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Sample records for intestinal absorptive cells

  1. Starfruit Leaves as Glucose Absorption Inhibitor in Mice’s Small Intestinal Epithelial Cells

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    Rifqi Y Muhammad

    2016-12-01

    Full Text Available Background: Starfruit (Averrhoa carambola leaves contain flavone derivatives that exhibit anti-hyperglycemic effects. This study aims to determine the effect of starfruit leaves in reducing glucose absorption in intestinal epithelial cells of mice. Methods: This study was done by performing perfusion on the small intestines of mice. The mice that were used in this study were divided into four groups. The control group was given glucose solution without infused starfruit leaves whereas, the remaining 3 groups were given 3 mmol (540 mg/dL glucose solution with infused starfruit leaves of varying concentrations; 200, 400, and 600 mg/kg. Samples were collected at 0, 15th, 30th, 45th, and 60th minute. The sample was tested for glucose levels using spectrophotometry. Results: Test of significance showed a significant difference between the control group and the test group with p < 0.05. Conclusions: Starfruit leaves have a reduction effect towards glucose absorption in the small intestines in Wistar strains where the group using 600 mg/kg of infused starfruit leaves have the most significant effect as compared to other groups.

  2. The Relationship Between Intestinal Iron Absorption and Hepatic Parenchymal Cell Damage

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    Kim, Mok Hyun; Hahn, Shin Suck [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1971-09-15

    more, or the liver was irradiated with a single dose of 12,000 rads or more. The results of liver function tests which done simultaneously remained within normal limit except SGOT and SGPR which were somewhat increased. 3. In each case, there has been good correlation between the extent of liver cell damage and degree of increased iron absorption rate or serum iron level. 4. The method of liver damage appeared to make no obvious difference in the pattern of iron deposit in liver. This may be partly due to the fact that tissue specimens were obtained too late, for by this time the elevated serum iron level had returned within normal range and the pathological changes were almost healed. 5. The possible factors and relationship between intestinal iron absorption and hepatic parenchymal cell damage has been discussed.

  3. The Relationship Between Intestinal Iron Absorption and Hepatic Parenchymal Cell Damage

    International Nuclear Information System (INIS)

    Kim, Mok Hyun; Hahn, Shin Suck

    1971-01-01

    more, or the liver was irradiated with a single dose of 12,000 rads or more. The results of liver function tests which done simultaneously remained within normal limit except SGOT and SGPR which were somewhat increased. 3. In each case, there has been good correlation between the extent of liver cell damage and degree of increased iron absorption rate or serum iron level. 4. The method of liver damage appeared to make no obvious difference in the pattern of iron deposit in liver. This may be partly due to the fact that tissue specimens were obtained too late, for by this time the elevated serum iron level had returned within normal range and the pathological changes were almost healed. 5. The possible factors and relationship between intestinal iron absorption and hepatic parenchymal cell damage has been discussed.

  4. Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells

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    Kei Saito

    2017-09-01

    Full Text Available 5-Aminolevulinic acid (ALA is a precursor for the biosynthesis of porphyrins and heme. Although the oral administration of ALA has been widely applied in clinical settings, the dynamics of its absorption, metabolism, and excretion within enterocytes remain unknown. In this study, after enterocytic differentiation, Caco-2 cells were incubated with 200 µM ALA and/or 100 µM sodium ferrous citrate (SFC for up to 72 h. Both ALA and the combination of ALA and SFC promoted the synthesis of heme, without affecting the expression of genes involved in intestinal iron transport, such as DMT1 and FPN. The enhanced heme synthesis in Caco-2 cells was more pronounced under the effect of the combination of ALA and SFC than under the effect of ALA alone, as reflected by the induced expression of heme oxygenase 1 (HO-1, as well as a reduced protein level of the transcriptional corepressor Bach1. Chromatin immunoprecipitation analysis confirmed Bach1 chromatin occupancy at the enhancer regions of HO-1, which were significantly decreased by the addition of ALA and SFC. Finally, Transwell culture of Caco-2 cells suggested that the administered ALA to the intestinal lumen was partially transported into vasolateral space. These findings enhance our understanding of the absorption and metabolism of ALA in enterocytes, which could aid in the development of a treatment strategy for various conditions such as anemia.

  5. Human intestinal absorption of imidacloprid with Caco-2 cells as enterocyte model

    International Nuclear Information System (INIS)

    Brunet, Jean-Luc; Maresca, Marc; Fantini, Jacques; Belzunces, Luc P.

    2004-01-01

    In order to assess the risk to mammals of a chronic exposure to imidacloprid (IMI), we investigated its absorption with the human intestinal Caco-2 cell line. Measurements of transepithelial transport revealed an apparent permeability coefficient of 21.6 x 10 -6 ± 3.2 x 10 -6 cm/s reflecting a 100% absorption. The comparison of apical to basal (A-B) and basal to apical (B-A) transports showed that the monolayer presents a basal to apical polarized transport. Studies of apical uptake demonstrated that the transport was concentration-dependent and not saturable from 5 to 200 μM. Arrhenius plot analysis revealed two apparent activation energies, E a(4-12deg . C) = 63.8 kJ/mol and E a(12-37deg. C) 18.2 kJ/mol, suggesting two temperature-dependent processes. IMI uptake was equivalent when it was performed at pH 6.0 or 7.4. Depletion of Na + from the transport buffer did not affect the uptake, indicating that a sodium-dependent transporter was not involved. Decrease of uptake with sodium-azide or after cell surface trypsin (Ti) treatment suggested the involvement of a trypsin-sensitive ATP-dependent transporter. Investigations on apical efflux demonstrated that initial velocities paralleled the increase of loading concentrations. A cell surface trypsin treatment did not affect the apical efflux. The lack of effect when the efflux was performed against an IMI concentration gradient suggested that an energy-dependent transporter was involved. However, the inhibition of P-glycoproteins (P-gp) and multidrug resistance-associated proteins (MRP) by taxol, vincristine, and daunorubicine had no effect on IMI intracellular accumulation suggesting the involvement of transporters distinct from classical ATP binding cassette transport (ABC-transport) systems. All results suggest that IMI is strongly absorbed in vivo by inward and outward active transporters

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

    International Nuclear Information System (INIS)

    Artursson, P.; Karlsson, J.

    1991-01-01

    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 - 8 to 5 x 10 - 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 - 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 - 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 - 7 cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption

  7. Gintonin absorption in intestinal model systems

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    Byung-Hwan Lee

    2018-01-01

    Conclusion: The present study shows that gintonin could be absorbed in the intestine through transcellular and paracellular diffusion, and active transport. In addition, the lipid component of gintonin might play a key role in its intestinal absorption.

  8. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

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    Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)

    2011-01-07

    Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin

  9. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    International Nuclear Information System (INIS)

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-01

    Research highlights: → Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. → Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. → The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [ 14 C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [ 14 C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather

  10. Binding of navy bean (Phaseolus vulgaris) lectin to the intestinal cells of the rat and its effect on the absorption of glucose

    International Nuclear Information System (INIS)

    Donatucci, D.A.; Liener, I.E.; Gross, C.J.

    1987-01-01

    The main objectives of this investigation were to study the binding of a lectin from navy beans with the epithelial cells of the rat intestine and to assess the effect of such binding on the ability of the intestine to absorb glucose. A Scatchard plot, based on the binding of 125 I-labeled lectin to isolated intestinal epithelial cells, was used to calculate an association constant (Ka) of 15 x 10(6)M-1 and the number of binding sites per cell, 12 x 10(6). Metabolic studies were conducted over a period of 5 d on groups of rats fed raw or autoclaved navy bean flour and casein with or without the purified lectin. Growth, protein digestibility, biological value and net protein utilization were significantly lower in animals that had been fed raw navy bean flour or casein plus lectin than in control groups fed diets containing autoclaved navy bean flour or casein alone. Vascular perfusion was used to measure the rate of uptake of glucose by the intestines of rats that had received the various dietary treatments. The rate of absorption of [ 14 C]glucose by intestines from rats fed raw navy bean flour or casein plus lectin was approximately one-half that of their counterparts fed the autoclaved flour or casein alone. These results provide evidence that the lectin, by virtue of its interference with intestinal absorption, is responsible, at least in part, for the nutritional inferiority of raw navy beans

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

    NARCIS (Netherlands)

    Westerhout, J.; Steeg, E. van de; Grossouw, D.; Zeijdner, E.E.; Krul, C.A.M.; Verwei, M.; Wortelboer, H.M.

    2014-01-01

    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,

  12. Mitochondrial DNA polymerase editing mutation, PolgD257A, disturbs stem-progenitor cell cycling in the small intestine and restricts excess fat absorption.

    Science.gov (United States)

    Fox, Raymond G; Magness, Scott; Kujoth, Gregory C; Prolla, Tomas A; Maeda, Nobuyo

    2012-05-01

    Changes in intestinal absorption of nutrients are important aspects of the aging process. To address this issue, we investigated the impact of accelerated mitochondrial DNA mutations on the stem/progenitor cells in the crypts of Lieberkühn in mice homozygous for a mitochondrial DNA polymerase gamma mutation, Polg(D257A), that exhibit accelerated aging phenotype. As early as 3-7 mo of age, the small intestine was significantly enlarged in the PolgD257A mice. The crypts of the PolgD257A mice contained 20% more cells than those of their wild-type littermates and exhibited a 10-fold increase in cellular apoptosis primarily in the stem/progenitor cell zones. Actively dividing cells were proportionally increased, yet a significantly smaller proportion of cells was in the S phase of the cell cycle. Stem cell-derived organoids from PolgD257A mice failed to develop fully in culture and exhibited fewer crypt units, indicating an impact of the mutation on the intestinal epithelial stem/progenitor cell maintenance. In addition, epithelial cell migration along the crypt-villus axis was slowed and less organized, and the ATP content in the villi was significantly reduced. On a high-fat, high-carbohydrate diet, PolgD257A mice showed significantly restricted absorption of excess lipids accompanied by an increase in fecal steatocrits. We conclude that the PolgD257A mutation causes cell cycle dysregulation in the crypts leading to the age-associated changes in the morphology of the small intestine and contributes to the restricted absorption of dietary lipids.

  13. Biotin absorption by distal rat intestine

    International Nuclear Information System (INIS)

    Bowman, B.B.; Rosenberg, I.H.

    1987-01-01

    We used the in vivo intestinal loop approach, with short (10-min) and long (3-h) incubations, to examine biotin absorption in proximal jejunum, distal ileum, cecum and proximal colon. In short-term studies, luminal biotin disappearance from rat ileum was about half that observed in the jejunum, whereas absorption by proximal colon was about 12% of that in the jejunum. In 3-h closed-loop studies, the absorption of 1.0 microM biotin varied regionally. Biotin absorption was nearly complete in the small intestine after 3 h; however, only about 15% of the dose had been absorbed in the cecum and 27% in the proximal colon after 3 h. Independent of site of administration, the major fraction of absorbed biotin was recovered in the liver; measurable amounts of radioactive biotin were also present in kidney and plasma. The results support the potential nutritional significance for the rat of biotin synthesized by bacteria in the distal intestine, by demonstrating directly an absorptive capability of mammalian large bowel for this vitamin

  14. Intestinal perfusion in the study of intestinal absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Several techniques for studying absorption by means of intestinal perfusion have been developed. While the principle is simple, the practice is complicated by absorption of the solvent and by excretion of fluid into the lumen. To improve reliability a ''marker'' is incorporated into the system; it should behave as nearly as possible like the nutrient of interest, except that it should be unabsorbable. A great many markers, including several labelled with radionuclides, have been developed for use with numerous nutrients, and perfusion methods using double or triple tubes or occlusive balloons have been tested. The perfusion technique is too complicated for routine diagnostic use, but it offers at present the only possibility of studying the function of defined sections of the small intestine in the intact human. (author)

  15. Intestinal absorption of copper: influence of carbohydrates.

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    Wapnir, R A; Balkman, C

    1992-02-01

    Macronutrients can modulate the intestinal absorption of trace elements by binding the metal or altering mucosal function. We investigated whether certain simple and complex carbohydrates modify copper (Cu) absorption, using an in vivo perfusion technique in the rat. Corn syrup solids, which contain a mixture of glucose polymers of diverse length, added at either 20 or 50 mosm/kg enhanced Cu absorption from a 31.5 microM (2 mg/liter) Cu solution (128 +/- 11 and 130 +/- 11 pmol/min x cm, respectively, vs 101 +/- 4 pmol/min x cm, P less than 0.05, in the absence of carbohydrate). This was concomitant with a stimulation of net water absorption (1.05 +/- 0.08 and 0.84 +/- 0.08 microliter/min x cm, respectively, vs 0.63 +/- 0.02 microliter/min x cm with no carbohydrate, P less than 0.05). Glucose, fructose, lactose, or sucrose had no influence on Cu absorption, although they altered water exchanges, an effect attributable to a reduction of the outflow component of fluid recirculation. Low concentrations of lactose resulted in a greater accumulation of Cu in the intestinal mucosa (8.75 +/- 0.71 micrograms/g vs 5.77 +/- 0.68 micrograms/g for controls, P less than 0.05). Hence, solutes that moderately stimulate mucosa-to-serosa fluid influx in a progressive manner, such as glucose polymers, may contribute to functionally increase Cu absorption. Conversely, conditions which tend to reduce water inflow or increase water outflow across the small intestinal mucosa, as may occur with high lactose diets or in cases of chronic diarrhea, may have negative effects.

  16. Effect of colchicine on rat small intestinal absorptive cells. II. Distribution of label after incorporation of [3H]fucose into plasma membrane glycoproteins

    International Nuclear Information System (INIS)

    Ellinger, A.; Pavelka, M.; Gangl, A.

    1983-01-01

    By means of radioautography the influence was tested of various periods (5, 15, 30, 40 min, 2 hr) of pretreatment with colchicine, administered intraperitoneally to rats at a dosage of 0.5 mg/100 g of body weight, on the intracellular pathway of [ 3 H]fucose in absorptive cells of the small intestine. Administration of colchicine for 30 min and longer time intervals causes delay in the insertion of [ 3 H]fucose into the oligosaccharide chains of glycoconjugates in the Golgi apparatus, and results in redistribution of the label apparent over the different portions of the plasma membrane. In controls, at 2 and 4 hr after administration of [ 3 H]fucose the apical plasma membrane is strongly labeled. Colchicine causes equalization of the reaction of apical and basolateral regions of the plasma membrane: the number of silver grains attributable to the apical plasma membrane is reduced; following treatment with colchicine, apical portions of the plasma membrane comprise 31.6 +/- 1.8% of the silver grains, 38.6 +/- 3.8% are attributable to basolateral membrane regions. The colchicine-induced equalization of the density of label of apical and basolateral regions of the plasma membrane, in addition to the occurrence of basolateral microvillus borders, suggests microtubules to be important in the maintenance of the polar organization of small intestinal absorptive cells

  17. Intestinal absorption and secretion of 65Zn in the rat

    International Nuclear Information System (INIS)

    Methfessel, A.H.; Spencer, H.

    1974-01-01

    A single dose of 65 Zn Cl 2 was given by intubation to the intact rat or was instilled into the lumen of ligated intestinal sacs to determine the absorption, or injected intravenously via the tail vein to determine intestinal secretion of 65 Zn. Results indicated that the small intestine plays a major role in the absorption and secretion of zinc and that aging decreases the absorption of zinc for the duodenum of the rat

  18. In vivo and In vitro Evaluations of Intestinal Gabapentin Absorption

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Frølund, Sidsel; Nøhr, Martha Kampp

    2015-01-01

    of gabapentin by both in vivo and in vitro investigations METHODS: Pharmacokinetic parameters were determined following a range of intravenous (5-100 mg/kg) and oral doses (10-200 mg/kg) in rats. Transepithelial transport (50 μM-50 mM) and apical uptake of gabapentin (0.01-50 mM) were investigated in Caco-2...... cells. The effect of co-application of the LAT-inhibitor, BCH, and the b(0,+)-substrate, L-lysine, on intestinal transport of gabapentin was evaluated in vivo and in vitro. RESULTS: Gabapentin showed dose-dependent oral absorption kinetics and dose-independent disposition kinetics. Co-application of BCH...... inhibited intestinal absorption in vivo and apical uptake in vitro, whereas no effect was observed following co-application of L-lysine. CONCLUSIONS: The present study shows for the first time that BCH was capable of inhibiting intestinal absorption of gabapentin in vivo. Furthermore, in Caco-2 cell...

  19. Intestinal absorption of biotin in the rat

    International Nuclear Information System (INIS)

    Bowman, B.B.; Selhub, J.; Rosenberg, I.H.

    1986-01-01

    We examined the absorption of biotin using the in vivo intestinal loop technique. Jejunal segments from male rats were filled with solutions containing [ 3 H]biotin and [ 14 C]inulin in Krebs-Ringer phosphate buffer, pH 6.5. Absorption was determined on the basis of luminal tritium disappearance after correction for inulin recovery. At biotin concentrations of 0.1 and 5.0 microM, luminal biotin disappearance was linear for at least 10 min. At biotin concentrations ranging from 2.3 nM to 75 microM, 10-28% of the administered dose was absorbed in 10 min. The concentration dependence of luminal biotin disappearance is consistent with the presence of both saturable and nonsaturable (linear) components of biotin uptake, with estimated Km = 9.6 microM and Jmax = 75.2 pmol/(2.5 cm loop X min). The rate constant for nonsaturable uptake is 3.1 pmol/(2.5 cm loop X min X microM). We conclude that at biotin concentrations less than 5 microM, biotin absorption proceeds largely by the saturable process, whereas at concentrations above 25 microM, nonsaturable uptake predominates. Additional studies demonstrated significantly less biotin uptake in the ileum than in the jejunum, a finding in agreement with previous in vitro studies

  20. Drug absorption from the irradiated rat small intestine in situ

    International Nuclear Information System (INIS)

    Venho, V.M.K.

    1976-01-01

    The absorption of acidic drugs phenobarbitone and sulphafurazole, basic drugs mecamylamine and quinidine, and a neutral drug isoniazid was studied in situ. Rats were irradiated 750 rad whole-body with 60 Co and the absorption experiment was done three and six days thereafter using the cannulated small intestine of urethane-anaesthetized rats. Drug disappearance from the intestinal lumen and drug levels in the whole blood and intestinal wall were measured. In control rats phenobarbitone showed the most rapid absorption and mecamylamine the slowest. Irradiation retarded the disappearance of all drugs from the intestinal lumen on the third postirradiation day. Fluid absorption was also diminished. On the sixth postirradiation day the absorption of phenobarbitone, sulphafurazole and mecamylamine had returned to the control level, but the absorption of quinidine and isoniazid was still retarded. After i.v. administration of drugs they were not significantly excreted into the intestinal contents and irradiation did not modify excretion. The distribution of drugs between the intestinal fluid and the intestinal wall was complete in the first 10 min of experiment. Mecamylamine and quinidine were lowered in the whole blood by irradiation. Blood levels of drugs did not correlate well to the rate of disappearance of drugs from the intestinal lumen. The reversible changes in absorption induced by irradiation are probably secondary effects of irradiation on intestinal morphology, permeability and transport capacity, composition, and possibly blood flow. (orig.) [de

  1. Transport of radiolabelled glycoprotein to cell surface and lysosome-like bodies of absorptive cells in cultured small-intestinal tissue from normal subjects and patients with a lysosomal storage disease

    International Nuclear Information System (INIS)

    Ginsel, L.A.; Onderwater, J.J.M.; Daems, W.T.

    1979-01-01

    The transport of 3 H-fucose and 3 H-glucosamine-labelled glycoproteins in the absorptive cells of cultured human small-intestinal tissue was investigated with light- and electron-microscopical autoradiography. The findings showed that these glycoproteins were completed in the Golgi apparatus and transported in small vesicular structures to the apical cytoplasm of these cells. Since this material arrived in the cell coat on the microvilli and in the lysosome-like bodies simultaneously, a crinophagic function of these organelles in the regulation of the transport or secretion of cell-coat material was supported. In the absorptive cells of patients with fucosidosis or Hunter's type of lysosomal storage disease, a similar transport of cell-coat material to the lysosome-like bodies and a congenital defect of a lysosomal hydrolase normally involved in the degradation of cell-coat material, can explain the accumulation of this material in the dense bodies. (orig.) [de

  2. Absorption of l-methionine from the human small intestine

    Science.gov (United States)

    Schedl, Harold P.; Pierce, Charles E.; Rider, Alan; Clifton, James A.

    1968-01-01

    Absorption of L-methionine was measured in all parts of the human small intestine using transintestinal intubation and perfusion. In four normal subjects, adsorption was higher in the proximal than in the distal intestine. In two patients with nontropical sprue in relapse, there was a proximal zone of low absorption with higher absorption distally. In all parts of the small intestine, absorption showed rate-limiting kinetics as methionine concentration was increased. In normal subjects, the proximal Km (Michaelis constant) was more than 3 times higher than the distal, which suggests a difference in transport mechanisms between the two segments. PMID:12066784

  3. 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...

  4. Factors in the intestinal absorption of oral cholecystopaques.

    Science.gov (United States)

    Amberg, J R; Thompson, W M; Golberger, L; Williamson, S; Alexander, R; Bates, M

    1980-01-01

    Interest in the pharmacokinetics of cholecystopaques initially centered on transport from blood to bile. The data obtained in this effort have been valuable and have shown that the maximal iodine concentration achievable in the bile is quite similar for all of the currently available compounds. This concentration is, of course, dose dependent. the transport of contrast material from the bowel to the blood has been shown to be quite variable. Considerable progress was made in understanding this. The tremendous differences in absorption of iopanoic acid depending upon the pH of the administered solution was an initial revelation. The development of the concept that there is a water layer through which the cholecystopaque must pass before reaching the lipid membrane of the intestinal cell has added clarity to understanding the difference in absorption between water-soluble and water-insoluble cholecystopaques. A complete knowledge of what might enhance or inhibit absorption is not known. There is beginning to be an understanding of how intestinal dose relates to plasma levels. This should lead to an optimal dose-timing scheme for each cholecystopaque. The basic assumption is that the highest iodine concentration in the gallbladder leads to the most accurate cholecystography. If this is true, the gallbladder needs to be offered bile at the maximum concentrations during the period preceding filming. To accomplish this, the appropriate plasma level necessary for maximum excretion is needed. Experimental data suggest that our current clinical methods in regard to dose and dose timing need revision to optimize cholecystography. This revision needs to take place with a careful look at toxicity. Accepting the present premise that oral cholecystography can be improved, perhaps without a significant increase in morbidity, a fundamental question to be asked is: is it worth it?

  5. Effect of zinc supplements on the intestinal absorption of calcium

    International Nuclear Information System (INIS)

    Spencer, H.; Rubio, N.; Kramer, L.; Norris, C.; Osis, D.

    1987-01-01

    Pharmacologic doses of zinc are widely used as zinc supplements. As calcium and zinc may compete for common absorption sites, a study was carried out on the effect of a pharmacologic dose of zinc on the intestinal absorption of calcium in adult males. The analyzed dietary zinc intake in the control studies was normal, averaging 14.6 mg/day. During the high zinc study, 140 mg zinc as the sulfate was added daily for time periods ranging from 17 to 71 days. The studies were carried out during both a low calcium intake averaging 230 mg/day and during a normal calcium intake of 800 mg/day. Calcium absorption studies were carried out during the normal and high zinc intake by using an oral tracer dose of Ca-47 and determining plasma levels and urinary and fecal excretions of Ca-47. The study has shown that, during zinc supplementation, the intestinal absorption of calcium was significantly lower during a low calcium intake than in the control study, 39.3% vs 61% respectively, p less than 0.001. However, during a normal calcium intake of 800 mg/day, the high zinc intake had no significant effect on the intestinal absorption of calcium. These studies have shown that the high zinc intake decreased the intestinal absorption of calcium during a low calcium intake but not during a normal calcium intake

  6. Modulation of intestinal absorption of calcium

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, P; Dupuis, Y [Ecole Pratique des Hautes Etudes, 75 - Paris (France); Paris-11 Univ., 92 - Chatenay-Malabry (France))

    1975-01-01

    Absorption of ingested calcium (2ml of a 10mM CaCl/sub 2/ solution + /sup 45/Ca) by the adult rat was shown to be facilitated by the simultaneous ingestion of an active carbohydrate, L-arabinose. As the carbohydrate concentration is increased from 10 to 200mM, the absorption of calcium is maximised at a level corresponding to about twice the control absorption level. A similar doubling of calcium absorption is obtained when a 100mM concentration of any one of a number of other carbohydrates is ingested simultaneously with a 10mM CaCl/sub 2/ solution. Conversely, the simultaneous ingestion of increasing doses (10 to 100mM) of phosphate (NaH/sub 2/PO/sub 4/) with a 10mM CaCl/sub 2/ solution results in decreased /sup 45/Ca absorption and retention by the adult rat. The maximum inhibition of calcium absorption by phosphate is independent of the concentration of the ingested calcium solution (from 5 to 50mM CaCl/sub 2/). The simultaneous ingestion of CaCl/sub 2/ (10mM) with lactose and sodium phosphate (50 and 10mM respectively) shows that the activation effect of lactose upon /sup 45/Ca absorption may be partly dissimulated by the presence of phosphate. These various observations indicate that, within a large concentration range (2 to 50mM CaCl/sub 2/) calcium absorption appears to be a precisely modulated diffusion process. Calcium absorption varies (between minimum and maximum levels) as a function of the state of saturation by the activators (carbohydrates) and inhibitors (phosphate) of the calcium transport system.

  7. New insights into the molecular mechanism of intestinal fatty acid absorption.

    Science.gov (United States)

    Wang, Tony Y; Liu, Min; Portincasa, Piero; Wang, David Q-H

    2013-11-01

    Dietary fat is one of the most important energy sources of all the nutrients. Fatty acids, stored as triacylglycerols (also called triglycerides) in the body, are an important reservoir of stored energy and derived primarily from animal fats and vegetable oils. Although the molecular mechanisms for the transport of water-insoluble amphipathic fatty acids across cell membranes have been debated for many years, it is now believed that the dominant means for intestinal fatty acid uptake is via membrane-associated fatty acid-binding proteins, that is, fatty acid transporters on the apical membrane of enterocytes. These findings indicate that intestinal fatty acid absorption is a multistep process that is regulated by multiple genes at the enterocyte level, and intestinal fatty acid absorption efficiency could be determined by factors influencing intraluminal fatty acid molecules across the brush border membrane of enterocytes. To facilitate research on intestinal, hepatic and plasma triacylglycerol metabolism, it is imperative to establish standard protocols for precisely and accurately measuring the efficiency of intestinal fatty acid absorption in humans and animal models. In this review, we will discuss the chemical structure and nomenclature of fatty acids and summarize recent progress in investigating the molecular mechanisms underlying the intestinal absorption of fatty acids, with a particular emphasis on the physical chemistry of intestinal lipids and the molecular physiology of intestinal fatty acid transporters. A better understanding of the molecular mechanism of intestinal fatty acid absorption should lead to novel approaches to the treatment and the prevention of fatty acid-related metabolic diseases that are prevalent worldwide. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  8. Basic studies on digestion and absorption in the small intestine, 7

    International Nuclear Information System (INIS)

    Ohki, Masahisa

    1980-01-01

    The absorption of 14 C-labeled fatty acids (caproic acid, oleic acid and stearic acid) was investigated. These were emulsified with an ultrasonic mixer for 60 min, and intestine treated with physiological saline and 10% pluronic F68 solution was used. Caproic acid was absorbed very rapidly and solely through the portal vein. Oleic acid and stearic acid were absorbed slowly through the lymphatics, with the former being absorbed faster. In physiological saline-treated intestine, oleic acid was transported into both the portal vein and lymphatic ducts. 10% Pluronic F68 solution did not change the absorption of caproic acid and oleic acid, but accelerated that of stearic acid. Autoradiographic studies demonstrated that each fatty acid was absorbed into absorptive cells in a different fashion, and long chain fatty acids required a long period of time for transport from the intestinal cells to the circulating blood. (author)

  9. In vivo studies of biotin absorption in distal rat intestine

    International Nuclear Information System (INIS)

    Bowman, B.B.; Rosenberg, I.H.

    1986-01-01

    The authors have extended their previous studies of biotin absorption in rat proximal jejunum (PJ) to examine biotin absorptive capacity of rat ileum (I) and proximal colon (PC) using in vivo intestinal loop technique. Intestinal loops (2.5 cm) were filled with 0.3 ml of solution containing ( 3 H)-biotin and ( 14 C)-inulin in phosphate buffer, pH 6.5. Biotin absorption was determined on the basis of luminal biotin disappearance after correction for inulin recovery and averaged (pmol/loop-10 min; X +/- SEM). In related experiments, 5-cm loops of PJ, distal I (DI), or PC were filled with 0.5 ml of solution of similar composition (1.0 μM biotin). The abdominal cavity was closed and the rats were allowed to recover from anesthesia, then sacrificed 3 hr after injection. Biotin absorption averaged 96.2% (PJ), 93.2% (DI), and 25.8% (PC) of the dose administered. These differences were reflected in the radioactive biotin content of plasma and intestinal loop, kidney, and liver. These data demonstrate significant biotin absorption in rat DI and PC, as required if the intestinal microflora are to be considered as a source of biotin for the host

  10. Can lipid nanoparticles improve intestinal absorption?

    Science.gov (United States)

    Mendes, M; Soares, H T; Arnaut, L G; Sousa, J J; Pais, A A C C; Vitorino, C

    2016-12-30

    Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Hydroxycitric acid delays intestinal glucose absorption in rats

    NARCIS (Netherlands)

    Wielinga, PY; Wachters-Hagedoorn, RE; Bouter, B; van Dijk, TH; Stellaard, F; Nieuwenhuizen, AG; Verkade, HJ; Scheurink, AJW; Nieuwenhuizen, Arie G.; Verkade, Henkjan J.

    In this study, we investigated in rats if hydroxycitric acid (HCA) reduces the postprandial glucose response by affecting gastric emptying or intestinal glucose absorption. We compared the effect of regulator HCA (310 mg/kg) and vehicle (control) on the glucose response after an intragastric or

  12. Absorption and metabolism of the food contaminant 3-chloro-1,2-propanediol (3-MCPD) and its fatty acid esters by human intestinal Caco-2 cells.

    Science.gov (United States)

    Buhrke, Thorsten; Weisshaar, Rüdiger; Lampen, Alfonso

    2011-10-01

    3-Chloro-1,2-propanediol (3-MCPD) fatty acid esters are formed upon thermal processing of fat-containing foods in the presence of chloride ions. Upon hydrolytic cleavage, these substances could release free 3-MCPD. This compound is toxicologically well characterised and displayed cancerogenic potential in rodent models. Recently, serious contaminations of different food products with 3-MCPD fatty acid esters have been reported. In regard to a risk assessment, the key question is to which degree these 3-MCPD fatty acid esters are hydrolysed in the human gut. Therefore, the aim of the present project was to examine the hydrolysis of 3-MCPD fatty acid esters and the resulting release of free 3-MCPD by using differentiated Caco-2 cells, a cellular in vitro model for the human intestinal barrier. Here, we show that 3-MCPD fatty acid esters at a concentration of 100 μM were neither absorbed by the cells nor the esters were transported via a Caco-2 monolayer. 3-MCPD-1-monoesters were hydrolysed in the presence of Caco-2 cells. In contrast, a 3-MCPD-1,2-diester used in this study was obviously absorbed and metabolised by the cells. Free 3-MCPD was not absorbed by the cells, but the substance migrated through a Caco-2 monolayer by paracellular diffusion. From these in vitro studies, we conclude that 3-MCPD-1-monoesters are likely to be hydrolysed in the human intestine, thereby increasing the burden with free 3-MCPD. In contrast, intestinal cells seem to have the capacity to metabolise 3-MCPD diesters, thereby detoxifying the 3-MCPD moiety.

  13. Importance of intestinal absorption of amino acids in regard to the efficiency of feed proteins in poultry

    International Nuclear Information System (INIS)

    Larbier, M.; Blum, J.C.

    1976-01-01

    The absorption of 14 C(U) L-lysine was studied in vivo (perfusion of isolated intestinal folds) and in vitro (incubation of fragments of intestine) in the chicken and duck during growth. Factors that increase the nutritional efficiency of proteins, e.g. amino-acid deficiency, accelerate intestinal absorption. On the other hand, factors that reduce protein efficiency, be they nutritional (excess amino acids), physiological (age; sex: female compared with male; species: duck compared with chicken) or pathological (experimental coccidiosis), slow down the absorption of lysine. The results are discussed bearing in mind that the absorption rate has a double significance. It plays a part in digestive utilization; it may also reflect metabolic utilization to the extent that transfer through the intestinal mucosa is comparable to incorporation in the cells of the organism. (author)

  14. Absorption mechanism of three curcumin constituents through in situ intestinal perfusion method

    Directory of Open Access Journals (Sweden)

    Y.-H. Wang

    2017-09-01

    Full Text Available This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.

  15. Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity

    Directory of Open Access Journals (Sweden)

    Ekin Bolukbasi

    2017-10-01

    Full Text Available Reduced activity of nutrient-sensing signaling networks can extend organismal lifespan, yet the underlying biology remains unclear. We show that the anti-aging effects of rapamycin and reduced intestinal insulin/insulin growth factor (IGF signaling (IIS require the Drosophila FoxA transcription factor homolog Fork Head (FKH. Intestinal FKH induction extends lifespan, highlighting a role for the gut. FKH binds to and is phosphorylated by AKT and Target of Rapamycin. Gut-specific FKH upregulation improves gut barrier function in aged flies. Additionally, it increases the expression of nutrient transporters, as does lowered IIS. Evolutionary conservation of this effect of lowered IIS is suggested by the upregulation of related nutrient transporters in insulin receptor substrate 1 knockout mouse intestine. Our study highlights a critical role played by FKH in the gut in mediating anti-aging effects of reduced IIS. Malnutrition caused by poor intestinal absorption is a major problem in the elderly, and a better understanding of the mechanisms involved will have important therapeutic implications for human aging.

  16. Studies on the intestinal absorption of vitamin B2

    International Nuclear Information System (INIS)

    Yamaguchi, Keiko; Moriwaki, Chiaki

    1978-01-01

    The intestinal absorption of vitamin B 2 was studied by in situ mesenteric perfusion system. Free form riboflavin (FR), FMN and FAD (1 mg each) were injected into the ligated jejunum of rat which was infused Krebs Ringer bicarbonate solution from the superior mesenteric artery. Perfusate was recovered from the mesenteric vein and the recoveries of the total riboflavin during 120 min after the administration of these 3 types vitamin B 2 were 1.0, 1.5 and 2.8%, respectively. Furthermore, riboflavin and its esters were detected in the perfusates from 14 C-FR and 14 C-FAD given rats. There was a considerable amount of labeled substance which was not vitamin B 2 derivatives in the radiopaperchromatogram of the perfusate of 14 C-FR dosed rats, and it is suggested that a portion of riboflavin is decomposed in the process of absorption. (auth.)

  17. Update on small intestinal stem cells

    OpenAIRE

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-01-01

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to id...

  18. Intestinal absorption and distribution of 14C-palmitic acid in an young Indian freshwater major carp, Labeo rohita (Hamilton)

    International Nuclear Information System (INIS)

    Sinha, G.M.; Chakrabarti, P.

    1983-01-01

    The mechanism of absorption and distribution of radioactive lipids in the various regions of the intestine and hepatopancreas of young Labeo rohita (Ham.) was investigated after feeding with small-sized earthworms (Pheretima posthuma), preinjected with 14 C-Palmitic acid. Dietary free fatty acids were mainly absorbed in the various regions (anterior, middle and posterior) of the intestine-the absorption capacity, however, varying greatly from region to region. The absorption of free fatty acids through the luminal brush border of the various regions of the intestine started at 24 hr of post-feeding (h.p.f.) with labelled diet and recorded its peak during 32 +- 2 h.p.f. However, middle intestine was found to be more active for such absorption than the other two regions (anterior and posterior). Incorporation of labelled Palmitic acid in the columnar epithelial cells and its subsequent transportation in the hepatic tissues, via lymphatic systems took place with in a short interval after absorption. However, absorption was completed within 40 h.p.f. when deposition of radioactive lipids was found to be maximum in the columnar epithelial cells of the various regions of the intestine and hepatic tissues. (author)

  19. Intestinal absorption of water-soluble vitamins in health and disease.

    Science.gov (United States)

    Said, Hamid M

    2011-08-01

    understanding of the mechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. © The Authors Journal compilation © 2011 Biochemical Society

  20. Antioxidant and antiapoptotic properties of melatonin restore intestinal calcium absorption altered by menadione.

    Science.gov (United States)

    Carpentieri, A; Marchionatti, A; Areco, V; Perez, A; Centeno, V; Tolosa de Talamoni, N

    2014-02-01

    The intestinal Ca²⁺ absorption is inhibited by menadione (MEN) through oxidative stress and apoptosis. The aim of this study was to elucidate whether the antioxidant and antiapoptotic properties of melatonin (MEL) could protect the gut against the oxidant MEN. For this purpose, 4-week-old chicks were divided into four groups: (1) controls, (2) treated i.p. with MEN (2.5 μmol/kg of b.w.), (3) treated i.p. with MEL (10 mg/kg of b.w.), and (4) treated with 10 mg MEL/kg of b.w after 2.5 μmol MEN/kg of b.w. Oxidative stress was assessed by determination of glutathione (GSH) and protein carbonyl contents as well as antioxidant enzyme activities. Apoptosis was assayed by the TUNEL technique, protein expression, and activity of caspase 3. The data show that MEL restores the intestinal Ca²⁺ absorption altered by MEN. In addition, MEL reversed the effects caused by MEN such as decrease in GSH levels, increase in the carbonyl content, alteration in mitochondrial membrane permeability, and enhancement of superoxide dismutase and catalase activities. Apoptosis triggered by MEN in the intestinal cells was arrested by MEL, as indicated by normalization of the mitochondrial membrane permeability, caspase 3 activity, and DNA fragmentation. In conclusion, MEL reverses the inhibition of intestinal Ca²⁺ absorption produced by MEN counteracting oxidative stress and apoptosis. These findings suggest that MEL could be a potential drug of choice for the reversal of impaired intestinal Ca²⁺ absorption in certain gut disorders that occur with oxidative stress and apoptosis.

  1. Intestinal absorption of chromium as affected by wheat bran

    International Nuclear Information System (INIS)

    Keim, K.S.; Holloway, C.L.; Hegsted, M.

    1986-01-01

    This study was designed to investigate the influence of dietary fiber, as found in wheat bran, on the absorption of chromium. Twenty male Sprague-Dawley rats were divided into two groups of 10. The control was fed a semi-purified diet containing casein, methionine, cornstarch, sucrose, corn oil, mineral and vitamin mix, and choline bitartrate. The experimental group was fed the same diet but with soft red winter wheat bran added to a level of 35% of the diet at the expense of sucrose. To determine chromium absorption and uptake by selected tissues, rats were fasted for 24 hr, fed 5 g of the respective diet, 2 hr later intubated with 100μCi of Cr-51of sacrificed 24 hr later. The rats wee housed in metabolic cages after the Cr-51 intubation. The addition of wheat brand to the diet did not significantly affect chromium absorption as measured by percent dose of Cr-51 in the 24 hr urine. The percent dose in the control group was 0.68 +/- 0.20% (mean +/- SEM) and in the experimental group 0.63 +/- 0.24% (mean +/-SEM) (N.S.). The cr-51 uptake of liver, spleen, jejunum, and blood was not statistically different between groups. These results indicate that dietary fiber as found in wheat bran does not impair intestinal absorption of chromium

  2. Transporters for the Intestinal Absorption of Cholesterol, Vitamin E, and Vitamin K

    OpenAIRE

    Yamanashi, Yoshihide; Takada, Tappei; Kurauchi, Ryoya; Tanaka, Yusuke; Komine, Toko; Suzuki, Hiroshi

    2017-01-01

    Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using ge...

  3. Immunological demonstration of intestinal absorption and digestion of protein macromolecules in the trout (Salmo gairdneri).

    Science.gov (United States)

    Georgopoulou, U; Sire, M F; Vernier, J M

    1986-01-01

    An immunofluorescence technique using antibodies against the Fc and Fab fragments of human IgG (IgGH) was used to study the absorption of proteins by the intestinal epithelial cells of rainbow trout after oral or anal administration. Cellular absorption of a high molecular weight protein, hepatitis-B surface antigen (HBsAg), was also studied by using two monoclonal antibodies, one specific for the confirmation of the antigen (implying disulfide bridges), and the other that reacts with the constituent polypeptides. Both absorbed IgGH and HBsAg were seen to be segregated in the apical vacuolar system, a characteristic feature of intestinal epithelial cells. The same antibodies were used with an everted sac technique in conjunction with immunofluorescence, to show the intravacuolar degradation of IgGH and HBsAg following absorption. By using an antibody against cathepsin D, it was possible to demonstrate, by immunofluorescence, the localization of this enzyme in the same vacuolar system. After coupling the antibody to peroxidase or to the protein A/colloidalgold complex, the ultrastructural antigenic sites of cathepsin D could be seen to be localized in the interior of the vacuoles. The vacuolar localization of a cathepsin B activity was determined by incubating sections of intestinal mucosa, or isolated epithelial cells, with a specific synthetic substrate (Z-Ala-Arg-Arg-methoxynaphthylamide). The supranuclear hyaloplasmic vacuoles of intestinal epithelial cells may be considered to be phagolysosomes that assure the degradation of absorbed proteins. This function may be of fundamental importance in the in the nutritional processes of this species.

  4. Improvement of intestinal absorption of forsythoside A in weeping forsythia extract by various absorption enhancers based on tight junctions.

    Science.gov (United States)

    Zhou, Wei; Qin, Kun Ming; Shan, Jin Jun; Ju, Wen Zheng; Liu, Shi Jia; Cai, Bao Chang; Di, Liu Qing

    2012-12-15

    Forsythoside A (FTA), one of the main active ingredients in weeping forsythia extract, possesses strong antibacterial, antioxidant and antiviral effects, and its content was about 8% of totally, higher largely than that of other ingredients, but the absolute bioavailability orally was approximately 0.5%, which is significant low influencing clinical efficacies of its oral preparations. In the present study, in vitro Caco-2 cell, in situ single-pass intestinal perfusion and in vivo pharmacokinetics study were performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test, measurement of total amount of protein and the activity of LDH and morphology observation, respectively. The pharmacological effects such as antioxidant activity improvement by absorption enhancers were verified by PC12 cell damage inhibition rate after H₂O₂ insults. The observations from in vitro Caco-2 cell showed that the absorption of FTA in weeping forsythia extract could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/ml was safe for the Caco-2 cells, but water-soluble chitosan at different concentrations was all safe for these cells. The observations from single-pass intestinal perfusion in situ model showed that duodenum, jejunum, ileum and colon showed significantly concentration-dependent increase in P(eff)-value, and that P(eff)-value in the ileum and colon groups, where sodium caprate was added, was higher than that of duodenum and jejunum groups, but P(eff)-value in the jejunum group was higher than that of duodenum, ileum and colon groups where water-soluble chitosan was added. Intestinal mucosal toxicity studies showed no

  5. In vivo kinetics of intestinal absorption of riboflavin in rats

    International Nuclear Information System (INIS)

    Feder, S.; Daniel, H.; Rehner, G.

    1991-01-01

    To investigate absorption kinetics of riboflavin under in vivo conditions, with blood and lymph circulation intact, the small intestine of anesthetized rats was perfused with [ 14 C]riboflavin in a concentration range between 0.31 and 10.00 mumol/L. Apart from the uptake of riboflavin from the perfusate, passage of the vitamin into the portal (vena portae) and peripheral (vena femoralis) blood was determined. The absorption proved to be a dual process: at low substrate concentrations (less than 2 mumol/L) a saturable component predominated; at higher concentrations simple diffusion was found to be the prevailing uptake mechanism. The apparent transport constant of the saturable component was calculated to be 0.38 mumol/L. [ 14 C]flavin concentrations in the portal and peripheral blood were estimated as a function of the riboflavin concentration of the perfusion media. The dual character of the absorption was reflected by the portal blood flavin levels. Due to the high retaining and equalizing capacity of the liver, the [ 14 C]flavin level of the peripheral blood was relatively low and obeyed saturation kinetics. Constants of elimination, determined by pharmacokinetic calculations, were different for the two blood compartments but independent of the concentration of riboflavin in the perfusion media

  6. Effect of lactose on intestinal absorption of calcium

    International Nuclear Information System (INIS)

    Labat, Marie-Louise

    1972-01-01

    Calcium absorption was immediately increased when lactose was administered in large amounts in the intestine of standard rats fed on a vitamin D diet. The same effect could be reproduced with lactulose, a glucid un-hydrolyzed by lactase and unabsorbed. The occurrence of a saturation process for high doses of calcium agrees with a biochemical process through a carrier; this process was not inhibited by actinomycin D, which does not agree with a 'de novo' synthesis of a calcium binding protein; yet activation of the preexisting protein cannot be excluded. The intestinal effect of lactose resulted in an inhibition of bone catabolism in the adult normocalcemic rat indicating a possible interference of thyrocalcitonin. Finally in the young rat, hypocalcemic by lack of vitamin D, on account of the lactose effect, calcium can be considered as a 'third messenger' in the chain of intracellular events between the interaction of the parathyroid hormone with the bone receptor and the expression of its activity. (author) [fr

  7. Intestinal absorption of PLAGA microspheres in the rat.

    Science.gov (United States)

    Damgé, C; Aprahamian, M; Marchais, H; Benoit, J P; Pinget, M

    1996-12-01

    Rhodamine B-labelled poly (DL-lactide-co-glycolide) (PLAGA) microspheres of 2 different sizes, 1-5 microns and 5-10 microns, were administered as a single dose (1.44 x 10(9) and 1.83 x 10(8) particles, respectively) into the ileal lumen of adult rats. The content of rhodamine in the mesenteric vein and ileal lumen was analysed periodically from 10 min to 48 h as well as the distribution of microspheres in the intestinal mucosa and various other tissues. The concentration of rhodamine decreased progressively in the intestinal lumen and was negligible after 24 h. The number of microspheres in the mesenteric vein increased rapidly and reached a maximum after 4 h whatever the size of the particles. It then decreased progressively, but more rapidly with microspheres > 5 microns than with microspheres PLAGA microspheres mainly crossed the intestinal mucosa at the site of Peyer's patches where microspheres of 5 microns were retained in the ileal lumen. A few small microspheres were occasionally observed in the epithelial cells. Only the smallest particles were recovered in the liver, lymph nodes and spleen while basement membranes were always labelled. It is concluded that PLAGA microspheres could be useful for the oral delivery of antigens if their size is between 1 and 5 microns.

  8. Update on small intestinal stem cells.

    Science.gov (United States)

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-08-07

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration.

  9. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    Directory of Open Access Journals (Sweden)

    de Mello Maria

    2002-04-01

    Full Text Available Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein: pregnant (N, tumor-bearing (WN, pair-fed rats (Np. Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine: leucine (L, tumor-bearing (WL and pair-fed with leucine (Lp. Non pregnant rats (C, which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

  10. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice Roston de; Gomes-Marcondes, Maria Cristina Cintra

    2002-01-01

    It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones

  11. [Recent knowledge about intestinal absorption and cleavage of carotenoids].

    Science.gov (United States)

    Borel, P; Drai, J; Faure, H; Fayol, V; Galabert, C; Laromiguière, M; Le Moël, G

    2005-01-01

    Our knowledge about intestinal absorption and cleavage of carotenoids has rapidly grown during the last years. New facts about carotenoid absorption have emerged while some controversies about cleavage are close to end. The knowledge of the absorption and conversion processes is indispensable to understand and interpret the perturbations that can occur in the metabolism of carotenoids and vitamin A. Recently, it has been shown that the absorption of certain carotenoids is not passive - as believed for a long time - but is a facilitated process that requires, at least for lutein, the class B-type 1 scavenger receptor (SR-B1). Various epidemiological and clinical studies have shown wide variations in carotenoid absorption from one subject to another, such differences are now explained by the structure of the concerned carotenoid, by the nature of the food that is absorbed with the carotenoid, by diverse exogenous factors like the intake of medicines or interfering components, by diet factors, by genetic factors, and by the nutritional status of the subject. Recently, the precise mechanism of beta-carotene cleavage by betabeta-carotene 15,15' monooxygenase (EC 1.14.99.36) - formerly called beta-carotene 15,15' dioxygenase (ex EC 1.13.11.21) - has been discovered, and a second enzyme which cleaves asymmetrically the beta-carotene molecule has been found. beta-carotene 15,15' monooxygenase only acts on the 15,15' bond, thus forming two molecules of retinal from one molecule of beta-carotene by central cleavage. Even though the betabeta-carotene 15,15' monooxygenase is much more active on the beta-carotene molecule, a study has shown that it can act on all carotenoids. Searchers now agree that other enzymes that can catalyse an eccentric cleavage of carotenoids probably exist, but under physiological conditions the betabeta-carotene 15,15' monooxygenase is by far the most active, and it is mainly effective in the small bowel mucosa and in the liver. However the

  12. Ursodeoxycholic and deoxycholic acids: A good and a bad bile acid for intestinal calcium absorption.

    Science.gov (United States)

    Rodríguez, Valeria; Rivoira, María; Marchionatti, Ana; Pérez, Adriana; Tolosa de Talamoni, Nori

    2013-12-01

    The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal Ca(2+) absorption and to find out whether the inhibition of this process caused by NaDOC could be prevented by UDCA. Chicks were employed and divided into four groups: (a) controls, (b) treated with 10mM NaDOC, (c) treated with 60 μg UDCA/100g of b.w., and (d) treated with 10mM NaDOC and 60 μg UDCA/100g of b.w. UDCA enhanced intestinal Ca(2+) absorption, which was time and dose-dependent. UDCA avoided the inhibition of intestinal Ca(2+) absorption caused by NaDOC. Both bile acids altered protein and gene expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption, but in the opposite way. UDCA aborted the oxidative stress produced by NaDOC in the intestine. UDCA and UDCA plus NaDOC increased vitamin D receptor protein expression. In conclusion, UDCA is a beneficial bile acid for intestinal Ca(2+) absorption. Contrarily, NaDOC inhibits the intestinal cation absorption through triggering oxidative stress. The use of UDCA in patients with cholestasis would be benefited because of the protective effect on the intestinal Ca(2+) absorption, avoiding the inhibition caused by hydrophobic bile acids and neutralizing the oxidative stress. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.

    Science.gov (United States)

    David, Dahlgren; Carl, Roos; Pernilla, Johansson; Christer, Tannergren; Anders, Lundqvist; Peter, Langguth; Markus, Sjöblom; Erik, Sjögren; Hans, Lennernäs

    2018-05-11

    Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients (CPEs), or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system. The absorption-enhancing effects of AMEs/CPEs with different mechanisms (chitosan, sodium caprate, sodium dodecyl sulfate (SDS)) have previously been evaluated in the rat single-pass intestinal perfusion (SPIP) model. However, it remains unclear whether these SPIP data are predictive in a more in vivo like model. The same excipients were in this study evaluated in rat and dog intraintestinal bolus models. SDS and chitosan did exert an absorption-enhancing effect in both bolus models, but the effect was substantially lower than those observed in the rat SPIP model. This illustrates the complexity of the AME/CPE effects, and indicates that additional GI physiological factors need to be considered in their evaluation. We therefore recommend that AME/CPE evaluations obtained in transit-independent, preclinical permeability models (e.g. Ussing, SPIP) should be verified in animal models better able to predict in vivo relevant GI effects, at multiple excipient concentrations. Copyright © 2018. Published by Elsevier B.V.

  14. CD36 mediates both cellular uptake of very long chain fatty acids and their intestinal absorption in mice.

    Science.gov (United States)

    Drover, Victor A; Nguyen, David V; Bastie, Claire C; Darlington, Yolanda F; Abumrad, Nada A; Pessin, Jeffrey E; London, Erwin; Sahoo, Daisy; Phillips, Michael C

    2008-05-09

    The intestine has an extraordinary capacity for fatty acid (FA) absorption. Numerous candidates for a protein-mediated mechanism of dietary FA absorption have been proposed, but firm evidence for this process has remained elusive. Here we show that the scavenger receptor CD36 is required both for the uptake of very long chain FAs (VLCFAs) in cultured cells and the absorption of dietary VLCFAs in mice. We found that the fraction of CD36-dependent saturated fatty acid association/absorption in these model systems is proportional to the FA chain length and specific for fatty acids and fatty alcohols containing very long saturated acyl chains. Moreover, intestinal VLCFA absorption is completely abolished in CD36-null mice fed a high fat diet, illustrating that the predominant mechanism for VLCFA absorption is CD36-dependent. Together, these findings represent the first direct evidence for protein-facilitated FA absorption in the intestine and identify a novel therapeutic target for the treatment of diseases characterized by elevated VLCFA levels.

  15. Investigation of the effective components of the flowers of Trollius chinensis from the perspectives of intestinal bacterial transformation and intestinal absorption.

    Science.gov (United States)

    Guo, Lina; Qiao, Shanshan; Hu, Junhong; Li, Deli; Zheng, Shiqi; Shi, Duozhi; Liu, Junxiu; Wang, Rufeng

    2017-12-01

    The flowers of Trollius chinensis Bunge (Ranunculaceae), used for respiratory tract infections, mainly contain flavonoids, phenolic acids, and alkaloids; however, the effective components are debatable because of their unclear in vivo activities. This study investigates the effective components from the perspectives of biotransformation and absorption. Both single person derived- and multiple people-derived intestinal florae were used to investigate the biotransformation of aqueous extract of the flowers of T. chinensis (AEOF) at the concentrations of 15.0, 30.0, and 60.0 mg/mL, respectively, for 72 h. Both human colon adenocarcinoma cell line (Caco-2) monolayers and everted gut sacs were employed to evaluate the intestinal absorption of the intestinal bacterial transformed AEOF at the concentrations of 10, 20, and 30 mg/mL, respectively, for 180 min. 2″-O-β-l-Galactopyranosylorientin, orientin, vitexin, quercetin, veratric acid, proglobeflowery acid, and trolline in AEOF were not transformed by intestinal bacteria, while isoquercetin and trollioside were completely transformed. The P app values of 2″-O-β-l-galactopyranosylorientin, orientin, and vitexin calculated based on the experimental data of intestinal absorption were at the levels of 10 -5 , whereas those of veratric acid, proglobeflowery acid, and trolline were at 10 -4 . The mass ratio of flavonoids to phenolic acids to alkaloids changed from 16:10:7 to 9:12:8 before and after absorption. The dominant position of flavonoids was replaced by phenolic acids after absorption. In addition to flavonoids which are usually considered as the dominant effective ones, phenolic acids and alkaloids should be also very important for the efficacy of these flowers.

  16. Transporters for the Intestinal Absorption of Cholesterol, Vitamin E, and Vitamin K.

    Science.gov (United States)

    Yamanashi, Yoshihide; Takada, Tappei; Kurauchi, Ryoya; Tanaka, Yusuke; Komine, Toko; Suzuki, Hiroshi

    2017-04-03

    Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol. Surprisingly, detailed analyses of these cholesterol transporters have revealed that they can also transport vitamin E and vitamin K, providing clues to uncover the molecular mechanisms underlying the intestinal absorption of these fat-soluble vitamins. In this review, we focus on the membrane proteins (Niemann-Pick C1 like 1, scavenger receptor class B type I, cluster of differentiation 36, and ATP-binding cassette transporter A1) that are (potentially) involved in the intestinal absorption of cholesterol, vitamin E, and vitamin K and discuss their physiological and pharmacological importance. We also discuss the related uncertainties that need to be explored in future studies.

  17. Estimation of the Intestinal Absorption and Metabolism Behaviors of 2- and 3-Monochloropropanediol Esters.

    Science.gov (United States)

    Kaze, Naoki; Watanabe, Yomi; Sato, Hirofumi; Murota, Kaeko; Kotaniguchi, Miyako; Yamamoto, Hiroshi; Inui, Hiroshi; Kitamura, Shinichi

    2016-08-01

    The regioisomers of the di- and mono-oleate of monochloropropanediol (MCPD) have been synthesized and subsequently hydrolyzed with pancreatic lipase and pancreatin to estimate the intestinal digestion and absorption of these compounds after their intake. The hydrolysates were analyzed by HPLC using a corona charged aerosol detection system, which allowed for the separation and detection of the different regioisomers of the MCPD esters. The hydrolysates were also analyzed by GC-MS to monitor the free MCPD. The results indicated that the two acyl groups of 2-MCPD-1,3-dioleate were smoothly hydrolyzed by pancreatic lipase and pancreatin to give free 2-MCPD. In contrast, the hydrolysis of 3-MCPD-1,2-dioleate proceeded predominantly at the primary position to produce 3-MCPD-2-oleate. 2-MCPD-1-oleate and 3-MCPD-1-oleate were further hydrolyzed to free 2- and 3-MCPD by pancreatic lipase and pancreatin, although the hydrolysis of 3-MCPD-2-oleate was 80 % slower than that of 3-MCPD-1-oleate. The intestinal absorption characteristics of these compounds were evaluated in vitro using a Caco-2 cell monolayer. The results revealed that the MCPD monooleates, but not the MCPD dioleates, were hydrolyzed to produce the free MCPD in the presence of the Caco-2 cells. The resulting free MCPD permeated the Caco-2 monolayer most likely via a diffusion mechanism because their permeation profiles were independent of the dose. Similar permeation profiles were obtained for 2- and 3-MCPDs.

  18. Oral absorption of peptides and nanoparticles across the human intestine: Opportunities, limitations and studies in human tissues.

    Science.gov (United States)

    Lundquist, P; Artursson, P

    2016-11-15

    In this contribution, we review the molecular and physiological barriers to oral delivery of peptides and nanoparticles. We discuss the opportunities and predictivity of various in vitro systems with special emphasis on human intestine in Ussing chambers. First, the molecular constraints to peptide absorption are discussed. Then the physiological barriers to peptide delivery are examined. These include the gastric and intestinal environment, the mucus barrier, tight junctions between epithelial cells, the enterocytes of the intestinal epithelium, and the subepithelial tissue. Recent data from human proteome studies are used to provide information about the protein expression profiles of the different physiological barriers to peptide and nanoparticle absorption. Strategies that have been employed to increase peptide absorption across each of the barriers are discussed. Special consideration is given to attempts at utilizing endogenous transcytotic pathways. To reliably translate in vitro data on peptide or nanoparticle permeability to the in vivo situation in a human subject, the in vitro experimental system needs to realistically capture the central aspects of the mentioned barriers. Therefore, characteristics of common in vitro cell culture systems are discussed and compared to those of human intestinal tissues. Attempts to use the cell and tissue models for in vitro-in vivo extrapolation are reviewed. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Lymphoid cells in chicken intestinal epithelium

    DEFF Research Database (Denmark)

    Bjerregaard, P

    1975-01-01

    The intraepithelial lymphoid cells of chicken small intestine were studied by light microscopy using 1 mu Epon sections, and by electron microscopy. Three cell types were found: small lymphocytes, large lymphoid cells, and granular cells. These cells correspond to the theliolymphocytes and globule...

  20. Transport of trans-tiliroside (kaempferol-3-β-D-(6"-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestine.

    Science.gov (United States)

    Luo, Zijun; Morgan, Michael R A; Day, Andrea J

    2015-01-01

    1. Absorption and metabolism of tiliroside (kaempferol 3-β-D-(6"-p-coumaroyl)-glucopyranoside) and its related compounds kaempferol, kaempferol-3-glucoside and p-coumaric acid were investigated in the small intestinal Caco-2 cell model. Apparent permeation (Papp) was determined as 0.62 × 10(-6) cm/s, 3.1 × 10(-6) cm/s, 0 and 22.8 × 10(-6) cm/s, respectively. 2. Mechanistic study showed that the transportation of tiliroside, kaempferol-3-glucoside and p-coumaric acid in Caco-2 model were transporter(s) involved, while transportation of kaempferol was solely by passive diffusion mechanism. 3. Efflux transporters, multi-drug-resistance-associated protein-2 (MRP2), were shown to play a role in limiting the uptake of tiliroside. Inhibitors of MRP2, (MK571 and rifampicin) and co-incubation with kaempferol (10 μM), increased transfer from the apical to the basolateral side by three to five fold. 4. Metabolites of kaempferol-3-glucoside and p-coumaric acid were not detected in the current Caco-2 model, while tiliroside was metabolised to a limited extent, with two tiliroside mono-glucuronides identified; and kaempferol was metabolised to a higher extent, with three mono-glucuronides and two mono-sulfates identified. 5. In conclusion, tiliroside was metabolised and transported across Caco-2 cell membrane to a limited extent. Transportation could be increased by applying MRP2 inhibitors or co-incubation with kaempferol. It is proposed that tiliroside can be absorbed by human; future pharmacokinetics studies are warranted in order to determine the usefulness of tiliroside as a bioactive agent.

  1. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption

    Science.gov (United States)

    Patel, Chirag; Douard, Veronique; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P.

    2015-01-01

    Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.—Patel, C., Douard, V., Yu, S., Gao, N., Ferraris, R. P. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption. PMID:26071406

  2. 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

  3. Intestinal endocrine cells in radiation enteritis

    NARCIS (Netherlands)

    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

  4. Recent Advances in Intestinal Stem Cells.

    Science.gov (United States)

    McCabe, Laura R; Parameswaran, Narayanan

    2017-09-01

    The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here. The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs. ISC niche cells, including Paneth, immune and myofibroblast cells secrete factors that regulate ISC proliferation. Finally, several studies indicate that the microbiome metabolites regulate ISC growth. ISC cells can be plastic and integrate a complexity of environmental/niche cues to trigger or suppress proliferation as needed.

  5. Intestinal cholesterol transport: Measuring cholesterol absorption and its reverse

    NARCIS (Netherlands)

    Jakulj, L.

    2013-01-01

    Intestinal cholesterol transport might serve as an attractive future target for cardiovascular disease reduction, provided that underlying molecular mechanisms are more extensively elucidated, combined with improved techniques to measure changes in cholesterol fluxes and their possible

  6. A modified physiological BCS for prediction of intestinal absorption in drug discovery.

    Science.gov (United States)

    Zaki, Noha M; Artursson, Per; Bergström, Christel A S

    2010-10-04

    In this study, the influence of physiologically relevant media on the compound position in a biopharmaceutical classification system (BCS) which resembled the intestinal absorption was investigated. Both solubility and permeability limited compounds (n = 22) were included to analyze the importance of each of these on the final absorption. Solubility was determined in three different dissolution media, phosphate buffer pH 6.5 (PhB 6.5), fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF) at 37 °C, and permeability values were determined using the 2/4/A1 cell line. The solubility data and membrane permeability values were used for sorting the compounds into a BCS modified to reflect the fasted and fed state. Three of the seven compounds sorted as BCS II in PhB 6.5 (high permeability, low solubility) changed their position to BCS I when dissolved in FaSSIF and/or FeSSIF (high permeability, high solubility). These were low dosed (20 mg or less) lipophilic molecules displaying solvation limited solubility. In contrast, compounds having solid-state limited solubility had a minor increase in solubility when dissolved in FaSSIF and/or FeSSIF. Although further studies are needed to enable general cutoff values, our study indicates that low dosed BCS Class II compounds which have solubility normally restricted by poor solvation may behave as BCS Class I compounds in vivo. The large series of compounds investigated herein reveals the importance of investigating solubility and dissolution under physiologically relevant conditions in all stages of the drug discovery process to push suitable compounds forward, to select proper formulations, and to reduce the risk of food effects.

  7. [Production, absorption and excretion of phenols in intestinal obstruction].

    Science.gov (United States)

    Kawamoto, M

    1986-11-01

    In intestinal obstruction, phenols were produced in the distended loop proximal to obstruction by enteric bacteria. Clinically, in 17 cases of non-strangulated intestinal obstruction, phenols were detected in 15 cases and mean concentration of phenols was 4.2 +/- 9.7 micro g/ml(mean +/- 1 SD). In the fraction of phenols, p-cresol was detected in 15 cases and mean concentration was 3.8 +/- 7.7 and phenol was detected in 4 cases and mean concentration was 0.5 +/- 2.6. Phenols were decreased as clinical improvement of intestinal obstruction. Enteric bacteria in enteric juice ranged from 10(4) to 10(10)/ml and its change paralleled to phenols concentration. Mean urinary concentration of phenols in intestinal obstruction was increased to 297 +/- 415 mg/day compared to control (less than 50 mg/day). Its change also paralleled to phenols concentration in enteric juice. Closed ileal loop was made in dogs and phenols were infused in the loop. Phenols were increased in the portal vein 5 min after the infusion and in the femoral vein 60 min after the infusion. Phenols, which was thought to be toxic to the host, were proved to be produced in the distended intestine and excreted from the kidney.

  8. Transcriptome changes during intestinal cell differentiation

    DEFF Research Database (Denmark)

    Tadjali, Mehrdad; Seidelin, Jakob B; Olsen, Jørgen

    2002-01-01

    The expression of 18149 genes have been analysed during the differentiation of the human intestinal cell line Caco-2. cDNA probes from undifferentiated and differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an array on a nylon membrane. A remarkable change in the transc......The expression of 18149 genes have been analysed during the differentiation of the human intestinal cell line Caco-2. cDNA probes from undifferentiated and differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an array on a nylon membrane. A remarkable change...... cells by performing reverse transcriptase-polymerase chain reaction on RNA extracted from laser dissected intestinal crypt and villi. In a screen of eight transcripts one - SART3 - was identified as a marker for human colonic crypts....

  9. Tests of intestinal absorption of 3H labelled enzymes (wobenzym)

    International Nuclear Information System (INIS)

    Steffen, C.; Menzel, J.; Smolen, J.

    1979-01-01

    0.2 g of an enzyme mixture (Wobenzym) labelled with 3 H-acetic anhydride, were given orally to guinea pigs, which were arranged in 4 groups of 5 animals. The animals of each group were sacrificed at intervals of 30 minutes, 2, 4 and 24 hours after application. Radioactivity of the small and large intestine, plasma, urine, liver, heart, kidney, and skeletal muscle were determined. It could be shown that the labelled mixture of enzymes was absorbed from the intestine and was demonstrable in significant amounts in plasma, urine, heart, kidney, liver and skeletal muscle. (author)

  10. Iodine Absorption Cells Purity Testing

    Directory of Open Access Journals (Sweden)

    Jan Hrabina

    2017-01-01

    Full Text Available This article deals with the evaluation of the chemical purity of iodine-filled absorption cells and the optical frequency references used for the frequency locking of laser standards. We summarize the recent trends and progress in absorption cell technology and we focus on methods for iodine cell purity testing. We compare two independent experimental systems based on the laser-induced fluorescence method, showing an improvement of measurement uncertainty by introducing a compensation system reducing unwanted influences. We show the advantages of this technique, which is relatively simple and does not require extensive hardware equipment. As an alternative to the traditionally used methods we propose an approach of hyperfine transitions’ spectral linewidth measurement. The key characteristic of this method is demonstrated on a set of testing iodine cells. The relationship between laser-induced fluorescence and transition linewidth methods will be presented as well as a summary of the advantages and disadvantages of the proposed technique (in comparison with traditional measurement approaches.

  11. Evidence for Enhanced Intestinal Absorption of Digoxin by P ...

    African Journals Online (AJOL)

    Purpose: To investigate the influence of macrolides as P-glycoprotein inhibitors on the level of intestinal ... The effective permeability of the drug was calculated after analyzing the ... associated with oral formulation factors such ... high performance liquid chromatography ..... pharmacokinetics of intravenous digoxin in.

  12. Intestinal absorption of dinitrophenyl-lysine and effect of immunization with dinitrophenylated bovine serum albumin

    International Nuclear Information System (INIS)

    Shimura, Fumio; Shimura, Junko; Shimazaki, Shigeki; Hosoya, Norimasa

    1983-01-01

    The intestinal absorption of dinitrophenyl-lysine (DNP-lys) was studied with a special interest on the role of the immune system in the absorption of small molecules which are recognized as nonself. [ 3 H]-DNP- lys was rapidly absorbed by ligated intestinal loops in situ via a saturable and unique route. When [ 3 H]-DNP-lys was preincubated with the immume serum obtained from rats immunized with dinitrophenylated bovine serum albumin (DNP-BSA), the [ 3 H]-DNP-lys absorption was depressed. The absorption of [ 3 H]-DNP-lys in DNP-BSA-immunized rats was depressed compared to the control. The results obtained suggest that the immune system play a role in avoiding the absorption of small molecules with antigenicity. (author)

  13. Iodine Absorption Cells Purity Testing

    Czech Academy of Sciences Publication Activity Database

    Hrabina, Jan; Zucco, M.; Philippe, Ch.; Pham, Minh Tuan; Holá, Miroslava; Acef, O.; Lazar, Josef; Číp, Ondřej

    2017-01-01

    Roč. 17, č. 1 (2017), s. 1-13, č. článku 17010102. ISSN 1424-8220 R&D Projects: GA ČR GA15-18430S; GA MŠk(CZ) LO1212; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : iodine cells * absorption spectroscopy * laser spectroscopy * laser standards * frequency stability Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 2.677, year: 2016

  14. Transcriptome changes during intestinal cell differentiation

    DEFF Research Database (Denmark)

    Tadjali, Mehrdad; Seidelin, Jakob B; Olsen, Jørgen Lillelund

    2002-01-01

    The expression of 18149 genes have been analysed during the differentiation of the human intestinal cell line Caco-2. cDNA probes from undifferentiated and differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an array on a nylon membrane. A remarkable change in the transc...

  15. 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

  16. Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione.

    Science.gov (United States)

    Marchionatti, Ana M; Perez, Adriana V; Diaz de Barboza, Gabriela E; Pereira, Beatriz M; Tolosa de Talamoni, Nori G

    2008-02-01

    Menadione (MEN) inhibits intestinal calcium absorption by a mechanism not completely understood. The aim of this work was to find out the role of mitochondria in this inhibitory mechanism. Hence, normal chicks treated with one i.p. dose of MEN were studied in comparison with controls. Intestinal calcium absorption was measured by the in situ ligated intestinal segment technique. GSH, oxidoreductase activities from the Krebs cycle and enzymes of the antioxidant system were measured in isolated mitochondria. Mitochondrial membrane potential was measured by a flow cytometer technique. DNA fragmentation and cytochrome c localization were determined by immunocytochemistry. Data indicate that in 30 min, MEN decreases intestinal Ca(2+) absorption, which returns to the control values after 10 h. GSH was only decreased for half an hour, while the activity of malate dehydrogenase and alpha-ketoglutarate dehydrogenase was diminished for 48 h. Mn(2+)-superoxide dismutase activity was increased in 30 min, whereas the activity of catalase and glutathione peroxidase remained unaltered. DNA fragmentation and cytochrome c release were maximal in 30 min, but were recovered after 15 h. In conclusion, MEN inhibits intestinal Ca(2+) absorption by mitochondrial dysfunction as revealed by GSH depletion and alteration of the permeability triggering the release of cytochrome c and DNA fragmentation.

  17. Changes in intestinal absorption of nutrients and brush border glycoproteins after total parenteral nutrition in rats.

    Science.gov (United States)

    Miura, S; Tanaka, S; Yoshioka, M; Serizawa, H; Tashiro, H; Shiozaki, H; Imaeda, H; Tsuchiya, M

    1992-01-01

    The effect of total parenteral nutrition on nutrients absorption and glycoprotein changes of brush border membrane was examined in rat small intestine. In total parenteral nutrition rats, a marked decrease in activity of brush border enzymes was observed mainly in the proximal and middle segments of the intestine. Galactose perfusion of jejunal segment showed that hexose absorption was significantly inhibited, while intestinal absorption of glycine or dipeptide, glycylglycine was not significantly affected by total parenteral nutrition treatment. When brush border membrane glycoprotein profile was examined by [3H]-glucosamine or [3H]-fucose incorporation into jejunal loops, significant changes were observed in the glycoprotein pattern of brush border membrane especially in the high molecular weight range over 120 kDa after total parenteral nutrition treatment, suggesting strong dependency of glycoprotein synthesis on luminal substances. Molecular weight of sucrase isomaltase in brush border membrane detected by specific antibody showed no significant difference, however, in total parenteral nutrition and control rats. Also, molecular weight of specific sodium glucose cotransporter of intestinal brush border membrane detected by selective photoaffinity labelling was not altered in total parenteral nutrition rats. It may be that prolonged absence of oral food intake may produce significant biochemical changes in brush border membrane glycoprotein and absorptive capacity of small intestine, but these changes were not observed in all brush border membrane glycoproteins. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1582592

  18. Interactions between the intestinal microbiota and innate lymphoid cells

    Science.gov (United States)

    Chen, Vincent L; Kasper, Dennis L

    2014-01-01

    The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells. PMID:24418741

  19. Effect of various absorption enhancers based on tight junctions on the intestinal absorption of forsythoside A in Shuang-Huang-Lian, application to its antivirus activity.

    Science.gov (United States)

    Zhou, Wei; Zhu, Xuan Xuan; Yin, Ai Ling; Cai, Bao Chang; Wang, Hai Dan; Di, Liuqing; Shan, Jin Jun

    2014-01-01

    Forsythoside A (FTA), one of the main active ingredients in Shuang-Huang-Lian (SHL), possesses strong antibacterial, antioxidant and antiviral effects, and its pharmacological effects was higher than that of other ingredients, but the absolute bioavailability orally was approximately 0.72%, which was significantly low, influencing clinical efficacies of its oral preparations seriously. In vitro Caco-2 cell and in vivo pharmacokinetics study were simultaneously performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test and morphology observation, respectively. The pharmacological effects such as antivirus activity improvement by absorption enhancers were verified by MDCK damage inhibition rate after influenza virus propagation. The observations from in vitro Caco-2 cell showed that the absorption of FTA in SHL could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/mL was safe, but water-soluble chitosan at different concentrations was all safe for these cells. In pharmacokinetics study, water-soluble chitosan at dosage of 50 mg/kg improved the bioavailability of FTA in SHL to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with SHL with water-soluble chitosan at dosage of 50 mg/kg prevented MDCK damage after influenza virus propagation better significantly than that of control. Water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antivirus activity in vitro in SHL.

  20. Tests of intestinal absorption using carbon-14-labeled isotopes

    International Nuclear Information System (INIS)

    Fromm, H.; Sarva, R.P.

    1983-01-01

    Beta radiation-emitting isotopes are being used increasingly in diagnostic gastroenterology for the study of absorption. The major reason for the popularity of radioisotopes is that their use is convenient for patient and physician alike. They often obviate naso- or orointestinal intubation and the collection, storage, and analysis of stool. The radioactivity used for the studies of digestive and absorptive processes is small and is not hazardous. In spite of the safety of the radiolabeled compounds, their use is restricted in children and pregnant women. Therefore, for most tests, promising alternative methods that make use of the stable isotope of carbon, /sup 13/C, instead of the radioactive /sup 14/C have been developed. The analysis of stable isotopes requires more sophisticated technology than that of radioactive compounds, however. Only a few centers presently are equipped and staffed to analyze stable isotopes on a routine basis. In contrast, the analysis of radioactive isotopes has become a routine procedure in almost ever major laboratory. The last decade has brought the development of several radioactive absorption tests. The clinically most useful tests relate to the study of bile acid, fat, lactose, and xylose absorption. All of these tests utilize the excretion rate of /sup 14/CO/sub 2/ in breath after ingestion of a /sup 14/C-labeled compound as a measure of the rate of its absorption or malabsorption

  1. Intestinal absorption of calcium and magnesium in rats

    International Nuclear Information System (INIS)

    Erhart, J.

    1981-01-01

    Absorption of Ca and Mg was studied in isolated and perfused jejunum segments of rats using radioactive 45 Ca and 28 Mg. At ion concentrations of 1.5 and 10 mmol in the bath solution, the influence of uraemia, 1,25-(OH) 2 D 3 and the complementary ion was investigated. Absorption of Ca ++ was found to be slightly reduced by uraemia and renormalized by 1,25-(OH) 2 D 3 substitution. Transport of Ca ++ was significantly increased in the presence of Mg ++ , both in healthy rats and in animals with chronic uraemia. Mg ++ absorption, in contrast, was significantly reduced in rats with uraemia, and 1,25-(OH) 2 D 3 substitution was found to reduce it even further. In the presence of Ca ++ , transport of Mg ++ was lowered both in healthy rats and in rats with chronic uraemia. (MG) [de

  2. Localization and role of NPC1L1 in cholesterol absorption in human intestine.

    Science.gov (United States)

    Sané, Alain Théophile; Sinnett, Daniel; Delvin, Edgard; Bendayan, Moise; Marcil, Valérie; Ménard, Daniel; Beaulieu, Jean-François; Levy, Emile

    2006-10-01

    Recent studies have documented the presence of Niemann-Pick C1-Like 1 (NPC1L1) in the small intestine and its capacity to transport cholesterol in mice and rats. The current investigation was undertaken to explore the localization and function of NPC1L1 in human enterocytes. Cell fractionation experiments revealed an NPC1L1 association with apical membrane of the enterocyte in human jejunum. Signal was also detected in lysosomes, endosomes, and mitochondria. Confirmation of cellular NPC1L1 distribution was obtained by immunocytochemistry. Knockdown of NPC1L1 caused a decline in the ability of Caco-2 cells to capture micellar [(14)C]free cholesterol. Furthermore, this NPC1L1 suppression resulted in increased and decreased mRNA levels and activity of HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and of ACAT, the key enzyme in cholesterol esterification, respectively. An increase was also noted in the transcriptional factor sterol-regulatory element binding protein that modulates cholesterol homeostasis. Efforts were devoted to define the impact of NPC1L1 knockdown on other mediators of cholesterol uptake. RT-PCR evidence is presented to show the significant decrease in the levels of scavenger receptor class B type I (SR-BI) with no changes in ABCA1, ABCG5, and cluster determinant 36 in NPC1L1-deficient Caco-2 cells. Together, our data suggest that NPC1L1 contributes to intestinal cholesterol homeostasis and possibly cooperates with SR-BI to mediate cholesterol absorption in humans.

  3. Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2016-12-01

    The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

  4. Prediction of Human Intestinal Absorption of Compounds Using Artificial Intelligence Techniques.

    Science.gov (United States)

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2017-01-01

    Information about Pharmacokinetics of compounds is an essential component of drug design and development. Modeling the pharmacokinetic properties require identification of the factors effecting absorption, distribution, metabolism and excretion of compounds. There have been continuous attempts in the prediction of intestinal absorption of compounds using various Artificial intelligence methods in the effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are large numbers of individual predictive models available for absorption using machine learning approaches. Six Artificial intelligence methods namely, Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis were used for prediction of absorption of compounds. Prediction accuracy of Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis for prediction of intestinal absorption of compounds was found to be 91.54%, 88.33%, 84.30%, 86.51%, 79.07% and 80.08% respectively. Comparative analysis of all the six prediction models suggested that Support vector machine with Radial basis function based kernel is comparatively better for binary classification of compounds using human intestinal absorption and may be useful at preliminary stages of drug design and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Lecithin inhibits fatty acid and bile salt absorption from rat small intestine in vivo.

    Science.gov (United States)

    Saunders, D R; Sillery, J

    1976-12-01

    During digestion of a fatty meal, long chain free fatty acids (FFA) and lecithin are among the lipids solubilized in intestinal contents as mixed micelles with bile salts. We hypothesized that if lecithin were not hydrolyzed, the mixed micelles would be abnormal, and absorption of FFA and bile salts would be depressed. To test this hypothesis, isolated segments of rat small intestine were infused in vivo with micellar solutions of 2 mMolar linoleic acid and 10 mMolar taurocholate to which was added 3 mMolar 1-palmitoyl, 2-oleoyl lecithin (a common lecithin in bile and food), or 1-palmitoyl lysolecithin (the hydrolytic product of lecithin). Absorption of FFA and bile salt was measured under steady state conditions using a single-pass technique. Lecithin depressed the rate of FFA absorption by 40% (p less than 0.025) in jejunal and ileal segments whereas lysolecithin was associated with normal rates of FFA absorption. Lecithin also reduced taurocholate absorption from the ileum by 30% (p less than 0.05). These data support the idea that lecithin may depress FFA and bile salt absorption from the small intestine in pancreatic insufficiency.

  6. Iron metabolism in experimental rickets. Pt. 1. Intestinal absorption of iron in rat rickets

    International Nuclear Information System (INIS)

    Pronicka, E.

    1975-01-01

    Investigations were carried out on iron 59 Fe absorption in rats with experimental rickets. It was found that rats with rickets as compared with controls do not show any significant differences in the degree of iron absorption in fasting state. The percent of absorbed iron increases when it is administered after previous feeding of rats. A greater rise in iron absorption after feeding was shown also by rats with rickets. On the other hand, administration of a shock dose of vitamin D at the time of rickets development causes after 7 days a significant decrease in total iron absorption given to fed rats. An excess of calcium in the diet of rats does not seem to impair directly the absorption of iron. The possibility of the causative effect of vitamin D deficiency on the composition of intestinal contents on changes in the degree of iron absorption observed after feeding of rats with rickets, is discussed. (author)

  7. Iron metabolism in experimental rickets. I. Intestinal absorption of iron in rat rickets

    Energy Technology Data Exchange (ETDEWEB)

    Pronicka, E [Pomorska Akademia Medyczna, Szczecin (Poland)

    1975-01-01

    Investigations were carried out on iron /sup 59/Fe absorption in rats with experimental rickets. It was found that rats with rickets as compared with controls do not show any significant differences in the degree of iron absorption in fasting state. The percent of absorbed iron increases when it is administered after previous feeding of rats. A greater rise in iron absorption after feeding was shown also by rats with rickets. On the other hand, administration of a shock dose of vitamin D at the time of rickets development causes after 7 days a significant decrease in total iron absorption given to fed rats. An excess of calcium in the diet of rats does not seem to impair directly the absorption of iron. The possibility of the causative effect of vitamin D deficiency on the composition of intestinal contents on changes in the degree of iron absorption observed after feeding of rats with rickets, is discussed.

  8. Follow-up of treated coeliac patients: Sugar absorption test and intestinal biopsies compared

    NARCIS (Netherlands)

    Uil, J. J.; van Elburg, R. M.; van Overbeek, F. M.; Meyer, J. W.; Mulder, C. J.; Heymans, H. S.

    1996-01-01

    Objective: To determine whether the sugar absorption test (SAT) during follow-up of patients with coeliac disease on a gluten-free diet (GFD) correlates with improvement of the villous architecture of the small intestine. Methods: The SAT was performed in coeliacs at diagnosis and during follow-up

  9. Creep feed intake during lactation enhances net absorption in the small intestine after weaning

    NARCIS (Netherlands)

    Kuller, W.I.; Beers-Schreurs, van H.M.G.; Soede, N.M.; Langendijk, P.; Taverne, M.A.M.; Kemp, B.; Verheijden, J.H.M.

    2007-01-01

    The aim of the study was to measure the effect of creep feeding during lactation on net absorption in the small intestine at 4 days after weaning. Intermittent suckling was used to increase creep feed intake during lactation. Creep feed containing chromic oxide was provided. Based on the colour of

  10. Effect of dietary calcium and phosphorus on intestinal calcium absorption and vitamin D metabolism

    International Nuclear Information System (INIS)

    Ribovich, M.L.; DeLuca, H.F.

    1978-01-01

    To understand better dietary regulation of intestinal calcium absorption, a quantitative assessment of the metabolites in plasma and duodenum of rats given daily doses of radioactive vitamin D 3 and diets differing in calcium and phosphorus content was made. All known vitamin D metabolites were ultimately identified by high-pressure liquid chromatography. In addition to the known metabolites (25-hydroxyvitamin D 3 , 24,25-dihydroxyvitamin D 3 , 1,25-dihydroxyvitamin D 3 , 25,26-dihydroxyvitamin D 3 , and 1,24,25-trihydroxyvitamin D 3 ), several new and unidentified metabolites were found. In addition to 1,25-dihydroxyvitamin D 3 and 1,24,25-trihydroxyvitamin D 3 , the levels of some of the unknown metabolites could be correlated with intestinal calcium transport. However, whether or not any of these metabolites plays a role in the stimulation of intestinal calcium absorption by low dietary calcium or low dietary phosphorus remains unknown

  11. Studies on intestinal absorption in postoperative patients with carcinoma of esophagus and gastric cardia

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimura, Y; Inoguchi, T [Kurume Univ., Fukuoka (Japan). School of Medicine

    1974-08-01

    The function of intestinal absorption and gastric and pancreatic secretion were observed to evaluate several factors affected to intestinal absorption in cases of carcinoma of esophagus and gastric cardia after operation. To compare fat absorption and assimilation between medium chain triglyceride (MCT) and long chain triglyceride (LCT), /sup 14/C-labeled fats were used. The effect of different types of anastomosis; i.e. Billroth I and Billroth II type-pathway, and also the effect of truncal vagotomy on digestion and absorption of fats was studied. In results, the types of anastomosis and truncal vagotomy had no significant effect on digestion and absorption of carbohydrate, but the digestion and absorption of protein and fat were impaired after operation, especially in fat. In Billroth I type-pathway, the impaired digestion and absorption were slight. In Billroth II type-pathway, imbalance in the mixing time of the diet and the digestive juice according to the dumping of ingested food into jejunum and quick passage through the jejunum; so called pancreatico-cibal asynchrony, probably caused impaired digestion of fat. It was considered that truncal vagotomy had caused steatorrhea in the early stage of postoperation. Gastric remnant and reconstructive stomach almost lost its secretory function after operation of esophageal cancer, but pancreatic exocrine secretory function remained after vagotomy. Intestinal absorption of MCT was better than it was of LCT even in cases of postoperative malabsorption. So MCT administration is considered as effective method for caloric intake in cases of esophageal cancer and cancer of gastric cardia, which have operative risk and take long time for the recovery in the function of digestion and absorption after operation. (auth)

  12. Radiobiology of intestinal epithelium stem cells

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.

    1988-01-01

    After a single or three-fold whole body irradiation of mice with a dose of 4 Gy and the time interval for the proliferation to be restored (5 days or 3 weeks) the survival curve for stem cells of small intestine epithelium with regard to radiation dose was the same as that for non-preirradiated mice. This indicated that the proliferative potential of stem cells in these experimental conditions was not reduced

  13. Therapeutic effect of an elemental diet on proline absorption across the irradiated rat small intestine

    International Nuclear Information System (INIS)

    Mohiuddin, M.; Kramer, S.

    1978-01-01

    Active absorption of [ 3 H]L-proline across the intestinal wall was used to measure functional change following irradiation of the exteriorized rat small intestine and to see whether an elemental amino acid diet would modify these changes. Segments (15 cm) of the exteriorized upper ileum of male Wistar rats were exposed to 1000 rad. Active transport against a concentration gradient of [ 3 H]L-proline from this irradiated segment was measured using the everted sac technique on days 1, 3, 7, 10, 14, 21, and 30 post-irradiation. Irradiated rats maintained on a normal diet showed depression of absorptive function with only partial recovery by day 30. Irradiated rats maintained on an elemental amino acid diet also showed an initial drop in function but then recovered absorptive function completely by day 7

  14. SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells

    Energy Technology Data Exchange (ETDEWEB)

    Noah, Taeko K.; Kazanjian, Avedis [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Whitsett, Jeffrey [Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Neonatology and Pulmonary Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Shroyer, Noah F., E-mail: noah.shroyer@cchmc.org [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States)

    2010-02-01

    Background and Aims: SPDEF (also termed PDEF or PSE) is an ETS family transcription factor that regulates gene expression in the prostate and goblet cell hyperplasia in the lung. Spdef has been reported to be expressed in the intestine. In this paper, we identify an important role for Spdef in regulating intestinal epithelial cell homeostasis and differentiation. Methods: SPDEF expression was inhibited in colon cancer cells to determine its ability to control goblet cell gene activation. The effects of transgenic expression of Spdef on intestinal differentiation and homeostasis were determined. Results: In LS174T colon cancer cells treated with Notch/{gamma}-secretase inhibitor to activate goblet cell gene expression, shRNAs that inhibited SPDEF also repressed expression of goblet cell genes AGR2, MUC2, RETLNB, and SPINK4. Transgenic expression of Spdef caused the expansion of intestinal goblet cells and corresponding reduction in Paneth, enteroendocrine, and absorptive enterocytes. Spdef inhibited proliferation of intestinal crypt cells without induction of apoptosis. Prolonged expression of the Spdef transgene caused a progressive reduction in the number of crypts that expressed Spdef, consistent with its inhibitory effects on cell proliferation. Conclusions: Spdef was sufficient to inhibit proliferation of intestinal progenitors and induce differentiation into goblet cells; SPDEF was required for activation of goblet cell associated genes in vitro. These data support a model in which Spdef promotes terminal differentiation into goblet cells of a common goblet/Paneth progenitor.

  15. Soybean β-conglycinin induces inflammation and oxidation and causes dysfunction of intestinal digestion and absorption in fish.

    Directory of Open Access Journals (Sweden)

    Jin-Xiu Zhang

    Full Text Available β-Conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR, feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na(+,K(+-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-Conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD, catalase (CAT, glutathione-S-transferase (GST, glutathione peroxidase (GPx and glutathione reductase (GR activities and glutathione (GSH content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8, tumor necrosis factor-α (TNF-α, and transforming growth factor-β (TGF-β genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects.

  16. Development and Characterization of a Human and Mouse Intestinal Epithelial Cell Monolayer Platform

    Directory of Open Access Journals (Sweden)

    Kenji Kozuka

    2017-12-01

    Full Text Available Summary: We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages. Ion transport phenotypes of monolayers from the proximal and distal colon and small intestine matched the known and unique physiology of these intestinal segments. The cultures secreted serotonin, GLP-1, and FGF19 and upregulated the epithelial sodium channel in response to known biologically active agents, suggesting intact secretory and absorptive functions. A screen of over 2,000 pharmacologically active compounds for inhibition of potassium ion transport in the mouse distal colon cultures led to the identification of a tool compound. : Siegel and colleagues describe their development of a human and mouse intestinal epithelial cell monolayer platform that maintains the cellular, molecular, and functional characteristics of tissue for each intestinal segment. They demonstrate the platform's application to drug discovery by screening a library of over 2,000 compounds to identify an inhibitor of potassium ion transport in the mouse distal colon. Keywords: intestinal epithelium, organoids, monolayer, colon, small intestine, phenotype screening assays, enteroid, colonoid

  17. Intestinal absorption of dietary fat from a liquid diet perfused in rats at a submaximum level

    International Nuclear Information System (INIS)

    Simko, V.; Kelley, R.E.

    1988-01-01

    The small intestine of rats was perfused in vivo for 2 h with a nutritionally complete liquid diet (68% calories from fat as corn oil). As the perfusion increased from 106 mg/2 h, the intestinal disappearance of the 14 C-triolein marker remained proportional to the load up to 2359 mg fat/2 h. Despite a decrease in absorption from 70 to 17%, this represents a very large fat intake. Fat absorption improved when medium-chain triglycerides or octanoic acid replaced corn oil (both p less than 0.01). Linoleic acid was absorbed from the diet less than corn oil (p less than 0.01). Dry ox bile reduced fat absorption (p less than 0.05); lipase and an antacid had no effect. Corn oil perfused alone was absorbed better than from the diet (p less than 0.01). Data with 14 C-triolein was confirmed by dry-weight disappearance of the diet and by net intestinal water balance. Usual feeding underutilizes a large reserve for fat absorption. This reserve should be considered in therapeutic nutrition

  18. Excretion and intestinal absorption of tritiated glutamic acid by carp, Cyprinus Carpio

    International Nuclear Information System (INIS)

    Watabe, Terushia; Kistner, G.

    1986-01-01

    Excretion and intestinal absorption of tritiated glutamic acid by carp was investigated. Approximately 80% of orally administered tritium was excreted at a half life value of 1.4 h and an observed slower excretion of 7 days for the remainder. Tritium incorporated in glutamic acid was efficiently retained at the site of absorption, i.e. intestine, liver, gill, kidney, blood and muscle. A dual marking experiment using tritiated glutamic acid and 14 C-market glutamic acid showed higher excretion of tritium by factors 2.0 to 4.9 than that of 14 C. Tritiated glutamic acid is considered to be mainly incorporated in the citric acid cycle soon after administration and the release of tritium in tritiated water through the cycle is assumed as causing the initial rapid excretion of tritium in carp. The intestinal absorption of glutamic acid was likely to depend on its concentration in the administered solution. The maximum level of absorption is estimated to be 0.1 m mol/0.5 h for one year old carp. The results obtained here would make it possible to estimate the tritium contamination of fish due to tritiated glutamic acid entering the food chain. (orig.)

  19. Intestinal fluid absorption in anadromous salmonids: importance of tight junctions and aquaporins

    Directory of Open Access Journals (Sweden)

    Kristina eSundell

    2012-09-01

    Full Text Available The anadromous salmonid life cycle includes both fresh water (FW and seawater (SW stages. The parr-smolt transformation (smoltification pre–adapt the fish to SW while still in FW. The osmoregulatory organs change their mode of action from a role of preventing water inflow in FW, to absorb ions to replace water lost by osmosis in SW. During smoltification, the drinking rate increases, in the intestine the ion and fluid transport increases and is further elevated after SW entry. In SW, the intestine absorbs ions to create an inwardly directed water flow which is accomplished by increased Na+,K+-ATPase (NKA activity in the basolateral membrane, driving ion absorption via ion channels and/or co-transporters. This review will aim at discussing the expression patterns of the ion transporting proteins involved in intestinal fluid absorption in the FW stage, during smoltification and after SW entry. Of equal importance for intestinal fluid absorption as the active absorption of ions, is the permeability of the epithelium to ions and water. During the smoltification the increase in NKA activity and water uptake in SW is accompanied by decreased paracellular permeability suggesting a redirection of the fluid movement from a paracellular route in FW, to a transcellular route in SW. Increased transcellular fluid absorption could be achieved by incorporation of aquaporins (AQPs into the enterocyte membranes and/or by a change in fatty acid profile of the enterocyte lipid bilayer. An increased incorporation of unsaturated fatty acids into the membrane phospholipids will increase water permeability by enhancing the fluidity of the membrane. A second aim of the present review is therefore to discuss the presence and regulation of expression of AQPs in the enterocyte membrane as well as to discuss the profile of fatty acids present in the membrane phospholipids during different stages of the salmonid lifecycle.

  20. Intestinal Stem Cell Niche: The Extracellular Matrix and Cellular Components

    Directory of Open Access Journals (Sweden)

    Laween Meran

    2017-01-01

    Full Text Available The intestinal epithelium comprises a monolayer of polarised columnar cells organised along the crypt-villus axis. Intestinal stem cells reside at the base of crypts and are constantly nourished by their surrounding niche for maintenance, self-renewal, and differentiation. The cellular microenvironment including the adjacent Paneth cells, stromal cells, smooth muscle cells, and neural cells as well as the extracellular matrix together constitute the intestinal stem cell niche. A dynamic regulatory network exists among the epithelium, stromal cells, and the matrix via complex signal transduction to maintain tissue homeostasis. Dysregulation of these biological or mechanical signals could potentially lead to intestinal injury and disease. In this review, we discuss the role of different intestinal stem cell niche components and dissect the interaction between dynamic matrix factors and regulatory signalling during intestinal stem cell homeostasis.

  1. Avian species differences in the intestinal absorption of xenobiotics (PCB, dieldrin, Hg2+)

    Science.gov (United States)

    Serafin, J.A.

    1984-01-01

    1. Intestinal absorption of a polychlorinated biphenyl, dieldrin, and mercury (from HgCl2) was measured in adult Northern bobwhites, Eastern screech owls, American kestrels, black-crowned night-herons and mallards in vivo by an in situ luminal perfusion technique.2. Bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards.3. Mallards absorbed less dieldrin and mercury than black-crowned night-herons.4. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards.5. Pronounced differences in xenobiotic absorption rates between bobwhites, screech owls and kestrels on the one hand, and black-crowned night-herons and mallards on the other, raise the possibility that absorptive ability may be associated with the phylogenetic classification of birds.

  2. Intestinal absorption and retention of cadmium in neonatal pigs compared to rats and guinea pigs

    International Nuclear Information System (INIS)

    Sasser, L.B.; Jarboe, G.E.

    1980-01-01

    The purpose of this study was to measure intestinal absorption and retention of cadmium in the newborn pig and to compare data from the pig, rat and guinea pig, three species that differ greatly in their ability to absorb macromolecules at birth. Newborn pigs were administered a single oral dose of 50 μCi of /sup 115m/Cd 24 hours after birth and killed at intervals between 1 and 14 days after dosing. Cd absorption and gastrointestinal retention were then determined; these data were compared with similar data from the rat and guinea pig. Cd absorption in the neonate appears to be a two-step process; mucosal uptake of Cd from the lumen, probably by pinocytosis, followed by transfer of a portion of this Cd into the body. This transfer process is similar, but does not entirely coincide with changes associated with protein absorption in the neonate

  3. Transepithelial transport of flavanone in intestinal Caco-2 cell monolayers

    International Nuclear Information System (INIS)

    Kobayashi, Shoko; Konishi, Yutaka

    2008-01-01

    Our recent study [S. Kobayashi, S. Tanabe, M. Sugiyama, Y. Konishi, Transepithelial transport of hesperetin and hesperidin in intestinal Caco-2 cell monolayers, Biochim. Biophys. Acta, 1778 (2008) 33-41] shows that the mechanism of absorption of hesperetin involves both proton-coupled active transport and transcellular passive diffusion. Here, as well as analyzing the cell permeability of hesperetin, we also study the transport of other flavanones, naringenin and eriodictyol, using Caco-2 cell monolayers. Similar to hesperetin mentioned, naringenin and eriodictyol showed proton-coupled polarized transport in apical-to-basolateral direction in non-saturable manner, constant permeation in the apical-to-basolateral direction (J ap→bl ) irrespective of the transepithelial electrical resistance (TER), and preferable distribution into the basolateral side after apical loading in the presence of a proton gradient. Furthermore, the proton-coupled J ap→bl of hesperetin, naringenin and eriodictyol, were inhibited by substrates of the monocarboxylic acid transporter (MCT), such as benzoic acid, but not by ferulic acid. In contrast, both benzoic and ferulic acids have no stimulatory effect on J ap→bl of each flavanone by trans-stimulation analysis. These results indicates that proton-driven active transport is commonly participated in the absorption of flavanone in general, and that its transport is presumed to be unique other than MCT-mediated transport for absorption of phenolic acids (PAs), sodium-dependent MCT (SMCT) nor anion exchanger-mediated transport

  4. Effect of absorbable and nonabsorbable sugars on intestinal calcium absorption in humans

    International Nuclear Information System (INIS)

    Griessen, M.; Speich, P.V.; Infante, F.; Bartholdi, P.; Cochet, B.; Donath, A.; Courvoisier, B.; Bonjour, J.P.

    1989-01-01

    The effects of glucose, galactose, and lactitol on intestinal calcium absorption and gastric emptying were studied in 9, 8, and 20 healthy subjects, respectively. Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by a deconvolution method. The gastric emptying rate was determined with /sup 99m/Tc-diethylenetriaminepentaacetic acid and was expressed as the half-time of the emptying curve. Each subject was studied under two conditions: (a) with calcium alone and (b) with calcium plus sugar. Glucose and galactose increased the calcium mean transit time and improved the total fractional calcium absorption by 30% (p less than 0.02). Lactitol decreased the mean rate of absorption (p less than 0.001) and reduced the total fractional calcium absorption by 15% (p less than 0.001). The gastric emptying rate did not appear to influence directly the kinetic parameters of calcium absorption. These results show that both glucose and galactose exert the same stimulatory effect as lactose on calcium absorption in subjects with normal lactase whereas lactitol mimics the effects of lactose in lactase-deficient patients. Thus the absorbability of sugars determines their effect on calcium absorption

  5. Effects of quercetin and menadione on intestinal calcium absorption and the underlying mechanisms.

    Science.gov (United States)

    Marchionatti, Ana M; Pacciaroni, Adriana; Tolosa de Talamoni, Nori G

    2013-01-01

    Quercetin (QT) could be considered as a potential therapeutic agent for different diseases due to its antioxidant, anti-inflammatory, antiviral and anticancer properties. This study was designed to investigate the ability of QT to protect the chick intestine against menadione (MEN) induced injury in vivo and in vitro. Four-week old chicks (Gallus gallus) were treated i.p. with 2.5μmol of MEN/kg b.w. or with i.l. 50μM QT or both. QT protected the intestinal Ca(2+) absorption against the inhibition caused by MEN, but QT alone did not modify. Glutathione (GSH) depletion provoked by MEN in chick enterocytes was abolished by QT treatment, whereas QT alone did not modify the intestinal GSH content. The enhancement of GSH peroxidase activity produced by MEN was blocked by QT treatment. In contrast, superoxide dismutase activity remained high after simultaneous treatment of enterocytes with MEN and QT. The flavonol also avoided changes in the mitochondrial membrane permeability (swelling) produced by MEN. The FasL/Fas/caspase-3 pathway was activated by MEN, effect that was abrogated by QT. In conclusion, QT may be useful in preventing inhibition of chick intestinal Ca(2+) absorption caused by MEN or other substances that deplete GSH, by blocking the oxidative stress and the FasL/Fas/caspase-3 pathway activation. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. In Silico Prediction for Intestinal Absorption and Brain Penetration of Chemical Pesticides in Humans.

    Science.gov (United States)

    Chedik, Lisa; Mias-Lucquin, Dominique; Bruyere, Arnaud; Fardel, Olivier

    2017-06-30

    Intestinal absorption and brain permeation constitute key parameters of toxicokinetics for pesticides, conditioning their toxicity, including neurotoxicity. However, they remain poorly characterized in humans. The present study was therefore designed to evaluate human intestine and brain permeation for a large set of pesticides ( n = 338) belonging to various chemical classes, using an in silico graphical BOILED-Egg/SwissADME online method based on lipophilicity and polarity that was initially developed for drugs. A high percentage of the pesticides (81.4%) was predicted to exhibit high intestinal absorption, with a high accuracy (96%), whereas a lower, but substantial, percentage (38.5%) displayed brain permeation. Among the pesticide classes, organochlorines ( n = 30) constitute the class with the lowest percentage of intestine-permeant members (40%), whereas that of the organophosphorus compounds ( n = 99) has the lowest percentage of brain-permeant chemicals (9%). The predictions of the permeations for the pesticides were additionally shown to be significantly associated with various molecular descriptors well-known to discriminate between permeant and non-permeant drugs. Overall, our in silico data suggest that human exposure to pesticides through the oral way is likely to result in an intake of these dietary contaminants for most of them and brain permeation for some of them, thus supporting the idea that they have toxic effects on human health, including neurotoxic effects.

  7. Intestinal absorption of water-soluble vitamins in health and disease

    OpenAIRE

    Said, Hamid M.

    2011-01-01

    Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth an...

  8. Consensus hologram QSAR modeling for the prediction of human intestinal absorption.

    Science.gov (United States)

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

    Consistent in silico models for ADME properties are useful tools in early drug discovery. Here, we report the hologram QSAR modeling of human intestinal absorption using a dataset of 638 compounds with experimental data associated. The final validated models are consistent and robust for the consensus prediction of this important pharmacokinetic property and are suitable for virtual screening applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd

    2014-01-01

    Vigabatrin is an antiepileptic drug substance mainly used in pediatric treatment of infantile spasms. The main source of nutrition for infants is breast milk and/or infant formula. Our hypothesis was that infant formula may affect the intestinal absorption of vigabatrin. The aim was therefore...... to investigate the potential effect of coadministration of infant formula with vigabatrin on the oral absorption in vitro and in vivo. The effect of vigabatrin given with an infant formula on the oral uptake and transepithelial transport was investigated in vitro in Caco-2 cells. In vivo effects of infant...... formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin...

  10. Simultaneous in vivo determination of calcium and phosphate effective intestinal absorption in the rat

    International Nuclear Information System (INIS)

    Ladizesky, M.; Mautalen, C.A.; Cabrejas, M.; Degrossi, O.J.

    1978-01-01

    A description is given of a technique which allows a more precise assessment of the interrelation between calcium and phosphate transport systems. Rats were given an i.p. or oral dose of 47 Ca with 40 Ca as carrier and/or 32 P with 31 P as carrier. The animals were sacrificed and activities in body and excised gastrointestinal tract determined. The 1.28 MeV photopeak activity was measured for calcium 47, and phosphorus 32 activity was determined by measuring the Bremsstrahlung produced by this isotope in the rat's body in the 80 to 200 keV range. The rates of intestinal absorption of calcium and phosphate differed; there seemed to be no urinary excretion of the radioisotopes within 3 hours. The reciprocal influence of calcium and phosphate on the intestinal absorption was also studied. The technique is simple and allows the simultaneous in vivo measurement of the effective intestinal absorption of calcium and phosphate. (U.K.)

  11. Calcium absorption in rat large intestine in vivo: availability of dietary calcium

    International Nuclear Information System (INIS)

    Ammann, P.; Rizzoli, R.; Fleisch, H.

    1986-01-01

    Calcium absorption in the large intestine of the rat was investigated in vivo. After a single injection of 45 CaCl 2 into the cecum, 26.0 +/- 2.5% (mean +/- SE, n = 9) of the 45 CaCl 2 injected disappeared. This absorption was modulated by 1,25-dihydroxyvitamin D3, increased to 64.0 +/- 4.2% under a low-Ca diet, and increased under low-Pi diet. In contrast, when the difference of nonradioactive Ca in the cecal content and the feces was measured, only 4.1 +/- 4.6% (not significant) was absorbed. Secretion of intravenously injected 45 Ca into the lumen was small and not altered by any of the conditions tested. When cecum contents were placed into duodenal tied loops, 14 +/- 6.2% were absorbed in situ when 45 Ca was given orally, whereas when 45 Ca was directly added to the content 35.6 +/- 4.6% were absorbed (P less than 0.02). These results indicate that the large intestine has an important vitamin D-dependent Ca absorptive system detectable if 45 Ca is injected into the cecum. However, it is not effective in vivo because the Ca arriving in the large intestine appears to be no longer in an absorbable form

  12. Endocrine cells in the denervated intestine

    Science.gov (United States)

    Santos, Gilda C; Zucoloto, Sérgio; Garcia, Sérgio B

    2000-01-01

    This study deals with the effects of myenteric denervation of the proximal jejunum on endocrine cell population of the crypt-villus unit, 5 months after treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on average 100 g were allocated to two groups: the BAC group − the proximal jejunal serosa was treated with 2 mm BAC for 30 min, and the control group − treated with saline solution (0,9% NaCl). There was a significant reduction in neurone number in the jejunal myenteric plexus of the BAC group and the endocrine cell population (serotoninergic and argyrophilic cells) was significantly increased in this intestine segment. In conclusion, the present findings provide further evidence that the myenteric denervation induced by BAC may lead to the development of a local imbalance of the neurotransmitters, with a consequent induction of enteroendocrine cell (argyrophilic and serotoninergic cells) hyperplasia in the crypt and villus. PMID:10971748

  13. Intestinal Stem Cell Dynamics: A Story of Mice and Humans.

    Science.gov (United States)

    Hodder, Michael C; Flanagan, Dustin J; Sansom, Owen J

    2018-06-01

    Stem cell dynamics define the probability of accumulating mutations within the intestinal epithelium. In this issue of Cell Stem Cell, Nicholson et al. (2018) report that human intestinal stem cell dynamics differ significantly from those of mice and establish that oncogenic mutations are more likely to expand; therefore, "normal" epithelium may carry multiple mutations. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Sequential cancer mutations in cultured human intestinal stem cells

    NARCIS (Netherlands)

    Drost, Jarno; van Jaarsveld, Richard H.; Ponsioen, Bas; Zimberlin, Cheryl; van Boxtel, Ruben; Buijs, Arjan; Sachs, Norman; Overmeer, René M.; Offerhaus, G. Johan; Begthel, Harry; Korving, Jeroen; van de Wetering, Marc; Schwank, Gerald; Logtenberg, Meike; Cuppen, Edwin; Snippert, Hugo J.; Medema, Jan Paul; Kops, Geert J. P. L.; Clevers, Hans

    2015-01-01

    Crypt stem cells represent the cells of origin for intestinal neoplasia. Both mouse and human intestinal stem cells can be cultured in medium containing the stem-cell-niche factors WNT, R-spondin, epidermal growth factor (EGF) and noggin over long time periods as epithelial organoids that remain

  15. Effects of dietary glucose and sodium chloride on intestinal glucose absorption of common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Qin, Chaobin; Yang, Liping; Zheng, Wenjia; Yan, Xiao; Lu, Ronghua; Xie, Dizhi; Nie, Guoxing

    2018-01-08

    The co-transport of sodium and glucose is the first step for intestinal glucose absorption. Dietary glucose and sodium chloride (NaCl) may facilitate this physiological process in common carp (Cyprinus carpio L.). To test this hypothesis, we first investigated the feeding rhythm of intestinal glucose absorption. Carps were fed to satiety once a day (09:00 a.m.) for 1 month. Intestinal samples were collected at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00. Result showed that food intake greatly enhanced sodium/glucose cotransporter 1 (SGLT1) and glucose transporter type 2 (GLUT2) expressions, and improved glucose absorption, with highest levels at 09:00 a.m.. Then we designed iso-nitrogenous and iso-energetic diets with graded levels of glucose (10%, 20%, 30%, 40% and 50%) and NaCl (0%, 1%, 3% and 5%), and submitted to feeding trial for 10 weeks. The expressions of SGLT1 and GLUT2, brush border membrane vesicles (BBMVs) glucose transport and intestinal villus height were determined after the feeding trial. Increasing levels of dietary glucose and NaCl up-regulated mRNA and protein levels of SGLT1 and GLUT2, enhanced BBMVs glucose transport in the proximal, mid and distal intestine. As for histological adaptive response, however, high-glucose diet prolonged while high-NaCl diet shrank intestinal villus height. Furthermore, we also found that higher mRNA levels of SGLT1 and GLUT2, higher glucose transport capacity of BBMVs, and higher intestinal villus were detected in the proximal and mid intestine, compared to the distal part. Taken together, our study indicated that intestinal glucose absorption in carp was primarily occurred in the proximal and mid intestine, and increasing levels of dietary glucose and NaCl enhanced intestinal glucose absorption in carp. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Controlling the frontier: regulatory T-cells and intestinal homeostasis.

    Science.gov (United States)

    Bollrath, Julia; Powrie, Fiona M

    2013-11-30

    The intestine represents one of the most challenging sites for the immune system as immune cells must be able to mount an efficient response to invading pathogens while tolerating the large number and diverse array of resident commensal bacteria. Foxp3(+) regulatory T-cells (Tregs) play a non-redundant role at maintaining this balance. At the same time Treg cell differentiation and function can be modulated by the intestinal microbiota. In this review, we will discuss effector mechanisms of Treg cells in the intestine and how these cells can be influenced by the intestinal microbiota. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Fractional intestinal absorption and retention of calcium measured by whole-body counting. Application of a power function model

    International Nuclear Information System (INIS)

    Pors Nielsen, S.; Baerenholdt, O.; Munck, O.

    1975-01-01

    By application of a power function model, fractional intestinal calcium absorption was investigated with a new technique involving whole-body counting after successive oral and intravenous administration of standard doses of 47 Ca. The fractional calcium retention 7 days after the oral load of 47 Ca was also measured. Fractional calcium retention averaged 30.3% in normal subjects and 11.5% in 11 patients with intestinal malabsorption. In the same groups fractional calcium absorption averaged 46.6% and 16.4%, respectively. Fractional calcium retention and intestinal calcium absorption were significantly correlated to body surface area, and there was a well-defined relation between fractional retention and absorption of calcium. These studies demonstrate that measurements of fractional retention and fractional intestinal absorption of calcium can be combined by the use of a whole-body counter, that fractional retention and intestinal absorption are proportional to total body surface area and therefore probably also to the total bone mass, and that fractional retention and absorption are so closely interrelated that frational absorption can be estimated from fractional retention with reasonable accuracy in normal subjects. (auth.)

  18. IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis

    DEFF Research Database (Denmark)

    Luda, Katarzyna M.; Joeris, Thorsten; Persson, Emma K.

    2016-01-01

    The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence...... dependent DCs in the maintenance of intestinal T cell homeostasis....

  19. Absorption of magnesium in intestinal loop studied by the multitracer technique

    International Nuclear Information System (INIS)

    Yoshida, Shozo; Yamasaki, Mineo; Morikawa, Hajime

    2004-01-01

    We investigated Mg absorption in the intestine, and pregnancy-associated changes in Mg absorption by the rat everted gut sac method. Heavy ion beam accelerated by ring-cyclotron was irradiated to a titanium target and the radioactive multitracer solution which includes 28 Mg was made. 9 weeks old female Wistar rats (non-pregnancy, 6∼20th day of the pregnancy) were fasted overnight and anesthetized. Four segments of the intestine were isolated and everted to prepare sac specimens with mucosa outside. Each specimen was filled with multitracer solution and was immersed in the same solution. After incubation the multitracer solutions in both of inside and outside the sacs were removed. The radioactivity of the each sample was determined by gamma-ray spectrometry. In non-pregnant state, the active transport of Mg from mucosal side into serosal side exists only in colon. This active transport of Mg in colon during pregnancy was significantly decreased than in non-pregnant state. The mechanism and importance of the decrease in Mg absorption during pregnancy are still unclear. In humans, the intracellular and extracellular Mg concentrations decrease with the normal pregnancy course, especially in preeclampsia. The association between the changes in active Mg absorption during pregnancy and the pathogenesis should be clarified as early as possible. (author)

  20. Innate Lymphoid Cells in Intestinal Inflammation

    Science.gov (United States)

    Geremia, Alessandra; Arancibia-Cárcamo, Carolina V.

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an increased risk of

  1. Innate Lymphoid Cells in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Alessandra Geremia

    2017-10-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an

  2. Evolutionary insights into postembryonic development of adult intestinal stem cells

    Directory of Open Access Journals (Sweden)

    Ishizuya-Oka Atsuko

    2011-11-01

    Full Text Available Abstract In the adult vertebrate intestine, multi-potent stem cells continuously generate all of the epithelial cells throughout the adulthood. While it has long been known that the frog intestine is formed via the development of adult intestinal stem cells during thyroid hormone (TH-dependent metamorphosis, the basic structure of the adult intestine is formed by birth in mammals and it is unclear if the subsequent maturation of the intestine involves any changes in the intestinal stem cells. Two recent papers showing that B lymphocyte-induced maturation protein 1 (Blimp1 regulates postnatal epithelial stem cell reprogramming during mouse intestinal maturation support the model that adult intestinal stem cells are developed during postembryonic development in mammals, in a TH-dependent process similar to intestinal remodeling during amphibian metamorphosis. Since the formation of the adult intestine in both mammals and amphibians is closely associated with the adaptation from aquatic to terrestrial life during the peak of endogenous TH levels, the molecular mechanisms by which the adult stem cells are developed are likely evolutionally conserved.

  3. Effect of lactose on intestinal absorption of calcium; Effet du lactose sur l'absorption intestinale du calcium

    Energy Technology Data Exchange (ETDEWEB)

    Labat, Marie-Louise

    1972-06-15

    Calcium absorption was immediately increased when lactose was administered in large amounts in the intestine of standard rats fed on a vitamin D diet. The same effect could be reproduced with lactulose, a glucid un-hydrolyzed by lactase and unabsorbed. The occurrence of a saturation process for high doses of calcium agrees with a biochemical process through a carrier; this process was not inhibited by actinomycin D, which does not agree with a 'de novo' synthesis of a calcium binding protein; yet activation of the preexisting protein cannot be excluded. The intestinal effect of lactose resulted in an inhibition of bone catabolism in the adult normocalcemic rat indicating a possible interference of thyrocalcitonin. Finally in the young rat, hypocalcemic by lack of vitamin D, on account of the lactose effect, calcium can be considered as a 'third messenger' in the chain of intracellular events between the interaction of the parathyroid hormone with the bone receptor and the expression of its activity. (author) [French] Le lactose introduit en quantite importante dans l'intestin augmente immediatement l'absorption du calcium chez le rat normal recevant par ailleurs de la vitamine D. Cet effet peut etre reproduit par le lactulose, glucide non hydrolyse par la lactase et non absorbe. L'apparition d'un phenomene de saturation pour les doses elevees de calcium s'accorde avec un mecanisme biochimique mettant en jeu un transporteur. Ce mecanisme n'est pas inhibe par l'actinomycine D, ce qui ne s'accorde pas avec une synthese 'de novo' de proteine transporteuse liant le calcium; on ne peut toutefois exclure une activation de cette proteine preexistante. L'effet intestinal du lactose a pour consequence l'inhibition du catabolisme osseux chez le rat adulte normocalcemique; ceci pose le probleme d'une intervention eventuelle de la thyrocalcitonine. Enfin, l'effet lactose nous permet d'attribuer au calcium le role de 'troisieme messager' dans la chaine d

  4. Defining new criteria for selection of cell-based intestinal models using publicly available databases

    Directory of Open Access Journals (Sweden)

    Christensen Jon

    2012-06-01

    Full Text Available Abstract Background The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies. Results We made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics. Conclusions This study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models

  5. Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2015-03-01

    The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

  6. Microenvironmental regulation of stem cells in intestinal homeostasis and cancer

    NARCIS (Netherlands)

    Medema, Jan Paul; Vermeulen, Louis

    2011-01-01

    The identification of intestinal stem cells as well as their malignant counterparts, colon cancer stem cells, has undergone rapid development in recent years. Under physiological conditions, intestinal homeostasis is a carefully balanced and efficient interplay between stem cells, their progeny and

  7. Polymer nanocomposites enhance S-nitrosoglutathione intestinal absorption and promote the formation of releasable nitric oxide stores in rat aorta.

    Science.gov (United States)

    Wu, Wen; Perrin-Sarrado, Caroline; Ming, Hui; Lartaud, Isabelle; Maincent, Philippe; Hu, Xian-Ming; Sapin-Minet, Anne; Gaucher, Caroline

    2016-10-01

    Alginate/chitosan nanocomposite particles (GSNO-acNCPs), i.e. S-nitrosoglutathione (GSNO) loaded polymeric nanoparticles incorporated into an alginate and chitosan matrix, were developed to increase the effective GSNO loading capacity, a nitric oxide (NO) donor, and to sustain its release from the intestine following oral administration. Compared with free GSNO and GSNO loaded nanoparticles, GSNO-acNCPs promoted 2.7-fold GSNO permeation through a model of intestinal barrier (Caco-2 cells). After oral administration to Wistar rats, GSNO-acNCPs promoted NO storage into the aorta during at least 17h, as highlighted by (i) a long-lasting hyporeactivity to phenylephrine (decrease in maximum vasoconstrictive effect of aortic rings) and (ii) N-acetylcysteine (a thiol which can displace NO from tissues)-induced vasodilation of aorxxtic rings preconstricted with phenylephrine. In conclusion, GSNO-acNCPs enhance GSNO intestinal absorption and promote the formation of releasable NO stores into the rat aorta. GSNO-acNCPs are promising carriers for chronic oral application devoted to the treatment of cardiovascular diseases. Copyright © 2016. Published by Elsevier Inc.

  8. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

    Science.gov (United States)

    Bevins, Charles L; Salzman, Nita H

    2011-05-01

    Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.

  9. Intestinal synthesis and absorption of vitamin B-12 in channel catfish

    International Nuclear Information System (INIS)

    Limsuwan, T.; Lovell, R.T.

    1981-01-01

    A feeding experiment conducted in a controlled environment and using a vitamin B12-deficient, but otherwise nutritionally complete, purified diet revealed that intestinal microorganisms in channel catfish synthesized approximately 1.4 ng of vitamin B12 per gram of bodyweight per day. Removal of cobalt from the diet or supplementation with an antibiotic (succinylsulfathiazole) significantly reduced the rate of intestinal synthesis and liver stores of vitamin B12. Radiolabeled vitamin B12 in the blood, liver, kidneys, and spleen of fish fed 60Co in the diet indicated that the intestinally synthesized vitamin was absorbed by the fish. The primary route of absorption was directly from the digestive tract into the blood because coprophagy was prevented in the rearing aquariums and the amount of vitamin B12 dissolved in the aquarium water was too low for gill absorption. Dietary supplementation of vitamin B12 was not necessary for normal growth and erythrocyte formation in channel catfish in a 24-week feeding period. A longer period, however, may have caused a vitamin deficiency since liver-stored vitamin B 12 decreased between the 2nd and 24th weeks

  10. Effects of dithiocarbamates on intestinal absorption and organ distribution of cadmium chloride in mice

    International Nuclear Information System (INIS)

    Andersen, O.; Nielsen, J.B.; Jones, M.M.

    1989-01-01

    Earlier publications have demonstrated that diethyldithiocarbamate (DDC) antagonizes the acute toxicity of injected CdCl 2 but enhances the acute toxicity of orally administered CdCl 2 , most likely due to the high lipophilicity of DDC and the complex formed with the Cd ++ ion. This study demonstrates that the hydrophilic dithiocarbamates dihydroxyethyldithiocarbamate (DHE-DTC) and N-methyl-N-glucamyl dithiocarbamate (NMG-DTC) also enhance the intestinal absorption of orally administered CdCl 2 in mice, although less efficiently than DDC. After oral as well as intraperitoneal administration 15 min. after a single oral dose of CdCl 2 the dithiocarbamates tested enhanced the intestinal cadmium uptake with a relative efficiency, DDC>DHE-DTC>NMG-DTC, which correlated to the lipophilicity of both the dithiocarbamates and the complexes formed with the Cd ++ ion. Intraperitoneal administration of DDC induced extensive changes in the relative organ distribution of absorbed cadmium, compared to the distribution of CdCl 2 administered alone. However, the only noticeable effect of administration of DHE-DTC and NMG-DTC was decreased gastrointestinal deposition of cadmium, irrespective of the administration route of the dithiocarbamates. Earlier studies have demonstrated that DDC and various other dithiocarbamates are capable of mobilizing intracellular cadmium deposits, presumably due to some lipophilicity. This study demonstrates that these dithiocarbamates may also enchance the intestinal absorption of cadmium. (author)

  11. [Effects of nandrolone decanoate on bone mineral content and intestinal absorption of calcium].

    Science.gov (United States)

    Nuti, R; Righi, G A; Turchetti, V; Vattimo, A

    1984-01-28

    To evaluate the effects of a long-term treatment with nandrolone decanoate on metabolism of the skeleton, a double-blind randomized study was carried out in women with joint diseases without metabolic bone derangement. Ten patients were treated with 50 mg of nandrolone decanoate every three weeks for two years; in six subjects a treatment with placebo was performed. As it concerns plasma calcium and phosphate, serum alkaline phosphatase, urinary excretion of calcium, phosphate, hydroxyproline and cAMP, as parathyroid index, it was not observed significant differences in the two examined groups. While in placebo group at the end of the study the intestinal radiocalcium remained unchanged and bone mineral content showed a slight decrease, on the contrary nandrolone decanoate treatment promoted a significant improvement in intestinal calcium absorption and an increase in bone mineral content.

  12. MRP2 mediated drug-drug interaction: indomethacin increases sulfasalazine absorption in the small intestine, potentially decreasing its colonic targeting.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2010-02-15

    We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. Copyright 2009 Elsevier B.V. All rights reserved.

  13. Intestinal absorption and biliary elimination of glycyrrhizic acid diethyl ester in rats

    Directory of Open Access Journals (Sweden)

    Koga K

    2013-10-01

    Full Text Available Kenjiro Koga,1 Mayuri Kawamura,1 Hiroshi Iwase,2 Nobuji Yoshikawa31Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, 2Research Division, 3Research and Development Division, Cokey Systems Co, Ltd, Matsusaka, JapanBackground: The purpose of this study was to evaluate absorption and elimination from the gastrointestinal tract of glycyrrhizic acid diethyl ester (GZ-DE which was prepared as a prodrug of glycyrrhizic acid (a poorly absorbed compound in rats.Methods: After the GZ-DE solution was administered via the intravenous, intraduodenal, intraileal, and stomach routes, GZ-DE and GZ concentrations in bile were determined by high-performance liquid chromatography. The stability of GZ-DE was estimated from residual GZ-DE and GZ produced in GZ-DE solutions prepared with distilled water, a pH 1.2 solution, 0.9% NaCl solution, and phosphate-buffered solution (pH 7.4 at 37°C.Results: GZ-DE was eliminated into bile by the pharmacokinetic parameters of apparent distribution rate constant (4.56 ± 0.36 per hour and apparent elimination rate constant (0.245 ± 0.042 per hour. After intravenous and intraduodenal administration of GZ-DE, the concentration ratio of GZ-DE to GZ in bile was approximately 4:1, and the bioavailability of GZ containing GZ-DE was three-fold higher compared with the bioavailability of GZ after intraduodenal administration. GZ-DE was immediately precipitated in pH 1.2 solution and was converted to GZ by hydrolysis in pH 7.4 solution.Conclusion: Improvement of intestinal absorption of GZ was made possible by administration of GZ-DE into the intestine where absorption of GZ is lower than in the strong acidic environment of the stomach. However, because the elimination rate in bile simulated from kinetic parameters of GZ-DE was higher than the conversion rate from GZ-DE to GZ by hydrolysis, it is thought that the availability of GZ as a revolutionary prodrug was not high from the

  14. Prediction of intestinal absorption and blood-brain barrier penetration by computational methods.

    Science.gov (United States)

    Clark, D E

    2001-09-01

    This review surveys the computational methods that have been developed with the aim of identifying drug candidates likely to fail later on the road to market. The specifications for such computational methods are outlined, including factors such as speed, interpretability, robustness and accuracy. Then, computational filters aimed at predicting "drug-likeness" in a general sense are discussed before methods for the prediction of more specific properties--intestinal absorption and blood-brain barrier penetration--are reviewed. Directions for future research are discussed and, in concluding, the impact of these methods on the drug discovery process, both now and in the future, is briefly considered.

  15. Wnt, stem cells and cancer in the intestine.

    NARCIS (Netherlands)

    Pinto, D.; Clevers, J.C.

    2005-01-01

    The intestinal epithelium is a self-renewing tissue which represents a unique model for studying interconnected cellular processes such as proliferation, differentiation, cell migration and carcinogenesis. Although the stem cells of the intestine have not yet been physically characterized or

  16. Stem cell self-renewal in intestinal crypt

    NARCIS (Netherlands)

    Simons, B.D.; Clevers, H.

    2011-01-01

    As a rapidly cycling tissue capable of fast repair and regeneration, the intestinal epithelium has emerged as a favored model system to explore the principles of adult stem cell biology. However, until recently, the identity and characteristics of the stem cell population in both the small intestine

  17. Mechanistic insights of intestinal absorption and renal conservation of folate in chronic alcoholism.

    Science.gov (United States)

    Wani, Nissar Ahmad; Thakur, Shilpa; Najar, Rauf Ahmad; Nada, Ritambhara; Khanduja, Krishan Lal; Kaur, Jyotdeep

    2013-03-01

    Folate mediated one-carbon metabolism is of fundamental importance for various cellular processes, including DNA synthesis and methylation of biological molecules. Due to the exogenous requirement of folate in mammals, there exists a well developed epithelial folate transport system for regulation of normal folate homeostasis. The intestinal and renal folate uptake is tightly and diversely regulated and disturbances in folate homeostasis like in alcoholism have pathological consequences. The study was sought to delineate the regulatory mechanism of folate uptake in intestine and reabsorption in renal tubular cells that could evaluate insights of malabsorption during alcoholism. The folate transporters PCFT and RFC were found to be associated with lipid rafts of membrane surfaces in intestine and kidney. Importantly, the observed lower intestinal and renal folate uptake was associated with decreased levels of folate transporter viz. PCFT and RFC in lipid rafts of intestinal and renal membrane surfaces. The decreased association of folate transporters in lipid rafts was associated with decreased protein and mRNA levels. In addition, immunohistochemical studies showed that alcoholic conditions deranged that localization of PCFT and RFC. These findings could explain the possible mechanistic insights that may result in folate malabsorption during alcoholism. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. 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.

  19. Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells

    Science.gov (United States)

    2010-01-01

    Background Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD) in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'). To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria. Results C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase). Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics. Conclusion These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients. PMID:21040540

  20. Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells

    Directory of Open Access Journals (Sweden)

    Kalischuk Lisa D

    2010-11-01

    Full Text Available Abstract Background Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'. To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria. Results C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase. Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics. Conclusion These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients.

  1. Establishment of primary bovine intestinal epithelial cell culture and clone method.

    Science.gov (United States)

    Zhan, Kang; Lin, Miao; Liu, Ming-Mei; Sui, Yang-Nan; Zhao, Guo-Qi

    2017-01-01

    The aim of this study was to establish bovine intestinal epithelial cell (BIEC) line and provide a novel clone cell method. Although various strategies of bovine cell culture and clone techniques have been reported, these methods remain not established. Here, we culture successfully primary BIECs and establish a novel clone cell method. Our result showed that BIECs could be successfully cultured and passaged about generation 5. These cellular aggregates and clusters were adherent loosely at day 2 of culture. Cell aggregates and clusters start to proliferate after approximately 4 d. The BIECs showed positive reaction against cytokeratin 18, E-cadherin, and characteristics of epithelial-like morphology. In addition, the fatty acid-binding proteins (FABPs), villin, and intestinal peptidase (IP) band were positive in BIECs. Our results suggest that the establishment of culturing and clone BIEC methods will apply to isolate and clone other primary cells. These BIECs could therefore contribute to the study of bovine intestinal nutrient absorption and regulation, immune regulation, and the pathogenesis of the bovine intestinal disease, which will provide intestinal cell model in vitro.

  2. Studies on the in vitro absorption of spice principles--curcumin, capsaicin and piperine in rat intestines.

    Science.gov (United States)

    Suresh, D; Srinivasan, K

    2007-08-01

    A comparative evaluation of the absorbability of three structurally similar and physiologically active spice principles in an in vitro system consisting of everted rat intestinal sacs was made. When everted sacs of rat intestines were incubated with 50-1000 microg of curcumin in 10 ml incubation medium, absorption of the spice principle was maximum at 100 microg concentration. The amount of absorbed curcumin present in the serosal fluid was negligible. This and the comparatively lower recovery of the original compound suggested that curcumin to some extent undergoes a modification during absorption. For similar concentrations of added piperine, about 44-63% of piperine disappeared from the mucosal side. Absorption of piperine which was maximum at 800 microg per 10 ml was about 63%. The absolute amounts of piperine absorbed in this in vitro system exceeded the amounts of curcumin. The absorbed piperine could be traced in both the serosal fluid and in the intestinal tissue, indicating that piperine did not undergo any metabolic change during the process of absorption. 7-12% of the absorbed piperine was found in the serosal fluid. When everted sacs of rat intestines were incubated with 10-500 microg of capsaicin, a maximum of 82-88% absorption could be seen in the lower concentrations, and the amount of absorbed capsaicin did not proportionately increase at higher concentrations. A relatively higher percentage of the absorbed capsaicin could be seen in the serosal fluid as compared to curcumin or piperine. When these spice active principles were associated with mixed micelles, their in vitro intestinal absorption was relatively higher. Curcumin absorption in everted intestinal sac increased from 48.7% to 56.1% when the same was present in micelles. In the case of capsaicin and piperine, increase in absorption was 27.8-44.4% and 43.4-57.4%, respectively, when they were present in micelles as compared to its native form.

  3. Thyroid hormone regulation of adult intestinal stem cells: Implications on intestinal development and homeostasis.

    Science.gov (United States)

    Sun, Guihong; Roediger, Julia; Shi, Yun-Bo

    2016-12-01

    Organ-specific adult stem cells are essential for organ homeostasis, tissue repair and regeneration. The formation of such stem cells often takes place during postembryonic development, a period around birth in mammals when plasma thyroid hormone concentration is high. The life-long self-renewal of the intestinal epithelium has made mammalian intestine a valuable model to study the function and regulation and adult stem cells. On the other hand, much less is known about how the adult intestinal stem cells are formed during vertebrate development. Here, we will review some recent progresses on this subject, focusing mainly on the formation of the adult intestine during Xenopus metamorphosis. We will discuss the role of thyroid hormone signaling pathway in the process and potential molecular conservations between amphibians and mammals as well as the implications in organ homeostasis and human diseases.

  4. Effect of dietary phosphorus on intestinal phosphorus absorption in growing Holstein steers.

    Science.gov (United States)

    Feng, X; Ronk, E; Hanigan, M D; Knowlton, K F; Schramm, H; McCann, M

    2015-05-01

    The effect of dietary P intake on intestinal P absorption was evaluated in growing Holstein steers. Diets varying in P content (0.15, 0.27, 0.36, and 0.45%, DM basis) were fed to 8 steers (174±10kg of BW) fitted with permanent duodenal and ileal cannulas in a replicated 4×4 Latin square with 14-d periods. Ytterbium-labeled corn silage and cobalt-EDTA were used as particulate and liquid phase markers, respectively, to measure digesta flow. Duodenal and ileal samples and spot urine samples were collected every 9 h from d 11 to 14. Total fecal collection was conducted on d 11 to 14 with fecal bags. Blood samples were collected from the coccygeal vessel on d 14. Feed, digesta, and fecal samples were analyzed for total P and inorganic P. Data were analyzed using PROC GLIMMIX in SAS with a model including treatment, square, period, and interaction of treatment and square. Preplanned contrasts were used to evaluate linear and quadratic treatment effects. Results were reported as least squares means. Dry matter intake (mean=4.90kg/d, 2.8% of BW) and apparent DM digestibility (mean=78.1%) were unaffected by treatment. Duodenal and ileal flow of total P increased linearly with increasing P intake (13.4, 18.5, 23.0, and 27.4g/d; 6.80, 7.87, 8.42, and 10.4g/d). Increasing P intake increased the quantity of P absorbed from the small intestine linearly (6.96, 11.1, 14.6, and 17.2g/d), but absorption efficiency was unchanged (mean=59.6%). Phosphorus was absorbed on a net basis from the large intestine, but this was not affected by treatment and was a small proportion of total P absorption. Blood inorganic P increased linearly with increased dietary P (4.36, 6.31, 7.68, and 8.5mg/dL) and salivary P secretion was unchanged (mean=5.79g/d), suggesting that rumen function was prioritized during short-term P deficiency. These data showing an absence of change in absorption efficiency and salivary P secretion in the face of short-term P deficiency may be used to improve published

  5. Enhancement of intestinal water absorption and sodium transport by glycerol in rats.

    Science.gov (United States)

    Wapnir, R A; Sia, M C; Fisher, S E

    1996-12-01

    Glycerol (Gly) is a hydrophilic, absorbable, and energy-rich solute that could make water absorption more efficient. We investigated the use of Gly in a high-energy beverage containing corn syrup (CS) by using a small intestine perfusion procedure in the rat, an approach shown earlier to provide good preclinical information. The effectiveness of several formulations with Gly and CS was compared with commercial products and to experimental formulas where Gly substituted for glucose (Glc). The CS-Gly combination was more effective than preparations on the market containing sucrose and Glc-fructose syrups (G-P and G-L, respectively) in maintaining a net water absorption balance in the test jejunal segment [CS-Gly = 0.21 +/- 0.226, G-L = -1.516 +/- 0.467, and G-P = -0.299 +/- 0.106 (SE) microliter.min-1.cm-1 (P = 0.0113)] and in reducing sodium release into the lumen [CS-Gly = -133.2 +/- 16.2, G-L = -226.7 +/- 25.2, and G-P = -245.6 +/- 23.4 nmol.min-1.cm-1 (P = 0.0022)]. In other preparations, at equal CS concentrations (60 and 80 g/l, respectively), Gly clearly improved net water absorption over a comparable Glc-containing product [CS60-Gly = 0.422 +/- 0.136 and CS80-Gly = 0.666 +/- 0.378 vs. CS60-Glc = -0.282 +/- 0.200 and CS80-Glc = -1.046 +/- 0.480 microliters.min-1.cm-1 (P = 0.0019)]. On the basis of the data of this rat intestine perfusion model, Gly could be a useful ingredient in energy-rich beverages and might enhance fluid absorption in humans.

  6. [Multiple analysis of the difference in intestinal absorption between the main components and the extract of Glycyrrhiza uralensis].

    Science.gov (United States)

    Wu, Qing-Qing; Chen, Yan; Xin, Ran; Wang, Jin-Yan; Zhou, Lei; Yuan, Ling; Jia, Xiao-Bin

    2012-05-01

    The aim of this study is to investigate the rat intestinal absorption behavior of two main active components, liquiritin, glycyrrhizin and the extract of Glycyrrhiza uralensis. The rat intestinal perfusion model was employed. Concentrations of the compounds of the interest in the intestinal perfusate, bile and plasma samples were determined by HPLC and UPLC. At the same time, the intestinal enzymes incubation test and the partition coefficient determination, the absorption of liquiritin and glycyrrhizin alone and the extract were multiple analyzed. The results showed that the P(eff) (effective permeability) of liquiritin or glycyrrhizin alone or the extract was less than 0.3, which suggested their poor absorption in the intestine. The P(eff) of the two main active components or the extract was not significantly different in duodenum, jejunum, colon and ileum segment. The P(eff) of the glycyrrhizin in the extract had no significant difference in the four intestinal segments compared with the glycyrrhizin alone. The absorption of the liquiritin displayed significant difference (P components might not increase the amount of liquiritin and glycyrrhizin in the bile and plasma within the duration of the test.

  7. Stem cell self-renewal in intestinal crypt

    International Nuclear Information System (INIS)

    Simons, Benjamin D.; Clevers, Hans

    2011-01-01

    As a rapidly cycling tissue capable of fast repair and regeneration, the intestinal epithelium has emerged as a favored model system to explore the principles of adult stem cell biology. However, until recently, the identity and characteristics of the stem cell population in both the small intestine and colon has remained the subject of debate. Recent studies based on targeted lineage tracing strategies, combined with the development of an organotypic culture system, have identified the crypt base columnar cell as the intestinal stem cell, and have unveiled the strategy by which the balance between proliferation and differentiation is maintained. These results show that intestinal stem cells operate in a dynamic environment in which frequent and stochastic stem cell loss is compensated by the proliferation of neighboring stem cells. We review the basis of these experimental findings and the insights they offer into the mechanisms of homeostatic stem cell regulation.

  8. Intestinal absorption of cytidine diphosphate choline and its changes in the digestive tract

    International Nuclear Information System (INIS)

    Yashima, Keisuke; Takamatsu, Masatoshi; Okuda, Kunio

    1975-01-01

    Intestinal absorption of cytidine diphosphate choline (CDP-choline), its structural changes in the digestive tract, and hepatic uptake have been investigated in rats using 14 C-labeled ( 14 CH 3 attached to N of choline) and 3 H-labeled (at C 5 of pyrimidine) compounds. The results indicate that: 1) CDP-choline is relatively stable in the stomach, but is quickly degraded into cytidine and choline in the intestine; 2) The hepatic uptakes of 14 C and 3 H reach the maximum in two to three hours after oral administration; 3) Whereas the amount of 14 C remaining in the gut is inversely related to the hepatic uptake, no similar correlation is seen with 3 H-labeled CDP-choline, and 4) Extrahepatic uptake of 14 C and 3 H is very small. The possibility of phosphorylation in the mucosa of choline and cytidine has been discussed, based on the differences in relative amount of radioactivity in individual broken-down products in the intestinal lumen and mucosa. (auth.)

  9. Intestinal Epithelial Cell Endoplasmic Reticulum Stress and Inflammatory Bowel Disease Pathogenesis: An Update Review

    Directory of Open Access Journals (Sweden)

    Xiaoshi Ma

    2017-10-01

    Full Text Available The intestinal epithelial cells serve essential roles in maintaining intestinal homeostasis, which relies on appropriate endoplasmic reticulum (ER function for proper protein folding, modification, and secretion. Exogenous or endogenous risk factors with an ability to disturb the ER function can impair the intestinal barrier function and activate inflammatory responses in the host. The last decade has witnessed considerable progress in the understanding of the functional role of ER stress and unfolded protein response (UPR in the gut homeostasis and its significant contribution to the pathogenesis of inflammatory bowel disease (IBD. Herein, we review recent evidence supporting the viewpoint that deregulation of ER stress and UPR signaling in the intestinal epithelium, including the absorptive cells, Paneth cells, goblet cells, and enteroendocrine cells, mediates the action of genetic or environmental factors driving colitis in experimental animals and IBD patients. In addition, we highlight pharmacologic application of chaperones or small molecules that enhance protein folding and modification capacity or improve the function of the ER. These molecules represent potential therapeutic strategies in the prevention or treatment of IBD through restoring ER homeostasis in intestinal epithelial cells.

  10. General considerations regarding intestinal absorption of radionuclides as a function of age

    International Nuclear Information System (INIS)

    Metivier, H.; Fritsch, P.; Lataillade, G.

    1987-01-01

    Although enhanced absorption of radionuclides from the GI tract has been confirmed in recent years in many animal species, the species-dependent variations in GI absorption by neonates make it difficult to extrapolate animal data to humans. Numerous measurements have been made in 1 to 2 day-old animals, but fewer studies have covered the entire neonatal period up to weaning. For plutonium, sufficiently good inter-species agreement was obtained to assume that its absorption by the GI tract remains significantly high until weaning. The same was reported for neptunium absorption by hamsters but a preliminary experiment with baboons seems to refuse this, and the problem of extrapolation to humans from species more closely related to man remains unsolved. The fact that effects of different factors such as the chemical form of radionuclides, the neonatal transfer of immunoglobulins and intestinal wall permeability, has not been definitely proved also makes such extrapolation difficult. Because the baboon resembles man more than other animals as regards lifespan, length of gestation, the birth of only one animal at a time, the weaning time, the length of adolescence and the time of sexual maturation, it seems to be the animal species most likely to provide suitable data for extrapolation to human. 21 refs.; 3 figs.; 3 tabs

  11. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage

    NARCIS (Netherlands)

    P. Aparicio-Domingo (Patricia); M. Romera Hernández (Mónica); J.J. Karrich (Julien J.); F.H.J. Cornelissen (Ferry); N. Papazian (Natalie); D.J. Lindenbergh-Kortleve (Dicky); J.A. Butler (James A.); L. Boon (Louis); M. Coles (Mark); J.N. Samsom (Janneke); T. Cupedo (Tom)

    2015-01-01

    textabstractDisruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence

  12. Does lead use the intestinal absorptive pathways of iron? Impact of iron status on murine 210Pb and 59Fe absorption in duodenum and ileum in vivo

    International Nuclear Information System (INIS)

    Elsenhans, Bernd; Janser, Heinz; Windisch, Wilhelm; Schuemann, Klaus

    2011-01-01

    Highlights: → Absorption of 210 Pb increases much less than that of 59 Fe in murine duodena. → 210 Pb-absorption is almost equally high in murine duodenal and ileal segments. → 59 Fe absorption is much lower in ileal than in duodenal segments. → There must be an additional DMT1-independet pathway for intestinal Pb absorption. -- Abstract: Background: Human isotope studies and epidemiological trials are controversial as to whether lead absorption shares the absorptive pathways of iron and whether body lead content can be reduced by iron supplementation. Aim: To compare the impact of iron-deficiency on 59 Fe- and 210 Pb-absorption rates in duodenal and ileal segments. Methods: 59 Fe- and 210 Pb-absorption was determined in ligated duodenal and ileal segments from juvenile and adult iron-deficient and iron-adequate C57Bl6 wild-type mice (n = 6) in vivo at luminal concentrations corresponding to human exposure (Fe: 1 and 100 μmol/L; Pb: 1 μmol/L). Results and discussion: 59 Fe-absorption increased 10-15-fold in iron-deficient duodena from adult and adolescent mice. Ileal 59 Fe-absorption was 4-6 times lower than in iron-adequate duodena showing no adaptation to iron-deficiency. This in accordance to expectation as the divalent metal transport 1 (DMT1) shows low ileal expression levels. Juvenile 59 Fe-absorption was about twice as high as in adult mice. In contrast, duodenal 210 Pb-absorption was increased only 1.5-1.8-fold in iron-deficiency in juvenile and adult mice and, again in contrast to 59 Fe, ileal 210 Pb-absorption was as high as in iron-adequate duodena. Conclusions: The findings suggest a DMT1-independent pathway to mediate lead absorption along the entire small intestine in addition to DMT1-mediated duodenal uptake. Ileal lead absorption appears substantial, due the much longer residence of ingesta in the distal small intestine. Differences in lead-solubility and -binding to luminal ligands can, thus, explain the conflicting findings regarding the

  13. Intestinal Stem Cell Markers in the Intestinal Metaplasia of Stomach and Barrett's Esophagus.

    Directory of Open Access Journals (Sweden)

    Bo Gun Jang

    Full Text Available Gastric intestinal metaplasia (IM is a highly prevalent preneoplastic lesion; however, the molecular mechanisms regulating its development remain unclear. We have previously shown that a population of cells expressing the intestinal stem cell (ISC marker LGR5 increases remarkably in IM. In this study, we further investigated the molecular characteristics of these LGR5+ cells in IM by examining the expression profile of several ISC markers. Notably, we found that ISC markers-including OLFM4 and EPHB2-are positively associated with the CDX2 expression in non-tumorous gastric tissues. This finding was confirmed in stomach lesions with or without metaplasia, which demonstrated that OLFM4 and EPHB2 expression gradually increased with metaplastic progression. Moreover, RNA in situ hybridization revealed that LGR5+ cells coexpress several ISC markers and remained confined to the base of metaplastic glands, reminiscent to that of normal intestinal crypts, whereas those in normal antral glands expressed none of these markers. Furthermore, a large number of ISC marker-expressing cells were diffusely distributed in gastric adenomas, suggesting that these markers may facilitate gastric tumorigenesis. In addition, Barrett's esophagus (BE-which is histologically similar to intestinal metaplasia-exhibited a similar distribution of ISC markers, indicating the presence of a stem cell population with intestinal differentiation potential. In conclusion, we identified that LGR5+ cells in gastric IM and BE coexpress ISC markers, and exhibit the same expression profile as those found in normal intestinal crypts. Taken together, these results implicate an intestinal-like stem cell population in the pathogenesis of IM, and provide an important basis for understanding the development and maintenance of this disease.

  14. Bovine lactoferrin regulates cell survival, apoptosis and inflammation in intestinal epithelial cells and preterm pig intestine.

    Science.gov (United States)

    Nguyen, Duc Ninh; Jiang, Pingping; Stensballe, Allan; Bendixen, Emøke; Sangild, Per T; Chatterton, Dereck E W

    2016-04-29

    Bovine lactoferrin (bLF) may modulate neonatal intestinal inflammation. Previous studies in intestinal epithelial cells (IECs) indicated that moderate bLF doses enhance proliferation whereas high doses trigger inflammation. To further elucidate cellular mechanisms, we profiled the porcine IEC proteome after stimulation with bLF at 0, 0.1, 1 and 10g/L by LC-MS-based proteomics. Key pathways were analyzed in the intestine of formula-fed preterm pigs with and without supplementation of 10g/L bLF. Levels of 123 IEC proteins were altered by bLF. Low bLF doses (0.1-1g/L) up-regulated 11 proteins associated with glycolysis, energy metabolism and protein synthesis, indicating support of cell survival. In contrast, a high bLF dose (10g/L) up-regulated three apoptosis-inducing proteins, down-regulated five anti-apoptotic and proliferation-inducing proteins and 15 proteins related to energy and amino acid metabolism, and altered three proteins enhancing the hypoxia inducible factor-1 (HIF-1) pathway. In the preterm pig intestine, bLF at 10g/L decreased villus height/crypt depth ratio and up-regulated the Bax/Bcl-2 ratio and HIF-1α, indicating elevated intestinal apoptosis and inflammation. In conclusion, bLF dose-dependently affects IECs via metabolic, apoptotic and inflammatory pathways. It is important to select an appropriate dose when feeding neonates with bLF to avoid detrimental effects exerted by excessive doses. The present work elucidates dose-dependent effects of bLF on the proteomic changes of IECs in vitro supplemented with data from a preterm pig study confirming detrimental effects of enteral feeding with the highest dose of bLF (10g/L). The study contributes to further understanding on mechanisms that bLF, as an important milk protein, can regulate the homeostasis of the immature intestine. Results from this study urge neonatologists to carefully consider the dose of bLF to supplement into infant formula used for preterm neonates. Copyright © 2016 Elsevier B

  15. Regional distribution and variation of gamma-globulin absorption from the small intestine of the neonatal calf

    International Nuclear Information System (INIS)

    Fetcher, A.; Gay, C.C.; McGuire, T.C.; Barbee, D.D.; Parish, S.M.

    1983-01-01

    125I-labeled immunoglobulin (Ig)G1 in colostral whey was used to determine the region of maximum absorption of Ig from the small intestine of the neonatal calf and the variation in Ig absorption among calves at the intestinal level. In experiment 1, 5 segments (approx 5%, 35%, 60%, 80%, and 95% of the duodenocecal length) were formed in the small intestine of 9 colostrum-deprived calves shortly after birth. These segments were injected with colostral whey containing 125I-IgG1 4 hours after birth, and uptake, transfer, and absorption (defined as uptake plus transfer) were determined for each segment 2 hours later. Raw data were adjusted for the milligrams of IgG1 injected per gram of intestinal tissue to obtain the least squares mean (LSM) value. The LSM values for absorption of IgG1 from distal segments 3, 4, and 5 were significantly greater (P less than 0.05) than those values for proximal segments 1 and 2. The region of the maximum IgG1 absorption was the lower small intestine, 60% to 80% of the duodenocecal length. There was also an indication of independence between uptake and transfer in each of the segments. Significant differences (P less than 0.05) were present among calves in the LSM values for uptake and absorption, but not for transfer. In experiment 2, thoracic ducts of 8 newborn calves were cannulated 4 to 5 hours after birth. At 6 hours after birth, colostral whey with 125I-IgG1 was injected into an intestinal segment (approx 60% to 80% of the duodenocecal length)

  16. Effect of petroleum vapors inhalation on intestinal absorption of glucose and some amino acids in the rat

    International Nuclear Information System (INIS)

    Szablicka, E.; Oledzka, R.

    1989-01-01

    The proper intestinal absorption of nutrients, particularly sugars and amino acids, is necessary to keep the organism healthy. It is well known that various toxic compounds present in the environment can have an unfavorable influence. On the other hand it is also known that crude oil which pollutes the aqueous environment affects birds' gastrointestinal tract. Little is known about the influence of petroleum vapors on the gastrointestinal tract of animals and humans. The present study was undertaken to determine the effect of petroleum vapors inhalation on intestinal absorption of some nutrients (glucose, leucine, methionine) in rats

  17. Hydrodynamic Impacts on Dissolution, Transport and Absorption from Thousands of Drug Particles Moving within the Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, James G.

    2017-11-01

    Following tablet disintegration, clouds of drug particles 5-200 μm in diameter pass through the intestines where drug molecules are absorbed into the blood. Release rate depends on particle size, drug solubility, local drug concentration and the hydrodynamic environment driven by patterned gut contractions. To analyze the dynamics underlying drug release and absorption, we use a 3D lattice Boltzmann model of the velocity and concentration fields driven by peristaltic contractions in vivo, combined with a mathematical model of dissolution-rate from each drug particle transported through the grid. The model is empirically extended for hydrodynamic enhancements to release rate by local convection and shear-rate, and incorporates heterogeneity in bulk concentration. Drug dosage and solubility are systematically varied along with peristaltic wave speed and volume. We predict large hydrodynamic enhancements (35-65%) from local shear-rate with minimal enhancement from convection. With high permeability boundary conditions, a quasi-equilibrium balance between release and absorption is established with volume and wave-speed dependent transport time scale, after an initial transient and before a final period of dissolution/absorption. Supported by FDA.

  18. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    International Nuclear Information System (INIS)

    Horita, Nobukatsu; Tsuchiya, Kiichiro; Hayashi, Ryohei; Fukushima, Keita; Hibiya, Shuji; Fukuda, Masayoshi; Kano, Yoshihito; Mizutani, Tomohiro; Nemoto, Yasuhiro; Yui, Shiro; Okamoto, Ryuichi; Nakamura, Tetsuya; Watanabe, Mamoru

    2014-01-01

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus

  19. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    Energy Technology Data Exchange (ETDEWEB)

    Horita, Nobukatsu [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Tsuchiya, Kiichiro, E-mail: kii.gast@tmd.ac.jp [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Hayashi, Ryohei [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Department of Gastroenterology and Metabolism, Hiroshima University (Japan); Fukushima, Keita; Hibiya, Shuji; Fukuda, Masayoshi; Kano, Yoshihito; Mizutani, Tomohiro; Nemoto, Yasuhiro; Yui, Shiro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Okamoto, Ryuichi; Nakamura, Tetsuya [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Watanabe, Mamoru [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan)

    2014-11-28

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus.

  20. Deoxynivalenol as a contaminant of broiler feed: intestinal development, absorptive functionality, and metabolism of the mycotoxin.

    Science.gov (United States)

    Yunus, A W; Blajet-Kosicka, A; Kosicki, R; Khan, M Z; Rehman, H; Böhm, J

    2012-04-01

    Deoxynivalenol (DON) has been recently documented to deteriorate intestinal morphology in chickens at dietary doses that are regarded as safe for this species. The present trial was conducted to explore the significance of these morphological changes in relation to intestinal absorptive functionality and DON metabolism. Ross broilers at 7 d of age were fed either a basal diet (0.265 ± 0.048 mg of DON/kg; 0.013 ± 0.001 mg of zearalenone/kg), a low DON diet (1.68 mg of DON/kg; 0.145 ± 0.007 mg of zearalenone/kg), or a high DON diet (12.209 ± 1.149 mg of DON/kg; 1.094 ± 0.244 mg of zearalenone/kg). The DON diets (to variable degrees) progressively decreased the relative density (weight:length) of the small intestine with increasing exposure length, which could be correlated with a decrease in villus height in the small intestine. Short circuit current of the jejunal epithelium, reflecting transport function of the epithelium per unit area, was reduced (P = 0.001) in the birds fed the high DON diet. The increasing dietary level of DON linearly (P = 0.035) increased the length of the jejunum in wk 4 of exposure, resulting in conservation of macronutrient retention. Upon challenging the birds with a fixed amount of DON after wk 5 of exposure, higher (P ≤ 0.033) amounts of DON and the detoxification metabolite (de-epoxy-DON) were found at 5 h postchallenge in the guts of birds raised on the DON diets. The increasing level of previous exposure to DON linearly (P = 0.040) decreased the plasma level of DON in the birds at 1 h postchallenge. The amounts of zearalenone and its analogs in the gut and plasma also followed a trend similar to that for DON. These data suggest that intestines in chickens may adapt to a chronic DON challenge by morphological and functional modifications. The birds having previous exposure to Fusarium mycotoxins showed moderate detoxification coupled with reduced transfer of the mycotoxins to systemic circulation. Some metabolites of

  1. Intestinal absorption of radiocalcium. Measurement by the oral and intraveinous activity ratio and by the inverse convolution method

    International Nuclear Information System (INIS)

    Monnier, L.; Collet, H.; Suquet, P.; Mirouze, J.

    1975-01-01

    The intestinal absorption of calcium was measured by a double isotopic labelling method, the results being obtained by a mathematical deconvolution technique. This analytical method was compared with the simple measurement of the plasma radioactivity ratio for the two isotopes administered orally and intraveinously respectively. The study covered 29 determinations. It was possible to estimate the total fractional absorption of calcium (TFACa) by calculating the average of the 47 Ca/ 45 Ca quotients measured on the 3rd and 8th hour after simultaneous administration of 45 Ca intraveinously and 47 Ca by mouth. The advantages of this method are obvious: need for only two blood samplings, simplicity of calculations which nevertheless give TFACa values comparable to those obtained by deconvolution analysis. However the only information supplied by the quotients method is the total fractional absorption, whereas inverse convolution analysis provides several interesting parameters such as the maximum absorption and the mean transit time of radiocalcium through the intestinal wall [fr

  2. Inhibition of intestinal radiocaesium absorption from Chernobyl contaminated whey by hexacyanoferrates(II) in pigs

    International Nuclear Information System (INIS)

    Dresow, B.; Asmus, J.; Fischer, R.; Nielsen, P.; Heinrich, H.C.

    1993-01-01

    The inhibition of radiocaesium transfer from Chernobyl contaminated whey powder to the pork and liver of fattening pigs using various dosages of different hexacyanoferrate (II) compounds (HCF) was studied under normal feeding conditions. Increasing amounts of all three hexacyanoferates tested resulted in a dose-dependent reduction in the 134+137 Cs activity concentration in all of the tissues sampled. KFe[Fe(CN) 6 ] and NE 4 Fe(CN) 6 ] were effective to the same extent while Fe 4 [Fe(CN) 6 ] 3 was less effective at dosages of 1-3 g d -1 HCF. Administration of 10 g d -1 HCF resulted in an almost complete inhibition (>99%) of intestinal radiocaesium absorption for all three compounds. (Author)

  3. 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.

    Science.gov (United States)

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), 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 determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

  4. Activated STAT5 Confers Resistance to Intestinal Injury by Increasing Intestinal Stem Cell Proliferation and Regeneration

    Directory of Open Access Journals (Sweden)

    Shila Gilbert

    2015-02-01

    Full Text Available Intestinal epithelial stem cells (IESCs control the intestinal homeostatic response to inflammation and regeneration. The underlying mechanisms are unclear. Cytokine-STAT5 signaling regulates intestinal epithelial homeostasis and responses to injury. We link STAT5 signaling to IESC replenishment upon injury by depletion or activation of Stat5 transcription factor. We found that depletion of Stat5 led to deregulation of IESC marker expression and decreased LGR5+ IESC proliferation. STAT5-deficient mice exhibited worse intestinal histology and impaired crypt regeneration after γ-irradiation. We generated a transgenic mouse model with inducible expression of constitutively active Stat5. In contrast to Stat5 depletion, activation of STAT5 increased IESC proliferation, accelerated crypt regeneration, and conferred resistance to intestinal injury. Furthermore, ectopic activation of STAT5 in mouse or human stem cells promoted LGR5+ IESC self-renewal. Accordingly, STAT5 promotes IESC proliferation and regeneration to mitigate intestinal inflammation. STAT5 is a functional therapeutic target to improve the IESC regenerative response to gut injury.

  5. Plasticity of intestinal epithelial cells in regeneration and cancer

    NARCIS (Netherlands)

    Tetteh, Paul W.

    2015-01-01

    Cellular plasticity refers to the ability of a cell to change its fate or identity in response to external or intrinsic factors. Regeneration of the intestinal epithelium after injury is driven mainly by plasticity of crypt stem cells that can rapidly divide to replace all the lost cells. Stem cell

  6. Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.

    Science.gov (United States)

    Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca; Zhang, Hongbo; Mäkilä, Ermei M; Kauppila, Jussi; Sarmento, Bruno; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2014-08-01

    Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (P(app)) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. 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

  8. Intestinal alkaline phosphatase: selective endocytosis from the enterocyte brush border during fat absorption

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, Lise-Lotte; Immerdal, Lissi

    2007-01-01

    explants. By immunofluorescence microscopy, fat absorption caused a translocation of IAP from the enterocyte brush border to the interior of the cell, whereas other brush-border enzymes were unaffected. By electron microscopy, the translocation occurred by a rapid (5 min) induction of endocytosis via...

  9. The intestinal absorption of dietary cholesterol by hypercholesterolemic (type II) and normocholesterolemic humans.

    Science.gov (United States)

    Connor, W E; Lin, D S

    1974-04-01

    The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia. To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat. Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast. In some instances [1alpha-(3)H]cholesterol was the radioactive marker. The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol. The amount of absorbed and reexcreted labeled cholesterol proved negligible. Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days. Plasma specific activity curves were usually maximal at 48 h. Normal subjects absorbed 44.5+/-9.3 (SD) of the administered cholesterol (range 25.9-60.3). Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 47.6+/-12.6% (range 29.3-67.3). Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (42.1+/-9.3 vs. 48.9+/-9.8%). Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk. At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered. Cholesterol absorption was 42.3+/-6.0% and 45.4+/-8.3% for the two dietary periods, respectively. The absolute cholesterol absorption was linearly

  10. Intestinal stem cells in the adult Drosophila midgut

    International Nuclear Information System (INIS)

    Jiang, Huaqi; Edgar, Bruce A.

    2011-01-01

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: ► The homeostasis and regeneration of adult fly midguts are mediated by ISCs. ► Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). ► EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. ► Notch signaling regulates ISC self-renewal and differentiation.

  11. Mechanisms involved in the intestinal digestion and absorption of dietary vitamin A.

    Science.gov (United States)

    Harrison, E H; Hussain, M M

    2001-05-01

    Dietary retinyl esters are hydrolyzed in the intestine by the pancreatic enzyme, pancreatic triglyceride lipase (PTL), and intestinal brush border enzyme, phospholipase B. Recent work on the carboxylester lipase (CEL) knockout mouse suggests that CEL may not be involved in dietary retinyl ester digestion. The possible roles of the pancreatic lipase-related proteins (PLRP) 1 and 2 and other enzymes require further investigation. Unesterified retinol is taken up by the enterocytes, perhaps involving both diffusion and protein-mediated facilitated transport. Once in the cell, retinol is complexed with cellular retinol-binding protein type 2 (CRBP2) and the complex serves as a substrate for reesterification of the retinol by the enzyme lecithin:retinol acyltransferase (LRAT). Retinol not bound to CRBP2 is esterified by acyl-CoA acyltransferase (ARAT). The retinyl esters are incorporated into chylomicrons, intestinal lipoproteins that transport other dietary lipids such as triglycerides, phospholipids, and cholesterol. Chylomicrons containing newly absorbed retinyl esters are then secreted into the lymph.

  12. 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

  13. Low Zinc Status and Absorption Exist in Infants with Jejunostomies or Ileostomies Which Persists after Intestinal Repair

    Directory of Open Access Journals (Sweden)

    Steven A. Abrams

    2012-09-01

    Full Text Available There is very little data regarding trace mineral nutrition in infants with small intestinal ostomies. Here we evaluated 14 infants with jejunal or ileal ostomies to measure their zinc absorption and retention and biochemical zinc and copper status. Zinc absorption was measured using a dual-tracer stable isotope technique at two different time points when possible. The first study was conducted when the subject was receiving maximal tolerated feeds enterally while the ostomy remained in place. A second study was performed as soon as feasible after full feeds were achieved after intestinal repair. We found biochemical evidence of deficiencies of both zinc and copper in infants with small intestinal ostomies at both time points. Fractional zinc absorption with an ostomy in place was 10.9% ± 5.3%. After reanastamosis, fractional zinc absorption was 9.4% ± 5.7%. Net zinc balance was negative prior to reanastamosis. In conclusion, our data demonstrate that infants with a jejunostomy or ileostomy are at high risk for zinc and copper deficiency before and after intestinal reanastamosis. Additional supplementation, especially of zinc, should be considered during this time period.

  14. Computational Studies of Drug Release, Transport and Absorption in the Human Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.

    2016-11-01

    Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.

  15. Dietary inulin intake and age can significantly affect intestinal absorption of calcium and magnesium in rats: a stable isotope approach

    Science.gov (United States)

    Coudray, Charles; Rambeau, Mathieu; Feillet-Coudray, Christine; Tressol, Jean Claude; Demigne, Christian; Gueux, Elyett; Mazur, Andrzej; Rayssiguier, Yves

    2005-01-01

    Background previous studies have shown that non-digestible inulin-type fructan intake can increase intestinal mineral absorption in both humans and animals. However, this stimulatory effect on intestinal absorption may depend on experimental conditions such as duration of fermentable fiber intake, mineral diet levels and animals' physiological status, in particular their age. Objectives the aim of this study was to determine the effect of inulin intake on Ca and Mg absorption in rats at different age stages. Methods eighty male Wistar rats of four different ages (2, 5, 10 and 20 months) were randomized into either a control group or a group receiving 3.75% inulin in their diet for 4 days and then 7.5% inulin for three weeks. The animals were fed fresh food and water ad libitum for the duration of the experiment. Intestinal absorption of Ca and Mg was determined by fecal monitoring using stable isotopic tracers. Ca and Mg status was also assessed. Results absorption of Ca and Mg was significantly lower in the aged rats (10 and 20 mo) than in the young and adult rat groups. As expected, inulin intake increased Ca and Mg absorption in all four rat groups. However, inulin had a numerically greater effect on Ca absorption in aged rats than in younger rats whereas its effect on Mg absorption remained similar across all four rat age groups. Conclusion the extent of the stimulatory effect of inulin on absorption of Ca may differ according to animal ages. Further studies are required to explore this effect over longer inulin intake periods, and to confirm these results in humans. PMID:16253138

  16. Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation

    Directory of Open Access Journals (Sweden)

    Andrea C. Lei-Leston

    2017-09-01

    Full Text Available Pattern recognition receptors (PRR, such as NOD-like receptors (NLRs, sense conserved microbial signatures, and host danger signals leading to the coordination of appropriate immune responses. Upon activation, a subset of NLR initiate the assembly of a multimeric protein complex known as the inflammasome, which processes pro-inflammatory cytokines and mediates a specialized form of cell death known as pyroptosis. The identification of inflammasome-associated genes as inflammatory bowel disease susceptibility genes implicates a role for the inflammasome in intestinal inflammation. Despite the fact that the functional importance of inflammasomes within immune cells has been well established, the contribution of inflammasome expression in non-hematopoietic cells remains comparatively understudied. Given that intestinal epithelial cells (IEC act as a barrier between the host and the intestinal microbiota, inflammasome expression by these cells is likely important for intestinal immune homeostasis. Accumulating evidence suggests that the inflammasome plays a key role in shaping epithelial responses at the host–lumen interface with many inflammasome components highly expressed by IEC. Recent studies have exposed functional roles of IEC inflammasomes in mucosal immune defense, inflammation, and tumorigenesis. In this review, we present the main features of the predominant inflammasomes and their effector mechanisms contributing to intestinal homeostasis and inflammation. We also discuss existing controversies in the field and open questions related to their implications in disease. A comprehensive understanding of the molecular basis of intestinal inflammasome signaling could hold therapeutic potential for clinical translation.

  17. Synthesis of protein in intestinal cells exposed to cholera toxin

    International Nuclear Information System (INIS)

    Peterson, J.W.; Berg, W.D. Jr.; Coppenhaver, D.H.

    1987-01-01

    The mechanism by which cyclic adenosine monophosphate (AMP), formed by intestinal epithelial cells in response to cholera toxin, ultimately results in alterations in water and electrolyte transport is poorly understood. Several studies have indicated that inhibitors of transcription or translation block much of the transport of ions and water in the intestine and edema formation in tissue elicited by cholera toxin. Data presented in this study confirmed the inhibitory effects of cycloheximide on cholera toxin-induced fluid accumulation in the rabbit intestinal loop model. Neither cycloheximide nor actinomycin D altered the amount of cyclic AMP that accumulated in intestinal cells and Chinese hamster ovary cells exposed to cholera toxin. An increase in [ 3 H] leucine incorporation was readily demonstrable in intestinal epithelial cells from rabbits challenged with Vibrio cholerae. Similarly, intestinal epithelial cells incubated with cholera toxin for 4 hr synthesized substantially more protein than controls as determined by relative incorporation of [ 35 S] methionine. Most of the new protein synthesized in response to cholera toxin was membrane associated and of high molecular weight. The possible significance of the toxin-induced protein relative to cholera pathogenesis was discussed

  18. Interstitial cells of Cajal in human small intestine. Ultrastructural identification and organization between the main smooth muscle layers

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johannes; Thuneberg, Lars

    1991-01-01

    Anatomy, interstitial cells of Cajal, small intestine, gut motility, pacemaker cells, smooth muscle......Anatomy, interstitial cells of Cajal, small intestine, gut motility, pacemaker cells, smooth muscle...

  19. Very late onset small intestinal B cell lymphoma associated with primary intestinal lymphangiectasia and diffuse cutaneous warts

    OpenAIRE

    Bouhnik, Y; Etienney, I; Nemeth, J; Thevenot, T; Lavergne-Slove, A; Matuchansky, C

    2000-01-01

    As only a handful of lymphoma cases have been reported in conjunction with primary intestinal lymphangiectasia, it is not yet clear if this association is merely fortuitous or related to primary intestinal lymphangiectasia induced immune deficiency. We report on two female patients, 50 and 58 years old, who developed small intestinal high grade B cell lymphoma a long time (45 and 40 years, respectively) after the initial clinical manifestations of primary intestinal lymphangiectasia. They pre...

  20. Small intestinal absorption in patients with chronic obstructive pulmonary disease complicated by cor pulmonale - A pilot study

    DEFF Research Database (Denmark)

    Andersen, Sara Korsgaard; Hardis, Anne L S; Tupper, Oliver Djurhuus

    2018-01-01

    BACKGROUND: Cor pulmonale is a common complication to Chronic Obstructive Pulmonary Disease (COPD), and may result in increased pressure in the inferior caval vein and stasis of the liver. The chronic pulmonary hypertension may lead to stasis in the veins from the small intestine and thereby...... compromise absorption of nutrients. AIM: To investigate whether patients with pulmonary hypertension have reduced absorption capacity compared to COPD patients without cor pulmonale. METHODS: Absorption of d-xylose (25 g) and zinc (132 mg), administered as a single dose, was tested in 14 COPD patients, seven...

  1. BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation

    Science.gov (United States)

    Reddy, Vishruth K.; Short, Sarah P.; Barrett, Caitlyn W.; Mittal, Mukul K.; Keating, Cody E.; Thompson, Joshua J.; Harris, Elizabeth I.; Revetta, Frank; Bader, David M.; Brand, Thomas; Washington, M. Kay; Williams, Christopher S.

    2016-01-01

    Blood Vessel Epicardial Substance (BVES/Popdc1) is a junctional-associated transmembrane protein that is underexpressed in a number of malignancies and regulates epithelial-to-mesenchymal transition. We previously identified a role for BVES in regulation of the Wnt pathway, a modulator of intestinal stem cell programs, but its role in small intestinal (SI) biology remains unexplored. We hypothesized that BVES influences intestinal stem cell programs and is critical to SI homeostasis after radiation injury. At baseline, Bves−/− mice demonstrated increased crypt height, as well as elevated proliferation and expression of the stem cell marker Lgr5 compared to wildtype (WT) mice. Intercross with Lgr5-EGFP reporter mice confirmed expansion of the stem cell compartment in Bves−/− mice. To examine stem cell function after BVES deletion, we employed ex vivo 3D-enteroid cultures. Bves−/− enteroids demonstrated increased stemness compared to WT, when examining parameters such as plating efficiency, stem spheroid formation, and retention of peripheral cystic structures. Furthermore, we observed increased proliferation, expression of crypt-base columnar “CBC” and “+4” stem cell markers, amplified Wnt signaling, and responsiveness to Wnt activation in the Bves−/− enteroids. Bves expression was downregulated after radiation in WT mice. Moreover, after radiation, Bves−/− mice demonstrated significantly greater small intestinal crypt viability, proliferation, and amplified Wnt signaling in comparison to WT mice. Bves−/− mice also demonstrated elevations in Lgr5 and Ascl2 expression, and putative damage-responsive stem cell populations marked by Bmi1 and TERT. Therefore, BVES is a key regulator of intestinal stem cell programs and mucosal homeostasis. PMID:26891025

  2. A multi-chamber microfluidic intestinal barrier model using Caco-2 cells for drug transport studies

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin; Trier, Sofie; Rahbek, Ulrik L

    2018-01-01

    with platinum wires, enabling parallel real-time monitoring of barrier integrity for the eight chambers. Additionally, the translucent porous Teflon membrane enabled optical monitoring of cell monolayers. The device was developed and tested with the Caco-2 intestinal model, and compared to the conventional...... through permeability studies of mannitol, dextran and insulin, alone or in combination with the absorption enhancer tetradecylmaltoside (TDM). The thiol-ene-based microchip material and electrodes were highly compatible with cell growth. In fact, Caco-2 cells cultured in the device displayed...

  3. Effect of cholecalciferol and 1,25-dihydroxycholecalciferol on the intestinal absorption of zinc in the chick

    International Nuclear Information System (INIS)

    Koo, S.I.; Fullmer, C.S.; Wasserman, R.H.

    1980-01-01

    The effect of cholecalciferol on the intestinal absorption of 65 Zn was assessed in zinc-deficient and zinc-replete rachitic chicks, using the in situ ligated loop techniques. Cholecalciferol did not significantly affect 65 Zn absorption in either group, although the synthesis of the intestinal calcium-binding protein (CaBP) in both groups was similar. In an analogous study, 1,25-dihydroxycholecalciferol increased 47 Ca absorption and induced the synthesis of CaBP but exerted no effect on 65 Zn absorption in zinc-deficient rachitic chicks. When fed a diet adequate in cholecalciferol, more CaBP was present in the intestine of the zinc-adequate group than in the zinc-deficient group, possibly due to the greater rate of growth and therefore the greater need for calcium by the former group. These results suggest that cholecalciferol and its most active metabolite do not directly affect zinc absorption and, by inference, that the vitamin D-dependent transport mechanism is not involved in zinc homeostasis, or in the interaction between calcium and zinc

  4. Occurrence of lymphoid cells in the intestine of the Goldfish

    NARCIS (Netherlands)

    Weinberg, Steven

    1975-01-01

    The Goldfish intestine normally contains a large number of lymphocytes, many of them being present in the epithelial layer. After stimulation with antigen, the number of lymphoid cells does not increase, but the proportion of large pyroninophilic cells and plasma cells does. It seems therefore that

  5. Intestinal dendritic cells in the regulation of mucosal immunity

    DEFF Research Database (Denmark)

    Bekiaris, Vasileios; Persson, Emma K.; Agace, William Winston

    2014-01-01

    immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive....... The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality...

  6. Intestinal absorption, organ distribution, and urinary excretion of the rare sugar D-psicose

    Directory of Open Access Journals (Sweden)

    Tsukamoto I

    2014-10-01

    Full Text Available Ikuko Tsukamoto,1,* Akram Hossain,2,3,* Fuminori Yamaguchi,2 Yuko Hirata,2 Youyi Dong,2 Kazuyo Kamitori,2 Li Sui,2 Machiko Nonaka,2 Masaki Ueno,4 Kazuyuki Nishimoto,5 Hirofumi Suda,5 Kenji Morimoto,6 Tsuyoshi Shimonishi,7,† Madoka Saito,8 Tao Song,9 Ryoji Konishi,1 Masaaki Tokuda2 1Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan; 2Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan; 3Matsutani Chemical Industry Co, Ltd, Itami, Japan; 4Department of Inflammation Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan; 5Division of Radioisotope Research, Life Science Research Center, Kagawa University, Kagawa, Japan; 6Rare Sugar Research Center, Kagawa University, Kagawa, Japan; 7IZUMORING LLC, Miki, Kita, Kagawa, Japan; 8Department of Pharmacy, Okayama University Hospital, Okayama, Japan; 9The First Affiliated Hospital, China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work†Tsuyoshi Shimonishi has passed away Background: The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia. Methods: This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of 14C-labeled D-psicose or glucose intravenously to C3H mice. Results: Following oral administration, D-psicose easily moved to blood. The maximum blood

  7. The effect of haem biosynthesis inhibitors and inducers on intestinal iron absorption and liver haem biosynthetic enzyme activities

    International Nuclear Information System (INIS)

    Laftah, A.H.; Simpson, R.J.; Peters, T.J.; Raja, K.B.

    2008-01-01

    The relation between haem biosynthesis and intestinal iron absorption is not well understood, we therefore investigated the effect of compounds that alter haem metabolism on duodenal iron absorption. CD1 mice were treated with either an inhibitor (succinyl acetone (SA)) or stimulator (2-allyl-2-isopropylacetamide (AIA)) of haem biosynthesis. 5-Aminolaevulinic acid (ALA) dehydratase and urinary ALA and porphobilinogen (PBG) levels, were determined. Intestinal iron absorption was assayed with in vivo and in vitro techniques. Liver hepcidin (Hamp1) and duodenal iron transporter mRNA levels were measured using RT-PCR. AIA caused increased hepatic ALA synthase (1.6-fold) and ALA dehydratase (1.4-fold, both p < 0.005) activities and increased urinary ALA and PBG excretion (2.1- and 1.4-fold, p < 0.005, p < 0.05, respectively). In vivo intestinal iron absorption was reduced to 49% of control (p < 0.005). Mice treated with SA showed decreased urinary ALA and PBG levels (75 and 55% control, both p < 0.005) and reductions in both ALA synthase and ALA dehydratase activities (77 and 56% control, p < 0.05, p < 0.005, respectively) in the liver. Liver and duodenal haem and cytochrome oxidase levels were not significantly decreased. Iron absorption was enhanced (1.26-fold, p < 0.05) and hepatic Hamp1 mRNA was reduced (53% of control, p < 0.05). In vitro duodenal iron uptake after mice were injected with SA also demonstrated an increase in Fe(III) reduction and uptake (1.27- and 1.41-fold, p < 0.01 respectively). Simultaneous injections of SA and ALA blocked the enhancing effect on iron absorption seen with SA alone. We conclude that alterations in haem biosynthesis can influence iron absorption and in particular, the intermediate ALA seems to be an inhibitor of iron absorption

  8. Intestinal stromal cells in mucosal immunity and homeostasis.

    Science.gov (United States)

    Owens, B M J; Simmons, A

    2013-03-01

    A growing body of evidence suggests that non-hematopoietic stromal cells of the intestine have multiple roles in immune responses and inflammation at this mucosal site. Despite this, many still consider gut stromal cells as passive structural entities, with past research focused heavily on their roles in fibrosis, tumor progression, and wound healing, rather than their contributions to immune function. In this review, we discuss our current knowledge of stromal cells in intestinal immunity, highlighting the many immunological axes in which stromal cells have a functional role. We also consider emerging data that broaden the potential scope of their contribution to immunity in the gut and argue that these so-called "non-immune" cells are reclassified in light of their diverse contributions to intestinal innate immunity and the maintenance of mucosal homeostasis.

  9. Optimization of micro-fabricated porous membranes for intestinal epithelial cell culture and in vitro modeling of the human intestinal barrier

    Science.gov (United States)

    Nair Gourikutty Sajay, Bhuvanendran; Yin, Chiam Su; Ramadan, Qasem

    2017-12-01

    In vitro modeling of organs could provide a controlled platform for studying physiological events and has great potential in the field of pharmaceutical development. Here, we describe the characterization of in vitro modeling of the human intestinal barrier mimicked using silicon porous membranes as a substrate. To mimic an intestinal in vivo setup as closely as possible, a porous substrate is required in a dynamic environment for the cells to grow rather than a static setup with an impermeable surface such as a petri dish. In this study, we focus on the detailed characterization of Caco-2 cells cultured on a silicon membrane with different pore sizes as well as the effect of dynamic fluid flow on the model. The porous silicon membrane together with continuous perfusion of liquid applying shear stress on the cells enhances the differentiation of polarized cells by providing access to the both their basal and apical surfaces. Membranes with pore sizes of 0.5-3 µm were used and a shear stress of ~0.03 dyne cm-2 was created by applying a low flow rate of 20 nl s-1. By providing these optimized conditions, cells were able to differentiate with columnar morphology, which developed microvilli structures on their apical side and tight junctions between adjacent cells like those in a healthy human intestinal barrier. In this setup, it is possible to study the important cellular functions of the intestine such as transport, absorption and secretion, and thus this model has great potential in drug screening.

  10. Enhancing the intestinal absorption of molecules containing the polar guanidino functionality: a double-targeted prodrug approach.

    Science.gov (United States)

    Sun, Jing; Dahan, Arik; Amidon, Gordon L

    2010-01-28

    A prodrug strategy was applied to guanidino-containing analogues to increase oral absorption via hPEPT1 and hVACVase. l-Valine, l-isoleucine, and l-phenylalanine esters of [3-(hydroxymethyl)phenyl]guanidine (3-HPG) were synthesized and evaluated for transport and activation. In HeLa/hPEPT1 cells, Val-3-HPG and Ile-3-HPG exhibited high affinity to hPEPT1 (IC(50): 0.65 and 0.63 mM, respectively), and all three l-amino acid esters showed higher uptake (2.6- to 9-fold) than the parent compound 3-HPG. Val-3-HPG and Ile-3-HPG demonstrated remarkable Caco-2 permeability enhancement, and Val-3-HPG exhibited comparable permeability to valacyclovir. In rat perfusion studies, Val-3-HPG and Ile-3-HPG permeabilities were significantly higher than 3-HPG and exceeded/matched the high-permeability standard metoprolol, respectively. All the l-amino acid 3-HPG esters were effectively activated in HeLa and Caco-2 cell homogenates and were found to be good substrates of hVACVase (k(cat)/K(m) in mM(-1) x s(-1): Val-3-HPG, 3370; Ile-3-HPG, 1580; Phe-3-HPG, 1660). In conclusion, a prodrug strategy is effective at increasing the intestinal permeability of polar guanidino analogues via targeting hPEPT1 for transport and hVACVase for activation.

  11. Cell lineage identification and stem cell culture in a porcine model for the study of intestinal epithelial regeneration.

    Directory of Open Access Journals (Sweden)

    Liara M Gonzalez

    Full Text Available Significant advances in intestinal stem cell biology have been made in murine models; however, anatomical and physiological differences between mice and humans limit mice as a translational model for stem cell based research. The pig has been an effective translational model, and represents a candidate species to study intestinal epithelial stem cell (IESC driven regeneration. The lack of validated reagents and epithelial culture methods is an obstacle to investigating IESC driven regeneration in a pig model. In this study, antibodies against Epithelial Adhesion Molecule 1 (EpCAM and Villin marked cells of epithelial origin. Antibodies against Proliferative Cell Nuclear Antigen (PCNA, Minichromosome Maintenance Complex 2 (MCM2, Bromodeoxyuridine (BrdU and phosphorylated Histone H3 (pH3 distinguished proliferating cells at various stages of the cell cycle. SOX9, localized to the stem/progenitor cells zone, while HOPX was restricted to the +4/'reserve' stem cell zone. Immunostaining also identified major differentiated lineages. Goblet cells were identified by Mucin 2 (MUC2; enteroendocrine cells by Chromogranin A (CGA, Gastrin and Somatostatin; and absorptive enterocytes by carbonic anhydrase II (CAII and sucrase isomaltase (SIM. Transmission electron microscopy demonstrated morphologic and sub-cellular characteristics of stem cell and differentiated intestinal epithelial cell types. Quantitative PCR gene expression analysis enabled identification of stem/progenitor cells, post mitotic cell lineages, and important growth and differentiation pathways. Additionally, a method for long-term culture of porcine crypts was developed. Biomarker characterization and development of IESC culture in the porcine model represents a foundation for translational studies of IESC-driven regeneration of the intestinal epithelium in physiology and disease.

  12. Transport of sennosides and sennidines from Cassia angustifolia and Cassia senna across Caco-2 monolayers--an in vitro model for intestinal absorption.

    Science.gov (United States)

    Waltenberger, B; Avula, B; Ganzera, M; Khan, I A; Stuppner, H; Khan, S I

    2008-05-01

    Laxative effects of Senna preparations are mainly mediated by rheinanthrone, a metabolite formed in the intestinal flora from dianthrones. Nevertheless, it was not clear whether dianthrones are bioavailable at all and contribute to the overall effects of this important medicinal plant. Using the Caco-2 human colonic cell line as an in vitro model of the human intestinal mucosal barrier, the bioavailability of dianthrones was studied in apical to basolateral (absorptive) and basolateral to apical (secretive) direction. Permeability coefficients (P(c)) and percent transport were calculated based on quantitations by HPLC. From the data obtained it was concluded that sennosides A and B, as well as their aglycones sennidine A and B are transported through the Caco-2 monolayers in a concentration-dependent manner and their transport was linear with time. The absorption in apical to basolateral direction was poor and P(c) values were comparable to mannitol. The transport was higher in the secretory direction, indicating a significant efflux (e.g. by efflux pumps) of the (poorly) absorbed compounds in the intestinal lumen again. Our findings support the general understanding that the laxative effects of Senna are explainable mainly by metabolites and not by the natively present dianthrones.

  13. Determination of Heavy Metals in Meat, Intestine, Liver, Eggs, and Chicken Using Neutron Activation Analysis and Atomic Absorption Spectrometry

    International Nuclear Information System (INIS)

    Surtipanti, S.; Suwirma, S.; Yumiarti, S.; Mellawati, Yune

    1995-01-01

    The elements As, Cd, Co, Cr, Fe, Hg, Ni, Pb, Sb, se and Zn in meat, intestine, and liver of cow and goat, as well as in broiler, local breed chicken and eggs have been determined using Neutron Activation Analysis and Atomic Absorption Spectrometry. Mercury was determined after being separated radiochemically. The results showed that concentration of the essential elements studied i.e. Cr, Cu, Fe, Zn, Co, and Ni were higher in liver and intestine than in the meat, but still in the normal range, while toxic elements As, Cd, and Pb were undetectable in all samples. (author). 8 refs., 6 tabs

  14. Determination of Heavy Metals in Meat, Intestine, Liver, Eggs, and Chicken Using Neutron Activation Analysis and Atomic Absorption Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Surtipanti, S; Suwirma, S; Yumiarti, S; Mellawati, Yune [National Atomic Energy Agency, Jakarta (Indonesia), Center for the Application of Isotopes Radiation

    1995-01-01

    The elements As, Cd, Co, Cr, Fe, Hg, Ni, Pb, Sb, se and Zn in meat, intestine, and liver of cow and goat, as well as in broiler, local breed chicken and eggs have been determined using Neutron Activation Analysis and Atomic Absorption Spectrometry. Mercury was determined after being separated radiochemically. The results showed that concentration of the essential elements studied i.e. Cr, Cu, Fe, Zn, Co, and Ni were higher in liver and intestine than in the meat, but still in the normal range, while toxic elements As, Cd, and Pb were undetectable in all samples. (author). 8 refs., 6 tabs.

  15. Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte

    2015-01-01

    Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic...... and predictive significance in CRC patients. This review provides an overview of the intestinal stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), B cell–specific Moloney murine leukemia virus insertion site 1 (BMI1), Musashi1 (MSI1), and sex-determining region y-box 9 (SOX9......) and their implications in human CRC. The exact roles of the intestinal stem cell markers in CRC development and progression remain unclear; however, high expression of these stem cell markers have a potential prognostic significance and might be implicated in chemotherapy resistance...

  16. Mechanisms of mercurial and arsenical inhibition of tyrosine absorption in intestine of the winter flounder Pseudopleuronectus americanus

    International Nuclear Information System (INIS)

    Musch, M.W.; Chauncey, B.; Schmid, E.C.; Kinne, R.K.; Goldstein, L.

    1990-01-01

    Effects of HgCl2 (100 microM) para-chloromercuribenzene sulfonate (PCMBS) (1 mM), and oxophenylarsine (OPA) (250 microM) were determined on (a) the rate of Na pump activity in intact winter flounder intestine; (b) activity of Na-K-ATPase in tissue homogenates; and (c) Na-dependent and Na-independent uptake of tyrosine in brush border membrane vesicles. Initial rate of uptake (influx) of 86Rb from the serosal solution of tissues mounted in Ussing chambers, a measure of Na-K-ATPase activity in the intact cell, was inhibited by all three agents with differing time courses. Rapidly permeating HgCl2 inhibited influx to the same degree as ouabain at 30 min, whereas the effects of PCMBS and OPA required 90 min. Cell potassium was also measured as an indirect indicator of ATPase activity and cell membrane permeability. All three agents decreased cell K, although effects on cell K lagged behind those for inhibition of the ATPase. At the concentrations used in the Ussing chamber (or at one-tenth concentration), all agents completely inhibited Na-K-ATPase activity in enzyme assays performed with tissue homogenates. In contrast, only HgCl2 decreased Na-dependent uptake of tyrosine by brush border membrane vesicles. These results suggest that mercurial and arsenical effects on tyrosine absorption are due to inhibition of the Na-K-ATPase thus decreasing the driving force for the cellular uptake by the Na-tyrosine cotransport system. Direct effects on Na-tyrosine cotransport may play a role in the inhibition observed with HgCl2, but not for PCMBS or OPA

  17. Interpreting heterogeneity in intestinal tuft cell structure and function.

    Science.gov (United States)

    Banerjee, Amrita; McKinley, Eliot T; von Moltke, Jakob; Coffey, Robert J; Lau, Ken S

    2018-05-01

    Intestinal tuft cells are a morphologically unique cell type, best characterized by striking microvilli that form an apical tuft. These cells represent approximately 0.5% of gut epithelial cells depending on location. While they are known to express chemosensory receptors, their function has remained unclear. Recently, numerous groups have revealed startling insights into intestinal tuft cell biology. Here, we review the latest developments in understanding this peculiar cell type's structure and function. Recent advances in volumetric microscopy have begun to elucidate tuft cell ultrastructure with respect to its cellular neighbors. Moreover, single-cell approaches have revealed greater diversity in the tuft cell population than previously appreciated and uncovered novel markers to characterize this heterogeneity. Finally, advanced model systems have revealed tuft cells' roles in mucosal healing and orchestrating type 2 immunity against eukaryotic infection. While much remains unknown about intestinal tuft cells, these critical advances have illuminated the physiological importance of these previously understudied cells and provided experimentally tractable tools to interrogate this rare cell population. Tuft cells act as luminal sensors, linking the luminal microbiome to the host immune system, which may make them a potent clinical target for modulating host response to a variety of acute or chronic immune-driven conditions.

  18. TRAPping telomerase within the intestinal stem cell niche

    OpenAIRE

    Pech, Matthew F; Artandi, Steven E

    2011-01-01

    Recent work from Hans Clevers' lab reveals high telomerase activity and telomere length in dividing LGR5-positive intestinal stem cells. They further report random chromosome segregation and thus challenge the ‘immortal strand' hypothesis at least for this stem cell population.

  19. Bone Marrow Derivation of Interstitial Cells of Cajal in Small Intestine Following Intestinal Injury

    Directory of Open Access Journals (Sweden)

    Dengqun Liu

    2010-01-01

    Full Text Available Interstitial cells of Cajal (ICCs in gastrointestinal tract are specialized cells serving as pacemaker cells. The origin of ICCs is currently not fully characterized. In this work, we aimed to study whether bone marrow-derived cells (BMDCs could contribute to the origin of ICCs in the muscular plexus of small intestine using GFP-C57BL/6 chimeric mice.Engraftment of BMDCs in the intestine was investigated for GFP expression. GFP positive bone marrow mononuclear cells reached a proportion of 95.65%±3.72% at different times in chimerism. Donor-derived cells distributed widely in all the layers of the gastrointestinal tract. There were GFP positive BMDCs in the myenteric plexus, which resembled characteristics of ICCs, including myenteric location, c-Kit positive staining, and ramified morphology. Donor-derived ICCs in the myenteric plexus contributed to a percentage ranging 9.25%±4.9% of all the ICCs in the myenteric plexus. In conclusion, here we described that donor-derived BMDCs might differentiate into gastrointestinal ICCs after radiation injury, which provided an alternative source for the origin of the ICCs in the muscular plexus of adult intestine. These results further identified the plasticity of BMDCs and indicated therapeutic implications of BMDCs for the gastrointestinal dysmotility caused by ICCs disorders.

  20. Techniques and problems in studying intestinal absorption with radioactive isotopes in children

    International Nuclear Information System (INIS)

    James, W.P.T.; Waterlow, J.C.

    1976-01-01

    Radioactive isotopes give substantial promise for assisting the study of gastrointestinal absorption in children in that they allow reduction or elimination of the collection of blood, urine and faeces specimens. These operations are particularly difficult and unreliable in infants, on whom greatest interest in paediatric gastroenterology is centred in the tropics. Here intestinal malabsorption is most commonly associated with malnutrition, lactose intolerance, gastroenteritis, parasitic infestation and iron-deficiency anaemia. Two general techniques that have been employed are whole-body counting and analyses of 14 CO 2 exhaled in the breath after the feeding of 14 C-labelled nutrients. The former is advantageous if radionuclides suitable for the test at hand exist; the latter may be hard to interpret because of problems in the distribution and metabolism of the nutrient and intermediary products. Proper selection and understanding of the tests is particularly important in paediatric work, where the use of radioactive tracer techniques is unacceptable merely for the convenience of the investigator. (author)

  1. Evaluation of Intestinal Absorption and Bioavailability of a Bergenin-Phospholipid Complex Solid Dispersion in Rats.

    Science.gov (United States)

    Gao, Haoshi; Wei, Yue; Xi, Long; Sun, Yuanyuan; Zhang, Tianhong

    2018-05-01

    Bergenin (BN) is a Biopharmaceutics Classification System class IV (BCS IV) drug with poor hydrophilicity and lipophilicity and is potentially eliminated by the efflux function of P-glycoprotein (P-gp). These factors may explain its low oral bioavailability. In the present study, a BN-phospholipid complex solid dispersion (BNPC-SD) was prepared by solvent evaporation and characterized based on differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, infrared diffraction, solubility, octanol-water partition coefficient, and in vitro dissolution. To investigate how P-gp can inhibit BN absorption in vivo, the P-gp inhibitor verapamil was co-administered with BNPC-SD to Sprague Dawley rats. By in situ single-pass intestinal perfusion, the membrane permeability of BN from BNPC-SD was higher than that of BN given alone and was improved further by co-administered verapamil. A pharmacokinetics study was done in Sprague Dawley rats, with plasma BN levels estimated by high-performance liquid chromatography. C max and AUC 0 → t values for BN were significantly higher for BNPC-SD than for BN given alone and were increased further by verapamil. Thus, the relative oral bioavailability of BNPC-SD as well as BNPC-SD co-administered with verapamil was 156.33 and 202.46%, respectively, compared with the value for BN given alone. These results showed that BNPC-SD can increase the oral bioavailability of BCS IV drugs.

  2. Radioprotection of intestinal crypt cells by cox-inhibitors

    International Nuclear Information System (INIS)

    Bisnar, Paul O.; Dones, Rosa Angela S.A.; Serna, Paulene-Ver A.; Deocaris, Chester C.; Guttierez, Kalangitan V.; Deocaris, Custer C.

    2006-01-01

    The regulation of tissue homeostasis in the gastrointestinal epithelium after epithelial injury focuses on the prostaglandins(PGs) as its major mediators. The two cyclooxygenase isoforms, cox-1 and cox-2, catalyze synthesis of PGs. Cox-1 is the predominant cyclooxygenase isoform found in the normal intestine. In contrast, cox-2 is present at low levels in normal intestine but is elevated at sites of inflammation, and in adenomas and carcinomas. To study the effects of various commercially-available cox-inhibitors (Ketorolac: cox-1 selective; Celecoxib: cox-2 selective; and Indocid: cox-1/2 non-selective), we determine mouse crypt epithelial cell fate after genotoxic injury with whole-body gamma-ray exposure at 15 Gy. Intestinal tissues of mice treated with cox-2 inhibitors that showed invariable apoptotic event, however, have increased occurrence of regenerating cells. Our results suggest a potential application of cox-2 selective inhibitors as radioprotective agent for normal cells after radiotherapy. (Author)

  3. Wnt control of stem cells and differentiation in the intestinal epithelium

    International Nuclear Information System (INIS)

    Pinto, Daniel; Clevers, Hans

    2005-01-01

    The intestinal epithelium represents a very attractive experimental model for the study of integrated key cellular processes such as proliferation and differentiation. The tissue is subjected to a rapid and perpetual self-renewal along the crypt-villus axis. Renewal requires division of multipotent stem cells, still to be morphologically identified and isolated, followed by transit amplification, and differentiation of daughter cells into specialized absorptive and secretory cells. Our understanding of the crucial role played by the Wnt/β-catenin signaling pathway in controlling the fine balance between cell proliferation and differentiation in the gut has been significantly enhanced in recent years. Mutations in some of its components irreversibly lead to carcinogenesis in humans and in mice. Here, we discuss recent advances related to the Wnt/β-catenin signaling pathway in regulating intestinal stem cells, homeostasis, and cancer. We emphasize how Wnt signaling is able to maintain a stem cell/progenitor phenotype in normal intestinal crypts, and to impose a very similar phenotype onto colorectal adenomas

  4. Homing of immune cells: role in homeostasis and intestinal inflammation.

    Science.gov (United States)

    Hart, Ailsa L; Ng, Siew C; Mann, Elizabeth; Al-Hassi, Hafid Omar; Bernardo, David; Knight, Stella C

    2010-11-01

    Rather like a satellite navigation system directing a vehicle to a particular destination defined by post-code, immune cells have homing molecules or "immune post-codes" enabling them to be recruited to specific organs, such as the intestine or skin. An efficient system would be designed such that the site of entry of an antigen influences the homing of effector T cells back to the appropriate organ. For example, to mount an immune response against an intestinal pathogen, T cells with a propensity to home to the gut to clear the infection would be induced. In health, there is such a sophisticated and finely tuned system in operation, enabling an appropriate balance of immune activity in different anatomical compartments. In disease states such as inflammatory bowel disease (IBD), which is characterized by intestinal inflammation and often an inflammatory process involving other organs such as skin, joints, liver, and eye, there is accumulating evidence that there is malfunction of this immune cell trafficking system. The clinical importance of dysregulated immune cell trafficking in IBD is reflected in recently proven efficacious therapies that target trafficking pathways such as natalizumab, an α4 integrin antibody, and Traficet-EN, a chemokine receptor-9 (CCR9) antagonist. Here we review the mechanisms involved in the homing of immune cells to different tissues, in particular the intestine, and focus on alterations in immune cell homing pathways in IBD. Unraveling the mechanisms underlying the immune post-code system would assist in achieving the goal of tissue-specific immunotherapy.

  5. Synthesis and Physicochemical Evaluation of Entecavir-Fatty Acid Conjugates in Reducing Food Effect on Intestinal Absorption

    Directory of Open Access Journals (Sweden)

    Hyuck Jun Jung

    2018-03-01

    Full Text Available The oral bioavailability of entecavir (EV, an anti-viral agent commonly prescribed to treat hepatitis B infections, is drastically reduced under a post-prandial state. This is primarily due to its low permeability in the gastrointestinal tract. To reduce the food effect on the intestinal absorption of the nucleotide analogue, four lipidic prodrugs were synthesized via the esterification of the primary alcohol of EV with fatty acids (hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid. EV-3-dodecanoate (or EV-C12 exhibited high solubility in a fed state simulated intestinal fluid (78.8 μg/mL, with the acceptable calculated logP value (3.62 and the lowest hydrolysis rate (22.5% for 12 h in simulated gastric fluid, pH 1.2. Therefore, it was chosen as a candidate to improve intestinal absorption of EV, especially under a fed state condition. Physical characterization using scanning electron microscopy, a differential scanning calorimeter, and X-ray powder diffraction revealed that EV-C12 had a rectangular-shaped crystalline form, with a melting point of about 170 °C. In a release test in biorelevant media, such as fasted and fed state-simulated intestinal and/or gastric fluid, more than 90% of the prodrug was released within 2 h in all media tested. These data suggest that this lipidic prodrug might have the potential to alleviate the negative food effect on the intestinal absorption of EV with increased therapeutic efficacy and patient compliance.

  6. 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

  7. Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis.

    Science.gov (United States)

    Hasebe, Takashi; Fujimoto, Kenta; Kajita, Mitsuko; Fu, Liezhen; Shi, Yun-Bo; Ishizuya-Oka, Atsuko

    2017-04-01

    In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are removed by apoptosis, and the adult epithelial stem (AE) cells appear concomitantly. They proliferate and differentiate to form the adult epithelium (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by regulating the expression of various genes including Notch receptor. To study the role of Notch signaling, we have analyzed the expression of its components, including the ligands (DLL and Jag), receptor (Notch), and targets (Hairy), in the metamorphosing intestine by real-time reverse transcription-polymerase chain reaction and in situ hybridization or immunohistochemistry. We show that they are up-regulated during both natural and TH-induced metamorphosis in a tissue-specific manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover, up-regulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a γ-secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH-induced up-regulation of LGR5, an adult intestinal stem cell marker, was suppressed by GSI treatment. Our results suggest that Notch signaling plays a role in stem cell development by regulating the expression of Hairy genes during intestinal remodeling. Furthermore, we show with organ culture experiments that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory cells and reduction of absorptive cells. Our findings here thus provide evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028-1039. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  8. The Effects of Dietary Calcium and/or Iron Deficiency upon Murine Intestinal Calcium Binding Protein Activity and Calcium Absorption

    OpenAIRE

    McDonald, Catherine M.

    1980-01-01

    Iron deficiency has been shown to impair calcium absorption, leading to decreased bone mass. Vitamin D3-dependent calcium binding protein (CaBP) has been demonstrated to be necessary for the active transport of calcium in the intestine of numerous species. Iron deficiency might affect the activity of the calcium binding protein. Four experimental diets were formulated as follows: Diet 1, iron adequate, calcium adequate; Diet 2, iron deficient, calcium adequate; Diet 3, iron adequate, calci...

  9. PTHrP regulates water absorption and aquaporin expression in the intestine of the marine sea bream (Sparus aurata, L.).

    Science.gov (United States)

    Carvalho, Edison S M; Gregório, Sílvia F; Canário, Adelino V M; Power, Deborah M; Fuentes, Juan

    2015-03-01

    Water ingestion by drinking is fundamental for ion homeostasis in marine fish. However, the fluid ingested requires processing to allow net water absorption in the intestine. The formation of luminal carbonate aggregates impacts on calcium homeostasis and requires epithelial HCO3(-) secretion to enable water absorption. In light of its endocrine importance in calcium handling and the indication of involvement in HCO3(-) secretion the present study was designed to expose the role of the parathyroid hormone-related protein (PTHrP) in HCO3(-) secretion, water absorption and the regulation of aqp1 gene expression in the anterior intestine of the sea bream. HCO3(-) secretion rapidly decreased when PTHrP(1-34) was added to anterior intestine of the sea bream mounted in Ussing chambers. The effect achieved a maximum inhibition of 60% of basal secretion rates, showing a threshold effective dose of 0.1 ng ml(-1) compatible with reported plasma values of PTHrP. When applied in combination with the adenylate cyclase inhibitor (SQ 22.536, 100 μmol l(-1)) or the phospholipase C inhibitor (U73122, 10 μmol l(-1)) the effect of PTHrP(1-34) on HCO3(-) secretion was reduced by about 50% in both cases. In parallel, bulk water absorption measured in intestinal sacs was sensitive to inhibition by PTHrP. The inhibitory action conforms to a typical dose-response curve in the range of 0.1-1000 ng ml(-1), achieves a maximal effect of 60-65% inhibition from basal rates and shows threshold significant effects at hormone levels of 0.1 ng ml(-1). The action of PTHrP in water absorption was completely abolished in the presence of the adenylate cyclase inhibitor (SQ 22.536, 100 μmol l(-1)) and was insensitive to the phospholipase C inhibitor (U73122, 10 μmol l(-1)). In vivo injections of PTHrP(1-34) or the PTH/PTHrP receptor antagonist PTHrP(7-34) evoked respectively, a significant decrease or increase of aqp1ab, but not aqp1a. Overall the present results suggest that PTHrP acts as a key

  10. Orexins control intestinal glucose transport by distinct neuronal, endocrine and direct epithelial pathways. : Orexins regulate intestinal glucose absorption

    OpenAIRE

    Ducroc, Robert; Voisin, Thierry; El Firar, Aadil; Laburthe, Marc

    2007-01-01

    International audience; Objective : Orexins are neuropeptides involved in energy homeostasis. We investigated the effect of orexin A (OxA) and OxB on intestinal glucose transport in the rat. Research Design and Methods : Injection of orexins led to a decrease in the blood glucose level in OGTT. Effects of orexins on glucose entry were analysed in Ussing chamber using the Na+-dependent increase in short-circuit current to quantify jejunal glucose transport. Results & Conclusions : The rapid an...

  11. Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2

    NARCIS (Netherlands)

    Simmini, Salvatore; Bialecka, Monika; Huch, Meritxell; Kester, Lennart; van de Wetering, Marc; Sato, Toshiro; Beck, Felix; van Oudenaarden, Alexander; Clevers, Hans; Deschamps, Jacqueline

    2014-01-01

    The endodermal lining of the adult gastro-intestinal tract harbours stem cells that are responsible for the day-to-day regeneration of the epithelium. Stem cells residing in the pyloric glands of the stomach and in the small intestinal crypts differ in their differentiation programme and in the gene

  12. Fusion of intestinal epithelial cells with bone marrow derived cells is dispensable for tissue homeostasis

    NARCIS (Netherlands)

    de Jong, Joan H.; Rodermond, Hans M.; Zimberlin, Cheryl D.; Lascano, Valeria; de Sousa E Melo, Felipe; Richel, Dick J.; Medema, Jan Paul; Vermeulen, Louis

    2012-01-01

    The epithelial lining of the intestine is characterized by an immense cellular turn-over ascertaining an extensive regenerative capacity. Multiple reports suggest that besides the local intestinal stem cell pool, circulating cells of bone marrow origin (BMDCs) contribute to this process by fusing

  13. Effect of pH, buffer concentration and buffer composition on the absorption of theophylline from the small intestine of the rat

    NARCIS (Netherlands)

    Blaey, C.J. de; Schurgers, N.

    1984-01-01

    The absorption of theophylline from the small intestine of the rat was investigated using buffer solutions of different pH (3.0–9.2), composition and concentration. The technique used, encloses luminal perfusion of an intestinal loop with collection of the blood draining the perfused loop, which

  14. 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

  15. Intestinal absorption and excretion of zinc in streptozotocin-diabetic rats as affected by dietary zinc and protein

    International Nuclear Information System (INIS)

    Johnson, W.T.; Canfield, W.K.

    1985-01-01

    65 Zn was used to examine the effects of dietary zinc and protein on true zinc absorption and intestinal excretion of endogenous zinc by an isotope dilution technique in streptozotocin-diabetic and control rats. Four groups each of diabetic and control rats were fed diets containing 20 ppm Zn, 20% egg white protein (HMHP); 20 ppm Zn, 10% egg white protein (HMLP); 10 ppm Zn, 20% egg white protein (LMHP); and 10 ppm Zn, 10% egg white protein (LMLP). Measurement of zinc balance was begun 9 d after an i.m. injection of 65 Zn. True zinc absorption and the contribution of endogenous zinc to fecal zinc excretion were calculated from the isotopically labeled and unlabeled zinc in the feces, duodenum and kidney. Results from the isotope dilution study indicated that diabetic rats, but not control rats, absorbed more zinc from 20 ppm zinc diets than from 10ppm zinc diets and that all rats absorbed more zinc from 20% protein diets than from 10% protein diets. Furthermore, all rats excreted more endogenous zinc from their intestines when dietary zinc and protein levels resulted in greater zinc absorption. In diabetic and control rats, consuming equivalent amounts of zinc, the amount of zinc absorbed was not significantly different, but the amount of zinc excreted by the intestine was less in the diabetic rats. Decreased intestinal excretion of endogenous zinc may be a homeostatic response to the increased urinary excretion of endogenous zinc in the diabetic rats and may also lead to the elevated zinc concentrations observed in some organs of the diabetic rats

  16. Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells.

    Science.gov (United States)

    Moorefield, Emily C; Andres, Sarah F; Blue, R Eric; Van Landeghem, Laurianne; Mah, Amanda T; Santoro, M Agostina; Ding, Shengli

    2017-08-29

    Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFP Low ), activatable reserve IESC and enteroendocrine cells (Sox9-EGFP High ), Sox9-EGFP Sublow progenitors, and Sox9-EGFP Negative differentiated lineages. Crypt-villus morphology, cellular composition and apoptosis were measured by histology. IESC function was assessed by crypt culture, and proliferation by flow cytometry and histology. Main findings were confirmed in Lgr5-EGFP and Lgr5-LacZ mice. Aging-associated gene expression changes were analyzed by Fluidigm mRNA profiling. Crypts culture from old mice yielded fewer and less complex enteroids. Histology revealed increased villus height and Paneth cells per crypt in old mice. Old mice showed increased numbers and hyperproliferation of Sox9-EGFP Low IESC and Sox9-EGFP High cells. Cleaved caspase-3 staining demonstrated increased apoptotic cells in crypts and villi of old mice. Gene expression profiling revealed aging-associated changes in mRNAs associated with cell cycle, oxidative stress and apoptosis specifically in IESC. These findings provide new, direct evidence for aging associated IESC dysfunction, and define potential biomarkers and targets for translational studies to assess and maintain IESC function during aging.

  17. Intestinal stem cells in the adult Drosophila midgut

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Huaqi, E-mail: Huaqi.Jiang@UTSouthwestern.edu [Department of Developmental Biology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX, 75235 (United States); Edgar, Bruce A., E-mail: b.edgar@dkfz.de [ZMBH-DKFZ Alliance, Im Neuenheimer Feld 282, D-69120 Heidelberg (Germany); Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109 (United States)

    2011-11-15

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: Black-Right-Pointing-Pointer The homeostasis and regeneration of adult fly midguts are mediated by ISCs. Black-Right-Pointing-Pointer Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). Black-Right-Pointing-Pointer EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. Black-Right-Pointing-Pointer Notch signaling regulates ISC self-renewal and differentiation.

  18. Esterification of xanthophylls by human intestinal Caco-2 cells.

    Science.gov (United States)

    Sugawara, Tatsuya; Yamashita, Kyoko; Asai, Akira; Nagao, Akihiko; Shiraishi, Tomotaka; Imai, Ichiro; Hirata, Takashi

    2009-03-15

    We recently found that peridinin, which is uniquely present in dinoflagellates, reduced cell viability by inducing apoptosis in human colon cancer cells. Peridinin is also found in edible clams and oysters because the major food sources of those shellfish are phytoplanktons such as dinoflagellates. Little is known, however, about the fate of dietary peridinin and its biological activities in mammals. The aim of the present study was to investigate the enzymatic esterification of xanthophylls, especially peridinin which is uniquely present in dinoflagellates, using differentiated cultures of Caco-2 human intestinal cells. We found that peridinin is converted to peridininol and its fatty acid esters in differentiated Caco-2 cells treated with 5mumol/L peridinin solubilized with mixed micelles. The cell homogenate was also able to deacetylate peridinin and to esterify peridininol. Other xanthophylls, such as fucoxanthin, astaxanthin and zeaxanthin, were also esterified, but at relatively lower rates than peridinin. In this study, we found the enzymatic esterification of xanthophylls in mammalian intestinal cells for the first time. Our results suggest that the esterification of xanthophylls in intestinal cells is dependent on their polarity.

  19. File list: Oth.Dig.20.AllAg.Intestinal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Unc.Dig.50.AllAg.Intestinal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Oth.Dig.10.AllAg.Intestinal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. Insulin resistance in vascular endothelial cells promotes intestinal tumour formation

    DEFF Research Database (Denmark)

    Wang, X; Häring, M-F; Rathjen, Thomas

    2017-01-01

    in vascular endothelial cells. Strikingly, these mice had 42% more intestinal tumours than controls, no change in tumour angiogenesis, but increased expression of vascular cell adhesion molecule-1 (VCAM-1) in primary culture of tumour endothelial cells. Insulin decreased VCAM-1 expression and leukocyte...... adhesion in quiescent tumour endothelial cells with intact insulin receptors and partly prevented increases in VCAM-1 and leukocyte adhesion after treatment with tumour necrosis factor-α. Knockout of insulin receptors in endothelial cells also increased leukocyte adhesion in mesenteric venules...

  3. Stem cells and cancer of the stomach and intestine.

    Science.gov (United States)

    Vries, Robert G J; Huch, Meritxell; Clevers, Hans

    2010-10-01

    Cancer in the 21st century has become the number one cause of death in developed countries. Although much progress has been made in improving patient survival, tumour relapse is one of the important causes of cancer treatment failure. An early observation in the study of cancer was the heterogeneity of tumours. Traditionally, this was explained by a combination of genomic instability of tumours and micro environmental factors leading to diverse phenotypical characteristics. It was assumed that cells in a tumour have an equal capacity to propagate the cancer. This model is currently known as the stochastic model. Recently, the Cancer stem cell model has been proposed to explain the heterogeneity of a tumour and its progression. According to this model, the heterogeneity of tumours is the result of aberrant differentiation of tumour cells into the cells of the tissue the tumour originated from. Tumours were suggested to contain stem cell-like cells, the cancer stem cells or tumour-initiating cells, which are uniquely capable of propagating a tumour much like normal stem cells fuel proliferation and differentiation in normal tissue. In this review we discuss the normal stem cell biology of the stomach and intestine followed by both the stochastic and cancer stem cell models in light of recent findings in the gastric and intestinal systems. The molecular pathways underlying normal and tumourigenic growth have been well studied, and recently the stem cells of the stomach and intestine have been identified. Furthermore, intestinal stem cells were identified as the cells-of-origin of colon cancer upon loss of the tumour suppressor APC. Lastly, several studies have proposed the positive identification of a cancer stem cell of human colon cancer. At the end we compare the cancer stem cell model and the stochastic model. We conclude that clonal evolution of tumour cells resulting from genetic mutations underlies tumour initiation and progression in both cancer models. This

  4. Intestinal bacteria and the regulation of immune cell homeostasis.

    Science.gov (United States)

    Hill, David A; Artis, David

    2010-01-01

    The human intestine is colonized by an estimated 100 trillion bacteria. Some of these bacteria are essential for normal physiology, whereas others have been implicated in the pathogenesis of multiple inflammatory diseases including IBD and asthma. This review examines the influence of signals from intestinal bacteria on the homeostasis of the mammalian immune system in the context of health and disease. We review the bacterial composition of the mammalian intestine, known bacterial-derived immunoregulatory molecules, and the mammalian innate immune receptors that recognize them. We discuss the influence of bacterial-derived signals on immune cell function and the mechanisms by which these signals modulate the development and progression of inflammatory disease. We conclude with an examination of successes and future challenges in using bacterial communities or their products in the prevention or treatment of human disease.

  5. Differentiation-dependent activation of the human intestinal alkaline phosphatase promoter by HNF-4 in intestinal cells

    DEFF Research Database (Denmark)

    Olsen, Line; Bressendorff, Simon; Troelsen, Jesper T

    2005-01-01

    The intestinal alkaline phosphatase gene (ALPI) encodes a digestive brush-border enzyme, which is highly upregulated during small intestinal epithelial cell differentiation. To identify new putative promoter motifs responsible for the regulation of ALPI expression during differentiation of the en...

  6. Testing the absorption of the extracts of Coreopsis tinctoria Nutt. in the intestinal canal in rats using an Ussing chamber.

    Science.gov (United States)

    Wang, Jian; Aierken, Guzhalinuer; Li, Xinxia; Li, Linlin; Mao, Xinmin

    2016-06-20

    Coreopsis tinctoria Nutt mainly distributed in Hetian region of Xinjiang at an altitude of 3000m, which is used as Uyghur traditional medicine because of its clearing heat, promoting circulation and removing toxicity and antihypertension, ect. effect. This research was to study the four ingredients in the extracts of Coreopsis tinctoria Nutt. that are absorbed in different intestinal segments in rats to lay the foundation for further study on the effective constituents, tissue distribution, metabolism, and spectrum-effect relationships of these extracts. High, medium, and low concentrations were prepared according to their pharmacological effects. Quantitative analysis multi-components by single marker was used to test the cumulative absorption volume Q, absorption rate constant Ka, and apparent permeability coefficient Papp of the four main ingredients in C. tinctoria Nutt. extract in different intestinal segments in rats using a Ussing chamber model and high-performance liquid chromatography. The Papp of chlorogenic acid and flavanomarein in the duodenum, jejunum, ileum, and colon were 1.0×10(-6) to 10×10(-6)cms(-1). Papp of marein in the duodenum and jejunum was <1.0×10(-6), and was 1.0×10(-6) to 10×10(-6)cms(-1) in the ileum and colon. Papp of 3,5-O-dicaffeoylquinic acid in the duodenum was <1.0×10(-6)cms(-1), while it was 1.0×(1)0(-6) to 10×10(-6)cms(-1) in the jejunum, ileum, and colon. All four chemical components of the plant extract can be absorbed by the intestinal canal of rats, which conforms to zero-order absorption; the ileum presented the best absorption. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Wnt, RSPO and Hippo Signalling in the Intestine and Intestinal Stem Cells.

    Science.gov (United States)

    Kriz, Vitezslav; Korinek, Vladimir

    2018-01-08

    In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling. There is growing evidence for multiple crosstalk between Hippo and Wnt/β-catenin signalling. In the ON state, Hippo signalling results in serine/threonine phosphorylation of Yes-associated protein (YAP1) and tafazzin (TAZ), promoting formation of the β-catenin destruction complex. In contrast, YAP1 or TAZ dephosphorylation (and YAP1 methylation) results in β-catenin destruction complex deactivation and β-catenin nuclear localization. In the Hippo OFF state, YAP1 and TAZ are engaged with the nuclear β-catenin and participate in the β-catenin-dependent transcription program. Interestingly, YAP1/TAZ are dispensable for intestinal homeostasis; however, upon Wnt pathway hyperactivation, the proteins together with TEA domain (TEAD) transcription factors drive the transcriptional program essential for intestinal cell transformation. In addition, in many CRC cells, YAP1 phosphorylation by YES proto-oncogene 1 tyrosine kinase (YES1) leads to the formation of a transcriptional complex that includes YAP1, β-catenin and T-box 5 (TBX5) DNA-binding protein. YAP1/β-catenin/T-box 5-mediated transcription is necessary for CRC cell proliferation and survival. Interestingly, dishevelled (DVL) appears to be an important mediator involved in both Wnt and Hippo (YAP1/TAZ) signalling and some of the DVL functions were assigned to the nuclear DVL

  8. Coating with luminal gut-constituents alters adherence of nanoparticles to intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Heike Sinnecker

    2014-12-01

    Full Text Available Background: Anthropogenic nanoparticles (NPs have found their way into many goods of everyday life. Inhalation, ingestion and skin contact are potential routes for NPs to enter the body. In particular the digestive tract with its huge absorptive surface area provides a prime gateway for NP uptake. Considering that NPs are covered by luminal gut-constituents en route through the gastrointestinal tract, we wanted to know if such modifications have an influence on the interaction between NPs and enterocytes.Results: We investigated the consequences of a treatment with various luminal gut-constituents on the adherence of nanoparticles to intestinal epithelial cells. Carboxylated polystyrene particles 20, 100 and 200 nm in size represented our anthropogenic NPs, and differentiated Caco-2 cells served as model for mature enterocytes of the small intestine. Pretreatment with the proteins BSA and casein consistently reduced the adherence of all NPs to the cultured enterocytes, while incubation of NPs with meat extract had no obvious effect on particle adherence. In contrast, contact with intestinal fluid appeared to increase the particle-cell interaction of 20 and 100 nm NPs.Conclusion: Luminal gut-constituents may both attenuate and augment the adherence of NPs to cell surfaces. These effects appear to be dependent on the particle size as well as on the type of interacting protein. While some proteins will rather passivate particles towards cell attachment, possibly by increasing colloid stability or camouflaging attachment sites, certain components of intestinal fluid are capable to modify particle surfaces in such a way that interactions with cellular surface structures result in an increased binding.

  9. 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

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step...... not imply low intestinal permeability, as indicated by the BDDCS, merely low duodenal/jejunal permeability....... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...

  10. IRF8 dependent classical dendritic cells are essential for intestinal T cell homeostasis

    DEFF Research Database (Denmark)

    Luda, K.; Joeris, Thorsten; Persson, E. K.

    2016-01-01

    The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 dependent DCs have reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8ab+ andCD4+CD8......aa+ T cells; the latter requiring b8 integrin expression by migratory IRF8 dependent CD103+CD11b- DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI derived MLN DCs......, and inefficient T cell localization to the SI. Finally, mice with a DC deletion in IRF8 lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8...

  11. Dendritic Cells in the Gut: Interaction with Intestinal Helminths

    Directory of Open Access Journals (Sweden)

    Fela Mendlovic

    2010-01-01

    Full Text Available The mucosal environment in mammals is highly tolerogenic; however, after exposure to pathogens or danger signals, it is able to shift towards an inflammatory response. Dendritic cells (DCs orchestrate immune responses and are highly responsible, through the secretion of cytokines and expression of surface markers, for the outcome of such immune response. In particular, the DC subsets found in the intestine have specialized functions and interact with different immune as well as nonimmune cells. Intestinal helminths primarily induce Th2 responses where DCs have an important yet not completely understood role. In addition, this cross-talk results in the induction of regulatory T cells (T regs as a result of the homeostatic mucosal environment. This review highlights the importance of studying the particular relation “helminth-DC-milieu” in view of the significance that each of these factors plays. Elucidating the mechanisms that trigger Th2 responses may provide the understanding of how we might modulate inflammatory processes.

  12. Intestinal absorption, organ distribution, and urinary excretion of the rare sugar D-psicose

    Science.gov (United States)

    Tsukamoto, Ikuko; Hossain, Akram; Yamaguchi, Fuminori; Hirata, Yuko; Dong, Youyi; Kamitori, Kazuyo; Sui, Li; Nonaka, Machiko; Ueno, Masaki; Nishimoto, Kazuyuki; Suda, Hirofumi; Morimoto, Kenji; Shimonishi, Tsuyoshi; Saito, Madoka; Song, Tao; Konishi, Ryoji; Tokuda, Masaaki

    2014-01-01

    Background The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia. Methods This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of 14C-labeled D-psicose or glucose intravenously to C3H mice. Results Following oral administration, D-psicose easily moved to blood. The maximum blood concentration (48.5±15.6 μg/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33% within 2 hours. Accumulation to organs was detected only in the liver. Following intravenous administration, blood concentration was decreased with the half-life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour. Similarly to the results obtained with oral administration, accumulation to organs was detected only in the liver. Seven days after the single-dose oral administration, the remaining amounts in the whole body were less than 1%. Autoradiography of mice showed results similar to those in rats. High signals of 14C-labeled D-psicose were observed in liver, kidney, and bladder. Interestingly, no accumulation of D-psicose was observed in the brain. Conclusion D-psicose was absorbed well after oral administration and eliminated rapidly after both oral and intravenous administrations, with short duration of action. The study provides valuable pharmacokinetic data for further drug development of D-psicose. Because the findings were mainly based on animal

  13. Development of Functional Microfold (M Cells from Intestinal Stem Cells in Primary Human Enteroids.

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    Joshua D Rouch

    Full Text Available Intestinal microfold (M cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs, and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting.Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium.Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2 in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells.Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an

  14. Absorption kinetics of vitamin E nanoemulsion and green tea microstructures by intestinal in situ single perfusion technique in rats.

    Science.gov (United States)

    Saratale, Rijuta Ganesh; Lee, Hee-Seok; Koo, Yong Eui; Saratale, Ganesh Dattatraya; Kim, Young Jun; Imm, Jee Young; Park, Yooheon

    2018-04-01

    The absorption kinetics of food ingredients such as nanoemulsified vitamin E and green tea microstructures were evaluated by the intestinal in situ single perfusion technique. Absorption rate, sub-acute oral toxicity and organ morphology in a rat model were examined. The intestinal in situ single perfusion technique and HPLC analysis were applied to investigate the absorption rate of selected materials by examining time-dependent changes in the serum levels of catechin and dl-α-tocopherol. The acute toxicity test and histopathological evaluation were applied to analyze the safety of microsized green tea and nanosized vitamin E in a rat model. Total serum dl-α-tocopherol levels significantly increased with nanosized vitamin E administration (PE until 90min after administration showed significantly increased absorption rate of serum dl-α-tocopherol levels at each time point (10min interval) (PE and microsized green tea did not show signs of acute toxicity or death after 14days of observation. In addition, macroscopic analysis showed that there were no changes in representative organ sections of rats following the oral administration of food-related nanoscale materials. We successfully demonstrated that using nanosized vitamin E increased absorption rate to a greater extent than normal food-related material, and these results occurs via safety analyses on food-related nanoscale materials for human consumption. These results could be useful for the design and development of novel nanoemulsified vitamin E and microsized green tea formulations that can overcome the problem of their bioavailability and improve their efficacy while still maintaining their essential therapeutic efficacies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Foxl1-Expressing Mesenchymal Cells Constitute the Intestinal Stem Cell NicheSummary

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    Reina Aoki

    2016-03-01

    Full Text Available Background & Aims: Intestinal epithelial stem cells that express leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5 and/or B cell specific Moloney murine leukemia virus integration site 1 (Bmi1 continuously replicate and generate differentiated cells throughout life. Previously, Paneth cells were suggested to constitute an epithelium-intrinsic niche that regulates the behavior of these stem cells. However, ablating Paneth cells has no effect on the maintenance of functional stem cells. Here, we show definitively that a small subset of mesenchymal subepithelial cells expressing the winged-helix transcription factor forkhead box l1 (Foxl1 are a critical component of the intestinal stem cell niche. Methods: We genetically ablated Foxl1+ mesenchymal cells in adult mice using 2 separate models by expressing either the human or simian diphtheria toxin receptor under Foxl1 promoter control. Conclusions: Killing Foxl1+ cells by diphtheria toxin administration led to an abrupt cessation of proliferation of both epithelial stem- and transit-amplifying progenitor cell populations that was associated with a loss of active Wnt signaling to the intestinal epithelium. Therefore, Foxl1-expressing mesenchymal cells constitute the fundamental niche for intestinal stem cells. Keywords: Intestinal Stem Cell Niche, Wnt, Mesenchyme

  16. Concise review: the yin and yang of intestinal (cancer) stem cells and their progenitors

    NARCIS (Netherlands)

    Stange, D.E.; Clevers, H.

    2013-01-01

    The intestine has developed over the last few years into a prime model system for adult stem cell research. Intestinal cells have an average lifetime of 5 days, moving within this time from the bottom of intestinal crypts to the top of villi. This rapid self-renewal capacity combined with an easy to

  17. Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation.

    Science.gov (United States)

    Peled, Jonathan U; Devlin, Sean M; Staffas, Anna; Lumish, Melissa; Khanin, Raya; Littmann, Eric R; Ling, Lilan; Kosuri, Satyajit; Maloy, Molly; Slingerland, John B; Ahr, Katya F; Porosnicu Rodriguez, Kori A; Shono, Yusuke; Slingerland, Ann E; Docampo, Melissa D; Sung, Anthony D; Weber, Daniela; Alousi, Amin M; Gyurkocza, Boglarka; Ponce, Doris M; Barker, Juliet N; Perales, Miguel-Angel; Giralt, Sergio A; Taur, Ying; Pamer, Eric G; Jenq, Robert R; van den Brink, Marcel R M

    2017-05-20

    Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.

  18. Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration.

    Science.gov (United States)

    Schall, K A; Holoyda, K A; Grant, C N; Levin, D E; Torres, E R; Maxwell, A; Pollack, H A; Moats, R A; Frey, M R; Darehzereshki, A; Al Alam, D; Lien, C; Grikscheit, T C

    2015-08-01

    Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation. Copyright © 2015 the American Physiological Society.

  19. Maltitol inhibits small intestinal glucose absorption and increases insulin mediated muscle glucose uptake ex vivo but not in normal and type 2 diabetic rats.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2017-02-01

    This study investigated the effects of maltitol on intestinal glucose absorption and muscle glucose uptake using ex vivo and in vivo experimental models. The ex vivo experiment was conducted in isolated jejunum and psoas muscle from normal rats. The in vivo study investigated the effects of a single bolus dose of maltitol on gastric emptying, intestinal glucose absorption and digesta transit in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in the presence of insulin but not in the absence of insulin. In contrast, maltitol did not significantly (p > 0.05) alter small intestinal glucose absorption or blood glucose levels as well as gastric emptying and digesta transit in normal or type 2 diabetic rats. The results suggest that maltitol may not be a suitable dietary supplement for anti-diabetic food and food products to improve glycemic control.

  20. The Inside Story of Shigella Invasion of Intestinal Epithelial Cells

    Science.gov (United States)

    Carayol, Nathalie; Tran Van Nhieu, Guy

    2013-01-01

    As opposed to other invasive pathogens that reside into host cells in a parasitic mode, Shigella, the causative agent of bacillary dysentery, invades the colonic mucosa but does not penetrate further to survive into deeper tissues. Instead, Shigella invades, replicates, and disseminates within the colonic mucosa. Bacterial invasion and spreading in intestinal epithelium lead to the elicitation of inflammatory responses responsible for the tissue destruction and shedding in the environment for further infection of other hosts. In this article, we highlight specific features of the Shigella arsenal of virulence determinants injected by a type III secretion apparatus (T3SA) that point to the targeting of intestinal epithelial cells as a discrete route of invasion during the initial event of the infectious process. PMID:24086068

  1. Absorção de anticorpos do colostro em bezerros: I. Estudo no intestino delgado proximal Colostral antibodies absorption in dairy calves: I. Proximal small intestine study

    Directory of Open Access Journals (Sweden)

    Rosana Bessi

    2002-11-01

    Full Text Available Com o objetivo de estudar a morfologia e determinar a localização da enzima fosfatase ácida na região anterior do intestino delgado, do nascimento ao fechamento intestinal, foram coletadas amostras de 15 bezerros machos em três idades: ao nascer sem que houvesse a ingestão de colostro; três horas após a ingestão da primeira refeição de colostro e aos três dias de idade. Observou-se a presença de células vacuoladas do duodeno ao jejuno médio no recém-nascido, preenchidas por material absorvido após a ingestão de colostro. Foram verificadas mudanças nas características morfológicas aos três dias de idade, com o início da detecção de reação da fosfatase ácida em lisossomos, indicando ação enzimática sobre o material absorvido. A morfologia aos três dias de idade pode representar o diferente estádio de maturação das células epiteliais do intestino delgado de bezerros, indicando que o processo depende das características da primeira geração de células desta região do intestino.The objective of this study was to study the morphology and the localization of acid phosphatase at calves anterior small intestine, from birth to intestinal closure. Fifteen male dairy calves were used in this study, which were aged: unsuckled neonatal, three hours after colostrum ingestion and three days old. Vacuolated cells from duodenum to medium jejunum could be found in the newborn calf, which have shown absorbed material after colostrum ingestion. Changes at the morphological characteristics and the initiation of phosphatase acid reaction in lysosomes were observed in calves aged three days old. The three days old morphology can represent a different phase of epithelium cells maturation of calves small intestine indicating that the absorption process is dependent of the first generation of cells from this intestinal region.

  2. Lycopene reduces cholesterol absorption through the downregulation of Niemann-Pick C1-like 1 in Caco-2 cells.

    Science.gov (United States)

    Zou, Jun; Feng, Dan

    2015-11-01

    Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Tomato lycopene has been found to have a hypocholesterolemic effect, and the effect was considered to be related to inhibition of cholesterol synthesis. However, since plasma cholesterol levels are also influenced by the absorption of cholesterol in the gut, the present study is to investigate whether lycopene affects cholesterol absorption in the intestinal Caco-2 cells. The Caco-2 cells were pretreated with lycopene at different concentrations for 24 h and then incubated with radioactive micellar cholesterol for 2 h. The absorption of radioactive cholesterol was quantified by liquid scintillation. The expression of Niemann-Pick C1-like 1 (NPC1L1) and liver X receptor α (LXRα) was analyzed by Western blot and qPCR. We found that lycopene dose dependently inhibited cholesterol absorption and the expression of NPC1L1 protein and NPC1L1 mRNA. The inhibitory effects of lycopene on cholesterol absorption and NPC1L1 expression could be prevented by blockade of the LXRα pathway. This study provides the first evidence that lycopene inhibits cholesterol absorption in the intestinal cells and this inhibitory effect of lycopene is mediated, at least in part, by LXRα-NPC1L1 signaling pathway. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. 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.

  4. Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats

    NARCIS (Netherlands)

    M. Verburg (Melissa); I.B. Renes (Ingrid); H.P. Meijer; J.A. Taminiau; H.A. Büller (Hans); A.W.C. Einerhand (Sandra); J. Dekker (Jan)

    2000-01-01

    textabstractProliferation, differentiation, and cell death were studied in small intestinal and colonic epithelia of rats after treatment with methotrexate. Days 1-2 after treatment were characterized by decreased proliferation, increased apoptosis, and decreased numbers and depths

  5. Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.

    Science.gov (United States)

    Sugawara, Reiko; Lee, Eun-Jung; Jang, Min Seong; Jeun, Eun-Ji; Hong, Chun-Pyo; Kim, Jung-Hwan; Park, Areum; Yun, Chang Ho; Hong, Sung-Wook; Kim, You-Me; Seoh, Ju-Young; Jung, YunJae; Surh, Charles D; Miyasaka, Masayuki; Yang, Bo-Gie; Jang, Myoung Ho

    2016-04-04

    Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+)T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra. © 2016 Sugawara et al.

  6. Acoustic absorption behaviour of an open-celled aluminium foam

    International Nuclear Information System (INIS)

    Han Fusheng; Seiffert, Gary; Zhao Yuyuan; Gibbs, Barry

    2003-01-01

    Metal foams, especially close-celled foams, are generally regarded as poor sound absorbers. This paper studies the sound absorption behaviour of the open-celled Al foams manufactured by the infiltration process, and the mechanisms involved. The foams show a significant improvement in sound absorption compared with close-celled Al foams, because of their high flow resistance. The absorption performance can be further enhanced, especially at low frequencies, if the foam panel is backed by an appropriate air gap. Increasing the air-gap depth usually increases both the height and the width of the absorption peak and shifts the peak towards lower frequencies. The foam samples with the smallest pore size exhibit the best absorption capacities when there is no air gap, whereas those with medium pore sizes have the best overall performance when there is an air gap. The typical maximum absorption coefficient, noise reduction coefficient and half-width of the absorption peak are 0.96-0.99, 0.44-0.62 and 1500-3500 Hz, respectively. The sound dissipation mechanisms in the open-celled foams are principally viscous and thermal losses when there is no air-gap backing and predominantly Helmholtz resonant absorption when there is an air-gap backing

  7. Linking stem cell function and growth pattern of intestinal organoids.

    Science.gov (United States)

    Thalheim, Torsten; Quaas, Marianne; Herberg, Maria; Braumann, Ulf-Dietrich; Kerner, Christiane; Loeffler, Markus; Aust, Gabriela; Galle, Joerg

    2018-01-15

    Intestinal stem cells (ISCs) require well-defined signals from their environment in order to carry out their specific functions. Most of these signals are provided by neighboring cells that form a stem cell niche, whose shape and cellular composition self-organize. Major features of this self-organization can be studied in ISC-derived organoid culture. In this system, manipulation of essential pathways of stem cell maintenance and differentiation results in well-described growth phenotypes. We here provide an individual cell-based model of intestinal organoids that enables a mechanistic explanation of the observed growth phenotypes. In simulation studies of the 3D structure of expanding organoids, we investigate interdependences between Wnt- and Notch-signaling which control the shape of the stem cell niche and, thus, the growth pattern of the organoids. Similar to in vitro experiments, changes of pathway activities alter the cellular composition of the organoids and, thereby, affect their shape. Exogenous Wnt enforces transitions from branched into a cyst-like growth pattern; known to occur spontaneously during long term organoid expansion. Based on our simulation results, we predict that the cyst-like pattern is associated with biomechanical changes of the cells which assign them a growth advantage. The results suggest ongoing stem cell adaptation to in vitro conditions during long term expansion by stabilizing Wnt-activity. Our study exemplifies the potential of individual cell-based modeling in unraveling links between molecular stem cell regulation and 3D growth of tissues. This kind of modeling combines experimental results in the fields of stem cell biology and cell biomechanics constituting a prerequisite for a better understanding of tissue regeneration as well as developmental processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Notch lineages and activity in intestinal stem cells determined by a new set of knock-in mice.

    Directory of Open Access Journals (Sweden)

    Silvia Fre

    Full Text Available The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFP(SAT, demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues.

  9. The use of protein hydrolysate improves the protein intestinal absorption in undernourished mice infected with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Coutinho Eridan M.

    2002-01-01

    Full Text Available Patients residing in endemic areas for schistosomiasis in Brazil are usually undernourished and when they develop the hepatosplenic clinical form of the disease should usually receive hospital care, many of them being in need of nutritional rehabilitation before specific treatment can be undertaken. In the mouse model, investigations carried out in our laboratory detected a reduced aminoacid uptake in undernourished animals which is aggravated by a superimposed infection with Schistosoma mansoni. However, in well-nourished infected mice no dysfunction occurs. In this study, we tried to improve the absorptive intestinal performance of undernourished mice infected with S. mansoni by feeding them with hydrolysed casein instead of whole casein. The values obtained for the coefficient of protein intestinal absorption (cpia among well-nourished mice were above 90% (either hydrolysed or whole protein. In undernourished infected mice, however, the cpia improved significantly after feeding them with hydrolysed casein, animals reaching values close to those obtained in well-nourished infected mice.

  10. The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers

    NARCIS (Netherlands)

    Muñoz, Javier; Stange, Daniel E.; Schepers, Arnout G.; van de Wetering, Marc; Koo, Bon-Kyoung; Itzkovitz, Shalev; Volckmann, Richard; Kung, Kevin S.; Koster, Jan; Radulescu, Sorina; Myant, Kevin; Versteeg, Rogier; Sansom, Owen J.; van Es, Johan H.; Barker, Nick; van Oudenaarden, Alexander; Mohammed, Shabaz; Heck, Albert J. R.; Clevers, Hans

    2012-01-01

    Two types of stem cells are currently defined in small intestinal crypts: cycling crypt base columnar (CBC) cells and quiescent '+4' cells. Here, we combine transcriptomics with proteomics to define a definitive molecular signature for Lgr5(+) CBC cells. Transcriptional profiling of FACS-sorted

  11. Absorption of plant-incorporated nuclear fuel cycle elements from the gastro-intestinal tract

    International Nuclear Information System (INIS)

    Sullivan, M.F.; Garland, T.R.; Cataldo, D.A.; Schreckhise, R.G.

    1979-01-01

    Soybean plants (Glycine max cv Williams) grown hydroponically on solutions containing ammonium pertechnetate ( 95 Tcsup(m)O - 4 ) were fed to rats (omnivores) and guinea pigs (herbivores). Absorption of plant-incorporated technetium was compared with absorption of inorganic 95 Tcsup(m) from a gavaged solution or with absorption of 95 Tcsup(m) added to non-radioactive soybean tissues. In a second study absorption of plutonium from alfalfa (Medicago sativa cv Ladak) grown on soil amended with either 238 Pu nitrate or 238 Pu-DTPA was compared with absorption of gavaged 238 Pu solutions and 238 Pu mixed with non-radioactive alfalfa. Incorporation of 95 Tcsup(m) into soybean tissues resulted in decreased absorption by both animal species. In contrast, incorporation of 238 Pu in alfalfa resulted in an increased absorption when compared with controls that were administered inorganic 238 Pu. These results suggest that organic binding may alter, in either direction, absorption of nuclear fuel cycle elements. (author)

  12. P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Cuiping, E-mail: yangsophia76@hotmail.com; Zhang, Tianhong, E-mail: wdzth@sina.com; Li, Zheng, E-mail: lizh2524@126.com; Xu, Liang, E-mail: wj24998@163.com; Liu, Fei, E-mail: liufeipharm@163.com; Ruan, Jinxiu, E-mail: ruanjx1936@yahoo.com.cn; Liu, Keliang, E-mail: keliangliu55@126.com; Zhang, Zhenqing, E-mail: zhangzhenqingpharm@163.com

    2013-12-15

    Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10{sup −5} to 2.85 × 10{sup −5} cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C{sub max}) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC{sub 0–12} {sub h}) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C{sub max

  13. P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

    International Nuclear Information System (INIS)

    Yang, Cuiping; Zhang, Tianhong; Li, Zheng; Xu, Liang; Liu, Fei; Ruan, Jinxiu; Liu, Keliang; Zhang, Zhenqing

    2013-01-01

    Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10 −5 to 2.85 × 10 −5 cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C max ) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC 0–12 h ) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C max and AUC of aconitine. • P

  14. Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Colin R Lickwar

    2017-08-01

    Full Text Available The intestinal epithelium serves critical physiologic functions that are shared among all vertebrates. However, it is unknown how the transcriptional regulatory mechanisms underlying these functions have changed over the course of vertebrate evolution. We generated genome-wide mRNA and accessible chromatin data from adult intestinal epithelial cells (IECs in zebrafish, stickleback, mouse, and human species to determine if conserved IEC functions are achieved through common transcriptional regulation. We found evidence for substantial common regulation and conservation of gene expression regionally along the length of the intestine from fish to mammals and identified a core set of genes comprising a vertebrate IEC signature. We also identified transcriptional start sites and other putative regulatory regions that are differentially accessible in IECs in all 4 species. Although these sites rarely showed sequence conservation from fish to mammals, surprisingly, they drove highly conserved IEC expression in a zebrafish reporter assay. Common putative transcription factor binding sites (TFBS found at these sites in multiple species indicate that sequence conservation alone is insufficient to identify much of the functionally conserved IEC regulatory information. Among the rare, highly sequence-conserved, IEC-specific regulatory regions, we discovered an ancient enhancer upstream from her6/HES1 that is active in a distinct population of Notch-positive cells in the intestinal epithelium. Together, these results show how combining accessible chromatin and mRNA datasets with TFBS prediction and in vivo reporter assays can reveal tissue-specific regulatory information conserved across 420 million years of vertebrate evolution. We define an IEC transcriptional regulatory network that is shared between fish and mammals and establish an experimental platform for studying how evolutionarily distilled regulatory information commonly controls IEC development

  15. Action of cholera toxin in the intestinal epithelial cells

    International Nuclear Information System (INIS)

    Hyun, C.S.

    1982-01-01

    The primary event in the action of cholera toxin on the isolated chick intestinal epithelial cell is its interaction with the cell membrane. This involves a large number (17 million per cell) of high affinity binding sites which belong to a single class. Binding of biologically active 125 I-labeled toxin is rapid, temperature-dependent, reversible, and saturable over a wide range of concentrations and includes only a small contribution from nonspecific sites. A characteristic lag phase of 10 min occurs following the complete binding of toxin before any increase in cellular cAMP levels can be detected in the isolated cells. The response (elevation of cellular cAMP) of the enterocytes to cholera toxin is linear with time for 40-50 min and causes a six- to eight-fold increase over control levels at steady stae. cAMP and agents that increase cAMP production inhibit Cl - -independent Na + influx into the isolated enterocytes whereas chlorporomazine (CPZ) which completely abolishes toxin-induced elevation of cAMP both reverses and prevents the cAMP-mediated inhibition of Na + entry. Correlation between cellular cAMP levels and the magnitude of Na + influx into the enterocytes provides evidence for a cAMP-mediated control of intestinal Na + uptake, which may represent the mechanistic basis for the antiabsorptive effect of CT and Na + during induction of intestinal secretion. The effect of cAMP on Na + but no Cl - influx in our villus cell preparation can be partially explained in terms of a cAMP-regulated Na + /H + neutral exchange system

  16. Inhibition of EV71 by curcumin in intestinal epithelial cells.

    Science.gov (United States)

    Huang, Hsing-I; Chio, Chi-Chong; Lin, Jhao-Yin

    2018-01-01

    EV71 is a positive-sense single-stranded RNA virus that belongs to the Picornaviridae family. EV71 infection may cause various symptoms ranging from hand-foot-and-mouth disease to neurological pathological conditions such as aseptic meningitis, ataxia, and acute transverse myelitis. There is currently no effective treatment or vaccine available. Various compounds have been examined for their ability to restrict EV71 replication. However, most experiments have been performed in rhabdomyosarcoma or Vero cells. Since the gastrointestinal tract is the entry site for this pathogen, we anticipated that orally ingested agents may exert beneficial effects by decreasing virus replication in intestinal epithelial cells. In this study, curcumin (diferuloylmethane, C21H20O6), an active ingredient of turmeric (Curcuma longa Linn) with anti-cancer properties, was investigated for its anti-enterovirus activity. We demonstrate that curcumin treatment inhibits viral translation and increases host cell viability. Curcumin does not exert its anti-EV71 effects by modulating virus attachment or virus internal ribosome entry site (IRES) activity. Furthermore, curcumin-mediated regulation of mitogen-activated protein kinase (MAPK) signaling pathways is not involved. We found that protein kinase C delta (PKCδ) plays a role in virus translation in EV71-infected intestinal epithelial cells and that curcumin treatment decreases the phosphorylation of this enzyme. In addition, we show evidence that curcumin also limits viral translation in differentiated human intestinal epithelial cells. In summary, our data demonstrate the anti-EV71 properties of curcumin, suggesting that ingestion of this phytochemical may protect against enteroviral infections.

  17. Inhibition of EV71 by curcumin in intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Hsing-I Huang

    Full Text Available EV71 is a positive-sense single-stranded RNA virus that belongs to the Picornaviridae family. EV71 infection may cause various symptoms ranging from hand-foot-and-mouth disease to neurological pathological conditions such as aseptic meningitis, ataxia, and acute transverse myelitis. There is currently no effective treatment or vaccine available. Various compounds have been examined for their ability to restrict EV71 replication. However, most experiments have been performed in rhabdomyosarcoma or Vero cells. Since the gastrointestinal tract is the entry site for this pathogen, we anticipated that orally ingested agents may exert beneficial effects by decreasing virus replication in intestinal epithelial cells. In this study, curcumin (diferuloylmethane, C21H20O6, an active ingredient of turmeric (Curcuma longa Linn with anti-cancer properties, was investigated for its anti-enterovirus activity. We demonstrate that curcumin treatment inhibits viral translation and increases host cell viability. Curcumin does not exert its anti-EV71 effects by modulating virus attachment or virus internal ribosome entry site (IRES activity. Furthermore, curcumin-mediated regulation of mitogen-activated protein kinase (MAPK signaling pathways is not involved. We found that protein kinase C delta (PKCδ plays a role in virus translation in EV71-infected intestinal epithelial cells and that curcumin treatment decreases the phosphorylation of this enzyme. In addition, we show evidence that curcumin also limits viral translation in differentiated human intestinal epithelial cells. In summary, our data demonstrate the anti-EV71 properties of curcumin, suggesting that ingestion of this phytochemical may protect against enteroviral infections.

  18. Inhibition of EV71 by curcumin in intestinal epithelial cells

    Science.gov (United States)

    Chio, Chi-Chong; Lin, Jhao-Yin

    2018-01-01

    EV71 is a positive-sense single-stranded RNA virus that belongs to the Picornaviridae family. EV71 infection may cause various symptoms ranging from hand-foot-and-mouth disease to neurological pathological conditions such as aseptic meningitis, ataxia, and acute transverse myelitis. There is currently no effective treatment or vaccine available. Various compounds have been examined for their ability to restrict EV71 replication. However, most experiments have been performed in rhabdomyosarcoma or Vero cells. Since the gastrointestinal tract is the entry site for this pathogen, we anticipated that orally ingested agents may exert beneficial effects by decreasing virus replication in intestinal epithelial cells. In this study, curcumin (diferuloylmethane, C21H20O6), an active ingredient of turmeric (Curcuma longa Linn) with anti-cancer properties, was investigated for its anti-enterovirus activity. We demonstrate that curcumin treatment inhibits viral translation and increases host cell viability. Curcumin does not exert its anti-EV71 effects by modulating virus attachment or virus internal ribosome entry site (IRES) activity. Furthermore, curcumin-mediated regulation of mitogen-activated protein kinase (MAPK) signaling pathways is not involved. We found that protein kinase C delta (PKCδ) plays a role in virus translation in EV71-infected intestinal epithelial cells and that curcumin treatment decreases the phosphorylation of this enzyme. In addition, we show evidence that curcumin also limits viral translation in differentiated human intestinal epithelial cells. In summary, our data demonstrate the anti-EV71 properties of curcumin, suggesting that ingestion of this phytochemical may protect against enteroviral infections. PMID:29370243

  19. Intestinal cell proliferation following hyperthermia-radiation combinations

    International Nuclear Information System (INIS)

    Burholt, D.R.; Wilkinson, D.A.; Shrivastava, P.N.

    1987-01-01

    The present work is an investigation of the extent to which hyperthermia enhances x-ray induced inhibition of intestinal epithelial cell proliferation in mice. Hyperthermia was achieved by whole body immersion of anesthetized ice in a temperature controlled water bath (+-0.1 0 C). Post-treatment proliferative activity was monitored by determining the incorporation of /sup 3/H-TdR into intestinal crypt cells and by the counting of epithelial cell mitotic figures. Initial levels of cell kill were assessed by the microcolony crypt survival technique. All heat treatments were 41.5 0 C for 0.5h. Heat alone reduced the /sup 3/H-TdR incorporation to 50% of the control value by 2h post-treatment. This was followed by a return to control value by 10h and a slight hyperplasia at 24h. Heat either immediately before or after 2Gy abdominal field x-irradiation produced a prolonged period of depressed cell proliferation: /sup 3/H-TdR incorporation remained below control value for the first 24h. As the heat and radiation were separated in time from each other (up to 4h) the interaction between the two decreased. The development of thermotolerance was observed following the second and third treatment during either a heat-only or a heat-radiation multifraction treatments schedule with the treatment spaced 24h apart

  20. IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis.

    Science.gov (United States)

    Luda, Katarzyna M; Joeris, Thorsten; Persson, Emma K; Rivollier, Aymeric; Demiri, Mimoza; Sitnik, Katarzyna M; Pool, Lieneke; Holm, Jacob B; Melo-Gonzalez, Felipe; Richter, Lisa; Lambrecht, Bart N; Kristiansen, Karsten; Travis, Mark A; Svensson-Frej, Marcus; Kotarsky, Knut; Agace, William W

    2016-04-19

    The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8αβ(+) and CD4(+)CD8αα(+) T cells; the latter requiring β8 integrin expression by migratory IRF8 dependent CD103(+)CD11b(-) DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Contrasting effects of the stomach and small intestine of rats on copper absorption

    International Nuclear Information System (INIS)

    Fields, M.; Craft, N.; Lewis, C.; Holbrook, J.; Rose, A.; Reiser, S.; Smith, J.C.

    1986-01-01

    Since the severity of copper deficiency has been shown to be enhanced by feeding diets containing fructose but ameliorated by diets containing starch, we decided to investigate the effect of fructose or starch on copper absorption. As copper transport has been reported to occur also from the stomach, it was possible that copper absorption is inhibited by fructose already from that tissue. Under anesthesia, stomachs of 72 rats fed copper-deficient or supplemented diets containing fructose or starch were ligated prior to the oral administration of 64 Cu. Gastric absorption of 64 Cu was studied when the isotope was administered by gastric tube either in diet containing fructose or starch or in water. 64 Cu was not absorbed from the stomach regardless of the type of dietary treatment, copper status or whether the copper was administered either in diet or in water. In addition, the absorption of 64 Cu from a diet containing either fructose or starch or from a saline solution was studied using the isolated ligated duodenal loop. When 64 Cu was administered with dietary fructose 64 Cu retention and absorption were impaired when compared to starch. When 64 Cu was administered in saline solution, differences in retention and absorption between the four dietary groups disappeared. It is suggested that the requirements for copper rather than the decreased absorption of copper are responsible at least in part for the more pronounced severity of copper deficiency in rats fed fructose compared to those fed starch

  2. Absorção de anticorpos do colostro em bezerros: II. Estudo no intestino delgado distal Colostral antibodies absorption in calves: II. Distal small intestine

    Directory of Open Access Journals (Sweden)

    Rosana Bessi

    2002-11-01

    Full Text Available Com o objetivo de estudar a morfologia e determinar a localização da enzima fosfatase ácida na região distal do intestino delgado de bezerros, do nascimento ao fechamento intestinal, foram coletadas amostras de 15 animais machos em três idades: ao nascer sem que houvesse a ingestão de colostro; três horas após a ingestão da primeira refeição de colostro e aos três dias de idade. Observou-se, ao nascimento, a presença de um grande vacúolo, que dominava todo o citoplasma das células epiteliais do jejuno distal e íleo. Após a ingestão de colostro, verificou-se o acúmulo de material absorvido nesses vacúolos. Foi detectada a reação de fosfatase ácida nas células absortivas de bezerros recém-nascidos, antes e após a ingestão de colostro. Aos três dias de idade, uma nova população de células geralmente não vacuoladas, com sistema endocítico apical reduzido, foi observada recobrindo as vilosidades intestinais. Portanto, em bezerros a maturação do epitélio absortivo do intestino delgado distal pode iniciar-se com o aumento da atividade enzimática nos vacúolos absortivos, culminando com a rápida substituição das células fetais por células diferenciadas não pinocíticas, o que determinaria o término da transferência de anticorpos maternos.The localization of acid phosphatase at distal small intestine and its morphology were studied f0rom birth to intestinal closure from fifteen male dairy calves aged: unsuckled neonatal, three hours after colostrum ingestion and three days old. At birth, the presence of a large vacuole was found and it expanded all over the epithelial cells cytoplasm at distal jejunum and ileum. For colostrum fed calves, ingested material could be observed in the vacuole. The phosphatase acid reaction was detected in the absorptive cells of suckled and unsuckled newborn calves. Calves aged three days old, a new population of non-vacuolated cells and reduced apical endocytic system were found

  3. Distinct intestinal adaptation for vitamin B12 and bile acid absorption revealed in a new mouse model of massive ileocecal resection.

    Science.gov (United States)

    Matsumoto, Yuka; Mochizuki, Wakana; Akiyama, Shintaro; Matsumoto, Taichi; Nozaki, Kengo; Watanabe, Mamoru; Nakamura, Tetsuya

    2017-09-15

    Ileocecal resection (ICR), one of several types of intestinal resection that results in short bowel syndrome (SBS), causes severe clinical disease in humans. We here describe a mouse model of massive ICR in which 75% of the distal small intestine is removed. We demonstrate that mice underwent 75% ICR show severe clinical signs and high mortality, which may recapitulate severe forms of human SBS, despite an adaptive response throughout the remnant intestine. By using this model, we also investigated whether the epithelium of the remnant intestine shows enhanced expression of factors involved in region-specific functions of the ileum. Cubn mRNA and its protein product, which play an essential role in vitamin B12 absorption in the ileum, are not compensatory up-regulated in any part of the remnant intestine, demonstrating a clear contrast with post-operative up-regulation of genes involved in bile acid absorption. Our study suggests that functional adaptation by phenotypical changes in the intestinal epithelium is not a general feature for nutrient absorption systems that are confined to the ileum. We also propose that the mouse model developed in this study will become a unique system to facilitate studies on SBS with ICR in humans. © 2017. Published by The Company of Biologists Ltd.

  4. Distinct intestinal adaptation for vitamin B12 and bile acid absorption revealed in a new mouse model of massive ileocecal resection

    Directory of Open Access Journals (Sweden)

    Yuka Matsumoto

    2017-09-01

    Full Text Available Ileocecal resection (ICR, one of several types of intestinal resection that results in short bowel syndrome (SBS, causes severe clinical disease in humans. We here describe a mouse model of massive ICR in which 75% of the distal small intestine is removed. We demonstrate that mice underwent 75% ICR show severe clinical signs and high mortality, which may recapitulate severe forms of human SBS, despite an adaptive response throughout the remnant intestine. By using this model, we also investigated whether the epithelium of the remnant intestine shows enhanced expression of factors involved in region-specific functions of the ileum. Cubn mRNA and its protein product, which play an essential role in vitamin B12 absorption in the ileum, are not compensatory up-regulated in any part of the remnant intestine, demonstrating a clear contrast with post-operative up-regulation of genes involved in bile acid absorption. Our study suggests that functional adaptation by phenotypical changes in the intestinal epithelium is not a general feature for nutrient absorption systems that are confined to the ileum. We also propose that the mouse model developed in this study will become a unique system to facilitate studies on SBS with ICR in humans.

  5. Regeneration of stem-cells in intestinal epithelium after irradiation

    International Nuclear Information System (INIS)

    Hendry, J.H.

    1979-01-01

    Stem-cells can be defined as pluripotent progenitor cells, capable of both self-renewal and differentitation into all the functional end-cells typical of that cell family. Intestinal crypts contain population of cells which is capable of a) self-renewal following the severe depletion after radiation injury, b) replacing all other cypt cell types, and c) regeneration following repeated depletion (in colon). These are the properties of stem cells. Most measurements of the rate of regeneration of these cells following the severe depletion by radiation have been made by employing large test dose at increasing times. Such measurements have produced widely differing rates of increase in the survival under the test dose, from 4 hours (macrocolonies in jejunum) to 43 hours (microcolonies in stomach). In other tissues, large single test doses have been used to derive the time of doubling survival ratio e.g. for epidermal clones. Although cryptogenic cell number per crypt can be virtually restored by day 4 after a single dose and probably after many such doses, the status quo cannot be reached until the number of crypts is restored to normal. Stem cell numbers form a necessary part of the integrity of epitheliums. The quality of the stem cell function of survivors as expressed in the differentiated progeny, and the maintenance of function of the supportive environment are equally important for late radiation damage. (Yamashita, S.)

  6. SITS-sensitive Cl- conductance pathway in chick intestinal cells

    International Nuclear Information System (INIS)

    Montrose, M.; Randles, J.; Kimmich, G.A.

    1987-01-01

    The unidirectional influx of 36 Cl - into isolated chick epithelial cells is 30% inhibited by 300 μM SITS. Characteristics of the SITS-sensitive flux pathway were examined in terms of sensitivity to changes in membrane potential and intracellular pH. Potential dependence was evaluated using unidirectional influx of [ 14 C]tetraphenylphosphonium ([ 14 C]-TPP + ) as a qualitative sensor of diffusion potentials created by experimentally imposed gradients of CL - . Steady-state distribution of [ 14 C]methylamine ([ 14 C]MA) was used to examine for Cl - -dependent changes in intracellular pH. Imposed Na + gradients, but not Cl - gradients, induce changes in [ 14 C]MA distribution. SITS does not alter the [ 14 C]MA distribution observed in cells with imposed gradients of Na + and Cl - . Both results suggest that inhibition of Cl - influx. However, if relative permeabilities for ion pairs via conductance pathways are compared, it can be shown that SITS causes a marked reduction of P Cl relative to either P Na or P K . SITS also inhibits electrically induced influx of [ 14 C]TPP + or [ 14 C]α-methylglucoside driven by imposed Cl - influx can be blocked by SITS. These observations are all consistent with a SITS-sensitive Cl - conductance pathway associated with the plasma membrane of chick intestinal cells. No Cl - -OH - exchange capability can be detected for chick intestinal cells

  7. Enhancing oral vaccine potency by targeting intestinal M cells.

    Directory of Open Access Journals (Sweden)

    Ali Azizi

    2010-11-01

    Full Text Available The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells.

  8. 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

  9. Cdx2 modulates proliferation in normal human intestinal epithelial crypt cells

    International Nuclear Information System (INIS)

    Escaffit, Fabrice; Pare, Frederic; Gauthier, Remy; Rivard, Nathalie; Boudreau, Francois; Beaulieu, Jean-Francois

    2006-01-01

    The homeobox gene Cdx2 is involved in the regulation of the expression of intestine specific markers such as sucrase-isomaltase and lactase-phlorizin hydrolase. Previous studies performed with immortalized or transformed intestinal cell lines have provided evidence that Cdx2 can promote morphological and functional differentiation in these experimental models. However, no data exist concerning the implication of this factor in normal human intestinal cell physiology. In the present work, we have investigated the role of Cdx2 in normal human intestinal epithelial crypt (HIEC) cells that lack this transcription factor. The establishment of HIEC cells expressing Cdx2 in an inducible manner shows that forced expression of Cdx2 significantly alters the proliferation of intestinal crypt cells and stimulates dipeptidylpeptidase IV expression but is not sufficient to trigger intestinal terminal differentiation. These observations suggest that Cdx2 requires additional factors to activate the enterocyte differentiation program in normal undifferentiated cells

  10. Human Primary Intestinal Epithelial Cells as an Improved In Vitro Model for Cryptosporidium parvum Infection

    Science.gov (United States)

    Cabada, Miguel M.; Nichols, Joan; Gomez, Guillermo; White, A. Clinton

    2013-01-01

    The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected with Cryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells support Cryptosporidium better than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involving Cryptosporidium and other intestinal pathogens. PMID:23509153

  11. Culture of human intestinal epithelial cell using the dissociating enzyme thermolysin and endothelin-3

    OpenAIRE

    Liu, Z.; Zhang, P.; Zhou, Y.; Qin, H.; Shen, T.

    2010-01-01

    Epithelium, a highly dynamic system, plays a key role in the homeostasis of the intestine. However, thus far a human intestinal epithelial cell line has not been established in many countries. Fetal tissue was selected to generate viable cell cultures for its sterile condition, effective generation, and differentiated character. The purpose of the present study was to culture human intestinal epithelial cells by a relatively simple method. Thermolysin was added to improve the yield of epithel...

  12. Acoustic absorption behaviour of an open-celled aluminium foam

    CERN Document Server

    Han Fu Sheng; Zhao Yu Yuan; Gibbs, B

    2003-01-01

    Metal foams, especially close-celled foams, are generally regarded as poor sound absorbers. This paper studies the sound absorption behaviour of the open-celled Al foams manufactured by the infiltration process, and the mechanisms involved. The foams show a significant improvement in sound absorption compared with close-celled Al foams, because of their high flow resistance. The absorption performance can be further enhanced, especially at low frequencies, if the foam panel is backed by an appropriate air gap. Increasing the air-gap depth usually increases both the height and the width of the absorption peak and shifts the peak towards lower frequencies. The foam samples with the smallest pore size exhibit the best absorption capacities when there is no air gap, whereas those with medium pore sizes have the best overall performance when there is an air gap. The typical maximum absorption coefficient, noise reduction coefficient and half-width of the absorption peak are 0.96-0.99, 0.44-0.62 and 1500-3500 Hz, r...

  13. Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2017-04-01

    Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC 50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU 50 = 3.5% ± 1.6%) or without insulin (GU 50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

  14. Culture of human intestinal epithelial cell using the dissociating enzyme thermolysin and endothelin-3

    Directory of Open Access Journals (Sweden)

    Z. Liu

    2010-05-01

    Full Text Available Epithelium, a highly dynamic system, plays a key role in the homeostasis of the intestine. However, thus far a human intestinal epithelial cell line has not been established in many countries. Fetal tissue was selected to generate viable cell cultures for its sterile condition, effective generation, and differentiated character. The purpose of the present study was to culture human intestinal epithelial cells by a relatively simple method. Thermolysin was added to improve the yield of epithelial cells, while endothelin-3 was added to stimulate their growth. By adding endothelin-3, the achievement ratio (viable cell cultures/total cultures was enhanced to 60% of a total of 10 cultures (initiated from 8 distinct fetal small intestines, allowing the generation of viable epithelial cell cultures. Western blot, real-time PCR and immunofluorescent staining showed that cytokeratins 8, 18 and mouse intestinal mucosa-1/39 had high expression levels in human intestinal epithelial cells. Differentiated markers such as sucrase-isomaltase, aminopeptidase N and dipeptidylpeptidase IV also showed high expression levels in human intestinal epithelial cells. Differentiated human intestinal epithelial cells, with the expression of surface markers (cytokeratins 8, 18 and mouse intestinal mucosa-1/39 and secretion of cytokines (sucrase-isomaltase, aminopeptidase N and dipeptidylpeptidase IV, may be cultured by the thermolysin and endothelin-3 method and maintained for at least 20 passages. This is relatively simple, requiring no sophisticated techniques or instruments, and may have a number of varied applications.

  15. Action of cholera toxin in the intestinal epithelial cells

    International Nuclear Information System (INIS)

    Hyun, C.S.

    1982-01-01

    The primary event in the action of cholera toxin on the isolated chick intestinal epithelial cell is its interaction with a large number of high affinity binding sites in the cell membrane. Binding of 125 I-labeled toxin is rapid, temperature-dependent, reversible, and saturable over a wide range of concentrations and includes only a small contribution from nonspecific sites. A characteristic lag phase of 10 min occurs following the complete binding of toxin before any increase in cellular cAMP levels can be detected. The response (elevation of cellular cAMP) is linear with time for 40 to 50 min and causes a six- to eight-fold increase over control levels (10 to 15 picomole cAMP/mg cellular protein) at steady state. cAMP and agents that increase cAMP production inhibit Cl - -independent Na + influx into the isolated enterocytes whereas chlorpromazine (CPZ) which completely abolishes toxin-induced elevation of cAMP both reverses and prevents the cAMP-mediated inhibition of Na + entry. Correlation between cellular cAMP levels and the magnitude of Na + influx provides evidence for a cAMP-mediated control of intestinal Na + uptake, which may represent the mechanistic basis for the antiabsorptive effect of CT on Na + during induction of intestinal secretion. The effect of cAMP on Na + but not Cl - influx preparations can be partially explained in terms of a cAMP-regulated Na + /H + neutral exchange system. Data on the coupling relationship between Na + transport and the intra- and extracellular pH in the enterocytes show that an amiloride-sensitive electroneutral Na + /H + exchange process occurs. This coupling between Na + and H + is partially inhibited by CT and dbcAMP, suggesting that the Na + /H + exchange may be a cAMP-regulated process. 31 references, 32 figures, 5 tables

  16. Inhibition of glucose intestinal absorption by kaempferol 3-O-α-rhamnoside purified from Bauhinia megalandra leaves.

    Science.gov (United States)

    Rodríguez, Patricia; González-Mujica, Freddy; Bermúdez, Jairo; Hasegawa, Masahisa

    2010-12-01

    Glucose intestinal absorption (GIA) is one of the factors that increase glycemia. Its reduction could be an important factor in decreasing hyperglycemia in diabetic patients. It has been shown that the aqueous extract of Bauhinia megalandra leaves inhibits GIA. In the present study we identified a compound present in the extract of B. megalandra responsible for the biological effect. The methanol extract of B. megalandra leaves was fractionated using different solvents, and high-speed counter-current chromatography yielding two pure compounds identified by (1)H NMR and (13)C NMR as kaempferol 3-O-α-rhamnoside and quercetin 3-O-α-rhamnoside. The first one increased the K(M) without changes in the V(MAX) of GIA. In addition it exerted an additive inhibitory effect, on GIA, when combined with phlorizin. We suggest that kaempferol 3-O-α-rhamnoside is a competitive inhibitor of intestinal SGLT1 cotransporter. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Intestinal absorption and biliary secretion of ursodeoxycholic acid and its taurine conjugate

    NARCIS (Netherlands)

    Rudolph, G; Kloeters-Plachky, P; Sauer, P; Stiehl, A

    Background Ursodeoxycholic acid (UDCA) and its taurine conjugate (TUDCA) exert a protective effect in cholestatic liver diseases. A greater hepatoprotective effect of TUDCA has been suggested. Absorption appears to be a limiting factor and up to now has not been studied in man. Methods We studied

  18. Cyclin-dependent kinases regulate apoptosis of intestinal epithelial cells

    Science.gov (United States)

    Bhattacharya, Sujoy; Ray, Ramesh M.; Johnson, Leonard R.

    2014-01-01

    Homeostasis of the gastrointestinal epithelium is dependent upon a balance between cell proliferation and apoptosis. Cyclin-dependent kinases (Cdks) are well known for their role in cell proliferation. Previous studies from our group have shown that polyamine-depletion of intestinal epithelial cells (IEC-6) decreases cyclin-dependent kinase 2 (Cdk2) activity, increases p53 and p21Cip1 protein levels, induces G1 arrest, and protects cells from camptothecin (CPT)-induced apoptosis. Although emerging evidence suggests that members of the Cdk family are involved in the regulation of apoptosis, their roles directing apoptosis of IEC-6 cells are not known. In this study, we report that inhibition of Cdk1, 2, and 9 (with the broad range Cdk inhibitor, AZD5438) in proliferating IEC-6 cells triggered DNA damage, activated p53 signaling, inhibited proliferation, and induced apoptosis. By contrast, inhibition of Cdk2 (with NU6140) increased p53 protein and activity, inhibited proliferation, but had no effect on apoptosis. Notably, AZD5438 sensitized, whereas, NU6140 rescued proliferating IEC-6 cells from CPT-induced apoptosis. However, in colon carcinoma (Caco2) cells with mutant p53, treatment with either AZD5438 or NU6140 blocked proliferation, albeit more robustly with AZD5438. Both Cdk inhibitors induced apoptosis in Caco2 cells in a p53-independent manner. In serum starved quiescent IEC-6 cells, both AZD5438 and NU6140 decreased TNF- /CPT-induced activation of p53 and, consequently, rescued cells from apoptosis, indicating that sustained Cdk activity is required for apoptosis of quiescent cells. Furthermore, AZD5438 partially reversed the protective effect of polyamine depletion whereas NU6140 had no effect. Together, these results demonstrate that Cdks possess opposing roles in the control of apoptosis in quiescent and proliferating cells. In addition, Cdk inhibitors uncouple proliferation from apoptosis in a p53-dependent manner. PMID:24242917

  19. The absorption and retention of plutonium in the small intestine of neonate rat

    International Nuclear Information System (INIS)

    Fritsch, P.; Beauvallet, M.; Metivier, H.; Masse, R.; Moutairou, K.

    1987-01-01

    Ligated segments of rat intestine were used to study the effect of age on the jejunal transfer and retention of different chemical forms of soluble Pu(IV). After instillation of Pu-carbonate a 5-fold increase of transfer was observed for 1 week old animals as compared to adults. This transfer value decreased gradually until weaning. Such an age-related decrease was also observed after the instillation of Pu-transferrin for 2 weeks as compared to 12 week-old rats, but in the same range of age, no significant modification could be demonstrated after the instillation of Pu-DTPA complex. Similar modifications related to the age of animals were observed after either perfusion or instillation of the Pu-carbonate and Pu-DTPA chemical forms. Measurement of the area of the intestinal lumen allowed to establish that, in the jejunum, for the chemical forms of Pu studied, no increase of Pu retention could be observed in neonates as compared to adults. Therefore, no relationship could be established between transfer of Pu and its jejunal retention. 9 refs.; 3 tabs

  20. Human intestinal dendritic cells as controllers of mucosal immunity

    Directory of Open Access Journals (Sweden)

    David Bernardo

    2013-06-01

    Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  1. Live Cells Decreased Methane Production in Intestinal Content of Pigs

    Directory of Open Access Journals (Sweden)

    Y. L. Gong

    2013-06-01

    Full Text Available An in vitro gas production technique was used in this study to elucidate the effect of two strains of active live yeast on methane (CH4 production in the large intestinal content of pigs to provide an insight to whether active live yeast could suppress CH4 production in the hindgut of pigs. Treatments used in this study include blank (no substrate and no live yeast cells, control (no live yeast cells and yeast (YST supplementation groups (supplemented with live yeast cells, YST1 or YST2. The yeast cultures contained 1.8×1010 cells per g, which were added at the rates of 0.2 mg and 0.4 mg per ml of the fermented inoculum. Large intestinal contents were collected from 2 Duroc×Landrace×Yorkshire pigs, mixed with a phosphate buffer (1:2, and incubated anaerobically at 39°C for 24 h using 500 mg substrate (dry matter (DM basis. Total gas and CH4 production decreased (p<0.05 with supplementation of yeast. The methane production reduction potential (MRP was calculated by assuming net methane concentration for the control as 100%. The MRP of yeast 2 was more than 25%. Compared with the control group, in vitro DM digestibility (IVDMD and total volatile fatty acids (VFA concentration increased (p<0.05 in 0.4 mg/ml YST1 and 0.2 mg/ml YST2 supplementation groups. Proportion of propionate, butyrate and valerate increased (p<0.05, but that of acetate decreased (p<0.05, which led to a decreased (p<0.05 acetate: propionate (A: P ratio in the both YST2 treatments and the 0.4 mg/ml YST 1 supplementation groups. Hydrogen recovery decreased (p<0.05 with yeast supplementation. Quantity of methanogenic archaea per milliliter of inoculum decreased (p<0.05 with yeast supplementation after 24 h of incubation. Our results suggest that live yeast cells suppressed in vitro CH4 production when inoculated into the large intestinal contents of pigs and shifted the fermentation pattern to favor propionate production together with an increased population of acetogenic

  2. Advanced three-dimensional culture of equine intestinal epithelial stem cells.

    Science.gov (United States)

    Stewart, A Stieler; Freund, J M; Gonzalez, L M

    2018-03-01

    Intestinal epithelial stem cells are critical to epithelial repair following gastrointestinal injury. The culture of intestinal stem cells has quickly become a cornerstone of a vast number of new research endeavours that range from determining tissue viability to testing drug efficacy for humans. This study aims to describe the methods of equine stem cell culture and highlights the future benefits of these techniques for the advancement of equine medicine. To describe the isolation and culture of small intestinal stem cells into three-dimensional (3D) enteroids in horses without clinical gastrointestinal abnormalities. Descriptive study. Intestinal samples were collected by sharp dissection immediately after euthanasia. Intestinal crypts containing intestinal stem cells were dissociated from the underlying tissue layers, plated in a 3D matrix and supplemented with growth factors. After several days, resultant 3D enteroids were prepared for immunofluorescent imaging and polymerase chain reaction (PCR) analysis to detect and characterise specific cell types present. Intestinal crypts were cryopreserved immediately following collection and viability assessed. Intestinal crypts were successfully cultured and matured into 3D enteroids containing a lumen and budding structures. Immunofluorescence and PCR were used to confirm the existence of stem cells and all post mitotic, mature cell types, described to exist in the horse intestinal epithelium. Previously frozen crypts were successfully cultured following a freeze-thaw cycle. Tissues were all derived from normal horses. Application of this technique for the study of specific disease was not performed at this time. The successful culture of equine intestinal crypts into 3D "mini-guts" allows for in vitro studies of the equine intestine. Additionally, these results have relevance to future development of novel therapies that harness the regenerative potential of equine intestine in horses with gastrointestinal disease

  3. Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover

    OpenAIRE

    Gibson, P; Birchall, I; Rosella, O; Albert, V; Finch, C; Barkla, D; Young, G

    1998-01-01

    Background—The functions of urokinase in intestinal epithelia are unknown. 
Aims—To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon. 
Methods—Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequ...

  4. Bovine TLR2 and TLR4 mediate Cryptosporidium parvum recognition in bovine intestinal epithelial cells.

    Science.gov (United States)

    Yang, Zhengtao; Fu, Yunhe; Gong, Pengtao; Zheng, Jingtong; Liu, Li; Yu, Yuqiang; Li, Jianhua; Li, He; Yang, Ju; Zhang, Xichen

    2015-08-01

    Cryptosporidium parvum (C. parvum) is an intestinal parasite that causes diarrhea in neonatal calves. It results in significant morbidity of neonatal calves and economic losses for producers worldwide. Innate resistance against C. parvum is thought to depend on engagement of pattern recognition receptors. However, the role of innate responses to C. parvum has not been elucidated in bovine. The aim of this study was to evaluate the role of TLRs in host-cell responses during C. parvum infection of cultured bovine intestinal epithelial cells. The expressions of TLRs in bovine intestinal epithelial cells were detected by qRT-PCR. To determine which, if any, TLRs may play a role in the response of bovine intestinal epithelial cells to C. parvum, the cells were stimulated with C. parvum and the expression of TLRs were tested by qRT-PCR. The expression of NF-κB was detected by western blotting. Further analyses were carried out in bovine TLRs transfected HEK293 cells and by TLRs-DN transfected bovine intestinal epithelial cells. The results showed that bovine intestinal epithelial cells expressed all known TLRs. The expression of TLR2 and TLR4 were up-regulated when bovine intestinal epithelial cells were treated with C. parvum. Meanwhile, C. parvum induced IL-8 production in TLR2 or TLR4/MD-2 transfected HEK293 cells. Moreover, C. parvum induced NF-κB activation and cytokine expression in bovine intestinal epithelial cells. The induction of NF-κB activation and cytokine expression by C. parvum were reduced in TLR2-DN and TLR4-DN transfected cells. The results showed that bovine intestinal epithelial cells expressed all known TLRs, and bovine intestinal epithelial cells recognized and responded to C. parvum via TLR2 and TLR4. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. ADAM10 regulates Notch function in intestinal stem cells of mice.

    Science.gov (United States)

    Tsai, Yu-Hwai; VanDussen, Kelli L; Sawey, Eric T; Wade, Alex W; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C; Samuelson, Linda C; Dempsey, Peter J

    2014-10-01

    A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Distinct Roles for Intestinal Epithelial Cell-Specific Hdac1 and Hdac2 in the Regulation of Murine Intestinal Homeostasis.

    Science.gov (United States)

    Gonneaud, Alexis; Turgeon, Naomie; Boudreau, François; Perreault, Nathalie; Rivard, Nathalie; Asselin, Claude

    2016-02-01

    The intestinal epithelium responds to and transmits signals from the microbiota and the mucosal immune system to insure intestinal homeostasis. These interactions are in part conveyed by epigenetic modifications, which respond to environmental changes. Protein acetylation is an epigenetic signal regulated by histone deacetylases, including Hdac1 and Hdac2. We have previously shown that villin-Cre-inducible intestinal epithelial cell (IEC)-specific Hdac1 and Hdac2 deletions disturb intestinal homeostasis. To determine the role of Hdac1 and Hdac2 in the regulation of IEC function and the establishment of the dual knockout phenotype, we have generated villin-Cre murine models expressing one Hdac1 allele without Hdac2, or one Hdac2 allele without Hdac1. We have also investigated the effect of short-term deletion of both genes in naphtoflavone-inducible Ah-Cre and tamoxifen-inducible villin-Cre(ER) mice. Mice with one Hdac1 allele displayed normal tissue architecture, but increased sensitivity to DSS-induced colitis. In contrast, mice with one Hdac2 allele displayed intestinal architecture defects, increased proliferation, decreased goblet cell numbers as opposed to Paneth cells, increased immune cell infiltration associated with fibrosis, and increased sensitivity to DSS-induced colitis. In comparison to dual knockout mice, intermediary activation of Notch, mTOR, and Stat3 signaling pathways was observed. While villin-Cre(ER) Hdac1 and Hdac2 deletions led to an impaired epithelium and differentiation defects, Ah-Cre-mediated deletion resulted in blunted proliferation associated with the induction of a DNA damage response. Our results suggest that IEC determination and intestinal homeostasis are highly dependent on Hdac1 and Hdac2 activity levels, and that changes in the IEC acetylome may alter the mucosal environment. © 2015 Wiley Periodicals, Inc.

  7. Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro.

    Science.gov (United States)

    Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

    2006-04-01

    Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37 degrees C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (x 3; P wine, were significantly elevated approximately two fold (P moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases.

  8. Effect of gastric anacidity on the intestinal absorption of liver bound 57Co-labelled cobalamins

    International Nuclear Information System (INIS)

    Kittang, E.

    1987-01-01

    57 Co-labelled cyanocobalamin injected in rabbit was transformed within the liver to 57 Co-labelled desoxyadenosylcobalamin and methylcovalamin. The absorption of 57 Co-labelled liver bound cobalamins could be determined with acceptable accuracy by the double isotope fecal excretion method. Treatment with the H 2-receptor antagonist, ranitidine, did not result in decreased absorption of 57 Co-labelled liver bound cobalamins in healthy individuals. R-protein and the R-proteincobalamin complex were determined by the FPLC Mono S chromatography method with a high degree of correlation to the charcoal method in saliva, gastric and duodenal juice, and with a high degree of reproducibility. Omeprazole markedly inhibited the gastric acid and pepsin secretion, but did nor inhibit the IF secretion. Omeprazole treatment resulted in anacidity in 14 of 17 individuals, but did not reduce the absorption of liver bound 57 Co-labelled cobalamins. The intrinsic factor concentration in gastric aspirates measured during the study was unchanged during omeprazole treatment. The release of cobalamins from liver homogenate was markedly inhibited by neutralized gastric juice in vitro, probably due to decreased pepsin mediated proteolysis. In vivo the cobalamin release from liver homogenate was modestly inhibited in the stomach but was unaffected in jejunum during omeprazole treatment. The major part of 57 Co-labelled liver cobalamins bound to R-protein in acid and neutral gastric juice in vitro, and omeprazole induced anacidity, did not influence the cobalamin binding either in gastric or jejunal juice in vivo

  9. Communication between B-Cells and Microbiota for the Maintenance of Intestinal Homeostasis

    Directory of Open Access Journals (Sweden)

    Yuying Liu

    2013-10-01

    Full Text Available The human intestine is populated with an extremely dense and diverse bacterial community. Commensal bacteria act as an important antigenic stimulus producing the maturation of gut-associated lymphoid tissue (GALT. The production of immunoglobulin (Ig A by B-cells in the GALT is one of the immune responses following intestinal colonization of bacteria. The switch of B-cells from IgM to IgA-producing cells in the Peyer’s patches and neighboring lamina propria proceeds by T-cell-dependent and T-cell-independent mechanisms. Several grams of secretory IgA (SIgA are released into the intestine each day. SIgA serves as a first-line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. SIgA has a capacity to directly quench bacterial virulence factors, influence the composition of the intestinal microbiota, and promote the transportation of antigens across the intestinal epithelium to GALT and down-regulate proinflammatory responses associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the reciprocal interactions between intestinal B cells and bacteria, specifically, the formation of IgA in the gut, the role of intestinal IgA in the regulation of bacterial communities and the maintenance of intestinal homeostasis, and the effects of probiotics on IgA levels in the gastrointestinal tract.

  10. Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine.

    Directory of Open Access Journals (Sweden)

    Daniel N Frank

    Full Text Available Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD protein Perilipin-2 (Plin2 in mice largely abrogates long-term deleterious effects of a high fat (HF diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 null mice raised on a standard chow diet were randomized to either low fat (LF or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels, histochemical (enterocyte CLD content, and fecal microbiome parameters. Plin2-null mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity.

  11. Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine.

    Science.gov (United States)

    Frank, Daniel N; Bales, Elise S; Monks, Jenifer; Jackman, Matthew J; MacLean, Paul S; Ir, Diana; Robertson, Charles E; Orlicky, David J; McManaman, James L

    2015-01-01

    Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD) protein Perilipin-2 (Plin2) in mice largely abrogates long-term deleterious effects of a high fat (HF) diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 null mice raised on a standard chow diet were randomized to either low fat (LF) or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels), histochemical (enterocyte CLD content), and fecal microbiome parameters. Plin2-null mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity.

  12. Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro

    Science.gov (United States)

    Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

    2006-01-01

    Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37°C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (× 3; P<0.001) and quercetin-3-O-glucoside (× 1.5; P<0.01) associated with them, compared with sacs incubated in the dealcoholised equivalent. In addition, both tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to the whole wine, were significantly elevated approximately two fold (P<0.05; P<0.01, respectively). Similar results were obtained when sacs were incubated in Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside with or without alcohol, and, although effects on the apparent absorption of Q and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O-glucuronide and I were significantly increased by the presence of alcohol (P<0.01 and P<0.001, respectively). It is therefore plausible that the moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases. PMID:16444288

  13. Fermented soya bean (tempe) extracts reduce adhesion of enterotoxigenic Escherichia coli to intestinal epithelial cells

    NARCIS (Netherlands)

    Roubos-van den Hil, P.J.; Nout, M.J.R.; Beumer, R.R.; Meulen, van der J.; Zwietering, M.H.

    2009-01-01

    Aims: This study aimed to investigate the effect of processed soya bean, during the successive stages of tempe fermentation and different fermentation times, on adhesion of enterotoxigenic Escherichia coli (ETEC) K88 to intestinal brush border cells as well as Caco-2 intestinal epithelial cells; and

  14. Peroxisomes in intestinal and gallbladder epithelial cells of the stickleback, Gasterosteus aculeatus L. (Teleostei)

    NARCIS (Netherlands)

    Ruiter, A.J.H. de; Veenhuis, M.; Wendelaar Bonga, S.E.

    1988-01-01

    The occurrence of microbodies in the epithelial cells of the intestine and gallbladder of the stickleback, Gasterosteus aculeatus L., is described. In the intestine the organelles are predominantly located in the apical and perinuclear zone of the cells and may contain small crystalline cores. In

  15. Formation of a Hydroxymethylfurfural-Cysteine Adduct and Its Absorption and Cytotoxicity in Caco-2 Cells.

    Science.gov (United States)

    Zhao, Qianzhu; Zou, Yueyu; Huang, Caihuan; Lan, Ping; Zheng, Jie; Ou, Shiyi

    2017-11-15

    Adducts of 5-hydroxymethylfurfural (HMF)-amino acids are formed during food processing and digestion; the elimination capacity of in vitro intestinal digests of biscuits, instant noodles, and potato crisps for HMF is 652, 727, and 540 μg/g, respectively. However, the safety of these adducts is unknown. In this study, an HMF-cysteine adduct named 1-dicysteinethioacetal-5-hydroxymehtylfurfural (DCH), which was found to be produced in the gastrointestinal tract after HMF intake, was prepared to test its effect toward Caco-2 cells. Compared with HMF, the adduct displayed lower cytotoxicity against Caco-2 cells with an IC 50 value of 31.26 mM versus 14.95 mM (HMF). The DCH did not induce cell apoptosis, whereas HMF significantly increased the apoptosis rate after incubation at concentrations of 16, 32, and 48 mM for 72 h. DCH showed an absorption rate considerably lower than that of HMF by Caco-2 cells. Lower absorption of DCH may result in lower toxicity compared with HMF against Caco-2 cells. Intracellular transformation of DCH has been observed.

  16. Oral Administration of Probiotics Increases Paneth Cells and Intestinal Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Silvia I. Cazorla

    2018-04-01

    Full Text Available The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431 and L. paracasei CNCM I-1518 (Lp 1518 to 42 days old mice, increases the number of Paneth cells on small intestine, and the antimicrobial activity against the pathogens Staphylococcus aureus and Salmonella Typhimurium in the intestinal fluids. Specifically, strong damage of the bacterial cell with leakage of cytoplasmic content, and cellular fragmentation were observed in S. Typhimurium and S. aureus. Even more important, probiotics increase the antimicrobial activity of the intestinal fluids at the different ages, from weaning (21 days old to old age (180 days old. Intestinal antimicrobial activity stimulated by oral probiotics, do not influence significantly the composition of total anaerobic bacteria, lactobacilli and enterobacteria in the large intestine, at any age analyzed. This result, together with the antimicrobial activity observed against the same probiotic bacteria; endorse the regular consumption of probiotics without adverse effect on the intestinal homeostasis in healthy individuals. We demonstrate that oral probiotics increase intestinal antimicrobial activity and Paneth cells in order to strengthen epithelial barrier against pathogens. This effect would be another important mechanism by which probiotics protect the host mainly against infectious diseases.

  17. Exogenous glucagon-like peptide-1 attenuates glucose absorption and reduces blood glucose concentration after small intestinal glucose delivery in critical illness.

    Science.gov (United States)

    Miller, Asaf; Deane, Adam M; Plummer, Mark P; Cousins, Caroline E; Chapple, Lee-Anne S; Horowitz, Michael; Chapman, Marianne J

    2017-03-01

    To evaluate the effect of exogenous glucagonlike peptide-1 (GLP-1) on small intestinal glucose absorption and blood glucose concentrations during critical illness. A prospective, blinded, placebo-controlled, cross-over, randomised trial in a mixed medical-surgical adult intensive care unit, with 12 mechanically ventilated critically ill patients, who were suitable for receiving small intestinal nutrient. On consecutive days, in a randomised order, participants received intravenous GLP-1 (1.2 pmol/ kg/min) or placebo (0.9% saline) as a continuous infusion over 270 minutes. After 6 hours of fasting, intravenous infusions of GLP-1 or placebo began at T = -30 min (in which T = time), with the infusion maintained at a constant rate until study completion at T = 240 min. At T = 0 min, a 100 mL bolus of mixed liquid nutrient meal (1 kcal/mL) containing 3 g of 3-O-methyl-D-gluco-pyranose (3-OMG), a marker of glucose absorption, was administered directly into the small intestine, via a post-pyloric catheter, over 6 minutes. Blood samples were taken at regular intervals for the measurement of plasma glucose and 3-OMG concentrations. Intravenous GLP-1 attenuated initial small intestinal glucose absorption (mean area under the curve [AUC] 0-30 for 3-OMG: GLP-1 group, 4.4 mmol/L/min [SEM, 0.9 mmol/L/min] v placebo group, 6.5 mmol/L/min [SEM, 1.0 mmol/L/min]; P = 0.01), overall small intestinal glucose absorption (mean AUC 0-240 for 3-OMG: GLP-1, 68.2 mmol/L/ min [SEM, 4.7 mmol/L/min] v placebo, 77.7 mmol/L/min [SEM, 4.4 mmol/lLmin]; P = 0.02), small intestinal glucose absorption and overall blood glucose concentration (mean AUC 0-240 for blood glucose: GLP-1, 2062 mmol/L/min [SEM, 111 mmol/L/min] v placebo 2328 mmol/L/min [SEM, 145 mmol/L/min]; P = 0.005). Short-term administration of exogenous GLP-1 reduces small intestinal glucose absorption for up to 4 hours during critical illness. This is likely to be an additional mechanism for the glucose-lowering effect of this agent.

  18. Interstitial cells of Cajal and Auerbach's plexus. A scanning electron microscopical study of guinea-pig small intestine

    DEFF Research Database (Denmark)

    Jessen, Harry; Thuneberg, Lars

    1991-01-01

    Anatomy, interstitial cells of Cajal, myenteric plexus, small intestine, guinea-pig, scanning electron microscopy......Anatomy, interstitial cells of Cajal, myenteric plexus, small intestine, guinea-pig, scanning electron microscopy...

  19. The recruitability and cell-cycle state of intestinal stem cells

    International Nuclear Information System (INIS)

    Potten, C.S.; Chadwick, C.; Ijiri, K.; Tsubouchi, S.; Hanson, W.R.

    1984-01-01

    Evidence is presented which suggests that the crypts of the small intestine contain at least two discrete but interdependent classes of stem cells, some with discrete cell kinetic properties and some with discrete radiation responses or radiosensitivities. Very low doses of X rays or gamma rays, or neutrons, kill a few cells in the stem cell regions of the crypt in a sensitive dose-dependent manner. Similar doses generate several different cell kinetic responses within either the clonogenic fraction or the cells at the stem cell position within the crypt. The cell kinetic responses range from apparent recruitment of G0 clonogenic cells into cycle, to a marked shortening of the average cell cycle of the cells at the stem cell position. It is suggested that the cell kinetic changes may be the consequence of the cell destruction

  20. Transfer of milk prolactin ro the plasma of neonatal rats by intestinal absorption

    Energy Technology Data Exchange (ETDEWEB)

    Whitworth, N S; Grosvenor, C E [Tennessee Univ., Memphis (USA). Dept. of Physiology and Biophysics

    1978-11-01

    Prolactin passes from the systemic circulation of lactating rats into the milk where it can be consumed by the young rats during suckling. /sup 131/- labelled rat prolactin was detected in the plasma of 9- to 14-day-old rats after being nursed by mothers previously injected with /sup 131/I-labelled rat prolactin and after the pups had received /sup 131/I-labelled rat prolactin by gastric intubation. It was estimated that 16% of the /sup 131/I-labelled rat prolactin given by gastric intubation subsequently appeared in the plasma of the neonate. Gastric administration of 10.5 or 21.0 ..mu..g B-1 rat prolactin significantly raised the level of prolactin in the plasma of 13-day-old pups, but a similar increase was not observed when 27-day-old rats were given 46.2 ..mu..g B-1 prolactin by gastric intubation. The concentration of prolactin in the plasma of 13-to 14-day-old rats rose to 55 ng/ml 30 min after the onset of nursing by mothers whose mammary glands were full of milk, whereas the concentration in the plasma of mothers with empty mammary glands remained at basal values. It is concluded that the intestine of the newborn is permeable to prolactin and that milk may constitute an exogeneous source of prolactin for the suckled offspring.

  1. PGE2 suppresses intestinal T cell function in thermal injury: a cause of enhanced bacterial translocation.

    Science.gov (United States)

    Choudhry, M A; Fazal, N; Namak, S Y; Haque, F; Ravindranath, T; Sayeed, M M

    2001-09-01

    Increased gut bacterial translocation in burn and trauma patients has been demonstrated in a number of previous studies, however, the mechanism for such an increased gut bacterial translocation in injured patients remains poorly understood. Utilizing a rat model of burn injury, in the present study we examined the role of intestinal immune defense by analyzing the T cell functions. We investigated if intestinal T cells dysfunction contributes to bacterial translocation after burn injury. Also our study determined if burn-mediated alterations in intestinal T cell functions are related to enhanced release of PGE2. Finally, we examined whether or not burn-related alterations in intestinal T cell function are due to inappropriate activation of signaling molecule P59fyn, which is required for T cell activation and proliferation. The results presented here showed an increase in gut bacterial accumulation in mesenteric lymph nodes after thermal injury. This was accompanied by a decrease in the intestinal T cell proliferative responses. Furthermore, the treatments of burn-injured animals with PGE2 synthesis blocker (indomethacin or NS398) prevented both the decrease in intestinal T cell proliferation and enhanced bacterial translocation. Finally, our data suggested that the inhibition of intestinal T cell proliferation could result via PGE2-mediated down-regulation of the T cell activation-signaling molecule P59fyn. These findings support a role of T cell-mediated immune defense against bacterial translocation in burn injury.

  2. JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Camilla A. Richmond

    2018-01-01

    Full Text Available The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs and slowly cycling, reserve ISCs (r-ISCs. Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, r-ISCs proved highly resistant to injury, while CBC ISCs underwent apoptosis. Moreover, r-ISCs were induced to proliferate and functionally contribute to intestinal regeneration. Further analysis revealed that the inflammatory cytokines interferon gamma and tumor necrosis factor alpha led to r-ISC activation in enteroid culture, which could be blocked by the JAK/STAT inhibitor, tofacitinib. These results highlight an important role for r-ISCs in response to acute intestinal inflammation and show that JAK/STAT-1 signaling is required for the r-ISC regenerative response.

  3. Vitamin B 12 absorption: correction of intestinal retention by whole-body profile activity of vitamin B 12-58 cobalt and by double tracer technique

    International Nuclear Information System (INIS)

    Goncalves, M.R. Bencke; Gheldof, R.; Paternot, L. van Tricht; Delmotte, E.; Verschaeren, A.; Martin, P.; Verhas, M.; Universidade Federal, Rio de Janeiro, RJ

    1997-01-01

    Full text. Intestinal retention could give false negative results in determining the whole-body retention of vitamin B 12 absorption (WBC B12-58Co). After having validate the WBC B12-58Co, taking the Schilling test as reference, we have studied the feasibility to evaluate the intestinal contamination by measurement of the profile activity distribution of vitamin B12-58Co and by a double tracer technique (WBC B12-58Co/ WBC 51 Cr Cl3). Methodology: twenty five patients were studied for the setting up of the new methodology. For eleven of them the WBC B12-58 Co retention was measured at the 7th day after the oral administration of 37KBq of B12-58Co using a four detectors whole body counter. One week later, a Schilling test was performed after the oral absorption of 18,5 KBq B12-57Co. Results were expressed as %ID. In these patients, one single peak of hepatic activity was observed on the whole body profile and thus no further intestinal correction was needed. In order to evaluate the intestinal contribution, we made in nine other patients the profile of the whole body distribution of activity at 1 h, 1 week and two weeks after the oral administration of B12-58Co. For five other patients a double tracer technique was used for intestinal correction after the simultaneous oral administration of 37 KBq of B12-58Co and 1,85 MBq of 51 Cr Cl3. The B12-58Co absorption was evaluated after intestinal correction based on subtraction of the 51Cr Cl3 contribution after the formula: B12-58Co(%ID) = WBC B12-58Co - WBC 51 Cr Cl3/1 - WBC 51 Cr Cl3. Results: the correlation with the Schilling test was found excellent: r=0,94 (n=11). The normality for WBC retention (n=7) was define as 53,2 +-12,4% ID (SD). For nine patients studied at the 7th day, the presence of a double peak (hepatic and intestinal peaks) allowed the subtraction by exponential extrapolation; the correction range was 4,4% to 37,2%. With the exception of one observation there was no difference in the measure of vitamin

  4. Serratia marcescens is injurious to intestinal epithelial cells.

    Science.gov (United States)

    Ochieng, John B; Boisen, Nadia; Lindsay, Brianna; Santiago, Araceli; Ouma, Collins; Ombok, Maurice; Fields, Barry; Stine, O Colin; Nataro, James P

    2014-01-01

    Diarrhea causes substantial morbidity and mortality in children in low-income countries. Although numerous pathogens cause diarrhea, the etiology of many episodes remains unknown. Serratia marcescens is incriminated in hospital-associated infections, and HIV/AIDS associated diarrhea. We have recently found that Serratia spp. may be found more commonly in the stools of patients with diarrhea than in asymptomatic control children. We therefore investigated the possible enteric pathogenicity of S. marcescens in vitro employing a polarized human colonic epithelial cell (T84) monolayer. Infected monolayers were assayed for bacterial invasion, transepithelial electrical resistance (TEER), cytotoxicity, interleukin-8 (IL-8) release and morphological changes by scanning electron microscopy. We observed significantly greater epithelial cell invasion by S. marcescens compared to Escherichia coli strain HS (p = 0.0038 respectively). Cell invasion was accompanied by reduction in TEER and secretion of IL-8. Lactate dehydrogenase (LDH) extracellular concentration rapidly increased within a few hours of exposure of the monolayer to S. marcescens. Scanning electron microscopy of S. marcescens-infected monolayers demonstrated destruction of microvilli and vacuolization. Our results suggest that S. marcescens interacts with intestinal epithelial cells in culture and induces dramatic alterations similar to those produced by known enteric pathogens.

  5. Effects of steroids and sex reversal on intestinal absorption of L-(/sup 14/C)leucine in vivo, in rainbow trout, Salmo gairdneri

    Energy Technology Data Exchange (ETDEWEB)

    Habibi, H.R.; Ince, B.W.

    1983-12-01

    The effects of steroids (17 alpha-methyltestosterone (MT), 17 beta-oestradiol (E2)), and of sex reversal (XX male) on intestinal absorption and accumulation of L-(/sup 14/C)leucine (5 mM), were investigated in unanaesthetized rainbow trout (Salmo gairdneri), using an in vivo gut perfusion technique. Each steroid was luminally perfused through the gut at a concentration of 50 micrograms/ml perfusate, during five separate perfusions carried out on the same fish at 30-min intervals (perfusion periods 1 to 5), for a total of 120 min at 14 degrees. Experiments were also conducted on masculinized, genetically female trout (XX male) with steroid-free perfusate. MT treatment significantly increased the intestinal absorption of radioleucine during periods 1 and 2, whilst E2 was without effect. Neither MT nor E2 influenced intestinal accumulation (mid- and hindgut) of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. Sex reversal, however, whilst having no effect on leucine absorption, nevertheless significantly increased intestinal accumulation of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. The effects observed in the present study are in agreement with previous work in trout using everted gut sac preparations. It is suggested that the growth-promoting effects of anabolic-androgenic steroids in fish may be partly explained by their action on gastrointestinal function.

  6. L-Theanine Administration Modulates the Absorption of Dietary Nutrients and Expression of Transporters and Receptors in the Intestinal Mucosa of Rats

    Directory of Open Access Journals (Sweden)

    Qiongxian Yan

    2017-01-01

    Full Text Available L-theanine has various advantageous functions for human health; whether or not it could mediate the nutrients absorption is unknown yet. The effects of L-theanine on intestinal nutrients absorption were investigated using rats ingesting L-theanine solution (0, 50, 200, and 400 mg/kg body weight per day for two weeks. The decline of insulin secretion and glucose concentration in the serum was observed by L-theanine. Urea and high-density lipoprotein were also reduced by 50 mg/kg L-theanine. Jejunal and ileac basic amino acids transporters SLC7a1 and SLC7a9, neutral SLC1a5 and SLC16a10, and acidic SLC1a1 expression were upregulated. The expression of intestinal SGLT3 and GLUT5 responsible for carbohydrates uptake and GPR120 and FABP2 associated with fatty acids transport were inhibited. These results indicated that L-theanine could inhibit the glucose uptake by downregulating the related gene expression in the small intestine of rats. Intestinal gene expression of transporters responding to amino acids absorption was stimulated by L-theanine administration.

  7. The in vivo pharmacokinetics, tissue distribution and excretion investigation of mesaconine in rats and its in vitro intestinal absorption study using UPLC-MS/MS.

    Science.gov (United States)

    Liu, Xiuxiu; Tang, Minghai; Liu, Taohong; Wang, Chunyan; Tang, Qiaoxin; Xiao, Yaxin; Yang, Ruixin; Chao, Ruobing

    2017-12-27

    1. Mesaconine, an ingredient from Aconitum carmichaelii Debx., has been proven to have cardiac effect. For further development and better pharmacological elucidation, the in vivo process and intestinal absorptive behavior of mesaconine should be investigated comprehensively. 2. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of mesaconine in rat plasma, tissue homogenates, urine and feces to investigate the in vivo pharmacokinetic profiles, tissue distribution and excretion. The intestinal absorptive behavior of mesaconine was investigated using in vitro everted rat gut sac model. 3. Mesaconine was well distributed in tissues and a mass of unchanged form was detected in feces. It was difficultly absorbed into blood circulatory system after oral administration. The insufficient oral bioavailability of mesaconine may be mainly attributed to its low intestinal permeability due to a lack of lipophilicity. The absorption of mesaconine in rat's intestine is a first-order process with the passive diffusion mechanism.

  8. Effects of steroids and sex reversal on intestinal absorption of L-[14C]leucine in vivo, in rainbow trout, Salmo gairdneri

    International Nuclear Information System (INIS)

    Habibi, H.R.; Ince, B.W.

    1983-01-01

    The effects of steroids (17 alpha-methyltestosterone (MT), 17 beta-oestradiol (E2)), and of sex reversal (XX male) on intestinal absorption and accumulation of L-[ 14 C]leucine (5 mM), were investigated in unanaesthetized rainbow trout (Salmo gairdneri), using an in vivo gut perfusion technique. Each steroid was luminally perfused through the gut at a concentration of 50 micrograms/ml perfusate, during five separate perfusions carried out on the same fish at 30-min intervals (perfusion periods 1 to 5), for a total of 120 min at 14 degrees. Experiments were also conducted on masculinized, genetically female trout (XX male) with steroid-free perfusate. MT treatment significantly increased the intestinal absorption of radioleucine during periods 1 and 2, whilst E2 was without effect. Neither MT nor E2 influenced intestinal accumulation (mid- and hindgut) of radioleucine, and accumulation of 14 C-solutes in skeletal muscle. Sex reversal, however, whilst having no effect on leucine absorption, nevertheless significantly increased intestinal accumulation of radioleucine, and accumulation of 14 C-solutes in skeletal muscle. The effects observed in the present study are in agreement with previous work in trout using everted gut sac preparations. It is suggested that the growth-promoting effects of anabolic-androgenic steroids in fish may be partly explained by their action on gastrointestinal function

  9. An X-ray absorption spectroelectrochemical cell for radioactive solutions

    International Nuclear Information System (INIS)

    Rettig, D.; Herrmann, S.; Mitschke, F.; Vonau, W.; Brendler, V.; Geipel, G.; Reich, T.; Bernhard, G.

    2002-01-01

    A spectroelectrochemical cell was designed and constructed for measurement of X-ray absorption spectra under electrochemical control of the redox potential of actinide-containing solutions. A first inactive test demonstrated the feasibility of an Ag anode as a non-gassing auxiliary electrode in chloride solutions. (orig.)

  10. Enhancing the intestinal absorption of low molecular weight chondroitin sulfate by conjugation with α-linolenic acid and the transport mechanism of the conjugates.

    Science.gov (United States)

    Xiao, Yuliang; Li, Pingli; Cheng, Yanna; Zhang, Xinke; Sheng, Juzheng; Wang, Decai; Li, Juan; Zhang, Qian; Zhong, Chuanqing; Cao, Rui; Wang, Fengshan

    2014-04-25

    The purpose of this report was to demonstrate the effect of amphiphilic polysaccharides-based self-assembling micelles on enhancing the oral absorption of low molecular weight chondroitin sulfate (LMCS) in vitro and in vivo, and identify the transepithelial transport mechanism of LMCS micelles across the intestinal barrier. α-Linolenic acid-low molecular weight chondroitin sulfate polymers(α-LNA-LMCS) were successfully synthesized, and characterized by FTIR, (1)HNMR, TGA/DSC, TEM, laser light scattering and zeta potential. The significant oral absorption enhancement and elimination half-life (t₁/₂) extension of LNA-LMCS2 in rats were evidenced by intragastric administration in comparison with CS and LMCS. Caco-2 transport studies demonstrated that the apparent permeability coefficient (Papp) of LNA-LMCS2 was significantly higher than that of CS and LMCS (p<0.001), and no significant effects on the overall integrity of the monolayer were observed during the transport process. In addition, α-LNA-LMCS micelles accumulated around the cell membrane and intercellular space observed by confocal laser scanning microscope (CLSM). Furthermore, evident alterations in the F-actin cytoskeleton were detected by CLSM observation following the treatment of the cell monolayers with α-LNA-LMCS micelles, which further certified the capacity of α-LNA-LMCS micelles to open the intercellular tight junctions rather than disrupt the overall integrity of the monolayer. Therefore, LNA-LMCS2 with low cytotoxicity and high bioavailability might be a promising substitute for CS in clinical use, such as treating osteoarthritis, atherosclerosis, etc. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Microbiome-mediated bile acid modification: Role in intestinal drug absorption and metabolism.

    Science.gov (United States)

    Enright, Elaine F; Griffin, Brendan T; Gahan, Cormac G M; Joyce, Susan A

    2018-04-13

    Once regarded obscure and underappreciated, the gut microbiota (the microbial communities colonizing the gastrointestinal tract) is gaining recognition as an influencer of many aspects of human health. Also increasingly apparent is the breadth of interindividual variation in these co-evolved microbial-gut associations, presenting novel quests to explore implications for disease and therapeutic response. In this respect, the unearthing of the drug-metabolizing capacity of the microbiota has provided impetus for the integration of microbiological and pharmacological research. This review considers a potential mechanism, 'microbial bile acid metabolism', by which the intricate interplay between the host and gut bacteria may influence drug pharmacokinetics. Bile salts traditionally regarded as biological surfactants, synthesized by the host and biotransformed by gut bacteria, are now also recognized as signalling molecules that affect diverse physiological processes. Accumulating data indicate that bile salts are not equivalent with respect to their physicochemical properties, micellar solubilization capacities for poorly water-soluble drugs, crystallization inhibition tendencies nor potencies for bile acid receptor activation. Herein, the origin, physicochemical properties, physiological functions, plasticity and pharmaceutical significance of the human bile acid pool are discussed. Microbial dependant differences in the composition of the human bile acid pool, simulated intestinal media and commonly used preclinical species is highlighted to better understand in vivo performance predictiveness. While the precise impact of an altered gut microbiome, and consequently bile acid pool, in the biopharmaceutical setting remains largely elusive, the objective of this article is to aid knowledge acquisition through a detailed review of the literature. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. File list: NoD.Dig.10.AllAg.Intestinal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Dig.10.AllAg.Intestinal_stem_cells mm9 No description Digestive tract Intestina...l stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Dig.10.AllAg.Intestinal_stem_cells.bed ...

  13. File list: NoD.Dig.20.AllAg.Intestinal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Dig.20.AllAg.Intestinal_stem_cells mm9 No description Digestive tract Intestina...l stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Dig.20.AllAg.Intestinal_stem_cells.bed ...

  14. File list: InP.Dig.20.AllAg.Intestinal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Dig.20.AllAg.Intestinal_stem_cells mm9 Input control Digestive tract Intestinal... stem cells SRX856960,SRX1091861,SRX1091862,SRX193723 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Dig.20.AllAg.Intestinal_stem_cells.bed ...

  15. Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells.

    Science.gov (United States)

    Atarashi, Koji; Tanoue, Takeshi; Ando, Minoru; Kamada, Nobuhiko; Nagano, Yuji; Narushima, Seiko; Suda, Wataru; Imaoka, Akemi; Setoyama, Hiromi; Nagamori, Takashi; Ishikawa, Eiji; Shima, Tatsuichiro; Hara, Taeko; Kado, Shoichi; Jinnohara, Toshi; Ohno, Hiroshi; Kondo, Takashi; Toyooka, Kiminori; Watanabe, Eiichiro; Yokoyama, Shin-Ichiro; Tokoro, Shunji; Mori, Hiroshi; Noguchi, Yurika; Morita, Hidetoshi; Ivanov, Ivaylo I; Sugiyama, Tsuyoshi; Nuñez, Gabriel; Camp, J Gray; Hattori, Masahira; Umesaki, Yoshinori; Honda, Kenya

    2015-10-08

    Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse

    NARCIS (Netherlands)

    Merlos-Suarez, A.; Barriga, F.M.; Jung, P.; Iglesias, M.; Cespedes, M.V.; Rossell, D.; Sevillano, M.; Hernando-Momblona, X.; da Silva-Diz, V.; Munoz, P.; Clevers, H.; Sancho, E.; Mangues, R.; Batlle, E.

    2011-01-01

    A frequent complication in colorectal cancer (CRC) is regeneration of the tumor after therapy. Here, we report that a gene signature specific for adult intestinal stem cells (ISCs) predicts disease relapse in CRC patients. ISCs are marked by high expression of the EphB2 receptor, which becomes

  17. The fate of epithelial cells in the human large intestine.

    Science.gov (United States)

    Barkla, D H; Gibson, P R

    1999-08-01

    One hundred and forty biopsies of the colon and rectum, collected during routine colonoscopies of 51 patients aged 19 to 74 years, were examined using light microscopy and transmission and scanning electron microscopy. The results indicated that surface epithelial cells undergo apoptosis, passing through fenestrations in the basement membrane to where they enter the lamina propria and are taken up by macrophages; and it is hypothesized that apoptotic cells are carried through the fenestrations on a current of fluid. The study also found that epithelial cells positioned over the crypts are better attached and more robust than those more distant from the crypt opening; and it is further hypothesized that, after reaching the top of the crypts, some goblet cells cease secreting mucus and pass onto the surface compartment of absorptive cells. An unexpected finding was that the lower regions of the crypts commonly contain isolated necrotic colonocytes. Apoptotic cells were rarely observed in the crypt epithelium. The findings of this study support the "recycling" model of epithelial cell death in the surface compartment of the human colon.

  18. Soybean extracts increase cell surface ZIP4 abundance and cellular zinc levels: a potential novel strategy to enhance zinc absorption by ZIP4 targeting.

    Science.gov (United States)

    Hashimoto, Ayako; Ohkura, Katsuma; Takahashi, Masakazu; Kizu, Kumiko; Narita, Hiroshi; Enomoto, Shuichi; Miyamae, Yusaku; Masuda, Seiji; Nagao, Masaya; Irie, Kazuhiro; Ohigashi, Hajime; Andrews, Glen K; Kambe, Taiho

    2015-12-01

    Dietary zinc deficiency puts human health at risk, so we explored strategies for enhancing zinc absorption. In the small intestine, the zinc transporter ZIP4 functions as an essential component of zinc absorption. Overexpression of ZIP4 protein increases zinc uptake and thereby cellular zinc levels, suggesting that food components with the ability to increase ZIP4 could potentially enhance zinc absorption via the intestine. In the present study, we used mouse Hepa cells, which regulate mouse Zip4 (mZip4) in a manner indistinguishable from that in intestinal enterocytes, to screen for suitable food components that can increase the abundance of ZIP4. Using this ZIP4-targeting strategy, two such soybean extracts were identified that were specifically able to decrease mZip4 endocytosis in response to zinc. These soybean extracts also effectively increased the abundance of apically localized mZip4 in transfected polarized Caco2 and Madin-Darby canine kidney cells and, moreover, two apically localized mZip4 acrodermatitis enteropathica mutants. Soybean components were purified from one extract and soyasaponin Bb was identified as an active component that increased both mZip4 protein abundance and zinc levels in Hepa cells. Finally, we confirmed that soyasaponin Bb is capable of enhancing cell surface endogenous human ZIP4 in human cells. Our results suggest that ZIP4 targeting may represent a new strategy to improve zinc absorption in humans. © 2015 Authors; published by Portland Press Limited.

  19. Intestinal Stem Cell Niche Insights Gathered from Both In Vivo and Novel In Vitro Models

    Directory of Open Access Journals (Sweden)

    Nikolce Gjorevski

    2017-01-01

    Full Text Available Intestinal stem cells are located at the base of the crypts and are surrounded by a complex structure called niche. This environment is composed mainly of epithelial cells and stroma which provides signals that govern cell maintenance, proliferation, and differentiation. Understanding how the niche regulates stem cell fate by controlling developmental signaling pathways will help us to define how stem cells choose between self-renewal and differentiation and how they maintain their undifferentiated state. Tractable in vitro assay systems, which reflect the complexity of the in vivo situation but provide higher level of control, would likely be crucial in identifying new players and mechanisms controlling stem cell function. Knowledge of the intestinal stem cell niche gathered from both in vivo and novel in vitro models may help us improve therapies for tumorigenesis and intestinal damage and make autologous intestinal transplants a feasible clinical practice.

  20. Antigen presentation by small intestinal epithelial cells uniquely enhances IFN-γ secretion from CD4{sup +} intestinal intraepithelial lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Ryo; Yamada, Kiyoshi; Iwamoto, Taku; Maeda, Nana; Emoto, Tetsuro; Shimizu, Makoto; Totsuka, Mamoru, E-mail: atotuka@mail.ecc.u-tokyo.ac.jp

    2013-06-14

    Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4{sup +} IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4{sup +} IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4{sup +} IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4{sup +} IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4{sup +} LPLs and primed splenic CD4{sup +} T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4{sup +} IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo.

  1. Antigen presentation by small intestinal epithelial cells uniquely enhances IFN-γ secretion from CD4+ intestinal intraepithelial lymphocytes

    International Nuclear Information System (INIS)

    Hatano, Ryo; Yamada, Kiyoshi; Iwamoto, Taku; Maeda, Nana; Emoto, Tetsuro; Shimizu, Makoto; Totsuka, Mamoru

    2013-01-01

    Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4 + IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4 + IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4 + IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4 + IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4 + LPLs and primed splenic CD4 + T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4 + IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo

  2. Influence of intoxication with vanadium compounds on the intestinal absorption of calcium in the rat

    International Nuclear Information System (INIS)

    Witkowska, D.; Oledzka, R.; Pietrzyk, B.

    1986-01-01

    Calcium is transferred to the plasma after absorption from the gastrointestinal tract and by resorption from the bone. It is recognized that many environmental poisons, e.g. heavy metal, pesticides etc. cause alterations in calcium homeosthasis in human beings and experimental animals. Although vanadium is not considered to be as important a health hazard to man as lead or cadmium it must be nevertheless regarded as a dangerous pollutant. There exists an obvious risk of pollution by and poisoning due to the high vanadium content of crude oil and the industrial use of vanadium as a steel additive. The toxic effects of this element and its compounds in many biological systems have been reviewed in detail but little is known about vanadium influence on calcium metabolism. The present study was undertaken to determine the effect of various treatments with vanadium compounds, containing vanadium as VO 2+ (VOSO 4 ) and VO 3 (NaVO 3 ) ions, exert on calcium transport through the rat duodenum

  3. 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.

  4. Chemical form of selenium affects its uptake, transport, and glutathione peroxidase activity in the human intestinal Caco-2 cell model.

    Science.gov (United States)

    Zeng, Huawei; Jackson, Matthew I; Cheng, Wen-Hsing; Combs, Gerald F

    2011-11-01

    Determining the effect of selenium (Se) chemical form on uptake, transport, and glutathione peroxidase activity in human intestinal cells is critical to assess Se bioavailability at nutritional doses. In this study, we found that two sources of L-selenomethionine (SeMet) and Se-enriched yeast each increased intracellular Se content more effectively than selenite or methylselenocysteine (SeMSC) in the human intestinal Caco-2 cell model. Interestingly, SeMSC, SeMet, and digested Se-enriched yeast were transported at comparable efficacy from the apical to basolateral sides, each being about 3-fold that of selenite. In addition, these forms of Se, whether before or after traversing from apical side to basolateral side, did not change the potential to support glutathione peroxidase (GPx) activity. Although selenoprotein P has been postulated to be a key Se transport protein, its intracellular expression did not differ when selenite, SeMSC, SeMet, or digested Se-enriched yeast was added to serum-contained media. Taken together, our data show, for the first time, that the chemical form of Se at nutritional doses can affect the absorptive (apical to basolateral side) efficacy and retention of Se by intestinal cells; but that, these effects are not directly correlated to the potential to support GPx activity.

  5. De Novo Formation of Insulin-Producing “Neo-β Cell Islets” from Intestinal Crypts

    Directory of Open Access Journals (Sweden)

    Yi-Ju Chen

    2014-03-01

    Full Text Available The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet β cell program, we performed an in vivo screen by expressing three β cell “reprogramming factors” in a wide spectrum of tissues. We report that transient intestinal expression of these factors—Pdx1, MafA, and Ngn3 (PMN—promotes rapid conversion of intestinal crypt cells into endocrine cells, which coalesce into “neoislets” below the crypt base. Neoislet cells express insulin and show ultrastructural features of β cells. Importantly, intestinal neoislets are glucose-responsive and able to ameliorate hyperglycemia in diabetic mice. Moreover, PMN expression in human intestinal “organoids” stimulates the conversion of intestinal epithelial cells into β-like cells. Our results thus demonstrate that the intestine is an accessible and abundant source of functional insulin-producing cells.

  6. Genome-wide analysis of CDX2 binding in intestinal epithelial cells (Caco-2)

    DEFF Research Database (Denmark)

    Boyd, Mette; Hansen, Morten; Jensen, Tine G K

    2010-01-01

    The CDX2 transcription factor is known to play a crucial role in inhibiting proliferation, promoting differentiation and the expression of intestinal specific genes in intestinal cells. The overall effect of CDX2 in intestinal cells has previously been investigated in conditional knock-out mice......, revealing a critical role of CDX2 in the formation of the normal intestinal identity. The identification of direct targets of transcription factors is a key problem in the study of gene regulatory networks. The ChIP-seq technique combines chromatin immunoprecipitation (ChIP) with next generation sequencing...... resulting in a high throughput experimental method of identifying direct targets of specific transcription factors. The method was applied to CDX2, leading to the identification of the direct binding of CDX2 to several known and novel target genes in the intestinal cell. Examination of the transcript levels...

  7. Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.

    Science.gov (United States)

    Nishino, Yukiko; Kubota, Aya; Kanazawa, Takanori; Takashima, Yuuki; Ozeki, Tetsuya; Okada, Hiroaki

    2012-11-01

    A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration. Copyright © 2012 Wiley Periodicals, Inc.

  8. In vitro assessment of potential intestinal absorption of some phenolic families and carboxylic acids from commercial instant coffee samples.

    Science.gov (United States)

    López-Froilán, R; Ramírez-Moreno, E; Podio, N S; Pérez-Rodríguez, M L; Cámara, M; Baroni, M V; Wunderlin, D A; Sánchez-Mata, M C

    2016-06-15

    Coffee is one of the most consumed beverages in the world, being a source of bioactive compounds as well as flavors. Hydroxycinnamic acids, flavonols, and carboxylic acids have been studied in the samples of instant coffee commercialized in Spain. The studies about contents of food components should be complemented with either in vitro or in vivo bioaccessibility studies to know the amount of food components effectively available for functions in the human body. In this sense, a widely used in vitro model has been applied to assess the potential intestinal absorption of phenolic compounds and organic acids. The contents of hydroxycinnamic acids and flavonols were higher in instant regular coffee samples than in the decaffeinated ones. Bioaccessible phenolic compounds in most analyzed samples account for 20-25% of hydroxycinnamic acids and 17-26% of flavonols. This could mean that a great part of them can remain in the gut, acting as potential in situ antioxidants. Quinic, acetic, pyroglutamic, citric and fumaric acids were identified in commercial instant coffee samples. Succinic acid was found in the coffee blend containing chicory. All carboxylic acids showed a very high bioaccessibility. Particularly, acetic acid and quinic acid were found in higher contents in the samples treated with the in vitro simulation of gastrointestinal processes, compared to the original ones, which can be explained by their cleavage from chlorogenic acid during digestion. This is considered as a positive effect, since quinic acid is considered as an antioxidant inducer.

  9. Pharmacokinetics and Bioavailability of the Isoflavones Formononetin and Ononin and Their in Vitro Absorption in Ussing Chamber and Caco-2 Cell Models.

    Science.gov (United States)

    Luo, Li-Yu; Fan, Miao-Xuan; Zhao, Hai-Yu; Li, Ming-Xing; Wu, Xu; Gao, Wen-Yuan

    2018-03-21

    Formononetin and its glycoside ononin are bioactive isoflavones widely present in legumes. The present study investigated the pharmacokinetics, bioavailability, and in vitro absorption of formononetin and ononin. After an oral administration to rats, formononetin showed a higher systemic exposure over ononin. The oral bioavailability of formononetin and ononin were 21.8% and 7.3%, respectively. Ononin was more bioavailable than perceived, and its bioavailability reached 21.7% when its metabolite formononetin was taken into account. Both formononetin and ononin exhibited better absorption in large intestine segments than that in small intestine segments. Formononetin displayed a better permeability in all intestinal segments over ononin. Transport of formononetin across Caco-2 cell monolayer was mainly through passive diffusion, while ononin was actively pumped out by MRP2 but not P-gp. The results provide evidence for better understanding of the pharmacological actions of formononetin and ononin, which advocates more in vivo evaluations or human trials.

  10. Mechanisms and Regulation of Intestinal Absorption of Water-soluble Vitamins: Cellular and Molecular Aspects

    DEFF Research Database (Denmark)

    Nexø, Ebba; Said, Hamid M

    2012-01-01

    The water-soluble vitamins represent a group of structurally and functionally unrelated compounds that share the common feature of being essential for normal cellular functions, growth, and development. With the exception of some endogenous production of niacin, human cells cannot synthesize...

  11. Enabling the intestinal absorption of highly polar antiviral agents: ion-pair facilitated membrane permeation of zanamivir heptyl ester and guanidino oseltamivir.

    Science.gov (United States)

    Miller, Jonathan M; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L

    2010-08-02

    Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a critical step toward making them oral drugs. The counterion 1-hydroxy-2-naphthoic acid (HNAP) was utilized to enhance the lipophilicity and permeability of the highly polar drugs. HNAP substantially increased the log P of the drugs by up to 3.7 log units. Binding constants (K(11(aq))) of 388 M(-1) for ZHE-HNAP and 2.91 M(-1) for GO-HNAP were obtained by applying a quasi-equilibrium transport model to double-reciprocal plots of apparent octanol-buffer distribution coefficients versus HNAP concentration. HNAP enhanced the apparent permeability (P(app)) of both compounds across Caco-2 cell monolayers in a concentration-dependent manner, as substantial P(app) (0.8-3.0 x 10(-6) cm/s) was observed in the presence of 6-24 mM HNAP, whereas no detectable transport was observed without counterion. Consistent with a quasi-equilibrium transport model, a linear relationship with slope near 1 was obtained from a log-log plot of Caco-2 P(app) versus HNAP concentration, supporting the ion-pair mechanism behind the permeability enhancement. In the rat jejunal perfusion assay, the addition of HNAP failed to increase the effective permeability (P(eff)) of GO. However, the rat jejunal permeability of ZHE was significantly enhanced by the addition of HNAP in a concentration-dependent manner, from essentially zero without HNAP to 4.0 x 10(-5) cm/s with 10 mM HNAP, matching the P(eff) of the high-permeability standard metoprolol. The success of ZHE-HNAP was explained by its >100-fold stronger K(11(aq)) versus GO-HNAP, making ZHE-HNAP less prone to dissociation and ion-exchange with competing endogenous anions and able to remain intact during membrane permeation. Overall, this

  12. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh

    2009-10-01

    In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

  13. Wnt target gene analysis in colorectal cancer and intestinal stem cells

    NARCIS (Netherlands)

    van der Flier, L.G.

    2009-01-01

    The intestinal epithelium is a specialized simple epithelium that lines the gut and performs primary functions of digestion, absorption and forms a barrier against luminal pathogens. It is organized in invaginations called crypts and finger-like protrusions called villi. The crypts harbor

  14. CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury.

    Science.gov (United States)

    Stzepourginski, Igor; Nigro, Giulia; Jacob, Jean-Marie; Dulauroy, Sophie; Sansonetti, Philippe J; Eberl, Gérard; Peduto, Lucie

    2017-01-24

    The intestinal epithelium is continuously renewed by intestinal epithelial stem cells (IESCs) positioned at the base of each crypt. Mesenchymal-derived factors are essential to maintain IESCs; however, the cellular composition and development of such mesenchymal niche remains unclear. Here, we identify pericryptal CD34 + Gp38 + αSMA - mesenchymal cells closely associated with Lgr5 + IESCs. We demonstrate that CD34 + Gp38 + cells are the major intestinal producers of the niche factors Wnt2b, Gremlin1, and R-spondin1, and are sufficient to promote maintenance of Lgr5 + IESCs in intestinal organoids, an effect mainly mediated by Gremlin1. CD34 + Gp38 + cells develop after birth in the intestinal submucosa and expand around the crypts during the third week of life in mice, independently of the microbiota. We further show that pericryptal CD34 + gp38 + cells are rapidly activated by intestinal injury, up-regulating niche factors Gremlin1 and R-spondin1 as well as chemokines, proinflammatory cytokines, and growth factors with key roles in gut immunity and tissue repair, including IL-7, Ccl2, Ptgs2, and Amphiregulin. Our results indicate that CD34 + Gp38 + mesenchymal cells are programmed to develop in the intestine after birth to constitute a specialized microenvironment that maintains IESCs at homeostasis and contribute to intestinal inflammation and repair after injury.

  15. [Construction of research system for processing mechanism of traditional Chinese medicine based on chemical composition transformation combined with intestinal absorption barrier].

    Science.gov (United States)

    Sun, E; Xu, Feng-Juan; Zhang, Zhen-Hai; Wei, Ying-Jie; Tan, Xiao-Bin; Cheng, Xu-Dong; Jia, Xiao-Bin

    2014-02-01

    Based on practice of Epimedium processing mechanism for many years and integrated multidisciplinary theory and technology, this paper initially constructs the research system for processing mechanism of traditional Chinese medicine based on chemical composition transformation combined with intestinal absorption barrier, which to form an innovative research mode of the " chemical composition changes-biological transformation-metabolism in vitro and in vivo-intestinal absorption-pharmacokinetic combined pharmacodynamic-pharmacodynamic mechanism". Combined with specific examples of Epimedium and other Chinese herbal medicine processing mechanism, this paper also discusses the academic thoughts, research methods and key technologies of this research system, which will be conducive to systematically reveal the modem scientific connotation of traditional Chinese medicine processing, and enrich the theory of Chinese herbal medicine processing.

  16. Intestinal Transportations of Main Chemical Compositions of Polygoni Multiflori Radix in Caco-2 Cell Model

    Directory of Open Access Journals (Sweden)

    Jie Yu

    2014-01-01

    Full Text Available Context. Polygoni Multiflori Radix (PMR is originated from the root of Polygonum multiflorum Thunb. and used in oriental countries for centuries. However, little researches pay close attention to the absorption of its major constituents. Objective. Transepithelial transport of TSG, RL, PL, and four anthraquinones is carried out. Materials and Methods. Caco-2 cell monolayer, which represented a well-established model for the study of intestinal transport of nutrients and xenobiotics, was used in this paper. Results. The apparent permeability coefficients (Papp in the Caco-2 cell monolayers were TSG (2.372 × 10−9 < EG (2.391 × 10−9 < EN (2.483 × 10−9 < PL (4.917 × 10−9 < RN (1.707 × 10−8 < RL (1.778 × 10−8 < AE (1.952 × 10−8. Thus, RN, RL, and AE were considered partly absorbed, while other constituents were hardly absorbed. Discussion and Conclusion. Glycosides showed poor permeabilities than aglycones. In the meantime, TSG and EN gave out poor recovery rates in this assay, which indicated that TSG and EN may accumulate or metabolise in the Caco-2 cells. In silico prediction indicated that Gibbs energy (r=0.751, p<0.05 and heat of form (r=0.701, p<0.05 were strongly positively correlated with Papp.

  17. NMR imaging of cell phone radiation absorption in brain tissue

    Science.gov (United States)

    Gultekin, David H.; Moeller, Lothar

    2013-01-01

    A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry. PMID:23248293

  18. Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover

    Science.gov (United States)

    Gibson, P; Birchall, I; Rosella, O; Albert, V; Finch, C; Barkla, D; Young, G

    1998-01-01

    Background—The functions of urokinase in intestinal epithelia are unknown. 
Aims—To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon. 
Methods—Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequentially from the crypt-villus axis of the rat small intestine. In separate experiments, urokinase activity and epithelial kinetics (measured stathmokinetically) were measured in homogenates of distal colonic mucosa of 14 groups of eight rats fed diets known to alter epithelial turnover. 
Results—From the crypt base, an ascending gradient of expression and activity of urokinase was associated with the epithelial cells. Median mucosal urokinase activities in each of the dietary groups of rats correlated positively with autologous median number of metaphase arrests per crypt (r=0.68; p<0.005) and per 100 crypt cells (r=0.75; p<0.001), but not with crypt column height. 
Conclusions—Localisation of an enzyme capable of leading to digestion of cell substratum in the region where cells are loosely attached to their basement membrane, and the association of its activity with indexes of cell turnover, suggest a role for urokinase in facilitating epithelial cell loss in the intestine. 

 Keywords: urokinase; intestinal epithelium; colon; epithelial proliferation PMID:9824347

  19. Mechanisms of Cell Polarity-Controlled Epithelial Homeostasis and Immunity in the Intestine

    NARCIS (Netherlands)

    Klunder, Leon J.; Faber, Klaas Nico; Dijkstra, Gerard; van IJzendoorn, Sven C. D.

    Intestinal epithelial cell polarity is instrumental to maintain epithelial homeostasis and balance communications between the gut lumen and bodily tissue, thereby controlling the defense against gastrointestinal pathogens and maintenance of immune tolerance to commensal bacteria. In this review, we

  20. Indian hedgehog regulates intestinal stem cell fate through epithelial-mesenchymal interactions during development

    NARCIS (Netherlands)

    Kosinski, C.; Stange, D.E.; Xu, C.; Chan, A.S.; Ho, C.; Yuen, S.T.; Mifflin, R.C.; Powell, D.W.; Clevers, H.; Leung, S.Y.; Chen, X.N.

    2010-01-01

    BACKGROUND & AIMS: Intestinal stem cells (ISCs) are regulated by the mesenchymal environment via physical interaction and diffusible factors. We examined the role of Indian hedgehog (Ihh) in mesenchymal organization and the mechanisms by which perturbations in epithelial-mesenchymal interactions

  1. Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells

    Directory of Open Access Journals (Sweden)

    Yu Takahashi

    2017-09-01

    Full Text Available Visceral fat accumulation as observed in Crohn's disease and obesity is linked to chronic gut inflammation, suggesting that accumulation of gut adipocytes can trigger local inflammatory signaling. However, direct interactions between intestinal epithelial cells (IECs and adipocytes have not been investigated, in part because IEC physiology is difficult to replicate in culture. In this study, we originally prepared intact, polarized, and cytokine responsive IEC monolayers from primary or induced pluripotent stem cell-derived intestinal organoids by simple and repeatable methods. When these physiological IECs were co-cultured with differentiated adipocytes in Transwell, pro-inflammatory genes were induced in both cell types, suggesting reciprocal inflammatory activation in the absence of immunocompetent cells. These inflammatory responses were blocked by nuclear factor-κB or signal transducer and activator of transcription 3 inhibition and by anti-tumor necrosis factor- or anti-interleukin-6-neutralizing antibodies. Our results highlight the utility of these monolayers for investigating IEC biology. Furthermore, this system recapitulates the intestinal epithelium–mesenteric fat signals that potentially trigger or worsen inflammatory disorders such as Crohn's disease and obesity-related enterocolitis.

  2. Nanoscale dimples for improved absorption in organic solar cells

    DEFF Research Database (Denmark)

    Goszczak, Arkadiusz Jaroslaw; Rubahn, Horst-Günter; Madsen, Morten

    Organic solar cells (OSC’s) have attracted much attention in the past years due to their potential low-cost, light-weight and mechanical flexibility. A method for improving the power conversion efficiencies of the devices is by incorporating structured electrodes in the solar cell architecture......, as they can improve light absorption in the active layers of the devices. In this direction, a cheap and large-scale compatible method for structuring the electrodes in OSC’s is by the use of Anodic Alumina Oxide (AAO) membranes. In the present work, Al films of high purity and low roughness are formed via e...

  3. Lipopolysaccharide-binding protein: localization in secretory granules of Paneth cells in the mouse small intestine

    DEFF Research Database (Denmark)

    Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte

    2009-01-01

    Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase protein involved in the host's response to endotoxin and mainly synthesized and secreted to the blood by the liver. But in addition, LBP is also made by extrahepatic cells, including the enterocyte-like cell line Caco-2. To study...... in closer detail the synthesis and storage of LBP in the intestinal mucosal epithelium, we performed an immunolocalization of LBP in mouse small intestine. By immunofluorescence microscopy, an antibody recognizing the 58-60 kDa protein of LBP distinctly labeled a small population of cells located deep...... into the crypts. This cell population was also positive for lysozyme and alpha-defensin 4, identifying Paneth cells as the main intestinal LBP-producing cells. By immunogold electron microscopy, intense labeling was observed in the secretory granules of these cells. We conclude that Paneth cells express LBP...

  4. PAF-Myc-Controlled Cell Stemness Is Required for Intestinal Regeneration and Tumorigenesis.

    Science.gov (United States)

    Kim, Moon Jong; Xia, Bo; Suh, Han Na; Lee, Sung Ho; Jun, Sohee; Lien, Esther M; Zhang, Jie; Chen, Kaifu; Park, Jae-Il

    2018-03-12

    The underlying mechanisms of how self-renewing cells are controlled in regenerating tissues and cancer remain ambiguous. PCNA-associated factor (PAF) modulates DNA repair via PCNA. Also, PAF hyperactivates Wnt/β-catenin signaling independently of PCNA interaction. We found that PAF is expressed in intestinal stem and progenitor cells (ISCs and IPCs) and markedly upregulated during intestinal regeneration and tumorigenesis. Whereas PAF is dispensable for intestinal homeostasis, upon radiation injury, genetic ablation of PAF impairs intestinal regeneration along with the severe loss of ISCs and Myc expression. Mechanistically, PAF conditionally occupies and transactivates the c-Myc promoter, which induces the expansion of ISCs/IPCs during intestinal regeneration. In mouse models, PAF knockout inhibits Apc inactivation-driven intestinal tumorigenesis with reduced tumor cell stemness and suppressed Wnt/β-catenin signaling activity, supported by transcriptome profiling. Collectively, our results unveil that the PAF-Myc signaling axis is indispensable for intestinal regeneration and tumorigenesis by positively regulating self-renewing cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2009-04-01

    To investigate the potential interaction between grapefruit juice (GFJ) and the oral microtubule polymerization inhibitor colchicine, a P-gp and CYP3A4 substrate. Colchicine intestinal epithelial transport was investigated across Caco-2 cell monolayers in both AP-BL and BL-AP directions, in the absence/presence of known P-gp inhibitors (verapamil and quinidine). The concentration-dependent effects of GFJ and its major constituents (6'-7'-dihydroxybergamottin, naringin and naringenin) on colchicine Caco-2 mucosal secretion were examined. The effect of GFJ on colchicine intestinal-permeability was then investigated in-situ in the rat perfusion model, in both jejunum and ileum. Colchicine exhibited 20-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion, which was reduced by verapamil/quinidine. Colchicine AP-BL permeability was increased and BL-AP was decreased by GFJ in a concentration-dependent manner (IC(50) values of 0.75% and 0.46% respectively), suggesting inhibition of efflux transport, rather than metabolizing enzyme. Similar effects obtained following pre-experiment incubation with GFJ, even though the juice was not present throughout the transepithelial study. 6'-7'-Dihydroxybergamottin, naringin and naringenin displayed concentration-dependent inhibition on colchicine BL-AP secretion (IC(50) values of 90, 592 and 11.6 microM respectively). Ten percent GFJ doubled colchicine rat in-situ ileal permeability, and increased 1.5-fold jejunal permeability. The data suggest that GFJ may augment colchicine oral bioavailability. Due to colchicine narrow therapeutic-index and severely toxic side-effects, awareness of this interaction is prudent.

  6. Intestinal absorption of /sup 47/Ca in elderly patients with osteoporosis, Paget's disease, and osteomalacia. Effects of calcitonin, oestrogen, and vitamin D2

    Energy Technology Data Exchange (ETDEWEB)

    Lender, M.; Verner, E.; Stankiewicz, H.; Menczel, J.

    1977-01-01

    The intestinal absorption of /sup 47/Ca was studied in elderly patients. A standard dose of 10 ..mu..Ci of /sup 47/Ca was given orally. The radioactivity was measured in the plasma, and expressed as percentage of the administered dose per litre plasma. As a control group served 12 patients aged 60--80 years, hospitalized for observation for various reasons, receiving no medical treatment and not suffering from any known metabolic bone diseases or other metabolic pathological conditions. Results of kinetic curves demonstrate in elderly patients a decreased absorption with maximum specific activity in plasma reached at 120 min, when compared to data from the literature referring to a group of young people with a mean age of 35 years. Oestrogen treatment, given as ethinyl oestradiol 10 ..mu..g once daily per os for 10 days proved to increase /sup 47/Ca absorption as was demonstrated in 2 patients with osteoporosis. The effect of calcitonin (160 MRC units given 45 min before the test) on calcium absorption, in 5 patients with Paget's disease or osteoporosis appears as biphasic: in the first hour depressing calcium absorption and then in the second and third hours increasing the absorption, suggesting a hyperparathyroid state secondary to the calcitonin effect. The vitamin D2 treatment proved to increase calcium absorption.

  7. Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes

    NARCIS (Netherlands)

    Schepers, A.G.; Vries, R.G.J.; van den Born, M.M.W.; van de Wetering, M.L.; Clevers, H.

    2011-01-01

    Somatic cells have been proposed to be limited in the number of cell divisions they can undergo. This is thought to be a mechanism by which stem cells retain their integrity preventing disease. However, we have recently discovered intestinal crypt stem cells that persist for the lifetime of a mouse,

  8. Mechanisms of Cell Polarity-Controlled Epithelial Homeostasis and Immunity in the Intestine.

    Science.gov (United States)

    Klunder, Leon J; Faber, Klaas Nico; Dijkstra, Gerard; van IJzendoorn, Sven C D

    2017-07-05

    Intestinal epithelial cell polarity is instrumental to maintain epithelial homeostasis and balance communications between the gut lumen and bodily tissue, thereby controlling the defense against gastrointestinal pathogens and maintenance of immune tolerance to commensal bacteria. In this review, we highlight recent advances with regard to the molecular mechanisms of cell polarity-controlled epithelial homeostasis and immunity in the human intestine. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  9. Radioprotective effect of dextran sulphate and aerogenic hypoxia on intestinal crypt stem cells in mice

    International Nuclear Information System (INIS)

    Vacek, A.; Bartonickova, A.; Rotkovska, D.; Konoplyanikova, O.A.; Konoplyanikov, A.G.

    1991-01-01

    A single intraperitoneal injection of dextran sulfate given 6 h before irradiation produced higher numbers of microcolonies of intestinal crypt stem cells in whole-body irradiated mice than an injection of saline in control mice. If dextran sulfate and hypoxia are combined, the radioprotective effect of hypoxia on intestinal crypt stem cells depends on the time interval between irradiation and administration of dextran sulfate. (author). 2 figs., 12 refs

  10. Gut microbiota regulates NKG2D ligand expression on intestinal epithelial cells

    DEFF Research Database (Denmark)

    Hansen, Camilla Hartmann Friis; Holm, Thomas L.; Krych, Lukasz

    2013-01-01

    Intestinal epithelial cells (IECs) are one of a few cell types in the body with constitutive surface expression of natural killer group 2 member D (NKG2D) ligands, although the magnitude of ligand expression by IECs varies. Here, we investigated whether the gut microbiota regulates the NKG2D ligand...... expression is kept in check by an intestinal regulatory immune milieu induced by members of the gut microbiota, for example A. muciniphila....

  11. Regulation of T-cell Responses in the Inflamed Intestine

    NARCIS (Netherlands)

    M.A. Van Leeuwen (Marieke)

    2015-01-01

    markdownabstract__Abstract__ The intestinal immune system protects the mucosal surfaces from pathogenic microorganisms. On the other hand it maintains tolerance towards dietary antigens and non-pathogenic microorganisms. The immune system continuously tailors these inflammatory and tolerogenic

  12. c-Kit mutation reduce intestinal epithelial cell proliferation and migration, but not influence intestinal permeability stimulated by lipopolysaccharide.

    Science.gov (United States)

    Xue, Hong; Wang, Feng Yun; Kang, Qian; Tang, Xu Dong

    2018-06-20

    The proto-oncogene c-kit, as a marker of interstitial cells of Cajal (ICCs) in the gastrointestinal tract, plays an important role in the ICCs. Although limited evidences showed c-kit is present in the colonic epithelium but its roles remain unclear. In the present study, we aimed to investigate the expression, location and function of c-kit in the intestinal epithelium. Immunofluorescence, western blotting, and RT-PCR were performed to detect the expression and location of c-kit in the intestinal mucosa of WT mice. We investigated intestinal epithelial proliferation and migration in vivo by performing 5-Bromodeoxyuridine (BrdU) incorporation and Ki-67 staining in WT and Wads m/m mice. An Ussing chamber with fluorescein-isothiocyanate dextran 4000 was used to detect the transepithelial electric resistance (TER), short circuit current (ISC) and permeability across ex vivo colon segments under control and endotoxaemia conditions. We demonstrated that c-kit was located and expressed in the gut crypt compartment in WT mice, which was demonstrated in the c-kit mutant mice (Wads m/m ). In addition, both the number of proliferating cells and the percentage of the distance migrated were lower in the Wads m/m mice than those in the WT mice. Moreover, the intestinal permeability, TER and tight junction were unaltered in the Wads m/m mice under endotoxic conditions compared with those in both the control condition and the WT mice. Altogether, these observations imply that the expression of c-kit in the colonic epithelium is involved in the proliferation and permeability of the colonic epithelium. Copyright © 2018. Published by Elsevier GmbH.

  13. The absorption factor of crystalline silicon PV cells: a numerical and experimental study

    NARCIS (Netherlands)

    Santbergen, R.; Zolingen, van R.J.C.

    2008-01-01

    The absorption factor of a PV cell is defined as the fraction of incident solar irradiance that is absorbed by the cell. This absorption factor is one of the major parameters determining the cell temperature under operational conditions. Experimentally the absorption factor can be derived from

  14. The role of CD103+ Dendritic cells in the intestinal mucosal immune system.

    Directory of Open Access Journals (Sweden)

    Darren Thomas Ruane

    2011-07-01

    Full Text Available While dendritic cells (DC are central to the induction and regulation of adaptive immunity, these cells are very heterogenous and specific subsets can be characterized based on the expression of cell surface markers and functional properties. Intestinal CD103+ DCs are the subject of particular interest due to their role in regulating mucosal immunity. Since the epithelial surfaces are constantly exposed to a high antigenic load, tight regulation of innate and adaptive intestinal immune responses is vital as intestinal inflammation can have detrimental consequences for the host. Strategically positioned within the lamina propria, CD103+ DCs play an important role in maintaining intestinal immune homeostasis. These cells are required for the induction of tolerogenic immune responses and imprinting gut homing phenotypic changes on antigen-specific T cells. Recent insights into their development and regulatory properties have revealed additional immunoregulatory roles and further highlighted their importance for intestinal immunity. In this review we discuss the nature of the intestinal CD103+ DC population and the emerging roles of these cells in the regulation of mucosal immunity.

  15. Effects of fasting and refeeding on intestinal cell proliferation and apoptosis in hammerhead shark (Sphyrna lewini

    Directory of Open Access Journals (Sweden)

    Hideya Takahashi

    2014-04-01

    Full Text Available Objective: To examine the effects of fasting and refeeding on intestinal cell proliferation and apoptosis in an opportunistic predator, hammerhead shark (Sphyrna lewini of elasmobranch fishes which are among the earliest known extant groups of vertebrates to have the valvular intestine typical for the primitive species. Methods: Animals were euthanized after 5-10 d of fasting or feeding, or after 10-day fasting and 5-day refeeding. Intestinal apoptosis and cell proliferation were assessed by using oligonucleotide detection assay, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry of proliferating cells nuclear antigen. Results: Plasma levels of cholesterol and glucose were reduced by fasting. Intestinal apoptosis generally decreased during fasting. Numerous apoptotic cells were observed around the tips of the villi, primarily in the epithelium in the fed sharks, whereas fewer labeled nuclei were detected in the epithelium of fasted sharks. Refeeding returned intestinal apoptosis to the level in the fed sharks. Proliferating cells were observed in the epithelium around the troughs of the villi and greater in number in fed sharks, whereas fewer labeled nuclei were detected in fasted sharks. Conclusions: The cell turnover is modified in both intestinal epithelia of the shark and the murines by fasting/feeding, but in opposite directions. The difference may reflect the feeding ecology of the elasmobranchs, primitive intermittent feeders.

  16. Posaconazole plasma exposure correlated to intestinal mucositis in allogeneic stem cell transplant patients.

    Science.gov (United States)

    Vanstraelen, Kim; Prattes, Juergen; Maertens, Johan; Lagrou, Katrien; Schoemans, Hélène; Peersman, Nele; Vermeersch, Pieter; Theunissen, Koen; Mols, Raf; Augustijns, Patrick; Annaert, Pieter; Hoenigl, Martin; Spriet, Isabel

    2016-08-01

    Low posaconazole plasma concentrations (PPCs) are frequently encountered in allogeneic hematopoietic stem cell transplant (HSCT) patients, due to variable gastrointestinal absorption. In this study, the impact of intestinal mucositis on posaconazole exposure is investigated. A prospective pharmacokinetic study was performed including allogeneic HSCT patients receiving posaconazole prophylaxis with the oral suspension or tablets. Steady state PPCs were determined using high-performance liquid chromatography-fluorescence detection at the day of transplantation (=day 0), day +7, and +14. Citrulline was measured using liquid chromatography-tandem mass spectrometry to evaluate severity of mucositis, at baseline (day -7 or -6), and at day 0, +7 and +14. Additionally, citrulline plasma concentrations and steady state trough PPCs were determined in hematological patients without HSCT or mucositis. Thirty-four HSCT patients received posaconazole oral suspension together with 25 cL of Coca Cola, 6 HSCT patients received posaconazole tablets and 33 hematological patients not receiving HSCT received posaconazole oral suspension. The median (interquartile range) average PPC was 0.26 mg/L (0.17-0.43), 0.67 mg/L (0.27-1.38), and 1.08 mg/L (0.96-1.38), with suspension in HSCT patients, suspension in hematological patients and tablets in HSCT patients, respectively. A higher trough PPC was encountered with the oral suspension when citrulline plasma concentrations were above 10 μmol/L compared to values below 10 μmol/L (p < 0.001), whereas for tablets, average PPCs remained high with citrulline plasma concentrations below or above 10 μmol/L (p = 0.64). Posaconazole tablets should be preferred to suspension in HSCT patients immediately after transplantation to prevent insufficient plasma exposure due to intestinal mucositis.

  17. LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose.

    Science.gov (United States)

    Powell, David R; Smith, Melinda; Greer, Jennifer; Harris, Angela; Zhao, Sharon; DaCosta, Christopher; Mseeh, Faika; Shadoan, Melanie K; Sands, Arthur; Zambrowicz, Brian; Ding, Zhi-Ming

    2013-05-01

    LX4211 [(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol], a dual sodium/glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor, is thought to decrease both renal glucose reabsorption by inhibiting SGLT2 and intestinal glucose absorption by inhibiting SGLT1. In clinical trials in patients with type 2 diabetes mellitus (T2DM), LX4211 treatment improved glycemic control while increasing circulating levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). To better understand how LX4211 increases GLP-1 and PYY levels, we challenged SGLT1 knockout (-/-) mice, SGLT2-/- mice, and LX4211-treated mice with oral glucose. LX4211-treated mice and SGLT1-/- mice had increased levels of plasma GLP-1, plasma PYY, and intestinal glucose during the 6 hours after a glucose-containing meal, as reflected by area under the curve (AUC) values, whereas SGLT2-/- mice showed no response. LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone. However, GLP-1 and GIP levels were not increased in LX4211-treated mice and were decreased in SGLT1-/- mice, 5 minutes after oral glucose, consistent with studies linking decreased intestinal SGLT1 activity with reduced GLP-1 and GIP levels 5 minutes after oral glucose. These data suggest that LX4211 reduces intestinal glucose absorption by inhibiting SGLT1, resulting in net increases in GLP-1 and PYY release and decreases in GIP release and blood glucose excursions. The ability to inhibit both intestinal SGLT1 and renal SGLT2 provides LX4211 with a novel dual mechanism of action for improving glycemic control in patients with T2DM.

  18. Improvement of intestinal absorption of forsythoside A and chlorogenic acid by different carboxymethyl chitosan and chito-oligosaccharide, application to Flos Lonicerae-Fructus Forsythiae herb couple preparations.

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    Full Text Available The current study aims to investigate the effect of chitosan derivatives on the intestinal absorption and bioavailabilities of forsythoside A (FTA and Chlorogenic acid (CHA, the major active components in Flos Lonicerae-Fructus Forsythiae herb couple. Biopharmaceutics and pharmacokinetics properties of the two compounds have been characterized in vitro, in situ as well as in rats. Based on the identified biopharmaceutics characteristics of the two compounds, the effect of chitosan derivatives as an absorption enhancer on the intestinal absorption and pharmacokinetics of FTA and CHA in pure compound form as well as extract form were investigated in vitro, in situ and in vivo. Both FTA and CHA demonstrated very limited intestinal permeabilities, leading to oral bioavailabilities being only 0.50% and 0.13% in rats, respectively. Results from both in vitro, in situ as well as in vivo studies consistently indicated that Chito-oligosaccharide (COS at dosage of 25 mg/kg could enhance intestinal permeabilities significantly as well as the in vivo bioavailabilities of both FTA and CHA than CMCs in Flos Lonicerae-Fructus Forsythiae herb couple preparations, and was safe for gastrointestine from morphological observation. Besides, treatment with Flos Lonicerae-Fructus Forsythiae herb couple preparations with COS at the dosage of 25 mg/kg prevented MDCK damage after influenza virus propagation, which was significantly better than control. The current findings not only identified the usefulness of COS for the improved delivery of Flos Lonicerae-Fructus Forsythiae preparations but also demonstrated the importance of biopharmaceutical characterization in the dosage form development of traditional Chinese medicine.

  19. Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology

    NARCIS (Netherlands)

    J. Foulke-Abel (Jennifer); J. In (Julie); Yin, J. (Jianyi); N.C. Zachos (Nicholas C.); O. Kovbasnjuk (Olga); M.K. Estes (Mary K.); H.R. de Jonge (Hugo); M. Donowitz (Mark)

    2016-01-01

    textabstractBackground & Aims Human intestinal crypt-derived enteroids are a model of intestinal ion transport that require validation by comparison with cell culture and animal models. We used human small intestinal enteroids to study neutral Na+ absorption and stimulated fluid and anion secretion

  20. 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.

  1. 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.

  2. Crohn's disease intestinal CD4+ T cells have impaired interleukin-10 productionwhich is not restored by probiotic bacteria

    DEFF Research Database (Denmark)

    Hvas, Christian L; Kelsen, Jens; Agnholt, Jørgen

    2007-01-01

    OBJECTIVE: Crohn's disease (CD) has been associated with low mucosal interleukin (IL)-10 production, but the mechanism behind this deficiency remains unclear. The aim of this study was to investigate IL-10 and interferon (IFN)-gamma production in intestinal CD4+ T cells from CD patients and healthy...... volunteers (HV) and to examine how this was affected by bacterial products and the presence or absence of autologous dendritic cells. MATERIAL AND METHODS: We cultured intestinal CD4+ T cells from CD patients (n=9) and HV (n=6) and differentiated dendritic cells from their peripheral monocytes. Intestinal T...... this imbalance in CD, but tended to do so in HV. When there were no dendritic cells, CD intestinal T cells responded to autologous bacteria with an increased IFN-gamma production (2.3+/-1.3 ng/ml) compared with HV intestinal T cells (0.3+/-0.2 ng/ml). CONCLUSIONS: Crohn's disease intestinal CD4+ T cells display...

  3. Enteroendocrine cells are specifically marked by cell surface expression of claudin-4 in mouse small intestine.

    Directory of Open Access Journals (Sweden)

    Takahiro Nagatake

    Full Text Available Enteroendocrine cells are solitary epithelial cells scattered throughout the gastrointestinal tract and produce various types of hormones, constituting one of the largest endocrine systems in the body. The study of these rare epithelial cells has been hampered by the difficulty in isolating them because of the lack of specific cell surface markers. Here, we report that enteroendocrine cells selectively express a tight junction membrane protein, claudin-4 (Cld4, and are efficiently isolated with the use of an antibody specific for the Cld4 extracellular domain and flow cytometry. Sorted Cld4+ epithelial cells in the small intestine exclusively expressed a chromogranin A gene (Chga and other enteroendocrine cell-related genes (Ffar1, Ffar4, Gpr119, and the population was divided into two subpopulations based on the activity of binding to Ulex europaeus agglutinin-1 (UEA-1. A Cld4+UEA-1- cell population almost exclusively expressed glucose-dependent insulinotropic polypeptide gene (Gip, thus representing K cells, whereas a Cld4+UEA-1+ cell population expressed other gut hormone genes, including glucagon-like peptide 1 (Gcg, pancreatic polypeptide-like peptide with N-terminal tyrosine amide (Pyy, cholecystokinin (Cck, secretin (Sct, and tryptophan hydroxylase 1 (Tph1. In addition, we found that orally administered luminal antigens were taken up by the solitary Cld4+ cells in the small intestinal villi, raising the possibility that enteroendocrine cells might also play a role in initiation of mucosal immunity. Our results provide a useful tool for the cellular and functional characterization of enteroendocrine cells.

  4. Intestinal epithelial cell-specific RARα depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system.

    Science.gov (United States)

    Jijon, H B; Suarez-Lopez, L; Diaz, O E; Das, S; De Calisto, J; Yaffe, M B; Pittet, M J; Mora, J R; Belkaid, Y; Xavier, R J; Villablanca, E J

    2018-05-01

    Retinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined. Here we demonstrate that lack of RA receptor α (RARα) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells. Mechanistically, lack of RARα resulted in increased KLF4 + goblet cell precursors in the distal bowel, whereas RA treatment inhibited klf4 expression and goblet cell differentiation in zebrafish. These changes in secretory cells are associated with increased Reg3g, reduced luminal bacterial detection, and an underdeveloped intestinal immune system, as evidenced by an almost complete absence of lymphoid follicles and gut resident mononuclear phagocytes. This underdeveloped intestinal immune system shows a decreased ability to clear infection with Citrobacter rodentium. Collectively, our findings indicate that epithelial cell-intrinsic RARα signaling is critical to the global development of the intestinal immune system.

  5. Short Bowel Patients Treated for Two Years with Glucagon-Like Peptide 2: Effects on Intestinal Morphology and Absorption, Renal Function, Bone and Body Composition, and Muscle Function

    Directory of Open Access Journals (Sweden)

    P. B. Jeppesen

    2009-01-01

    Full Text Available Background and aims. In a short-term study, Glucagon-like peptide 2 (GLP-2 has been shown to improve intestinal absorption in short bowel syndrome (SBS patients. This study describes longitudinal changes in relation to GLP-2 treatment for two years. Methods. GLP-2, 400 micrograms, s.c.,TID, were offered, to eleven SBS patients keeping parenteral support constant. 72-hour nutritional balance studies were performed at baseline, weeks 13, 26, 52 during two years intermitted by an 8-week washout period. In addition, mucosal morphometrics, renal function (by creatinine clearance, body composition and bone mineral density (by DEXA, biochemical markers of bone turnover (by s-CTX and osteocalcin, PTH and vitamin D, and muscle function (NMR, lungfunction, exercise test were measured. Results. GLP-2 compliance was >93%. Three of eleven patients did not complete the study. In the remaining 8 patients, GLP-2 significantly reduced the fecal wet weight from approximately 3.0 to approximately 2.0 kg/day. This was accompanied by a decline in the oral wet weight intake, maintaining intestinal wet weight absorption and urinary weight constant. Renal function improved. No significant changes were demonstrated in energy intake or absorption, and GLP-2 did not significantly affect mucosal morphology, body composition, bone mineral density or muscle function. Conclusions. GLP-2 treatment reduces fecal weight by approximately 1000 g/d and enables SBS patients to maintain their intestinal fluid and electrolyte absorption at lower oral intakes. This was accompanied by a 28% improvement in creatinine clearance.

  6. Nano-sized water-in-oil-in-water emulsion enhances intestinal absorption of calcein, a high solubility and low permeability compound.

    Science.gov (United States)

    Koga, Kenjiro; Takarada, Nobuo; Takada, Kanji

    2010-02-01

    Our goal was to develop safe and stable multilayer emulsions capable of enhancing intestinal absorption of biopharmaceutics classification system (BCS) class III drugs. First, w/o emulsions were prepared using calcein as a model BCS class III compound and condensed ricinoleic acid tetraglycerin ester as a hydrophobic emulsifier. Then water-in-oil-in-water (w/o/w) emulsions were prepared with shirasu porous glass (SPG) membranes. Particle size analyses and calcein leakage from oil droplets in w/o/w emulsions led us to select stearic acid hexaglycerin esters (HS-11) and Gelucire 44/14 as hydrophilic emulsifiers. Analyses of the absorption-enhancing effects of w/o/w emulsions on intestinal calcein absorption in rats showed that calcein bioavailability after intraduodenal (i.d.) administration of HS-11 or Gelucire 44/14+polyvinyl alcohol (PVA) w/o/w emulsions prepared with 0.1-microm pore-sized SPGs was significantly higher than that of the calcein control. However, serum calcein concentration vs. time profiles after i.d. administration of w/o/w emulsions prepared with 1.1-microm and 30-microm pore-sized SPGs and an emulsion prepared with a calcein-containing outer water phase were comparable to control profiles. These results suggested that HS-11 or Gelucire 44/14+PVA are safe outer water phase additives and that 0.1-microm pore-sized SPGs are important for preparing w/o/w emulsions that enhanced intestinal calcein absorption. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  7. Intestinal Epithelial Cells Modulate Antigen-Presenting Cell Responses to Bacterial DNA

    Science.gov (United States)

    Campeau, J. L.; Salim, S. Y.; Albert, E. J.; Hotte, N.

    2012-01-01

    Intestinal epithelial cells and antigen-presenting cells orchestrate mucosal innate immunity. This study investigated the role of bacterial DNA in modulating epithelial and bone marrow-derived antigen-presenting cells (BM-APCs) and subsequent T-lymphocyte responses. Murine MODE-K epithelial cells and BM-APCs were treated with DNA from either Bifidobacterium breve or Salmonella enterica serovar Dublin directly and under coculture conditions with CD4+ T cells. Apical stimulation of MODE-K cells with S. Dublin DNA enhanced secretion of cytokines from underlying BM-APCs and induced interleukin-17 (IL-17) and gamma interferon (IFN-γ) secretion from CD4+ T cells. Bacterial DNA isolated from either strain induced maturation and increased cytokine secretion from BM-APCs. Conditioned medium from S. Dublin-treated MODE-K cells elicited an increase in cytokine secretion similar to that seen for S. Dublin DNA. Treatment of conditioned medium from MODE-K cells with RNase and protease prevented the S. Dublin-induced increased cytokine secretion. Oral feeding of mice with B. breve DNA resulted in enhanced levels of colonic IL-10 and transforming growth factor β (TGFβ) compared with what was seen for mice treated with S. Dublin DNA. In contrast, feeding mice with S. Dublin DNA increased levels of colonic IL-17 and IL-12p70. T cells from S. Dublin DNA-treated mice secreted high levels of IL-12 and IFN-γ compared to controls and B. breve DNA-treated mice. These results demonstrate that intestinal epithelial cells are able to modulate subsequent antigen-presenting and T-cell responses to bacterial DNA with pathogenic but not commensal bacterial DNA inducing effector CD4+ T lymphocytes. PMID:22615241

  8. Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin.

    Science.gov (United States)

    Ji, Hongyu; Tang, Jingling; Li, Mengting; Ren, Jinmei; Zheng, Nannan; Wu, Linhua

    2016-01-01

    The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin. The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin. The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p curcumin for SLNs was significantly improved (p curcumin solution. Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.

  9. Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of Notch

    DEFF Research Database (Denmark)

    López-Arribillaga, Erika; Rodilla, Verónica; Pellegrinet, Luca

    2015-01-01

    Genetic data indicate that abrogation of Notch-Rbpj or Wnt-β-catenin pathways results in the loss of the intestinal stem cells (ISCs). However, whether the effect of Notch is direct or due to the aberrant differentiation of the transit-amplifying cells into post-mitotic goblet cells is unknown. T...

  10. TGFβR signalling controls CD103+CD11b+ dendritic cell development in the intestine

    NARCIS (Netherlands)

    L.J. Bain (Lisa); Montgomery, J. (J.); C.L. Scott (C.); J.M. Kel (Junda); M.J.H. Girard-Madoux (Mathilde); L. Martens (Liesbet); Zangerle-Murray, T.F.P. (T. F.P.); J.L. Ober-Blöbaum (Julia); D.J. Lindenbergh-Kortleve (Dicky); J.N. Samsom (Janneke); S. Henri (Sandrine); T. Lawrence (Toby); Y. Saeys (Yvan); B. Malissen (Bernard); M. Dalod (Marc); B.E. Clausen (Bjorn); Mowat, A.M. (A. McI.)

    2017-01-01

    textabstractCD103+CD11b+ dendritic cells (DCs) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGFβR1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1

  11. Immobilization of chlorine dioxide modified cells for uranium absorption

    International Nuclear Information System (INIS)

    He, Shengbin; Ruan, Binbiao; Zheng, Yueping; Zhou, Xiaobin; Xu, Xiaoping

    2014-01-01

    There has been a trend towards the use of microorganisms to recover metals from industrial wastewater, for which various methods have been reported to be used to improve microorganism adsorption characteristics such as absorption capacity, tolerance and reusability. In present study, chlorine dioxide(ClO 2 ), a high-efficiency, low toxicity and environment-benign disinfectant, was first reported to be used for microorganism surface modification. The chlorine dioxide modified cells demonstrated a 10.1% higher uranium adsorption capacity than control ones. FTIR analysis indicated that several cell surface groups are involved in the uranium adsorption and cell surface modification. The modified cells were further immobilized on a carboxymethylcellulose (CMC) matrix to improve their reusability. The cell-immobilized adsorbent could be employed either in a high concentration system to move vast UO 2 2+ ions or in a low concentration system to purify UO 2 2+ contaminated water thoroughly, and could be repeatedly used in multiple adsorption-desorption cycles with about 90% adsorption capacity maintained after seven cycles. - Highlights: • Chlorine dioxide was first reported to be used for microorganism surface modification. • The chlorine dioxide modified cells demonstrated a 10.1% higher uranium adsorption capacity than control ones. • The chlorine dioxide modified cells were further immobilized by carboxymethylcellulose to improve their reusability

  12. Carotenoid absorption, chylomicron response curves, the influence of β-carotene supplementation on immune function and the measurement of natural killer cell function

    International Nuclear Information System (INIS)

    Southon, S.

    1997-01-01

    Absorption of β-carotene from raw, uncooked vegetables can be very low. Particle size of uncooked foods is particularly important; β-carotene absorption from pureed or finely chopped vegetables is considerably higher than from whole or sliced raw vegetables. Cooking procedures (boiling/steaming) improves the chemical extractability of carotenoids from foods and also appears to improve absorption. Dietary fat stimulates bile flow from the gall bladder which facilitates the emulsification of fat and fat soluble dietary components into lipid micelles within the small intestine. Without micelle formation carotenoids are very poorly absorbed. Several studies have shown that the absence of dietary fat or very low fat diets substantially reduces β-carotene absorption in human volunteers. Carotenoid absorption is thought to be a passive process. The assumption is that carotenoids within lipid micelles come into contact with the intestinal epithelial cell membranes and that transport from micelles to the plasma membrane and cytosol of the cell occur together with the transport of fatty acids. β-carotene appears simultaneously in lymph with newly absorbed fat from a meal and thus it is assumed that they move together across the plasma membrane and within the mucosal cell

  13. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

    Energy Technology Data Exchange (ETDEWEB)

    Tang, J.; Jiang, Y. [Southern Medical University, Nanfang Hospital, Department of Anesthesia, Guangzhou, China, Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou (China); Tang, Y.; Chen, B. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China); Sun, X. [Laboratory of Traditional Chinese Medicine Syndrome, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou (China); Su, L.; Liu, Z. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China)

    2013-06-25

    Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries.

  14. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

    International Nuclear Information System (INIS)

    Tang, J.; Jiang, Y.; Tang, Y.; Chen, B.; Sun, X.; Su, L.; Liu, Z.

    2013-01-01

    Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries

  15. Fermented soya bean (tempe) extracts reduce adhesion of enterotoxigenic Escherichia coli to intestinal epithelial cells.

    Science.gov (United States)

    Roubos-van den Hil, P J; Nout, M J R; Beumer, R R; van der Meulen, J; Zwietering, M H

    2009-03-01

    This study aimed to investigate the effect of processed soya bean, during the successive stages of tempe fermentation and different fermentation times, on adhesion of enterotoxigenic Escherichia coli (ETEC) K88 to intestinal brush border cells as well as Caco-2 intestinal epithelial cells; and to clarify the mechanism of action. Tempe was prepared at controlled laboratory scale using Rhizopus microsporus var. microsporus as the inoculum. Extracts of raw, soaked and cooked soya beans reduced ETEC adhesion to brush border cells by 40%. Tempe extracts reduced adhesion by 80% or more. ETEC adhesion to Caco-2 cells reduced by 50% in the presence of tempe extracts. ETEC K88 bacteria were found to interact with soya bean extracts, and this may contribute to the observed decrease of ETEC adhesion to intestinal epithelial cells. Fermented soya beans (tempe) reduce the adhesion of ETEC to intestinal epithelial cells of pig and human origin. This reduced adhesion is caused by an interaction between ETEC K88 bacteria and soya bean compounds. The results strengthen previous observations on the anti-diarrhoeal effect of tempe. This effect indicates that soya-derived compounds may reduce adhesion of ETEC to intestinal cells in pigs as well as in humans and prevent against diarrhoeal diseases.

  16. Zinc sulfide in intestinal cell granules of Ancylostoma caninum adults

    Energy Technology Data Exchange (ETDEWEB)

    Gianotti, A.J.; Clark, D.T.; Dash, J. (Portland State Univ., OR (USA))

    1991-04-01

    A source of confusion has existed since the turn of the century about the reddish brown, weakly birefringent 'sphaerocrystals' located in the intestines of strongyle nematodes, Strongylus and Ancylostoma. X-ray diffraction and energy dispersive spectrometric analyses were used for accurate determination of the crystalline order and elemental composition of the granules in the canine hookworm Ancylostoma caninum. The composition of the intestinal pigmented granules was identified unequivocally as zinc sulfide. It seems most probable that the granules serve to detoxify high levels of metallic ions (specifically zinc) present due to the large intake of host blood.

  17. Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings.

    Science.gov (United States)

    Hedin, Charlotte R; McCarthy, Neil E; Louis, Petra; Farquharson, Freda M; McCartney, Sara; Taylor, Kirstin; Prescott, Natalie J; Murrells, Trevor; Stagg, Andrew J; Whelan, Kevin; Lindsay, James O

    2014-10-01

    Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups. Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip. Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ(2)=80.4, df=20, pmicrobiological variables. Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation.

    Science.gov (United States)

    Kurashima, Yosuke; Goto, Yoshiyuki; Kiyono, Hiroshi

    2013-12-01

    Continuous exposure of intestinal mucosal surfaces to diverse microorganisms and their metabolites reflects the biological necessity for a multifaceted, integrated epithelial and immune cell-mediated regulatory system. The development and function of the host cells responsible for the barrier function of the intestinal surface (e.g., M cells, Paneth cells, goblet cells, and columnar epithelial cells) are strictly regulated through both positive and negative stimulation by the luminal microbiota. Stimulation by damage-associated molecular patterns and commensal bacteria-derived microbe-associated molecular patterns provokes the assembly of inflammasomes, which are involved in maintaining the integrity of the intestinal epithelium. Mucosal immune cells located beneath the epithelium play critical roles in regulating both the mucosal barrier and the relative composition of the luminal microbiota. Innate lymphoid cells and mast cells, in particular, orchestrate the mucosal regulatory system to create a mutually beneficial environment for both the host and the microbiota. Disruption of mucosal homeostasis causes intestinal inflammation such as that seen in inflammatory bowel disease. Here, we review the recent research on the biological interplay among the luminal microbiota, epithelial cells, and mucosal innate immune cells in both healthy and pathological conditions. © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Dll1- and Dll4-mediated Notch signaling is required for homeostasis of intestinal stem cells

    Science.gov (United States)

    Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H.; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

    2011-01-01

    Background & Aims Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors, due to their conversion into post-mitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SC), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiological ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Methods Trasgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ERT2). Results Notch1 signaling was found to be activated in intestinal SC. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into post-mitotic goblet cells, concomitant with loss of SC (Olfm4+, Lgr5+ and Ascl2+). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Conclusions Notch signaling in SC and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SC. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. PMID:21238454

  20. Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells.

    Science.gov (United States)

    Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

    2011-04-01

    Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Transgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ER(T2)). Notch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4(+), Lgr5(+), and Ascl2(+)). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Notch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports development of intestinal inflammation

    Directory of Open Access Journals (Sweden)

    Boehm Franziska

    2012-07-01

    Full Text Available Abstract Background Mice lacking Foxp3+ regulatory T (Treg cells develop severe tissue inflammation in lung, skin, and liver with premature death, whereas the intestine remains uninflamed. This study aims to demonstrate the importance of Foxp3+ Treg for the activation of T cells and the development of intestinal inflammation. Methods Foxp3-GFP-DTR (human diphtheria toxin receptor C57BL/6 mice allow elimination of Foxp3+ Treg by treatment with Dx (diphtheria toxin. The influence of Foxp3+ Treg on intestinal inflammation was tested using the CD4+ T-cell transfer colitis model in Rag−/− C57BL/6 mice and the acute DSS-colitis model. Results Continuous depletion of Foxp3+ Treg in Foxp3-GFP-DTR mice led to dramatic weight loss and death of mice by day 28. After 10 days of depletion of Foxp3+ Treg, isolated CD4+ T-cells were activated and produced extensive amounts of IFN-γ, IL-13, and IL-17A. Transfer of total CD4+ T-cells isolated from Foxp3-GFP-DTR mice did not result in any changes of intestinal homeostasis in Rag−/− C57BL/6 mice. However, administration of DTx between days 14 and 18 after T-cell reconstitution, lead to elimination of Foxp3+ Treg and to immediate weight loss due to intestinal inflammation. This pro-inflammatory effect of Foxp3+ Treg depletion consecutively increased inflammatory cytokine production. Further, the depletion of Foxp3+ Treg from Foxp3-GFP-DTR mice increased the severity of acute dSS-colitis accompanied by 80% lethality of Treg-depleted mice. CD4+ effector T-cells from Foxp3+ Treg-depleted mice produced significantly more pro-inflammatory cytokines. Conclusion Intermittent depletion of Foxp3+ Treg aggravates intestinal inflammatory responses demonstrating the importance of Foxp3+ Treg for the balance at the mucosal surface of the intestine.

  2. Bioavailability and the mechanisms of intestinal absorption of iron from ferrous ascorbate and ferric polymaltose in experimental animals

    International Nuclear Information System (INIS)

    Johnson, G.; Jacobs, P.

    1990-01-01

    The comparative bioavailability from matching quantities of iron in the form of ferrous ascorbate or ferric polymaltose was defined in rats. Studies were carried out in the intact animals under basal conditions and also when requirements for this metal were either increased or decreased by manipulating stores or erythropoietic activity. No significant difference was found in the total quantity of iron absorbed from either salt or complex under any of these circumstances, suggesting that the mucosal mechanism regulating the overall process was common to both. However, the rate of transfer from the lumen into portal blood was distinctive, reaching a maximum with salt at 30 min compared to 24 h for the complex. To explore the possibility that iron from the two sources was initially handled by different subcellular pathways, the radiolabeled compounds were instilled into loops of bowel that had been isolated between ligatures in vivo. Enterocytes were harvested and fractionated, and incorporation into ferritin and transferrin was determined using RIA. From salt, iron appeared rapidly in duodenal but not ileal ferritin, whereas mucosal transferrin increased under conditions of stimulated absorption, suggesting that this protein may act as a shuttle for the metal. In contrast, iron from polymaltose showed a cumulative incorporation into duodenal ferritin over time that correlated with iron absorption, defined by the appearance of radiolabel in the serum and in the carcass; a similar pattern was demonstrable in ileal mucosal cells. Conversely, binding of iron to transferrin was minimal. No iron polymaltose was found within the mucosal cells. It is suggested that the low rate of iron transfer from this ferric complex may reflect its extracellular breakdown in the lumen of the gastrointestinal tract

  3. Se interlayer in CIGS absorption layer for solar cell devices

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Kyu; Sim, Jae-Kwan [Semiconductor Materials Process Laboratory, School of Advanced Materials Engineering, Research Center for Advanced Materials Development, Chonbuk National University, Deokjin-Dong 664-14, Jeonju 561-756 (Korea, Republic of); Kissinger, N.J. Suthan [Department of General Studies, Physics Group, Jubail University College, Royal Commission for Jubail, Jubail 10074 (Saudi Arabia); Song, Il-Seok; Kim, Jin-Soo; Baek, Byung-Joon [Semiconductor Materials Process Laboratory, School of Advanced Materials Engineering, Research Center for Advanced Materials Development, Chonbuk National University, Deokjin-Dong 664-14, Jeonju 561-756 (Korea, Republic of); Lee, Cheul-Ro, E-mail: crlee7@jbnu.ac.kr [Semiconductor Materials Process Laboratory, School of Advanced Materials Engineering, Research Center for Advanced Materials Development, Chonbuk National University, Deokjin-Dong 664-14, Jeonju 561-756 (Korea, Republic of)

    2015-06-05

    Highlights: • Se interlayer is deposited between the CuGa and CuIn/In/Mo/STS stacked layer. • Both CIG precursor layers were selenized at 500 °C for 1 h. • SIMS depth profile shows that Ga distribution is uniform by Se interlayer. • The efficiency was improved for the CIGS solar cell by Se interlayer. - Abstract: A CIGS absorber layer with high gallium contents in the space-charge region can reduce the carrier recombination and improve the open circuit voltage V{sub oc}. Therefore, controlling Ga grading on top of CIGS thin film solar cells is the main objective of this experiment. To reduce Selenium (Se) vacancy, it is important that the diffusion of Ga elements into Se vacancy between Mo back contact and CIGS absorption layer would be controlled. In order to reduce Se vacancy and confirm Ga inter-diffusion, two CIGS solar cells were fabricated by converting CIG precursor with and without Se interlayer. The copper-indium metallic precursors were fabricated corresponding to the sequence CuIn/In/Mo/STS on stainless steel (STS) substrates by sequential direct current magnetron sputtering while Se layer was evaporated by rapid thermal annealing (RTA) system to obtain a Se/CuIn/In/Mo/STS stack. CuGa precursor layer was also fabricated on the Se/CuIn/In/Mo/STS stack. Finally, both CuGa/Se/CuIn/In/Mo/STS and CuGa/CuIn/In/Mo/STS stacks were selenized at 500 °C for 1 h. It was clearly observed from the secondary ion mass spectroscopy (SIMS) and X-ray diffraction (XRD) that there was a change between the fabricated CIGS absorption layers and the amount of Ga elements. Furthermore, the Ga elements gradually decreased from the top to the bottom layer of the CIGS absorption layer. We also discussed the effect of Se interlayer in the CIGS absorption layer and its influence on the solar cell’s performance.

  4. Se interlayer in CIGS absorption layer for solar cell devices

    International Nuclear Information System (INIS)

    Lee, Seung-Kyu; Sim, Jae-Kwan; Kissinger, N.J. Suthan; Song, Il-Seok; Kim, Jin-Soo; Baek, Byung-Joon; Lee, Cheul-Ro

    2015-01-01

    Highlights: • Se interlayer is deposited between the CuGa and CuIn/In/Mo/STS stacked layer. • Both CIG precursor layers were selenized at 500 °C for 1 h. • SIMS depth profile shows that Ga distribution is uniform by Se interlayer. • The efficiency was improved for the CIGS solar cell by Se interlayer. - Abstract: A CIGS absorber layer with high gallium contents in the space-charge region can reduce the carrier recombination and improve the open circuit voltage V oc . Therefore, controlling Ga grading on top of CIGS thin film solar cells is the main objective of this experiment. To reduce Selenium (Se) vacancy, it is important that the diffusion of Ga elements into Se vacancy between Mo back contact and CIGS absorption layer would be controlled. In order to reduce Se vacancy and confirm Ga inter-diffusion, two CIGS solar cells were fabricated by converting CIG precursor with and without Se interlayer. The copper-indium metallic precursors were fabricated corresponding to the sequence CuIn/In/Mo/STS on stainless steel (STS) substrates by sequential direct current magnetron sputtering while Se layer was evaporated by rapid thermal annealing (RTA) system to obtain a Se/CuIn/In/Mo/STS stack. CuGa precursor layer was also fabricated on the Se/CuIn/In/Mo/STS stack. Finally, both CuGa/Se/CuIn/In/Mo/STS and CuGa/CuIn/In/Mo/STS stacks were selenized at 500 °C for 1 h. It was clearly observed from the secondary ion mass spectroscopy (SIMS) and X-ray diffraction (XRD) that there was a change between the fabricated CIGS absorption layers and the amount of Ga elements. Furthermore, the Ga elements gradually decreased from the top to the bottom layer of the CIGS absorption layer. We also discussed the effect of Se interlayer in the CIGS absorption layer and its influence on the solar cell’s performance

  5. 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.

  6. Perforated small intestine in a patient with T-cell lymphoma; a rare cause of peritonitis

    Directory of Open Access Journals (Sweden)

    Petrişor Banu

    2016-04-01

    Full Text Available The nontraumatic perforations of the small intestine are pathological entities with particular aspects in respect to diagnosis and treatment. These peculiarities derive from the nonspecific clinical expression of the peritonitis syndrome, and from the multitude of causes that might be the primary sources of the perforation: foreign bodies, inflammatory diseases, tumors, infectious diseases, etc. Accordingly, in most cases intestinal perforation is discovered only by laparotomy and the definitive diagnosis is available only after histopathologic examination. Small bowel malignancies are rare; among them, lymphomas rank third in frequency, being mostly B-cell non Hodgkin lymphomas. Only 10% of non-Hodgkin lymphomas are with T-cell. We report the case of a 57 years’ old woman with intestinal T-cell lymphoma, whose first clinical symptomatology was related to a complication represented by perforation of the small intestine. Laparotomy performed in emergency identified an ulcerative lesion with perforation in the jejunum, which required segmental enterectomy with anastomosis. The nonspecific clinical manifestations of intestinal lymphomas make from diagnosis a difficult procedure. Due to the fact that surgery does not have a definite place in the treatment of the small intestinal lymphomas (for cases complicated with perforation, and beyond the morbidity associated with the surgery performed in emergency conditions, prognosis of these patients is finally given by the possibility to control the systemic disease through adjuvant therapy.

  7. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.

    Science.gov (United States)

    Zhu, Shu; Ding, Siyuan; Wang, Penghua; Wei, Zheng; Pan, Wen; Palm, Noah W; Yang, Yi; Yu, Hua; Li, Hua-Bing; Wang, Geng; Lei, Xuqiu; de Zoete, Marcel R; Zhao, Jun; Zheng, Yunjiang; Chen, Haiwei; Zhao, Yujiao; Jurado, Kellie A; Feng, Ningguo; Shan, Liang; Kluger, Yuval; Lu, Jun; Abraham, Clara; Fikrig, Erol; Greenberg, Harry B; Flavell, Richard A

    2017-06-29

    Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. Conditional depletion of Nlrp9b or other inflammasome components in the intestine in vivo resulted in enhanced susceptibility of mice to rotavirus replication. Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens.

  8. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells

    Science.gov (United States)

    Zhu, Shu; Ding, Siyuan; Wang, Penghua; Wei, Zheng; Pan, Wen; Palm, Noah W; Yang, Yi; Yu, Hua; Li, Hua-Bing; Wang, Geng; Lei, Xuqiu; de Zoete, Marcel R.; Zhao, Jun; Zheng, Yunjiang; Chen, Haiwei; Zhao, Yujiao; Jurado, Kellie A.; Feng, Ningguo; Shan, Liang; Kluger, Yuval; Lu, Jun; Abraham, Clara; Fikrig, Erol; Greenberg, Harry B.; Flavell, Richard A.

    2018-01-01

    Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide1. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling2–5, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. Conditional depletion of Nlrp9b or other inflammasome components in the intestine in vivo resulted in enhanced susceptibility of mice to rotavirus replication. Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens. PMID:28636595

  9. Divergent Roles of Interferon-γ and Innate Lymphoid Cells in Innate and Adaptive Immune Cell-Mediated Intestinal Inflammation.

    Science.gov (United States)

    Brasseit, Jennifer; Kwong Chung, Cheong K C; Noti, Mario; Zysset, Daniel; Hoheisel-Dickgreber, Nina; Genitsch, Vera; Corazza, Nadia; Mueller, Christoph

    2018-01-01

    Aberrant interferon gamma (IFNγ) expression is associated with the pathogenesis of numerous autoimmune- and inflammatory disorders, including inflammatory bowel diseases (IBD). However, the requirement of IFNγ for the pathogenesis of chronic intestinal inflammation remains controversial. The aim of this study was thus to investigate the role of IFNγ in experimental mouse models of innate and adaptive immune cell-mediated intestinal inflammation using genetically and microbiota-stabilized hosts. While we find that IFNγ drives acute intestinal inflammation in the anti-CD40 colitis model in an innate lymphoid cell (ILC)-dependent manner, IFNγ secreted by both transferred CD4 T cells and/or cells of the lymphopenic Rag1 -/- recipient mice was dispensable for CD4 T cell-mediated colitis. In the absence of IFNγ, intestinal inflammation in CD4 T cell recipient mice was associated with enhanced IL17 responses; consequently, targeting IL17 signaling in IFNγ-deficient mice reduced T cell-mediated colitis. Intriguingly, in contrast to the anti-CD40 model of colitis, depletion of ILC in the Rag1 -/- recipients of colitogenic CD4 T cells did not prevent induction of colonic inflammation. Together, our findings demonstrate that IFNγ represents an essential, or a redundant, pro-inflammatory cytokine for the induction of intestinal inflammation, depending on the experimental mouse model used and on the nature of the critical disease inducing immune cell populations involved.

  10. Wnt signaling in adult intestinal stem cells and cancer

    Czech Academy of Sciences Publication Activity Database

    Krausová, Michaela; Kořínek, Vladimír

    2014-01-01

    Roč. 26, č. 3 (2014), s. 570-579 ISSN 0898-6568 R&D Projects: GA ČR GAP305/12/2347; GA ČR GAP305/11/1780 Institutional support: RVO:68378050 Keywords : Wnt * intestine * cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.315, year: 2014

  11. Centrosome/Cell cycle uncoupling and elimination in the endoreduplicating intestinal cells of C. elegans.

    Directory of Open Access Journals (Sweden)

    Yu Lu

    Full Text Available The centrosome cycle is most often coordinated with mitotic cell division through the activity of various essential cell cycle regulators, consequently ensuring that the centriole is duplicated once, and only once, per cell cycle. However, this coupling can be altered in specific developmental contexts; for example, multi-ciliated cells generate hundreds of centrioles without any S-phase requirement for their biogenesis, while Drosophila follicle cells eliminate their centrosomes as they begin to endoreduplicate. In order to better understand how the centrosome cycle and the cell cycle are coordinated in a developmental context we use the endoreduplicating intestinal cell lineage of C. elegans to address how novel variations of the cell cycle impact this important process. In C. elegans, the larval intestinal cells undergo one nuclear division without subsequent cytokinesis, followed by four endocycles that are characterized by successive rounds of S-phase. We monitored the levels of centriolar/centrosomal markers and found that centrosomes lose their pericentriolar material following the nuclear division that occurs during the L1 stage and is thereafter never re-gained. The centrioles then become refractory to S phase regulators that would normally promote duplication during the first endocycle, after which they are eliminated during the L2 stage. Furthermore, we show that SPD-2 plays a central role in the numeral regulation of centrioles as a potential target of CDK activity. On the other hand, the phosphorylation on SPD-2 by Polo-like kinase, the transcriptional regulation of genes that affect centriole biogenesis, and the ubiquitin/proteasome degradation pathway, contribute collectively to the final elimination of the centrioles during the L2 stage.

  12. The effect of administration of copper nanoparticles to chickens in drinking water on estimated intestinal absorption of iron, zinc, and calcium.

    Science.gov (United States)

    Ognik, Katarzyna; Stępniowska, Anna; Cholewińska, Ewelina; Kozłowski, Krzysztof

    2016-09-01

    Copper nanoparticles used as a dietary supplement for poultry could affect the absorption of mineral elements. Hence the aim of the study was to determine the effect of administration of copper nanoparticles to chickens in drinking water on intestinal absorption of iron, zinc, and calcium. The experiment was carried out on 126 chicks assigned to seven experimental groups of 18 birds each (3 replications of 6 individuals each). The control group (G-C) did not receive copper nanoparticles. Groups: Cu-5(7), Cu-10(7), and Cu-15(7) received gold nanoparticles in their drinking water in the amounts of 5 mg/L for group Cu-5(7), 10 mg/L for group Cu-10(7), and 15 mg/L for group Cu-15(7) during 8 to 14, 22 to 28, and 36 of 42 days of the life of the chicks. The birds in groups Cu-5(3), Cu-10(3), and Cu-15(3) received copper nanoparticles in the same amounts, but only during 8 to 10, 22 to 24, and 36 to 38 days of life. Blood for analysis was collected from the wing vein of all chicks at the age of 42 days. After the rearing period (day 42), six birds from each experimental group with body weight similar to the group average were slaughtered. The carcasses were dissected and samples of the jejunum were collected for analysis of absorption of selected minerals. Mineral absorption was tested using the in vitro gastrointestinal sac technique. Oral administration of copper nanoparticles to chickens in the amount of 5, 10, and 15 mg/L led to accumulation of this element in the intestinal walls. The highest level of copper nanoparticles applied increased Cu content in the blood plasma of the birds. The in vitro study suggests that copper accumulated in the intestines reduces absorption of calcium and zinc, but does not affect iron absorption. © 2016 Poultry Science Association Inc.

  13. Radiosensitivity of mice of different lines and age as determinated with reference to ''intestinal'' death and DNA repair in intestinal epithelium cells

    Energy Technology Data Exchange (ETDEWEB)

    Konoplyannikova, O.A.; Sklobovskaya, M.V.; Konoplyannikov, A.G.; Saenko, A.S. (Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii)

    A study was made of the influence of strain- and age-related differences on mouse mortality after irradiation with doses lying within the ''intestinal'' dose range, and also damages to stem cells of intestinal epithelium and induction and repair of single-strand DNA breaks in intestinal epitherium cells. Mice of different lines and age vary in LDsub(50/4) and stem cell radiosensitivity. There are no differences in the sedimentation constants of DNA fragments in alkaline lysates of intestinal crypts of intact mice of different age. Radiosensitivity determined with reference to single-strand breaks induction in DNA is similar with different mouse groups. Repair of single-strand DNA breaks of elderly mice is slower than that of young animals.

  14. Analysis of interactions of Salmonella type three secretion mutants with 3-D intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Andrea L Radtke

    Full Text Available The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2, double (SPI-1/2 and complete T3SS knockout (SPI-1/SPI-2: flhDC also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms.

  15. Culture media from hypoxia conditioned endothelial cells protect human intestinal cells from hypoxia/reoxygenation injury.

    Science.gov (United States)

    Hummitzsch, Lars; Zitta, Karina; Bein, Berthold; Steinfath, Markus; Albrecht, Martin

    2014-03-10

    Remote ischemic preconditioning (RIPC) is a phenomenon, whereby short episodes of non-lethal ischemia to an organ or tissue exert protection against ischemia/reperfusion injury in a distant organ. However, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms within the target organ and the released factors. Here we established a human cell culture model to investigate cellular and molecular effects of RIPC and to identify factors responsible for RIPC-mediated intestinal protection. Human umbilical vein cells (HUVEC) were exposed to repeated episodes of hypoxia (3 × 15 min) and conditioned culture media (CM) were collected after 24h. Human intestinal cells (CaCo-2) were cultured with or without CM and subjected to 90 min of hypoxia/reoxygenation injury. Reverse transcription-polymerase chain reaction, Western blotting, gelatin zymography, hydrogen peroxide measurements and lactate dehydrogenase (LDH) assays were performed. In HUVEC cultures hypoxic conditioning did not influence the profile of secreted proteins but led to an increased gelatinase activity (Pcultures 90 min of hypoxia/reoxygenation resulted in morphological signs of cell damage, increased LDH levels (Pculture model may help to unravel RIPC-mediated cellular events and to identify molecules released by RIPC. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal

    Science.gov (United States)

    Chandrakesan, Parthasarathy; May, Randal; Qu, Dongfeng; Weygant, Nathaniel; Taylor, Vivian E.; Li, James D.; Ali, Naushad; Sureban, Sripathi M.; Qante, Michael; Wang, Timothy C.; Bronze, Michael S.; Houchen, Courtney W.

    2015-01-01

    To date, no discrete genetic signature has been defined for isolated Dclk1+ tuft cells within the small intestine. Furthermore, recent reports on the functional significance of Dclk1+ cells in the small intestine have been inconsistent. These cells have been proposed to be fully differentiated cells, reserve stem cells, and tumor stem cells. In order to elucidate the potential function of Dclk1+ cells, we FACS-sorted Dclk1+ cells from mouse small intestinal epithelium using transgenic mice expressing YFP under the control of the Dclk1 promoter (Dclk1-CreER;Rosa26-YFP). Analysis of sorted YFP+ cells demonstrated marked enrichment (~6000 fold) for Dclk1 mRNA compared with YFP− cells. Dclk1+ population display ~6 fold enrichment for the putative quiescent stem cell marker Bmi1. We observed significantly greater expression of pluripotency genes, pro-survival genes, and quiescence markers in the Dclk1+ population. A significant increase in self-renewal capability (14-fold) was observed in in vitro isolated Dclk1+ cells. The unique genetic report presented in this manuscript suggests that Dclk1+ cells may maintain quiescence, pluripotency, and metabolic activity for survival/longevity. Functionally, these reserve characteristics manifest in vitro, with Dclk1+ cells exhibiting greater ability to self-renew. These findings indicate that quiescent stem-like functionality is a feature of Dclk1-expressing tuft cells. PMID:26362399

  17. Mast cells play no role in the pathogenesis of postoperative ileus induced by intestinal manipulation.

    Science.gov (United States)

    Gomez-Pinilla, Pedro J; Farro, Giovanna; Di Giovangiulio, Martina; Stakenborg, Nathalie; Némethova, Andrea; de Vries, Annick; Liston, Adrian; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Rodewald, Hans-Reimwer; Boeckxstaens, Guy E; Matteoli, Gianluca

    2014-01-01

    Intestinal manipulation (IM) during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI). However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC) resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3(Cre/+) , devoid of mast cells but with intact Kit signaling. The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. Kit(W-sh/W-sh) and Cpa3(Cre/+) mice, and by use of the mast cell stabilizer cromolyn. Kit(W-sh/W-sh) mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3(Cre/+) mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3(Cre/+) mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3(+/+) ). Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast cell inhibitors as a therapeutic approach to shorten POI.

  18. Mast cells play no role in the pathogenesis of postoperative ileus induced by intestinal manipulation.

    Directory of Open Access Journals (Sweden)

    Pedro J Gomez-Pinilla

    Full Text Available INTRODUCTION: Intestinal manipulation (IM during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI. However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3(Cre/+ , devoid of mast cells but with intact Kit signaling. DESIGN: The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. Kit(W-sh/W-sh and Cpa3(Cre/+ mice, and by use of the mast cell stabilizer cromolyn. RESULTS: Kit(W-sh/W-sh mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3(Cre/+ mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3(Cre/+ mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3(+/+ . Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. CONCLUSIONS: Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast

  19. Loss of Sonic hedgehog leads to alterations in intestinal secretory cell maturation and autophagy.

    Directory of Open Access Journals (Sweden)

    Jessica Gagné-Sansfaçon

    Full Text Available BACKGROUND: Intestinal epithelial cells express the Sonic and Indian hedgehog ligands. Despite the strong interest in gut hedgehog signaling in GI diseases, no studies have specifically addressed the singular role of intestinal epithelial cell Sonic hedgehog signaling. The aim of this study was to investigate the specific role of Sonic hedgehog in adult ileal epithelial homeostasis. METHODOLOGY/PRINCIPAL FINDINGS: A Sonic hedgehog intestinal epithelial conditional knockout mouse model was generated. Assessment of ileal histological abnormalities, crypt epithelial cell proliferation, epithelial cell fate, junctional proteins, signaling pathways, as well as ultrastructural analysis of intracellular organelles were performed in control and mutant mice. Mice lacking intestinal epithelial Sonic Hedgehog displayed decreased ileal crypt/villus length, decreased crypt proliferation as well as a decrease in the number of ileal mucin-secreting goblet cells and antimicrobial peptide-secreting Paneth cells during adult life. These secretory cells also exhibited disruption of their secretory products in mutant mice. Ultrastructural microscopy analysis revealed a dilated ER lumen in secretory cells. This phenotype was also associated with a decrease in autophagy. CONCLUSIONS/SIGNIFICANCE: Altogether, these findings indicate that the loss of Sonic hedgehog can lead to ileal secretory cell modifications indicative of endoplasmic reticulum stress, accompanied by a significant reduction in autophagy.

  20. Precision-cut intestinal slices as a culture system to analyze the infection of differentiated intestinal epithelial cells by avian influenza viruses.

    Science.gov (United States)

    Punyadarsaniya, Darsaniya; Winter, Christine; Mork, Ann-Kathrin; Amiri, Mahdi; Naim, Hassan Y; Rautenschlein, Silke; Herrler, Georg

    2015-02-01

    Many viruses infect and replicate in their host via the intestinal tract, e.g. many picornaviruses, several coronaviruses and avian influenza viruses of waterfowl. To analyze infection of enterocytes is a challenging task as culture systems for differentiated intestinal epithelial cells are not readily available and often have a life span that is too short for infection studies. Precision-cut intestinal slices (PCIS) from chicken embryos were prepared and shown that the epithelial cells lining the lumen of the intestine are viable for up to 4 days. Using lectin staining, it was demonstrated that α2,3-linked sialic acids, the preferred receptor determinants of avian influenza viruses, are present on the apical side of the epithelial cells. Furthermore, the epithelial cells (at the tips) of the villi were shown to be susceptible to infection by an avian influenza virus of the H9N2 subtype. This culture system will be useful to analyze virus infection of intestinal epithelial cells and it should be applicable also to the intestine of other species. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Metabolic changes during B cell differentiation for the production of intestinal IgA antibody.

    Science.gov (United States)

    Kunisawa, Jun

    2017-04-01

    To sustain the bio-energetic demands of growth, proliferation, and effector functions, the metabolism of immune cells changes dramatically in response to immunologic stimuli. In this review, I focus on B cell metabolism, especially regarding the production of intestinal IgA antibody. Accumulating evidence has implicated not only host-derived factors (e.g., cytokines) but also gut environmental factors, including the possible involvement of commensal bacteria and diet, in the control of B cell metabolism during intestinal IgA antibody production. These findings yield new insights into the regulation of immunosurveillance and homeostasis in the gut.

  2. Diacylglycerol kinase regulation of protein kinase D during oxidative stress-induced intestinal cell injury

    International Nuclear Information System (INIS)

    Song Jun; Li Jing; Mourot, Joshua M.; Mark Evers, B.; Chung, Dai H.

    2008-01-01

    We recently demonstrated that protein kinase D (PKD) exerts a protective function during oxidative stress-induced intestinal epithelial cell injury; however, the exact role of DAG kinase (DGK)ζ, an isoform expressed in intestine, during this process is unknown. We sought to determine the role of DGK during oxidative stress-induced intestinal cell injury and whether DGK acts as an upstream regulator of PKD. Inhibition of DGK with R59022 compound or DGKζ siRNA transfection decreased H 2 O 2 -induced RIE-1 cell apoptosis as measured by DNA fragmentation and increased PKD phosphorylation. Overexpression of kinase-dead DGKζ also significantly increased PKD phosphorylation. Additionally, endogenous nuclear DGKζ rapidly translocated to the cytoplasm following H 2 O 2 treatment. Our findings demonstrate that DGK is involved in the regulation of oxidative stress-induced intestinal cell injury. PKD activation is induced by DGKζ, suggesting DGK is an upstream regulator of oxidative stress-induced activation of the PKD signaling pathway in intestinal epithelial cells

  3. Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium

    NARCIS (Netherlands)

    Gerbe, F.; van Es, J.H.; Makrini, L.; Brulin, B.; Mellitzer, G.; Robine, S.; Romagnolo, B.; Shroyer, N.F.; Bourgaux, J.F.; Pignodel, C.; Clevers, H.; Jay, P.

    2011-01-01

    The unique morphology of tuft cells was first revealed by electron microscopy analyses in several endoderm-derived epithelia. Here, we explore the relationship of these cells with the other cell types of the intestinal epithelium and describe the first marker signature allowing their unambiguous

  4. Arthritis by autoreactive T cell lines obtained from rats after injection of intestinal bacterial cell wall fragments

    NARCIS (Netherlands)

    I. Klasen (Ina); J. Kool (Jeanette); M.J. Melief (Marie-José); I. Loeve (I.); W.B. van den Berg (Wim); A.J. Severijnen; M.P.H. Hazenberg (Maarten)

    1992-01-01

    markdownabstract__Abstract__ T cell lines (B13, B19) were isolated from the lymph nodes of Lewis rats 12 days after an arthritogenic injection of cell wall fragments of Eubacterium aerofaciens (ECW), a major resident of the human intestinal flora. These cell wall fragments consist of

  5. Actions of vasoactive intestinal peptide and secretin on chief cells prepared from guinea pig stomach

    International Nuclear Information System (INIS)

    Sutliff, V.E.; Raufman, J.P.; Jensen, R.T.; Gardner, J.D.

    1986-01-01

    Vasoactive intestinal peptide and secretin increased cellular cAMP and pepsinogen secretion in dispersed chief cells from guinea pig gastric mucosa. With each peptide there was a close correlation between the dose-response curve for changes in cellular cAMP and that for changes in pepsinogen secretion. Vasoactive intestinal peptide- (10-28) and secretin- (5-27) had no agonist activity and antagonized the actions of vasoactive intestinal peptide and secretin on cellular cAMP and pepsinogen secretion. Studies of binding of 125 I-vasoactive intestinal peptide and of 125 -secretin indicated that gastric chief cells possess four classes of binding sites for vasoactive intestinal peptide and secretin and that occupation of two of these classes of binding sites correlates with the abilities of vasoactive intestinal peptide and secretin to increase cellular cAMP and pepsinogen secretion. What function, in any, is mediated by occupation by the other two classes of binding sites remains to be determined

  6. Crypt base columnar stem cells in small intestines of mice are radioresistant

    NARCIS (Netherlands)

    Hua, G.; Thin, T.H.; Feldman, R.; Haimovitz-Friedman, A.; Clevers, H.; Fuks, Z.; Kolesnick, R.

    2012-01-01

    BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that

  7. Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation

    International Nuclear Information System (INIS)

    Leigh, B.R.; Khan, W.; Hancock, S.L.

    1995-01-01

    Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 μ/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 ± 0.7 per duodenal cross section for controls to 30.0 ± 1.7 after treatment with SCF (P=0.03). The TBI dose producing 50% mortality of 6 days (LD 50/6 ) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine. 29 refs., 4 figs

  8. Tolerogenic CX3CR1+ B cells suppress food allergy-induced intestinal inflammation in mice.

    Science.gov (United States)

    Liu, Z Q; Wu, Y; Song, J P; Liu, X; Liu, Z; Zheng, P Y; Yang, P C

    2013-10-01

    B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet. This study aims to investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy-induced intestinal inflammation in mice. The intestinal mucosa-derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs. A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)-β and carried integrin alpha v beta 6 (αvβ6). Exposure to recombinant αvβ6 and anti-IgM antibody induced naive B cells to differentiate into the TGF-β-producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy-induced intestinal Th2 pattern inflammation in mice. CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy-related Th2 pattern inflammation in mice. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Radiation, an ideal cytotoxic for the study of cell biology in the small intestine

    International Nuclear Information System (INIS)

    Potten, C.

    2003-01-01

    Epithelial tissues are highly polarised with the proliferative compartment sometimes subdivided into units of proliferation in many instances. My interests have been in trying to understand how many cellular constituents exist, what their function is and intercommunicants are that ensure appropriate steady state cell replacement rates. Radiation has proved to be a valuable tool to induce cell death, reproductive sterilisation, and regenerative proliferation in these systems, the responses to which can provide information on the number of regenerative cells (a function associated with stem cells). Such studies have helped define the epidermal proliferative units and the structurally similar units on the dorsal surface of the tongue. The radiation responses considered in conjunction with a wide range of cell kinetic lineage tracking and somatic mutation studies with complex mathematical modelling, provide insights into the functioning of the poliferative units (crypts) of the small intestine. Comparative studies have then been undertaken with the crypts in the large bowel. In the small intestine, which rarely develops cancer, various protective mechanisms have evolved to ensure the genetic integrity of the stem cell compartment. Stem cells in the small intestinal crypts have an intolerance of genotoxic damage (including that induced by very low doses of radiation), they do not undergo cell cycle arrest and repair but commit an altruistic p53 dependent cell suicide (apoptosis). This process is compromised in the large bowel by bcl-2 expression. Recent studies have suggested a second genome protection mechanism operating in the stem cells of the small intestinal crypts that may also have a p53 dependence. Such studies have allowed the cell lineages and genome protection mechanisms operating in the small intestinal crypts to be defined

  10. Experimental Investigation on an Absorption Refrigerator Driven by Solar Cells

    Directory of Open Access Journals (Sweden)

    Zi-Jie Chien

    2013-01-01

    Full Text Available This experiment is to study an absorption refrigerator driven by solar cells. Hand-held or carried in vehicle can be powered by solar energy in places without power. In the evenings or rainy days, it is powered by storage battery, and it can be directly powered by alternating current (AC power supply if available, and the storage battery can be charged full as a backup supply. The proposed system was tested by the alternation of solar irradiance 550 to 700 W/m2 as solar energy and 500ml ambient temperature water as cooling load. After 160 minutes, the proposal refrigerator can maintain the temperature at 5–8°C, and the coefficient of performance (COP of NH3-H2O absorption refrigeration system is about 0.25. Therefore, this system can be expected to be used in remote areas for refrigeration of food and beverages in outdoor activities in remote and desert areas or long-distance road transportation of food or low temperature refrigeration of vaccine to avoid the deterioration of the food or the vaccines.

  11. An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells.

    Science.gov (United States)

    Powell, Jonathan J; Thomas-McKay, Emma; Thoree, Vinay; Robertson, Jack; Hewitt, Rachel E; Skepper, Jeremy N; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A; Gomez-Morilla, Inmaculada; Grime, Geoffrey W; Kirkby, Karen J; Mabbott, Neil A; Donaldson, David S; Williams, Ifor R; Rios, Daniel; Girardin, Stephen E; Haas, Carolin T; Bruggraber, Sylvaine F A; Laman, Jon D; Tanriver, Yakup; Lombardi, Giovanna; Lechler, Robert; Thompson, Richard P H; Pele, Laetitia C

    2015-04-01

    In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.

  12. An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells

    Science.gov (United States)

    Powell, Jonathan J.; Thomas-McKay, Emma; Thoree, Vinay; Robertson, Jack; Hewitt, Rachel E.; Skepper, Jeremy N.; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A.; Gomez-Morilla, Inmaculada; Grime, Geoffrey W.; Kirkby, Karen J.; Mabbott, Neil A.; Donaldson, David S.; Williams, Ifor R.; Rios, Daniel; Girardin, Stephen E.; Haas, Carolin T.; Bruggraber, Sylvaine F. A.; Laman, Jon D.; Tanriver, Yakup; Lombardi, Giovanna; Lechler, Robert; Thompson, Richard P. H.; Pele, Laetitia C.

    2015-05-01

    In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule ‘programmed death-ligand 1’, whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.

  13. A20 restricts wnt signaling in intestinal epithelial cells and suppresses colon carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Ling Shao

    Full Text Available Colon carcinogenesis consists of a multistep process during which a series of genetic and epigenetic adaptations occur that lead to malignant transformation. Here, we have studied the role of A20 (also known as TNFAIP3, a ubiquitin-editing enzyme that restricts NFκB and cell death signaling, in intestinal homeostasis and tumorigenesis. We have found that A20 expression is consistently reduced in human colonic adenomas than in normal colonic tissues. To further investigate A20's potential roles in regulating colon carcinogenesis, we have generated mice lacking A20 specifically in intestinal epithelial cells and interbred these with mice harboring a mutation in the adenomatous polyposis coli gene (APC(min. While A20(FL/FL villin-Cre mice exhibit uninflamed intestines without polyps, A20(FL/FL villin-Cre APC(min/+ mice contain far greater numbers and larger colonic polyps than control APC(min mice. We find that A20 binds to the β-catenin destruction complex and restricts canonical wnt signaling by supporting ubiquitination and degradation of β-catenin in intestinal epithelial cells. Moreover, acute deletion of A20 from intestinal epithelial cells in vivo leads to enhanced expression of the β-catenin dependent genes cyclinD1 and c-myc, known promoters of colon cancer. Taken together, these findings demonstrate new roles for A20 in restricting β-catenin signaling and preventing colon tumorigenesis.

  14. Epidermal Growth Factor and Intestinal Barrier Function

    Directory of Open Access Journals (Sweden)

    Xiaopeng Tang

    2016-01-01

    Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

  15. In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

    Science.gov (United States)

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

    2012-10-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.

  16. In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

    Science.gov (United States)

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

    2012-01-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

  17. Naturally occurring glucagon-like peptide-2 (GLP-2) receptors in human intestinal cell lines.

    Science.gov (United States)

    Sams, Anette; Hastrup, Sven; Andersen, Marie; Thim, Lars

    2006-02-17

    Although clinical trials with GLP-2 receptor agonists are currently ongoing, the mechanisms behind GLP-2-induced intestinal epithelial growth remain to be understood. To approach the GLP-2 mechanism of action this study aimed to identify intestinal cell lines endogenously expressing the GLP-2 receptor. Here we report the first identification of a cell line endogenously expressing functional GLP-2 receptors. The human intestinal epithelial cell line, FHC, expressed GLP-2 receptor encoding mRNA (RT-PCR) and GLP-2 receptor protein (Western blot). In cultured FHC cells, GLP-2 induced concentration dependent cAMP accumulation (pEC(50)=9.7+/-0.04 (mean+/-S.E.M., n=4)). In addition, a naturally occurring human intestinal fibroblast cell line, 18Co, endogenously expressing GLP-2 receptor encoding mRNA (RT-PCR) and protein (Western blot) was identified. No receptor functionality (binding or G-protein signalling) could be demonstrated in 18Co cells. The identified gut-relevant cell lines provide tools for future clarification of the mechanisms underlying GLP-2-induced epithelial growth.

  18. Economical analysis of combined fuel cell generators and absorption chillers

    Directory of Open Access Journals (Sweden)

    M. Morsy El-Gohary

    2013-06-01

    Full Text Available This paper presents a co-generation system based on combined heat and power for commercial units. For installation of a co-generation system, certain estimates for this site should be performed through making assessments of electrical loads, domestic water, and thermal demand. This includes domestic hot water, selection of the type of power generator, fuel cell, and the type of air conditioning system, and absorption chillers. As a matter of fact, the co-generation system has demonstrated good results for both major aspects, economic and environmental. From the environmental point of view, this can be considered as an ideal solution for problems concerned with the usage of Chlorofluoro carbons. On the other hand, from the economic point of view, the cost analysis has revealed that the proposed system saves 4% of total cost through using the co-generation system.

  19. The cytotoxic effect of palytoxin on Caco-2 cells hinders their use for in vitro absorption studies.

    Science.gov (United States)

    Pelin, M; Sosa, S; Della Loggia, R; Poli, M; Tubaro, A; Decorti, G; Florio, C

    2012-02-01

    Palytoxin (PLTX), found in Palythoa zoanthids and Ostreopsis dinoflagellates, has also been detected in crabs and fish, through which it can enter into the food chain. Indeed, PLTX is considered the causative agent of several cases of human seafood poisoning resulting in systemic symptoms. Available epidemiological data on PLTX human toxicity suggest that the intestinal tract may be one of its in vivo targets and its potential site of access into the bloodstream. Hence, the purpose of this study was to investigate the suitability of the human intestinal Caco-2 cell line for evaluating PLTX oral absorption. A detailed analysis of PLTX cytotoxicity revealed a high sensitivity of Caco-2 cells: 4h toxin exposure reduced mitochondrial activity (MTT assay, EC(50) of 8.9±3.7×10(-12)M), cell density (SRB assay, EC(50) of 2.0±0.6×10(-11)M) and membrane integrity (LDH release, EC(50) of 4.5±1.4×10(-9)M and PI uptake, EC(50) of 1.0±0.8×10(-8)M). After low PLTX concentration (1.0×10(-11)M) exposure for 1-8h, followed by 24h recovery time in toxin-free medium, cell density reduction was only partially reversible. These results indicate that, due to the high susceptibility to PLTX cytotoxic effects, Caco-2 cells do not represent an appropriate and reliable model for investigating intestinal barrier permeation by this toxin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. The site of net absorption of Ca from the intestinal tract of growing pigs and effect of phytic acid, Ca level and Ca source on Ca digestibility.

    Science.gov (United States)

    González-Vega, J Caroline; Walk, Carrie L; Liu, Yanhong; Stein, Hans H

    2014-01-01

    An experiment was conducted to test the hypothesis that the standardised digestibility of Ca in calcium carbonate and Lithothamnium calcareum Ca is not different regardless of the level of dietary Ca, and that phytic acid affects the digestibility of Ca in these two ingredients to the same degree. The objectives were to determine where in the intestinal tract Ca absorption takes place and if there are measurable quantities of basal endogenous Ca fluxes in the stomach, small intestine or large intestine. Diets contained calcium carbonate or L. calcareum Ca as the sole source of Ca, 0% or 1% phytic acid and 0.4% or 0.8% Ca. A Ca-free diet was also formulated and used to measure endogenous fluxes and losses of Ca. Nine growing pigs (initial body weight 23.8 ± 1.3 kg) were cannulated in the duodenum and in the distal ileum, and faecal, ileal and duodenal samples were collected. Duodenal endogenous fluxes of Ca were greater (p calcareum Ca diets, but that was not the case if calcium carbonate was the source of Ca (interaction, p calcareum Ca was greater (p calcareum Ca. In conclusion, under the conditions of this experiment, standardised digestibility of Ca is not affected by the level of phytic acid, but may be affected by dietary Ca level depending on the Ca source. Calcium from calcium carbonate is mostly absorbed before the duodenum, but Ca from L. calcareum Ca is mostly absorbed in the jejunum and ileum.

  1. Probiotic Bifidobacterium species stimulate human SLC26A3 gene function and expression in intestinal epithelial cells

    Science.gov (United States)

    Kumar, Anoop; Hecht, Cameron; Priyamvada, Shubha; Anbazhagan, Arivarasu N.; Alakkam, Anas; Borthakur, Alip; Alrefai, Waddah A.; Gill, Ravinder K.

    2014-01-01

    SLC26A3, or downregulated in adenoma (DRA), plays a major role in mediating Cl− absorption in the mammalian intestine. Disturbances in DRA function and expression have been implicated in intestinal disorders such as congenital Cl− diarrhea and gut inflammation. We previously showed that an increase in DRA function and expression by Lactobacillus acidophilus and its culture supernatant (CS) might underlie antidiarrheal effects of this probiotic strain. However, the effects of Bifidobacterium species, important inhabitants of the human colon, on intestinal Cl−/HCO3− exchange activity are not known. Our current results demonstrate that CS derived from Bifidobacterium breve, Bifidobacterium infantis, and Bifidobacterium bifidum increased anion exchange activity in Caco-2 cells (∼1.8- to 2.4-fold). Consistent with the increase in DRA function, CS also increased the protein, as well as the mRNA, level of DRA (but not putative anion transporter 1). CS of all three Bifidobacterium sp. increased DRA promoter activity (−1,183/+114 bp) in Caco-2 cells (1.5- to 1.8-fold). Furthermore, the increase in DRA mRNA expression by CS of B. breve and B. infantis was blocked in the presence of the transcription inhibitor actinomycin D (5 μM) and the ERK1/2 MAPK pathway inhibitor U0126 (10 μM). Administration of live B. breve, B. infantis, and B. bifidum by oral gavage to mice for 24 h increased DRA mRNA and protein levels in the colon. These data demonstrate an upregulation of DRA via activation of the ERK1/2 pathway that may underlie potential antidiarrheal effects of Bifidobacterium sp. PMID:25143346

  2. 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.

  3. Developmental changes in intraepithelial T lymphocytes and NK cells in the small intestine of neonatal rats.

    Science.gov (United States)

    Pérez-Cano, Francisco J; Castellote, Cristina; González-Castro, Ana M; Pelegrí, Carme; Castell, Margarida; Franch, Angels

    2005-11-01

    The main objective of this study was to characterize developmental changes in small intestinal intraepithelial lymphocyte (IEL) subpopulations during the suckling period, thus contributing to the understanding of the development of diffuse gut-associated lymphoid tissue (GALT) and to the identification of early mechanisms that protect the neonate from the first contact with diet and gut microbial antigens. The study was performed by double labeling and flow cytometry in IEL isolated from the proximal and distal small intestine of 1- to 21-d-old Lewis rats. During the suckling period, intraepithelial natural killer (NK) cells changed from a typical systemic phenotype, CD8+, to a specific intestinal phenotype, CD8-. Analysis of CD8+ IEL revealed a progressive increase in the relative number of CD8+ IEL co-expressing TCRalphabeta, cells associated with acquired immunity, whereas the percentage of CD8+ cells expressing the NK receptor, i.e. cells committed to innate immunity, decreased. At weaning, IEL maturity was still not achieved, as revealed by a phenotypic pattern that differed from that of adult rats. Thus, late after weaning, the regulatory CD8+CD4+ T IEL population appeared and the NK population declined. In summary, the intestinal intraepithelial compartment undergoes changes in its lymphocyte composition associated with the first ingestion of food. These changes are focused on a relatively high proportion of NK cells during the suckling period, and after weaning, an expansion of the regulatory CD8+CD4+ T cells.

  4. Bacillus subtilis and yeast cell wall improve the intestinal health of broilers challenged by Clostridium perfringens.

    Science.gov (United States)

    Li, Z; Wang, W; Lv, Z; Liu, D; Guo, Y

    2017-12-01

    1. The objective was to investigate the effects of Bacillus subtilis, yeast cell wall (YCW) and their combination on intestinal health of broilers challenged by Clostridium perfringens over a 21-d period. 2. Using a 5 × 2 factorial arrangement of treatments, 800 1-d-old male Cobb 500 broilers were used to study the effects of feed additives (without additive or with zinc bacitracin, B. subtilis, YCW, and the combination of B. subtilis and YCW), pathogen challenge (without or with Clostridium perfringens challenge), and their interactive effects. 3. C. perfringens infection increased intestinal lesions scores, damaged intestinal histomorphology, increased serum endotoxin concentration, cytokine mRNA expression and intestinal population of C. perfringens and Escherichia coli and decreased ileal bifidobacteria numbers. The 4 additives decreased serum endotoxin. Zinc bacitracin tended to decrease cytokine mRNA expression and the intestinal number of C. perfringens and E. coli. B. subtilis, YCW and their combination increased cytokine mRNA expression. B. subtilis and YCW decreased the number of C. perfringens and E. coli in the ileum, and their combination decreased pathogens numbers in the ileum and caecum. 4. In conclusion, B. subtilis, YCW and their combination improved the intestinal health of NE-infected broilers, and could be potential alternatives to antibiotics.

  5. Primary intestinal T cell lymphomas in Indian patients - In search of enteropathic T cell lymphoma

    Directory of Open Access Journals (Sweden)

    Shet Tanuja

    2010-07-01

    Full Text Available Objective: This series of six intestinal T cell lymphomas (ITCL attempts to document enteropathy-associated T cell lymphoma (EATCL in India. Materials and Methods: A total of six ITCL were selected from 170 gastrointestinal lymphomas in last 10 years. Results: The cases studied included EATCL (4, ITCL with a CD4 positive phenotype (1 and ITCL NK/T cell type (1. Of the four EATCL, two occurred in the ileum, one in right colon and one in duodenum. In three EATCL cases, there was history of celiac disease or lactose intolerance and enteropathic changes were noted in the adjacent mucosa. These tumors had CD3+/CD8+/CD56 (+/-/CD4-/ Granzyme B+ immunophenotype. One EATCL was monomorphic small cell type (type II EATCL with a CD3+/CD8-CD56+/CD4-/ Granzyme B+ phenotype. EBER- ISH (Epstein Barr virus coded RNA′s- in situ hybridization revealed positive tumor cells in ITCL NK/T cell type and in bystander cells in three EATCL. Conclusion: ITCL are rare in Indian patients but do occur and comprise a mixture of the enteropathic and non-enteropathic subtypes.

  6. Experimental broadband absorption enhancement in silicon nanohole structures with optimized complex unit cells.

    Science.gov (United States)

    Lin, Chenxi; Martínez, Luis Javier; Povinelli, Michelle L

    2013-09-09

    We design silicon membranes with nanohole structures with optimized complex unit cells that maximize broadband absorption. We fabricate the optimized design and measure the optical absorption. We demonstrate an experimental broadband absorption about 3.5 times higher than an equally-thick thin film.

  7. Nanoparticle formulation of a poorly soluble cannabinoid receptor 1 antagonist improves absorption by rat and human intestine

    NARCIS (Netherlands)

    Siissalo, Sanna; De Waard, Hans; De Jager, Marina H.; Hayeshi, Rose; Frijlink, Henderik W.; Hinrichs, Wouter L.J.; Dinter-Heidorn, Heike; Van Dam, Annie; Proost, Johannes H.; Groothuis, Geny M.M.; De Graaf, Inge A.M.

    The inclusion of nanoparticles dispersed in a hydrophilic matrix is one of the formulation strategies to improve the bioavailability of orally administered Biopharmaceutics Classification System (BCS) class II and IV drugs by increasing their dissolution rate in the intestine. To confirm that the

  8. Lactoferrin targets T cells in the small intestine

    DEFF Research Database (Denmark)

    Nielsen, Sanne Mie; Hansen, Gert Helge; Danielsen, E Michael

    2010-01-01

    BACKGROUND: Lactoferrin (Lf) belongs to the transferrin family of non-heme iron-binding proteins and is found in milk and mucosal secretions. Consequently, it is now considered a multifunctional protein mainly involved in both the innate and adaptive immune defenses of the organism against various...... explants of pig small intestine by immunofluorescence and immunogold microscopy. RESULTS: Lf rapidly bound to the brush border and subsequently appeared in punctae in the apical cytoplasm, indicating internalization into an endosomal compartment. Essentially, no labeling was detected elsewhere...

  9. Paraneoplastic hypereosinophilia in a dog with intestinal T-cell lymphoma.

    Science.gov (United States)

    Marchetti, Veronica; Benetti, Cecilia; Citi, Simona; Taccini, Valentina

    2005-09-01

    A 9-year-old, intact male Doberman Pinscher was examined because of anorexia and weakness. Results of a CBC showed severe, microcytic, hypochromic anemia with mild eosinophilia (2944 cells/microL, reference interval 100-1250/microL) and thrombocytosis. Hypoferremia, hypoferritinemia, and a positive fecal occult blood test supported a diagnosis of iron deficiency anemia secondary to chronic intestinal hemorrhage. Abdominal ultrasound evaluation showed a thickened small intestinal loop, of which representative specimens were obtained during exploratory laparotomy. Histologically, the intestinal wall was infiltrated by a neoplastic population of large, round, lymphoid cells with vesicular chromatin, 1 or more prominent nucleoli, and a high number of mitotic figures. The cells were closely admixed with mature eosinophils, but were negative for metachromatic granules with toluidine blue. Immunohistochemically, tumor cells were positive for CD3, and negative for CD21, Pan B, and CD79a. A diagnosis of intestinal T-cell lymphoma was made. Chemotherapy was begun, with 30 mg/m;2 of doxorubicin administered intravenously every 3 weeks. Eosinophil concentration was 880/microL 2 weeks after surgery (on day 15 after presentation) but increased markedly to 62,914/microL on day 30, 62,400/microL on day 37, and 39,444/microL on day 58 after presentation. An association between hypereosinophilia and T-cell lymphoma is well established in human patients, in whom production of IL-5 by neoplastic T cells has been demonstrated. Hypereosinophilia has been reported only rarely with intestinal lymphoma in cats and horses, and with T-cell lymphoma in dogs.

  10. Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Holmberg, Fredrik Eo; Seidelin, Jakob B; Yin, Xiaolei

    2017-01-01

    models suggests that intestinal stem cell transplantation could constitute a novel treatment strategy to re-establish mucosal barrier function in patients with severe disease. Intestinal stem cells can be grownin vitroin organoid structures, though only a fraction of the cells contained are stem cells...... with regenerative capabilities. Hence, techniques to enrich stem cell populations are being pursued through the development of multiple two-dimensional and three-dimensional culture protocols, as well as co-culture techniques and multiple growth medium compositions. Moreover, research in support matrices allowing...... for efficient clinical application is in progress.In vitroculture is accomplished by modulating the signaling pathways fundamental for the stem cell niche with a suitable culture matrix to provide additional contact-dependent stimuli and structural support. The aim of this review was to discuss medium...

  11. Ultrastructure of interstitial cells of Cajal associated with deep muscular plexus of human small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Mikkelsen, H B; Thuneberg, L

    1992-01-01

    Evidence showing that interstitial cells of Cajal have important regulatory functions in the gut musculature is accumulating. In the current study, the ultrastructure of the deep muscular plexus and associated interstial cells of Cajal in human small intestine were studied to provide a reference...... a continuous basal lamina, caveolae, intermediate filaments, dense bodies, dense bands, and a well-developed subsurface smooth endoplasmic reticulum), but the arrangement of organelles was clearly different, and cisternae of granular endoplasmic reticulum were abundant. Interstitial cells of Cajal were......, and only few gap junctions with other interstitial cells of Cajal or with the musculature were observed. Compared with interstitial cells of Cajal from other mammals, those associated with the deep muscular plexus in the human small intestine more closely resemble smooth muscle cells...

  12. Development of microfluidic cell culture devices towards an in vitro human intestinal barrier model

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin

    to enable real-time detection of cell responses, adjustment of cellular stimulation etc. leading to establishment of conditional experiments. In this project, microfluidic systems engineering was leveraged to develop an eight chamber multi-layer microchip for intestinal barrier studies. Sandwiched between...... the layers was a modified Teflon porous membrane for cell culture. The novelty lies in modifying the surface of the porous Teflon support membrane using thiol-ene ‘click’ chemistry, thus allowing the modified Teflon membrane to be bonded between the chip layers to form an enclosed microchip. Successful...... application of the multi-layer microchip was demonstrated by integrating the microchip to an existing cell culture fluidic system to culture the human intestinal epithelial cells, Caco-2, for long term studies. Under the continuous low flow conditions, the cells differentiated into columnar cells displaying...

  13. Protective effect of NSA on intestinal epithelial cells in a necroptosis model.

    Science.gov (United States)

    Dong, Wei; Zhang, Min; Zhu, Yaxi; Chen, Yuanhan; Zhao, Xingchen; Li, Ruizhao; Zhang, Li; Ye, Zhiming; Liang, Xingling

    2017-10-17

    This study aimed to investigate the protective effect of the necroptosis inhibitor necrosulfonamide (NSA) on intestinal epithelial cells using a novel in vitro necroptosis model that mimics inflammatory bowel disease (IBD). 2,4,6-trinitrobenzenesulfonic acid (TNBS) was perfused into the rectum of BALB/c mice to established a colitis model. Pathologic injury and cell death were evaluated. A novel in vitro model of necroptosis was established in Caco-2 cells using TNF- α and Z-VAD-fmk, and the cells were treated with or without NSA. Morphologic changes, manner of cell death and the levels of phosphorylation of receptor-interacting protein kinase 3 (p-RIPK3) and mixed-lineage kinase domain-like (p-MLKL) were detected. In the TNBS-induced colitis in mice, TUNEL-positive and caspase-3-negative cells were observed in the intestinal mucosa, and p-RIPK3 was found to be elevated. Under the stimulation of TNF- α and Z-VAD-fmk, the morphologic damage in the Caco-2 cells was aggravated, the proportion of necrosis was increased, and the level of p-RIPK3 and p-MLKL were increased, confirming that the regulated cell death was necroptosis. NSA reversed the morphological abnormalities and reduced necrotic cell death induced by TNF- α and Z-VAD-fmk. NSA can inhibit necroptosis in intestinal epithelial cells in vitro and might confer a potential protective effect against IBD.

  14. Translocation of differently sized and charged polystyrene nanoparticles in in vitro intestinal cell models of increasing complexity

    NARCIS (Netherlands)

    Walczak, A.P.; Kramer, E.; Hendriksen, P.J.M.; Tromp, P.; Helsper, J.P.F.G.; Zande, M. van der; Rietjens, I.M.C.M.; Bouwmeester, H.

    2015-01-01

    Intestinal translocation is a key factor for determining bioavailability of nanoparticles (NPs) after oral uptake. Therefore, we evaluated three in vitro intestinal cell models of increasing complexity which might affect the translocation of NPs: a mono-culture (Caco-2 cells), a co-culture with

  15. Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling.

    Science.gov (United States)

    Troll, Joshua V; Hamilton, M Kristina; Abel, Melissa L; Ganz, Julia; Bates, Jennifer M; Stephens, W Zac; Melancon, Ellie; van der Vaart, Michiel; Meijer, Annemarie H; Distel, Martin; Eisen, Judith S; Guillemin, Karen

    2018-02-23

    Resident microbes promote many aspects of host development, although the mechanisms by which microbiota influence host tissues remain unclear. We showed previously that the microbiota is required for allocation of appropriate numbers of secretory cells in the zebrafish intestinal epithelium. Because Notch signaling is crucial for secretory fate determination, we conducted epistasis experiments to establish whether the microbiota modulates host Notch signaling. We also investigated whether innate immune signaling transduces microbiota cues via the Myd88 adaptor protein. We provide the first evidence that microbiota-induced, Myd88-dependent signaling inhibits host Notch signaling in the intestinal epithelium, thereby promoting secretory cell fate determination. These results connect microbiota activity via innate immune signaling to the Notch pathway, which also plays crucial roles in intestinal homeostasis throughout life and when impaired can result in chronic inflammation and cancer. © 2018. Published by The Company of Biologists Ltd.

  16. Porcine intestinal mast cells. Evaluation of different fixatives for histochemical staining techniques considering tissue shrinkage

    Directory of Open Access Journals (Sweden)

    J. Rieger

    2013-07-01

    Full Text Available Staining of mast cells (MCs, including porcine ones, is critically dependent upon the fixation and staining technique. In the pig, mucosal and submucosal MCs do not stain or stain only faintly after formalin fixation. Some fixation methods are particularly recommended for MC staining, for example the fixation with Carnoy or lead salts. Zinc salt fixation (ZSF has been reported to work excellently for the preservation of fixation-sensitive antigens. The aim of this study was to establish a reliable histological method for counting of MCs in the porcine intestinum. For this purpose, different tissue fixation and staining methods that also allow potential subsequent immunohistochemical investigations were evaluated in the porcine mucosa, as well as submucosa of small and large intestine. Tissues were fixed in Carnoy, lead acetate, lead nitrate, Zamboni and ZSF and stained subsequently with either polychromatic methylene blue, alcian blue or toluidine blue. For the first time our study reveals that ZSF, a heavy metal fixative, preserves metachromatic staining of porcine MCs. Zamboni fixation was not suitable for histochemical visualization of MCs in the pig intestine. All other tested fixatives were suitable. Alcian blue and toluidine blue co-stained intestinal goblet cells which made a prima facie identification of MCs difficult. The polychromatic methylene blue proved to be the optimal staining. In order to compare MC counting results of the different fixation methods, tissue shrinkage was taken into account. As even the same fixation caused shrinkage-differences between tissue from small and large intestine, different factors for each single fixation and intestinal localization had to be calculated. Tissue shrinkage varied between 19% and 57%, the highest tissue shrinkage was found after fixation with ZSF in the large intestine, the lowest one in the small intestine after lead acetate fixation. Our study emphasizes that MC counting results from

  17. The Role of Turmerones on Curcumin Transportation and P-Glycoprotein Activities in Intestinal Caco-2 Cells

    Science.gov (United States)

    Yue, Grace G.L.; Cheng, Sau-Wan; Yu, Hua; Xu, Zi-Sheng; Lee, Julia K.M.; Hon, Po-Ming; Lee, Mavis Y.H.; Kennelly, Edward J.; Deng, Gary; Yeung, Simon K.; Cassileth, Barrie R.; Fung, Kwok-Pui; Leung, Ping-Chung

    2012-01-01

    Abstract The rhizome of Curcuma longa (turmeric) is often used in Asia as a spice and as a medicine. Its most well-studied component, curcumin, has been shown to exhibit poor bioavailability in animal studies and clinical trials. We hypothesized that the presence of lipophilic components (e.g., turmerones) in turmeric extract would affect the absorption of curcumin. The effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein (P-gp) activities and mRNA expression were also evaluated. Results showed that in the presence of α- and aromatic turmerones, the amount of curcumin transported into the Caco-2 cells in 2 hours was significantly increased. α-Turmerone and verapamil (a P-gp inhibitor) significantly inhibited the efflux of rhodamine-123 and digoxin (i.e., inhibited the activity of P-gp). It is interesting that aromatic turmerone significantly increased the rhodamine-123 efflux and P-gp (MDR1 gene) mRNA expression levels. The effects of α- and aromatic turmerones on curcumin transport as well as P-gp activities were shown here for the first time. The presence of turmerones did affect the absorption of curcumin in vitro. These findings suggest the potential use of turmeric extract (including curcumin and turmerones), rather than curcumin alone, for treating diseases. PMID:22181075

  18. The role of turmerones on curcumin transportation and P-glycoprotein activities in intestinal Caco-2 cells.

    Science.gov (United States)

    Yue, Grace G L; Cheng, Sau-Wan; Yu, Hua; Xu, Zi-Sheng; Lee, Julia K M; Hon, Po-Ming; Lee, Mavis Y H; Kennelly, Edward J; Deng, Gary; Yeung, Simon K; Cassileth, Barrie R; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B S

    2012-03-01

    The rhizome of Curcuma longa (turmeric) is often used in Asia as a spice and as a medicine. Its most well-studied component, curcumin, has been shown to exhibit poor bioavailability in animal studies and clinical trials. We hypothesized that the presence of lipophilic components (e.g., turmerones) in turmeric extract would affect the absorption of curcumin. The effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein (P-gp) activities and mRNA expression were also evaluated. Results showed that in the presence of α- and aromatic turmerones, the amount of curcumin transported into the Caco-2 cells in 2 hours was significantly increased. α-Turmerone and verapamil (a P-gp inhibitor) significantly inhibited the efflux of rhodamine-123 and digoxin (i.e., inhibited the activity of P-gp). It is interesting that aromatic turmerone significantly increased the rhodamine-123 efflux and P-gp (MDR1 gene) mRNA expression levels. The effects of α- and aromatic turmerones on curcumin transport as well as P-gp activities were shown here for the first time. The presence of turmerones did affect the absorption of curcumin in vitro. These findings suggest the potential use of turmeric extract (including curcumin and turmerones), rather than curcumin alone, for treating diseases.

  19. Deoxynivalenol affects in vitro intestinal epithelial cell barrier integrity through inhibition of protein synthesis

    International Nuclear Information System (INIS)

    Van De Walle, Jacqueline; Sergent, Therese; Piront, Neil; Toussaint, Olivier; Schneider, Yves-Jacques; Larondelle, Yvan

    2010-01-01

    Deoxynivalenol (DON), one of the most common mycotoxin contaminants of raw and processed cereal food, adversely affects the gastrointestinal tract. Since DON acts as a protein synthesis inhibitor, the constantly renewing intestinal epithelium could be particularly sensitive to DON. We analyzed the toxicological effects of DON on intestinal epithelial protein synthesis and barrier integrity. Differentiated Caco-2 cells, as a widely used model of the human intestinal barrier, were exposed to realistic intestinal concentrations of DON (50, 500 and 5000 ng/ml) during 24 h. DON caused a concentration-dependent decrease in total protein content associated with a reduction in the incorporation of [ 3 H]-leucine, demonstrating its inhibitory effect on protein synthesis. DON simultaneously increased the paracellular permeability of the monolayer as reflected through a decreased transepithelial electrical resistance associated with an increased paracellular flux of the tracer [ 3 H]-mannitol. A concentration-dependent reduction in the expression level of the tight junction constituent claudin-4 was demonstrated by Western blot, which was not due to diminished transcription, increased degradation, or NF-κB, ERK or JNK activation, and was also observed for a tight junction independent protein, i.e. intestinal alkaline phosphatase. These results demonstrate a dual toxicological effect of DON on differentiated Caco-2 cells consisting in an inhibition of protein synthesis as well as an increase in monolayer permeability, and moreover suggest a possible link between them through diminished synthesis of the tight junction constituent claudin-4.

  20. 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

  1. 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.

  2. A Unique Cause of Intestinal and Splenic Infarction in a Sickle Cell Trait Patient

    OpenAIRE

    Asfaw, Sofya H.; Falk, Gavin A.; Morris-Stiff, Gareth; Tuthill, Ralph J.; Moorman, Matthew L.; Samotowka, Michael A.

    2013-01-01

    Sickle-cell trait is a common genetic abnormality in the African American population. A sickle-cell crisis in a patient with sickle-cell trait is uncommon at best. Abdominal painful crises are typical of patients with sickle cell anemia. The treatment for an abdominal painful crisis is usually medical and rarely surgical. We present the case of a cocaine-induced sickle-cell crisis in a sickle-cell trait patient that resulted in splenic, intestinal, and cerebral infarctions and multisystem org...

  3. IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Serkan I. Göktuna

    2014-06-01

    Full Text Available The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC therapy.

  4. Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation.

    Science.gov (United States)

    Koboziev, Iurii; Karlsson, Fridrik; Grisham, Matthew B

    2010-10-01

    The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is to provide an overview of the mechanisms involved in naive and effector T cell trafficking to the gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes and intestine in response to commensal enteric antigens under physiological conditions as well as during the induction of chronic gut inflammation. In addition, recent data suggests that the GALT may not be required for enteric antigen-driven intestinal inflammation in certain mouse models of IBD. These new data suggest a possible paradigm shift in our understanding of how and where naive T cells become activated to yield disease-producing effector cells. © 2010 New York Academy of Sciences.

  5. Radiosensitivity of mice of different lines and age as determinated with reference to ''intestinal'' death and DNA repair in intestinal epithelium cells

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.; Sklobovskaya, M.V.; Konoplyannikov, A.G.; Saenko, A.S.

    1982-01-01

    A study was made of the influence of strain- and age-related differences on mouse mortality after irradiation with doses lying within the ''intest+nal'' dose range, and also damages to stem cells of intestinal epithelium and induction and repair of single-strand DNA breaks in intestinal epitherium cells. Mice of different lines and age vary in LDsub(50/4) and stem cell radiosensitivity. There are no differences in the sedimentation constants of DNA fragments in alkaline lysates of intestinal crypts of intact mice of different age. Radiosensitivity determined with reference to single-strand breaks induction in DNA is similar with different mo use groups. Repair of single-strand DNA breaks of eldery mice is slower than that of young animals

  6. Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1987-01-01

    The role of extracellular amines such as noradrenaline and serotonin and their interaction with cyclic nucleotides and intracellular polyamines in the regulation of intestinal epithelial cell proliferation is reviewed with particular reference to the differences between normal and neoplastic cells. In respect to the normal epithelium of the small intestine there is a strong case to support the notion that cell proliferation is controlled by, amongst other things, sympathetic nerves. In colonic carcinomas, antagonists for certain serotonin receptors, for histamine H2 receptors and for dopamine D2 receptors inhibit both cell division and tumour growth. Because of the reproducible variations between tumour lines in the response to these antagonists, this inhibition appears to be due to a direct effect on the tumour cells rather than an indirect effect via the tumour host or stroma. This conclusion is supported by the cytocidal effects of toxic congeners of serotonin on the tumour cells. The most salient difference between the amine responses of normal and neoplastic cells relates to the issue of amine uptake. Proliferation of crypt cells is promoted by amine uptake inhibitors, presumably because they block amine re-uptake by the amine secreting cells--sympathetic neurones and enteroendocrine cells. However, tumour cell proliferation is strongly inhibited by amine uptake inhibitors, suggesting that neoplastic cells can, and need to take up the amine before being stimulated by it. Recent revelations in the field of oncogenes also support an important association between amines, cyclic nucleotides and cell division. The ras oncogenes code for a protein that is a member of a family of molecules which relay information from extracellular regulators, such as biogenic amines, to the intracellular regulators, including cyclic nucleotides. Evidence is presented suggesting that enteroendocrine cells, enterocytes, carcinoid tumour cells and adenocarcinoma cells all have the same

  7. Mesenteric blood flow, glucose absorption and blood pressure responses to small intestinal glucose in critically ill patients older than 65 years.

    Science.gov (United States)

    Sim, Jennifer A; Horowitz, M; Summers, M J; Trahair, L G; Goud, R S; Zaknic, A V; Hausken, T; Fraser, J D; Chapman, M J; Jones, K L; Deane, A M

    2013-02-01

    To compare nutrient-stimulated changes in superior mesenteric artery (SMA) blood flow, glucose absorption and glycaemia in individuals older than 65 years with, and without, critical illness. Following a 1-h 'observation' period (t (0)-t (60)), 0.9 % saline and glucose (1 kcal/ml) were infused directly into the small intestine at 2 ml/min between t (60)-t (120), and t (120)-t (180), respectively. SMA blood flow was measured using Doppler ultrasonography at t (60) (fasting), t (90) and t (150) and is presented as raw values and nutrient-stimulated increment from baseline (Δ). Glucose absorption was evaluated using serum 3-O-methylglucose (3-OMG) concentrations during, and for 1 h after, the glucose infusion (i.e. t (120)-t (180) and t (120)-t (240)). Mean arterial pressure was recorded between t (60)-t (240). Data are presented as median (25th, 75th percentile). Eleven mechanically ventilated critically ill patients [age 75 (69, 79) years] and nine healthy volunteers [70 (68, 77) years] were studied. The magnitude of the nutrient-stimulated increase in SMA flow was markedly less in the critically ill when compared with healthy subjects [Δt (150): patients 115 (-138, 367) versus health 836 (618, 1,054) ml/min; P = 0.001]. In patients, glucose absorption was reduced during, and for 1 h after, the glucose infusion when compared with health [AUC(120-180): 4.571 (2.591, 6.551) versus 11.307 (8.447, 14.167) mmol/l min; P AUC(120-240): 26.5 (17.7, 35.3) versus 40.6 (31.7, 49.4) mmol/l min; P = 0.031]. A close relationship between the nutrient-stimulated increment in SMA flow and glucose absorption was evident (3-OMG AUC(120-180) and ∆SMA flow at t (150): r (2) = 0.29; P 65 years, stimulation of SMA flow by small intestinal glucose infusion may be attenuated, which could account for the reduction in glucose absorption.

  8. The alteration in intestinal secretory immunoglobulin A and its secreting cells during ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Li-qun SUN

    2012-04-01

    Full Text Available Objective To investigate the change in intestinal secretion immunoglobulin A (sIgA level and IgA-secreting cells during ischemia/reperfusion (I/R injury. Methods Forty-eight BALB/c mice were randomly divided into 6 experimental groups in accordance with different reperfusion times (R2h, R6h, R12h, R24h, and R72h group, and one sham group (n=8. Bacterial translocation to distant organs (lung, spleen, and mesenteric lymph nodes was observed. The sIgA level of the intestinal tract was measured by enzyme-linked immunosorbent assay (ELISA. The B cell subgroup in the lymphocytes related to the intestinal tract was measured by flow cytometry. Results The bacterial translocation occurred during I/R injury, and the intestinal sIgA level decreased, and they showed an obvious negative correlation (r2=0.729. With the increase in intestinal I/R injury, the ratio of IgM+B220+ cells in the gut-associated lymphoid tissue increased, whereas the proportion of IgA+B220+ cells decreased. The most significant change was found in R12h group (P < 0.01. Conclusions The proportion of IgM+ B cells in the gut-associated lymphoid tissue increased, whereas that of IgA+ B cells reduced during I/R injury. These phenomena may cause sIgA level to reduce and bacterial translocation of the distant organs to occur.

  9. Study of Absorption Characteristics of the Total Saponins from Radix Ilicis Pubescentis in an In Situ Single-Pass Intestinal Perfusion (SPIP Rat Model by Using Ultra Performance Liquid Chromatography (UPLC

    Directory of Open Access Journals (Sweden)

    Guojun Kuang

    2017-11-01

    Full Text Available In contrast to the extensively reported therapeutic activities, far less attention has been paid to the intestinal absorption of the total saponins from Radix Ilicis Pubescentis (in Chinese Mao-Dong-Qing, MDQ. This study aimed to investigate the intestinal absorption characteristics of ilexgenin A (C1, ilexsaponin A1 (C2, ilexsaponin B1 (C3, ilexsaponin B2 (C4, ilexsaponin B3 (DC1, and ilexoside O (DC2 when administrated with the total saponins from MDQ (MDQ-TS. An UPLC method for simultaneous determination of C1, C2, C3, C4, DC1, and DC2 in intestinal outflow perfusate was developed and validated. The absorption characteristics of MDQ-TS were investigated by evaluating the effects of intestinal segments, drug concentration, P-glycoprotein (P-gp inhibitor (verapomil, endocytosis inhibitor (amantadine and ethylene diamine tetraacetic acid (EDTA, tight junction modulator on the intestinal transportation of MDQ-TS by using a single-pass intestinal perfusion (SPIP rat model, and the influence of co-existing components on the intestinal transport of the six saponins was discussed. The results showed that effective apparent permeability (Papp of C1, C2, C3, C4, and DC2 administrated in MDQ-TS form had no segment-dependent changes at low and middle dosage levels. C1, C2, C3, D4, DC1, and DC2 administrated in MDQ-TS form all exhibited excellent transmembrane permeability with Papp > 0.12 × 10−2 cm·min−1. Meanwhile, Papp and effective absorption rate constant (Ka values for the most saponins showed concentration dependence and saturation characteristics. After combining with P-gp inhibitor of verapamil, Papp of C2, C3, and DC1 in MDQ-TS group was significantly increased up to about 2.3-fold, 1.4-fold, and 3.4-fold, respectively in comparison to that of non-verapamil added group. Verapamil was found to improve the absorption of C2, C3, and DC1, indicating the involvement of an active transport mechanism in the absorption process. Compared with the

  10. Protein hydrolysate from canned sardine and brewing by-products improves TNF-α-induced inflammation in an intestinal-endothelial co-culture cell model.

    Science.gov (United States)

    Vieira, Elsa F; Van Camp, John; Ferreira, Isabel M P L V O; Grootaert, Charlotte

    2017-07-17

    The anti-inflammatory activity of sardine protein hydrolysates (SPH) obtained by hydrolysis with proteases from brewing yeast surplus was ascertained. For this purpose, a digested and desalted SPH fraction with molecular weight lower than 10 kDa was investigated using an endothelial cell line (EA.hy926) as such and in a co-culture model with an intestinal cell line (Caco-2). Effects of SPH <10 kDa on nitric oxide (NO) production, reactive oxygen species (ROS) inhibition and secretion of monocyte chemoattractant protein 1 (MCP-1), vascular endothelial growth factor (VEGF), chemokine IL-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) were evaluated in TNF-α-treated and untreated cells. Upon TNF-α treatment, levels of NO, MCP-1, VEGF, IL-8, ICAM-1 and endothelial ROS were significantly increased in both mono- and co-culture models. Treatment with SPH <10 kDa (2.0 mg peptides/mL) significantly decreased all the inflammation markers when compared to TNF-α-treated control. This protective effect was more pronounced in the co-culture model, suggesting that SPH <10 kDa Caco-2 cells metabolites produced in the course of intestinal absorption may provide a more relevant protective effect against endothelial dysfunction. Additionally, indirect cross-talk between two cell types was established, suggesting that SPH <10 kDa may also bind to receptors on the Caco-2 cells, thereby triggering a pathway to secrete the pro-inflammatory compounds. Overall, these in vitro screening results, in which intestinal digestion, absorption and endothelial bioactivity are simulated, show the potential of SPH to be used as a functional food with anti-inflammatory properties.

  11. Distribution and characterisation of CCK containing enteroendocrine cells of the mouse small and large intestine

    DEFF Research Database (Denmark)

    Fakhry, Josiane; Wang, Joyce; Martins, Patricia

    2017-01-01

    but positive cells were rare in the rectum. Immunoreactive EEC were as common in the caecum and proximal colon as they were in the duodenum and jejunum. CCK gene transcripts were found in the mucosa throughout the intestine but mRNA for gastrin, a hormone that can bind some anti-CCK antibodies, was only found...

  12. Impact of thymectomy and antilymphocytic serum on stem cells of the intestinal epithelium

    International Nuclear Information System (INIS)

    Aparovich, G.G.; Trufakin, V.A.

    1982-01-01

    The population of stem cells of the intestinal epithelium was studied under conditions of the disturbed balance in the immune system on F 1 (CBAxC57B1) mice. It has been shown that thymectomy in adult mice does not influence the stem region of the intestinal epithelium at early time of observation but causes a tendency to the changed number of epithelial stem cells in 4-6 months. Administration of specific sera against T-, B- and mixed lymphoid populations on the 1st day of observation produces an ambi us effect on the stem region and results in an increase of the number of epithelial stem cells on the 5th day. After administration of the antilymphocytic serum there have been determined morphological changes in the population of mature erythrocytes and undulatory fluctuations in the number of mitotic cells of the intestinal epithelium. These data suggest functional correlation of the intestinal epithelium and the state of the immunocompetent tissue [ru

  13. Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells

    NARCIS (Netherlands)

    Akbari, Peyman; Fink-Gremmels, Johanna; Willems, Rianne H.A.M.; Difilippo, Elisabetta; Schols, Henk A.; Schoterman, Margriet H.C.; Garssen, Johan; Braber, Saskia

    2017-01-01

    Purpose: The direct effects of galacto-oligosaccharides (GOS), including Vivinal® GOS syrup (VGOS) and purified Vivinal® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To

  14. Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

    NARCIS (Netherlands)

    The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; van der Heide, S.; van den Wijngaard, R. M.; de Jonge, W. J.; Boeckxstaens, G. E.

    2008-01-01

    Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

  15. Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

    NARCIS (Netherlands)

    The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; Van der Heide, S.; van den Wijngaard, R. M.; Boeckxstaens, G. E.; de Jonge, Wouter J.

    Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

  16. Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells

    International Nuclear Information System (INIS)

    Labadie, Karine; Pelletier, Isabelle; Saulnier, Aure; Martin, Javier; Colbere-Garapin, Florence

    2004-01-01

    Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface

  17. Genome-wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila

    Directory of Open Access Journals (Sweden)

    Xiankun Zeng

    2015-02-01

    Full Text Available The intestinal epithelium is the most rapidly self-renewing tissue in adult animals and maintained by intestinal stem cells (ISCs in both Drosophila and mammals. To comprehensively identify genes and pathways that regulate ISC fates, we performed a genome-wide transgenic RNAi screen in adult Drosophila intestine and identified 405 genes that regulate ISC maintenance and lineage-specific differentiation. By integrating these genes into publicly available interaction databases, we further developed functional networks that regulate ISC self-renewal, ISC proliferation, ISC maintenance of diploid status, ISC survival, ISC-to-enterocyte (EC lineage differentiation, and ISC-to-enteroendocrine (EE lineage differentiation. By comparing regulators among ISCs, female germline stem cells, and neural stem cells, we found that factors related to basic stem cell cellular processes are commonly required in all stem cells, and stem-cell-specific, niche-related signals are required only in the unique stem cell type. Our findings provide valuable insights into stem cell maintenance and lineage-specific differentiation.

  18. Stem Cells in the Intestine: Possible Roles in Pathogenesis of Irritable Bowel Syndrome.

    Science.gov (United States)

    Ratanasirintrawoot, Sutheera; Israsena, Nipan

    2016-07-30

    Irritable bowel syndrome is one of the most common functional gastrointestinal (GI) disorders that significantly impair quality of life in patients. Current available treatments are still not effective and the pathophysiology of this condition remains unclearly defined. Recently, research on intestinal stem cells has greatly advanced our understanding of various GI disorders. Alterations in conserved stem cell regulatory pathways such as Notch, Wnt, and bone morphogenic protein/TGF- β have been well documented in diseases such as inflammatory bowel diseases and cancer. Interaction between intestinal stem cells and various signals from their environment is important for the control of stem cell self-renewal, regulation of number and function of specific intestinal cell types, and maintenance of the mucosal barrier. Besides their roles in stem cell regulation, these signals are also known to have potent effects on immune cells, enteric nervous system and secretory cells in the gut, and may be responsible for various aspects of pathogenesis of functional GI disorders, including visceral hypersensitivity, altered gut motility and low grade gut inflammation. In this article, we briefly summarize the components of these signaling pathways, how they can be modified by extrinsic factors and novel treatments, and provide evidenced support of their roles in the inflammation processes. Furthermore, we propose how changes in these signals may contribute to the symptom development and pathogenesis of irritable bowel syndrome.

  19. Rorγt+ innate lymphoid cells in intestinal homeostasis and immunity.

    Science.gov (United States)

    Aparicio-Domingo, Patricia; Cupedo, Tom

    2011-01-01

    Innate lymphoid cells (ILC) combine innate and adaptive immune functions and are part of the first line of defense against mucosal infections. ILC are set apart from adaptive lymphocytes by their independence on RAG genes and the resulting absence of specific antigen receptors. In this review, we will discuss the biology and function of intestinal ILC that express the nuclear hormone receptor Rorγt (encoded by the Rorc gene) and highlight their role in intestinal homeostasis and immunity. Copyright © 2011 S. Karger AG, Basel.

  20. Quantitative rather than qualitative differences in gene expression predominate in intestinal cell maturation along distinct cell lineages

    International Nuclear Information System (INIS)

    Velcich, Anna; Corner, Georgia; Paul, Doru; Zhuang Min; Mariadason, John M.; Laboisse, Christian; Augenlicht, Leonard

    2005-01-01

    Several cell types are present in the intestinal epithelium that likely arise from a common precursor, the stem cell, and each mature cell type expresses a unique set of genes that characterizes its functional phenotype. Although the process of differentiation is intimately linked to the cessation of proliferation, the mechanisms that dictate intestinal cell fate determination are not well characterized. To investigate the reprogramming of gene expression during the cell lineage allocation/differentiation process, we took advantage of a unique system of two clonal derivatives of HT29 cells, Cl16E and Cl19A cells, which spontaneously differentiate as mucus producing goblet and chloride-secreting cells, respectively, as a function of time. By profiling gene expression, we found that these two cell lines show remarkably similar kinetics of change in gene expression and common clusters of coordinately regulated genes. This demonstrates that lineage-specific differentiation of intestinal epithelial cells is characterized overall by the sequential recruitment of functionally similar gene sets independent of the final phenotype of the mature cells

  1. The crypt and cell size kinetics in the irradiated intestinal epithelium in mice

    International Nuclear Information System (INIS)

    Kononenko, A.M.; Gagarin, A.U.

    1975-01-01

    A study has been made of changes in the average values of the axial cross-sectional area of the crypt and of cell area in this cross-section for eight days after a single whole-body exposure of male mice to 400 rad of X-rays. A small reduction in the crypt area in the destructive period gives way to a much greater increase in the normal dimensions of the area in the regenerative period. Two very considerable waves of anomalous increase are observed in the dimensions of the cryptal cell cross-sections, the first in the destructive and the second in the regenerative period. These fluctuations in cell dimensions do not occur around but above the control level, attaining the latter level only at the minimum (4th day). The size of the cryptal cells of the intact intestinal epithelium is evidently close to the minimum needed for enterocyte proliferation. The considerable increase in crypt dimensions in the regenerative period (beginning from the 6th day) is not due to the larger number of cells (they are even somewhat fewer than normal) but rather to a substantial increase in cell dimensions. Thus, according to these data, on the 6th-8th day after irradiation the intestinal epithelium deviates strongly from the stationary state. The index I sub(v), where I is the mitotic index and v the cell volume, was used to evaluate the changes in the value of the material stream, connected with proliferation, to the intestinal epithelium per cryptal cell. A considerable increase was found in this stream (hypertrophy of proliferative cells) in the intestinal epithelium restored after irradiation. (author)

  2. The Xenobiotic Transporter Mdr1 Enforces T Cell Homeostasis in the Presence of Intestinal Bile Acids.

    Science.gov (United States)

    Cao, Wei; Kayama, Hisako; Chen, Mei Lan; Delmas, Amber; Sun, Amy; Kim, Sang Yong; Rangarajan, Erumbi S; McKevitt, Kelly; Beck, Amanda P; Jackson, Cody B; Crynen, Gogce; Oikonomopoulos, Angelos; Lacey, Precious N; Martinez, Gustavo J; Izard, Tina; Lorenz, Robin G; Rodriguez-Palacios, Alex; Cominelli, Fabio; Abreu, Maria T; Hommes, Daniel W; Koralov, Sergei B; Takeda, Kiyoshi; Sundrud, Mark S

    2017-12-19

    CD4 + T cells are tightly regulated by microbiota in the intestine, but whether intestinalcells interface with host-derived metabolites is less clear. Here, we show that CD4 + T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn's disease-like ileitis following transfer into Rag1 -/- hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1 -/- mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn's disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Isolation and Flow Cytometry Analysis of Innate Lymphoid Cells from the Intestinal Lamina Propria.

    Science.gov (United States)

    Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

    2017-01-01

    The intestinal mucosa constitutes the biggest surface area of the body. It is constantly challenged by bacteria, commensal and pathogenic, protozoa, and food-derived irritants. In order to maintain homeostasis, a complex network of signaling circuits has evolved that includes contributions of immune cells. In recent years a subset of lymphocytes, which belong to the innate immune system, has caught particular attention. These so-called innate lymphoid cells (ILC) reside within the lamina propria of the small and large intestines and rapidly respond to environmental challenges. They provide immunity to various types of infections but may also contribute to organ homeostasis as they produce factors acting on epithelial cells thereby enhancing barrier integrity. Here, we describe how these cells can be isolated from their environment and provide an in-depth protocol how to visualize the various ILC subsets by flow cytometry.