: Experimental Measurements and Quantitative StructureActivity Relationship.

    Science.gov (United States)

    Oja, Mare; Maran, Uko

    2015-06-01

    In silico models for membrane permeability have been based on values measured for single pH. Depending on the diet (fasted/fed state) and part of human intestine the range of pH varies approximately from 2.4 to 8.0. This motivated to study and model the membrane permeability of chemicals considering the whole range of pH in the human intestine. For this, effective membrane permeability values were measured for 65 drugs and drug-like compounds using PAMPA method at four pHs (3, 5, 7.4, 9) over 48 h, introducing technological innovations for the time-dependence measurement. The highest permeability value of a compound from four pHs was used to derive QSAR analyzing a large pool of molecular descriptors and introducing new descriptor. Using stepwise forward selection approach a significant QSAR model was derived that included only two mechanistically relevant descriptors, the logarithmic octanol-water partition coefficient and hydrogen bonding surface area. Prediction confidence of the model was blind tested with a true external validation set of 15 compounds. The resulting QSAR model shows potential to combine permeability values from various pH-s into one descriptive and predictive model for estimating maximum permeability in human gastrointestinal tract. The QSAR model and data are available through the QsarDB repository (http://dx.doi.org/10.15152/QDB.137). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Nanosuspensions Containing Oridonin/HP-β-Cyclodextrin Inclusion Complexes for Oral Bioavailability Enhancement via Improved Dissolution and Permeability.

    Science.gov (United States)

    Zhang, Xingwang; Zhang, Tianpeng; Lan, Yali; Wu, Baojian; Shi, Zhihai

    2016-04-01

    Chemotherapy via oral route of anticancer drugs offers much convenience and compliance to patients. However, oral chemotherapy has been challenged by limited absorption due to poor drug solubility and intestinal efflux. In this study, we aimed to develop a nanosuspension formulation of oridonin (Odn) using its cyclodextrin inclusion complexes to enhance oral bioavailability. Nanosuspensions containing Odn/2 hydroxypropyl-β-cyclodextrin inclusion complexes (Odn-CICs) were prepared by a solvent evaporation followed by wet media milling technique. The nanosuspensions were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and dissolution. The resulting nanosuspensions were approximately 313.8 nm in particle size and presented a microcrystal morphology. Nanosuspensions loading Odn-CICs dramatically enhanced the dissolution of Odn. Further, the intestinal effective permeability of Odn was markedly enhanced in the presence of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and poloxamer. Bioavailability studies showed that nanosuspensions with Odn-CICs can significantly promote the oral absorption of Odn with a relative bioavailability of 213.99% (Odn suspensions as reference). Odn itself possesses a moderate permeability and marginal intestinal metabolism. Thus, the enhanced bioavailability for Odn-CIC nanosuspensions can be attributed to improved dissolution and permeability by interaction with absorptive epithelia and anti-drug efflux. Nanosuspensions prepared from inclusion complexes may be a promising approach for the oral delivery of anticancer agents.

  9. Intestinal microbiota and ulcerative colitis.

    Science.gov (United States)

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. Small intestine aspirate and culture

    Science.gov (United States)

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  11. Abnormal pressure in hydrocarbon environments

    Science.gov (United States)

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  12. Comparative field permeability measurement of permeable pavements using ASTM C1701 and NCAT permeameter methods.

    Science.gov (United States)

    Li, Hui; Kayhanian, Masoud; Harvey, John T

    2013-03-30

    Fully permeable pavement is gradually gaining support as an alternative best management practice (BMP) for stormwater runoff management. As the use of these pavements increases, a definitive test method is needed to measure hydraulic performance and to evaluate clogging, both for performance studies and for assessment of permeability for construction quality assurance and maintenance needs assessment. Two of the most commonly used permeability measurement tests for porous asphalt and pervious concrete are the National Center for Asphalt Technology (NCAT) permeameter and ASTM C1701, respectively. This study was undertaken to compare measured values for both methods in the field on a variety of permeable pavements used in current practice. The field measurements were performed using six experimental section designs with different permeable pavement surface types including pervious concrete, porous asphalt and permeable interlocking concrete pavers. Multiple measurements were performed at five locations on each pavement test section. The results showed that: (i) silicone gel is a superior sealing material to prevent water leakage compared with conventional plumbing putty; (ii) both methods (NCAT and ASTM) can effectively be used to measure the permeability of all pavement types and the surface material type will not impact the measurement precision; (iii) the permeability values measured with the ASTM method were 50-90% (75% on average) lower than those measured with the NCAT method; (iv) the larger permeameter cylinder diameter used in the ASTM method improved the reliability and reduced the variability of the measured permeability. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Frictional stability-permeability relationships for fractures in shales: Friction-Permeability Relationships

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Yi [Department of Energy and Mineral Engineering, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Elsworth, Derek [Department of Energy and Mineral Engineering, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Department of Geosciences, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Wang, Chaoyi [Department of Energy and Mineral Engineering, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Ishibashi, Takuya [Department of Energy and Mineral Engineering, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Fukushima Renewable Energy Institute, National Institute of Advanced Industrial Science and Technology, Koriyama Japan; Fitts, Jeffrey P. [Department of Civil and Environmental Engineering, Princeton University, Princeton New Jersey USA

    2017-01-01

    There is wide concern that fluid injection in the subsurface, such as for the stimulation of shale reservoirs or for geological CO2 sequestration (GCS), has the potential to induce seismicity that may change reservoir permeability due to fault slip. However, the impact of induced seismicity on fracture permeability evolution remains unclear due to the spectrum of modes of fault reactivation (e.g., stable versus unstable). As seismicity is controlled by the frictional response of fractures, we explore friction-stability-permeability relationships through the concurrent measurement of frictional and hydraulic properties of artificial fractures in Green River shale (GRS) and Opalinus shale (OPS). We observe that carbonate-rich GRS shows higher frictional strength but weak neutral frictional stability. The GRS fracture permeability declines during shearing while an increased sliding velocity reduces the rate of permeability decline. By comparison, the phyllosilicate-rich OPS has lower friction and strong stability while the fracture permeability is reduced due to the swelling behavior that dominates over the shearing induced permeability reduction. Hence, we conclude that the friction-stability-permeability relationship of a fracture is largely controlled by mineral composition and that shale mineral compositions with strong frictional stability may be particularly subject to permanent permeability reduction during fluid infiltration.

  14. Diabetes-induced mechanophysiological changes in the small intestine and colon

    DEFF Research Database (Denmark)

    Zhao, Mirabella; Liao, Donghua; Zhao, Jingbo

    2017-01-01

    The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities...... they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut...... and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients....

  15. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

    Directory of Open Access Journals (Sweden)

    Tomohiro Kawahara

    Full Text Available Human rotavirus (RV infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1, which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in

  16. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

    Science.gov (United States)

    Kawahara, Tomohiro; Makizaki, Yutaka; Oikawa, Yosuke; Tanaka, Yoshiki; Maeda, Ayako; Shimakawa, Masaki; Komoto, Satoshi; Moriguchi, Kyoko; Ohno, Hiroshi; Taniguchi, Koki

    2017-01-01

    Human rotavirus (RV) infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1), which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in mice administered

  17. Application of fluorescent tracer agent technology to point-of-care gastrointestinal permeability measurement

    Science.gov (United States)

    Dorshow, Richard B.; Shieh, Jeng-Jong; Rogers, Thomas E.; Hall-Moore, Carla; Shaikh, Nurmohammad; Talcott, Michael; Tarr, Phillip I.

    2016-03-01

    Gut dysfunction, often accompanied by increased mucosal permeability to gut contents, frequently accompanies a variety of human intestinal inflammatory conditions. These disorders include inflammatory bowel diseases (e.g., Crohn's Disease) and environmental enteropathy and enteric dysfunction, a condition strongly associated with childhood malnutrition and stunting in resource poor areas of the world. The most widely used diagnostic assay for gastrointestinal permeability is the lactulose to mannitol ratio (L:M) measurement. These sugars are administered orally, differentially absorbed by the gut, and then cleared from the body by glomerular filtration in the kidney. The amount of each sugar excreted in the urine is measured. The larger sugar, lactulose, is minimally absorbed through a healthy gut. The smaller sugar, mannitol, in contrast, is readily absorbed through both a healthy and injured gut. Thus a higher ratio of lactulose to mannitol reflects increased intestinal permeability. However, several issues prevent widespread use of the L:M ratio in clinical practice. Urine needs to be collected over time intervals of several hours, the specimen then needs to be transported to an analytical laboratory, and sophisticated equipment is required to measure the concentration of each sugar in the urine. In this presentation we show that fluorescent tracer agents with molecular weights similar to those of the sugars, selected from our portfolio of biocompatible renally cleared fluorophores, mimic the L:M ratio test for gut permeability. This fluorescent tracer agent detection technology can be used to overcome the limitations of the L:M assay, and is amenable to point-of-care clinical use.

  18. Effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid in rats.

    Science.gov (United States)

    Zhou, Yan; Jiao, Yang; Wei, Yu-Hui; Zhang, Guo-Rong; Zhang, Jian-Ping; Ren, Jiang-Xia; Zhang, Fan; Zhang, Guo-Qiang; Duan, Hao-Gang; Wu, Xin-An

    2013-03-01

    Pyridoxine is always simultaneously administered orally with isoniazid for tuberculosis patients in the clinic to prevent or treat the nervous system side effects induced by isoniazid. So the aim of this research was to investigate the effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid. The intestinal absorption of isoniazid with or without pyridoxine was investigated by the rat single-pass intestinal perfusion model in situ, and a high-performance liquid chromatographic method was applied to study the pharmacokinetics of isoniazid with or without pyridoxine. The results suggested that the intestinal apparent permeability (P app) and intestinal absorption rate constant (K a) for isoniazid (30 μg/ml) were decreased by 43.7 and 36.4 %, respectively, by co-perfused pyridoxine (40 μg/ml). In vivo, the effect of pyridoxine on isoniazid pharmacokinetic correlated with the doses of pyridoxine. The blood concentrations of isoniazid at the absorption phase were affected by co-administered pyridoxine, but the AUC and C max of isoniazid were not greatly affected by pyridoxine as expected from the inhibition by pyridoxine of the intestinal absorption of isoniazid, which could be caused by its rapid absorption phase. Therefore, although the intestinal absorption of isoniazid could be significantly inhibited by pyridoxine, the pharmacokinetics of isoniazid oral administration was not greatly affected by the decreased intestinal absorption of isoniazid due to its rapid absorption.

  19. Dietary soya saponins increase gut permeability and play a key role in the onset of soyabean-induced enteritis in Atlantic salmon ( Salmo salar L.).

    Science.gov (United States)

    Knudsen, David; Jutfelt, Fredrik; Sundh, Henrik; Sundell, Kristina; Koppe, Wolfgang; Frøkiaer, Hanne

    2008-07-01

    Saponins are naturally occurring amphiphilic molecules and have been associated with many biological activities. The aim of the present study was to investigate whether soya saponins trigger the onset of soyabean-induced enteritis in Atlantic salmon (Salmo salar L.), and to examine if dietary soya saponins increase the epithelial permeability of the distal intestine in Atlantic salmon. Seven experimental diets containing different levels of soya saponins were fed to seawater-adapted Atlantic salmon for 53 d. The diets included a fishmeal-based control diet, two fishmeal-based diets with different levels of added soya saponins, one diet containing 25% lupin kernel meal, two diets based on 25% lupin kernel meal with different levels of added soya saponins, and one diet containing 25% defatted soyabean meal. The effect on intestinal morphology, intestinal epithelial permeability and faecal DM content was examined. Fish fed 25% defatted soyabean meal displayed severe enteritis, whereas fish fed 25% lupin kernel meal had normal intestinal morphology. The combination of soya saponins and fishmeal did not induce morphological changes but fish fed soya saponins in combination with lupin kernel meal displayed significant enteritis. Increased epithelial permeability was observed in fish fed 25% defatted soyabean meal and in fish fed soya saponin concentrate independent of the protein source in the feed. The study demonstrates that soya saponins, in combination with one or several unidentified components present in legumes, induce an inflammatory reaction in the distal intestine of Atlantic salmon. Soya saponins increase the intestinal epithelial permeability but do not, per se, induce enteritis.

  20. Regulators of Intestinal Epithelial Migration in Sepsis.

    Science.gov (United States)

    Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

    2018-02-08

    The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

  1. The role of small intestinal bacterial overgrowth in Parkinson's disease.

    Science.gov (United States)

    Fasano, Alfonso; Bove, Francesco; Gabrielli, Maurizio; Petracca, Martina; Zocco, Maria Assunta; Ragazzoni, Enzo; Barbaro, Federico; Piano, Carla; Fortuna, Serena; Tortora, Annalisa; Di Giacopo, Raffaella; Campanale, Mariachiara; Gigante, Giovanni; Lauritano, Ernesto Cristiano; Navarra, Pierluigi; Marconi, Stefano; Gasbarrini, Antonio; Bentivoglio, Anna Rita

    2013-08-01

    Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale-IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society. Copyright © 2013 Movement

  2. Stages of Small Intestine Cancer

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  3. Intestinal inflammatory myofibroblastic tumour

    African Journals Online (AJOL)

    abdominal X-ray of patients 1, 3 and 4 demonstrated dilated small bowel loops with fluid levels in keeping with intestinal ... myxoid/vascular pattern characterised by a variable admixture of capillary-calibre blood vessels, .... in the present study had a past history of abdominal trauma or surgery. Ancillary histopathological ...

  4. Small intestine and microbiota.

    Science.gov (United States)

    Cotter, Paul D

    2011-03-01

    To highlight the recent studies which have enhanced our appreciation of the composition of the microbiota in the human small intestine and its relevance to the health of the host. In the past number of years, the composition of the microorganisms present in our small intestines has been the subject of greater scrutiny than ever before. These investigations have been possible as a consequence of the development and utilization of new molecular tools which have revolutionized the field of microbial ecology and have focused predominantly on the small intestinal microbiota associated with pediatric celiac disease, inflammatory bowel disease, irritable bowel syndrome and pouchitis. The impact of invasive procedures, such as small bowel transplant, ileostomy and ileal pouch anal anastomosis, on the ileal microbiota has also been investigated. The ever greater appreciation of the link between the small intestinal microbiota and the health status of the host has the potential to lead to the development of new strategies to alter this microbiota in a targeted way to prevent or treat specific disorders.

  5. Intestinal obstruction repair

    Science.gov (United States)

    ... Ileostomy and your diet Ileostomy - caring for your stoma Ileostomy - changing your pouch Ileostomy - discharge Ileostomy - what to ask your doctor Intestinal or bowel obstruction - discharge Low-fiber diet Surgical wound care - open Types of ileostomy When you have nausea ...

  6. adhesive intestinal obstruction

    African Journals Online (AJOL)

    2006-06-01

    Jun 1, 2006 ... obstruction. Brit. I. Surg. 1998; 85: 1071-1074. The acute abdomen: Intestinal obstruction. In: Primary surgery, Vol. 1. Edited by Maurice King et al. Oxford. Med. PubL, Oxford. 1990; 142-169. Fluids and electrolyte management. In: Essentials of pediatric surgery. Edited by Marc Rowe et al. Mosby,. St. Louis ...

  7. Intestinal Complications of IBD

    Science.gov (United States)

    ... localized pocket of pus caused by infection from bacteria. More common in Crohn’s than in colitis, an abscess may form in the intestinal wall—sometimes causing it to bulge out. Visible abscesses, such as those around the anus, look like boils and treatment often involves lancing. Symptoms of ...

  8. Intestinal failure in childhood

    African Journals Online (AJOL)

    Short bowel syndrome (SBS) was one of the first recognised conditions of protracted IF. With the increasing and successful use of long-term PN during the last three decades, several other causes of IF have emerged. Long-term PN and home-PN are the mainstay of therapy, independent of the nature of “Intestinal failure” ...

  9. Yogurt inhibits intestinal barrier dysfunction in Caco-2 cells by increasing tight junctions.

    Science.gov (United States)

    Putt, Kelley K; Pei, Ruisong; White, Heather M; Bolling, Bradley W

    2017-01-25

    Chronic inflammation disrupts intestinal barrier function and may contribute to the pathology of obesity and other diseases. The goal of this study was to determine the mechanism by which yogurt improves intestinal barrier function. Caco-2 cells were differentiated on Transwell inserts and used as a model of intestinal barrier permeability. Transepithelial electrical resistance (TEER) and flux of 4 kDa fluorescein isothiocyanate-dextran (FD) and lucifer yellow (LY) were used as indicators of monolayer integrity and paracellular permeability. Immunofluorescence microscopy and real time quantitative polymerase chain were used to assess the localization and expression of tight junction proteins known to regulate intestinal permeability. Differentiated cells were treated with a vehicle control (C), inflammatory stimulus (I) (interleukin-1β, tumor necrosis factor-α, interferon-γ, and lipopolysaccharide), or I and 0.03 g mL -1 yogurt (IY). After 48 h, I reduced Caco-2 TEER by 46%, while IY reduced TEER by only 27% (P effect on barrier function was reduced at latter stages of digestion.

  10. Curcumin and Chronic Kidney Disease (CKD: Major Mode of Action through Stimulating Endogenous Intestinal Alkaline Phosphatase

    Directory of Open Access Journals (Sweden)

    Siddhartha S. Ghosh

    2014-12-01

    Full Text Available Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa, has significant anti-inflammatory properties. Chronic kidney disease (CKD, an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is frequently associated with other inflammatory disease such as diabetes and cardiovascular disorders. This review will focus on the clinically relevant inflammatory molecules that play a role in CKD and associated diseases. Various enzymes, transcription factors, growth factors modulate production and action of inflammatory molecules; curcumin can blunt the generation and action of these inflammatory molecules and ameliorate CKD as well as associated inflammatory disorders. Recent studies have shown that increased intestinal permeability results in the leakage of pro-inflammatory molecules (cytokines and lipopolysaccharides from gut into the circulation in diseases such as CKD, diabetes and atherosclerosis. This change in intestinal permeability is due to decreased expression of tight junction proteins and intestinal alkaline phosphatase (IAP. Curcumin increases the expression of IAP and tight junction proteins and corrects gut permeability. This action reduces the levels of circulatory inflammatory biomolecules. This effect of curcumin on intestine can explain why, despite poor bioavailability, curcumin has potential anti-inflammatory effects in vivo and beneficial effects on CKD.

  11. Caco-2 cell permeability modelling: a neural network coupled genetic algorithm approach

    Science.gov (United States)

    Di Fenza, Armida; Alagona, Giuliano; Ghio, Caterina; Leonardi, Riccardo; Giolitti, Alessandro; Madami, Andrea

    2007-04-01

    The ability to cross the intestinal cell membrane is a fundamental prerequisite of a drug compound. However, the experimental measurement of such an important property is a costly and highly time consuming step of the drug development process because it is necessary to synthesize the compound first. Therefore, in silico modelling of intestinal absorption, which can be carried out at very early stages of drug design, is an appealing alternative procedure which is based mainly on multivariate statistical analysis such as partial least squares (PLS) and neural networks (NN). Our implementation of neural network models for the prediction of intestinal absorption is based on the correlation of Caco-2 cell apparent permeability ( P app) values, as a measure of intestinal absorption, to the structures of two different data sets of drug candidates. Several molecular descriptors of the compounds were calculated and the optimal subsets were selected using a genetic algorithm; therefore, the method was indicated as Genetic Algorithm-Neural Network (GA-NN). A methodology combining a genetic algorithm search with neural network analysis applied to the modelling of Caco-2 P app has never been presented before, although the two procedures have been already employed separately. Moreover, we provide new Caco-2 cell permeability measurements for more than two hundred compounds. Interestingly, the selected descriptors show to possess physico-chemical connotations which are in excellent accordance with the well known relevant molecular properties involved in the cellular membrane permeation phenomenon: hydrophilicity, hydrogen bonding propensity, hydrophobicity and molecular size. The predictive ability of the models, although rather good for a preliminary study, is somewhat affected by the poor precision of the experimental Caco-2 measurements. Finally, the generalization ability of one model was checked on an external test set not derived from the data sets used to build the models

  12. Tricellulin, occludin and claudin-3 expression in salmon intestine and kidney during salinity adaptation

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Madsen, Steffen

    2012-01-01

    and claudin-3 isoforms (a, b, c). A survey of tissue distribution in freshwater (FW) salmon showed that tricellulin expression was highest in the intestine. Occludin was detected in tissues with importance for epithelial transport and the order of expression was gill>intestine>kidney. The three claudin-3...... isoforms were expressed at highest level in kidney tissue. Transfer of juvenile FW salmon to seawater (SW) elevated intestinal tricellulin and occludin mRNA, and these transcripts were also elevated at the time of best SW-tolerance during the course of smoltification. In the kidney, expression...... is dynamically involved in reorganization of intestinal epithelium and possibly changed paracellular permeability during SW-acclimation. The increased renal tricellulin and claudin-3 expression in SW suggests a role in remodeling of the kidney during SW-acclimation....

  13. Effect of fluoride on the intestinal epithelial cell brush border membrane

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, R.; Upreti, R.K.; Kidwai, A.M.

    1987-07-01

    Fluoride consumed by man and animals is chiefly absorbed in the intestine. Chronic fluoride exposure causes mottled teeth and osteosclerosis. Over-fluoridation (126 mM) of drinking water have been reported to cause nausea, vomiting and diarrhea. Furthermore, the effect of acute and low concentrations of fluoride on gastric secretion, ion transport and other disorders have also been studied. Fluoride also causes alterations in the permeability of membranes and membrane bound enzymes. The intestinal cell lining plays an important role in digestion and absorption. It automatically becomes the most exposed site of contact to fluoride following ingestion. Earlier study have shown significant alterations in the formation of lipid peroxides in rat intestine following oral administration of fluoride. The present study was undertaken to investigate the damage of rat intestinal epithelium in situ caused by relatively high and low fluoride concentrations.

  14. Abnormal gastrointestinal accumulation of radiotracer by gastric bleeding during {sup 99m}Tc-MDP bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Kyung A.; Lee, Sang Woo; Lee, Jae Tae; Lee, Kyu Bo [College of Medicine, Kyungpook National Univ., Taegu (Korea, Republic of)

    1998-06-01

    We present a case in which a patient with acute hemorrhagic gastritis demonstrated abnormal gastrointestinal accumulation of radiotracer during {sup 99m}Tc-methylene diphosphonate (MDP) skeletal scintigraphy. A hemorrhagic gastritis was subsequently demonstrated by endoscopy. The mechanism for the intestinal localization of {sup 99m}Tc-MDP in this patients is not clear, but we guess that the extravasated blood containing the radiopharmaceutical cannot recirculate and stays at the bleeding site, so we can see the intestinal activity.

  15. Quantifying Evaporation in a Permeable Pavement System ...

    Science.gov (United States)

    Studies quantifying evaporation from permeable pavement systems are limited to a few laboratory studies and one field application. This research quantifies evaporation for a larger-scale field application by measuring the water balance from lined permeable pavement sections. The U.S. Environmental Protection Agency (USEPA) constructed a 0.4-ha parking lot in Edison, NJ, that incorporated three different permeable pavement types in the parking lanes – permeable interlocking concrete pavers (PICP), pervious concrete (PC), and porous asphalt (PA). An impermeable liner installed 0.4 m below the driving surface in four 11.6-m by 4.74-m sections per each pavement type captures all infiltrating water and routes it to collection tanks that can contain events up to 38 mm. Each section has a design impervious area to permeable pavement area ratio of 0.66:1. Pressure transducers installed in the underdrain collection tanks measured water level for 24 months. Level was converted to volume using depth-to-volume ratios for individual collection tanks. Using a water balance approach, the measured infiltrate volume was compared to rainfall volume on an event-basis to determine the rainfall retained in the pavement strata and underlying aggregate. Evaporation since the previous event created additional storage in the pavement and aggregate layers. Events were divided into three groups based on antecedent dry period (ADP) and three, four-month categories of potential e

  16. In vivo human buccal permeability of nicotine

    DEFF Research Database (Denmark)

    Adrian, Charlotte L; Olin, Helle B D; Dalhoff, Kim

    2006-01-01

    The aim was to examine the in vivo buccal pH-dependent permeability of nicotine in humans and furthermore compare the in vivo permeability of nicotine to previous in vitro permeability data. The buccal permeability of nicotine was examined in a three-way cross-over study in eight healthy non......-smokers using a buccal perfusion cell. The disappearance of nicotine from perfusion solutions with pH 6.0, 7.4, and 8.1 was studied for 3h. The apparent permeability of nicotine (P(app)) was determined at each pH value. Parotid saliva was collected in an attempt to assess systemic levels of nicotine....... The disappearance rate of nicotine increased significantly as the pH increased, which resulted in P(app) values of 0.57+/-0.55 x 10(-4), 2.10+/-0.23 x 10(-4), and 3.96+/-0.54 x 10(-4)cms(-1) (mean+/-S.D.) at pH 6.0, 7.4, and 8.1, respectively. A linear relationship (R(2)=0.993) was obtained between the P...

  17. Vascular permeability alterations induced by arsenic.

    Science.gov (United States)

    Chen, Shih-Chieh; Tsai, Ming-Hsien; Wang, Hsiu-Jen; Yu, Hsin-Su; Chang, Louis W

    2004-01-01

    The impact of arsenic on the integrity of blood vessels in vivo via in situ exposure (local injection) of arsenic was investigated. Vascular permeability changes were evaluated by means of the Evans blue assay and the India ink tracer techniques. Rats were intravenously injected with Evans blue followed by intradermal injections of various doses of sodium arsenite on the back skins of the animals. Evans blue at different time points was extracted and assayed as indices of vascular leakage. Skin at various time point injection sites was sampled for arsenic measurement via graphite furnace atomic absorption spectroscopy. Our time course study with Evans blue technique demonstrated a biphasic pattern of vascular permeability change: an early phase of permeability reduction and a later phase of permeability promotion at all dose levels tested. The India ink tracer technique also demonstrated a time-correlated increase in vascular labelling in the tissues examined, signifying an increase in vascular leakage with time. Moreover, we found that despite an early increase in tissue arsenic content at time of injection, tissue arsenic declined rapidly and returned to near control levels after 30-60 min. Thus, an inverse correlation between tissue arsenic content and the extent of vascular permeability was apparent. This study provides the first demonstration that in situ exposure to arsenic will produce vascular dysfunction (vascular leakage) in vivo.

  18. New chemical approach to permeability reduction

    Energy Technology Data Exchange (ETDEWEB)

    Presley, C.T.; Argabright, P.A.; Smith, R.E.; Phillips B.L.

    1974-01-01

    A new class of polyelectrolytes, polyisocyanurate salts, has been discovered at this laboratory. The most versatile member of this class, T/sub M/PI, possesses a number of unique properties, not the least of which is its hydrolysis in basic solution. The hydrolysis product is in the form of a colloidal suspension resulting from the opening of some hydrophilic isocyanurate salt rings to the more hydrophobic biuret moiety. The influence of base and T/sub M/PI concentrations on the rate of hydrolysis and, more importantly, the time to onset of particle formation, were investigated. The reaction of T/sub M/PI with base was shown to be an efficient method for generating particles, irreversibly, in porous media for the purpose of reducing permeability. The T/sub M/PI-based partial plugging process has a number of important advantages, namely: (1) the plugging agent is injected as a single solution; (2) the time available after mixing for placement of the solution in the reservoir (i.e., handling time) can be varied over rather wide limits; (3) the process can be designed so that the final permeability is essentially any desired fraction of the initial permeability; (4) the fractional permeability reduction appears to be independent of the initial permeability; and (5) the particles are not removed by subsequent water injection. (16 refs.)

  19. Flood Mitigation by Permeable Pavements in Chinese Sponge City Construction

    OpenAIRE

    Maochuan Hu; Xingqi Zhang; Yim Ling Siu; Yu Li; Kenji Tanaka; Hong Yang; Youpeng Xu

    2018-01-01

    It is important to evaluate the effectiveness of permeable pavements on flood mitigation at different spatial scales for their effective application, for example, sponge city construction in China. This study evaluated the effectiveness of three types of permeable pavements (i.e., permeable asphalts (PA), permeable concretes (PC), and permeable interlocking concrete pavers (PICP)) on flood mitigation at a community scale in China using a hydrological model. In addition, the effects of cloggin...

  20. Early Changes in Microbial Colonization Selectively Modulate Intestinal Enzymes, but Not Inducible Heat Shock Proteins in Young Adult Swine

    NARCIS (Netherlands)

    Arnal, M.E.; Zhang, J.; Messori, S.; Bosi, P.; Smidt, H.; Lallès, J.P.

    2014-01-01

    Metabolic diseases and obesity are developing worldwide in a context of plethoric intake of high energy diets. The intestine may play a pivotal role due to diet-induced alterations in microbiota composition and increased permeability to bacterial lipopolysaccharide inducing metabolic inflammation.

  1. Intestinal glucose transport and salinity adaptation in a euryhaline teleost

    International Nuclear Information System (INIS)

    Reshkin, S.J.; Ahearn, G.A.

    1987-01-01

    Glucose transport by upper and lower intestinal brush-border membrane vesicles of the African tilapia (Oreochromis mossambicus) was characterized in fish acclimated to either freshwater of full-strength sea water. D-[ 3 H]-glucose uptake by vesicles was stimulated by a transmembrane Na gradient, was electrogenic, and was enhanced by countertransport of either D-glucose or D-galactose. Glucose transport was greater in the upper intestine than in the lower intestine and in sea water animals rather than in fish acclimated to freshwater. Glucose influx (10-s uptake) involved both saturable and nonsaturable transport components. Sea water adaptation increased apparent glucose influx K/sub t/, J/sub max/, apparent diffusional permeability (P), and the apparent Na affinity of the cotransport system in both intestinal segments, but the stoichiometry of Na-glucose transfer (1:1) was unaffected by differential saline conditions or gut region. It is suggested that increased sugar transport in sea water animals is due to the combination of enhanced Na-binding properties and an increase in number or transfer rate of the transport proteins. Freshwater animals compensate for reduced Na affinity of the coupled process by markedly increasing the protein affinity for glucose

  2. Zonulin: A Potential Marker of Intestine Injury in Newborns

    Directory of Open Access Journals (Sweden)

    Anna Tarko

    2017-01-01

    Full Text Available Introduction. Zonulin (ZO, a new diagnostic biomarker of intestinal permeability, was tested in newborns presenting symptoms of infection and/or inflammation of the gut or being at risk of intestinal pathology. Material and Methods. Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing enterocolitis (NEC, rotavirus infection, and gastroschisis, also in extremely low gestational age babies, and in controls (healthy newborns. ZO concentration was compared to C-reactive protein (CRP and procalcitonin (PCT values, leucocyte and platelet count, basic demographic data, and the value of the Neonatal Therapeutic Intervention Scoring System (NTISS. Results. Median values of ZO were markedly higher in groups with rotavirus infection and gastroschisis (36.0 (1-3Q: 26.0–43.2 and 20.3 (1-3Q: 17.7–28.2 ng/ml, resp. versus controls (3.5 (1-3Q: 2.7–4.8 ng/ml. Its concentration in the NEC group was twice as high as in controls but did not reach statistical significance. ZO levels were not related to NTISS, CRP, and PCT. Conclusions. Zonulin is a promising biomarker of intestinal condition, markedly elevated in rotavirus infections. Its role in defining the severity of necrotizing enterocolitis and the risk for perforation is not well described and needs further evaluation. An increase in zonulin may not be parallel to the release of inflammatory markers, and low CRP should not exclude an injury to neonatal intestine.

  3. Zonulin: A Potential Marker of Intestine Injury in Newborns.

    Science.gov (United States)

    Tarko, Anna; Suchojad, Anna; Michalec, Marta; Majcherczyk, Małgorzata; Brzozowska, Aniceta; Maruniak-Chudek, Iwona

    2017-01-01

    Zonulin (ZO), a new diagnostic biomarker of intestinal permeability, was tested in newborns presenting symptoms of infection and/or inflammation of the gut or being at risk of intestinal pathology. Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing enterocolitis (NEC), rotavirus infection, and gastroschisis, also in extremely low gestational age babies, and in controls (healthy newborns). ZO concentration was compared to C-reactive protein (CRP) and procalcitonin (PCT) values, leucocyte and platelet count, basic demographic data, and the value of the Neonatal Therapeutic Intervention Scoring System (NTISS). Median values of ZO were markedly higher in groups with rotavirus infection and gastroschisis (36.0 (1-3Q: 26.0-43.2) and 20.3 (1-3Q: 17.7-28.2) ng/ml, resp.) versus controls (3.5 (1-3Q: 2.7-4.8) ng/ml). Its concentration in the NEC group was twice as high as in controls but did not reach statistical significance. ZO levels were not related to NTISS, CRP, and PCT. Zonulin is a promising biomarker of intestinal condition, markedly elevated in rotavirus infections. Its role in defining the severity of necrotizing enterocolitis and the risk for perforation is not well described and needs further evaluation. An increase in zonulin may not be parallel to the release of inflammatory markers, and low CRP should not exclude an injury to neonatal intestine.

  4. Intestinal Microbiota and the Innate Immune System - A Crosstalk in Crohn's Disease Pathogenesis.

    Science.gov (United States)

    Haag, Lea-Maxie; Siegmund, Britta

    2015-01-01

    Crohn's disease (CD) is a chronic, relapsing inflammatory disorder that can occur anywhere along the gastrointestinal tract. The precise etiology of CD is still unclear but it is widely accepted that a complex series of interactions between susceptibility genes, the immune system and environmental factors are implicated in the onset and perpetuation of the disease. Increasing evidence from experimental and clinical studies implies the intestinal microbiota in disease pathogenesis, thereby supporting the hypothesis that chronic intestinal inflammation arises from an abnormal immune response against the microorganisms of the intestinal flora in genetically susceptible individuals. Given that CD patients display changes in their gut microbiota composition, collectively termed "dysbiosis," the question raises whether the altered microbiota composition is a cause of disease or rather a consequence of the inflammatory state of the intestinal environment. This review will focus on the crosstalk between the gut microbiota and the innate immune system during intestinal inflammation, thereby unraveling the role of the microbiota in CD pathogenesis.

  5. Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of p-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine.

    Science.gov (United States)

    Dahan, Arik; Sabit, Hairat; Amidon, Gordon L

    2009-10-01

    The purpose of this study was to thoroughly characterize the efflux transporters involved in the intestinal permeability of the oral microtubule polymerization inhibitor colchicine and to evaluate the role of these transporters in limiting its oral absorption. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on colchicine bidirectional permeability were studied across Caco-2 cell monolayers, inhibiting one versus multiple transporters simultaneously. Colchicine permeability was then investigated in different regions of the rat small intestine by in situ single-pass perfusion. Correlation with the P-gp/MRP2 expression level throughout different intestinal segments was investigated by immunoblotting. P-gp inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), verapamil, and quinidine], and MRP2 inhibitors [3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), indomethacin, and p-aminohippuric acid (p-AH)] significantly increased apical (AP)-basolateral (BL) and decreased BL-AP Caco-2 transport in a concentration-dependent manner. No effect was obtained by the BCRP inhibitors fumitremorgin C (FTC) and pantoprazole. P-gp/MRP2 inhibitors combinations greatly reduced colchicine mucosal secretion, including complete abolishment of efflux (GF120918/MK571). Colchicine displayed low (versus metoprolol) and constant permeability along the rat small-intestine. GF120918 significantly increased colchicine permeability in the ileum with no effect in the jejunum, whereas MK571 augmented jejunal permeability without changing the ileal transport. The GF120918/MK571 combination caused an effect similar to that of MK571 alone in the jejunum and to that of GF120918 alone in the ileum. P-gp expression followed a gradient increasing from

  6. Fluorescently labeled methyl-beta-cyclodextrin enters intestinal epithelial Caco-2 cells by fluid-phase endocytosis.

    Directory of Open Access Journals (Sweden)

    Ferenc Fenyvesi

    Full Text Available Cyclodextrins are widely used excipients for increasing the bioavailability of poorly water-soluble drugs. Their effect on drug absorption in the gastrointestinal tract is explained by their solubility- and permeability-enhancement. The aims of this study were to investigate penetration properties of fluorescently labeled randomly methylated-beta-cyclodextrin (FITC-RAMEB on Caco-2 cell layer and examine the cellular entry of cyclodextrins on intestinal cells. The permeability of FITC-RAMEB through Caco-2 monolayers was very limited. Using this compound in 0.05 mM concentration the permeability coefficient was 3.35±1.29×10(-8 cm/s and its permeability did not change in the presence of 5 mM randomly methylated-beta-cyclodextrin. Despite of the low permeability, cellular accumulation of FITC-RAMEB in cytoplasmic vesicles was significant and showed strong time and concentration dependence, similar to the characteristics of the macropinocytosis marker Lucifer Yellow. The internalization process was fully inhibited at 0°C and it was drastically reduced at 37°C applying rottlerin, an inhibitor of macropinocytosis. Notably, FITC-RAMEB colocalized with the early endosome organizer Rab5a. These results have revealed that FITC-RAMEB is able to enter intestinal epithelial cells by fluid-phase endocytosis from the apical side. This mechanism can be an additional process which helps to overcome the intestinal barrier and contributes to the bioavailability enhancement of cyclodextrins.

  7. [Study on effect of oligochitosan in promoting intestinal absorption of protoberberine alkaloids in extracts from Corydalis saxicola total alkaloids].

    Science.gov (United States)

    Li, Xin-yang; Xie, Hui; Lu, Tu-lin; Shi, Yue-jiao; Zhang, Xing-de; Liu, Ting

    2015-05-01

    To investigate the effect of oligochitosan in promoting intestinal absorption of protoberberine alkaloids in extracts from Corydalis saxicola total alkaloids. The in vitro single-pass intestinal perfusion model in rats was established to study the changes in absorption kinetic parameters of dehydrocavidine, berberine hydrochloride and palmatine chloride in C. saxicola total alkaloids after the addition of different concentrations oligochitosan and evaluate the effect of oligochitosan in promoting intestinal absorption of the drugs. The concentration of oligochitosan had different effects on the absorption rate constant (Ka) and apparent permeability coefficient (Peff) of the three active component in rat intestines. Ka and Peff in 0.5% oligochitosan group significantly increased, indicating a stronger effect in promoting the absorption. Oligochitosan has a certain effect in promoting the intestinal absorptions of protoberberine alkaloids in C. saxicola total alkaloids.

  8. Altered erythrocyte cation permeability in familial pseudohyperkalaemia.

    Science.gov (United States)

    Dagher, G; Vantyghem, M C; Doise, B; Lallau, G; Racadot, A; Lefebvre, J

    1989-08-01

    1. Erythrocyte cation transport pathways have been investigated in a family with pseudohyperkalaemia. 2. Ouabain- and bumetanide-resistant Na+ and K+ effluxes in three pseudohyperkalaemic patients were not different from those of control subjects when assessed at 37 degrees C. 3. When the temperature was decreased to 20 degrees C and 9 degrees C, K+ passive permeability markedly increased and Na+ permeability remained unchanged in these patients. In contrast, in control subjects a reduction in temperature caused a marked reduction in Na+ and K+ passive permeability. 4. These findings could account for the marked increase in plasma K+ concentration observed at subphysiological temperatures. 5. The Na+-K+ co-transport pathway was reduced in all members of the family, but the Na+-K+ pump was reduced in only two of them. These alterations were independent from the pseudohyperkalaemic state.

  9. Mathematical models of skin permeability: an overview.

    Science.gov (United States)

    Mitragotri, Samir; Anissimov, Yuri G; Bunge, Annette L; Frasch, H Frederick; Guy, Richard H; Hadgraft, Jonathan; Kasting, Gerald B; Lane, Majella E; Roberts, Michael S

    2011-10-10

    Mathematical models of skin permeability play an important role in various fields including prediction of transdermal drug delivery and assessment of dermal exposure to industrial chemicals. Extensive research has been performed over the last several decades to yield predictions of skin permeability to various molecules. These efforts include the development of empirical approaches such as quantitative structure-permeability relationships and porous pathway theories as well as the establishment of rigorous structure-based models. In addition to establishing the necessary mathematical framework to describe these models, efforts have also been dedicated to determining the key parameters that are required to use these models. This article provides an overview of various modeling approaches with respect to their advantages, limitations and future prospects. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Negative permeability from random particle composites

    Science.gov (United States)

    Hussain, Shahid

    2017-04-01

    Artificial media, such as those composed of periodically-spaced wires for negative permittivity and split ring resonators for negative permeability have been extensively investigated for negative refractive index (NRI) applications (Smith et al., 2004; Pendry et al., 1999) [1,2]. This paper presents an alternative method for producing negative permeability: granular (or particulate) composites incorporating magnetic fillers. Artificial media, such as split-ring resonators, are designed to produce a magnetic resonance feature, which results in negative permeability over a narrow frequency range about the resonance frequency. The position of the feature is dependent upon the size of the inclusion. The material in this case is anisotropic, such that the feature is only observable when the materials are orientated in a specific direction relative to the applied field. A similar resonance can be generated in magnetic granular (particulate) materials: ferromagnetic resonance from the natural spin resonance of particles. Although the theoretical resonance profiles in granular composites shows the permeability dipping to negative values, this is rarely observed experimentally due to resonance damping effects. Results are presented for iron in spherical form and in flake form, dispersed in insulating host matrices. The two particle shapes show different permeability performance, with the magnetic flakes producing a negative contribution. This is attributed to the stronger coupling with the magnetic field resulting from the high aspect ratio of the flakes. The accompanying ferromagnetic resonance is strong enough to overcome the effects of damping and produce negative permeability. The size of random particle composites is not dictated by the wavelength of the applied field, so the materials are potentially much thinner than other, more traditional artificial composites at microwave frequencies.

  11. In situ permeability testing of rock salt

    International Nuclear Information System (INIS)

    Peterson, E.W.; Lagus, P.L.; Broce, R.D.; Lie, K.

    1981-04-01

    Storage of transuranic (TRU) wastes in bedded salt formations requires a knowledge of the in situ permeability of SENM rock salt. Since assumptions for safety assessments have been made in which these wastes could generate gas pressures on the order of the lithostatic pressure over geologic time scales, the permeability of the surrounding formation becomes an important parameter for determining the manner in which the gases will be contained or dispersed. This report describes the series of tests conducted in the AEC-7 borehole, located near the WIPP site, to determine the in situ gas flow characteristics of the bedded salt. In these tests, compressed air was injected into the borehole and flow into the surrounding formation measured. These measured flow rates were interpreted in terms of formation permeabilities and porosities which were, in turn, used as modeling parameters for the repository response analysis. Two series of field tests were performed. The first series consisted of a number of whole-hole flow tests conducted to provide preliminary design information required for future operation of a guarded straddle packer system capable of measuring permeabilities > or = 0.1 μdarcy. The second series of tests were conducted using the Systems, Science and Software (S-Cubed) designed guarded straddle packer system. In these interval permeability tests, 100-foot lengths of borehole were isolated and the flow characteristics of the surrounding formation examined. In this report, a complete description of the test procedures, instrumentation, and measurement techniques is first given. The analytical/numerical methods used for data interpretation are then presented, followed by results of the interval and permeability tests. (The whole-hole tests are summarized in Appendix A.) Conclusions are presented in the final section

  12. Somatosensory abnormalities in knee OA.

    Science.gov (United States)

    Wylde, Vikki; Palmer, Shea; Learmonth, Ian D; Dieppe, Paul

    2012-03-01

    The aim of this study was to use quantitative sensory testing (QST) to explore the range and prevalence of somatosensory abnormalities demonstrated by patients with advanced knee OA. One hundred and seven knee OA patients and 50 age- and sex-matched healthy participants attended a 1-h QST session. Testing was performed on the medial side of the knee and the pain-free forearm. Light-touch thresholds were assessed using von Frey filaments, pressure pain thresholds using a digital pressure algometer, and thermal sensation and pain thresholds using a Thermotest MSA. Significant differences in median threshold values from knee OA patients and healthy participants were identified using Mann-Whitney U-tests. The z-score transformations were used to determine the prevalence of the different somatosensory abnormalities in knee OA patients. Testing identified 70% of knee OA patients as having at least one somatosensory abnormality. Comparison of median threshold values between knee OA patients and healthy participants revealed that patients had localized thermal and tactile hypoaesthesia and pressure hyperalgesia at the osteoarthritic knee. Tactile hypoaesthesia and pressure hyperalgesia were also present at the pain-free forearm. The most prevalent somatosensory abnormalities were tactile hypoaesthesia and pressure hyperalgesia, evident in between 20 and 34% of patients. This study found that OA patients demonstrate an array of somatosensory abnormalities, of which the most prevalent were tactile hypoaesthesia and pressure hyperalgesia. Further research is now needed to establish the clinical implications of these somatosensory abnormalities.

  13. Arctigenin from Fructus Arctii (Seed of Burdock Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

    Directory of Open Access Journals (Sweden)

    Hee Soon Shin

    2015-01-01

    Full Text Available Fructus Arctii is used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect of F. Arctii extract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component of F. Arctii. We measured transepithelial electrical resistance (TEER value (as an index of barrier function and ovalbumin (OVA permeation (as an index of permeability to observe the changes of intestinal barrier function. The treatment of F. Arctii increased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component of F. Arctii increased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed that F. Arctii could enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin from F. Arctii could contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function.

  14. Arctigenin from Fructus Arctii (Seed of Burdock) Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

    Science.gov (United States)

    Shin, Hee Soon; Jung, Sun Young; Back, Su Yeon; Do, Jeong-Ryong; Shon, Dong-Hwa

    2015-01-01

    Fructus Arctii is used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect of F. Arctii extract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component of F. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment of F. Arctii increased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component of F. Arctii increased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed that F. Arctii could enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin from F. Arctii could contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function. PMID:26550018

  15. Small intestinal transplantation.

    LENUS (Irish Health Repository)

    Quigley, E M

    2012-02-03

    The past few years have witnessed a considerable shift in the clinical status of intestinal transplantation. A great deal of experience has been gained at the most active centers, and results comparable with those reported at a similar stage in the development of other solid-organ graft programs are now being achieved by these highly proficient transplant teams. Rejection and its inevitable associate, sepsis, remain ubiquitous, and new immunosuppressant regimes are urgently needed; some may already be on the near horizon. The recent success of isolated intestinal grafts, together with the mortality and morbidity attendant upon the development of advanced liver disease related to total parenteral nutrition, has prompted the bold proposal that patients at risk for this complication should be identified and should receive isolated small bowel grafts before the onset of end-stage hepatic failure. The very fact that such a suggestion has begun to emerge reflects real progress in this challenging field.

  16. Chronic intestinal pseudo-obstruction in systemic lupus erythematosus.

    Science.gov (United States)

    Perlemuter, G; Chaussade, S; Wechsler, B; Cacoub, P; Dapoigny, M; Kahan, A; Godeau, P; Couturier, D

    1998-07-01

    Chronic intestinal pseudo-obstruction (CIPO) reflects a dysfunction of the visceral smooth muscle or the enteric nervous system. Gastrointestinal manifestations are common in systemic lupus erythematosus (SLE) but CIPO has not been reported. Features of CIPO are reported in five patients with SLE. From 1988 to 1993, five patients with SLE or SLE-like syndrome were hospitalised for gastrointestinal manometric studies. CIPO was the onset feature in two cases. Antroduodenal manometry (three hours fasting, two hours fed) was performed in all patients, and oesophageal manometry in four. Intestinal hypomotility associated with reduced bladder capacity and bilateral ureteral distension was found in four patients and aperistalsis of the oesophagus in three. Treatment, which consisted of high dose corticosteroids, parenteral nutrition, promotility agents, and antibiotics, led to remission of both CIPO and urinary abnormalities in all cases. Antroduodenal manometry performed in two patients after remission showed increased intestinal motility. One patient died, and postmortem examination showed intestinal vasculitis. CIPO in SLE is a life threatening situation that can be reversed by treatment. It may be: (a) a complication or onset feature of the disease; (b) secondary to smooth muscle involvement; (c) associated with ureteral and vesical involvement; (d) the result of intestinal vasculitis.

  17. Development of an Improved Permeability Modification Simulator

    Energy Technology Data Exchange (ETDEWEB)

    Gao, H.W.; Elphnick, J.

    1999-03-09

    This report describes the development of an improved permeability modification simulator performed jointly by BDM Petroleum Technologies and Schlumberger Dowell under a cooperative research and development agreement (CRADA) with the US Department of Energy. The improved simulator was developed by modifying NIPER's PC-GEL permeability modification simulator to include a radial model, a thermal energy equation, a wellbore simulator, and a fully implicit time-stepping option. The temperature-dependent gelation kinetics of a delayed gel system (DGS) is also included in the simulator.

  18. The Permeability of Rubble Mound Breakwaters

    DEFF Research Database (Denmark)

    Williams, A.F.; Burcharth, H. F.; Adel, H. den

    1992-01-01

    The results of an extensive series of permeability experiments originally analysed by Shih (1990) are reinterpreted in the light of new experiments. It is proposed that the Forchheimer equation might not fully describe flow at the high Reynolds numbers found in the interior of rubble material....... A new series of tests designed to test for deviations from the Forchheimer equation and investigate the effects of material shape are described. While no evidence can be found to indicate a deviation from the Forchheimer equation a dependency of permeability and the surface roughness the material...

  19. Prediction of drug intestinal absorption in human using the Ussing chamber system: A comparison of intestinal tissues from animals and humans.

    Science.gov (United States)

    Miyake, Masateru; Koga, Toshihisa; Kondo, Satoshi; Yoda, Noriaki; Emoto, Chie; Mukai, Tadashi; Toguchi, Hajime

    2017-01-01

    An adequate evaluation system for drug intestinal absorption is essential in the pharmaceutical industry. Previously, we established a novel prediction system of drug intestinal absorption in humans, using the mini-Ussing chamber equipped with human intestinal tissues. In this system, the TI value was defined as the sum of drug amounts transported to the basal-side component (X corr ) and drug amounts accumulated in the tissue (T corr ), which are normalized by AUC of a drug in the apical compartment, as an index for drug absorption. In order to apply this system to the screening assay, it is important to understand the differences between animal and human tissues in the intestinal absorption of drugs. In this study, the transport index (TI) values of three drugs, with different levels of membrane permeability, were determined to evaluate the rank order of drug absorbability in intestinal tissues from rats, dogs, and monkeys. The TI values in small intestinal tissues in rats and dogs showed a good correlation with those in humans. On the other hand, the correlation of TI values in monkeys was lower compared to rats and dogs. The rank order of the correlation coefficient between human and investigated animal tissues was as follows: dog (r 2 =0.978), rat (r 2 =0.955), and monkey (r 2 =0.620). TI values in large intestinal tissues from rats (r 2 =0.929) and dogs (r 2 =0.808) also showed a good correlation. The obtained TI values in small intestinal tissues in rats and dogs were well correlated with the fraction of drug absorbed (F a ) in humans. From these results, the mini-Ussing chamber, equipped with intestinal tissues in rats and dogs, would be useful as a screening tool in the drug discovery stage. In addition, the obtained TI values can be used for the prediction of the F a in humans. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. The transport mechanism of cadmium by the small intestine of rats

    International Nuclear Information System (INIS)

    Taguchi, Tetsuya; Suzuki, Shosuke

    1979-01-01

    The mechanism of cadmium absorption was studied in vitro using the sacs of small intestines of male Sprague-Dawley rats. Relation between the concentration of cadmium in the mucosal fluid and the rate of transport of 109 Cd to the serosal fluid showed that the higher the concentration of cadmium, the greater the transport of 109 Cd. Wall uptake of 109 Cd was limited, and could be saturated at relatively low concentration. 109 Cd transport was not proportional to the cadmium concentration on the mucosal side, nor to the concentration of cadmium taken up by the intestinal walls. At the initial cadmium concentration of 50 μg/ml, there was no significant effect on the retention of 109 Cd in the intestinal walls, inspite of extremely large increase in the amount of 109 Cd transport into the serosal fluid. Cadmium could be transported across the intestinal walls against a gradient when the initial cadmium concentration on the mucosal side was raised to 50 μg/ml, which showed that the passage of 109 Cd across the intestinal walls could not be the result of uptake by the walls from the mucosal fluid, followed by simple diffusion into the serosal fluid. Cadmium transport through and retention within the intestinal walls was reduced by preliminary cadmium treatment, and it suggests that it induced some change in the permeability of the intestinal walls that facilitated the transmural passage of 109 Cd. (Kaihara, S.)

  1. The use of captisol (SBE7-β-CD) in oral solubility-enabling formulations: Comparison to HPβCD and the solubility-permeability interplay.

    Science.gov (United States)

    Beig, Avital; Agbaria, Riad; Dahan, Arik

    2015-09-18

    The aim of this research was to study the interaction of sulfobutyl ether7 β-cyclodextrin (captisol) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) with the poorly soluble antiarrhythmic drug amiodarone, and to investigate the consequent solubility-permeability interplay. Phase-solubility studies of amiodarone with the two cyclodextrins, followed by PAMPA and rat intestinal permeability experiments, were carried out, and the solubility-permeability interplay was then illustrated as a function of increasing cyclodextrin content. Equimolar levels of captisol allowed ∼10-fold higher amiodarone solubility than HPβCD, as well as binding constant. With both captisol and HPβCD, decreased in vitro and in vivo amiodarone apparent permeability was evident with increasing CD levels and increased apparent solubility. A theoretical model assuming direct proportionality between the apparent solubility increase allowed by the CD and permeability decrease was able to accurately predict the solubility-permeability tradeoff as a function of CD levels. In conclusion, the addition of ionic interactions (e.g. amiodarone-captisol) to hydrophobic interactions of the inclusion complex formation may result in synergic effect on solubilization; however, it is not merely the solubility that should be examined when formulating an oral poorly soluble compound, but the solubility-permeability balance, in order to maximize the overall drug exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Intestinal Obstruction due to Complete Transmural Migration of a Retained Surgical Sponge into the Intestine

    Directory of Open Access Journals (Sweden)

    Takashi Kato

    2012-12-01

    Full Text Available A 56-year-old woman with a history of gynecological surgery for cervical cancer 18 years previously was referred to our hospital for colicky abdominal pain, nausea and vomiting. Intestinal obstruction was diagnosed by contrast-enhanced computed tomography (CT which showed dilation of the small intestine and suggested obstruction in the terminal ileum. In addition, CT showed a thick-walled cavitary lesion communicating with the proximal jejunum. 18F-fluorodeoxyglucose positron emission tomography showed abnormal uptake at the same location as the cavitary lesion revealed by CT. The patient underwent laparotomy for the ileus and resection of the cavitary lesion. At laparotomy, we found a retained surgical sponge in the ileum 60 cm from the ileocecal valve. The cavitary tumor had two fistulae communicating with the proximal jejunum. The tumor was resected en bloc together with the transverse colon, part of the jejunum and the duodenum. Microscopic examination revealed fibrous encapsulation and foreign body giant cell reaction. Since a retained surgical sponge without radiopaque markers is extremely difficult to diagnose, retained surgical sponge should be considered in the differential diagnosis of intestinal obstruction in patients who have undergone previous abdominal surgery.

  3. Small intestinal cytochromes P450.

    Science.gov (United States)

    Kaminsky, L S; Fasco, M J

    1991-01-01

    Small intestinal cytochromes P450 (P450) provide the principal, initial source of biotransformation of ingested xenobiotics. The consequences of such biotransformation are detoxification by facilitating excretion, or toxification by bioactivation. P450s occur at highest concentrations in the duodenum, near the pylorus, and at decreasing concentrations distally--being lowest in the ileum. Highest concentrations occur from midvillus to villous tip, with little or none occurring in the crypts of Lieberkuehn. Microsomal P4503A, 2C8-10, and 2D6 forms have been identified in human small intestine, and P450s 2B1, possibly 2B2, 2A1, and 3A1/2 were located in endoplasmic reticulum of rodent small intestine, while P4502B4 has been purified to electrophoretic homogeneity from rabbit intestine. Some evidence indicates a differential distribution of P450 forms along the length of the small intestine and even along the villus. Rat intestinal P450s are inducible by xenobiotics--with phenobarbital (PB) inducing P4502B1, 3-methylcholanthrene (3-MC) inducing P4501A1, and dexamethasone inducing two forms of P4503A. Induction is most effectively achieved by oral administration of the agents, and is rapid--aryl hydrocarbon hydroxylase (AHH) was increased within 1 h of administration of, for example, 3-MC. AHH, 7-ethoxycoumarin O-deethylase (ECOD), and 7-ethoxyresorufin O-deethylase (EROD) have been used most frequently as substrates to characterize intestinal P450s. Dietary factors affect intestinal P450s markedly--iron restriction rapidly decreased intestinal P450 to beneath detectable values; selenium deficiency acted similarly but was less effective; Brussels sprouts increased intestinal AHH activity 9.8-fold, ECOD activity 3.2-fold, and P450 1.9-fold; fried meat and dietary fat significantly increased intestinal EROD activity; a vitamin A-deficient diet increased, and a vitamin A-rich diet decreased intestinal P450 activities; and excess cholesterol in the diet increased intestinal

  4. Incidentally detected small intestine intussusception caused by primary small intenstine carcinoma on {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Jong; Oh, So Won; Kim, Yu Kyeong [Dept. of Nuclear MedicineSeoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul (Korea, Republic of)

    2017-09-15

    Small intestine intussusception in adults is a rare condition mainly caused by primary or metastatic small intestine malignancy. Here, we present a 72-year-old male patient who was diagnosed with small intestine cancer that was presented as small intestine intussusception on hybrid {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). The patient was initially referred for an abnormality on a chest radiography and severe anemia. FDG PET/CT showed the lung lesion in the right upper lobe of lung as a high FDG uptake mass. Accidentally, FDG PET demonstrated another intense hypermetabolic intraluminal lesion in the small intestine accompanied with intussusception shown as a circumferential hypermetabolic wall. By pathologic examination, the patient was diagnosed as primary small intestine cancer with lung metastasis. This case highlights usefulness of hybrid FDG PET/CT to identify unexpected malignancy.

  5. Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice

    DEFF Research Database (Denmark)

    Sakamori, Ryotaro; Das, Soumyashree; Yu, Shiyan

    2012-01-01

    The constant self renewal and differentiation of adult intestinal stem cells maintains a functional intestinal mucosa for a lifetime. However, the molecular mechanisms that regulate intestinal stem cell division and epithelial homeostasis are largely undefined. We report here that the small GTPases...... reminiscent of human microvillus inclusion disease (MVID), a devastating congenital intestinal disorder that results in severe nutrient deprivation. Further analysis revealed that Cdc42-deficient stem cells had cell division defects, reduced capacity for clonal expansion and differentiation into Paneth cells...... activity in the intestinal epithelium, where continued cell division takes place. Furthermore, mice haploinsufficient for both Cdc42 and Rab8a in the intestine demonstrated abnormal crypt morphogenesis and epithelial transporter physiology, further supporting their functional interaction. These data...

  6. Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis

    DEFF Research Database (Denmark)

    Cramer, Stig P; Modvig, Signe; Simonsen, Helle Juhl

    2015-01-01

    as part of the diagnostic work-up at time of diagnosis. Eighteen healthy controls were included for comparison. Patients had magnetic resonance imaging and lumbar puncture performed within 4 weeks of onset of optic neuritis. Information on multiple sclerosis conversion was acquired from hospital records 2......Optic neuritis is an acute inflammatory condition that is highly associated with multiple sclerosis. Currently, the best predictor of future development of multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging. Previous research has found abnormalities...... in the permeability of the blood-brain barrier in normal-appearing white matter of patients with multiple sclerosis and here, for the first time, we present a study on the capability of blood-brain barrier permeability in predicting conversion from optic neuritis to multiple sclerosis and a direct comparison...

  7. Permeable pavement research – Edison, New Jersey

    Science.gov (United States)

    These are the slides for the New York City Concrete Promotional Council Pervious Concrete Seminar presentation. The basis for the project, the monitoring design and some preliminary monitoring data from the permeable pavement parking lot at the Edison Environmental Center are pre...

  8. Radionuclide assessment of pulmonary microvascular permeability

    Energy Technology Data Exchange (ETDEWEB)

    Groeneveld, A.B.J. [Medical Intensive Care Unit, Department of Internal Medicine, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam (Netherlands)

    1997-04-01

    The literature has been reviewed to evaluate the technique and clinical value of radionuclide measurements of microvascular permeability and oedema formation in the lungs. Methodology, modelling and interpretation vary widely among studies. Nevertheless, most studies agree on the fact that the measurement of permeability via pulmonary radioactivity measurements of intravenously injected radiolabelled proteins versus that in the blood pool, the so-called pulmonary protein transport rate (PTR), can assist the clinician in discriminating between permeability oedema of the lungs associated with the adult respiratory distress syndrome (ARDS) and oedema caused by an increased filtration pressure, for instance in the course of cardiac disease, i.e. pressure-induced pulmonary oedema. Some of the techniques used to measure PTR are also able to detect subclinical forms of lung microvascular injury not yet complicated by permeability oedema. This may occur after cardiopulmonary bypass and major vascular surgery, for instance. By paralleling the clinical severity and course of the ARDS, the PTR method may also serve as a tool to evaluate new therapies for the syndrome. Taken together, the currently available radionuclide methods, which are applicable at the bedside in the intensive care unit, may provide a gold standard for detecting minor and major forms of acute microvascular lung injury, and for evaluating the severity, course and response to treatment. (orig.). With 2 tabs.

  9. Vascular permeability in cerebral cavernous malformations

    DEFF Research Database (Denmark)

    Mikati, Abdul G; Khanna, Omaditya; Zhang, Lingjiao

    2015-01-01

    Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observ...

  10. Water permeability of pigmented waterborne coatings

    NARCIS (Netherlands)

    Donkers, P.A.J.; Huinink, H.P.; Erich, S.J.F.; Reuvers, N.J.W.; Adan, O.C.G.

    2013-01-01

    Coatings are used in a variety of applications. Last decades more and more coating systems are transforming from solvent to waterborne coating systems. In this study the influence of pigments on the water permeability of a waterborne coating system is studied, with special interest in the possible

  11. Foam film permeability: theory and experiment.

    Science.gov (United States)

    Farajzadeh, R; Krastev, R; Zitha, Pacelli L J

    2008-02-28

    The mass transfer of gas through foam films is a prototype of various industrial and biological processes. The aim of this paper is to give a perspective and critical overview of studies carried out to date on the mass transfer of gas through foam films. Contemporary experimental data are summarized, and a comprehensive overview of the theoretical models used to explain the observed effects is given. A detailed description of the processes that occur when a gas molecule passes through each layer that forms a foam film is shown. The permeability of the film-building surfactant monolayers plays an important role for the whole permeability process. It can be successfully described by the models used to explain the permeability of surfactant monolayers on aqueous sub-phase. For this reason, the present paper briefly discusses the surfactant-induced resistance to mass transfer of gases through gas-liquid interface. One part of the paper discusses the experimental and theoretical aspects of the foam film permeability in a train of foam films in a matrix or a cylinder. This special case is important to explain the gas transfer in porous media or in foams. Finally, this paper will highlight the gaps and challenges and sketch possible directions for future research.

  12. Cadmium substituted high permeability lithium ferrite

    Indian Academy of Sciences (India)

    Unknown

    3, 0⋅4, 0⋅5 and 0⋅6 were pre- pared by a double sintering ... Lithium ferrites; initial permeability; grain size; microstructure; magnetic properties. 1. Introduction ... The single-phase spinel nature of the samples was con- firmed from X-ray ...

  13. Variability of permeability with diameter of conduit

    Indian Academy of Sciences (India)

    section. If a porous system is conceived to be a bundle of capillary tubes of equal radii and length [4], the permeability k is expected to increase from zero from the wall–fluid boundary towards the centre of the flow. 2. Theoretical background. Limiting Navier–Stokes equations to incompressible fluids, we get. −. 1 ρ. ∂. ∂x.

  14. Programs for the calculi of blocks permeabilities

    International Nuclear Information System (INIS)

    Gomez Hernandez, J.J.; Sovero Sovero, H.F.

    1993-01-01

    This report studies the stochastic analysis of radionuclide transport. The permeability values of blocks are necessary to do a numeric model for the flux and transport problems in ground soils. The determination of block value by function on grill value is the objective of this program

  15. Modelling of water permeability in cementitious materials

    DEFF Research Database (Denmark)

    Guang, Ye; Lura, Pietro; van Breugel, K.

    2006-01-01

    This paper presents a network model to predict the permeability of cement paste from a numerical simulation of its microstructure. Based on a linked list pore network structure, the effective hydraulic conductivity is estimated and the fluid flow is calculated according to the Hagen-Poiseuille la...

  16. Lipo sarcoma in small intestine

    International Nuclear Information System (INIS)

    Rodriguez Iglesias, J.; Pineyro Gutierrez, A.; Taroco Medeiros, L.; Fein Kolodny, C.; Navarrete Pedocchi, H.

    1987-01-01

    A case is presented by primitive liposarcoma in small intestine , an extensive bibliographical review foreigner and national in this case. It detach the exceptional of the intestinal topography of the liposarcomas; and making stress in the relative value of the computerized tomography and ultrasonography in the diagnose of the small intestine tumors . As well as in the sarcomas of another topography, chemo and radiotherapy associated to the exeresis surgery, it can be of benefit [es

  17. Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms

    NARCIS (Netherlands)

    Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio; Fromm, M; Schulzke, JD

    2009-01-01

    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type I diabetes (TID), a hyperglycosaemia caused by a destructive autoimmune

  18. Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression.

    Science.gov (United States)

    Zuhl, Micah N; Lanphere, Kathryn R; Kravitz, Len; Mermier, Christine M; Schneider, Suzanne; Dokladny, Karol; Moseley, Pope L

    2014-01-15

    The objectives of this study are threefold: 1) to assess whether 7 days of oral glutamine (GLN) supplementation reduces exercise-induced intestinal permeability; 2) whether supplementation prevents the proinflammatory response; and 3) whether these changes are associated with upregulation of the heat shock response. On separate occasions, eight human subjects participated in baseline testing and in GLN and placebo (PLA) supplementation trials, followed by a 60-min treadmill run. Intestinal permeability was higher in the PLA trial compared with baseline and GLN trials (0.0604 ± 0.047 vs. 0.0218 ± 0.008 and 0.0272 ± 0.007, respectively; P supplementation (0, 4, and 6 mM) on heat-induced (37° or 41.8°C) heat shock protein 70 (HSP70), heat shock factor-1 (HSF-1), and occludin expression. HSF-1 and HSP70 levels increased in 6 mM supplementation at 41°C compared with 0 mM at 41°C (1.785 ± 0.495 vs. 0.6681 ± 0.290, and 1.973 ± 0.325 vs. 1.133 ± 0.129, respectively; P supplementation at 41°C and 6 mM at 41°C compared with 0 mM at 41°C (1.236 ± 0.219 and 1.849 ± 0.564 vs. 0.7434 ± 0.027, respectively; P supplementation prevented exercise-induced permeability, possibly through HSF-1 activation.

  19. Neuroimaging abnormalities in Griscelli's disease

    International Nuclear Information System (INIS)

    Sarper, Nazan; Akansel, Guer; Aydogan, Metin; Gedikbasi, Demet; Babaoglu, Kadir; Goekalp, Ayse Sevim

    2002-01-01

    Griscelli's disease is a rare autosomal recessive immunodeficiency syndrome. We report a 7-1/2-month-old white girl who presented with this syndrome, but initially without neurological abnormalities. Initial CT of the brain was normal. Despite haematological remission with chemotherapy, she developed neurological symptoms, progressing to coma. At this time, CT showed areas of coarse calcification in the globi pallidi, left parietal white matter and left brachium pontis. Hypodense areas were present in the genu and posterior limb of the internal capsule on the right side, as well as posterior aspects of both thalami, together with minimal generalised atrophy. MRI revealed areas of increased T2 signal and a focal area of abnormal enhancement in the subcortical white matter. Griscelli's disease should be added to the list of acquired neuroimaging abnormalities in infants. (orig.)

  20. Sub-core permeability and relative permeability characterization with Positron Emission Tomography

    Science.gov (United States)

    Zahasky, C.; Benson, S. M.

    2017-12-01

    This study utilizes preclinical micro-Positron Emission Tomography (PET) to image and quantify the transport behavior of pulses of a conservative aqueous radiotracer injected during single and multiphase flow experiments in a Berea sandstone core with axial parallel bedding heterogeneity. The core is discretized into streamtubes, and using the micro-PET data, expressions are derived from spatial moment analysis for calculating sub-core scale tracer flux and pore water velocity. Using the flux and velocity data, it is then possible to calculate porosity and saturation from volumetric flux balance, and calculate permeability and water relative permeability from Darcy's law. Full 3D simulations are then constructed based on this core characterization. Simulation results are compared with experimental results in order to test the assumptions of the simple streamtube model. Errors and limitations of this analysis will be discussed. These new methods of imaging and sub-core permeability and relative permeability measurements enable experimental quantification of transport behavior across scales.

  1. Modulation of inflammatory mediators by Opuntia ficus-indica and Prunus avium bioproducts using an in vitro cell-based model of intestinal inflammation

    OpenAIRE

    Nunes, Sara Alexandra Luis

    2011-01-01

    Dissertation to obtain a Master Degree in Biotechnology Inflammatory Bowel Diseases, namely Ulcerative colitis and Crohn’s disease, are chronic intestinal inflammatory disorders characterized by an excessive release of pro-inflammatory mediators, intestinal barrier dysfunction and altered permeability and excessive activation of NF-κB cascade that can lead to development of colon cancer. IBD conventional therapy involves multiple medications and long-term up to life-long treatments. Furthe...

  2. Hereditary intestinal polyposis syndromes.

    Science.gov (United States)

    Dean, P A

    1996-01-01

    Colorectal cancer is one of the most common cancers in the world, with overall mortality exceeding 40% even with treatment. Effective efforts for screening and prevention are most likely to succeed in patient groups identified as high risk for colorectal cancer, most notably the hereditary intestinal polyposis syndromes. In these syndromes, benign polyps develop throughout the intestinal tract prior to the development of colorectal cancer, marking the patient and associated family for precancer diagnosis followed by either close surveillance or preventive treatment. This review article was undertaken to discuss the most recent developments in the knowledge of hereditary intestinal polyposis syndromes, emphasizing the clinical approach to diagnosis and treatment relative to preventing the development of cancer. The most common of the hereditary polyposis syndromes is familial adenomatous polyposis (FAP), which is characterized by the development of hundreds to thousands of adenomatous polyps in the colon followed at an early age by colorectal cancer. Colorectal cancer can be prevented in this autosomal dominant condition by prophylactic colectomy, though a risk for other tumors, including periampullary cancers, remains throughout life. Variant of FAP associated with fewer and smaller polyps (hereditary flat adenoma syndrome), or even CNS tumors (Turcot's syndrome) also carry this high risk of colorectal cancer. Hereditary hamartomatous polyposis syndromes such as juvenile polyposis and Peutz-Jeghers syndrome (also autosomal dominant) are characterized by less frequent polyps. Though these are generally benign polyps, they are also associated with a significant risk of colorectal and other cancers. Other polyposis syndromes, including neurofibromatosis and Cowden's disease, do not carry this increased risk of colorectal cancer, and therefore affect different treatment strategies. Analysis of genetic factors responsible for these and other hereditary syndromes with

  3. Intestinal parasites : associations with intestinal and systemic inflammation

    NARCIS (Netherlands)

    Zavala, Gerardo A; García, Olga P; Camacho, Mariela; Ronquillo, Dolores; Campos-Ponce, Maiza; Doak, Colleen; Polman, Katja; Rosado, Jorge L

    2018-01-01

    AIMS: Evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. METHODS AND RESULTS: Plasma concentrations of CRP, leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and

  4. Intestinal transport and metabolism of acrylamide

    International Nuclear Information System (INIS)

    Zoedl, Bettina; Schmid, Diethart; Wassler, Georg; Gundacker, Claudia; Leibetseder, Valentin; Thalhammer, Theresia; Ekmekcioglu, Cem

    2007-01-01

    There has been an intensive debate whether dietary exposure to acrylamide could increase the risk of human cancer since the first description of the presence of acrylamide in food in 2002. As the intestinal mechanisms of acrylamide absorption are poorly investigated we studied the transport of acrylamide in differentiated Caco-2 cells and its effects on biotransformation enzymes (CYP2E1 and glutathione S-transferase) and glutathione levels. We found that the apparent permeability of [1- 14 C] acrylamide from the basal to the apical compartment was approximately 20% higher compared to that in the opposite direction. No differences were detected for apical-basal transport against a basal gradient. Transport rates from the apical to the basal chamber at 4 deg. C were about 50% lower than at 37 deg. C. Concentration dependent transport from apical to basal was linear. Predominantly, basal to apical transport was decreased when energy metabolism of the cells was inhibited by application of sodium azide and 2-deoxy-D-glucose. Finally, more acrylamide was transported at luminal pH 6 compared to pH 7.4 from basal to the apical direction. Increasing levels of acrylamide showed no effects on the activity of glutathione S-transferase but resulted in a depletion of total glutathione concentrations. In conclusion transport of acrylamide in the intestine is mediated primarily by passive processes possibly combined with a modest energy- and pH-dependent active secretory component. Depletion of cellular glutathione levels may be one potential mechanism for acrylamide (geno)toxicity

  5. Small-bowel permeability in collagenous colitis

    DEFF Research Database (Denmark)

    Wildt, Signe; Madsen, Jan L; Rumessen, Jüri J

    2006-01-01

    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...

  6. Altered membrane permeability in multidrug resistant Escherichia ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-02

    Nov 2, 2009 ... involvement during the transport of β - lactams in multidrug resistant Escherichia coli isolated from extra-intestinal infections. Also, the ... lactam resistance in multidrug resistant E. coli in ESBL and non-ESBL isolates. .... and decreased susceptibility to carbapenems, particularly ertapenem (Perez et al.,.

  7. Altered membrane permeability in multidrug resistant Escherichia ...

    African Journals Online (AJOL)

    The study was conducted with the objective of examining the outer membrane proteins and their involvement during the transport of β - lactams in multidrug resistant Escherichia coli isolated from extra-intestinal infections. Also, the response of gram negative bacterial biomembrane alteration was studied using extended ...

  8. Preliminary study of soil permeability properties using principal component analysis

    Science.gov (United States)

    Yulianti, M.; Sudriani, Y.; Rustini, H. A.

    2018-02-01

    Soil permeability measurement is undoubtedly important in carrying out soil-water research such as rainfall-runoff modelling, irrigation water distribution systems, etc. It is also known that acquiring reliable soil permeability data is rather laborious, time-consuming, and costly. Therefore, it is desirable to develop the prediction model. Several studies of empirical equations for predicting permeability have been undertaken by many researchers. These studies derived the models from areas which soil characteristics are different from Indonesian soil, which suggest a possibility that these permeability models are site-specific. The purpose of this study is to identify which soil parameters correspond strongly to soil permeability and propose a preliminary model for permeability prediction. Principal component analysis (PCA) was applied to 16 parameters analysed from 37 sites consist of 91 samples obtained from Batanghari Watershed. Findings indicated five variables that have strong correlation with soil permeability, and we recommend a preliminary permeability model, which is potential for further development.

  9. Influence of salinity on permeability characteristics of marine sediments

    Digital Repository Service at National Institute of Oceanography (India)

    Jose, U.V.; Bhat, S.T.; Nayak, B.U.

    that permeability increases with an increase in salt concentration for a given void ratio. This is explained by diffused double layer theory. Also, the rate of increase in permeability decreases with increase in salt concentration. The effect of salt concentration...

  10. Investigation clogging dynamic of permeable pavement systems using embedded sensors

    Science.gov (United States)

    Permeable pavement is a stormwater control measure commonly selected in both new and retrofit applications. However, there is limited information about the clogging mechanism of these systems that effects the infiltration. A permeable pavement site located at the Seitz Elementary...

  11. Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

    Science.gov (United States)

    Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

    2018-01-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Triorchidism: A Rare Genitourinary Abnormality

    African Journals Online (AJOL)

    During early adulthood it will be carried out by palpation, ultrasonography, semen analysis, serum testosterone and follicle stimulating hormone levels and during late adulthood follow up will be done by ultrasonography for malignancy every 2 years. CONCLUSION. Polyorchidism is a rare genitourinary abnormality and its.

  13. Chromosomal abnormalities associated with omphalocele.

    Science.gov (United States)

    Chen, Chih-Ping

    2007-03-01

    Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup (3q), dup (11p), inv (11), dup (1q), del (1q), dup (4q), dup (5p), dup (6q), del (9p), dup (15q), dup(17q), Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD) such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling.

  14. Chromosomal Abnormalities Associated With Omphalocele

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-03-01

    Full Text Available Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup(3q, dup(11p, inv(11, dup(1q, del(1q, dup(4q, dup(5p, dup(6q, del(9p, dup(15q, dup(17q, Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling.

  15. Admission haematological abnormalities and postoperative ...

    African Journals Online (AJOL)

    Admission haematological abnormalities and postoperative outcomes in neonates with acute surgical conditions in Alexandria, Egypt. HL Wella, SMM Farahat. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals ...

  16. Cytokines and intestinal inflammation.

    Science.gov (United States)

    Bamias, Giorgos; Cominelli, Fabio

    2016-11-01

    Cytokines of the intestinal microenvironment largely dictate immunological responses after mucosal insults and the dominance of homeostatic or proinflammatory pathways. This review presents important recent studies on the role of specific cytokines in the pathogenesis of intestinal inflammation. The particular mucosal effects of cytokines depend on their inherent properties but also the cellular origin, type of stimulatory antigens, intermolecular interactions, and the particular immunological milieu. Novel cytokines of the interleukin-1 (IL-1) family, including IL-33 and IL-36, have dominant roles in mucosal immunity, whereas more established ones such as IL-18 are constantly enriched with unique properties. Th17 cells are important mucosal constituents, although their profound plasticity, makes the specific set of cytokines they secrete more important than their mere numbers. Finally, various cytokines, such as tumor necrosis factor-α, IL-6, tumor necrosis factor-like cytokine 1A, and death receptor, 3 demonstrate dichotomous roles with mucosa-protective function in acute injury but proinflammatory effects during chronic inflammation. The role of cytokines in mucosal health and disease is increasingly revealed. Such information not only will advance our understanding of the pathogenesis of gut inflammation, but also set the background for development of reliable diagnostic and prognostic biomarkers and cytokine-specific therapies.

  17. Computed tomography for diagnosis of intestinal cytomegalovirus infection in AIDS

    International Nuclear Information System (INIS)

    Engelbrecht, V.; Schonlau, R.; Moedder, U.

    1994-01-01

    To check the value of computed tomography (CT) in the diagnosis of cytomegalovirus (CMV) infection of the intestine, CT findings in ten patients with coloscopically proven CMV infection were reviewed. All patients were chronically ill men with AIDS. In nine of the ten cases CT scans of the small intestine and/or colon disclosed abnormalities. The predominant alteration (9/9) was a symmetric wall thickening in the bowel segments involved (10-30 mm). The location and extent showed good agreement with the inflammatory areas seen on coloscopy. The cecum and terminal ileum were the regions most frequently affected. In seven of the nine patients with CT abnormalities CT revealed pericolonic inflammation, particularly around the cecum. Lymph nodes were increased but not enlarged. Comparison of the findings in intestinal CMV infection with those in other AIDS-related diseases suggests that CT may be to limit the differential diagnosis. Abdominal CT serves as suitable primary imaging modality for the initial evaluation of patients with AIDS and abdominal symptoms of unknow etiology. (orig.)

  18. Outcome of splanchnic blood flow determination in patients with suspected chronic intestinal ischaemia. A retrospective survey

    DEFF Research Database (Denmark)

    Møller, Søren; Madsen, Jan Lysgård

    2002-01-01

    BACKGROUND: Different diagnostic examinations have been applied in the management of patients with suspected intestinal ischaemia. In some centres, invasive determination of a meal-induced increase in splanchnic blood flow is used in the diagnostic process and in the selection of patients......: Seventy-three consecutive patients with suspected intestinal ischaemia were included during a 5-year period. Splanchnic blood flow was determined at baseline and after a standardized meal. The patients were classified into three groups according to the level of meal-induced increase in splanchnic blood...... a normal meal-induced response, 23 patients had a possible abnormal response and 10 patients had a definitive abnormal response, which gave evidence of chronic intestinal ischaemia. In the total patient population, the increase in splanchnic blood flow was significantly correlated to an increase in hepatic...

  19. Outcome of splanchnic blood flow determination in patients with suspected chronic intestinal ischaemia. A retrospective survey

    DEFF Research Database (Denmark)

    Møller, Søren; Madsen, Jan Lysgård

    2002-01-01

    a normal meal-induced response, 23 patients had a possible abnormal response and 10 patients had a definitive abnormal response, which gave evidence of chronic intestinal ischaemia. In the total patient population, the increase in splanchnic blood flow was significantly correlated to an increase in hepatic......BACKGROUND: Different diagnostic examinations have been applied in the management of patients with suspected intestinal ischaemia. In some centres, invasive determination of a meal-induced increase in splanchnic blood flow is used in the diagnostic process and in the selection of patients......: Seventy-three consecutive patients with suspected intestinal ischaemia were included during a 5-year period. Splanchnic blood flow was determined at baseline and after a standardized meal. The patients were classified into three groups according to the level of meal-induced increase in splanchnic blood...

  20. Hippo signalling directs intestinal fate

    DEFF Research Database (Denmark)

    le Bouteiller, Marie Catherine M; Jensen, Kim Bak

    2015-01-01

    Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal epit...