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Sample records for rats small intestine

  1. Small intestine biopotentials in rats after hypokinesia

    NASA Astrophysics Data System (ADS)

    Groza, P.; Stanciu, C.

    To study the effect of hypokinesia on rats small intestine (jejunum and ileum) biopotentials it was first necessary to characterize it. Biopotentials were recorded by intracellular placed microelectrodes from oral and caudal segments of the small intestine. The character of rats small intestine biopotentials differs from that of other species (man, cat, rabbit, dog, e.a.), the slow waves (SW) being smaller and the frequency of basal electrical rhythm higher (31.23 c/min orally and 24.50 caudally). Spike potentials are inscribed on the descending slope of SW but frequently delayed in each successive wave with a regular interval. Hypokinesia obtained by keeping rats in small cages for two weeks create only little changes in intestine biopotentials. The only clear difference was the increase of the slow waves amplitude. The other parameters were not specifically changed.

  2. Transport of deutherium oxide across isolated rat small intestine.

    PubMed Central

    Bywater, R J; Fisher, R B; Gardner, M L

    1975-01-01

    1. Transport of deuterium oxide from a luminal perfusate containing 1% D2O was studied in Fisher & Gardners (1974) isolated preparation of perfused rat small intestine. 2. The kinetics of appearance of D2O in the intestinal secretion at the serosal surface fitted well to a single exponential function. 3. The steady-state concentration of D2O in this secretion was not significantly different from the concentration in the luminal perfusate. 4. The total tissue water contained D2O at a concentration, on average, 5% lower than that in the luminal perfusate. 5. There is no evidence to suggest discrimination in transport across the intestinal mucosa between H2O and D2O. 6. The kinetics of wash-in of D2O to intestinal secretion show that the ratio of flux out of the lumen to reflux back to the lumen is 1-38;1. PMID:1177106

  3. Developmental changes of prostaglandin processing in rat small intestine

    SciTech Connect

    Koldovsky, O.; Bedrick, A.

    1986-03-01

    Cytoprotective prostaglandins are present in milk and can be absorbed intact from the gastrointestinal tract in suckling animals. To examine developmental changes in intestinal metabolism of PGF/sub 2..cap alpha../, everted sacs of small intestinal segments in suckling and weanling rats were prepared. Incubation (60 min) was performed in KRB buffer, pH 7.4 at 37/sup 0/C. Bathing mucosal fluid (MF) contained /sup 3/H-PGF/sub 2..cap alpha../. MF, intestinal wall (IW) and serosal fluid (SF) were analyzed quantitatively for total radioactivity, and qualitatively by organic solvent extraction followed by thin layer chromatography. Changes in MF radioactivity were minimal after incubation. SU had greater capacity for PGF/sub 2..cap alpha../ transfer into SF. Compared to WE, SU had greater proportion of intact, unmetabolized PGF/sub 2..cap alpha../ present in IW of all intestinal segments; i.e., in middle segment: 32.9% +/- 4.5 (mean +/- SEM) vs 17.1% +/- 2.4 (N = 6/group; p < 0.2). WE had more nonpolar PGF/sub 2..cap alpha../ degradation products present. In each age group, chromatographic patterns of IW and SF were similar for each intestinal region. Intestinal everted sacs of SU and WE transfer PGF/sub 2..cap alpha../. SU have a greater proportion and amount of unmetabolized PGF/sub 2..cap alpha../ present in IW and SF than WE. Possible functional significance to the integrity of intestinal mucosal of sucklings has to be considered.

  4. Early Adaptation of Small Intestine After Massive Small Bowel Resection in Rats

    PubMed Central

    Chen, Jie; Qin, Zhen; Shan, Hongmei; Xiao, Yongtao; Cai, Wei

    2015-01-01

    Background: It is important that the residual bowel adapts after massive resection. The necessary intestinal adaptation is a progressive recovery from intestinal failure through increase in absorptive surface area and functional capacity and includes both morphological and functional adaptations. Objectives: The aim of this study was to investigate intestinal morphological and functional adaptations of small bowel syndrome (SBS) model rats (SBS1W) 7 days after bowel resection. Materials and Methods: Male sprague–dawley rats (n = 20/group) underwent either a 75% proximal small bowel resection (SBS1W group) or a control operation (control group). Markers of morphological adaptation were revealed by TEM analysis of H&E-stained tissue samples. The intestinal barrier condition was assessed by BT, and sIgA concentration in intestinal mucus was measured by ELISA. Contractility and the slow wave rhythm of the entire intestinal remnant were measured and recorded. Results: The SBS1W group experienced more weight loss than control group and had a clearly different intestinal morphology as revealed in TEM images. Compared with control rats, the SBS1W group had a lower sIgA concentration in intestinal mucus and higher BT to lymph nodes (70% vs 40%; level I), portal blood (40% vs 10%; level II), and peripheral blood (60% vs 30%; level III). Disorder of spontaneous rhythmic contraction, irregular amplitude, and slow frequency were detected in the SBS1W group by a muscle strips test. Similarly, the slow wave of the entire intestinal remnant in the SBS1W group was irregular and uncoordinated. Conclusions: The finding of intestinal adaptation following massive SBR in SBS1W rats provides more understanding of the mechanisms of progressive recovery from the intestinal failure that underlies SBS. The mechanical, chemical, immunological, and biological barriers were all impaired at 7 days following bowel resection, indicating that the SBS model rats were still in the intestinal

  5. Cutaneous thermal injury alters macromolecular permeability of rat small intestine.

    PubMed

    Carter, E A; Tompkins, R G; Schiffrin, E; Burke, J F

    1990-03-01

    The intestinal epithelium normally provides a barrier function that prevents absorption of potentially harmful materials from the intestinal lumen. It has been postulated but never demonstrated that a cutaneous thermal injury will result in increased small-intestinal permeability. In a standardized 20% body surface area full-thickness scald injury, with polyethylene glycol 3350 and horseradish peroxidase used as permeability probes, small-intestinal permeability was examined regionally in an everted intestinal sac model. In the normal animals, the upper (proximal) and lower (distal) small intestine were less permeable to these probes than the middle segment. Within 6 hours after the injury, an increase in the mucosal uptake and transmural permeability was seen in all three small-intestinal segments; the most dramatic increase in permeability occurred in the ileum, p less than 0.01. The maximum increase in permeability was seen at 18 hours, and permeability was normal by 72 hours after the injury. This increase in intestinal permeability may represent a transient failure of the intestinal barrier function and may allow absorption of potentially toxic macromolecules from the intestinal lumen into the portal circulation early after thermal injury. Absorption of these macromolecules, such as endotoxin, may be potentially harmful by direct toxic actions or potentially helpful by activation of the immune system. PMID:2309150

  6. Effect of Phenobarbital on Chloramphonicol-Induced Toxicity in Rat Liver and Small Intestine

    PubMed Central

    Ahmadizadeh, Massumeh; Esmailpoor, Masood; Goodarzi, Zahra

    2013-01-01

    Objective(s): The aim of the present study is to determine the effect of Chloramphenicol (CAP) on rat liver and small intestine. Effect of phenobarbital (PB) on CAP toxicity was also investigated. Materials and Methods: Rats were received CAP at doses of 0, 200, 400 and 600 mg/kg. Another group was pretreated with 80 mg/kg PB 30 min prior to administration of various doses of CAP. The experiment was repeated for seven consecutive days. Blood was collected for determination of serum aspartate aminotransferase (AST) alanine aminotransferase (ALT). The liver and small intestine tissues were processed for light microscopy. Results: CAP induced a dose dependent elevation of AST and ALT and produced injury in the liver and small intestine when compared to control animals. PB markedly decreased AST and ALT levels and protected liver and small intestine against CAP-induced toxicity. Conclusion : This study suggested rat liver and small intestine have potential to bioactivate CAP. PMID:24570836

  7. [Mucosal ultrastructure of the rat small intestine after flight on the Kosmos-936 biosatellite].

    PubMed

    Iakovleva, N D; Pogudina, N A; Brodskiĭ, R A

    1981-01-01

    The mucous membrane of the small intestine midportion of rats from the flight (weightless and centrifuged), synchronous and vivarium groups was examined electron microscopically. Ultrastructural changes were seen in all experimental groups, although their level and rate of recovery were different. Artificial gravity on Cosmos-936 did not influence those changes significantly. The data obtained suggest that the above changes are morphological manifestations of the reaction of rat small intestine to the combined effects of space flight factors. PMID:7289543

  8. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    SciTech Connect

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-04-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-(/sup 14/C)xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in /sup 14/CO/sub 2/ excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an ..cap alpha../sub 2/-adrenergic agonist.

  9. Trophic effect of Efamol on the rat small-intestinal mucosa.

    PubMed

    Jenkins, A P; Thompson, R P

    1989-11-01

    1. The hypothesis that triacylglycerols are trophic to the small-intestinal mucosa of the rat was tested by comparing the action of the essential fatty acid-rich oil Efamol with that of glucose. 2. Two groups of nine female Wistar rats were pair-fed Vivonex HN with 50% calorie substitution by glucose or Efamol for 21 days. 3. Body weight gain was greater with glucose than with Efamol, but, despite this, whole gut weight, mucosal weight and mucosal protein were increased by Efamol in all small-intestinal segments. Total mucosal DNA was also increased with a significant change in the middle small-intestinal segment. These changes were associated with an increased crypt cell production rate. 4. Fasting plasma levels of peptidyltyrosyltyrosine ('peptide YY'), but not of enteroglucagon, were significantly elevated in the Efamol-fed group. 5. The data show a trophic effect of Efamol on the rat small-intestinal mucosa. Possible mechanisms are discussed. PMID:2582727

  10. Prostacyclin inhibits gastric emptying and small-intestinal transit in rats and dogs

    SciTech Connect

    Ruwart, M.J.; Rush, B.D.

    1984-08-01

    Prostacyclin (PGI2) antagonizes 16,16-dimethyl prostaglandin E2-induced diarrhea in rats, presumably by inhibiting the fluid accumulation of ''enteropooling'' in the small intestine. The effect of PGI2 on gastric emptying, small intestinal transit, and colonic transit was examined in rats and dogs to determine if interference with propulsion might also contribute to the antidiarrheal properties of this compound. Rats implanted with chronic duodenal cannulas were given subcutaneous PGI2 (0.1-1000 microgram/kg) followed 10 min later by intragastric /sup 2/Cr and a visually detectable duodenal transit marker. Forty-five minutes later, the animals were killed. Subcutaneous PGI2 inhibited gastric emptying maximally at 10 micrograms/kg. Small-intestinal transit was significantly decreased at 50 micrograms/kg and almost completely suppressed at 1.0 mg/kg. Subcutaneous naloxone (0.5 mg/kg) given 10 min before and 20 min after subcutaneous PGI2 administration did not block PGI2's effects. Intravenous or oral PGI2, had none of these effects. Small intestinal transit was only decreased by PGI2 infusion, suggesting that this parameter was more sensitive to a sustained blood level than gastric emptying. Hourly injections of subcutaneous PGI2 (0.5 mg/kg) had no effect on rat colonic transit measured over a 3-h period after deposition of the transit marker through a colonic cannula in a manner similar to that described for small-intestinal transit above. Small-intestinal transit was also measured in dogs given a barium suspension through a chronic duodenal cannula. In vehicle-treated dogs, barium reached the cecal area in an average of 2.8 h after instillation. In PGI2-treated dogs, barium never reached the cecum in the 5-h examination period. Thus, PGI2 inhibits gastric emptying in rat and small-intestinal transit in rat and dog but has no effect on rat colonic transit.

  11. Prostacyclin inhibits gastric emptying and small-intestinal transit in rats and dogs.

    PubMed

    Ruwart, M J; Rush, B D

    1984-08-01

    Prostacyclin (PGI2) antagonizes 16,16-dimethyl prostaglandin E2-induced diarrhea in rats, presumably by inhibiting the fluid accumulation of "enteropooling" in the small intestine. The effect of PGI2 on gastric emptying, small intestinal transit, and colonic transit was examined in rats and dogs to determine if interference with propulsion might also contribute to the antidiarrheal properties of this compound. Rats implanted with chronic duodenal cannulas were given subcutaneous PGI2 (0.1-1000 microgram/kg) followed 10 min later by intragastric 51Cr and a visually detectable duodenal transit marker. Forty-five minutes later, the animals were killed. Small-intestinal transit was expressed as the percentage of small intestinal length traveled by the visually detected marker. Gastric emptying was expressed as the percentage of the total 51Cr found in the small intestine. Subcutaneous PGI2 inhibited gastric emptying maximally at 10 micrograms/kg. Small-intestinal transit was significantly decreased at 50 micrograms/kg and almost completely suppressed at 1.0 mg/kg. Subcutaneous naloxone (0.5 mg/kg) given 10 min before and 20 min after subcutaneous PGI2 administration did not block PGI2's effects. Intravenous or oral PGI2 in doses as high as 0.2 or 10 mg/kg, respectively, had none of these effects. However, a high-dose intravenous bolus (1.0 mg/kg) or infusion (1.0 mg/kg X 45 min) both inhibited gastric emptying. Small intestinal transit was only decreased by PGI2 infusion, suggesting that this parameter was more sensitive to a sustained blood level than gastric emptying. Hourly injections of subcutaneous PGI2 (0.5 mg/kg) had no effect on rat colonic transit measured over a 3-h period after deposition of the transit marker through a colonic cannula in a manner similar to that described for small-intestinal transit above. Small-intestinal transit was also measured in dogs given a barium suspension through a chronic duodenal cannula. The animals simultaneously received

  12. Epithelioid cell cultures from rat small intestine. Characterization by morphologic and immunologic criteria.

    PubMed

    Quaroni, A; Wands, J; Trelstad, R L; Isselbacher, K J

    1979-02-01

    Rat small intestinal epithelial cell lines have been established in vitro and subcultured serially for periods up to 6 mo. These cells have an epithelioid morphology, grow as monolayers of closely opposed polygonal cells, and during the logarithmic phase of growth have a population doubling time of 19--22 h. Ultrastructural studies revealed the presence of microvilli, tight junctions, an extensive Golgi complex, and the presence of extracellular amorphous material similar in appearance to isolated basement membrane. These cells exhibit a number of features characteristic of normal cells in culture; namely, a normal rat diploid karyotype, strong density inhibition of growth, lack of growth in soft agar, and a low plating efficiency when seeded at low density. They did not produce tumors when injected in syngeneic animals. Immunochemical studies were performed to determine their origin using antisera prepared against rat small intestinal crypt cell plasma membrane, brush border membrane of villus cells and isolated sucrase-isomaltase complex. Antigenic determinants specific for small intestinal epithelial (crypt and villus) cells were demonstrated on the surface of the epithelioid cells, but they lacked immunological determinants specific for differentiated villus cells. An antiserum specifically staining extracellular material surrounding the cells cultured in vitro demonstrated cross-reactivity to basement membrane in rat intestinal frozen sections. It is concluded that the cultured epithelioid cells have features of undifferentiated small intestinal crypt cells. PMID:88453

  13. Metabolism of heme and bilirubin in rat and human small intestinal mucosa.

    PubMed Central

    Hartmann, F; Bissell, D M

    1982-01-01

    Formation of heme, bilirubin, and bilirubin conjugates has been examined in mucosal cells isolated from the rat upper small intestine. Intact, viable cells were prepared by enzymatic dissociation using a combined vascular and luminal perfusion and incubated with an isotopically labeled precursor, delta-amino-[2,3-3H]levulinic acid. Labeled heme and bile pigment were formed with kinetics similar to those exhibited by hepatocytes. Moreover, the newly formed bilirubin was converted rapidly to both mono- and diglucuronide conjugates. In addition, cell-free extracts of small intestinal mucosa from rats or humans exhibited a bilirubin-UDP-glucuronyl transferase activity that was qualitatively similar to that present in liver. The data suggest that the small intestinal mucosa normally contributes to bilirubin metabolism. PMID:6806320

  14. Microsomal quercetin glucuronidation in rat small intestine depends on age and segment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in 3 equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats, n=8/age using villin to control for enterocyte content. SI microsomal intrinsic clearance of quercetin...

  15. Effects of diabetes on development of small intestinal enzymes of infant rats.

    PubMed

    Wen, D; Henning, S J; Hazelwood, R L

    1988-01-01

    The effect of streptozotocin (SZ) on the development of small intestinal enzymes in postnatal rat pups was studied. SZ was injected ip on Day 10 and, if necessary, again on Day 12. On Days 15, 18, and 21, one pup from each group (including a vehicle-injected control (C) group) was decapitated under conditions which minimized stress. Plasma glucose, insulin (IRI), and corticosterone were measured, as were pancreatic IRI, liver glycogen, and liver membrane binding of IRI. Small intestinal segments were processed and analyzed for sucrase, lactase, maltase, and ileal acid beta-galactosidase activities. Our results indicate that plasma glucocorticoid levels remained virtually constant in both SZ and C groups, while the ontogenic profiles of sucrase and maltase in SZ rats were shifted toward an earlier appearance and a precocious maturation. Circulating levels of IRI were not reduced significantly by SZ despite the fact that pancreatic IRI was decreased 95%. Jejunal lactase, unlike data reported for diabetic rats, was not affected by SZ diabetes. Also, acid beta-galactosidase was unaltered in the SZ rat pups. It is concluded that possibly the elevated disaccharidases seen in diabetic postnatal rat pups are the direct effect of elevated blood glucose. If so, the SZ rat pup model may be a useful tool with which to study effects of glucose on intestinal enzymes in the absence of changes in plasma insulin. PMID:3124120

  16. Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats.

    PubMed

    Goldstein, Jorge; Morris, Winston E; Loidl, César Fabián; Tironi-Farinati, Carla; Tironi-Farinatti, Carla; McClane, Bruce A; Uzal, Francisco A; Fernandez Miyakawa, Mariano E

    2009-01-01

    Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel. PMID:19763257

  17. Clostridium perfringens Epsilon Toxin Increases the Small Intestinal Permeability in Mice and Rats

    PubMed Central

    Goldstein, Jorge; Morris, Winston E.; Loidl, César Fabián; Tironi-Farinatti, Carla; McClane, Bruce A.; Uzal, Francisco A.; Fernandez Miyakawa, Mariano E.

    2009-01-01

    Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel. PMID:19763257

  18. THE REDUCTION OF INORGANIC SULPHATE TO INORGANIC SULPHITE IN THE SMALL INTESTINE OF THE RAT.

    PubMed

    ROBINSON, H C

    1965-03-01

    1. Whole scrapings of rat intestinal mucosa were incubated with carrier-free sodium [(35)S]sulphate. Radioactivity was found in S-sulphocysteine and to a small extent in S-sulphoglutathione. 2. Whole scrapings of rat intestinal mucosa incubated with carrier-free sodium [(35)S]sulphate and oxidized glutathione formed S[(35)S]-sulphoglutathione as the main radioactive product. The amount of S[(35)S]-sulphocysteine formed was considerably lower than in a control that contained no oxidized glutathione. 3. The supernatant fraction of homogenates of rat intestinal mucosa catalyses the NADPH-dependent reduction of adenosine 3'-phosphate 5'-sulphatophosphate to inorganic sulphite. NADH or GSH fail to replace NADPH as reducing agents. 4. The formation of inorganic [(35)S]sulphite from inorganic [(35)S]-sulphate may account for the incorporation of [(35)S]sulphate into S-sulphoglutathione by the small intestine of the rat in vivo and in vitro. PMID:14340059

  19. The reduction of inorganic sulphate to inorganic sulphite in the small intestine of the rat

    PubMed Central

    Robinson, H. C.

    1965-01-01

    1. Whole scrapings of rat intestinal mucosa were incubated with carrier-free sodium [35S]sulphate. Radioactivity was found in S-sulphocysteine and to a small extent in S-sulphoglutathione. 2. Whole scrapings of rat intestinal mucosa incubated with carrier-free sodium [35S]sulphate and oxidized glutathione formed S[35S]-sulphoglutathione as the main radioactive product. The amount of S[35S]-sulphocysteine formed was considerably lower than in a control that contained no oxidized glutathione. 3. The supernatant fraction of homogenates of rat intestinal mucosa catalyses the NADPH-dependent reduction of adenosine 3′-phosphate 5′-sulphatophosphate to inorganic sulphite. NADH or GSH fail to replace NADPH as reducing agents. 4. The formation of inorganic [35S]sulphite from inorganic [35S]-sulphate may account for the incorporation of [35S]sulphate into S-sulphoglutathione by the small intestine of the rat in vivo and in vitro. PMID:14340059

  20. Protein synthesis of muscle fractions from the small intestine in alcohol fed rats.

    PubMed Central

    Preedy, V R; Peters, T J

    1990-01-01

    The effects of chronic ethanol feeding on the amounts and synthesis rates of cytoplasmic, contractile, and stromal protein fractions were investigated in the small intestine of eight pairs of immature and seven pairs of mature rats. Treated rats were fed ethanol as 36% of total energy in a nutritionally adequate liquid diet. Paired controls were fed isovolumetric amounts of the same diet in which ethanol was substituted by isocaloric glucose. After six weeks the total cytoplasmic and contractile protein content in immature rats was reduced by 18% and 31%, respectively (p less than or equal to 0.007). The decline in the stromal protein content (26%) was not statistically significant (p = 0.130). In mature rats the protein contents were also reduced in the cytoplasmic (25%, p = 0.035) and contractile (27%, p = 0.005) protein fractions, though the stromal protein fraction was unaltered (p = 0.913). In immature rats fractional rates of protein synthesis in cytoplasmic and contractile protein fractions of the small intestine were unaltered by chronic ethanol feeding (p less than or equal to 0.853). In mature rats, the synthesis rates of corresponding fractions declined, by 18% and 31%, respectively, but were also not statistically significant (p less than or equal to 0.369). Absolute rates of protein synthesis in immature rats fell by 6% (p = 0.549) in the cytoplasmic and 31% in the contractile protein fraction (p = 0.045). In mature rats, the corresponding reductions were 38% (p = 0.106) and 48% (p = 0.033), respectively. Virtually no radioactivity could be detected in the stromal fraction, signifying very low synthesis rates. Chronic ethanol feeding reduces the amount of protein in the small intestine of the immature and mature rat with the contractile protein fraction showing the greatest decrease. In the absence of statistically significant reductions in fractional synthesis rates a partial adaptation in turnover rates may have occurred. PMID:2323594

  1. Increased oxidative stress and disrupted small intestinal tight junctions in cigarette smoke-exposed rats.

    PubMed

    Li, Hongwei; Wu, Qi; Xu, Long; Li, Xue; Duan, Jianmin; Zhan, Jingyan; Feng, Jing; Sun, Xin; Chen, Huaiyong

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is a major public health problem, and cigarette smoke (CS) is the primary risk factor. The pathology is often observed in the lung, but COPD is also associated with intestinal barrier disruption, although the underlying mechanisms are poorly understood. To address this, a CS‑exposed rat model was evaluated in the present study by analyzing small intestinal gene expression using reverse transcription‑quantitative polymerase chain reaction. CS exposure caused upregulation of the nicotinamide adenine dinucleotide phosphate‑oxidase subunits nox2 and p22phox in the small intestine, while the antioxidative enzyme superoxide dismutase was downregulated. CS exposure also increased bax expression and decreased bcl‑2 expression. This was associated with an elevation of hypoxia‑inducible factor (HIF)‑1α. Claudin‑1 was decreased and claudin‑2 increased, indicating a loosening of small intestinal tight junctions (TJs). These data suggest that during the development of COPD, HIF‑1α expression is altered in the small intestine, which may be associated with the increased oxidative stress and apoptosis, eventually resulting in disruption of the intestinal TJs. PMID:25606848

  2. Small Intestine Disorders

    MedlinePlus

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

  3. Allosteric properties of phosphofructokinase from the epithelial cells of thermally injured rat small intestine.

    PubMed

    Khoja, S M; Salleh, M; Ardawi, M

    1987-01-01

    1. The allosteric properties of phosphofructokinase from the epithelial cells of thermally injured rat small intestine were studied and compared with those properties of the normal rats. 2. The fructose 6-phosphate saturation curve of mucosal phosphofructokinase from thermally injured rats (3 days post injury, 33% of body surface area) displayed cooperatively; the ratio of the activity observed at pH 7.0 in the presence of 0.5 mM fructose 6-phosphate and 2.5 mM-ATP to the optimal activity at pH 8.0, v 0.5/V, was 0.42 +/- 0.02 in the normal rats and 0.22 +/- 0.03 in the injured rats. 3. The enzyme from thermally injured rats was very sensitive to inhibition by ATP as compared to that from normal rats. 4. The enzyme from thermally injured rats was inhibited by citrate and phosphocreatine in a synergistic manner with ATP. 5. Activation under nearly cellular conditions was produced by ADP, AMP and glucose-1,6-biphosphate. 6. In general, the mucosal enzyme of thermally injured rats was more susceptible to inhibition or activation by various metabolites than the enzyme of the normal rats. 7. These results may suggest that mucosal phosphofructokinase of thermally injured rats may not be subject to the same control mechanism as the normal rats in vivo due to changes in the concentrations of fructose-2,6-biphosphate. PMID:2957148

  4. Arginine becomes an essential amino acid after massive resection of rat small intestine.

    PubMed

    Wakabayashi, Y; Yamada, E; Yoshida, T; Takahashi, H

    1994-12-23

    We compared effects of feeding arginine- and/or proline- deficient diets (-Arg, -Pro, and -Arg, Pro) with those of a complete diet (Complete) in rats whose small intestine had been massively resected. After 4 weeks, the rats fed -Arg and -Arg, Pro lost weight (a mean of 28 and 32 g, respectively), whereas those fed Complete and -Pro gained 80 and 58 g, respectively. The average nitrogen balance was about 117,100, -20 and -14 mg/day for Complete, -Pro, -Arg, and -Arg, Pro diets, respectively. The concentration of arginine in skeletal muscle was about 310, 330, 91, and 65 nmol/g for Complete, -Pro, -Arg, and -Arg, Pro, respectively; while plasma arginine concentration averaged 95, 107, 56, and 46 microM, respectively. The weight loss, the negative nitrogen balance, and the markedly reduced arginine concentration in the muscle observed in rats fed -Arg and -Arg, Pro clearly indicate that arginine becomes a strictly essential amino acid in the rats with massive resection of the small intestine. However, sufficient proline can be synthesized from arginine in tissues such as the liver and kidney in the absence of the small intestine. Plasma glutamine, citrulline in the muscle and plasma, urinary excretion of orotic acid and nitrate (to assess nitric oxide formation from arginine) were also measured, and the changes in these metabolites are discussed. PMID:7798273

  5. Biochemical investigation and gene expression analysis of the immunostimulatory functions of an edible Salacia extract in rat small intestine.

    PubMed

    Oda, Yuriko; Ueda, Fumitaka; Kamei, Asuka; Kakinuma, Chihaya; Abe, Keiko

    2011-01-01

    Roots and bark from plants belonging to genus Salacia of the family Hippocrateaceae (Salacia reticulata, Salacia oblonga, etc.) have been used for traditional Ayurvedic medicine, particularly for the treatment of diabetes. In our study, we evaluated the gene expression profiles in the small intestinal epithelium of rats that were given a Salacia plant extract to gain insight into its effects on the small intestine. In detail, DNA microarray analysis was performed to evaluate the gene expression profiles in the rat ileal epithelium. The intestinal bacterial flora was also studied using T-RFLP (Nagashima method) in these rats. Expressions of many immune-related genes, especially Th1-related genes associated with cell-mediated immunity, were found to increase in the small intestinal epithelium and the intestinal bacterial flora became similar to those in the case with Salacia plant extract administration. Our study thus revealed that Salacia plant extract exerts bioregulatory functions by boosting intestinal immunity. PMID:21328625

  6. Human, rat and chicken small intestinal Na+-Cl−-creatine transporter: functional, molecular characterization and localization

    PubMed Central

    Peral, M J; García-Delgado, M; Calonge, M L; Durán, J M; De La Horra, M C; Wallimann, T; Speer, O; Ilundáin, A A

    2002-01-01

    In spite of all the fascinating properties of oral creatine supplementation, the mechanism(s) mediating its intestinal absorption has(have) not been investigated. The purpose of this study was to characterize intestinal creatine transport. [14C]Creatine uptake was measured in chicken enterocytes and rat ileum, and expression of the creatine transporter CRT was examined in human, rat and chicken small intestine by reverse transcription-polymerase chain reaction, Northern blot, in situ hybridization, immunoblotting and immunohistochemistry. Results show that enterocytes accumulate creatine against its concentration gradient. This accumulation was electrogenic, Na+- and Cl−-dependent, with a probable stoichiometry of 2 Na+: 1 Cl−: 1 creatine, and inhibited by ouabain and iodoacetic acid. The kinetic study revealed a Km for creatine of 29 μm. [14C]Creatine uptake was efficiently antagonized by non-labelled creatine, guanidinopropionic acid and cyclocreatine. More distant structural analogues of creatine, such as GABA, choline, glycine, β-alanine, taurine and betaine, had no effect on intestinal creatine uptake, indicating a high substrate specificity of the creatine transporter. Consistent with these functional data, messenger RNA for CRT was detected only in the cells lining the intestinal villus. The sequences of partial clones, and of the full-length cDNA clone, isolated from human and rat small intestine were identical to previously cloned CRT cDNAs. Immunological analysis revealed that CRT protein was mainly associated with the apical membrane of the enterocytes. This study reports for the first time that mammalian and avian enterocytes express CRT along the villus, where it mediates high-affinity, Na+- and Cl−-dependent, apical creatine uptake. PMID:12433955

  7. Autoradiographic localization of opioid receptor types in the rat small intestine

    SciTech Connect

    Dashwood, M.R.; Sykes, R.M.; Thompson, C.S.

    1986-01-01

    The selective mu and delta ligands (/sup 3/H)DAGO and (/sup 3/H)DPDPE have been used to investigate the distribution of specific opioid subtypes in the rat small intestine by in vitro autoradiography. There was a greater density of (/sup 3/H)DPDPE binding at regions of the villi and crypts than (/sup 3/H)DAGO binding. These results suggest that the opioid receptors located in these regions are predominantly of the delta subtype.

  8. Digestive enzyme expression and epithelial structure of small intestine in neonatal rats after 16 days spaceflight

    NASA Astrophysics Data System (ADS)

    Miyake, M.; Yamasaki, M.; Hazama, A.; Ijiri, K.; Shimizu, T.

    It is important to assure whether digestive system can develop normally in neonates during spaceflight. Because the small intestine changes its function and structure drastically around weaning known as redifferentiation. Lactase expression declines and sucrase increases in small intestine for digestion of solid food before weaning. In this paper, we compared this enzyme transition and structural development of small intestine in neonatal rats after spaceflight. To find digestive genes differentially expressed in fight rats, DNA membrane macroarray was also used. Eight-day old rats were loaded to Space Shuttle Columbia, and housed in the animal facility for 16 days in space (STS-90, Neurolab mission). Two control groups (AGC; asynchronous ground control and VIV; vivarium) against flight group (FLT) were prepared. There was no difference in structure (crypt depth) and cell differentiation of epithelium between FLT and AGC by immunohistochemical analysis. We found that the amount of sucrase mRNA compared to lactase was decreased in FLT by RT-PCR. It reflected the enzyme transition was inhibited. Increase of 5 genes (APO A-I, APO A-IV, ACE, aFABP and aminopeptidase M) and decrease of carboxypeptidase-D were detected in FLT using macroarray. We think nutrition differences (less nourishment and late weaning) during spaceflight may cause inhibition of enzyme transition at least partly. The weightlessness might contribute to the inhibition through behavioral change.

  9. Adaptive response of growing rat small intestine to acute Adriamycin injury.

    PubMed

    Buts, J P; De Meyer, R; Van Craynest, M P; Maldague, P

    1983-01-01

    The response of the intestinal mucosa to Adriamycin (ADR) was studied in the duodenum, jejunum, and ileum of 25-day-old rats. A single injection of ADR resulted in decreases in mucosal DNA per centimeter of length and in sucrase activity, which were proportional to the doses given (2, 5, and 8 mg/kg). ADR at 2 mg/kg had no significant effect on body weight, gut length, epithelial structure, or mucosal protein content per unit length. The morphological modifications occurred mostly in the proximal intestine and consisted of villous atrophy and degenerative changes of villus and crypt cells. A single dose of 5 mg ADR/kg acutely affected the gut. At 48 and 96 h the changes were characterized by marked decreases in mucosal weight, DNA per centimeter, sucrase activity, and villous shortening. At 144 h, the ADR-treated intestine entered a highly proliferative state and showed increased villous height, mucosal weight, and DNA per centimeter. Although villous hyperplasia was observed at 144 and 192 h, the mucosal weight and DNA concentrations did not exceed the corresponding levels in the control. During the period of active epithelial proliferation, sucrase activity remained depressed. We conclude that in the growing rat: (a) the acute intestinal injury of ADR is short-lived, dose dependent, and predominates in the proximal small intestine; (b) the enteric mucosa reacts to cytotoxic injury by excessive proliferation of immature enterocytes; and (c) the hyperplastic response to ADR is confined to the mucosal epithelium. PMID:6886938

  10. Sugar alcohols enhance calcium transport from rat small and large intestine epithelium in vitro.

    PubMed

    Mineo, Hitoshi; Hara, Hiroshi; Tomita, Fusao

    2002-06-01

    We compared the effect of a variety of sugar alcohols on calcium absorption from the rat small and large intestine in vitro. An Ussing chamber technique was used to determine the net transport of Ca across the epithelium isolated from the jejunum, ileum, cecum, and colon of rats. The concentration of Ca in the serosal and mucosal Tris buffer solution was 1.25 mM and 10 mM, respectively. The Ca concentration in the serosal medium was determined after incubation for 30 min and the net Ca absorption was evaluated. The addition of 0.1-200 mM erythritol, xylitol, sorbitol, maltitol, palatinit, or lactitol to the mucosal medium affected net Ca absorption in the intestinal preparations. Differences in Ca transport were observed between portions of the intestine, but not between sugar alcohols tested. We concluded that sugar alcohols directly affect the epithelial tissue and promote Ca absorption from the small and large intestine in vitro. PMID:12064809

  11. Methyl donor deficiency affects small-intestinal differentiation and barrier function in rats.

    PubMed

    Bressenot, Aude; Pooya, Shabnam; Bossenmeyer-Pourie, Carine; Gauchotte, Guillaume; Germain, Adeline; Chevaux, Jean-Baptiste; Coste, Florence; Vignaud, Jean-Michel; Guéant, Jean-Louis; Peyrin-Biroulet, Laurent

    2013-02-28

    Dietary methyl donors and their genetic determinants are associated with Crohn's disease risk. We investigated whether a methyl-deficient diet (MDD) may affect development and functions of the small intestine in rat pups from dams subjected to the MDD during gestation and lactation. At 1 month before pregnancy, adult females were fed with either a standard food or a diet without vitamin B12, folate and choline. A global wall hypotrophy was observed in the distal small bowel (MDD animals 0·30 mm v. controls 0·58 mm; P< 0·001) with increased crypt apoptosis (3·37 v. 0·4%; P< 0·001), loss of enterocyte differentiation in the villus and a reduction in intestinal alkaline phosphatase production. Cleaved caspase-3 immunostaining (MDD animals 3·37% v. controls 0·4%, P< 0·001) and the Apostain labelling index showed increased crypt apoptosis (3·5 v. 1·4%; P= 0·018). Decreased proliferation was observed in crypts of the proximal small bowel with a reduced number of minichromosome maintenance 6 (MDD animals 52·83% v. controls 83·17%; P= 0·048) and proliferating cell nuclear antigen-positive cells (46·25 v. 59 %; P= 0·05). This lack of enterocyte differentiation in the distal small bowel was associated with an impaired expression of β-catenin and a decreased β-catenin-E-cadherin interaction. The MDD affected the intestinal barrier in the proximal small bowel by decreasing Paneth cell number after immunostaining for lysosyme (MDD animals 8·66% v. controls 21·66%) and by reducing goblet cell number and mucus production after immunostaining for mucin-2 (crypts 8·66 v. 15·33%; villus 7 v. 17%). The MDD has dual effects on the small intestine by producing dramatic effects on enterocyte differentiation and barrier function in rats. PMID:22794784

  12. Small intestinal ischemia and infarction

    MedlinePlus

    ... small intestine; Atherosclerosis - small intestine; Hardening of the arteries - small intestine ... Embolus: Blood clots can block one of the arteries supplying the intestine. People who have had a ...

  13. Toxic effect on the rat small intestine of chronic administration of asbestos in drinking water.

    PubMed

    Delahunty, T J; Hollander, D

    1987-12-01

    Sprague-Dawley rats were given a 0.5 g/l Chrysotile asbestos solution in their drinking water (approximately 7 mg/day ingested) for 1.5 years and compared to control rats of the same age. During this time there were no differences in weight or appearance of the asbestos-treated rats in comparison to controls maintained under the same conditions. However, when in vivo intestinal permeability studies were performed using a gavage/urinary collection technique, some significant changes were noted. The recovery of lactulose in the urine of asbestos-treated rats was 0.66 +/- 0.07%, significantly less than that of the controls (1.01 +/- 0.08, P less than 0.005). The recovery of mannitol was similarly decreased (2.2 +/- 0.28 vs. 3.0 +/- 0.17, P less than 0.02), but that of rhamnose was unchanged. Creatinine clearance studies indicated that there was no impairment of kidney function in the asbestos-treated group and polarized light microscopy did not reveal any asbestos fibers in sections of the small bowel. The results suggest that the chronic exposure of rats to asbestos fibers in the drinking water results in a decreased ability of the intestine to absorb some non-metabolizable sugars. PMID:3120357

  14. Morphometric and biomechanical remodeling of the small intestine during aging in rats.

    PubMed

    Zhao, Jingbo; Gregersen, Hans

    2015-12-16

    The present study aimed to study the morphometric and biomechanical remodeling of the small intestine during aging in rats. Twenty-four male Wistar rats, aged from 6 to 22 months, were used in the study. The body weight and the wet weight per length of duodenal and ileal segments were measured at the termination of the experiments. Morphometry data was obtained by measuring the wall thickness and cross-sectional area. The mechanical test was done as a step-wise distension experiment. The intestinal diameter and length were obtained from digitized images of the segments at pre-selected pressure levels and at the no-load and zero-stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero-stress state geometry. The duodenal and ileal dimensions increased slightly from 6 to 22 months, e.g. the wall thickness and the wall cross-sectional area increased about 4% and 25% for duodenum and 5% and 8% for ileum. The opening angle gradually decreased from 154 to 117 degrees for duodenum and from 144 to 87 degrees for ileum during aging. The circumferential stress-strain curves significantly shifted to the left after 22 months (p<0.05) whereas the longitudinal stress-strain curves significantly shifted to the left after 18 months (p<0.01) both for duodenum and ileum. The intestinal wall became stiffer circumferentially and longitudinally during the aging. Furthermore, the intestinal wall was stiffer longitudinally than circumferentially. In conclusion, pronounced morphometric and biomechanical remodeling occurred in the rat intestine during aging. PMID:26596717

  15. Prolactin and Prolactin Receptor Expression in Rat, Small Intestine, Intraepithelial Lymphocytes During Neonatal Developmen

    PubMed Central

    Urtishak, Sandra L.; Mckenna, Elizabeth A.; Mastro, Andrea M.

    2001-01-01

    Intraepithelial lymphocytes (IEL) are specialized T cells found between the epithelial cells of the small intestine. Because of their location, IEL are the first lymphocytes to contact intestinal bacteria and food antigens. In the neonate, IEL may be the first cells of the immune system to interact with milk-borne hormones including prolactin (PRL). PRL, an endocrine hormone abundant in breast milk, interacts with cells through surface receptors. PRL has been shown to function as an immunoregulator and may affect the development of the newborn's immune system. To determine if PRL plays a role in IEL development, small intestine IEL from rats of various ages were examined for the presence of surface prolactin receptor (PRL-R) and several lymphoid markers by flow cytometry. Between birth and 96 days of age about 80% of IEL were found to express PRL-R. These same cells also expressed the mRNA for PRL. Additionally, all of the IEL subpopulations examined were found to express PRL-R. Analysis of the normal development of rat IEL revealed an age related increase in total IEL, CD4 positive cells as well as a peak in interleukin-2 receptor (IL-2R) expression at weaning. In summary, the results indicate that IEL express PRL and PRL-R. In addition, an activation marker, IL-2R, changes in expression during neonatal development. PMID:11785680

  16. Noninvasive monitoring of small intestinal oxygen in a rat model of chronic mesenteric ischemia

    PubMed Central

    Fisher, Elaine M.; Khan, Mahmood; Salisbury, Ronald; Kuppusamy, Periannan

    2013-01-01

    We noninvasively monitored the partial pressure of oxygen (pO2) in rat small intestine using a model of chronic mesenteric ischemia by electron paramagnetic resonance oximetry (EPR) over a 7-day period. The particulate probe lithium octa-n-butoxynaphthalocyanine (LiNc-BuO) was embedded into the oxygen permeable material polydimethyl siloxane (PDMS) by cast-molding and polymerization (Oxy-Chip). A one-time surgical procedure was performed to place the Oxy-Chip on the outer wall of the small intestine (SI). The superior mesenteric artery (SMA) was banded to approximately 30% blood flow for experimental rats. Noninvasive measurement of pO2 was performed at baseline for control rats or immediate post-banding and on days 1, 3, and 7. The SI pO2 for control rats remained stable over the 7-day period. The pO2 on day 7 was 54.5 ± 0.9 mmHg (mean ± SE). SMA banded rats were significantly different from controls with a noted reduction in pO2 post banding with a progressive decline to a final pO2 of 20.9 ± 4.5 mmHg (mean ± SE; p = 0.02). All SMA-banded rats developed adhesions around the Oxy-Chip yet remained asymptomatic. The hypoxia marker Hypoxyprobe™ was used to validate low tissue pO2. Brown cytoplasmic staining was consistent with hypoxia. Mild brown staining was noted predominantly on the villus tips in control animals. SMA-banded rats had an extended region of hypoxic involvement in the villus with a higher intensity of cytoplasmic staining. Deep brown staining of the enteric nervous system neurons and connective tissue both within layers and in the mesentery were noted. SMA banded rats with lower pO2 values had a higher intensity of staining. Thus, monitoring SI pO2 using the probe Oxy-Chip provides a valid measure of tissue oxygenation. Tracking pO2 in conditions that produce chronic mesenteric ischemia will contribute to our understanding of intestinal tissue oxygenation and how changes impact symptom evolution and the trajectory of chronic disease. PMID

  17. Endoplasmic Reticulum Stress in Heat- and Shake-Induced Injury in the Rat Small Intestine

    PubMed Central

    Yin, Peng; Xu, Jianqin; He, Shasha; Liu, Fenghua; Yin, Jie; Wan, Changrong; mei, Chen; Yin, Yulong; Xu, Xiaolong; Xia, Zhaofei

    2015-01-01

    We investigated the mechanisms underlying damage to rat small intestine in heat- and shake-induced stress. Eighteen Sprague-Dawley rats were randomly divided into a control group and a 3-day stressed group treated 2 h daily for 3 days on a rotary platform at 35°C and 60 r/min. Hematoxylin and eosin-stained paraffin sections of the jejunum following stress revealed shedding of the villus tip epithelial cells and lamina propria exposure. Apoptosis increased at the villus tip and extended to the basement membrane. Photomicrographs revealed that the microvilli were shorter and sparser; the nuclear envelope invaginated and gaps in the karyolemma increased; and the endoplasmic reticulum (ER) swelled significantly. Gene microarray analysis assessed 93 differentially expressed genes associated with apoptosis, ER stress, and autophagy. Relevant genes were compiled from the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Forty-one genes were involved in the regulation of apoptosis, fifteen were related to autophagy, and eleven responded to ER stress. According to KEGG, the apoptosis pathways, mitogen-activated protein kinase(MAPK) signaling pathway, the mammalian target of rapamycin (mTOR) signaling pathway, and regulation of autophagy were involved. Caspase3 (Casp3), caspase12 (Casp12), and microtubule-associate proteins 1 light chain 3(LC3) increased significantly at the villus tip while mTOR decreased; phosphorylated-AKT (P-AKT) decreased. ER stress was involved and induced autophagy and apoptosis in rat intestinal damage following heat and shake stress. Bioinformatic analysis will help determine the underlying mechanisms in stress-induced damage in the small intestine. PMID:26636675

  18. Endoplasmic Reticulum Stress in Heat- and Shake-Induced Injury in the Rat Small Intestine.

    PubMed

    Yin, Peng; Xu, Jianqin; He, Shasha; Liu, Fenghua; Yin, Jie; Wan, Changrong; Mei, Chen; Yin, Yulong; Xu, Xiaolong; Xia, Zhaofei

    2015-01-01

    We investigated the mechanisms underlying damage to rat small intestine in heat- and shake-induced stress. Eighteen Sprague-Dawley rats were randomly divided into a control group and a 3-day stressed group treated 2 h daily for 3 days on a rotary platform at 35°C and 60 r/min. Hematoxylin and eosin-stained paraffin sections of the jejunum following stress revealed shedding of the villus tip epithelial cells and lamina propria exposure. Apoptosis increased at the villus tip and extended to the basement membrane. Photomicrographs revealed that the microvilli were shorter and sparser; the nuclear envelope invaginated and gaps in the karyolemma increased; and the endoplasmic reticulum (ER) swelled significantly. Gene microarray analysis assessed 93 differentially expressed genes associated with apoptosis, ER stress, and autophagy. Relevant genes were compiled from the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Forty-one genes were involved in the regulation of apoptosis, fifteen were related to autophagy, and eleven responded to ER stress. According to KEGG, the apoptosis pathways, mitogen-activated protein kinase(MAPK) signaling pathway, the mammalian target of rapamycin (mTOR) signaling pathway, and regulation of autophagy were involved. Caspase3 (Casp3), caspase12 (Casp12), and microtubule-associate proteins 1 light chain 3(LC3) increased significantly at the villus tip while mTOR decreased; phosphorylated-AKT (P-AKT) decreased. ER stress was involved and induced autophagy and apoptosis in rat intestinal damage following heat and shake stress. Bioinformatic analysis will help determine the underlying mechanisms in stress-induced damage in the small intestine. PMID:26636675

  19. Sympathetic axonopathies and hyperinnervation in the small intestine smooth muscle of aged Fischer 344 rats

    PubMed Central

    Phillips, Robert J.; Hudson, Cherie N.; Powley, Terry L.

    2013-01-01

    It is well documented that the intrinsic enteric nervous system of the gastrointestinal (GI) tract sustains neuronal losses and reorganizes as it ages. In contrast, age-related remodeling of the extrinsic sympathetic projections to the wall of the gut is poorly characterized. The present experiment, therefore, surveyed the sympathetic projections to the aged small intestine for axonopathies. Furthermore, the experiment evaluated the specific prediction that catecholaminergic inputs undergo hyperplastic changes. Jejunal tissue was collected from 3-, 8-, 16-, and 24-month-old male Fischer 344 rats, prepared as whole mounts consisting of the muscularis, and processed immunohistochemically for tyrosine hydroxylase, the enzymatic marker for norepinephrine, and either the protein CD163 or the protein MHCII, both phenotypical markers for macrophages. Four distinctive sympathetic axonopathy profiles occurred in the small intestine of the aged rat: (1) swollen and dystrophic terminals, (2) tangled axons, (3) discrete hyperinnervated loci in the smooth muscle wall, including at the bases of Peyer's patches, and (4) ectopic hyperplastic or hyperinnervating axons in the serosa/subserosal layers. In many cases, the axonopathies occurred at localized and limited foci, involving only a few axon terminals, in a pattern consistent with incidences of focal ischemic, vascular, or traumatic insult. The present observations underscore the complexity of the processes of aging on the neural circuitry of the gut, with age-related GI functional impairments likely reflecting a constellation of adjustments that range from selective neuronal losses, through accumulation of cellular debris, to hyperplasias and hyperinnervation of sympathetic inputs. PMID:24104187

  20. Longitudinal residual strain and stress-strain relationship in rat small intestine

    PubMed Central

    Dou, Yanling; Fan, Yanhua; Zhao, Jingbo; Gregersen, Hans

    2006-01-01

    Background To obtain a more detailed description of the stress-free state of the intestinal wall, longitudinal residual strain measurements are needed. Furthermore, data on longitudinal stress-strain relations in visceral organs are scarce. The present study aims to investigate the longitudinal residual strain and the longitudinal stress-strain relationship in the rat small intestine. Methods The longitudinal zero-stress state was obtained by cutting tissue strips parallel to the longitudinal axis of the intestine. The longitudinal residual stress was characterized by a bending angle (unit: degrees per unit length and positive when bending outwards). Residual strain was computed from the change in dimensions between the zero-stress state and the no-load state. Longitudinal stresses and strains were computed from stretch experiments in the distal ileum at luminal pressures ranging from 0–4 cmH2O. Results Large morphometric variations were found between the duodenum and ileum with the largest wall thickness and wall area in the duodenum and the largest inner circumference and luminal area in the distal ileum (p < 0.001). The bending angle did not differ between the duodenum and ileum (p > 0.5). The longitudinal residual strain was tensile at the serosal surface and compressive at the mucosal surface. Hence, the neutral axis was approximately in the mid-wall. The longitudinal residual strain and the bending angle was not uniform around the intestinal circumference and had the highest values on the mesenteric sides (p < 0.001). The stress-strain curves fitted well to the mono-exponential function with determination coefficients above 0.96. The α constant increased with the pressure, indicating the intestinal wall became stiffer in longitudinal direction when pressurized. Conclusion Large longitudinal residual strains reside in the small intestine and showed circumferential variation. This indicates that the tissue is not uniform and cannot be treated as a homogenous

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

    PubMed

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

    2015-09-01

    Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates. PMID:25891783

  2. Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis.

    PubMed

    Boyle, Erin C; Dombrowsky, Heike; Sarau, Jürgen; Braun, Janin; Aepfelbacher, Martin; Lautenschläger, Ingmar; Grassl, Guntram A

    2016-01-15

    Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion. Novel physiological consequences of Salmonella infection of the small intestine were also identified, namely, SPI-1-dependent vasoconstriction and SPI-1-independent reduction in the digestive and absorptive functions of the epithelium. Importantly, this is the first small animal model that allows for the study of Salmonella-induced fluid secretion. Another major advantage of this model is that one can specifically determine the contribution of resident cell populations. Accordingly, we can conclude that recruited cell populations were not involved in the pathological damage, inflammation induction, fluid accumulation, nutrient absorption deficiency, and vasoconstriction observed. Although fluid loss induced by Salmonella infection is hypothesized to be due to damage caused by recruited neutrophils, our data suggest that bacterial invasion and inflammation induction in resident cell populations are sufficient for fluid loss into the lumen. In summary, this model is a novel and useful tool that allows for detailed examination of the early physiopathological effects of Salmonella infection on the small intestine. PMID:26564721

  3. Regulation of the microvascular circulation in the leg muscles, pancreas and small intestine in rats.

    PubMed

    Maeda, Hisashi; Kurose, Tomoyuki; Kawamata, Seiichi

    2015-01-01

    To study the microvascular circulation, we examined the proportion of open and functioning capillaries in the leg muscles, pancreas and small intestine of anesthetized rats. Fluorescein isothiocyanate (FITC)-labeled Lycopersicon esculentum lectin was injected into the heart and allowed to circulate for 3 min to label open and functioning capillaries. Specimens were removed, frozen, sectioned and double-immunostained. Using one section, open and functioning capillaries were detected by immunostaining for this lectin bound to endothelial cells, while all capillaries were visualized by immunostaining for platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31). These capillaries were semi-automatically detected and counted by fluorescence microscopy. The percentages of open and functioning capillaries were as follows: the soleus muscle, 93.0 ± 5.5%; superficial zone of the gastrocnemius muscle, 90.8 ± 6.2%; deep zone of the gastrocnemius muscle, 95.6 ± 4.0%; the plantaris muscle, 94.1 ± 2.7%; the pancreas, 86.3 ± 11.7%; and the small intestine, 91.1 ± 4.9% (n = 8, each). There was no significant difference among these data by the Kruskal-Wallis test. This study clearly demonstrated that the proportions of open and functioning capillaries are high and similar among the leg muscles, pancreas and small intestine in spite of their structural and functional differences. This finding agrees with previous studies and supports the notion that the microvascular circulation is mainly controlled by changing of the blood flow in each capillary rather than changing the proportion of open and functioning capillaries. PMID:26140259

  4. Intestinal permeability and bacterial translocation following small bowel transplantation in the rat

    SciTech Connect

    Grant, D.; Hurlbut, D.; Zhong, R.; Wang, P.Z.; Chen, H.F.; Garcia, B.; Behme, R.; Stiller, C.; Duff, J. )

    1991-08-01

    In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. The present study evaluated gut barrier function following orthotopic (in continuity) intestinal grafting in rats. Graft histology, intestinal permeability, and bacterial translocation to the grafted mesenteric lymph nodes, the host's liver, and the host's spleen were assessed on the 3rd, 5th, and 7th postoperative days. The study group received no immunosuppression after allotransplantation. The two control groups included rats with isografts and rats with cyclosporine-treated allografts. On the 7th POD, the study animals had moderate transmural inflammation due to rejection, with normal histology in the isografts and CsA-treated allografts; increased intestinal permeability, measured by urinary excretion of oral 51Cr-EDTA (P less than 0.01); and increased number of bacteria in the MLN and spleen (P less than 0.05). The number of bacteria in the MLN and spleen of the study group positively correlated with the changes in intestinal permeability (P less than 0.05). Rejection of the orthotopic intestinal graft leads to increased intestinal permeability and bacterial translocation from the lumen of the graft to the host's reticuloendothelial system. Measures to improve gut barrier function and antibiotic therapy during rejection episodes may help reduce the incidence of septic complications after intestinal grafting.

  5. Whey protein hydrolysates enhance water absorption in the perfused small intestine of anesthetized rats.

    PubMed

    Ito, Kentaro; Yamaguchi, Makoto; Noma, Teruyuki; Yamaji, Taketo; Itoh, Hiroyuki; Oda, Munehiro

    2016-08-01

    We evaluated the effect of whey protein hydrolysates (WPH) on the water absorption rate in the small intestine using a rat small intestine perfusion model. The rate was significantly higher with 5 g/L WPH than with 5 g/L soy protein hydrolysates or physiological saline (p < 0.05). WPH dose-dependently increased the water absorption rate in the range of 1.25-10.0 g/L. WPH showed a significantly higher rate than an amino acid mixture whose composition was equal to that of WPH (p < 0.05). The addition of 4-aminomethylbenzoic acid, an inhibitor of PepT1, significantly suppressed WPH's enhancement of water absorption (p < 0.05). The rate of water absorption was significantly correlated with that of peptides/amino acids absorption in WPH (r = 0.82, p < 0.01). These data suggest that WPH have a high water absorption-promoting effect, to which PepT1 contributes. PMID:27055721

  6. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

    SciTech Connect

    Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2006-04-01

    Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor {beta} immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent.

  7. Syncollin is differentially expressed in rat proximal small intestine and regulated by feeding behavior.

    PubMed

    Tan, S; Hooi, S C

    2000-02-01

    Gradients of gene expression are maintained along the proximal-distal axis of the mammalian small intestine despite a continuously regenerating epithelium. To study the molecular mechanisms responsible for this phenomenon, we utilized a subtractive hybridization strategy to isolate genes differentially expressed in the duodenum but not ileum. We isolated and sequenced 15 clones. The clones were fragments of genes encoding lipases, proteases, and an esterase. A novel clone was characterized and subsequently shown to encode syncollin, a secretory granule protein that binds to syntaxin in a calcium-sensitive manner. RT-PCR and S1 nuclease protection assay were used to clarify the 5'-end of syncollin. Syncollin was expressed in the rat pancreas, spleen, duodenum, and colon. In situ hybridization localized syncollin expression in the pancreas to acinar cells and in the duodenum to villus epithelial cells. PMID:10666056

  8. Small bowel disaccharidase activity in the rat as affected by intestinal resection and pectin feeding.

    PubMed

    Koruda, M J; Rolandelli, R H; Settle, R G; Rombeau, J L

    1988-03-01

    This study investigated the effects of small bowel resection (SBR) and a pectin-supplemented elemental diet (ED) on intestinal disaccharidase activity. Rats underwent placement of feeding gastrostomy and swivel apparatus. Control animals were returned to their cages while resected animals underwent an 80% SBR. Postoperatively, animals received either a pectin-free ED or the ED supplemented with 2% pectin. After 2 wk jejunal and ileal mucosal sucrase, maltase, and lactase activities and protein content were determined. Feeding the ED after SBR resulted in significant increases in all three ileal segmental disaccharidase activities but only maltase activity was significantly increased in the jejunum. The pectin-supplemented ED, however, significantly enhanced the adaptation of jejunal and ileal segmental sucrase, maltase, and lactase activity to SBR with the increase in all three jejunal disaccharidase activities being significantly greater than that of the resected animals fed the ED alone. PMID:3126640

  9. Small intestinal response to 'elemental' and 'complete' liquid feeds in the rat: effect of dietary bulk.

    PubMed

    Maxton, D G; Cynk, E U; Thompson, R P

    1987-06-01

    The effect of oral isocaloric feeding on small intestinal structure and function was studied in the rat. The liquid 'elemental' enteral feed Vivonex HN, the liquid 'complete' feed Ensure and the same liquid complete feed with 9% bulk Enrich were compared with solid chow containing 21% bulk (normal rat chow), all given for four weeks. Weight gain was significantly less in the group fed Vivonex HN than that of any other groups. The bulkless Vivonex HN and Ensure increased proximal jejunal mass compared to Enrich with 9% bulk or to normal rat chow. Jejunal mucosal DNA and protein levels also tended to be higher in Ensure and Vivonex HN fed animals, as was jejunal sugar absorption. In the terminal ileum, however, total weight was decreased by both elemental and complete feeds with and without bulk, but particularly by the elemental diet. Bulkless feeds therefore increase jejunal and reduce terminal ileal mass. The striking atrophy of the terminal ileum produced by the elemental diet may be important for its efficacy in treating inflammatory bowel disease. PMID:3040541

  10. Penile enhancement using a porcine small intestinal submucosa graft in a rat model.

    PubMed

    Leungwattanakij, S; Pummangura, N; Ratana-Olarn, K

    2006-01-01

    Several biodegradable materials have been experimented for penile enhancement, but none show the potential for clinical use. This study was designed to use porcine small intestinal submucosa (SIS) augmenting the normal tunica albuginea to increase the functional girth of the rat penis. In all, 20 adult male Sprague-Dawley rats constituted the study population. The animals were divided into two groups: group 1 consisted of the control (n=10) and group 2 (n=10) consisted of rats that underwent penile enhancement by a longitudinal I-shaped incision of the tunica albuginea on both sides, and the dissection of the plane between tunica albuginea and cavernosal tissue was carried out (n=10). The incision was then patched with a 3 x 10 mm2 piece of SIS, using a 6/0 nylon suture material. The penile length and mid-circumference were then measured using a Vernier Caliper before and 2 months after surgery. All rat penises underwent histological examination using Masson's trichome and Verhoff's van Giesen's stain for collagen and elastic fibers. The penile length, mid-circumference and degree of fibrosis score were expressed as mean+/-s.e. (standard error) and analyzed using a Wilcoxon rank-sum test. A statistical significance was accepted at P-value < or =0.05. Our results showed similar preoperative penile length and circumference in both groups. However, 2 months after the surgery, the mean penile circumference of the SIS group has grown significantly larger than the control group, while the mean penile length remained unchanged. The histological study of the rat penises revealed minimal amounts of fibrosis under the graft, and the elastic fibers of the graft showed orientation in a circular manner. In conclusion, SIS appears promising for material use in a penile enhancement. PMID:16049525

  11. Perforin and granzyme B. Cytolytic proteins up-regulated during rejection of rat small intestine allografts.

    PubMed

    McDiarmid, S V; Farmer, D G; Kuniyoshi, J S; Robert, M; Khadavi, A; Shaked, A; Busuttil, R W

    1995-03-15

    Perforin and granzyme B are 2 cytolytic proteins specific to activated killer cells, particularly CTL. We have studied the mRNA expression of these 2 proteins by a reverse transcriptase polymerase chain reaction method in a unidirectional model of rat small intestine transplant rejection. The allograft group consisted of Lewis x Brown Norway F1 donors into Lewis recipients. The isograft controls were Lewis donors into Lewis recipients. Grafts were placed heterotopically and no immunosuppression was given. Five animals in each group were killed at postoperative days (POD) 3, 5, 7, 8, 9, 10, 12, and 14. mRNA was extracted and a semiquantitative reverse transcriptase polymerase chain reaction was performed. For the semiquantitative analysis, we compared scintillation counts from excised bands. Results were expressed as a percent activity compared with beta-actin. From the same tissue samples, a histologic evaluation was made and rejection was graded according to severity. The isograft controls showed no evidence of histologic rejection and a very low expression of mRNA for perforin and granzyme B from POD 3-14. In contrast, the allograft group began to show histologic evidence of mild rejection on POD 5. By day 7, rejection was moderately severe and associated with a significant up-regulation of perforin and granzyme B in the allografts compared with the controls (P < 0.01), which persisted through POD 14. Peak expression for perforin and granzyme B was on POD 10 and 8, respectively. We conclude that the up-regulation of perforin and granzyme B in rat small intestine transplant allografts is a useful marker of clinically important rejection. PMID:7886805

  12. Suppression by Trypanosoma brucei of anaphylaxis-mediated ion transport in the small intestine of rats.

    PubMed Central

    Gould, S S; Castro, G A

    1994-01-01

    The hypothesis that failure of hosts infected with Trypanosoma brucei to express type 1 hypersensitivity is related to this parasite's ability to down-regulate IgE production, and not to an innate lack of allergenicity of T. brucei antigens, was tested by studying anaphylaxis-induced changes in net epithelial ion transport in rats. Transport changes were quantified electrophysiologically in vitro, as a change in transmural short-circuit current when sensitized intestine was challenged with homologous antigen. Rats injected parenterally with trypanosome antigen elicited intestinal anaphylaxis in response to antigenic challenge, whereas the intestine of rats infected with T. brucei failed to respond. Infection with T. brucei also suppressed the anaphylactic response in rats sensitized to and challenged with ovalbumin and T. spiralis-derived antigens. In these cases suppression was related to the ability of T. brucei to block production of IgE, and not to the physiological failure of the epithelial response. However, in rats sensitized by infection with T. spiralis, neither the anaphylactic response nor IgE production were inhibited by T. brucei. Furthermore, intestinal mastocytosis normally associated with trichinosis was unaffected by the trypanosome infection. Results support the conclusion that the failure to express anaphylaxis in T. brucei-infected rats is due to the inhibition of IgE production and not to the lack of allergenicity of trypanosome antigens. PMID:8206518

  13. Effects of differing purified cellulose, pectin and hemicellulose fiber diets on mucosal morphology in the rat small and large intestine.

    PubMed

    Dirks, P; Freeman, H J

    1987-01-01

    The effects of increasing amounts of differing single-fiber sources in chemically-defined and nutritionally-equivalent diets on morphometric measurements of the rat small and large intestinal mucosa were examined. Male Wistar rats received a fiber-free diet, or diets containing 4.5% or 9.0% cellulose, pectin, or hemicellulose. Cellulose and pectin increased jejunal (but not ileal) villus and crypt heights, whereas hemicellulose increased ileal (but not jejunal) mucosal height. Moreover, cellulose and pectin (but not hemicellulose) increased crypt heights in cecum and proximal (but not distal) colon. Parallel increases in the mitotic index were seen with cellulose and pectin diets, but there was a decrease with hemicellulose, suggesting different mechanisms for altered patterns of cell renewal induced by orally-administered single-fiber sources. These changes indicate that differing single-fiber sources exert differential structural effects along the length of the small and large intestine in the rat. PMID:3028682

  14. Membrane transport of andrographolide in artificial membrane and rat small intestine.

    PubMed

    Daodee, Supawadee; Wangboonskul, Jinda; Jarukamjorn, Kanokwan; Sripanidkulchai, Bung-orn; Murakami, Teruo

    2007-06-15

    In the present study, the possible drug interactions of andrographolide with co-administering drugs such as acetaminophen, amoxycillin, aspirin, chlorpheniramine and norfloxacin to treat various infectious and inflammatory diseases that may be induced during absorption process were examined using artificial lipophilic membrane and everted rat intestine. The membrane transport of andrographolide across the artificial membrane was not affected by different pH of the medium (simulated gastric and intestinal fluids), different concentrations of andrographolide and co-administered drugs examined. In everted rat intestine, above co-administered drugs examined showed no significant effect on andrographolide membrane transport. The participation of efflux transporters such as P-glycoprotein and MRP2 in andrographolide transport was then examined, since andrographolide is a diterpene compound and some diterpene compounds are known as P-glycoprotein substrates. Cyclosporine, a P-glycoprotein/MRP2 inhibitor, significantly suppressed the efflux transport of andrographolide in distal region of intestine, whereas probenecid, an MRP inhibitor, showed no significant effect in both proximal and distal regions of intestine. These results suggest that P-glycoprotein, but not MRP, is participated in the intestinal absorption of andrographolide and P-glycoprotein-mediated drug interactions occur depending on the co-administered drugs and its concentrations. PMID:19093450

  15. Tissue engineering the small intestine.

    PubMed

    Spurrier, Ryan G; Grikscheit, Tracy C

    2013-04-01

    Short bowel syndrome (SBS) results from the loss of a highly specialized organ, the small intestine. SBS and its current treatments are associated with high morbidity and mortality. Production of tissue-engineered small intestine (TESI) from the patient's own cells could restore normal intestinal function via autologous transplantation. Improved understanding of intestinal stem cells and their niche have been coupled with advances in tissue engineering techniques. Originally described by Vacanti et al of Massachusetts General Hospital, TESI has been produced by in vivo implantation of organoid units. Organoid units are multicellular clusters of epithelium and mesenchyme that may be harvested from native intestine. These clusters are loaded onto a scaffold and implanted into the host omentum. The scaffold provides physical support that permits angiogenesis and vasculogenesis of the developing tissue. After a period of 4 weeks, histologic analyses confirm the similarity of TESI to native intestine. TESI contains a differentiated epithelium, mesenchyme, blood vessels, muscle, and nerve components. To date, similar experiments have proved successful in rat, mouse, and pig models. Additional experiments have shown clinical improvement and rescue of SBS rats after implantation of TESI. In comparison with the group that underwent massive enterectomy alone, rats that had surgical anastomosis of TESI to their shortened intestine showed improvement in postoperative weight gain and serum B12 values. Recently, organoid units have been harvested from human intestinal samples and successfully grown into TESI by using an immunodeficient mouse host. Current TESI production yields approximately 3 times the number of cells initially implanted, but improvements in the scaffold and blood supply are being developed in efforts to increase TESI size. Exciting new techniques in stem cell biology and directed cellular differentiation may generate additional sources of autologous intestinal

  16. Effect of mytilotoxin-contaminated mussels on small intestine disaccharidase activities in rat.

    PubMed

    Taboada, C; López, R; Sanromán, M

    1995-01-01

    An extract of mussels contaminated with Gonyaulax monilata was administered intragastrically to rats (1.5 or 2.0 ml extract/150 g body wt) 3 or 7 h before experiments. Intestinal disaccharidases were determined. Sucrase activity was changed in both mucosa and brush border after treatment. Maltase and lactase activities were affected only by the higher dosage. PMID:7671637

  17. A comparison of absorption of glycerol tristearate and glycerol trioleate by rat small intestine

    SciTech Connect

    Bergstedt, S.E.; Hayashi, H.; Kritchevsky, D.; Tso, P. )

    1990-09-01

    Generally, fats rich in saturated fatty acids raise serum cholesterol, whereas fats rich in polyunsaturated fatty acids lower it. There appear to be exceptions; e.g., stearic acid (18:0)-rich fats have little or no effect on serum cholesterol concentrations. This apparent lack of cholesterolemic effect of stearic acid-rich fat could be because intestinal absorption of fat is poor or subsequent plasma and/or tissue metabolism of fat is different. To investigate mechanisms involved, we compared intestinal digestion, uptake, and lymphatic transport of glycerol tristearate (TS) and glycerol trioleate (TO, 18:1). Two groups of rats bearing intestinal lymph fistulas were used. TO rats were fed intraduodenally for 8 h at a constant rate a lipid emulsion of 25 mumols/h of TO (labeled with glycerol tri(9,10 (n)-3H)oleate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline. TS rats were fed the same lipid emulsion except that TS replaced TO and the emulsion was labeled with glyceryl (1,3-14C)tristearate. The lymph triglyceride and radioactivity were determined. After infusion, the luminal and mucosal radioactive lipid content was analyzed. The results showed that there was significantly less lipid transported in the lymph of TS rats compared with TO rats. The results also showed a significant decrease in the absorption of TS as compared with TO. This was due in part to poor lipolysis. In addition, the lipid absorbed by the intestine of the TS rats was transported into lymph less efficiently than in TO rats.

  18. Microsomal Quercetin Glucuronidation in Rat Small Intestine Depends on Age and Segment

    PubMed Central

    Bolling, Bradley W.; Court, Michael H.; Blumberg, Jeffrey B.

    2011-01-01

    UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in three equidistant small intestine (SI) segments from 4-, 12-, 18-, and 28-month-old male Fischer 344 rats (n = 8/age) using villin to control for enterocyte content. SI microsomal intrinsic clearance of quercetin was increased 3- to 9-fold from 4 months in the proximal and distal SI at 12 and 18 months. Likewise, at 30 μM quercetin, SI microsomal glucuronidation activity was increased with age: 4.8- and 3.9-fold greater at 18 months than at 4 months. Quercetin UGT regioselectivity was not changed by age. The distal SI preferentially catalyzed glucuronidation at the 7-position, whereas the proximal SI produced the greatest proportion of 4′- and 3′-conjugates. Enterocyte UGT content in different SI segments was not consistently changed with age. In the proximal SI, UGT1A increased 64 and 150% at 12 and 18 months and UGT1A1, UGT1A7, and UGT1A8 were also increased at 12 and 18 months. However, age-related changes in expression were inconsistent in the medial and distal segments. Microsomal rates of quercetin glucuronidation and UGT expression were positively correlated with UGT1A1 content for all pooled samples (r = 0.467) and at each age (r = 0.538–0.598). UGT1A7 was positively correlated with total, 7-O- and 3-O-quercetin glucuronidation at 18 months. Thus, age-related differences in UGT quercetin glucuronidation depend on intestinal segment, are more pronounced in the proximal and distal segments and may be partially related to UGT1A1 and UGT1A7 content. PMID:21543555

  19. Changes in small intestinal morphology and digestive enzyme activity with oral administration of copper-loaded chitosan nanoparticles in rats.

    PubMed

    Han, Xin-Yan; Du, Wen-Li; Huang, Qi-Chun; Xu, Zi-Rong; Wang, Yi-Zheng

    2012-03-01

    The experiment was conducted to evaluate the effect of copper-loaded chitosan nanoparticles on the small intestinal morphology and activities of digestive enzyme and mucosal disaccharase in rats. Forty male Sprague-Dawley rats, with average body weight of 82 g, were randomly allotted to five groups (n = 8). All rats were received a basal diet (control) or the same basal diet added with 80 mg/kg BW CuSO(4), 80 mg/kg BW chitosan (CS-I), 80 mg/kg BW copper-loaded chitosan nanoparticles (CSN-I), 160 mg/kg BW copper-loaded chitosan nanoparticles (CSN-II), respectively. The experiment lasted 21 days. The results showed that the villus heights of the small intestinal mucosa in groups CSN-I and CSN-II were higher than those of the control, group CuSO(4) or CS-I. The crypt depth of duodenum and ileum mucosa in group CSN-I or CSN-II was depressed. Compared with the control, there were no significant effects of CuSO(4) or CS-I on the villus height and crypt depth of small intestinal mucosa. Supplementation with CSN improved the activities of trypsin, amylase and lipase in the small intestinal contents and maltase, sucrase and lactase of duodenum, jejunum, and ileum mucosa while there were no significant effects of CuSO(4) on the digestive enzyme activities of the small content compared with the control. The results indicated that intestinal morphology, activities of digestive enzyme in digesta and mucosal disaccharase were beneficially changed by treatment of copper-loaded chitosan nanoparticles. PMID:21882065

  20. Emu Oil Combined with Lyprinol™ Reduces Small Intestinal Damage in a Rat Model of Chemotherapy-Induced Mucositis.

    PubMed

    Mashtoub, Suzanne; Lampton, Lorrinne S; Eden, Georgina L; Cheah, Ker Y; Lymn, Kerry A; Bajic, Juliana E; Howarth, Gordon S

    2016-10-01

    Chemotherapy-induced mucositis is characterized by inflammation and ulcerating lesions lining the alimentary tract. Emu Oil and Lyprinol™ have independently demonstrated their therapeutic potential in intestinal inflammatory disorders, including mucositis. We investigated Emu Oil and Lyprinol™ in combination for their further potential to alleviate chemotherapy-induced mucositis in rats. Rats were gavaged with (1 ml) water, Olive Oil, Emu Oil + Olive Oil, Lyprinol™ + Olive Oil or Emu Oil + Lyprinol™ from Days 0 to 7, injected with saline (control) or 5-Fluorouracil (5-FU) on Day 5 and euthanized on Day 8. Myeloperoxidase (MPO) activity (indicative of acute inflammation), histological severity scores, and intestinal architecture were quantified. Myeloperoxidase activity was significantly increased in the jejunum and ileum following 5-FU, compared to saline controls. Both Olive Oil and Emu Oil + Lyprinol™ significantly reduced jejunal MPO levels (1.8-fold and 1.7-fold, respectively), whereas only Emu Oil + Lyprinol™ significantly decreased ileal MPO levels, relative to 5-FU controls. All oil treatments decreased histological severity scores in the jejunum and ileum, and normalized crypt depth in the mid small intestine, relative to 5-FU controls. Emu Oil combined with Lyprinol™ partially reduced acute small intestinal inflammation. Isolating bioactive constituents of these naturally sourced oils could provide a more targeted strategy to protect against intestinal mucositis. PMID:27618153

  1. Partial Enteral Nutrition Mitigated Ischemia/Reperfusion-Induced Damage of Rat Small Intestinal Barrier

    PubMed Central

    Wu, Chao; Wang, Xinying; Jiang, Tingting; Li, Chaojun; Zhang, Li; Gao, Xuejin; Tian, Feng; Li, Ning; Li, Jieshou

    2016-01-01

    Background and Aims: This study was designed to investigate a relatively optimum dose of partial enteral nutrition (PEN) which effectively attenuates intestinal barrier dysfunction initiated by ischemia/reperfusion injury (IRI). Methods: In experiment 1, 60 male Sprague-Dawley (SD) rats were subjected to intestinal IRI and assigned to six groups according to the different proportion of EN administrations: namely total parenteral nutrition (TPN or 0%EN), 10%EN, 20%EN, 40%EN, 60%EN, and total enteral nutrition (TEN or 100%) groups, the deficits of intraluminal calorie were supplemented by PN. In experiment 2, 50 male SD rats were subjected to intestinal IRI and divided into five groups based on the results of experiment 1: TPN, TEN, 20%EN, TPN plus pretreatment with NF-κB antagonist 30 min before IRI (TPN+PDTC), and TPN plus pretreatment with HIF-1α antagonist 30 min before IRI (TPN+YC-1) groups. Results: In experiment 1, previous IRI combined with subsequent EN shortage disrupted the structure of intestinal epithelial cell and tight junctions (TJs). While 20% dose of EN had an obviously protective effect on these detrimental consequences. In experiment 2, compared with TPN only, 20%EN exerted a significant protection of barrier function of intestinal epithelium. Analogous results were observed when TPN combined with specific NF-κB/HIF-1α inhibitors (PDTC and YC-1). Meanwhile, the expression of NF-κB/HIF-1α had a similar trend among the groups. Conclusions: Our findings indicate that 20%EN is the minimally effective dosage of EN which promotes the recovery of intestinal barrier function after IRI in a rat model. Furthermore, we discreetly speculate that this benefit is, at least partly, related to NF-κB/HIF-1α pathway expression. PMID:27548209

  2. Effect of White Kidney Beans (Phaseolus vulgaris L. var. Beldia) on Small Intestine Morphology and Function in Wistar Rats.

    PubMed

    Nciri, Nader; Cho, Namjun; Bergaoui, Nacef; El Mhamdi, Faiçal; Ben Ammar, Aouatef; Trabelsi, Najoua; Zekri, Sami; Guémira, Fathi; Ben Mansour, Abderraouf; Sassi, Fayçal Haj; Ben Aissa-Fennira, Fatma

    2015-12-01

    The chronic ingestion of raw or undercooked kidney beans (Phaseolus vulgaris L.) causes functional and morphological derangement in various tissues. The major objectives of this study were to investigate the gavage effects of a raw Beldia bean variety that is widely consumed in Tunisia, on the small intestine morphology and jejunal absorption of water, electrolytes, and glucose in Wistar rats. Twenty young male rats were randomly divided into two groups of 10 rats. The first group served as the control and was gavaged with 300 mg of a rodent pellet flour suspension (RPFS), whereas the second experimental group was challenged with 300 mg of a Beldia bean flour suspension (BBFS) for 10 days. Histological studies were performed using light and electron microcopy. The intestinal transport of water, sodium, potassium, and glucose was studied by perfusing the jejunal loops of the small bowels in vivo. The feeding experiments indicated that BBFS did not affect weight gain. Histomorphometric analyses showed that the villus heights, crypt depths, and crypt/villus ratios in the jejunum and ileum were greater in the BBFS-fed rats than controls. Electron microscopy studies demonstrated that the rats exposed to RPFS exhibited intact intestinal tracts; however, the BBFS-treated rats demonstrated intestinal alterations characterized by abnormal microvillus architectures, with short and dense or long and slender features, in addition to the sparse presence of vesicles near the brush border membrane. BBFS administration did not significantly affect glucose absorption. However, significant decreases were observed in water and electrolyte absorption compared with the uptake of the controls. In conclusion, raw Beldia beans distorted jejunum morphology and disturbed hydroelectrolytic flux. PMID:26488416

  3. Amino acid and peptide absorption from partial digests of proteins in isolated rat small intestine.

    PubMed Central

    Gardner, M L

    1978-01-01

    1. Absorption of each of sixteen amino acids, free and peptide-bound, has been measured in isolated rat small intestine perfused with five partial digests of proteins. 2. At low concentrations net absorption of each amino acid was proportional to its luminal concentration and independent of the nature of the amino acid. 3. A series of first-order multiple regressions was found to describe well the characteristics of absorption. 4. Rate constants for disappearance of free and peptide-bound amino acids from the lumen were closely similar. However, substantial back-flux occurred of amino acids derived from peptide hydrolysis. Hence 60-70% of the amino-N entering the serosal tissue fluid probably had left the lumen as free amino acids. 5. Intact peptides crossed the mucosa during absorption from a soy bean hydrolysate and in substantial quantities during absorption from one casein digest but not from another. With other hydrolysates there was no evidence for passage of peptides to the serosa. 6. In several cases there was a serious discrepancy between the amount of amino-N absorbed from the lumen and the amount accounted for as peptide or free amino acid in the serosal secretion. 7. The characteristics of absorption were similar (apart from the exceptions in 5 above) for all the digests studied except for soy bean hydrolysate. PMID:731590

  4. Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon

    PubMed Central

    2009-01-01

    Background Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB) on formation of aberrant crypt foci (ACF) in colons of male Fisher F344 rats (inbred strain). However, effects of BB on colon tumors and in both genders are unknown. Methods We examined efficacy of BB in inhibition of azoxymethane (AOM)-induced colon ACF and intestine tumors in male and female Sprague-Dawley rats (outbred strain). Pregnant rats were fed a diet with or without 10% BB powder; progeny were weaned to the same diet as their dam and received AOM as young adults. Results Male and female rats on control diet had similar numbers of ACF at 6 weeks after AOM administration. BB increased (P < 0.05) ACF numbers within the distal colon of female but not male rats. There was a significant (P < 0.05) diet by gender interaction with respect to total colon ACF number. Colon and duodenum tumor incidences were less in females than males at 17 weeks after AOM. BB tended (0.1 > P > 0.05) to reduce overall gastrointestinal tract tumor incidence in males, however, tumor incidence in females was unaffected (P > 0.1) by BB. There was a tendency (0.1 > P > 0.05) for fewer adenocarcinomas (relative to total of adenomatous polyps plus adenocarcinomas) in colons of female than male tumor-bearing rats; in small intestine, this gender difference was significant (P < 0.05). BB favored (P < 0.05) fewer adenocarcinomas and more adenomatous polyps (as a proportion of total tumor number) in female rat small intestine. Conclusion Results did not indicate robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in distal colon and tumor progression in duodenum, in gender-specific fashion. Data indicate the potential for slowing tumor progression (adenomatous polyp to adenocarcinoma) by BB. PMID:19758446

  5. Region-dependent absorption of faropenem shared with foscarnet, a phosphate transporter substrate, in the rat small intestine.

    PubMed

    Saitoh, Hiroshi; Sawazaki, Rinako; Oda, Masako; Kobayashi, Michiya

    2008-09-01

    Faropenem, a penem antibiotic, is orally active despite its hydrophilic nature. However, its intestinal absorption has not yet been characterised in detail. This study was undertaken to determine the factors regulating faropenem absorption using intestinal loops prepared in the rat duodenum, jejunum and terminal ileum. Faropenem disappearance was much greater than that of cefotaxime and meropenem, and faropenem disappeared more extensively from the terminal ileum than from the jejunum or duodenum. In contrast to faropenem, the disappearance of ceftibuten was much greater from the duodenum and jejunum than from the terminal ileum. As the accumulation and enzymatic degradation of faropenem was minimal in the intestinal mucosa, faropenem was considered to enter the portal vein smoothly after its disappearance from the intestinal loops. Faropenem disappearance was not significantly influenced by the presence of monocarboxylic acids, amino acids or bile acid. Dipeptides such as L-carnosine and glycylglycine slightly but significantly lowered faropenem disappearance from the terminal ileum. On the other hand, foscarnet exerted a marked inhibitory effect on faropenem disappearance, but the antiviral agent did not modulate ceftibuten absorption. The present results suggest that faropenem is in part absorbed via a phosphate transporter present in the rat small intestine. PMID:18614339

  6. alpha-Lactalbumin hydrolysate stimulates glucagon-like peptide-2 secretion and small intestinal growth in suckling rats.

    PubMed

    Izumi, Hirohisa; Ishizuka, Satoshi; Inafune, Ayako; Hira, Tohru; Ozawa, Kazuhiro; Shimizu, Takashi; Takase, Mitsunori; Hara, Hiroshi

    2009-07-01

    We investigated whether bovine milk constituents influenced glucagon-like peptide (GLP)-2 secretion and intestinal growth in suckling rats. Male Sprague-Dawley rats (14 d old) received i.g. infusions of a milk protein fraction, a lactose solution, or the cream fraction of milk. The serum concentration of GLP-2, but not GLP-1, markedly increased in rats administered milk protein compared with those given the lactose solution or the cream fraction from 60 to 120 min after administration. In another experiment, both casein (CN) and whey protein isolate stimulated GLP-2 secretion at 120 min after administration, but soy protein and ovalbumin did not. Stimulation of GLP-2 secretion by several milk proteins was similar, including alpha-CN, alpha-lactalbumin (alpha-La), and beta-lactoglobulin, in a separate experiment. A hydrolysate of alpha-La obtained by incubation with protease A extracted from Aspergillus oryzae (LaHPA) caused almost twice the GLP-2 release due to intact alpha-La and other alpha-La hydrolysates. Free amino acid concentrations and molecular size distributions did not differ among alpha-La hydrolysates, including LaHPA. In rat pups reared with milk formulae containing alpha-La or LaHPA, LaHPA significantly promoted small intestinal elongation and increased the number of crypt epithelial cells compared with a formula containing intact alpha-La. LaHPA administration also increased the maltase:lactase activity ratio, a marker of maturation of the intestinal mucosa. In conclusion, milk proteins stimulate GLP-2 secretion and contribute to growth and maturation of the small intestine in suckling rats. PMID:19494023

  7. Pretreatment of cromolyn sodium prior to reperfusion attenuates early reperfusion injury after the small intestine ischemia in rats

    PubMed Central

    Hei, Zi-Qing; Gan, Xiao-Liang; Luo, Gang-Jian; Li, Shang-Rong; Cai, Jun

    2007-01-01

    AIM: To investigate the effects of Cromolyn Sodium (CS) pretreated prior to reperfusion on the activity of intestinal mucosal mast cells (IMMC) and mucous membrane of the small intestine in ischemia-reperfusion (IR) injury of rats. METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups: sham group (group S), model group (group M), high and low dosage of CS groups, (treated with CS 50 mg/kg or 25 mg/kg, group C1 and C2). Intestinal IR damage was induced by clamping the superior mesenteric artery for 45 min followed by reperfusion for 60 min. CS was intravenouly administrated 15 min before reperfusion. Ultrastructure and counts of IMMC, intestinal structure, the expression of tryptase, levels of malondisldehyde (MDA), TNF-α, histamine and superoxide dismutase (SOD) activity of the small intestine were detected at the end of experiment. RESULTS: The degranulation of IMMC was seen in group M and was attenuated by CS treatment. Chiu’s score of group M was higher than the other groups. CS could attenuate the up-regulation of the Chiu’s score, the levels of MDA, TNF-α, and expression of tryptase and the down-regulation of SOD activity and histamine concentration. The Chiu’s score and MDA content were negatively correlated, while SOD activity was positively correlated to the histamine concentration respectively in the IR groups. CONCLUSION: Pretreated of CS prior to reperfusion protects the small intestine mucous from ischemia-reperfusion damage, the mechanism is inhibited IMMC from degranulation. PMID:17876882

  8. Protective effect of ellagic acid and pumpkin seed oil against methotrexate-induced small intestine damage in rats.

    PubMed

    El-Boghdady, Noha A

    2011-12-01

    Gastrointestinal toxicity is one of the most serious side effects in the methotrexate (MTX) treatment. This study was designed to investigate whether ellagic acid (EA) and/or pumpkin seed oil (PSO) had a protective effect on MTX-induced small intestine damage. Forty albino rats were randomized into five groups of 8 rats each. Group I served as a normal control group. In Group II, MTX was administered as a single dose (20 mg/kg) intraperitoneally. Groups III, IV and V were pre-treated respectively with either PSO (40 mg/kg), EA (10 mg/kg) or 0.2% DMSO (vehicle control) orally every day by gavage for 5 days and then they received MTX. All animals were sacrificed 5 days after the intraperitoneal injection of MTX for histopathological examination, estimation of serum prostaglandin E2 (PGE2) level, assay of tissue malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) levels and myloperoxidase (MPO), xanthine oxidase (XO) and adenosine deaminase (AD) activities. Administration of EA and/or PSO decreased the intestinal damage, PGE2, MDA and NO levels and MPO, XO and AD activities and increased GSH level. These results suggest that EA and PSO protect the small intestine of rats from MTX-induced damage through their antioxidant and anti-inflammatory effects and thus have potential as a promising drug in the prevention of undesired side effects of MTX. PMID:22329239

  9. Region-dependent disappearance of vinblastine in rat small intestine and characterization of its P-glycoprotein-mediated efflux system.

    PubMed

    Nakayama, A; Saitoh, H; Oda, M; Takada, M; Aungst, B J

    2000-10-01

    This study was aimed to characterize the absorption behavior of vinblastine (VLB), a well-known substrate of P-glycoprotein (P-gp), from rat small intestine, especially focusing on the regional-dependence of its efflux mediated by P-gp. VLB disappeared from duodenal and ileal loops of male Wistar rats fairly rapidly (30-60% in 30 min). In contrast, its disappearance from the jejunal loop was almost negligible and in some rats >100% of the jejunal dose was recovered. The radioactivity derived from [3H]VLB, which was absorbed from duodenum and ileum, was detected in the jejunal region. The jejunal appearance of radioactivity was increased when unlabeled VLB was present in the region in advance. The basolateral-to-apical transport of [3H]VLB across Caco-2 cell monolayers was greater when unlabeled VLB was added to the apical medium than when VLB-free buffer was applied to the apical side. When verapamil or cyclosporin A, potent modulators of P-gp, was added to the apical medium together with unlabeled VLB, enhanced basolateral-to-apical transport of [3H]VLB was disappeared. It is suggested that VLB absorption is strongly restricted by P-gp, especially in the jejunal region of the rat small intestine, and that the secretory transport via intestinal P-gp may be subject to trans-stimulation. Moreover, intravenously administered methylprednisolone and intramuscularly administered progesterone significantly enhanced the absorption of VLB, suggesting that parenterally administered P-gp modulators could influence the intestinal absorption of P-gp substrates. PMID:11033075

  10. The correlation of intragraft cytokine expression with rejection in rat small intestine transplantation.

    PubMed

    McDiarmid, S V; Farmer, D G; Kuniyoshi, J S; Robert, M; Khadavi, A; Shaked, A; Busuttil, R W

    1994-09-27

    Rejection continues to be a major cause of graft loss in small intestine transplantation (SIT). We have studied, by semiquantitative reverse transcriptase PCR (rtPCR), the intragraft expression of cytokines relevant to rejection in a rat model. Heterotopic SIT grafts were performed from Lewis x Brown Norway F1 donors into Lewis recipients. The isograft control was Lewis into Lewis. Five animals in each isograft and allograft group were sacrificed on POD 3, 5, 7, 8, 9, 10, 12, and 14. mRNA was isolated from portions of the terminal ileum and rtPCR performed to amplify message for interleukin-2 (IL-2), IL-2 receptor (IL-2R), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). Semiquantitative analysis was performed using 32P radionuclide incorporation and scintillation counting. The results were expressed as percent activity compared with beta-actin. Histologic correlation with cytokine expression was made. On POD 3 after SIT there was no evidence of rejection by histology and all cytokines studied showed no difference between the isograft and the allograft. On POD 5 the first evidence of mild rejection was seen on histology and IL-6, IFN-gamma, TNF-alpha showed a significant up regulation in the allograft that persisted through POD 14. mRNA for IL-2 was not significantly upregulated until POD 7 and persisted until POD 14. IL-2R was constitutively expressed in both isograft and allograft and was not a reliable predictor of rejection. Histologic rejection was moderately severe by POD 7 and severe between POD 8 and 14 correlating with the increasing expression of IL-6, IFN-gamma, and TNF-alpha. In summary, we have shown that increasing expression of mRNA for IL-6, IFN-gamma, and TNF-alpha not only correlated with severity of rejection but that upregulation began early when histologic evidence of rejection first occurred. PMID:7940688

  11. Small Intestinal Bacterial Overgrowth

    PubMed Central

    Dukowicz, Andrew C.; Levine, Gary M.

    2007-01-01

    Small intestinal bacterial overgrowth (SIBO), defined as excessive bacteria in the small intestine, remains a poorly understood disease. Initially thought to occur in only a small number of patients, it is now apparent that this disorder is more prevalent than previously thought. Patients with SIBO vary in presentation, from being only mildly symptomatic to suffering from chronic diarrhea, weight loss, and malabsorption. A number of diagnostic tests are currently available, although the optimal treatment regimen remains elusive. Recently there has been renewed interest in SIBO and its putative association with irritable bowel syndrome. In this comprehensive review, we will discuss the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of SIBO. PMID:21960820

  12. The post-natal development of cholecystokinin-like activity in the brain and small intestine of the rat.

    PubMed Central

    Brand, S J

    1982-01-01

    1. The post-natal development of cholecystokinin (CCK)-like activity was studied in the brain and small intestine of the rat. CCK-like biological activity was measured in extracts of these tissues by an in vitro rabbit gall-bladder bioassay. 2. Immediately after birth, the brain contained very little CCK-like activity whereas the proximal small intestine contained significant concentrations of CCK-like activity. The concentration of CCK-like activity in the brain increased rapidly during the third post-natal week and reached adult values by the end of the fourth week. The development of CCK-like activity in the proximal small intestine differed from that seen in the brain. The concentration of CCK-like activity increased during the first post-natal week. After this time, however, the concentration decreased and the adult values, therefore, were lower than those found immediately after birth. This decrease in concentration resulted from failure of the total content of CCK-like activity to increase despite rapid growth of the intestine. 3. The composition of CCK-like activity in neonatal extracts was determined by gel filtration chromatography with Sephadex G50. Extracts of neonatal brain and intestine contained more than one molecular form of CCK-like activity in contrast to the single peak of activity found in adult extracts. In the developing intestine smaller molecular forms were found in addition to the single larger form found in the adult and in the neonatal brain larger molecular forms were found in addition to the CCK octapeptide found in the adult. PMID:7108804

  13. Subacute effects of carbofuran on enzyme functions in rat small intestine.

    PubMed

    Gera, Nidhi; Kiran, Ravi; Mahmood, Akhtar

    2009-02-01

    The effect of carbofuran administration to rats has been studied on enzymes functions in rat intestine. Carbofuran was administrated 4.0 mg/kg body weight for 7 days or 2.8 mg/kg body weight for 30 days daily by Ryle's tube. Animals given carbofuran for 30 days exhibited retarded growth compared to control group. The activities of sucrase (56%), alkaline phosphatase (62%), leucine aminopeptidase (56%), and gamma-glutamyl trans peptidase (84%) were enhanced in animals given carbofuran for 7 days. Enhancement in the activities of alkaline phosphatase and leucine amino peptidase (92-96%) was also observed in animals exposed to carbofuran for 30 days, but the activities of sucrase (28%) and gamma-glutamyl transpeptidase (49%) were reduced under these conditions. There was no change in activities of maltase, lactase, and trehalase in pesticide-treated animals for 7 or 30 days. The activity of lactate dehydrogenase was enhanced (p < 0.001) in 7 days and 30 days induced carbofuran toxicity. The activities of glucose-6-phosphatase and glutamate pyruvate transaminase were also enhanced (p < 0.001) in pesticide-treated animals for 7 days, but were reduced by 46% and 26%, respectively, after 30 days of carbofuran exposure. The activity of glutamate oxaloacetate transaminase was unaltered in carbofuran toxicity. Kinetic analysis of brush border enzymes revealed a change in V(max) with no change in apparent Km. Western blot analysis of brush border sucrase, alkaline phosphatase, and leucine aminopeptidase corroborated the enzyme activity data. Intestinal histological revealed distruption of the villi, and comet assay showed disintegration of DNA in enterocytes of animals exposed to carbofuran for 30 days. These findings suggest that carbofuran toxicity may modulate digestive functions in rat intestine. PMID:19778259

  14. Enhanced visualization of small peptides absorbed in rat small intestine by phytic-acid-aided matrix-assisted laser desorption/ionization-imaging mass spectrometry.

    PubMed

    Hong, Seong-Min; Tanaka, Mitsuru; Yoshii, Saori; Mine, Yoshinori; Matsui, Toshiro

    2013-11-01

    Enhanced visualization of small peptides absorbed through a rat intestinal membrane was achieved by matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry (MALDI-IMS) with the aid of phytic acid as a matrix additive. Penetrants through intestinal peptide transporter 1, i.e., glycyl-sarcosine (Gly-Sar, 147.1 m/z) and antihypertensive dipeptide, Val-Tyr (281.2 m/z), were chosen for MALDI-IMS. The signal-to-noise (S/N) ratios of dipeptides Gly-Sar and Val-Tyr were seen to increase by 2.4- and 8.0-fold, respectively, when using a 2',4',6'-trihydroxyacetophenone (THAP) matrix containing 5.0 mM phytic acid, instead of the THAP matrix alone. Owing to the phytic-acid-aided MALDI-IMS method, Gly-Sar and Val-Tyr absorbed in the rat intestinal membrane were successfully visualized. The proposed imaging method also provided useful information on intestinal peptide absorption; to some extent, Val-Tyr was rapidly hydrolyzed to Tyr by peptidases located at the intestinal microvillus during the absorption process. In conclusion, the strongly acidic additive, phytic acid, is beneficial for enhancing the visualization of small peptides using MALDI-IMS, owing to the suppression of ionization-interfering salts in the tissue. PMID:24063774

  15. Small Intestinal Infections.

    PubMed

    Munot, Khushboo; Kotler, Donald P

    2016-06-01

    Small intestinal infections are extremely common worldwide. They may be bacterial, viral, or parasitic in etiology. Most are foodborne or waterborne, with specific etiologies differing by region and with diverse pathophysiologies. Very young, very old, and immune-deficient individuals are the most vulnerable to morbidity or mortality from small intestinal infections. There have been significant advances in diagnostic sophistication with the development and early application of molecular diagnostic assays, though these tests have not become mainstream. The lack of rapid diagnoses combined with the self-limited nature of small intestinal infections has hampered the development of specific and effective treatments other than oral rehydration. Antibiotics are not indicated in the absence of an etiologic diagnosis, and not at all in the case of some infections. PMID:27168147

  16. Experiment K-6-17. Structural changes and cell turnover in the rats small intestine induced by spaceflight

    NASA Technical Reports Server (NTRS)

    Phillips, R. W.; Sawyer, H. R.; Smirnov, K. V.

    1990-01-01

    The purpose of this project was to test the hypothesis that the generalized, whole body decrease in synthetic activity associated with microgravity conditions of space flight as evidenced by negative nitrogen balance and muscle atrophy (Nicogossian and Parker, 1982; Oganov, 1981), as well as inhibited lymphocyte proliferation (Bechler and Cogoli, 1986), would be evident in cells characterized by a rapid rate of turnover. As a model, researchers chose to study the turnover of mucosal cells lining the jejunum of the small intestine, since these cells are among the most rapidly proliferating in the body. Under normal conditions, epithelial cells that line the small intestine are continually produced in the crypts of Lieberkuhn. These cells migrate out of the crypts onto intestinal villi, are progressively pushed up the villus as new crypt cells are formed, and ultimately reach the tip of villi where they are then descquamated. In rats, the entire process, from initial proliferation in crypts to desquamation, takes approximately 2 days (Cairnie et al., 1965; Lipkin, 1973). In this study, researchers determined the mitotic index for mucosal cells lining the proximal, middle, and distal regions of the jejunum in rats from three treatment groups (synchronous control, vivarium control and flight), and measured the depth of the crypts of Lieberkuhn and the length of villi present in each of the three jejunal regions sampled.

  17. High wholegrain barley β-glucan lowers food intake but does not alter small intestinal macronutrient digestibility in ileorectostomised rats.

    PubMed

    Belobrajdic, Damien P; Hino, Shingo; Kondo, Takashi; Jobling, Stephen A; Morell, Matthew K; Topping, David L; Morita, Tatsuya; Bird, Anthony R

    2016-09-01

    Using barley cultivars differing widely in β-glucan content, we aimed to determine their effects on small intestinal macronutrient digestion in 24 ileorectostomised rats. The rats were fed 1 of 4 experimental diets, each containing a different barley variety, for 11 d. The diets had a content of 0, 2.1, 2.6 and 4.3 g of β-glucan/100 g. Feed intake and faecal excretion of fat, protein, starch, and non-starch polysaccharides were determined in the final 5 d of the study and apparent macronutrient digestibility calculated. Higher dietary levels of β-glucan (2.6% and 4.3%) lowered feed intake (by 15 and 19%, respectively) but final body weight was only lowered by the 4.3% β-glucan diet relative to rats fed the 0% β-glucan diet (all ps < 0.05). Protein, lipid and starch digestibility was unrelated to the dietary β-glucan content. Higher dietary levels of barley β-glucan lower feed intake of ileorectostomised rats, which is independent of intestinal fermentation and unrelated to macronutrient digestibility. PMID:27282074

  18. [Small intestine bacterial overgrowth].

    PubMed

    Leung Ki, E L; Roduit, J; Delarive, J; Guyot, J; Michetti, P; Dorta, G

    2010-01-27

    Small intestine bacterial overgrowth (SIBO) is a condition characterised by nutrient malabsorption and excessive bacteria in the small intestine. It typically presents with diarrhea, flatulence and a syndrome of malabsorption (steatorrhea, macrocytic anemia). However, it may be asymptomatic in the eldery. A high index of suspicion is necessary in order to differentiate SIBO from other similar presenting disorders such as coeliac disease, lactose intolerance or the irritable bowel syndrome. A search for predisposing factor is thus necessary. These factors may be anatomical (stenosis, blind loop), or functional (intestinal hypomotility, achlorydria). The hydrogen breath test is the most frequently used diagnostic test although it lacks standardisation. The treatment of SIBO consists of eliminating predisposing factors and broad-spectrum antibiotic therapy. PMID:20214190

  19. Inhibition characteristics of hypericin on rat small intestine glutathione-S-transferases.

    PubMed

    Tuna, Gamze; Kulaksiz Erkmen, Gulnihal; Dalmizrak, Ozlem; Dogan, Arin; Ogus, I Hamdi; Ozer, Nazmi

    2010-10-01

    Glutathione-S-transferases constitute a family of enzymes involving in the detoxification of xenobiotics, signalling cascades and serving as ligandins or/and catalyzing the conjugation of various chemicals and drugs. The widely expressed cytosolic GST-pi is a marker protein in various cancers and its increased concentration is linked to drug resistance. GST-pi is autoregulated by S-glutathionylation and it catalyzes the S-glutathionylation of other proteins in response to oxidative or nitrosative stress. S-glutathionylation of GST-pi results in multimer formation and the breakage of ligand binding interactions with c-Jun NH(2)-terminal kinase (JNK). Another widely expressed GST enzyme, GST-alpha is assumed as a marker in hepatocellular damage, is implicated in cancer, asthma, cardiovascular disease and response to chemotherapy. Although, it was shown that hypericin binds and inhibits GST-alpha and GST-pi, the inhibition characteristics have not been investigated in detail. The aim of this study was to investigate the effects of hypericin on major GSTs; GST-alpha and GST-pi purified from rat small intestine. When GSH used as varied substrate the inhibition pattern with hypericin was uncompetitive for GST-alpha (K(i)=0.16 + or - 0.02 microM) and noncompetitive for GST-pi (K(i) = 2.46 + or - 0.43 microM). While using CDNB (1-chloro-2,4-dinitrobenzene) as the varied substrate, the inhibition patterns were noncompetitive for GST-alpha and competitive for GST-pi; K(i) values for GST-alpha and GST-pi were 1.91 + or - 0.21 and 0.55 + or - 0.07 microM, respectively. Since hypericin accumulated in cancer cells and important in photodynamic therapy (PDT), inhibition of GST-alpha and GST-pi by hypericin might increase the effectivity of the treatment. Considering that GST-pi is responsible for the drug resistance its inhibition might increase the benefit obtained from chemotherapy. PMID:20637187

  20. Identification and Characterization of Phytohemagglutinins from White Kidney Beans (Phaseolus vulgaris L., var. Beldia) in the Rat Small Intestine.

    PubMed

    Nciri, Nader; Cho, Namjun; El Mhamdi, Faiçal; Ben Mansour, Abderraouf; Haj Sassi, Fayçal; Ben Aissa-Fennira, Fatma

    2016-01-01

    Although kidney bean (Phaseolus vulgaris L.) lectin toxicity is widely known, its effects in the gastrointestinal tract require further study. This investigation aimed to identify and characterize phytohemagglutinins (PHAs) in the small intestine and sera of rats following oral challenge with ground white beans. Twenty young, adult male rats were divided randomly into two groups of 10 animals each. The control group underwent gavage with a suspension of 300 mg of rodent pellet flour. The experimental group was administered a 300 mg Beldia bean flour suspension (BBFS). After 10 days of daily treatment, jejunal rinse liquid (JRL) and ileum rinse liquid and secretions, as well as sera, were collected. All biological fluids were screened for lectin reactivity using competitive inhibition ELISA, Ouchterlony double immunodiffusion, and immunoelectrophoresis techniques. The results revealed the presence of immunogenic intraluminal PHAs 3-4 h after the oral intake of the BBFS in the JRLs as well as in the jejunal and ileal secretions; however, no PHA was detectable in the rat sera. Ingestion of raw Beldia beans may lead to interaction between PHAs and the mucosa of the small intestine, potentially resulting in an inflammatory response. PMID:26561877

  1. Small Intestine Cancer Treatment

    MedlinePlus

    ... small intestine cancer include unexplained weight loss and abdominal pain. These and other signs and symptoms may be ... doctor if you have any of the following: Pain or cramps in the middle of the abdomen. Weight loss with no known reason. A lump ...

  2. Synergistic effects of thyroxine and dexamethasone on enzyme ontogeny in rat small intestine.

    PubMed

    McDonald, M C; Henning, S J

    1992-09-01

    The synergistic effects of dexamethasone (DEX) and thyroxine (T4) on the postnatal maturation of the 13-d-old rodent small intestine has been studied. Previous studies have shown that hydrocortisone and T4 produced a synergistic response in enzyme maturation. However, T4 elevates corticosteroid-binding globulin, which reduces the clearance of hydrocortisone. Thus, the apparent synergy between T4 and hydrocortisone may have been due to increased glucocorticoid availability. DEX, which does not bind to corticosteroid-binding globulin, was given (d8-12) at 25 pmol (i.e. 0.01 micrograms)/g body wt/d as established by a dose-response study in which this dose of DEX induced one third the maximum response in sucrase activity. In this way, synergy with T4 (130 pmol/g body wt/d, i.e. 0.1 micrograms/g body wt/d, d 5-12) could still be observed. Glucoamylase, lactase, acid beta-galactosidase, alkaline phosphatase, and sucrase activities were determined in two regions of the small intestine. Overall, the results for the two hormones administered alone showed intestinal maturation to be not significantly affected in the T4 group and partially stimulated in the DEX group. When combined, DEX + T4 synergistically increased jejunal sucrase, ileal glucoamylase, and duodenal alkaline phosphatase, and lowered ileal acid beta-galactosidase. The striking exceptions to the general pattern were two brush border enzymes that normally decline during intestinal maturation, namely ileal alkaline phosphatase and jejunal and ileal lactase. For these enzymes, DEX alone did not elicit precocious maturation, and there was no evidence for a synergistic interaction of these two hormones. Serum corticosterone concentrations also were measured. When corticosterone concentrations were compared with enzyme activity, no correlation was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1408467

  3. Small intestine contrast injection (image)

    MedlinePlus

    ... and throat, through the stomach into the small intestine. When in place, contrast dye is introduced and ... means of demonstrating whether or not the small intestine is normal when abnormality is suspected.

  4. Small intestine aspirate and culture

    MedlinePlus

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  5. Antispasmodic effects of myrrh due to calcium antagonistic effects in inflamed rat small intestinal preparations.

    PubMed

    Vissiennon, Cica; Goos, Karl-Heinz; Goos, Ole; Nieber, Karen

    2015-01-01

    Myrrh is the oleo-gum resin of mainly Commiphora molmol and as a powdered substance, one compound in the traditional medicinal product Myrrhinil-Intest®, which has been used for the treatment of unspecific, inflammatory intestinal disorders. The aim of the present study was to evaluate the antispasmodic effect of myrrh under healthy and inflamed conditions, and to evaluate a calcium-antagonistic effect as a possible mode of action. Therefore, an ethanolic myrrh extract was tested for its effects on muscle tone and acetylcholine-induced contractions in untreated and inflamed rat ileum/jejunum preparations. Inflammation was experimentally induced by 2,4,6-trinitrobenzene sulfonic acid (10 mM, 30 min). Additionally, the effect of the calcium channel agonist Bay K8644 in the presence of varying myrrh extract concentrations was examined. Myrrh extract (0.99 mg/mL) suppressed the acetylcholine-induced contraction down to 25.8 % in untreated and 15.2 % in inflamed preparations. Myrrh extract (0.15; 0.25 and 0.35 mg/mL) induced a concentration-dependent rightward shift of the Bay K8644 concentration-response curve in untreated and inflamed preparations with a significant EC50 shift. Schild analysis resulted in a pA2 value of 0.93 for untreated preparations. Increasing myrrh extract concentrations induced a concentration-dependent decrease of the agonistic maximum effect in untreated and inflamed preparations down to 15.8 % and 25.8 %, respectively, for the highest concentration leading to a pD2 value of 0.58. Myrrh extract reduced intestinal muscle tone and acetylcholine-induced contraction of untreated and inflamed ileum/jejunum preparations based on dual calcium antagonism characterized by a right shift of the agonistic dose-response curve and a depression of the maximum effect. The resulting reduction of intestinal motility and spasmolytic effects provide a rationale for the symptom treatment of intestinal disorders such as irritable bowel syndrome

  6. Excised segments of rat small intestine in Ussing chamber studies: A comparison of native and stripped tissue viability and permeability to drugs.

    PubMed

    Sjögren, Erik; Eriksson, Johanna; Vedin, Charlotta; Breitholtz, Katarina; Hilgendorf, Constanze

    2016-05-30

    Excised rat intestinal tissue mounted in an Ussing chamber can be used for intestinal permeability assessments in drug development. The outer layer of the intestine, the serosa and part of the muscle layer, is traditionally removed since it is considered a barrier to the diffusion of nutrients and oxygen as well as to that of pharmaceutical substances. However, the procedure for removing the serosal-muscle layer, i.e. stripping, is a technically challenging process in the pre-experimental preparation of the tissue which may result in tissue damage and reduced viability of the segment. In this study, the viability of stripped and native (non-stripped) rat small intestine tissue segments mounted in Ussing chambers was monitored and the apparent permeability of the tissue to a set of test compounds across both tissue preparations was determined. Electrical measurements, in particular the potential difference (PD) across the intestinal membrane, were used to evaluate the viability. In this study, there were no differences in initial PD (health status of the tissue) or PD over time (viability throughout the experiment) between native and stripped rat jejunum segments. Overall, there were also no significant differences in permeability between stripped and native rat intestinal tissue for the compounds in this study. Based on these results, we propose that stripping can be excluded from the preparation procedures for rat jejunal tissue for permeability studies when using the Ussing chamber technique. PMID:27073083

  7. Exercise training decreases gene expression of endo- and xeno-sensors in rat small intestine.

    PubMed

    Ngo Sock, Emilienne Tudor; Farahnak, Zahra; Lavoie, Jean-Marc

    2014-10-01

    The purpose of the study was to test the hypothesis that gene expression of members of the nuclear receptor (NR) superfamily known to act as endo- and xeno-sensors is reduced in the ileum of exercise-trained (Tr) rats. Healthy female rats were either treadmill-trained for 8 weeks, 5 times/week, or remained sedentary (Sed). Training resulted in a significant (p < 0.05) decrease in plasma free fatty acid (0.18 ± 0.01 to 0.15 ± 0.01 mmol/L) and glycerol (24.8 ± 0.8 to 18.7 ± 0.8 mg/L) concentrations. Gene expressions of NRs farnesoid X receptor (FXR; p < 0.05), liver X receptor (LXR; p < 0.05), pregnane X receptor (PXR; p < 0.01), and retinoid X receptor (RXR; p < 0.06) were reduced in the ileum of Tr compared with Sed animals. Tr was also associated with a reduction (p < 0.05) in gene expression of FXR downstream heterodimeric organite solute transporters α (OSTα) and β (OSTβ) involved in the transport of bile acids, LXR downstream genes heterodimeric ATP-binding cassette transporters (ABCG5/G8) involved in transport of absorbed cholesterol back to the lumen, and Niemann-Pick C1-like 1 (NPC1L1) involved in cholesterol absorption. These data indicate that exercise training lowers the expression of molecules involved in the defense system of the ileum against endobiotic and xenobiotic insults under normal conditions, thus, suggesting that regular exercise contributes to the intestinal maintenance of cholesterol and bile acid homeostasis. PMID:24933213

  8. How Is Small Intestine Adenocarcinoma Staged?

    MedlinePlus

    ... small intestine adenocarcinoma, by stage How is small intestine adenocarcinoma staged? Staging is a process that tells ... distant m etastasis (M). T categories for small intestine adenocarcinoma T categories of small intestine cancer describe ...

  9. The transmission of -125-I-labelled immunoglobulin G by proximal and distal regions of the small intestine of 16-day-old rats.

    PubMed Central

    Morris, B

    1975-01-01

    1. Standard doses of -125-I-labelled rat IgG were injected into the intestinal lumen of rats aged 16 days, and their sera were sampled 2 and 3 hr later. High concentration quotients were obtained after injection into the proximal small intestime, whereas very little immunoglobulin was transmitted from doses injected into the terminal 20 cm of the small intestine. 2. The villi of the terminal 18--20 cm of the small intestine of 16-day-old rats, the region from which very little transmission of IgG occurred, were lined by tall columnar absorptive cells with very larg supra-nuclear vacuoles. The extent of the terminal intestine, in which this cell type predominated in the absorptive epithelium, varied with age. The importance of defining the precise location of the region of the intestine under examination is stressed. 3. The experimental results and the histological observations are discussed in relation to (a) the results which have been obtained using PVP, which is unsuitable as an indicator of immunoglobulin transport in the rat and (b) the histological composition of the absorptive epithelium and the maturation changes which affect the epithelium between 18 and 21 days. Images A B C D PMID:1127610

  10. Absorption from a mixture of seventeen free amino acids by the isolated small intestine of the rat.

    PubMed Central

    Gardner, M L

    1976-01-01

    Absorption and secretion from a mixture of seventeen free amino acids has been measured in isolated perfused rat small intestine. 2. The absorption rate of an amino acid from this mixture is proportional to its concentration in the perfusate and independent of its chemical constitution. The constant of proportionality is the same as that previously observed when the perfusate contained peptides as well as amino acids. 3. Amino acids are concentrated, on average, sixfold during passage across the mucosa, and the free amino acid composition of the secretion into the tissue fluid is very similar to that of the luminal perfusate. 4. Peptides do not appear to be added to the tissue fluid during absorption of free amino acids. 5. It is concluded that the mechanisms for absorption of free amino acids are in general independent of those for absorption of peptides. PMID:1255532

  11. Effects of lactadherin on plasma D-lactic acid and small intestinal MUC2 and claudin-1 expression levels in rats with rotavirus-induced diarrhea

    PubMed Central

    XU, RUI; LEI, YI-HUI; SHI, JUN; ZHOU, YI-JUN; CHEN, YING-WEI; HE, ZHEN-JUAN

    2016-01-01

    The aim of the present study was to investigate the effects of lactadherin on plasma D-lactic acid and small intestinal mucin (MUC) 2 and claudin-1 expression levels in rats with diarrhea induced by rotavirus (RV) infection. A total of 75 seven-day-old healthy Sprague-Dawley rats were randomly divided into the following five groups: Control (C), RV infection (RVI), lactadherin before rotavirus infection (LBRI), lactadherin after rotavirus infection (LARI), and blank (B). On day 4 of artificial feeding, the rats in groups RVI, LBRI and LARI were intragastric administered 1×106 PFU RV; whereas the rats in groups C and B were intragastrically administered an equal volume of maintenance solution from the RV supernatant and normal saline, respectively. In the LBRI and LARI groups, rats received daily intragastric administration of 0.25 mg lactadherin for three days prior to and following infection with RV, respectively. The course of diarrheal symptoms was observed in each group and samples were collected on days 1, 4, and 7 post-infection in order to determine the mucosal morphology, plasma D-lactic acid levels and the expression levels of MUC2 and the intracellular junction protein, claudin-1, in the small intestine. On day 4 post-infection, the rats in group RVI demonstrated severely damaged small intestines and typical diarrheal characteristics, as detected by light microscopy; whereas rats in groups LBRI and LARI demonstrated intact small intestinal villi with partial vacuolation of epithelial cells and changes in the position of their nuclei. Electron microscopy demonstrated that the rats in the RVI group had sparse, shortened, disordered intestinal microvilli and widened intercellular junctions; whereas those in groups LBRI and LARI had long intestinal microvilli sparser compared with groups B and C and slightly widened intercellular junctions. Plasma D-lactic acid levels were increased in groups RVI, LBRI and LARI, as compared with groups B and C, and the

  12. Study on the small intestine absorptive kinetics characters of tanshinol and protocatechualdehyde of Salvia miltiorrhiza extracts in rats in vivo.

    PubMed

    Liang, Kai; Zhai, Shuiting; Zhang, Zhidong; Wang, Guoquan; Fu, Xiaoyang; Li, Tianxiao

    2016-07-01

    In order to provide scientific basis for clinical selection of drugs, to compare and analyze the effective constitutes and the intestinal absorption in vivo in rats of the compound salvia tablets and compound salvia dropping pills (taken as the representatives). Determine the contents of tanshinol, protocatechuic aldehyde, salvianolic acid B and tanshinone II A, cryptotanshinone, ginseng saponin Rg1 and Rb1 in the compound salvia tablets and compound salvia dropping pills by High Performance Liquid Chromatography (HPLC). The intestinal absorption condition of the tanshinol, protocatechuic aldehyde, salvianolic acid B of the compound salvia tablets and compound salvia dropping pills in rats were detected by intestinal perfusion experiment. Only the intake of protocatechuic aldehyde in the compound salvia tablets was higher than in the compound dropping pills, the intake of the other 6 effective constitutes were all lower than in the compound dropping pills. The intestinal absorption of protocatechuic aldehyde was rather complete, while the intestinal absorption of tanshinol and salvianolic acid B were not significant. The duodenum was the main absorption region of these three components. The absorption of protocatechuic aldehyde was different in different regions of the intestines. Each intake of the effective constitutes in the tablets and dropping pills were significantly different, and the rat intestinal absorption of part of the components were different. PMID:27592492

  13. Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line

    PubMed Central

    Han, Yueqin; Zhu, Yanping; Wang, Jinshen; Han, Yanqin; Qin, Daogang; Yang, Qiaozhi; Sun, Xiaojing; Chen, Lijun

    2016-01-01

    Objective(s): To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. Materials and Methods: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. Results: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. Conclusion: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia[PARANDCO1].

  14. Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine

    PubMed Central

    Kaneko, Atsushi; Omiya, Yuji; Ohbuchi, Katsuya; Ohno, Nagisa; Yamamoto, Masahiro

    2013-01-01

    The functional roles of transient receptor potential (TRP) channels in the gastrointestinal tract have garnered considerable attention in recent years. We previously reported that daikenchuto (TU-100), a traditional Japanese herbal medicine, increased intestinal blood flow (IBF) via adrenomedullin (ADM) release from intestinal epithelial (IE) cells (Kono T et al. J Crohns Colitis 4: 161–170, 2010). TU-100 contains multiple TRP activators. In the present study, therefore, we examined the involvement of TRP channels in the ADM-mediated vasodilatatory effect of TU-100. Rats were treated intraduodenally with the TRP vanilloid type 1 (TRPV1) agonist capsaicin (CAP), the TRP ankyrin 1 (TRPA1) agonist allyl-isothiocyanate (AITC), or TU-100, and jejunum IBF was evaluated using laser-Doppler blood flowmetry. All three compounds resulted in vasodilatation, and the vasodilatory effect of TU-100 was abolished by a TRPA1 antagonist but not by a TRPV1 antagonist. Vasodilatation induced by AITC and TU-100 was abrogated by anti-ADM antibody treatment. RT-PCR and flow cytometry revealed that an IEC-6 cell line originated from the small intestine and purified IE cells expressed ADM and TRPA1 but not TRPV1. AITC increased ADM release in IEC cells remarkably, while CAP had no effect. TU-100 and its ingredient 6-shogaol (6SG) increased ADM release dose-dependently, and the effects were abrogated by a TRPA1 antagonist. 6SG showed similar TRPA1-dependent vasodilatation in vivo. These results indicate that TRPA1 in IE cells may play an important role in controlling bowel microcirculation via ADM release. Epithelial TRPA1 appears to be a promising target for the development of novel strategies for the treatment of various gastrointestinal disorders. PMID:23275609

  15. Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat.

    PubMed

    McGinn, B J; Morrison, J D

    2016-06-28

    Experiments have been undertaken to determine the extent to which cholic acid conjugates of insulin were absorbed from the small intestine of anaesthetised rats by means of the bile salt transporters of the ileum. The measure used to assess the absorption of the cholyl-insulins was the amount of hypoglycaemia following infusion into the small intestine. Control experiments involving infusion of natural insulin into the ileum showed either nil absorption or absorption of a small amount of insulin as indicated by transient dip in the blood glucose concentration. However, when insulin was co-infused with the bile salt taurocholate, this was followed by a marked hypoglycaemic response which was specific to the ileum and did not occur on infusion into the jejunum. When the two cholyl conjugates of insulin were tested viz. B(29)-Lys-cholyl-insulin and B(1)-Phe-cholyl-insulin, both were biologically active as indicated by hypoglycaemic responses on systemic injection, though their potency was about 40% of that of natural insulin. While there was no evidence for the absorption of B(29)-Lys-cholyl-insulin when infused into the ileum, B(1)-Phe-cholyl-insulin did cause a long lasting hypoglycaemic response, indicating that absorption had occurred. Since the hypoglycaemic response was blocked on co-infusion with taurocholate and was absent for infusion of the conjugate into the jejunum, these results were taken as evidence that B(1)-Phe-cholyl-insulin had been taken up by the ileal bile salt transporters. This would indicate that B(1)-Phe-cholyl-insulin is worthy of further investigation for use in an oral insulin formulation. PMID:27084488

  16. Role of activation of cholinergic influences in recovery of electrical activity of the stomach and small intestine during the early postoperative period in rats.

    PubMed

    Tropskaya, N S; Solov'yova, G I; Popova, T S

    2007-02-01

    The effects of neostigmine and calcium pantothenate on electrical activity of the stomach and small intestine were studied in chronic experiments on rats after laparotomy with implantation of a probe into the jejunum and electrodes into different portions of the gastrointestinal tract. At the early terms after surgery, stimulation of endogenous acetylcholine release intensified electrical activity of the stomach, duodenum, and jejunum. Treatment with neostigmine and calcium pantothenate did not accelerate the recovery of the migrating myoelectrical complex, but promoted the recovery of the general intensity of action potential generation in the stomach and small intestine. PMID:17970199

  17. Protein and lipid refeeding changes protein metabolism and colonic but not small intestinal morphology in protein-depleted rats.

    PubMed

    Qu, Z; Ling, P R; Tahan, S R; Sierra, P; Onderdonk, A B; Bistrian, B R

    1996-04-01

    In this study, we fed rats a 2% casein AIN 76 diet for 2 wk to produce protein malnutrition. We determined in these animals the effects of different concentrations of dietary protein refeeding (2% and 20% casein) on recovery and gut mucosal repletion and the potential role of type of dietary fat in the regulation of protein metabolism and mucosal growth by providing conventional long-chain triglyceride (LCT), a structured lipid composed of long-, medium- and short-chain fatty acids (SC/SL), or a physical mixture of the same components present in the structured lipid given as individual pure triglycerides (SC/PM) along with adequate amounts of protein and energy. The results confirmed that protein malnutrition can be reversed rapidly by protein refeeding, as indicated by an increase in body weight, positive nitrogen balance, liver growth and elevations in plasma concentrations of insulin-like growth factor-1, leucine and albumin. In the colon, crypt cell number, crypt depth and number of crypt cells in the rapidly proliferating fraction of the colon were greater in rats fed the higher protein diet. However, the general architecture of small intestinal mucosa, including duodenum, jejunum and ileum, was not affected by protein malnutrition. Although the number of colonic cells was similar with fat refeeding, there were significantly fewer displaying the proliferating cell nuclear antigen in the colonic epithelium when rats were fed SC/PM compared with SC/SL. Therefore, changes in colonic mucosal proliferation were only seen with repletion by adequate protein and by SC/SL feeding. PMID:8613894

  18. Pancreatoduodenectomy as a source of human small intestine for Ussing chamber investigations and comparative studies with rat tissue.

    PubMed

    Haslam, Iain S; O'Reilly, Derek A; Sherlock, David J; Kauser, Ambareen; Womack, Chris; Coleman, Tanya

    2011-05-01

    A clear understanding of oral drug absorption is an important aspect of the drug development process. The permeability of drug compounds across intact sections of small intestine from numerous species, including man, has often been investigated using modified Ussing chambers. The maintenance of viable, intact tissue is critical to the success of this technique. This study therefore aimed to assess the viability and integrity of tissue from patients undergoing pancreatoduodenectomy, for use in cross-species Ussing chamber studies. Electrical parameters (potential difference, mV; short-circuit current, µA.cm(-2) ; resistance, Ω.cm(2) ) were monitored over the duration of each experiment, as was the permeability of the paracellular marker atenolol. The permeability values (Papp; cm/s × 10(-6) ) for a training-set of compounds, displaying a broad range of physicochemical properties and known human fraction absorbed values, were determined in both rat and human jejunum, as well as Caco-2 cell monolayers. The results indicate that human jejunum sourced from pancreatoduodenectomy remained viable and intact for the duration of experiments. Permeability values generated in rat and human jejunum correlate well (R(2) = 0.86), however the relationship between permeability in human tissue and Caco-2 cells was comparatively weak (R(2) = 0.58). Relating permeability to known human fraction absorbed (hFabs) values results in a remarkably similar relationship to both rat and human jejunum Papp values. It can be concluded that human jejunum sourced from pancreatoduodenectomy is a suitable source of tissue for Ussing chamber permeability investigations. The relationship between permeability and hFabs is comparable to results reported using alternative test compounds. PMID:21416475

  19. Emu Oil Reduces Small Intestinal Inflammation in the Absence of Clinical Improvement in a Rat Model of Indomethacin-Induced Enteropathy

    PubMed Central

    Abimosleh, Suzanne M.; Tran, Cuong D.; Howarth, Gordon S.

    2013-01-01

    Nonsteroidal-anti-inflammatory-drug (NSAID) enteropathy is characterized by small intestinal damage and ulceration. Emu Oil (EO) has previously been reported to reduce intestinal inflammation. Aim. We investigated EO for its potential to attenuate NSAID-enteropathy in rats. Methods. Male Sprague Dawley rats (n = 10/group) were gavaged with Water, Olive Oil (OO), or EO (0.5 mL; days 0–12) and with 0.5 mL Water or the NSAID, Indomethacin (8 mg/kg; days 5–12) daily. Disease activity index (DAI), 13C-sucrose breath test (SBT), organ weights, intestinal damage severity (IDS), and myeloperoxidase (MPO) activity were assessed. P < 0.05 was considered significant. Results. In Indomethacin-treated rats, DAI was elevated (days 10–12) and SBT values (56%) and thymus weight (55%) were decreased, relative to normal controls. Indomethacin increased duodenum (68%), colon (24%), SI (48%), caecum (48%), liver (51%) and spleen (88%) weights, IDS scores, and MPO levels (jejunum: 195%, ileum: 104%) compared to normal controls. Jejunal MPO levels were decreased (64%) by both EO and OO, although only EO decreased ileal MPO (50%), compared to Indomethacin controls. Conclusions. EO reduced acute intestinal inflammation, whereas other parameters of Indomethacin-induced intestinal injury were not affected significantly. Increased EO dose and/or frequency of administration could potentially improve clinical efficacy. PMID:23573127

  20. Specific responses in rat small intestinal epithelial mRNA expression and protein levels during chemotherapeutic damage and regeneration.

    PubMed

    Verburg, Melissa; Renes, Ingrid B; Van Nispen, Danielle J P M; Ferdinandusse, Sacha; Jorritsma, Marieke; Büller, Hans A; Einerhand, Alexandra W C; Dekker, Jan

    2002-11-01

    The rapidly dividing small intestinal epithelium is very sensitive to the cytostatic drug methotrexate. We investigated the regulation of epithelial gene expression in rat jejunum during methotrexate-induced damage and regeneration. Ten differentiation markers were localized on tissue sections and quantified at mRNA and protein levels relative to control levels. We analyzed correlations in temporal expression patterns between markers. mRNA expression of enterocyte and goblet cell markers decreased significantly during damage for a specific period. Of these, sucrase-isomaltase (-62%) and CPS (-82%) were correlated. Correlations were also found between lactase (-76%) and SGLT1 (-77%) and between I-FABP (-52%) and L-FABP (-45%). Decreases in GLUT5 (-53%), MUC2 (-43%), and TFF3 (-54%) mRNAs occurred independently of any of the other markers. In contrast, lysozyme mRNA present in Paneth cells increased (+76%). At the protein level, qualitative and quantitative changes were in agreement with mRNA expression, except for Muc2 (+115%) and TFF3 (+81%), which increased significantly during damage, following independent patterns. During regeneration, expression of each marker returned to control levels. The enhanced expression of cytoprotective molecules (Muc2, TFF3, lysozyme) during damage represents maintenance of goblet cell and Paneth cell functions, most likely to protect the epithelium. Decreased expression of enterocyte-specific markers represents decreased enterocyte function, of which fatty acid transporters were least affected. PMID:12417619

  1. The binding of proteins to isolated enterocytes from the small intestine of the neonatal rat.

    PubMed Central

    Mackenzie, N M; Morris, B; Morris, R

    1983-01-01

    IgG binds specifically to isolated jejunal enterocytes but not to ileal enterocytes; maximum binding occurred at pH 6. The ability of jejunal enterocytes to bind IgG was reduced to low levels at 20 days of age and was lost at 24 days. Human and rat IgG were bound specifically in similar amounts; human IgG displaced rat IgG with identical efficiency to rat IgG (ED50 = 50 nM). Much less bovine and sheep IgG were bound to enterocytes and the ED50s for these proteins were 150 nM and 2.5 microM, respectively. Rat IgG bound to jejunal enterocytes with high affinity (13.21 x 10(6)M-1) and to 4.83 x 10(6) sites per cell. Receptor protein was estimated to represent 0.18% of total cell protein. These observations are discussed in relation to the results of in vivo IgG transmission studies. It is estimated that the IgG transport mechanism, operating at maximum efficiency, requires that available IgG receptors would come into use once to twice per hour. PMID:6219063

  2. Comparative toxicogenomic analysis of oral Cr(VI) exposure effects in rat and mouse small intestinal epithelia

    SciTech Connect

    Kopec, Anna K.; Thompson, Chad M.; Kim, Suntae; Forgacs, Agnes L.; Zacharewski, Timothy R.

    2012-07-15

    Continuous exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water results in intestinal tumors in mice but not rats. Concentration-dependent gene expression effects were evaluated in female F344 rat duodenal and jejunal epithelia following 7 and 90 days of exposure to 0.3–520 mg/L (as sodium dichromate dihydrate, SDD) in drinking water. Whole-genome microarrays identified 3269 and 1815 duodenal, and 4557 and 1534 jejunal differentially expressed genes at 8 and 91 days, respectively, with significant overlaps between the intestinal segments. Functional annotation identified gene expression changes associated with oxidative stress, cell cycle, cell death, and immune response that were consistent with reported changes in redox status and histopathology. Comparative analysis with B6C3F1 mouse data from a similarly designed study identified 2790 differentially expressed rat orthologs in the duodenum compared to 5013 mouse orthologs at day 8, and only 1504 rat and 3484 mouse orthologs at day 91. Automated dose–response modeling resulted in similar median EC{sub 50}s in the rodent duodenal and jejunal mucosae. Comparative examination of differentially expressed genes also identified divergently regulated orthologs. Comparable numbers of differentially expressed genes were observed at equivalent Cr concentrations (μg Cr/g duodenum). However, mice accumulated higher Cr levels than rats at ≥ 170 mg/L SDD, resulting in a ∼ 2-fold increase in the number of differentially expressed genes. These qualitative and quantitative differences in differential gene expression, which correlate with differences in tissue dose, likely contribute to the disparate intestinal tumor outcomes. -- Highlights: ► Cr(VI) elicits dose-dependent changes in gene expression in rat intestine. ► Cr(VI) elicits less differential gene expression in rats compared to mice. ► Cr(VI) gene expression can be phenotypically anchored to intestinal changes. ► Species

  3. Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats

    PubMed Central

    2010-01-01

    Background An increase in the intestinal permeability is considered to be associated with the inflammatory tone and development in the obesity and diabetes, however, the pathogenesis of the increase in the intestinal permeability is poorly understood. The present study was performed to determine the influence of obesity itself as well as dietary fat on the increase in intestinal permeability. Methods An obese rat strain, Otsuka Long Evans Tokushima Fatty (OLETF), and the lean counter strain, Long Evans Tokushima Otsuka (LETO), were fed standard or high fat diets for 16 weeks. Glucose tolerance, intestinal permeability, intestinal tight junction (TJ) proteins expression, plasma bile acids concentration were evaluated. In addition, the effects of rat bile juice and dietary fat, possible mediators of the increase in the intestinal permeability in the obesity, on TJ permeability were explored in human intestinal Caco-2 cells. Results The OLETF rats showed higher glucose intolerance than did the LETO rats, which became more marked with the prolonged feeding of the high fat diet. Intestinal permeability in the OLETF rats evaluated by the urinary excretion of intestinal permeability markers (Cr-EDTA and phenolsulfonphthalein) was comparable to that in the LETO rats. Feeding the high fat diet increased intestinal permeability in both the OLETF and LETO rats, and the increases correlated with decreases in TJ proteins (claudin-1, claudin-3, occludin and junctional adhesion molecule-1) expression in the small, but not in the large intestine (cecum or colon). The plasma bile acids concentration was higher in rats fed the high fat diet. Exposure to bile juice and the fat emulsion increased TJ permeability with concomitant reductions in TJ protein expression (claudin-1, claudin-3, and junctional adhesion molecule-1) in the Caco-2 cell monolayers. Conclusion Excessive dietary fat and/or increased levels of luminal bile juice, but not genetic obesity, are responsible for the

  4. Region-Dependent Role of Cell-Penetrating Peptides in Insulin Absorption Across the Rat Small Intestinal Membrane.

    PubMed

    Khafagy, El-Sayed; Iwamae, Ruisha; Kamei, Noriyasu; Takeda-Morishita, Mariko

    2015-11-01

    We have reported that the cell-penetrating peptide (CPP) penetratin acts as a potential absorption enhancer in oral insulin delivery systems and that this action occurs through noncovalent intermolecular interactions. However, the region-dependent role of CPPs in intestinal insulin absorption has not been clarified. To identify the intestinal region where CPPs have the most effect in increasing insulin absorption, the region-dependent action of penetratin was investigated using in situ closed intestinal loops in rats. The order of the insulin area under the insulin concentration-time curve (AUC) increase effect by L-penetratin was ileum > jejunum > duodenum > colon. By contrast, the AUC order after coadministration of insulin with D-penetratin was colon > duodenum ≥ jejunum and ileum. We also compared the effects of the L- and D-forms of penetratin, R8, and PenetraMax on ileal insulin absorption. Along with the CPPs used in this study, L- and D-PenetraMax produced the largest insulin AUCs. An absorption study using ilea pretreated with CPPs showed that PenetraMax had no irreversible effect on the intestinal epithelial membrane. The degradation of insulin in the presence of CPPs was assessed in rat intestinal enzymatic fluid. The half-life (t 1/2) of insulin increased from 14.5 to 23.7 and 184.7 min in the presence of L- and D-PenetraMax, respectively. These enzymatic degradation-resistant effects might contribute partly to the increased ileal absorption of insulin induced by D-PenetraMax. In conclusion, this study demonstrated that the ability of the L- and D-forms of penetratin to increase intestinal insulin absorption was maximal in the ileum and the colon, respectively, and that D-PenetraMax is a powerful but transient enhancer of oral insulin absorption. PMID:26216471

  5. Pituitary regulation of postnatal small intestinal ontogeny in the rat: differential regulation of digestive hydrolase maturation by thyroxine and growth hormone.

    PubMed

    Castillo, R O; Glasscock, G F; Noren, K M; Reisenauer, A M

    1991-09-01

    During the third week of postnatal life, dramatic ontogenic changes occur in the morphology and enzymology of the small intestine of the infant rat, enabling the animal to make the transition from milk to solid food. To investigate the roles of T4 and GH in regulation of these changes, infant rats were hypophysectomized on day 6 of life by the transauricular technique. Hypophysectomy resulted in diminution of somatic and intestinal growth as well as abnormal maturation of the disaccharidases lactase, sucrase, and maltase when measured on day 25. Administration of either T4 or GH to hypophysectomized animals resulted in moderately increased intestinal growth, while complete restoration of small intestinal growth resulted from administration of the combination of both hormones. Although T4, GH, or the combination of hormones reduced lactase activities, T4 alone produced normal maturation of sucrase and maltase. Neither hypophysectomy nor hormone replacement affected aminooligopeptidase. The molecular structure of lactase, analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was not altered to a major degree in hypophysectomized animals or animals that received hormone replacement, but minor alterations were evident in sucrase structure in hypophysectomy. These studies indicate that 1) T4 and GH actively participate in postnatal regulation of small intestinal ontogeny; 2) thyroid hormones act directly on developing intestinal tissues to independently produce the normal maturation of the disaccharidases by mechanisms that are not likely to involve alterations in processing of the enzyme-protein; and 3) maturation of aminooligopeptidase is not regulated by pituitary hormones, in distinct contrast to the disaccharidases. PMID:1874180

  6. Changes in Enteric Neurons of Small Intestine in a Rat Model of Irritable Bowel Syndrome with Diarrhea

    PubMed Central

    Li, Shan; Fei, Guijun; Fang, Xiucai; Yang, Xilin; Sun, Xiaohong; Qian, Jiaming; Wood, Jackie D; Ke, Meiyun

    2016-01-01

    Background/Aims Physical and/or emotional stresses are important factors in the exacerbation of symptoms in irritable bowel syndrome (IBS). Several lines of evidence support that a major impact of stress on the gastrointestinal tract occurs via the enteric nervous system. We aimed to evaluate histological changes in the submucosal plexus (SMP) and myenteric plexus (MP) of the distal ileum in concert with the intestinal motor function in a rat model of IBS with diarrhea. Methods The rat model was induced by heterotypic chronic and acute stress (CAS). The intestinal transit was measured by administering powdered carbon by gastric gavage. Double immunohistochemical fluorescence staining with whole-mount preparations of SMP and MP of enteric nervous system was used to assess changes in expression of choline acetyltransferase, vasoactive intestinal peptide, or nitric oxide synthase in relation to the pan neuronal marker, anti-Hu. Results The intestinal transit ratio increased significantly from control values of 50.8% to 60.6% in the CAS group. The numbers of enteric ganglia and neurons in the SMP were increased in the CAS group. The proportions of choline acetyltransferase- and vasoactive intestinal peptide-immunoreactive neurons in the SMP were increased (82.1 ± 4.3% vs. 76.0 ± 5.0%, P = 0.021; 40.5 ± 5.9% vs 28.9 ± 3.7%, P = 0.001), while nitric oxide synthase-immunoreactive neurons in the MP were decreased compared with controls (23.3 ± 4.5% vs 32.4 ± 4.5%, P = 0.002). Conclusions These morphological changes in enteric neurons to CAS might contribute to the dysfunction in motility and secretion in IBS with diarrhea. PMID:26645247

  7. The digestion and transmission of labelled immunoglobulin G by enterocytes of the proximal distal regions of the small intestine of young rats.

    PubMed Central

    Morris, B; Morris, R

    1977-01-01

    Density gradient centrifugation of samples prepared from proximal gut homogenates after intra-lumenal injection of 125I-labelled IgG, was used to prepare batches of IgG fragments according to sedimentation coefficients. 2. Ultrafiltration was employed to partition the radioactivity in the vascular compartments, viscera and carcasses of rats aged 14-15 days, 2 hr after the injection of standard doses of labelled IgG into the proximal and distal regions of the small intestine. 3. Radioactive samples prepared by these methods were re-introduced into young rats by intra-cardiac injection, and the rate at which they were removed from the vascular compartment was assessed. 4. Proximal enterocytes transmitted about 39% of the IgG which had been removed from the intestine in intact form. Most of this was retained in the vascular compartment; they degraded up to about 57% of the total removed into fragments less than 1000 mol. wt. and about 4% into intermediate sized fragments. 5. Distal enterocytes degraded almost 90% of the IgG processed into fragments less than 1000 mol. wt., about 8% as fragments greater than 100,000 mol. wt. 6. Fragments, of all sizes, were cleared rapidly from the circulation into the viscera and carcass. 7. The relevance of these results to protein transmission and digestion by the rat small intestine is discussed. PMID:599447

  8. Inhibitory effects of extractives from leaves of Morus alba on human and rat small intestinal disaccharidase activity.

    PubMed

    Oku, Tsuneyuki; Yamada, Mai; Nakamura, Mariko; Sadamori, Naoki; Nakamura, Sadako

    2006-05-01

    The inhibitory effect on human and rat intestinal disaccharidase by the extractive from the leaves of Morus alba (ELM) containing 0.24 % 1-deoxynojirimycin equivalent and its inhibitory activities were investigated by the modified Dahlqvist method. In the presence of 1000-fold diluted ELM solution, the sucrase activity of four human samples was inhibited by 96 % and that of maltase and isomaltase by 95 and 99 %, respectively. The activities of trehalase and lactase were inhibited by 44 and 38 %, respectively. The human disaccharidase activities varied from sample to sample because the samples were obtained from different resected regions after surgery. However, the ratio of the inhibitory effect for sucrase, maltase, isomaltase, trehalase and lactase was very similar among the four samples, and also that of resembled rat intestinal disaccharides. The inhibitory constant of the 1-deoxynojirimycin equivalent for sucrase, maltase and isomaltase was 2.1 x 10(-4), 2.5 x 10(-4) and 4.5 x 10(-4) mm, respectively, and these inhibitory activities were shown, using rat brush border membrane vesicles, to be competitive. These results demonstrate that digestion is inhibited when an appropriate amount of ELM is orally ingested with sucrose or polysaccharide in man. When ELM was orally administered in a sucrose solution to fasted rats, the elevation in blood glucose was significantly suppressed, depending on the concentration of ELM given. These results suggest that ELM could be used as an ingredient in health foods and in foods that help to prevent diabetes. PMID:16611383

  9. Absorption of amino acids and peptides from a complex mixture in the isolated small intestine of the rat.

    PubMed Central

    Gardner, M L

    1975-01-01

    Amino acid and peptide absorption from a pancreatic digest of casein at low concentration by an isolated preparation of perfused rat small intestine has been measured. 2. The rate of absorption of each amino acid (free or peptide-bound) is closely proportional to its concentration in the perfusate; this implies a constant Vmax/Km ration for all amino acids in the mixture. 3. There is a high correlation between the compositions of luminal perfusate and secretion into the tissue fluid (apart from the content of glutamic and aspartic acids and alanine). 4. The concentrations of each free amino acid are, on average, 9 times as great in secretion as in lumen; the total peptide-N concentration in secretion is approximately 4 times that in the lumen. 5. The rate of absorption of each free amino acid is highly negatively dependent on the rate of absorption of that amino acid in peptide-bound form, in addition to being positively dependent on the perfusate concentration of free amino acid. 6. While peptide-bound proline appears to be well absorbed, free proline liberated by hydrolysis appears to pass back into the lumen as well as into the tissue fluid. Substantial back flux of hydrolysis products may occur for all amino acids. 7. About one-third of the amino acids appearing in the secretion on the serosal surface are peptide-bound. 8. The rate of absorption of peptides appears to determine the rate of their hydrolysis which probably occurs mainly after entry into the mucosal cells. PMID:1204629

  10. Small intestinal bacterial overgrowth syndrome

    PubMed Central

    Bures, Jan; Cyrany, Jiri; Kohoutova, Darina; Förstl, Miroslav; Rejchrt, Stanislav; Kvetina, Jaroslav; Vorisek, Viktor; Kopacova, Marcela

    2010-01-01

    Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO. PMID:20572300

  11. Sonography of the small intestine

    PubMed Central

    Nylund, Kim; Ødegaard, Svein; Hausken, Trygve; Folvik, Geir; Lied, Gülen Arslan; Viola, Ivan; Hauser, Helwig; Gilja, Odd-Helge

    2009-01-01

    In the last two decades, there has been substantial development in the diagnostic possibilities for examining the small intestine. Compared with computerized tomography, magnetic resonance imaging, capsule endoscopy and double-balloon endoscopy, ultrasonography has the advantage of being cheap, portable, flexible and user- and patient-friendly, while at the same time providing the clinician with image data of high temporal and spatial resolution. The method has limitations with penetration in obesity and with intestinal air impairing image quality. The flexibility ultrasonography offers the examiner also implies that a systematic approach during scanning is needed. This paper reviews the basic scanning techniques and new modalities such as contrast-enhanced ultrasound, elastography, strain rate imaging, hydrosonography, allergosonography, endoscopic sonography and nutritional imaging, and the literature on disease-specific findings in the small intestine. Some of these methods have shown clinical benefit, while others are under research and development to establish their role in the diagnostic repertoire. However, along with improved overall image quality of new ultrasound scanners, these methods have enabled more anatomical and physiological changes in the small intestine to be observed. Accordingly, ultrasound of the small intestine is an attractive clinical tool to study patients with a range of diseases. PMID:19294761

  12. Stages of Small Intestine Cancer

    MedlinePlus

    ... small intestine cancer include unexplained weight loss and abdominal pain. These and other signs and symptoms may be ... doctor if you have any of the following: Pain or cramps in the middle of the abdomen. Weight loss with no known reason. A lump ...

  13. [The functional state of the mitochondrial respiratory chain of the small intestine enterocytes of the rats under the low dose rate X-ray total external exposure].

    PubMed

    2013-01-01

    The influence of the low-rate ionizing radiation (0.055 Gy/min) at the doses of 0.1; 0.5 and 1.0 Gy on the functional state of the mitochondria respiratory chain of the rat small intestine enterocytes was investigated. The dysfunction of the electron transport chain enzymes andchanges in the content of cytochromes b, c, a in themitochondrial inner membrane were revealed 1, 12 and 24 hours after exposure to radiation. The re- vealed disorders indicate early membrane sensitivity to the radiation effect. The inhibition of the H+ -ATPase activity in the studied dose range indicates the decrease of the mitochondrial energy capacity. PMID:25508872

  14. The effects of corticosterone and cortisone on the uptake of polyvinyl pyrrolidone and the transmission of immunoglobulin G by the small intestine in young rats.

    PubMed Central

    Morris, B; Morris, R

    1976-01-01

    1. The distribution of polyvinyl pyrrolidone along the intestinal lumen and in the intestinal wall, following oral administration to normal and corticosterone treated rats, was found to be extremely variable. Valid comparisons between the two groups of animals could not be made using this technique. 2. Three, 4 and 5 days after corticosterone treatment there was no significant change in the uptake of 125I-labelled polyvinyl pyrrolidone from standard doses injected into ligated segments of the distal small intestine; nor did the treatment induce precocious replacement of the absorptive cells in this region. Cortisone induced precocious cell replacement, a process which took up to 4 days to complete, and also led to a marked reduction in the uptake of 125I-labelled polyvinyl pyrrolidone from ligated segments of the distal intestine. 3. Three days after treatment with corticosterone (5 mg I.P. at 12 days) there was a marked reduction of labelled immunoglobulin G transport into the blood. Four and 5 days after treatment there was some recovery of the immunoglobulin G transport function. Three days after treatment with cortisone (5 mg I.P. at 12 days) there was closure of the gut to labelled immunoglobulin G. 4. The relevance of these results to antibody transmission and the termination of immunoglobulin transport is discussed. PMID:1249782

  15. General Information about Small Intestine Cancer

    MedlinePlus

    ... Small Intestine Cancer Treatment (PDQ®)–Patient Version General Information About Small Intestine Cancer Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  16. Extrusion decreases the negative effects of kidney bean on enzyme and transport activities of the rat small intestine.

    PubMed

    Marzo, F; Milagro, F I; Urdaneta, E; Barrenetxe, J; Ibañez, F C

    2011-10-01

    The objective of the present study was to evaluate the influence of raw and extruded kidney bean (Phaseolus vulgaris L. var. Pinto) consumption on the gut physiology of young growing rats. The intestinal enzyme activity (sucrase, maltase, Na(+) /K(+) ATPase, aminopeptidase N, dipeptidylpeptidase IV, alkaline phosphatase) and the uptake of sugar (d-galactose) and amino acids (l-leucine) were measured in brush border membrane vesicles. Five groups of growing male Wistar rats were fed ad libitum for 15 days on five different 10% protein diets: one containing casein as the main source of protein (Control, C), and four containing raw (RKB1, RKB6) or extruded kidney bean (EKB1, EKB6) at 1% and 6% of total protein content respectively. Extrusion treatment significantly reduced the content of bioactive factors (phytates, tannins) and abolished lectins, trypsin, chymotrypsin, and α-amylase inhibitory activities. Rats fed raw beans (especially RKB6) showed lower growth rate and food intake as compared to those fed extruded legumes, probably due to the high levels of lectins and other anti-nutritive factors in the raw beans. Gut enzymatic activities and uptake of d-galactose and l-leucine were lower in RKB6 and RKB1-fed animals, although they significantly improved in the groups fed extruded beans. Enzymatic activity and uptake in EKB1 were similar to those of casein-fed rats, whereas the uptake and growth rate of EKB6 were different to the control. This is attributable to the higher non-thermolabile biofactor content in the EKB6 diet, especially phytates and tannins, than in EKB1. This article shows the dose-dependent toxicological effects of bioactive factors contained in kidney beans on gut function. The extrusion process reduced their adverse impact on gut physiology and growth rate. PMID:21114542

  17. [Sarcomas of the small intestine].

    PubMed

    Beyrouti, M L; Abid, M; Beyrouti, R; Ben Amar, M; Gargouri, F; Frikha, F; Affes, N; Boujelbene, S; Ghorbel, A

    2005-03-12

    Sarcomas of the small intestine are rare, clearly differentiated, malignant, mesenchymatous tumours that can be of smooth muscle, Schwann cell or fibroblastic origin. From a clinical point of view, the pain and abdominal mass are the 2 types of symptoms that frequently reveal the disease. In rare cases, sarcomas of the small intestine are manifested by an acute complication. No imaging method can clearly confirm the diagnosis. Before immunohistochemistry, differential diagnosis was made on undifferentiated mesenchymatous "stromal" tumours, which are also rare. Exeresis must be complete and without perforation of the tumour because of the risk of locoregional relapse. The benefits provided by chemotherapy and radiotherapy are limited because of the low mitotic activity of the tumour cells and its weak vascularisation. Long-term survival is limited by poor prognosis criteria: high grade malignancy, size greater than 5 cm, tumour extension, perforation of the tumour, quality of surgical resection and histological type. PMID:15859576

  18. Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats.

    PubMed

    Arslan, Aynur; Ozcicek, Fatih; Keskin Cimen, Ferda; Altuner, Durdu; Yarali, Oguzhan; Kurt, Nezahat; Tumkaya, Levent; Ozturk, Cengiz; Suleyman, Halis

    2015-01-01

    The effect of resveratrol on the damage induced by methotrexate (MTX) in rat duodenum and jejunum tissue was investigated and evaluated in comparison with famotidine. The rats were divided into four groups as healthy group (HG), resveratrol+MTX (RMTX) group, famotidine+MTX (FMTX) group and the control group which received MTX (MTXC). RMTX group was given resveratrol 25 mg/kg and FMTX group famotidin 25 mg/kg, while MTXC and HG groups were orally administered distilled water once a day for 30 days. The rats in RMTX, FMTX and MTXC groups were given MTX of 5 mg/kg dose by the same way for 30 days. At the end of this period, amount of MDA, 8-OH/Gua and tGSH, and MPO gene expression were measured in the duodenal and jejunal tissues and the results were histopathologically evaluated. Resveratrol and famotidine were found to significantly prevent elevation of the MDA, 8-OH/Gua and MPO parameters with MTX and decrease of the levels of tGSH in the duodenal and jejunal tissues. Both drugs prevented severe damage to the villus and crypt epithelium in the duodenum and jejunum, congestion and hemorrhage, inflammatory cell infiltration and necrosis in the mucosa and submucosa due to MTX administration. Resveratrol could be considered in the clinical practice for treatment of the tissue damage in the intestines due to use of MTX, in comparison with famotidine. Resveratrol may be more advantageous than famotidine in long-term use against MTX toxicity since it does not inhibit gastric acid secretion. PMID:26379839

  19. Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats

    PubMed Central

    Arslan, Aynur; Ozcicek, Fatih; Keskin Cimen, Ferda; Altuner, Durdu; Yarali, Oguzhan; Kurt, Nezahat; Tumkaya, Levent; Ozturk, Cengiz; Suleyman, Halis

    2015-01-01

    The effect of resveratrol on the damage induced by methotrexate (MTX) in rat duodenum and jejunum tissue was investigated and evaluated in comparison with famotidine. The rats were divided into four groups as healthy group (HG), resveratrol+MTX (RMTX) group, famotidine+MTX (FMTX) group and the control group which received MTX (MTXC). RMTX group was given resveratrol 25 mg/kg and FMTX group famotidin 25 mg/kg, while MTXC and HG groups were orally administered distilled water once a day for 30 days. The rats in RMTX, FMTX and MTXC groups were given MTX of 5 mg/kg dose by the same way for 30 days. At the end of this period, amount of MDA, 8-OH/Gua and tGSH, and MPO gene expression were measured in the duodenal and jejunal tissues and the results were histopathologically evaluated. Resveratrol and famotidine were found to significantly prevent elevation of the MDA, 8-OH/Gua and MPO parameters with MTX and decrease of the levels of tGSH in the duodenal and jejunal tissues. Both drugs prevented severe damage to the villus and crypt epithelium in the duodenum and jejunum, congestion and hemorrhage, inflammatory cell infiltration and necrosis in the mucosa and submucosa due to MTX administration. Resveratrol could be considered in the clinical practice for treatment of the tissue damage in the intestines due to use of MTX, in comparison with famotidine. Resveratrol may be more advantageous than famotidine in long-term use against MTX toxicity since it does not inhibit gastric acid secretion. PMID:26379839

  20. Crypts, villi and microvilli in the small intestine of the rat. A stereological study of their variability within and between animals.

    PubMed Central

    Mayhew, T M; Middleton, C

    1985-01-01

    Small intestines from normal adult rats were quantified by optical and electron microscopy using stereological principles devised for the purpose. Five segments per bowel were examined. Baseline data characterising villi, microvilli and crypts of Lieberkühn were used to study differences between segments and between animals. Intestines fixed by in situ perfusion had, on average, 100 cm2 of primary mucosa. This basic surface was amplified to 500 cm2 by villi and to 1 m2 by the microvilli of enterocytes. Villous and microvillous surface areas may scale to body weight in the same way as metabolic requirements. Proximodistal gradients in mucosal architecture existed for the volumes and surface areas of villi and for the numbers, lengths, diameters and surface areas of microvilli. Most variables were higher proximally and declined towards the terminal ileum. The volume of crypts stayed constant throughout the entire intestine and ratios between villous dimensions (volumes and surface areas) and crypt volume did not vary between animals. Findings are discussed in the context of regional differences in bowel function and of their relevance to studies of epithelial kinetics. PMID:4077708

  1. Precocious alteration of digestive enzyme activities in small intestine and pancreas by chronic oral administration of protease inhibitor in suckling rats.

    PubMed

    Harada, E; Syuto, B

    1991-01-01

    1. The role of endogenous CCK in the development of digestive enzyme activities in small intestine and pancreas was investigated in suckling rats. Synthetic protease inhibitor (camostat 100 micrograms/g bwt) was orally administered twice daily for 5 days from 11 days of age. 2. Pancreatic hypertrophy and hyperplasia, and alteration of pancreatic enzyme composition, especially decreases in amylase activity and increases in trypsin and chymotrypsin activities were produced by camostat treatment. These changes were completely suppressed by simultaneous administration of the potent CCK receptor antagonist L-364,718 (1 microgram/g bwt). 3. With camostat treatment, intestinal lactase activity decreased to 41%, while maltase and sucrase activities increased 3 and 2.5 times respectively. These changes in enzyme activities were not affected by the application of L-364,718. 4. The mucosal disaccharidase and pancreatic enzyme activities could not be modified by chronic subcutaneous injection of camostat. The precocious induction of maltase and sucrase activities by camostat treatment was also observed in the adrenalectomized pups. 5. These results indicate that pancreatic growth accompanied by alteration of digestive enzyme composition in the suckling rats is regulated by endogenous CCK, but the precocious induction of disaccharidase activities is not mediated by endogenous CCK released by camostat treatment. PMID:1685962

  2. Changes in plasma and hepatic lipids, small intestinal histology and pancreatic enzyme activity due to aging and dietary fiber in rats.

    PubMed

    Schneeman, B O; Richter, D

    1993-07-01

    Rats were fed either a control diet or a control diet supplemented with wheat bran, psyllium husk or oat bran to increase intake of fiber. Groups of rats were killed after 3.5, 10, 15, or 18.5 mo of consuming the diets. Plasma cholesterol and triglyceride concentrations were significantly higher in 18.5-mo-old than younger animals. Fiber supplementation did not prevent the age-related increase in lipids. Cecal weight, including contents, was higher in the psyllium husk and oat bran groups than control, and smooth muscle thickness in the ileum of psyllium husk and oat bran animals was greater than control. The score for torn villi in the small intestine was lower than expected in the wheat bran group. Amylase activity in the pancreas declined significantly with age in all groups. In aging animals fiber supplementation may enhance ileal compensation for decreases in proximal intestinal function but does not prevent age-related changes in the gut or in lipid concentrations. PMID:7686573

  3. Administration of insulin-like growth factor-I (IGF-I) peptides for three days stimulates proliferation of the small intestinal epithelium in rats.

    PubMed Central

    Steeb, C B; Trahair, J F; Read, L C

    1995-01-01

    It has previously been shown that longterm administration of insulin-like growth factor-I (IGF-I) or the analogue Long R3 IGF-I (LR3IGF-I) selectively stimulate growth of the gastrointestinal tract in gut resected, dexamethasone treated, and normal rats. In this study, the short-term effects of IGF-I administration on intestinal proliferation have been investigated. Female rats (110 g, five-six/group) were infused for three days with 2.5 mg/kg/day of either IGF-I or LR3IGF-I and compared with vehicle treated or untreated control rats. LR3IGF-I but not IGF-I increased body weight and wet tissue weight of the small and large intestine (+20%), compared with controls. Tissue weight responses were independent of food intake and were reflected in the histology of the tissue. In LR3IGF-I treated animals, duodenal and ileal crypts length were increased by 13 and 22%, respectively, associated with an increase in crypt cell number. No such histological changes were seen in IGF-I treated rats. Tritiated thymidine labelling indices were significantly increased after administration of either IGF-I or LR3IGF-I (up to 14%) in both the duodenum and ileum. In IGF-I treated rats, increased nuclear labelling was not associated with an increase in the crypt compartment. In contrast, LR3IGF-I induced proportional increments in thymidine labelling and crypt size, suggesting that LR3IGF-I is not only more potent than the native peptide but also induced proliferative events more rapidly. In the colon, the thymidine labelling index was low, however, a non-significant increase in the number of cells labelled with thymidine was seen. These results suggest that within a three day treatment period intestinal mitogenesis is more advanced in animals treated with LR3IGF-I. The differences in proliferative response between the two peptides may be accounted for by variations in pharmacokinetics, clearance rates, and interactions with circulating and tissue specific binding proteins. PMID:8549937

  4. Administration of insulin-like growth factor-I (IGF-I) peptides for three days stimulates proliferation of the small intestinal epithelium in rats.

    PubMed

    Steeb, C B; Trahair, J F; Read, L C

    1995-11-01

    It has previously been shown that longterm administration of insulin-like growth factor-I (IGF-I) or the analogue Long R3 IGF-I (LR3IGF-I) selectively stimulate growth of the gastrointestinal tract in gut resected, dexamethasone treated, and normal rats. In this study, the short-term effects of IGF-I administration on intestinal proliferation have been investigated. Female rats (110 g, five-six/group) were infused for three days with 2.5 mg/kg/day of either IGF-I or LR3IGF-I and compared with vehicle treated or untreated control rats. LR3IGF-I but not IGF-I increased body weight and wet tissue weight of the small and large intestine (+20%), compared with controls. Tissue weight responses were independent of food intake and were reflected in the histology of the tissue. In LR3IGF-I treated animals, duodenal and ileal crypts length were increased by 13 and 22%, respectively, associated with an increase in crypt cell number. No such histological changes were seen in IGF-I treated rats. Tritiated thymidine labelling indices were significantly increased after administration of either IGF-I or LR3IGF-I (up to 14%) in both the duodenum and ileum. In IGF-I treated rats, increased nuclear labelling was not associated with an increase in the crypt compartment. In contrast, LR3IGF-I induced proportional increments in thymidine labelling and crypt size, suggesting that LR3IGF-I is not only more potent than the native peptide but also induced proliferative events more rapidly. In the colon, the thymidine labelling index was low, however, a non-significant increase in the number of cells labelled with thymidine was seen. These results suggest that within a three day treatment period intestinal mitogenesis is more advanced in animals treated with LR3IGF-I. The differences in proliferative response between the two peptides may be accounted for by variations in pharmacokinetics, clearance rates, and interactions with circulating and tissue specific binding proteins. PMID:8549937

  5. Effect of dietary fat on the small intestinal mucosa.

    PubMed

    Maxton, D G; Cynk, E U; Jenkins, A P; Thompson, R P

    1989-09-01

    The presence of food within the small intestinal lumen promotes mucosal cell proliferation. To define the trophic role of triglycerides, three groups of eight female Wistar rats were isocalorically fed for four weeks with either Vivonex, or Vivonex with 50% calorie substitution with an essential fatty acid mixture, or Vivonex with 50% calorie substitution with a saturated fatty acid mixture. Although Vivonex caused greater body weight gain, both essential fatty acids and saturated fatty acids increased small intestinal weight, mucosal weight, protein and DNA overall, and in each of three intestinal segments (proximal, middle and distal), compared with Vivonex. Mucosal indices were similar for essential fatty acids and saturated fatty acids. These results show that triglycerides, regardless of essential fatty acid content, are trophic to the rat small intestinal mucosa. PMID:2806993

  6. An investigation into the relationship between small intestinal fluid secretion and systemic arterial blood pressure in the anesthetized rat.

    PubMed

    Lucas, Michael L; Morrison, James D

    2015-05-01

    The effects of changes in the steady level of diastolic blood pressure on fluid flux across the jejunum has been investigated in the anesthetized rat during perfusion with a nutrient-free and Na(+)-free solution. Diastolic blood pressure was manipulated by intravenous infusions, during the jejunal perfusions, of vasodilators (vasoactive intestinal polypeptide, acetyl-β-methylcholine, and phentolamine) and a vasoconstrictor (arginine vasopressin), each of which acts through a different cellular mechanism. The outcome was that fluid flux was related by a parabolic relationship with diastolic blood pressure in which net secretion occurred over the range 40-100 mmHg, whereas net absorption was recorded at diastolic pressures exceeding 100 mmHg and below 40 mmHg. Against a background of normal absorption promoted by perfusion with 145 mmol L(-1) Na(+)/5 mmol L(-1) glucose solution, reductions in diastolic blood pressure markedly reduced the mean rate of fluid absorption by 58% overall, whereas the rate of glucose absorption remained unchanged. Our results were explained on the basis that vasodilatation led to increased capillary pressure and then to net filtration of fluid from the mesenteric capillary bed. Experiments in which Escherichia coli heat-stable toxin was added to the jejunal perfusate confirmed the absence of a secretory response, which was consistent with the absence of effect of the toxin on diastolic blood pressure. PMID:26019291

  7. An investigation into the relationship between small intestinal fluid secretion and systemic arterial blood pressure in the anesthetized rat

    PubMed Central

    Lucas, Michael L; Morrison, James D

    2015-01-01

    The effects of changes in the steady level of diastolic blood pressure on fluid flux across the jejunum has been investigated in the anesthetized rat during perfusion with a nutrient-free and Na+-free solution. Diastolic blood pressure was manipulated by intravenous infusions, during the jejunal perfusions, of vasodilators (vasoactive intestinal polypeptide, acetyl-β-methylcholine, and phentolamine) and a vasoconstrictor (arginine vasopressin), each of which acts through a different cellular mechanism. The outcome was that fluid flux was related by a parabolic relationship with diastolic blood pressure in which net secretion occurred over the range 40–100 mmHg, whereas net absorption was recorded at diastolic pressures exceeding 100 mmHg and below 40 mmHg. Against a background of normal absorption promoted by perfusion with 145 mmol L−1 Na+/5 mmol L−1 glucose solution, reductions in diastolic blood pressure markedly reduced the mean rate of fluid absorption by 58% overall, whereas the rate of glucose absorption remained unchanged. Our results were explained on the basis that vasodilatation led to increased capillary pressure and then to net filtration of fluid from the mesenteric capillary bed. Experiments in which Escherichia coli heat-stable toxin was added to the jejunal perfusate confirmed the absence of a secretory response, which was consistent with the absence of effect of the toxin on diastolic blood pressure. PMID:26019291

  8. Irreversible electroporation on the small intestine

    PubMed Central

    Phillips, M A; Narayan, R; Padath, T; Rubinsky, B

    2012-01-01

    Background: Non-thermal irreversible electroporation (NTIRE) has recently been conceived as a new minimally invasive ablation method, using microsecond electric fields to produce nanoscale defects in the cell membrane bilayer and induce cell death while keeping all other molecules, including the extracellular matrix, intact. Here, we present the first in vivo study that examines the effects of NTIRE on the small intestine, an organ whose collateral damage is of particular concern in the anticipated use of NTIRE for treatment of abdominal cancers. Methods: A typical NTIRE electrical protocol was applied directly to the rat small intestine and histological analysis was used to examine the effect of NTIRE over time. Results: The application of NTIRE led to complete cell ablation in the targeted tissue, but the animal did not show any physiological effects of the procedure and the intestine showed signs of recovery, developing an epithelial layer 3 days post treatment and regenerating its distinct layers within a week. Conclusion: Our results indicate that this novel procedure can be used for abdominal cancer treatment while minimising collateral damage to adjacent tissues because of the unique ability of the NTIRE ablation method to target the cell membrane. PMID:22223084

  9. Alcohol and the small intestine.

    PubMed

    Persson, J

    1991-01-01

    Several alterations of the small-intestinal morphology and function have been documented after alcohol ingestion. There are morphologic changes macroscopically and microscopically after acute alcohol administration in the proximal part of the small intestine, which are quickly reversible. There are no macroscopic changes and, in most patients, very discrete light microscopic changes in the small intestine after chronic alcohol ingestion. The ultrastructural changes are, however, profound, as seen by both transmission and scanning electron microscopy. The permeability is probably increased, permitting entrance of possible noxious agents, which may explain some of the extraintestinal tissue damage observed in chronic alcoholism. The transit is increased, at least after acute alcohol administration, perhaps contributing to the diarrhea commonly seen after heavy drinking. Several of the enzymes located in the brush border are affected; lactase activity can be depressed and perhaps result in a transient milk intolerance in predisposed individuals. The activity of GGT is increased and may partly account for the GGT elevation in serum after heavy drinking. Other enzymes, such as Na(+)-K(+)-ATPase, can be inhibited and result in a decreased absorption of substances that require active, energy-dependent transport mechanisms. The secretion of water and electrolytes may be increased (an effect on cAMP?). The absorption of several nutrients, vitamins, and other elements is disturbed. The bacterial flora is increased and changed, which may give rise to symptoms and also increase the production of acetaldehyde by bacterial metabolism of ethanol. Acetaldehyde is more toxic than ethanol, and an increased concentration of acetaldehyde can possibly accentuate the damage to the liver and other organs. The bacterial overgrowth can possibly cause endotoxinemia. Although studies on alcohol-related intestinal alterations have been relatively sparse, the acute and chronic effects of

  10. Effect of colchicine on rat small intestinal absorptive cells. II. Distribution of label after incorporation of (/sup 3/H)fucose into plasma membrane glycoproteins

    SciTech Connect

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

    1983-12-01

    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 (/sup 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 (/sup 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 (/sup 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.

  11. [The functional state of the mitochondrial respiratory chain of the small intestine enterocytes of the rats under the low dose rate X-ray total external exposure].

    PubMed

    Khizhniak, S V; Stepanova, L I; Grubskaia, L V; Voĭtsitskiĭ, V M

    2013-01-01

    The influence of the low-rate ionizing radiation (0.055 Gy/min) at the doses of 0.1; 0.5 and 1.0 Gy on the functional state of the mitochondria respiratory chain of the rat small intestine enterocytes was investigated. The dysfunction of the electron transport chain enzymes and changes in the content of cytochromes b, c, a in the mitochondrial inner membrane were revealed 1, 12 and 24 hours after exposure to radiation. The revealed disorders indicate early membrane sensitivity to the radiation effect. The inhibition of the H+ -ATPase activity in the studied dose range indicates the decrease of the mitochondrial energy capacity. PMID:25486741

  12. Protection of Radiation-Induced Damage to the Hematopoietic System, Small Intestine and Salivary Glands in Rats by JNJ7777120 Compound, a Histamine H4 Ligand

    PubMed Central

    Martinel Lamas, Diego J.; Carabajal, Eliana; Prestifilippo, Juan P.; Rossi, Luis; Elverdin, Juan C.; Merani, Susana; Bergoc, Rosa M.; Rivera, Elena S.; Medina, Vanina A.

    2013-01-01

    Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg) starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG) function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01). This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01). JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy. PMID:23922686

  13. Effects of ε-viniferin, a dehydrodimer of resveratrol, on transepithelial active ion transport and ion permeability in the rat small and large intestinal mucosa.

    PubMed

    Karaki, Shin-Ichiro; Ishikawa, Junji; Tomizawa, Yuka; Kuwahara, Atsukazu

    2016-05-01

    ε-Viniferin is a dehydrodimer of resveratrol, a polyphenol synthesized in many plants, including grapevine. The present study investigated the effects of ε-viniferin and resveratrol on epithelial secretory and barrier functions in isolated rat small and large intestinal mucosa. Mucosa-submucosa tissue preparations of various segments of the rat large and small intestines were mounted on Ussing chambers, and short-circuit current (Isc) and tissue conductance (Gt) were continuously measured. The mucosal addition of ε-viniferin (>10(-5) mol/L) and resveratrol (>10(-4) mol/L) to the cecal mucosa, which was the most sensitive region, induced an increase in Isc and a rapid phase decrease (P-1) followed by rapid (P-2) and broad (P-3) peak increases in Gt in concentration-dependent manners. Mucosal ε-viniferin (10(-4) mol/L), but not resveratrol (10(-4) mol/L), increased the permeability of FITC-conjugated dextran (4 kDa). The mucosal ε-viniferin-evoked changes in Isc (Cl(-) secretion), but not in Gt, were attenuated by a selective cyclooxygenase (COX)-1 inhibitor and a selective EP4 prostaglandin receptor. The mucosal ε-viniferin-evoked increase in Isc was partially attenuated, and P-2, but not P-1 or P-3, change in Gt was abolished by a transient receptor potential cation channel, subfamily A, member 1 (TRPA1) inhibitor. Moreover, the mucosal ε-viniferin concentration-dependently attenuated the mucosal propionate (1 mmol/L)-evoked increases in Isc and Gt Immunohistochemical studies revealed COX-1-immunoreactive epithelial cells in the cecal crypt. The present study showed that mucosal ε-viniferin modulated transepithelial ion transport and permeability, possibly by activating sensory epithelial cells expressing COX-1 and TRPA1. Moreover, mucosal ε-viniferin decreased mucosal sensitivity to other luminal molecules such as short-chain fatty acids. In conclusion, these results suggest that ε-viniferin modifies intestinal mucosal transport and barrier

  14. Clinical radiology of the small intestine

    SciTech Connect

    Herlinger, H.; Maglinte, D.

    1989-01-01

    This book discussed embryology, anatomy, physiology, and immunology of the small intestine. Radiographic procedures in the small intestine especially enterolysis are presented. Focus is on the role of other types of imaging techniques including sonography, computed tomography, radionuclide imaging, angiography, biopsy, and enteroscopy.

  15. Methotrexate administration induces differential and selective protein tyrosine nitration and cysteine nitrosylation in the subcellular organelles of the small intestinal mucosa of rats.

    PubMed

    Natarajan, Kasthuri; Abraham, Premila

    2016-05-01

    Gastrointestinal toxicity is one of the most frequent dose limiting side effects of methotrexate (MTX), a commonly used chemotherapeutic drug. Peroxynitrite (PON) overproduction is reported to contribute to MTX induced gastrointestinal mucositis. However, the consequence of PON overproduction i.e. protein tyrosine nitration and protein cysteine nitrosylation, the subcellular distribution of these modified proteins and their molecular weights have not been investigated yet. Mucositis was induced in Wistar rats by the administration of 3 consecutive i.p. injections of MTX. Tyrosine nitrated proteins and cysteine nitrosylated proteins were determined in the subcellular organelles fractions of mucosa using immunoprecipitation and western blot. The proteins in the subcellular fractions were separated by 1D electrophoresis, and probed with anti -nitrotyrosine antibody and anti-nitrosocysteine antibody. After MTX treatment, a general increase in protein tyrosine nitration as well as a change in the spectrum of proteins that underwent nitration was observed. The relative densities of the 3 nitrotyrosine protein adducts were as follows: Mitochondria > cytosol > microsomes > nucleus. In the mitochondrial fraction increased nitration of 12 kDa, 25 kDa 29Kda, 47 kDa, and 62Kda proteins, in the cytosol increased nitration of 12 kDa, 19 kDa, 45 kDa, and 60 kDa proteins and in the nuclear fraction increased nitration of 17 kDa, 35 kDa, and 58 kDa proteins was observed. On the other hand, MTX treatment resulted to a general decrease in protein cysteine nitrosylation in all the subcellular fractions. These results suggest that MTX induced, PON mediated small intestinal injury is mediated by differential nitration and nitrosylation of proteins in the subcellular organelles with increased protein tyrosine nitration and decreased cysteine nitrosylation. In addition MTX treatment results in selective nitration and nitrosylation of proteins in the intestinal mucosa. This

  16. Quantitative proteomic analysis reveals heat stress-induced injury in rat small intestine via activation of the MAPK and NF-κB signaling pathways.

    PubMed

    He, Shasha; Hou, Xiaolin; Xu, Xiaolong; Wan, Changrong; Yin, Peng; Liu, Xiaoxi; Chen, Yuping; Shu, Banchao; Liu, Fenghua; Xu, Jianqin

    2015-03-01

    The intestinal epithelium plays a critical role in absorbing nutrients and maintaining the integrity of the gut barrier. Extreme heat stress induces damage to the intestinal epithelium. However, the protein expression changes and the mechanism behind this damage remain poorly understood. In this study, morphological observation showed that heat stress induced desquamation of intestinal epithelial cells, and destruction of intestinal microvilli and mitochondria. Heat stress-induced changes in the intestinal proteome were quantified using the iTRAQ method followed by mass spectrometry and software analysis. A total of 1689 proteins were identified in rat intestine tissue, of which 41 showed significantly altered expression between the heat stressed and control groups. However, these proteins with significant alterations were involved in biological processes such as cellular assembly and organization, developmental disorder, organismal injury and abnormalities, and inflammation. We found that members of the MAPK and NF-κB signaling pathways act as hub proteins in the network interaction analysis. Furthermore, western blot analysis verified that the MAPK and NF-κB signaling pathways were activated by heat stress as expected. This study suggests that heat stress induces cell cytoskeleton reorganization and an inflammatory response, and the activation of the MAPK and NF-κB signaling pathways, which may ultimately contribute to intestinal injury. PMID:25537883

  17. Small intestinal ischemia and infarction

    MedlinePlus

    ... the bowel are reconnected. In some cases, a colostomy or ileostomy is needed. The blockage of arteries ... Intestinal infarction may require a colostomy or ileostomy, which may be ... is common in these cases. People who have a large amount ...

  18. Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Li; Deng, Yuanxiong; Yu, Sen; Lu, Shousi; Xie, Lin; Liu, Xiaodong

    2008-05-01

    Previous studies demonstrated anti-diabetic effects of berberine. However, the facts that berberine had low bioavailability and poor absorption through the gut wall indicated that berberine might exert its antihyperglycaemic effect in the intestinal tract before absorption. The purpose of this study was to investigate whether berberine attenuates disaccharidase activities and beta-glucuronidase activity in the small intestine of streptozotocin (STZ)-induced diabetic rats. Two groups of STZ-induced diabetic rats were treated with protamine zinc insulin (10 U/Kg) subcutaneously twice daily and berberine (100 mg/Kg) orally once daily for 4 weeks, respectively. Both age-matched normal rats and diabetic control rats received physiological saline only. Fasting blood glucose levels, body weight, intestinal disaccharidase and beta-glucuronidase activities in duodenum, jejunum and ileum were assessed for changes. Our findings suggested that berberine treatment significantly decreases the activities of intestinal disaccharidases and beta-glucuronidase in STZ-induced diabetic rats. The results demonstrated that the inhibitory effect on intestinal disaccharidases and beta-glucuronidase of berberine might be one of the mechanisms for berberine as an antihyperglycaemic agent. PMID:18557425

  19. Small intestine bleeding due to multifocal angiosarcoma

    PubMed Central

    Zacarias Föhrding, Luisa; Macher, Arne; Braunstein, Stefan; Knoefel, Wolfram Trudo; Topp, Stefan Andreas

    2012-01-01

    We report a case of an 84-year-old male patient with primary small intestinal angiosarcoma. The patient initially presented with anemia and melena. Consecutive endoscopy revealed no signs of upper or lower active gastrointestinal bleeding. The patient had been diagnosed 3 years previously with an aortic dilation, which was treated with a stent. Computed tomography suggested an aorto-intestinal fistula as the cause of the intestinal bleeding, leading to operative stent explantation and aortic replacement. However, an aorto-intestinal fistula was not found, and the intestinal bleeding did not arrest postoperatively. The constant need for blood transfusions made an exploratory laparotomy imperative, which showed multiple bleeding sites, predominately in the jejunal wall. A distal loop jejunostomy was conducted to contain the small intestinal bleeding and a segmental resection for histological evaluation was performed. The histological analysis revealed a less-differentiated tumor with characteristic CD31, cytokeratin, and vimentin expression, which led to the diagnosis of small intestinal angiosarcoma. Consequently, the infiltrated part of the jejunum was successfully resected in a subsequent operation, and adjuvant chemotherapy with paclitaxel was planned. Angiosarcoma of the small intestine is an extremely rare malignant neoplasm that presents with bleeding and high mortality. Early diagnosis and treatment are essential to improve outcome. A small intestinal angiosarcoma is a challenging diagnosis to make because of its rarity, nonspecific symptoms of altered intestinal function, nonspecific abdominal pain, severe melena, and acute abdominal signs. Therefore, a quick clinical and histological diagnosis and decisive measures including surgery and adjuvant chemotherapy should be the aim. PMID:23197897

  20. The use of bi-layer silk fibroin scaffolds and small intestinal submucosa matrices to support bladder tissue regeneration in a rat model of spinal cord injury

    PubMed Central

    Chung, Yeun Goo; Algarrahi, Khalid; Franck, Debra; Tu, Duong D.; Adam, Rosalyn M.; Kaplan, David L.; Estrada, Carlos R.; Mauney, Joshua R.

    2014-01-01

    Adverse side-effects associated with enterocystoplasty for neurogenic bladder reconstruction have spawned the need for the development of alternative graft substitutes. Bi-layer silk fibroin (SF) scaffolds and small intestinal submucosa (SIS) matrices were investigated for their ability to support bladder tissue regeneration and function in a rat model of spinal cord injury (SCI). Bladder augmentation was performed with each scaffold configuration in SCI animals for 10 wk of implantation and compared to non-augmented control groups (normal and SCI alone). Animals subjected to SCI alone exhibited a 72% survival rate (13/18) while SCI rats receiving SIS and bi-layer SF scaffolds displayed respective survival rates of 83% (10/12) and 75% (9/12) over the course of the study period. Histological (Masson’s trichrome analysis) and immunohistochemical (IHC) evaluations demonstrated both implant groups supported de novo formation of smooth muscle layers with contractile protein expression [α-smooth muscle actin (α-SMA) and SM22α] as well as maturation of multi-layer urothelia expressing cytokeratin (CK) and uroplakin 3A proteins. Histomorphometric analysis revealed bi-layer SF and SIS scaffolds respectively reconstituted 64% and 56% of the level of α-SMA+ smooth muscle bundles present in SCI-alone controls, while similar degrees of CK+ urothelium across all experimental groups were detected. Parallel evaluations showed similar degrees of vascular area and synaptophysin+ boutons in all regenerated tissues compared to SCI-alone controls. In addition, improvements in certain urodynamic parameters in SCI animals, such as decreased peak intravesical pressure, following implantation with both matrix configurations were also observed. The data presented in this study detail the ability of acellular SIS and bi-layer SF scaffolds to support formation of innervated, vascularized smooth muscle and urothelial tissues in a neurogenic bladder model. PMID:24917031

  1. The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model

    PubMed Central

    Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

    2016-01-01

    Background/Aims DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Methods Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. Results The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. Conclusions DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway. PMID:27114435

  2. Survival after total body irradiation: Effects of irradiation of exteriorized small intestine. (Reannouncement with new availability information)

    SciTech Connect

    Vriesendorp, H.M.; Vigneulle, R.M.; Kitto, G.; Pelky, T.; Taylor, P.

    1993-12-31

    Rats receiving lethal irradiation to their exteriorized small intestine with pulsed 18 MVp bremsstrahlung radiation live about 4 days longer than rats receiving a dose of total-body irradiation (TBI) causing intestinal death. The LD50 for intestinal irradiation is approximately 6 Gy higher than the LD50 for intestinal death after TBI. Survival time after exteriorized intestinal irradiation can be decreased, by adding abdominal irradiation. Adding thoracic or pelvic irradiation does not alter survival time. Shielding of large intestine improves survival after irradiation of the rest of the abdomen while the small intestine is also shielded. The kinetics of histological changes in small intestinal tissues implicate the release of humoral factors after irradiation of the abdomen. Radiation injury develops faster in the first (proximal) 40 cm of the small intestine and is expressed predominantly as shortening in villus height. In the last (distal) 40 cm of the small intestine, the most pronounced radiation effect is a decrease in the number of crypts per millimeter. Irradiation (20 Gy) of the proximal small intestine causes 92 % mortality (median survival 10 days). Irradiation (20 Gy) of the distal small intestine causes 27% mortality (median survival > 30 days). In addition to depletion of crypt stem cells in the small intestine, other issues (humoral factors, irradiated subsection of the small intestine and shielding of the large intestine) appear to influence radiation-induced intestinal mortality.

  3. A case of small intestinal endometrioid adenocarcinoma.

    PubMed

    Ogi, Yusuke; Yamaguchi, Tomohiro; Kinugasa, Yusuke; Shiomi, Akio; Kagawa, Hiroyasu; Yamakawa, Yushi; Numata, Masakatsu; Furutani, Akinobu; Abe, Masakazu

    2016-12-01

    Endometriosis generally occurs in the ovary. Intestinal endometriosis is rare. About 1 % of all endometriosis cases become malignant. Malignant transformation of small intestinal endometriosis is very rare. A 55-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy and omentectomy for endometriosis 7 years ago presented to her primary care doctor with melena. A tumor was detected in the right lower abdomen by ultrasonography. The doctor referred her to our hospital. Computed tomography demonstrated a lobulated tumor ventral to the right common iliac vessels. Magnetic resonance imaging demonstrated that the tumor had heterogeneous intensity on T2-weighted images. Several small cysts with high intensity were observed caudal to the tumor on T2-weighted images. We performed partial small intestinal resection for the lesion. The tumor was diagnosed as endometrioid adenocarcinoma of the small intestine. She has been relapse-free for 5 years after surgery. Only three cases of malignant transformation of small intestinal endometriosis have been reported previously. It is very rare for long-term survival to be obtained with surgery alone, as in our case. This case report highlights the imaging findings for malignant transformation of intestinal endometriosis. PMID:27624553

  4. Changes in the structure and regeneration mode of the rat small intestinal mucosa following benzalkonium chloride treatment.

    PubMed

    Holle, G E

    1991-11-01

    Tritiated thymidine was administered IP to rats that had been exposed to benzalkonium chloride in the duodenum, jejunum, and ileum, resulting in neuronal ablation. Epithelial cell proliferation and migration were studied 21 and 7 days after treatment. Significant hyperplasia and hypertrophy of the villi and crypts was seen from day 7 on. This was half as pronounced as that of the muscle layer, whose maximal percent increase was not seen until day 21. In the crypt, the proliferation had increased significantly (65% 3H index corrected) and its zone had expanded proportionally to the total crypt depth. After an average of 36 hours in the ileum (48 hours in normal rats), labeled cells reached the tip of the lengthened villi, reflecting significantly accelerated migration. Concerning the distributional pattern of the labeled cells in the crypt, a nonsignificant shift to the lower two thirds of the crypt could be distinguished. From this the author concludes that treatment with benzalkonium chloride influences the proliferation and migration of the epithelial cells in the treated area. These alterations may result from loss of the myenteric plexus, but other factors cannot be excluded. PMID:1936797

  5. Acute and chronic exposure to ethanol and the electrophysiology of the brush border membrane of rat small intestine.

    PubMed Central

    al-Balool, F; Debnam, E S; Mazzanti, R

    1989-01-01

    In this study we have investigated the effects of (a) chronic ethanol intake on glucose and galactose absorption across the rat jejunum in vivo and on the potential difference across the isolated brush border membrane (Vm) and (b) acute exposure to ethanol (4% or 8%) and acetaldehyde (0.25%) on changes in Vm associated with Na(+)-dependent galactose absorption across the jejunum and ileum. Chronic ethanol intake was associated with hyperpolarization of Vm and an enhanced galactose but not glucose transport. Acute ethanol and acetaldehyde were without effect on Vm whether or not galactose was present. We conclude that while a greater electrochemical gradient across the brush border membrane is a likely explanation for the stimulation of galactose absorption induced by ethanol feeding, factors other than changes in Vm are responsible for the inhibitory effects of acute ethanol. PMID:2612984

  6. Systematic studies on the paracellular permeation of model permeants and oligonucleotides in the rat small intestine with chenodeoxycholate as enhancer.

    PubMed

    Tsutsumi, Keiko; Li, S Kevin; Hymas, Richard V; Teng, Ching-Leou; Tillman, Lloyd G; Hardee, Gregory E; Higuchi, William I; Ho, Norman F H

    2008-01-01

    The objective of this study was to mechanistically and quantitatively analyze chenodeoxycholate-enhanced paracellular transport of polar permeants and oligonucleotides in the rat jejunum and ileum. Micellar chenodeoxycholate solutions were used to perturbate the tight junctions. Supporting studies included assessment of the aqueous boundary layer (ABL) with ABL-controlled permeants, measurements of the permeability coefficients and fluxes of the bile acid in dilute and micellar concentrations, and determinations of pore sizes with paracellular probes (urea, mannitol, and raffinose). The paracellular permeability coefficients, P(para), of two model oligonucleotides (ON3 and ON6; 12- and 24-mers with 11 and 23 negative charges, respectively) were determined. The enhanced permeabilities paralleled the increased fluxes of micellar bile salt solutions into mesenteric blood and the opening of the tight junctions as compared to controls. As the pore radius increased from 0.7 nm to a maximum of 2.4 nm in the jejunum and ileum, the absorption of ON3 was enhanced up to sixfold in the jejunum and about 14-fold in the ileum with P(para) values between 0.5 x 10(-6) and 6 x 10(-6) cm/s, whereas ON6 was enhanced up to twofold in the jejunum and fivefold in the ileum with permeabilities between 0.3 x 10(-6) and 2 x 10(-6) cm/s. PMID:17847071

  7. Intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion method in the rat.

    PubMed

    Cook, Thomas J; Shenoy, Smriti S

    2003-03-01

    The intestinal transport of chlorpyrifos (CPF), an organothiophosphate pesticide, was investigated using the single-pass intestinal perfusion (SPIP) technique in male, Sprague-Dawley rats. SPIP was performed in each isolated region of the small intestine (i.e. duodenum, jejunum and ileum) with three concentrations of CPF (0.1, 2.0 and 10 microM) at a flow rate of 0.25 ml/min. Preliminary binding and stability studies were conducted to ensure that the loss of CPF in the SPIP study can be attributed to intestinal absorption. The effective permeability (P(eff)) of CPF was determined for each segment and concentration. CPF exhibits a high intestinal permeability over the length of the small intestine indicative of compounds that are well absorbed. Decreases in permeability values at the highest CPF concentration studied in the duodenum and ileum suggest a saturable transport process. Based on these results, passive, transcellular diffusion dominates the intestinal transport mechanism of CPF, with a saturable transport process evident in the duodenum and ileum. The P(eff) of CPF is in the range of drugs with high intestinal permeability and high fraction of dose absorbed indicating that CPF readily crosses the intestine. The dependence of CPF's P(eff) on concentration in the duodenum and ileum suggests that CPF is transported by a combination of mechanisms across the intestine. Using established relationships, the human fraction dose absorbed for CPF was estimated to be >99%. The permeability values obtained from this study may be useful in models of exposure assessment. PMID:12499115

  8. Small intestinal obstruction caused by anisakiasis.

    PubMed

    Takano, Yuichi; Gomi, Kuniyo; Endo, Toshiyuki; Suzuki, Reika; Hayashi, Masashi; Nakanishi, Toru; Tateno, Ayumi; Yamamura, Eiichi; Asonuma, Kunio; Ino, Satoshi; Kuroki, Yuichiro; Nagahama, Masatsugu; Inoue, Kazuaki; Takahashi, Hiroshi

    2013-01-01

    Small intestinal anisakiasis is a rare disease that is very difficult to diagnose, and its initial diagnosis is often surgical. However, it is typically a benign disease that resolves with conservative treatment, and unnecessary surgery can be avoided if it is appropriately diagnosed. This case report is an example of small intestinal obstruction caused by anisakiasis that resolved with conservative treatment. A 63-year-old man admitted to our department with acute abdominal pain. A history of raw fish (sushi) ingestion was recorded. Abdominal CT demonstrated small intestinal dilatation with wall thickening and contrast enhancement. Ascitic fluid was found on the liver surface and in the Douglas pouch. His IgE (RIST) was elevated, and he tested positive for the anti-Anisakis antibodies IgG and IgA. Small intestinal obstruction by anisakiasis was highly suspected and conservative treatment was performed, ileus tube, fasting, and fluid replacement. Symptoms quickly resolved, and he was discharged on the seventh day of admission. Small intestinal anisakiasis is a relatively uncommon disease, the diagnosis of which may be difficult. Because it is a self-limiting disease that usually resolves in 1-2 weeks, a conservative approach is advisable to avoid unnecessary surgery. PMID:24455340

  9. Dissociation of a ferric maltol complex and its subsequent metabolism during absorption across the small intestine of the rat.

    PubMed Central

    Barrand, M. A.; Callingham, B. A.; Dobbin, P.; Hider, R. C.

    1991-01-01

    1. The fate and disposition of [59Fe]-ferric [3H]-maltol after intravenous administration were investigated in anaesthetized rats. Immediate dissociation of ferric iron from maltol took place in the circulation even with high doses of ferric maltol (containing 1 mg elemental iron). In plasma samples withdrawn within 1 min of injection and subjected to gel filtration, 59Fe eluted with the high molecular weight proteins whilst the tritium was associated with low molecular weight material. 2. The rates of elimination of 59Fe and of tritium from the plasma and their ultimate fate were very different. The half life for 59Fe in the plasma was around 70 min and 59Fe appeared mainly in the bone marrow and liver. There was an initial rapid exit of tritium from the plasma with a half life of around 12 min. This was followed either by a plateau or by a rise in tritium levels, involving entry of maltol metabolites into the circulation. These metabolites could be recovered in the urine. 3. Entry of 59Fe and of tritium into the blood plasma after intraduodenal administration of [59Fe]-ferric [3H]-maltol was also very different. At low doses of ferric maltol (containing 100 micrograms elemental iron), the tritium appeared in the plasma in highest amounts within seconds and then decreased whilst there was a slow rise in 59Fe levels. At higher doses of ferric maltol (containing 7 mg elemental iron), levels of 59Fe in the plasma were highest at 5 min and then fell whereas tritium levels rose steadily. Mucosal processing of 59Fe prevented further entry of iron at high dose into the circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1364845

  10. Effects of methotrexate on intestinal transit in rats

    SciTech Connect

    Curd, C.D.; Manno, J.E.; Stewart, J.J.

    1985-10-01

    A study was designed to determine the effects of methotrexate (MTX) on rat intestinal transit. Adult male rats were implanted with indwelling cannulas in the proximal duodenum 5 to 7 days prior to experimentation. After recovery from surgery, groups of animals were treated with either saline (1.0 ml/kg/day) or MTX at 0.5, 1.25, 3.125, or 7.8 mg/kg/day (ip) for 3 consecutive days (Days 1-3). On each of the next 5 consecutive days (Days 4-8) weight and intestinal transit determinations were made in animals from each test group following a 24-hr fast. Intestinal transit was determined by measuring the progression of an intraduodenally administered bolus of radioactive chromium (Na/sub 2//sup 51/CrO/sub 4/, 0.5 mu Ci) through the small intestine. When compared with saline-treated controls, intestinal transit was significantly (p less than 0.05) increased on 1 or more of the 5 test days in animals treated with doses of MTX greater than 0.5 mg/kg/day. When compared with animals treated with saline, animals treated with MTX lost a greater percentage of their initial body weight after the fast period. Plasma concentrations of MTX, determined at various time intervals after 3.125 mg/kg given daily for 1 to 3 consecutive days, peaked at 15 and 30 min after each injection and diminished to undetectable levels after 4 hr. The results indicate that 3 days of parenteral therapy with MTX significantly increases rat intestinal transit. The intestinal effects appear to be transient and are proportional to the total dose of drug administered over the 3-day period. The intestinal effects of MTX occur from 1 to several days after peak plasma concentrations of drug and are associated with a reduced ability to sustain body weight after a 24-hr fast.

  11. Bile loss in the acute intestinal radiation syndrome in rats

    SciTech Connect

    Geraci, J.P.; Dunston, S.G.; Jackson, K.L.; Mariano, M.S.; Holeski, C.; Eaton, D.L.

    1987-01-01

    The effects of bile duct ligation (BDL), choledochostomy, bile acid sequestering within the intestinal lumen by cholestyramine, and fluid and electrolyte replacement on survival time and development of diarrhea after whole-body exposure to doses of ionizing radiation that result in death from acute intestinal injury were studied. BDL significantly prolonged survival and delayed the onset of diarrhea after exposure to /sup 137/Cs gamma rays, fission neutrons, or cyclotron-produced neutrons in the range of doses that produce intestinal death or death from a combination of intestinal and hematopoietic injuries. Cannulation of the bile duct with exteriorized bile flow (choledochostomy) to protect the irradiated intestine from the mucolytic action of bile salts did not duplicate the effect of BDL in increasing survival time. Choledochostomy without fluid replacement eliminated the occurrence of diarrhea in 15.4 Gy irradiated rats. Diarrhea did occur in irradiated animals with choledochostomy if they received duodenal injections of fluid and electrolytes to replace the fluid lost as a result of bile drainage. Duodenal injection of fluid and electrolytes had no significant effect on survival time in irradiated rats. Injection of fluid and electrolytes into the peritoneal cavity of irradiated rats resulted in an increase in survival time that was comparable to that observed after BDL. Addition of antibiotics to the peritoneally injected fluid and electrolytes further increased survival time (up to 9 days). This survival time approached that seen in animals receiving the same radiation dose but which had the intestine exteriorized and shielded to minimize radiation injury to the intestine. Postmortem histological examinations of the irradiated small intestine showed mucosal regeneration in these long-term survivors receiving fluid and antibiotic therapy.

  12. The response of the small intestine to vitamin D. Isolation and properties of chick intestinal polyribosomes

    PubMed Central

    Emtage, J. Spencer; Lawson, D. Eric M.; Kodicek, Egon

    1974-01-01

    Undegraded polyribosome preparations may be obtained from chick intestinal mucosa if ribonuclease activity is strictly controlled. This is best achieved by homogenization of the mucosa directly in rat liver cell-sap. 2. The extent of amino acid incorporation by chick intestinal polyribosomes is greatly influenced by the source of the cell-sap. Sephadex-treated intestinal cell-sap caused impaired incorporation and release of completed polypeptide chains, whereas Sephadex-treated rat liver cell-sap promoted the polymerization of up to 90 amino acids per ribosome. Under optimum conditions 30–35% of the nascent polypeptide chains are completed and released. 3. The preparation of an antiserum against the calcium-binding protein formed in response to vitamin D is described. It is shown that the antiserum is highly specific for calcium-binding protein. 4. This antiserum was used to investigate the ability of chick intestinal polyribosomes to synthesize calciumbinding protein. Only polyribosomes from chicks receiving vitamin D have the ability to synthesize calcium-binding protein. Moreover, the product formed in vitro has the same electrophoretic mobility as calcium-binding protein synthesized in vivo. 5. It is concluded that one of the main functions of vitamin D in the small intestine is to induce the synthesis de novo of calcium-binding protein. PMID:4455190

  13. An energy supply network of nutrient absorption coordinated by calcium and T1R taste receptors in rat small intestine

    PubMed Central

    Mace, Oliver J; Lister, Norma; Morgan, Emma; Shepherd, Emma; Affleck, Julie; Helliwell, Philip; Bronk, John R; Kellett, George L; Meredith, David; Boyd, Richard; Pieri, Myrtani; Bailey, Pat D; Pettcrew, Rachel; Foley, David

    2009-01-01

    T1R taste receptors are present throughout the gastrointestinal tract. Glucose absorption comprises active absorption via SGLT1 and facilitated absorption via GLUT2 in the apical membrane. Trafficking of apical GLUT2 is rapidly up-regulated by glucose and artificial sweeteners, which act through T1R2 + T1R3/α-gustducin to activate PLC β2 and PKC βII. We therefore investigated whether non-sugar nutrients are regulated by taste receptors using perfused rat jejunum in vivo. Under different conditions, we observed a Ca2+-dependent reciprocal relationship between the H+/oligopeptide transporter PepT1 and apical GLUT2, reflecting the fact that trafficking of PepT1 and GLUT2 to the apical membrane is inhibited and activated by PKC βII, respectively. Addition of l-glutamate or sucralose to a perfusate containing low glucose (20 mm) each activated PKC βII and decreased apical PepT1 levels and absorption of the hydrolysis-resistant dipeptide l-Phe(ΨS)-l-Ala (1 mm), while increasing apical GLUT2 and glucose absorption within minutes. Switching perfusion from mannitol to glucose (75 mm) exerted similar effects. l-Glutamate induced rapid GPCR internalization of T1R1, T1R3 and transducin, whereas sucralose internalized T1R2, T1R3 and α-gustducin. We conclude that l-glutamate acts via amino acid and glucose via sweet taste receptors to coordinate regulation of PepT1 and apical GLUT2 reciprocally through a common enterocytic pool of PKC βII. These data suggest the existence of a wider Ca2+ and taste receptor-coordinated transport network incorporating other nutrients and/or other stimuli capable of activating PKC βII and additional transporters, such as the aspartate/glutamate transporter, EAAC1, whose level was doubled by l-glutamate. The network may control energy supply. PMID:19001049

  14. Effect of saponin on the transmucosal passage of beta-lactoglobulin across the proximal small intestine of normal and beta-lactoglobulin-sensitised rats.

    PubMed

    Gee, J M; Wal, J M; Miller, K; Atkinson, H; Grigoriadou, F; Wijnands, M V; Penninks, A H; Wortley, G; Johnson, I T

    1997-02-28

    The ability of saponins and glycoalkaloids to permeabilise the mammalian intestinal barrier has been previously demonstrated in vitro, leading to the hypothesis that membranolytic saponins may facilitate transfer to the tissues of otherwise excluded macromolecules. An enhanced uptake of, for instance, potentially allergenic species from the lumen is one of the factors that may affect the induction of food allergy, and its presentation in already sensitised individuals. In the experiments described here, an increase in the transmucosal uptake of the milk allergen beta-lactoglobulin (beta LG) was assessed in non-sensitised and sensitised Brown Norway rats in the presence of Gypsophila saponin. Isolated jejunal loops were exposed in vivo to either beta LG followed by saponin, saponin followed by beta LG or the two compounds simultaneously. Portal vein blood samples were collected and assayed for beta LG and rat mucosal mast cell protease (RCMP II) activity. Mucosal tissue was also examined histologically and assayed for histamine content. Sham-operated animals, exposed to physiological buffer alone, were included as controls and beta LG measurements corrected for this component which was negligible. No transfer of beta LG occurred in the absence of saponin in non-sensitised rats, whereas a significant enhancement was observed in the presence of saponin. beta LG was detected in the portal circulation of sensitised rats exposed to beta LG alone; however addition of saponin to the intestinal lumen further enhanced this uptake, possibly by an independent mechanism. Histological examination of the mucosal epithelium exposed to saponin revealed damage, especially at the villus tips. Mucosal histamine and serum RCMP II concentrations were consistent with the differences observed between sensitised and non-sensitised animals. It is concluded that exposure to food constituents capable of permeabilising the mucosal epithelium may increase the risk of sensitisation to dietary

  15. [Intestinal absorption kinetics of Polygonum capitatum extract in rats].

    PubMed

    Yang, Wu; Hou, Jia; Lu, Yuan; Chen, Peng-cheng; Liao, Shang-gao; Huang, Yong

    2015-11-01

    A UPLC-ESI-MS/MS method was used to determinate the main active fractions gallic acid, protocatechuic acid, myricetrin, hyperoside and quercitrin in Polygonum capitatum extracts by in situ intestinal perfusion models; the absorption rate constants and cumulative penetration rate of absorption were calculated. The effect of different drug concentrations, different intestine segments, bile and P-gp inhibitors on the absorption mechanism of Gallic acid and other compositions in P. capitatum extracts. The experimental results showed that gallic acid, protocatechuic acid, myricetrin and quercitrin were observed saturated at high concentration (P < 0.05). Bile had significant inhibition effect on protocatechuic acid absorption and had promotion effect on myricetrin and hyperoside absorption (P < 0.05). P-gp inhibitor verapamil could significantly enhance the absorption of Protocatechuic acid (P < 0.05). The overall trend for absorption of various compositions was that small intestine > colon. This indicated that the absorption mechanism of P. capitatum extracts in rat intestine was in line with fist-order kinetics characteristics. The composition could be absorbed in all of the different intestinal segments, and the absorption was mainly concentrated in small intestine. The protocatechuic acid may be the substrate of P-gp. PMID:27071271

  16. Quantitative assessment of the transmission of labelled protein by the proximal and distal regions of the small intestine of young rats.

    PubMed Central

    Morris, B; Morris, R

    1976-01-01

    1. The plasma volume in rats aged 15-16 days was measured by dilution analysis using homologous, 125I-labelled immunoglobulin G. A mean plasma volume of 5-53 ml./100 g and a mean blood volume of 8-01 ml./100 g were obtained.2. After the injection of labelled immunoglobulin G into the heart, homogenates of various abdominal organs and of the carcass were prepared. Labelled immunoglobulin G left the vascular compartment at a rate of about 9-10%/hr over a 3 hr period. About 11% of the labelled immunoglobulin G was catabolized in 2 hr. 3. The data obtained from these studies was used to make quantitative estimates of the amount of intact immunoglobulin G transmitted from the proximal intestine and from the ileum after the intra-intestinal injection of 1000 mug of labelled immunoglobulin G.Homogenates of the experimental animals were prepared and it was estimated that over 40% of the labelled immunoglobulin G was transmitted as intact protein from the proximal intestine. The results suggest that no intact immunoglobulin G was transmitted from the ileum, but about 15% of the protein removed from the ileum was recovered in the whole body as degraded fragments precipitable with trichloroacetic acid. 4. These observations are discussed in the context of the transmission of antibodies, and their relevance to the receptor hypothesis is considered. PMID:1263138

  17. Epidemiology of cancer of the small intestine

    PubMed Central

    Pan, Sai Yi; Morrison, Howard

    2011-01-01

    Cancer of the small intestine is very uncommon. There are 4 main histological subtypes: adenocarcinomas, carcinoid tumors, lymphoma and sarcoma. The incidence of small intestine cancer has increased over the past several decades with a four-fold increase for carcinoid tumors, less dramatic rises for adenocarcinoma and lymphoma and stable sarcoma rates. Very little is known about its etiology. An increased risk has been noted for individuals with Crohn’s disease, celiac disease, adenoma, familial adenomatous polyposis and Peutz-Jeghers syndrome. Several behavioral risk factors including consumption of red or smoked meat, saturated fat, obesity and smoking have been suggested. The prognosis for carcinomas of the small intestine cancer is poor (5 years relative survival < 30%), better for lymphomas and sarcomas, and best for carcinoid tumors. There has been no significant change in long-term survival rates for any of the 4 histological subtypes. Currently, with the possible exceptions of obesity and cigarette smoking, there are no established modifiable risk factors which might provide the foundation for a prevention program aimed at reducing the incidence and mortality of cancers of the small intestine. More research with better quality and sufficient statistical power is needed to get better understanding of the etiology and biology of this cancer. In addition, more studies should be done to assess not only exposures of interest, but also host susceptibility. PMID:21461167

  18. Epidemiology of cancer of the small intestine.

    PubMed

    Pan, Sai Yi; Morrison, Howard

    2011-03-15

    Cancer of the small intestine is very uncommon. There are 4 main histological subtypes: adenocarcinomas, carcinoid tumors, lymphoma and sarcoma. The incidence of small intestine cancer has increased over the past several decades with a four-fold increase for carcinoid tumors, less dramatic rises for adenocarcinoma and lymphoma and stable sarcoma rates. Very little is known about its etiology. An increased risk has been noted for individuals with Crohn's disease, celiac disease, adenoma, familial adenomatous polyposis and Peutz-Jeghers syndrome. Several behavioral risk factors including consumption of red or smoked meat, saturated fat, obesity and smoking have been suggested. The prognosis for carcinomas of the small intestine cancer is poor (5 years relative survival < 30%), better for lymphomas and sarcomas, and best for carcinoid tumors. There has been no significant change in long-term survival rates for any of the 4 histological subtypes. Currently, with the possible exceptions of obesity and cigarette smoking, there are no established modifiable risk factors which might provide the foundation for a prevention program aimed at reducing the incidence and mortality of cancers of the small intestine. More research with better quality and sufficient statistical power is needed to get better understanding of the etiology and biology of this cancer. In addition, more studies should be done to assess not only exposures of interest, but also host susceptibility. PMID:21461167

  19. Treatment Option Overview (Small Intestine Cancer)

    MedlinePlus

    ... small intestine cancer include unexplained weight loss and abdominal pain. These and other signs and symptoms may be ... doctor if you have any of the following: Pain or cramps in the middle of the abdomen. Weight loss with no known reason. A lump ...

  20. Small intestinal permeability in older adults

    PubMed Central

    Valentini, Luzia; Ramminger, Sara; Haas, Verena; Postrach, Elisa; Werich, Martina; Fischer, André; Koller, Michael; Swidsinski, Alexander; Bereswill, Stefan; Lochs, Herbert; Schulzke, Jörg‐Dieter

    2014-01-01

    Abstract It is not yet clear whether intestinal mucosal permeability changes with advancing age in humans. This question is of high importance for drug and nutrition approaches for older adults. Our main objective was to answer the question if small intestinal barrier integrity deteriorates with healthy aging. We conducted a cross‐sectional study including the pooled data of 215 nonsmoking healthy adults (93 female/122 male), 84 of whom were aged between 60 and 82 years. After a 12‐h fast, all participants ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 5 h afterwards and analyzed for test sugars. The permeability index (PI = lactulose/mannitol) was used to assess small intestinal permeability. Low‐grade inflammation defined by high‐sensitivity C‐reactive protein ≥1 mL/L and kidney function (estimated glomerular filtration rate) were determined in the older age group. The PI was similar in older compared to younger adults (P =0.887). However, the urinary recovery of lactulose and mannitol was lower in the older adults and this change was neither associated with urinary volume nor glomerular filtration rate. The PI was not significantly correlated with low‐grade inflammation or presence of noninsulin‐dependent type 2 diabetes. However, it significantly deteriorated in the copresence of both conditions compared to low‐grade inflammation alone (P =0.043) or type 2 diabetes alone (P =0.015). Small intestinal mucosal barrier does not deteriorate with age per se. But low‐grade inflammation coupled with minor disease challenges, such as type 2 diabetes, can compromise the small intestinal barrier. PMID:24771689

  1. Flow and mixing by small intestine villi.

    PubMed

    Lim, Y F; de Loubens, C; Love, R J; Lentle, R G; Janssen, P W M

    2015-06-01

    Flow and mixing in the small intestine are multi-scale processes. Flows at the scale of the villi (finger-like structures of ≈500 μm length) are poorly understood. We developed a three-dimensional lattice-Boltzmann model to gain insight into the effects of villous movements and the rheology of digesta on flow, mixing and absorption of nutrients at the periphery of the intestinal lumen. Our model simulated the hydrodynamic consequences of villi movements that resulted from folding of the mucosa during longitudinal contractions. We found that cyclic approximation and separation of groups of villi generated laminar eddies at the edges of the group and augmented mass transfers in the radial direction between the inter-villous space and the intestinal lumen which improved the absorption of nutrients and mixing at the periphery of the lumen. This augmentation was greater with highly diffusible nutrients and with high levels of shear-thinning (pseudoplasticity) of the fluid. We compared our results with bulk flows simulations done by previous workers and concluded that villous movements during longitudinal contractions is a major radial mixing mechanism in the small intestine and increases mixing and absorption around the mucosa despite adverse rheology. PMID:25968481

  2. Intestinal disaccharidase activity following pancreatic duct occlusion in the rat.

    PubMed

    Hauer-Jensen, M; Christensen, K; Wilson, H D; Schedl, H P

    1987-01-01

    The influence of pancreatic secretions on growth and brush-border enzyme activity, throughout the entire small intestine, was examined in the rat. Pancreatic secretions were excluded from the gut lumen by stapling the pancreatic ducts, without interruption of bile flow. The entire small intestine was studied as four segments; the duodenum and three distal segments of equal length. Weight of intestine and mucosa, and mucosal sucrase, isomaltase, lactase, and alkaline phosphatase activity were measured 10-15 days following pancreatic duct occlusion, or sham-operation. The duodenum of pancreatic duct-occluded animals exhibited significant hypertrophy. In general, specific and total disaccharidase activities were greater in duct-occluded animals than in controls throughout the intestine. The increase was more pronounced in distal than in proximal segments. The sucrase/isomaltase ratio was significantly greater in pancreatic duct-occluded animals than in controls in the two distal segments. Alkaline phosphatase activity was not affected by pancreatic duct occlusion. The greater relative increase of disaccharidase activities and sucrase/isomaltase activity ratios in the distal segments of duct-occluded animals, indicates a more important regulatory role of pancreatic enzymes in the distal small intestine. It is concluded that regulation of intestinal brush-border enzyme activity by pancreatic secretion is selective for enzyme and site as follows: disaccharidases, but not alkaline phosphatase, are regulated; the sucrase subunit of the sucrase/isomaltase complex is most sensitive to regulation, while lactase is least sensitive; and the regulatory effect on disaccharidases is greater in distal than in proximal intestine. PMID:3114740

  3. Chloride channels in the small intestinal cell line IEC-18.

    PubMed

    Basavappa, Srisaila; Vulapalli, Sreesatya Raju; Zhang, Hui; Yule, David; Coon, Steven; Sundaram, Uma

    2005-01-01

    Small intestinal crypt cells play a critical role in modulating Cl- secretion during digestion. The types of Cl- channels mediating Cl- secretion in the small intestine was investigated using the intestinal epithelial cell line, IEC-18, which was derived from rat small intestine crypt cells. In initial radioisotope efflux studies, exposure to forskolin, ionomycin or a decrease in extracellular osmolarity significantly increased 36Cl efflux as compared to control cells. Whole cell patch clamp techniques were subsequently used to examine in more detail the swelling-, Ca2+-, and cAMP-activated Cl- conductance. Decreasing the extracellular osmolarity from 290 to 200 mOsm activated a large outwardly rectifying Cl- current that was voltage-independent and had an anion selectivity of I- > Cl-. Increasing cytosolic Ca2+ by ionomycin activated whole cell Cl- currents, which were also outwardly rectifying but were voltage-dependent. The increase in intracellular Ca2+ levels with ionomycin was confirmed with fura-2 loaded IEC-18 cells. A third type of whole cell Cl- current was observed after increases in intracellular cAMP induced by forskolin. These cAMP-activated Cl- currents have properties consistent with cystic fibrosis transmembrane regulator (CFTR) Cl- channels, as the currents were blocked by glibenclamide or NPPB but insensitive to DIDS. In addition, the current-voltage relationship was linear and had an anion selectivity of Cl- > I-. Confocal immunofluorescence studies and Western blots with two different anti-CFTR antibodies confirmed the expression of CFTR. These results suggest that small intestinal crypt cells express multiple types of Cl- channels, which may all contribute to net Cl- secretion. PMID:15389550

  4. Effect of sulfite intake on intestinal enzyme activity in rats.

    PubMed

    Rodriguez Vieytes, M; Martinez-Sapiña, J; Taboada Montero, C; Lamas Aneiros, M

    1994-01-01

    Sulfites are usually added to food, beverages and pharmaceuticals as preservative antioxidants, bleaching agents, and dough conditioning agents. Ingestion of foods containing sulfites can cause abdominal pain, diarrhoea, seizures and death. Sulfite can react with cellular components and can cause toxicity. Changes in mucosal disaccharidases and phosphatase alkaline after sodium metabisulfite administration were investigated in the small intestine of rats. Female Wistar rats were given a diet supplemented with 0.25 or 2.5% sodium metabisulfite for 5 weeks. Sucrase, maltase, lactase and alkaline phosphatase were assayed in intestinal homogenates and in brush border membrane fractions. The intake of only 2.5% sulfite induced an increase in the specific activities of sucrase, maltase, and alkaline phosphatase compared to control levels (P < 0.05). Lactase levels were affected in a variable manner. The origin of such altered enzyme activities is still unknown. PMID:7958644

  5. Age-related increases in F344 rat intestine microsomal quercetin glucuronidation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to establish the extent age modifies intestinal quercetin glucuronidation capacity. Pooled microsomal fractions of three equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats (n=8/group) were employed to model the enzyme kinetics of UDP-gl...

  6. Enhanced intestinal permeability to 51Cr-labeled EDTA in dogs with small intestinal disease.

    PubMed

    Hall, E J; Batt, R M

    1990-01-01

    Intestinal permeability in dogs with small intestinal disease was measured by quantitation of 24-hour urinary excretion of 51Cr-labeled EDTA following intragastric administration. Permeability was high in dogs with a variety of naturally acquired small intestinal diseases including wheat-sensitive enteropathy of Irish Setters, small intestinal bacterial over-growth, and giardiasis, and permeability was decreased after successful treatment. These findings indicate that the assessment of intestinal permeability may be a useful technique for detecting small intestinal disease and for monitoring the efficacy of treatment in dogs. PMID:2104825

  7. [The activity of the lipid peroxidation processes in the mucosa of the rat small intestine and its morphofunctional state under acute irradiation and the administration of combined preparations created on a base of highly dispersed silica].

    PubMed

    Iakubovskiĭ, M M; Pentiuk, A A; Khmelnitskiĭ, O K; Oleĭnik, V N

    1997-01-01

    Morphofunctional and biochemical studies were carried out on bastard male rats (weight 200-240 g). The results showed that X-ray irradiation had induced structural alterations and elevation of lipid peroxidation in small intestine. Using of complex preparations defended this organ against pathological damages. The first preparation provided rat organisms with 100 ml/kg of silica, 2 mg/kg of beta-carotene, 30 mg/kg of alpha-tocopherol and 0.2 mg/kg of natrium selenite. The second preparation provided 100 mg/kg of silica, 10 mg/kg of dry Rhodiola extract, 0.1 mg/kg of tincture of Lagochilus [correction of Ladohilli] inebrians and 0.05 ml/kg of tincture of Aralia mandshurica. The third preparation provided organism with 100 mg/kg of silica and 20 mg/kg of thiobenzimidazole derivative. All these preparations had produced marked pharmacological effect. PMID:9244524

  8. Suppression of contractile activity in the small intestine by indomethacin and omeprazole.

    PubMed

    Lichtenberger, Lenard M; Bhattarai, Deepa; Phan, Tri M; Dial, Elizabeth J; Uray, Karen

    2015-05-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat a number of conditions, and proton pump inhibitors (PPIs) are often used to prevent NSAID-induced gastric mucosal damage; however, the effects of NSAIDs on intestinal motility are poorly understood. The purpose of the present study is to determine the effects of a prototypical NSAID, indomethacin, either alone or in conjunction with the PPI omeprazole, on intestinal motility. Rats were randomly divided into four groups treated with vehicle, omeprazole, indomethacin, or a combination of indomethacin and omeprazole. Intestinal motility and transit were measured along with inflammatory mediators in the intestinal smooth muscle, markers of mucosal damage, and bacterial counts in the intestinal wall. Indomethacin, but not omeprazole, caused mucosal injury indicated by lower gut bleeding; however, both omeprazole and indomethacin suppressed contractile activity and frequency in the distal part of the small intestine. Cotreatment with omeprazole did not reduce indomethacin-induced intestinal bleeding. Furthermore, although indomethacin caused increased inflammation as indicated by increased edema development and inflammatory mediators, cotreatment with omeprazole did not reduce inflammation in the intestinal smooth muscle or prevent the increased bacterial count in the intestinal wall induced by indomethacin. We conclude that both NSAID and PPI treatment suppressed contractile activity in the distal regions of the small intestine. The suppression of intestinal contractility was associated with increased inflammation in both cases; however, indomethacin and omeprazole appear to affect intestinal motility by different mechanisms. PMID:25721304

  9. Divergent Effect of Dezocine, Morphine and Sufentanil on Intestinal Motor Function in Rats

    PubMed Central

    Bian, Xiaocui; Zhou, Renlong; Yang, Yuting; Li, Peiying; Hang, Yannan; Hu, Youmin; Yang, Liqun; Wen, Daxiang

    2015-01-01

    Background: Opioid induced bowel dysfunction is the most common side effect of preoperatively administrated morphine, fentanyl and its derivative. However, the influence of dezocine on intestinal mobility is rarely reported. This study was designed to investigate the effects of dezocine, morphine and sufentanil on both intestinal smooth muscle contraction and propulsion in rats. Methods: Contractile tension and frequency of isolated rat small intestine smooth muscle were measured using tension transducer after incubation with different concentrations of dezocine, morphine and sufentanil. The propulsive rate of methylene blue in rat intestinal tract was measured 30 minutes after intraperitoneal injection of morphine, sufentanil and dezocine. Percent of change in contractile tension and contraction frequency compared to baseline level were calculated to evaluate muscle contraction. Propulsive rate of methylene blue was calculated as the percentage of methylene blue moving distance in intestinal tract compared to the length of the small intestine. Results: Morphine and sufentanil significantly increased the contractile tension of isolated small intestine smooth muscle at high doses. The contraction frequency did not change significantly among the 3 tested doses. Increasing the dose of dezocine from 1.7 mg.L-1 to 10.2 mg.L-1 did not change either the contractile tension or the contraction frequency. The propulsive rate of methylene blue in intestinal tract was significantly decreased after the treatment with morphine, sufentanil and dezocine (45.6%, 43.7%, and 42.1% respectively) compared to control group(57.1%), while the difference among the 3 drug groups were not significant. Conclusion: Morphine and sufentanil may dose dependently increase the contractile tension and contraction ability of isolated rat small intestine smooth muscle, while dezocine has no significant effect on intestine smooth muscle contraction. However, all these opioids might impair small

  10. Peptide neurons in the canine small intestine.

    PubMed

    Daniel, E E; Costa, M; Furness, J B; Keast, J R

    1985-07-01

    The distributions of peptide-containing nerve fibers and cell bodies in the canine small intestine were determined with antibodies raised against seven peptides: enkephalin, gastrin-releasing peptide (GRP), neuropeptide Y, neurotensin, somatostatin, substance P, and vasoactive intestinal peptide (VIP). Immunoreactive nerve cell bodies and fibers were found for each peptide except neurotensin. In the muscle layers there were numerous substance P, VIP, and enkephalin fibers, fewer neuropeptide Y fibers, and very few GRP or somatostatin fibers. The mucosa contained many VIP and substance P fibers, moderate numbers of neuropeptide Y, somatostatin, and GRP fibers and rare enkephalin fibers. Nerve cell bodies reactive for each of the six neural peptides were located in both the myenteric and submucous plexuses. The distributions of nerve cell bodies and processes in the canine small intestine show many similarities with other mammals, for example, in the distributions of VIP, substance P, neuropeptide Y, and somatostatin nerves. There are some major differences, such as the presence in dogs of numerous submucosal nerve cell bodies with enkephalinlike immunoreactivity and of GRP-like immunoreactivity in submucous nerve cell bodies and mucosal fibers. PMID:2411766

  11. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways including those that regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport and me...

  12. [Four Cases of Primary Small Intestinal Cancer].

    PubMed

    Nomi, Masako; Tanaka, Keita; Mase, Takahiro; Nagao, Shuji; Kawamoto, Shunji; Yoshida, Takahisa

    2015-11-01

    Primary small intestinal cancer is very rare. We experienced 4 cases from 2001 to 2013. Case 1: A 46-year-old man presented with abdominal pain and melena. Computed tomography (CT) revealed a tumor in the jejunum. We performed partial resection and lymph node dissection. The histological examination confirmed the diagnosis of moderately differentiated adenocarcinoma, SEN0H0P0M0. He has been recurrence-free for 13 years. Case 2: An 84-year-old woman presented with abdominal pain and vomiting. Gastroscopy showed a tumor in the upper jejunum, and she was diagnosed with adenocarcinoma. Postoperative diagnosis was SEN0H0P0M0. She has been alive for 7 years. Case 3: A 66-year-old woman presented with epigastric discomfort and back pain. Examinations confirmed poorly differentiated small intestinal adenocarcinoma with multiple liver and lymph node metastases. She refused chemotherapy and died 1 month later. Case 4: A 60-year-old man presented with abdominal pain and vomiting. CT revealed a tumor in the jejunum. Gastroscopic biopsy led to a diagnosis of poorly differentiated adenocarcinoma. We performed partial resection but there was extensive lymph node metastasis and peritoneal dissemination (cSIN2H0P3M1) so curative resection was impossible. Two courses of chemotherapy with S-1 and CDDP were administered. However, chemotherapy was not effective. He died 3.5 months after the first operation. Based on 2 of our cases, the prognosis for primary small intestine adenocarcinoma with lymph node metastasis or peritoneal dissemination was poor, with survival of less than 6 months. However, N0 cases without peritoneal dissemination can achieve long-term survival with curative resection. We report these cases with a review of previously reported cases in the literature. PMID:26805145

  13. Biaxial mechanical modeling of the small intestine.

    PubMed

    Bellini, Chiara; Glass, Paul; Sitti, Metin; Di Martino, Elena S

    2011-11-01

    Capsule endoscopes are pill-size devices provided with a camera that capture images of the small intestine from inside the body after being ingested by a patient. The interaction between intestinal tissue and capsule endoscopes needs to be investigated to optimize capsule design while preventing tissue damage. To that purpose, a constitutive model that can reliably predict the mechanical response of the intestinal tissue under complex mechanical loading is required. This paper describes the development and numerical validation of a phenomenological constitutive model for the porcine duodenum, jejunum and ileum. Parameters characterizing the mechanical behavior of the material were estimated from planar biaxial test data, where intestinal tissue specimens were simultaneously loaded along the circumferential and longitudinal directions. Specimen-specific Fung constitutive models were able to accurately predict the planar stress-strain behavior of the tested samples under a wide range of loading conditions. To increase model generality, average anisotropic constitutive relationships were also generated for each tissue region by fitting average stress-strain curves to the Fung potential. Due to the observed variability in the direction of maximum stiffness, the average Fung models were less anisotropic than the specimen-specific models. Hence, average isotropic models in the Neo-Hookean and Mooney-Rivlin forms were attempted, but they could not adequately describe the degree of nonlinearity in the tissue. Values of the R2 for the nonlinear regressions were 0.17, 0.44 and 0.93 for the average Neo-Hookean, Mooney-Rivlin and Fung models, respectively. Average models were successfully implemented into FORTRAN routines and used to simulate capsule deployment with a finite element method analysis. PMID:22098873

  14. Hyperosmolarity in the small intestine contributes to postprandial ghrelin suppression

    PubMed Central

    Overduin, Joost; Tylee, Tracy S.; Frayo, R. Scott

    2014-01-01

    Plasma levels of the orexigenic hormone ghrelin are suppressed by meals with an efficacy dependent on their macronutrient composition. We hypothesized that heterogeneity in osmolarity among macronutrient classes contributes to these differences. In three studies, the impact of small intestinal hyperosmolarity was examined in Sprague-Dawley rats. In study 1, isotonic, 2.5×, and 5× hypertonic solutions of several agents with diverse absorption and metabolism properties were infused duodenally at a physiological rate (3 ml/10 min). Jugular vein blood was sampled before and at 30, 60, 90, 120, 180, 240, and 300 min after infusion. Plasma ghrelin was suppressed dose dependently and most strongly by glucose. Hyperosmolar infusions of lactulose, which transits the small intestine unabsorbed, and 3-O-methylglucose (3-O-MG), which is absorbed like glucose but remains unmetabolized, also suppressed ghrelin. Glucose, but not lactulose or 3-O-MG, infusions increased plasma insulin. In study 2, intestinal infusions of hyperosmolar NaCl suppressed ghrelin, a response that was not attenuated by coinfusion with the neural blocker lidocaine. In study 3, we reconfirmed that the low-osmolar lipid emulsion Intralipid suppresses ghrelin more weakly than isocaloric (but hypertonic) glucose. Importantly, raising Intralipid's osmolarity to that of the glucose solution by nonabsorbable lactulose supplementation enhanced ghrelin suppression to that seen after glucose. Hyperosmolar ghrelin occurred particularly during the initial 3 postinfusion hours. We conclude that small intestinal hyperosmolarity 1) is sufficient to suppress ghrelin, 2) may combine with other postprandial mechanisms to suppress ghrelin, 3) might contribute to altered ghrelin regulation after gastric bypass surgery, and 4) may inform dietary modifications for metabolic health. PMID:24789208

  15. Meal-contingent intestinal lymph sampling from awake, unrestrained rats.

    PubMed

    Arnold, Myrtha; Dai, Yunting; Tso, Patrick; Langhans, Wolfgang

    2012-06-15

    Standard procedures for intestinal lymph collection involve continuous, quantitative drainage of the lymph fluid in anesthetized or restrained animals that are often euthanized within 48 h. We here describe a novel technique for the nonocclusive cannulation of the major intestinal lymph duct in rats that allows for repetitive in vivo sampling of intestinal lymph from unrestrained, awake, and ad libitum-fed animals. The distinctive feature of this novel technique is that a 5- to 7-mm long piece of Vialon tubing (OD/ID: 0.8/0.7 mm) with a small hole in its wall is first implanted into the major intestinal lymph duct for stabilization. The tapered tip (OD: ≈0.1 mm) of the catheter is then inserted into the hole of the tubing and fixed in place with a polyamid suture and a drop of tissue glue. In our hands, catheters implanted this way remain patent for up to 6 wk after surgery. In an initial experiment we collected lymph from six adult rats before (0) and 15, 30, 45, 60, 75, 90, 120, and 180 min (120 μl, each) after the onset of isocaloric (12.5 kcal) low-fat (LF) or high-fat (HF) test meals and measured active glucagon-like peptide-1 (GLP-1). Intestinal lymphatic GLP-1 concentration increased (P < 0.05) from ≈4 pmol/l (0 min) to a peak of 33 ± 6 (means ± SE) or 22 ± 4 pmol/l at 15 (HF) or 30 min (LF) after meal onset and gradually returned to baseline levels by 180 min. With this new technique fewer animals are required to generate physiologically relevant data for various aspects of gastrointestinal physiology that involve the lymphatic system. Furthermore, the advantage of this system is that the animal can act as its own control when the effect of different experimental protocols is tested. PMID:22513747

  16. Small intestinal bacterial overgrowth in dogs with chronic intestinal disease.

    PubMed

    Rutgers, H C; Batt, R M; Elwood, C M; Lamport, A

    1995-01-15

    Small intestinal bacterial overgrowth (SIBO) was diagnosed by quantitative bacterial culture of duodenal juice samples obtained endoscopically in 41 of 80 dogs that were admitted with chronic diarrhea, vomiting, or weight loss. Thirteen dogs had aerobic bacterial overgrowth, most frequently comprising Escherichia coli, staphylococci, and enterococci, and 28 dogs had mixed anaerobic overgrowth, most frequently including Clostridium and Bacteroides spp. Affected dogs comprised 23 breeds, including 10 German Shepherd Dogs and median age at diagnosis was 2 years (range, 6 months to 11 years). High serum folate and low serum cobalamin concentrations had fair specificity (79 and 87%, respectively), but low sensitivity (51 and 24%, respectively) in detecting SIBO. Histologic examination of duodenal biopsy specimens did not reveal abnormalities (26/41 dogs), or revealed mild to moderate lymphocytic (12/41) or eosinophilic (2/41) infiltrates, or lymphosarcoma (1/41). Oral antibiotic treatment was effective in 77% (23/30 dogs), but prolonged treatment (> 4 weeks) was required to control signs and prevent recurrence in 50% (15/30). Corticosteroids were used alone in a dog with eosinophilic enteritis and in combination with antibiotics in 4 dogs with marked gastrointestinal lymphocytic/plasmacytic infiltrates. This study suggested that SIBO may be observed in dogs of many breeds, without an obvious primary cause, and that, although results of indirect tests may be suggestive of SIBO, bacterial culture of duodenal juice samples remains necessary for definitive diagnosis. PMID:7751219

  17. Radioautographic visualization of differences in the pattern of (/sup 3/H)uridine and (/sup 3/H)orotic acid incorporation into the RNA of migrating columnar cells in the rat small intestine

    SciTech Connect

    Uddin, M.; Altmann, G.G.; Leblond, C.P.

    1984-05-01

    The epithelium of rat small intestine was radioautographed to examine whether RNA is synthesized by the salvage pathway as shown after (/sup 3/H)uridine injection or by the de novo pathway as shown after (/sup 3/H)orotic acid injection. The two modes of RNA synthesis were thus investigated during the migration of columnar cells from crypt base to villus top, and the rate of synthesis was assessed by counting silver grains over the nucleolus and nucleoplasm at six levels along the duodenal epithelium - that is, in the base, mid, and top regions of the crypts and in the base, mid, and top regions of the villi. Concomitant biochemical analyses established that, after injection of either (5-/sup 3/H)uridine or (5-/sup 3/H)orotic acid: (a) buffered glutaraldehyde fixative was as effective as perchloric acid or trichloroacetic acid in insolubilizing the nucleic acids of rat small intestine; (b) a major fraction of the nucleic acid label was in RNA, that is, 91% after (/sup 3/H)uridine and 72% after (/sup 3/H)orotic acid, with the rest in DNA; and (c) a substantial fraction of the RNA label was in poly A/sup +/ RNA (presumed to be messenger RNA). In radioautographs of duodenum prepared after (/sup 3/H)uridine injection, the count of silver grains was high over nucleolus and nucleoplasm in crypt base cells and gradually decreased at the upper levels up to the villus base. In the rest of the villus, the grain count over the nucleolus was negligible, while over the nucleoplasm it was low but significant.

  18. Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in obstructive jaundice rats

    PubMed Central

    Chen, Jun; Dong, Jia-Tian; Li, Xiao-Jing; Gu, Ye; Cheng, Zhi-Jian; Cai, Yuan-Kun

    2015-01-01

    AIM: To observe the protective effect of glucagon-like peptide-2 (GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect. METHODS: Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase (ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14th day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A (IgA) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group. RESULTS: In the rat model, jaundice was obvious, and the rats’ activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced IgA expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group (P < 0.01). The increasing levels of the aforementioned markers were more significant in the obstructive jaundice group than in the GLP-2 group (P < 0.01). CONCLUSION: GLP-2 reduces intestinal mucosal injuries in obstructive jaundice rats, which might be attributed to increased intestinal IgA and reduced bilirubin and endotoxin. PMID:25593463

  19. [Vascular lesions of the small intestine].

    PubMed

    Yano, Tomonori; Yamamoto, Hironori

    2008-07-01

    Small-intestinal vascular lesions accounted for the bleeding source in a large percentage of the patients with mid-GI-bleeding. The progress of enteroscopy has been changing the diagnostic and therapeutic algorithm for them. There are 3 pathological conditions of vascular lesions. Angioectasia is characterized by venous/capillary lesions, Dieulafoy' s lesion is characterized by arterial lesions, and AVM is a condition in which arteries and veins are directly connected without capillary beds. We classified vascular lesions with consideration of the presence or absence of pulsatility. The presence or absence of arterial components provides important information in understanding the pathological conditions. This classification will be useful for selecting hemostatic procedure and outcome studies. PMID:18616125

  20. Protective effect of the traditional Chinese medicine xuesaitong on intestinal ischemia-reperfusion injury in rats

    PubMed Central

    Xu, Xuan; Li, Dengxiao; Gao, Hong; Gao, Yuejin; Zhang, Long; Du, Yuling; Wu, Jian; Gao, Pengfei

    2015-01-01

    Objective: We investigated the effect of xuesaitong on intestinal barrier dysfunction and related mechanisms in a rat model for intestinal ischemia-reperfusion. Methods: Rats were divided into sham-operated, disease-model and Xuesaitong-treated groups. In the disease-model and Xuesaitong-treated rats an intestinal ischemia-reperfusion injury (IRI) model was introduced, which was created by a temporary obstruction of the superior mesenteric artery (SMA). The xuesaitong group was pre-treated with injections into the abdominal cavity prior to the generation of the IRI model. Tissue changes were evaluated using H&E staining and electron microscopy. Samples were analyzed at 0, 3 and 24 h post IRI. Ascites volumes as well as small intestinal mucosa bleeding, injury scores, wet to dry weight ratios, and propulsions were evaluated. Apoptotic rates were determined with TUNNEL assays. Blood serum tumor necrosis factor-α (TNF-α) levels were measured using ELISA, and Bcl-2 and caspase-3 expression in small intestinal mucosa measured using immunohistochemistry. Results: We determined a significant increase of pathological damage to small intestinal tissues, intestinal wet to dry ratios, ascites volume, TNF-α levels, apoptosis rates of small intestinal mucosa, and expression of Bcl-2 and caspase-3 proteins in the disease-model group compared to the sham-operated group (P < 0.001), and intestinal motility was significantly decreased (P < 0.001). However, comparisons between disease-model and xuesaitong pre-treated animals revealed, that in the treatment group these changes occurred in significant less severities. Conclusions: Xuesaitong can effectively alleviate intestinal barrier dysfunction caused by ischemia-reperfusion injury by reducing TNF-α, up-regulating Bcl-2 and down-regulating caspase-3 expression, in addition to increasing peristalsis. PMID:25932105

  1. Intestinal elimination of sparfloxacin, fleroxacin, and ciprofloxacin in rats.

    PubMed Central

    Rubinstein, E; Dautrey, S; Farinoti, R; St Julien, L; Ramon, J; Carbon, C

    1995-01-01

    The intestinal transepithelial elimination of sparfloxacin and fleroxacin was compared with that of ciprofloxacin in a rat model following a single parenteral administration of 25 mg of each of the antibiotics per kg of body weight. All three fluoroquinolones were eliminated through the small intestine. Ciprofloxacin was eliminated in the proximal jejunum at a rate of 1.97 +/- 0.70 micrograms/cm2, while the elimination rates of fleroxacin and sparfloxacin were 0.64 +/- 026 and 0.21 +/- 0.10 micrograms/cm2, respectively, over a 90-min collection period. In the ileum, the elimination rates of ciprofloxacin, fleroxacin, and sparfloxacin over the same period were 1.44 +/- 0.77, 1.00 +/- 0.33, and 0.41 +/- 0.26 micrograms/mc2, respectively. These data suggest that these fluoroquinolones undergo a transepithelial elimination process in the small intestine. This route of elimination may be important in the therapy of bacterial diarrhea. PMID:7695338

  2. Portocaval shunt for hepatocyte package: challenging application of small intestinal graft in animal models.

    PubMed

    Iwasaki, Junji; Hata, Toshiyuki; Uemoto, Shinji; Fujimoto, Yasuhiro; Kanazawa, Hiroyuki; Teratani, Takumi; Hishikawa, Shuji; Kobayashi, Eiji

    2013-10-01

    In developing therapeutic alternatives to liver transplantation, we have used the strategy of applying a small intestinal segment as a scaffold for hepatocyte transplantation and also as a portocaval shunt (PCS) system to address both liver dysfunction and portal hypertension. The aim of this study was to investigate the feasibility of such an intestinal segment in animal models. Hepatocytes isolated from luciferase-transgenic Lewis rats were transplanted into jejunal segments of wild-type Lewis rats with mucosa removal without PCS application. Luciferase-derived luminescence from transplanted hepatocytes was stably detected for 30 days. Then, we performed autologous hepatocyte transplantation into the submucosal layer of an isolated and vascularized small intestinal segment in pigs. Transplanted hepatocytes were isolated from the resected left-lateral lobe of the liver. On day 7, hepatocyte clusters and bile duct-like structures were observed histologically. To create an intestinal PCS system in pigs, an auto-graft of the segmental ileum and interposing vessel graft were anastomosed to the portal vein trunk and inferior vena cava. However, thrombi were observed in vessels of the intestinal PCSs. We measured the correlation between infusion pressure and flow volume in whole intestines ex vivo in both species and found that the high pressure corresponding to portal hypertension was still insufficient to maintain the patency of the intestinal grafts. In conclusion, we demonstrated the feasibility of the small intestine as a scaffold for hepatocyte transplantation in rat and pig models, but PCS using an intestinal graft failed to maintain patency in a pig model. PMID:23974217

  3. Intestinal hormones and growth factors: Effects on the small intestine

    PubMed Central

    Drozdowski, Laurie; Thomson, Alan BR

    2009-01-01

    There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In partI, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part II will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids. PMID:19152442

  4. Transepithelial transport of glutathione in isolated perfused small intestine

    SciTech Connect

    Hagen, T.M.; Jones, D.P.

    1986-03-01

    Uptake of GSH was studied in isolated perfused segment of jejunum in the adult rat. Krebs-Henseleit buffer was infused through the superior mesenteric artery and fractions were collected from the portal vein. The maintenance of vascular and epithelial integrity was established by lack of transfer of /sup 14/C-inulin or /sup 14/C-polyethylene glycol from the lumen to the perfusate. (glycine-2-/sup 3/H)GSH was introduced in the lumen and perfusate fractions collected every min. With 1 mM GSH and 10 mM Gly in the lumen, transport into the perfusate was 220 nmol/min. Analysis by HPLC showed that 80% was at the intact tripeptide, GSH. No cysteinylgylcine was detected in the perfusate. Pretreatment of the segment with 0.25 mM acivicin and 1 mM buthionine sulfoximine had no significant effect on GSH transport rate, thus showing that degradation and resynthesis of GSH did not contribute to the appearance of GSH in the perfusate. GSH transport was inhibited 50% by replacing lumenal NaCl with choline Cl. Addition of 10 mM ..gamma..-Clu-Glu or 10 mM ophthalmic acid decreased the rat of transport by 60-70%. These results establish that transepithelial transport of intact GSH occurs in rat small intestine. This may allow utilization of dietary GSH or reutilization of biliary GSH. In addition, the results suggest that oral GSH may be of therapeutic benefit.

  5. Regional intestinal blood flow and nitric oxide synthase inhibition during sepsis in the rat.

    PubMed Central

    Klemm, K; Moody, F G

    1998-01-01

    OBJECTIVE: Regional circulatory changes in intestinal mucosa were evaluated after the onset of septic shock and the effect of nitric oxide (NO) inhibition on mucosal blood flow was investigated at different locations along the intestine. SUMMARY BACKGROUND DATA: The response of intestinal blood flow to different physiologic and pharmacologic stimuli is known to vary along the intestine, but limited data are available on regional alterations in intestinal blood flow during septic shock. These regional variations in intestinal blood flow could become important because NO inhibition might restore the circulation of one segment of the gut or exacerbate ischemia that may be occurring concomitantly in another segment of the intestine. METHODS: Mucosal blood flow was studied with fluorescent microspheres in conscious unrestrained rats before and 2, 4, and 6 hours after lipopolysaccharide (LPS, 20 mg/kg intraperitoneally) induced sepsis in the presence and absence of the nitric oxide synthase inhibitor N(G)-nitro-L-argininemethylester (L-NAME, 5 mg/kg subcutaneously). RESULTS: Control mucosal blood flow was significantly higher in the ileum than in the duodenum, jejunum, or colon. During LPS-induced sepsis, mucosal blood flow to the ileum decreased and perfusion to the remaining gut was preserved. This was accompanied by hypotension throughout the experiment. L-NAME administration during sepsis prevented hypotension and decreased mucosal blood flow to all segments of small intestine at 2 hours. In this group, mucosal blood flow to the proximal small intestine but not to the ileum returned to baseline levels at 4 and 6 hours. L-NAME alone decreased mucosal blood flow to the small intestine throughout the experiment. CONCLUSIONS: This study indicates that mucosal blood flow alterations during septic shock vary along the intestine, with a significant change only in the ileum, suggesting that perfusion in the small intestine is dependent on physiologic NO production. PMID

  6. Three-Dimensional Coculture Of Human Small-Intestine Cells

    NASA Technical Reports Server (NTRS)

    Wolf, David; Spaulding, Glen; Goodwin, Thomas J.; Prewett, Tracy

    1994-01-01

    Complex three-dimensional masses of normal human epithelial and mesenchymal small-intestine cells cocultured in process involving specially designed bioreactors. Useful as tissued models for studies of growth, regulatory, and differentiation processes in normal intestinal tissues; diseases of small intestine; and interactions between cells of small intestine and viruses causing disease both in small intestine and elsewhere in body. Process used to produce other tissue models, leading to advances in understanding of growth and differentiation in developing organisms, of renewal of tissue, and of treatment of myriad of clinical conditions. Prior articles describing design and use of rotating-wall culture vessels include "Growing And Assembling Cells Into Tissues" (MSC-21559), "High-Aspect-Ratio Rotating Cell-Culture Vessel" (MSC-21662), and "In Vitro, Matrix-Free Formation Of Solid Tumor Spheroids" (MSC-21843).

  7. Increased small intestinal apoptosis in coeliac disease.

    PubMed Central

    Moss, S F; Attia, L; Scholes, J V; Walters, J R; Holt, P R

    1996-01-01

    BACKGROUND: Coeliac disease (CD) mucosa is flattened despite epithelial hyperproliferation. AIMS: To establish mechanisms of cell loss in CD. PATIENTS: 14 controls, 17 active CD patients, and 16 maintained with gluten free diet. METHODS: Programmed cell death was examined in small intestinal biopsy specimens by staining fragmented DNA using terminal uridine deoxynucleotidyl nick end labelling (TUNEL), in comparison with haematoxylin and eosin stained adjacent sections. Double staining with anti-CD45 antibodies determined the origin of apoptotic cells. Apoptosis was graded from 1-3 (< 5, 5-20, > 20% respectively). Proliferating cells, immunostained by Ki-67 (MIB-1) antibody, were counted. RESULTS: Apoptotic cells were seen rarely by haematoxylin and eosin but more readily by TUNEL. In controls, 1.4 +/- 0.2% of epithelial cells were apoptotic (mean grade 1.1), mainly located in the upper villus. In active CD, frequent apoptotic cells were distributed throughout the crypt-villus unit (mean grade 2.4), decreasing after treatment to 1.1 (p < 0.001) even when still histologically abnormal. CD45 antibodies rarely stained apoptotic cells in active CD. The number of TUNEL positive cells correlated with proliferating cell number (p < 0.001). CONCLUSION: Enterocyte apoptosis is greatly increased in untreated CD, correlates with proliferation, and falls to normal with a gluten free diet, before histological improvement. Increased apoptosis may be responsible for villous atrophy in CD. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9038662

  8. A Revised Model for Dosimetry in the Human Small Intestine

    SciTech Connect

    John Poston; Nasir U. Bhuiyan; R. Alex Redd; Neil Parham; Jennifer Watson

    2005-02-28

    A new model for an adult human gastrointestinal tract (GIT) has been developed for use in internal dose estimations to the wall of the GIT and to the other organs and tissues of the body from radionuclides deposited in the lumenal contents of the five sections of the GIT. These sections were the esophasgus, stomach, small intestine, upper large intestine, and the lower large intestine. The wall of each section was separated from its lumenal contents.

  9. Macrophage Isolation from the Mouse Small and Large Intestine

    PubMed Central

    Harusato, Akihito; Geem, Duke; Denning, Timothy L.

    2016-01-01

    Macrophages play important roles in maintaining intestinal homeostasis via their ability to orchestrate responses to the normal microbiota as well as pathogens. One of the most important steps in beginning to understand the functions of these cells is the ability to effectively isolate them from the complex intestinal environment. Here, we detail methodology for the isolation and phenotypic characterization of macrophages from the mouse small and large intestine. PMID:27246032

  10. Distinct Human Stem Cell Populations in Small and Large Intestine

    PubMed Central

    Cramer, Julie M.; Thompson, Timothy; Geskin, Albert; LaFramboise, William; Lagasse, Eric

    2015-01-01

    The intestine is composed of an epithelial layer containing rapidly proliferating cells that mature into two regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for intestinal epithelial cells, no studies have directly compared stem cells derived from these anatomically distinct regions. Here, we examine intrinsic differences between primary epithelial cells isolated from human fetal small and large intestine, after in vitro expansion, using the Wnt agonist R-spondin 2. We utilized flow cytometry, fluorescence-activated cell sorting, gene expression analysis and a three-dimensional in vitro differentiation assay to characterize their stem cell properties. We identified stem cell markers that separate subpopulations of colony-forming cells in the small and large intestine and revealed important differences in differentiation, proliferation and disease pathways using gene expression analysis. Single cells from small and large intestine cultures formed organoids that reflect the distinct cellular hierarchy found in vivo and respond differently to identical exogenous cues. Our characterization identified numerous differences between small and large intestine epithelial stem cells suggesting possible connections to intestinal disease. PMID:25751518

  11. Internal frontier: The pathophysiology of the small intestine

    PubMed Central

    Sugimura, Haruhiko; Osawa, Satoshi

    2013-01-01

    Even though the small intestine occupies a major portion of the abdominal space and is essential for life, in most pathology textbooks any chapter on small intestinal diseases, especially in human beings, is typically shorter than those for other gastrointestinal organs. Clinical and experimental investigations of the small intestine in various clinical situations, such as nutrition management, obesity interventions, and emergency care, have elucidated several important biological problems associated with the small intestine, the last frontier of gastroenterology. In this issue, a review by Professor Basson and his team at Michigan State University sheds light on the changes in the human small intestine under various conditions based on their clinical and surgical experience. With the advent of recent innovations in enteroscopy, a form of endoscopy used to examine deep within the small intestine, the issue that they highlighted, i.e., mucosal adaptation and atrophy of the human small intestine, has emerged as a major and manageable challenge for gastroenterologists in general, including the readers of the World Journal of Gastroenterology. PMID:23345938

  12. The use of isolated enterocytes to study Phase I intestinal drug metabolism: validation with rat and pig intestine.

    PubMed

    Bonnefille, Philippe; Sezgin-Bayindir, Zerrin; Belkhelfa, Haouaria; Arellano, Cécile; Gandia, Peggy; Woodley, John; Houin, Georges

    2011-02-01

    An important step in the development of new drugs is to evaluate the extent of their metabolism during absorption in the small intestine. Reliable in vitro systems to do this can expediate the development process, but the current systems are often unsuitable because they lack the appropriate metabolic enzymes (e.g. Caco-2 cell monolayers) or are not representative of the physiological conditions present in the intact intestinal cells (e.g. isolated microsomes). The aim of this study was to validate the use of isolated intestinal epithelial cells (enterocytes), equivalent to hepatocytes, to evaluate Phase I drug metabolism. A method was developed to prepare enterocytes from rat and pig (as metabolically closer to man) that maintained good viability and activity for up to 90 min as judged by trypan blue exclusion and the release of the cytosolic enzyme lactate dehydrogenase. The Phase I metabolism of the established marker drugs: midazolam, bupropion and dextromethorphan were measured by LC-MS and confirmed the activities of the 3A, 2B and 2D families of CYP isoforms, respectively. The kinetic parameters, K(m) and V(max), were compared between isolated cells and isolated intestinal microsomes from the rat. The use of isolated intestinal cells is a simple and practical method to study the Phase I metabolism of drugs during their absorption and the potential for drug-drug interactions. The method could eventually be modified and usefully applied to human studies. PMID:21121944

  13. The quantitative assessment of normal canine small intestinal mucosa.

    PubMed

    Hart, I R; Kidder, D E

    1978-09-01

    Quanitative methods of assessing the architecture of small intestinal mucosa have been applied to biopsy material from normal dogs. Mucosal samples taken from four predetermined sites show that there are significant quantitative differences between the various levels of the small bowel. Animals of one year of age and older show no correlation between age or weight and mucosal dimensions. The significance of these findings, in relation to examination of biopsy material from cases of clinical small intestinal disease, is discussed. PMID:364574

  14. Diagnosis and treatment of small intestinal bacterial overgrowth.

    PubMed

    Ponziani, Francesca Romana; Gerardi, Viviana; Gasbarrini, Antonio

    2016-01-01

    A huge number of bacteria are hosted in the gastrointestinal tract, following a gradient increasing towards the colon. Gastric acid secretion and intestinal clearance provide the qualitative and quantitative partitioning of intestinal bacteria; small intestinal bacteria overgrowth (SIBO) occurs when these barrier mechanisms fail. Diagnosis of SIBO is challenging due to the low specificity of symptoms, the frequent association with other diseases of the gastrointestinal tract and the absence of optimal objective diagnostic tests. The therapeutic approach to SIBO is oriented towards resolving predisposing conditions, and is supported by antibiotic treatment to restore the normal small intestinal microflora and by modifications of dietary habits for symptomatic relief. In the near future, metagenomics and metabolomics will help to overcome the uncertainties of SIBO diagnosis and the pitfalls of therapeutic management, allowing the design of a personalized strategy based on the direct insight into the small intestinal microbial community. PMID:26636484

  15. Effect of hypokinesia on invertase activity of the mucosa of the small intestine

    NASA Technical Reports Server (NTRS)

    Abdusattarov, A.

    1980-01-01

    The effect of prolonged hypokinesia on the enzyme activity of the middle portion of the small intestine was investigated. Eighty-four mongrel white male rats weighing 170-180 g were divided into two equal groups. The experimental group were maintained in single cages under 30 days of hypokinetic conditions and the control animals were maintained under ordinary laboratory conditions. It is concluded that rates of invertase formation and its inclusion in the composition if the cellular membrane, if judged by the enzyme activity studied in sections of the small intestine, are subject to phase changes in the course of prolonged hypokinesia.

  16. Endurance exercise training programs intestinal lipid metabolism in a rat model of obesity and type 2 diabetes

    PubMed Central

    Hung, Yu‐Han; Linden, Melissa A.; Gordon, Alicia; Scott Rector, R.; Buhman, Kimberly K.

    2015-01-01

    Abstract Endurance exercise has been shown to improve metabolic outcomes in obesity and type 2 diabetes; however, the physiological and molecular mechanisms for these benefits are not completely understood. Although endurance exercise has been shown to decrease lipogenesis, promote fatty acid oxidation (FAO), and increase mitochondrial biosynthesis in adipose tissue, muscle, and liver, its effects on intestinal lipid metabolism remain unknown. The absorptive cells of the small intestine, enterocytes, mediate the highly efficient absorption and processing of nutrients, including dietary fat for delivery throughout the body. We investigated how endurance exercise altered intestinal lipid metabolism in obesity and type 2 diabetes using Otsuka Long‐Evans Tokushima Fatty (OLETF) rats. We assessed mRNA levels of genes associated with intestinal lipid metabolism in nonhyperphagic, sedentary Long‐Evans Tokushima Otsuka (LETO) rats (L‐Sed), hyperphagic, sedentary OLETF rats (O‐Sed), and endurance exercised OLETF rats (O‐EndEx). O‐Sed rats developed hyperphagia‐induced obesity (HIO) and type 2 diabetes compared with L‐Sed rats. O‐EndEx rats gained significantly less weight and fat pad mass, and had improved serum metabolic parameters without change in food consumption compared to O‐Sed rats. Endurance exercise resulted in dramatic up‐regulation of a number of genes in intestinal lipid metabolism and mitochondrial content compared with sedentary rats. Overall, this study provides evidence that endurance exercise programs intestinal lipid metabolism, likely contributing to its role in improving metabolic outcomes in obesity and type 2 diabetes. PMID:25602012

  17. In Vivo Physiological Experiments in the Random Positioning Macine: A Study on the Rat Intestinal Transit

    NASA Astrophysics Data System (ADS)

    Peana, A. T.; Marzocco, S.; Bianco, G.; Autore, G.; Pinto, A.; Pippia, P.

    2008-06-01

    The aim of this work is to evaluate the rat intestinal transit as well as the expression of enzymes involved in this process and in gastrointestinal homeostasis as ciclooxygenase (COX-1 and COX-2), the inducibile isoform of nitric oxide synthase (iNOS), ICAM-1 and heat shock proteins HSP70 and HSP90. The modeled microgravity conditions were performed utilizing a three-dimensional clinostat, the Random Positioning Machine (RPM). Our results indicate that modeled microgravity significantly reduce rat intestinal transit. Western blot analysis on small intestine tissues of RPM rats reveals a significant increase in iNOS expression, a significant reduction in COX-2 levels, while COX-1 expression remains unaltered, and a significant increase in ICAM-1 and HSP 70 expression. Also a significant increase in HSP 90 stomach expression indicates a strong effect of simulated low g on gastrointestinal homeostasis.

  18. Intestinal Assimilation of a Tetrapeptide in the Rat

    PubMed Central

    Smithson, Kenneth W.; Gray, Gary M.

    1977-01-01

    The small intestine is capable of taking up peptide nutrients of two or three amino acid residues, but the mechanism of intestinal assimilation of larger oligopeptides has not been established. The amino-oligopeptidase of the intestinal brush border possesses high specificity for oligopeptides having bulky side chains and is a candidate for a crucial role in the overall assimilation of dietary protein. Rat jejunum was used for in vitro gut sac and in vivo perfusion experiments with Gly-l-Leu-Gly-Gly (2 mM) as the test substrate with analysis of parent peptide and products by automatic ion-exchange chromatography. In these experiments, the tetrapeptide disappeared rapidly from the test solution (20 μmol/s per cm2 in vitro; 17 μmol/s per cm2 in vivo) by sequential removal of amino acid residues from the N-terminus to yield amino acids and the C-terminal dipeptide. In gut sac experiments, 61-100% of these products of hydrolysis appeared in the incubation medium and the remainder in the tissue. In contrast, only small amounts of hydrolytic products were found within intestinal lumen in vivo. Gly-l-Pro (10 mM), a peptide known to be transported intact but not to be hydrolyzed by the brush border aminopeptidase, failed to inhibit Gly-l-Leu-Gly-Gly disappearance suggesting that the tetrapeptide does not utilize the known intact transport mechanism. Hypoxic conditions (N2 atmosphere) in vitro markedly inhibited transport of glucose, leucine, and Gly-Gly but failed to impair Gly-l-Leu-Gly-Gly disappearance suggesting that the first step in assimilation of the tetrapeptide does not involve a transport process. Disappearance of the tetrapeptide was completely blocked by l-leucyl-β-naphthylamide (10 mM), a specific substrate for brush border aminopeptidase and by the phthalimido derivative of l-leucine bromomethyl ketone, a potent peptidase inhibitor. Hence, the amino-oligopeptidase at the intestinal surface appears to be essential for the initial stages of assimilation of

  19. Effects of psychological stress on small intestinal motility and expression of cholecystokinin and vasoactive intestinal polypeptide in plasma and small intestine in mice

    PubMed Central

    Cao, Shu-Guang; Wu, Wan-Chun; Han, Zhen; Wang, Meng-Ya

    2005-01-01

    AIM: To investigate the effects of psychological stress on small intestinal motility and expression of cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP) in plasma and small intestine, and to explore the relationship between small intestinal motor disorders and gastrointestinal hormones under psychological stress. METHODS: Thirty-six mice were randomly divided into psychological stress group and control group. A mouse model with psychological stress was established by housing the mice with a hungry cat in separate layers of a two-layer cage. A semi-solid colored marker (carbon-ink) was used for monitoring small intestinal transit. CCK and VIP levels in plasma and small intestine in mice were measured by radioimmunoassay (RIA). RESULTS: Small intestinal transit was inhibited (52.18±19.15% vs 70.19±17.79%, P<0.01) in mice after psychological stress, compared to the controls. Small intestinal CCK levels in psychological stress mice were significantly lower than those in the control group (0.75±0.53 μg/g vs 1.98±1.17 μg/g, P<0.01), whereas plasma CCK concentrations were not different between the groups. VIP levels in small intestine were significantly higher in psychological stress mice than those in the control group (8.45±1.09 μg/g vs 7.03±2.36 μg/g, P<0.01), while there was no significant difference in plasma VIP levels between the two groups. CONCLUSION: Psychological stress inhibits the small intestinal transit, probably by down-regulating CCK and up-regulating VIP expression in small intestine. PMID:15655834

  20. A Multicellular Approach Forms a Significant Amount of Tissue-Engineered Small Intestine in the Mouse

    PubMed Central

    Sala, Frédéric G.; Matthews, Jamil A.; Speer, Allison L.; Torashima, Yasuhiro; Barthel, Erik R.

    2011-01-01

    Tissue-engineered small intestine (TESI) has successfully been used to rescue Lewis rats after massive small bowel resection. In this study, we transitioned the technique to a mouse model, allowing investigation of the processes involved during TESI formation through the transgenic tools available in this species. This is a necessary step toward applying the technique to human therapy. Multicellular organoid units were derived from small intestines of transgenic mice and transplanted within the abdomen on biodegradable polymers. Immunofluorescence staining was used to characterize the cellular processes during TESI formation. We demonstrate the preservation of Lgr5- and DcamKl1-positive cells, two putative intestinal stem cell populations, in proximity to their niche mesenchymal cells, the intestinal subepithelial myofibroblasts (ISEMFs), at the time of implantation. Maintenance of the relationship between ISEMF and crypt epithelium is observed during the growth of TESI. The engineered small intestine has an epithelium containing a differentiated epithelium next to an innervated muscularis. Lineage tracing demonstrates that all the essential components, including epithelium, muscularis, nerves, and some of the blood vessels, are of donor origin. This multicellular approach provides the necessary cell population to regenerate large amounts of intestinal tissue that could be used to treat short bowel syndrome. PMID:21395443

  1. The release of rat intestinal cholecystokinin after oral trypsin inhibitor measured by bio-assay.

    PubMed Central

    Brand, S J; Morgan, R G

    1981-01-01

    The distribution, molecular form and release of cholecystokinin (CCK)-like activity in extracts of rat small intestine was studied with an in vitro gall-bladder bio-assay. In contrast to the reported heterogeneity of CCK-like immunoreactivity in the intestine, only a single molecular form of CCK-like activity was detected using the bio-assay. 2. The CCK-like activity eluted from Sephadex G50 with a Kav of 0.69, after the triacontriapeptide of cholecystokinin (CCK33) and before cholecystokinin octapeptide 2500, may represent the 22 amino acid peptide of CCK (CCK22). The bio-assay peak of CCK-like activity had pancreozymin activity and CCK/gastrin C terminal immunoreactivity. The CCK-like activity weas readily extracted from the small intestine at neutral pH, but subsequent treatment with cold 0.5 M-acetic acid extracted further CCK-like activity of the same molecular form as that recovered under neutral conditions. 3. The bio-assay detected no CCK-like activity, nor was pancreozymin-like activity found in fractions corresponding to CCK33 or CCK8 after Sephadex G50 chromatography of rat intestinal extracts. 4. Oral trypsin inhibitor was a potent stimulus for the release of CCK-like activity from the upper small intestine of the rat. After oral trypsin inhibitor release, CCK-like activity was rapidly resynthesized. PMID:7320918

  2. Fgf9 signaling regulates small intestinal elongation and mesenchymal development.

    PubMed

    Geske, Michael J; Zhang, Xiuqin; Patel, Khushbu K; Ornitz, David M; Stappenbeck, Thaddeus S

    2008-09-01

    Short bowel syndrome is an acquired condition in which the length of the small intestine is insufficient to perform its normal absorptive function. Current therapies are limited as the developmental mechanisms that normally regulate elongation of the small intestine are poorly understood. Here, we identify Fgf9 as an important epithelial-to-mesenchymal signal required for proper small intestinal morphogenesis. Mouse embryos that lack either Fgf9 or the mesenchymal receptors for Fgf9 contained a disproportionately shortened small intestine, decreased mesenchymal proliferation, premature differentiation of fibroblasts into myofibroblasts and significantly elevated Tgfbeta signaling. These findings suggest that Fgf9 normally functions to repress Tgfbeta signaling in these cells. In vivo, a small subset of mesenchymal cells expressed phospho-Erk and the secreted Tgfbeta inhibitors Fst and Fstl1 in an Fgf9-dependent fashion. The p-Erk/Fst/Fstl1-expressing cells were most consistent with intestinal mesenchymal stem cells (iMSCs). We found that isolated iMSCs expressed p-Erk, Fst and Fstl1, and could repress the differentiation of intestinal myofibroblasts in co-culture. These data suggest a model in which epithelial-derived Fgf9 stimulates iMSCs that in turn regulate underlying mesenchymal fibroblast proliferation and differentiation at least in part through inhibition of Tgfbeta signaling in the mesenchyme. Taken together, the interaction of FGF and TGFbeta signaling pathways in the intestinal mesenchyme could represent novel targets for future short bowel syndrome therapies. PMID:18653563

  3. Advances in small bowel neuroendocrine neoplasia Banck and Small intestine

    PubMed Central

    Banck, Michaela S.; Beutler, Andreas S.

    2015-01-01

    Purpose of review this review aims at summarizing progress in clinical trials and basic science redefining the diagnosis and treatment of well differentiated small intestine neuroendocrine tumors (SI-NET). Recent findings Two clinical trials demonstrated antitumor activity of the long-acting somatostatin analogues octreotide LAR and lanreotide for advanced SI-NET. The mTOR inhibitor everolimus is another treatment option for patients with SI-NET, but awaits definitive proof of benefit in the ongoing RADIANT-4 study. Two whole exome/genome-sequencing studies reported in the past year provided the first genome-wide analysis of large sets of SI-NET at nucleotide resolution. Candidate therapeutically relevant alterations were found to affect SRC, SMAD genes, AURKA, EGFR, HSP90, and PDGFR as well as mutually exclusive amplification of AKT1 or AKT2 and other alterations of PI3K/Akt/mTOR signaling genes. The gene CDKN1B is inactivated by small insertions/deletions in 8% of patients with SI-NET suggesting cell cycle inhibitors as new candidate drugs for SI-NET. Circulating tumor cells and tumor-derived RNA in the blood are promising clinical tests for SI-NET. Summary Clinical and genomic research may merge in the near future to re-shape clinical trials and to define the ‘personalized’ treatment options for patients with SI-NET. PMID:24441281

  4. Fasting stimulates 2-AG biosynthesis in the small intestine: role of cholinergic pathways.

    PubMed

    DiPatrizio, Nicholas V; Igarashi, Miki; Narayanaswami, Vidya; Murray, Conor; Gancayco, Joseph; Russell, Amy; Jung, Kwang-Mook; Piomelli, Daniele

    2015-10-15

    The endocannabinoids are lipid-derived signaling molecules that control feeding and energy balance by activating CB1-type cannabinoid receptors in the brain and peripheral tissues. Previous studies have shown that oral exposure to dietary fat stimulates endocannabinoid signaling in the rat small intestine, which provides positive feedback that drives further food intake and preference for fat-rich foods. We now describe an unexpectedly broader role for cholinergic signaling of the vagus nerve in the production of the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), in the small intestine. We show that food deprivation increases levels of 2-AG and its lipid precursor, 1,2-diacylglycerol, in rat jejunum mucosa in a time-dependent manner. This response is abrogated by surgical resection of the vagus nerve or pharmacological blockade of small intestinal subtype-3 muscarinic acetylcholine (m3 mAch) receptors, but not inhibition of subtype-1 muscarinic acetylcholine (m1 mAch). We further show that blockade of peripheral CB1 receptors or intestinal m3 mAch receptors inhibits refeeding in fasted rats. The results suggest that food deprivation stimulates 2-AG-dependent CB1 receptor activation through a mechanism that requires efferent vagal activation of m3 mAch receptors in the jejunum, which, in turn, may promote feeding after a fast. PMID:26290104

  5. Altered systemic bioavailability and organ distribution of azathioprine in methotrexate-induced intestinal mucositis in rats

    PubMed Central

    Karbelkar, Sadaf A.; Majumdar, Anuradha S.

    2016-01-01

    Objective: Intestinal mucositis is a significant problem haunting clinicians for decades. One of the major reasons for its occurrence is high-dose chemotherapy. The study is aimed at investigating effect of intestinal mucositis on pharmacokinetics, organ distribution, and bioavailability of azathioprine (AZA) (6-mercaptopurine). Materials and Methods: Intestinal mucositis was induced with methotrexate (MTX) (2.5 mg/kg). The oral absorption of AZA and 6-mercaptopurine (metabolite) levels were determined in control and MTX-treated rats: ex vivo (noneverted sac technique) and in vivo (pharmacokinetics and organ-distribution) using high-performance liquid chromatography. Immunohistochemistry was conducted to evaluate peptide transporter expression on luminal membrane of small intestine. Results: Intestinal permeation of AZA into systemic circulation of rats was lower after MTX administration, widely found in intestinal segments of mucositis-induced rats leading to decline in systemic bioavailability of AZA. Immunohistochemistry findings indicated diminution of peptide transporter expression representing hampered absorption of drugs absorbed via this transporter. Conclusion: Study outcome has thrown light on altered fate of AZA when administered to individuals with mucositis which suggests modified drug therapy. These findings can further be investigated in different drug classes which might be administered concomitantly in mucositis and study outcome can be further confirmed in mucositis patients in clinical practice also. PMID:27298491

  6. Effect of reserpine on the histochemical and biochemical properties of rat intestinal mucin

    SciTech Connect

    Forstner, J.; Roomi, N.; Khorasani, R.; Kuhns, W.; Forstner, G. )

    1991-04-01

    Biochemical and histochemical parameters of intestinal mucins were examined in control and reserpine-treated rats. An assay for intestinal mucin sulfotransferase was developed and the activity shown to increase 3.4 times over control levels in rats given intraperitonal reserpine (0.5 mg/kg body wt) daily for 7 days. Histochemical staining of intestinal sections revealed an increase in sulfomucins in goblet cells of reserpine-treated rats. The effects were prominent as early as 1 day following injection, particularly in the distal third of the small intestine, and during the next 6 days these changes spread progressively to the middle and proximal thirds. After 3 days of treatment mucins were purified from each intestinal segment and compared to control mucins with respect to composition and (35S)NaSO{sub 4} incorporation. Although individual amino acid and carbohydrate molar ratios were unchanged, the total carbohydrate and sulfate content of mucins in treated animals was elevated (two to three times above control) in the middle and distal thirds of the intestine. In vivo ({sup 35}S)SO{sub 4} incorporation into these mucins was also proportionaltely elevated, and was targetted to O-linked oligosaccharide side chains. These findings are consistent with an action of reserpine causing an increased production of mucin which is enriched in glycoprotein components bearing sulfated oligosaccharide chains. The relevance of these findings to the production of hypersulfated and hyperglycosylated mucins in cystic fibrosis is discussed.

  7. Simultaneously multiparametric spectroscopic monitoring of tissue viability in the brain and small intestine

    NASA Astrophysics Data System (ADS)

    Tolmasov, Michael; Barbiro-Michaely, Efrat; Mayevsky, Avraham

    2007-02-01

    Under body O II imbalance, the Autonomic Nervous System is responsible for redistribution of blood flow with preference to the most vital organs (brain, heart), while the less vital organs (intestine, GI tract) are hypoperfused. The aim of this study was to develop and use an animal model for real time monitoring of tissue viability in the brain, and the small intestine, under various levels of oxygen and blood supply. Male Wistar rats were anesthetized, the brain cortex and intestinal serosa were exposed and connected by optical fibers to the Multi-Site Multi-Parametric (MSMP) monitoring system. Tissue blood flow (TBF) and mitochondrial NADH redox state were monitored simultaneously in the two organs. The rats were subjected to short anoxia, 20 minutes hypoxia or epinephrine (2& 8μg/kg I.V.). Under oxygen deficiency, cerebral blood flow (CBF) was elevated, whereas intestinal TBF was reduced. Mitochondrial NADH was significantly elevated in both organs. Systemic injection of Adrenaline showed a dose-depended increase in systemic blood pressure and CBF response whereas, intestinal TBF similarly decreased in both doses. In addition, NADH was elevated (reduced form) in the intestine whereas oxidation was observed in the brain. In conclusion, our preliminary results may imply the ability of using of the MSMP for monitoring non-vital organs in order to detect early changes in the balance between oxygen supply and demand in the body.

  8. Effect of Candida albicans on Intestinal Ischemia-reperfusion Injury in Rats

    PubMed Central

    Yan, Lei; Wu, Chun-Rong; Wang, Chen; Yang, Chun-Hui; Tong, Guang-Zhi; Tang, Jian-Guo

    2016-01-01

    Background: Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperfusion injury (IIRI), and Candida albicans in human gut commonly elevates inflammatory cytokines in intestinal mucosa. This study aimed to explore the effect of C. albicans on IIRI. Methods: Fifty female Wistar rats were divided into five groups according to the status of C. albicans infection and IIRI operation: group blank and sham; group blank and IIRI; group cefoperazone plus IIRI; group C. albicans plus cefoperazone and IIRI (CCI); and group C. albicans plus cefoperazone and sham. The levels of inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and diamine oxidase (DAO) measured by enzyme-linked immunosorbent assay were used to evaluate the inflammation reactivity as well as the integrity of small intestine. Histological scores were used to assess the mucosal damage, and the C. albicans blood translocation was detected to judge the permeability of intestinal mucosal barrier. Results: The levels of inflammatory factors TNF-α, IL-6, and IL-1β in serum and intestine were higher in rats undergone both C. albicans infection and IIRI operation compared with rats in other groups. The levels of DAO (serum: 44.13 ± 4.30 pg/ml, intestine: 346.21 ± 37.03 pg/g) and Chiu scores (3.41 ± 1.09) which reflected intestinal mucosal disruption were highest in group CCI after the operation. The number of C. albicans translocated into blood was most in group CCI ([33.80 ± 6.60] ×102 colony forming unit (CFU)/ml). Conclusion: Intestinal C. albicans infection worsened the IIRI-induced disruption of intestinal mucosal barrier and facilitated the subsequent C. albicans translocation and dissemination. PMID:27411459

  9. Recombinant Thrombomodulin (Solulin) Ameliorates Early Intestinal Radiation Toxicity in a Preclinical Rat Model

    PubMed Central

    Pathak, Rupak; Wang, Junru; Garg, Sarita; Aykin-Burns, Nukhet; Petersen, Karl-Uwe; Hauer-Jensen, Martin

    2016-01-01

    Intestinal radiation toxicity occurs during and after abdominopelvic radiotherapy. Endothelial cells play a significant role in modulating radiation-induced intestinal damage. We demonstrated that the endothelial cell surface receptor thrombomodulin (TM), a protein with anticoagulant, antiinflammatory and antioxidant properties, mitigates radiation-induced lethality in mice. The goal of this study was to determine whether recombinant TM (Solulin) can protect the intestine from toxicity in a clinically relevant rat model. A 4 cm loop of rat small bowel was exposed to fractionated 5 Gy X radiation for 9 consecutive days. The animals were randomly assigned to receive daily subcutaneous injections of vehicle or Solulin (3 mg/kg/day or 10 mg/kg/day) for 27 days starting 4 days before irradiation. Early intestinal injury was assessed two weeks after irradiation by quantitative histology, morphometry, immunohistochemistry and luminol bioluminescence imaging. Solulin treatment significantly ameliorated intestinal radiation injury, made evident by a decrease in myeloperoxidase (MPO) activity, transforming growth factor beta (TGF-β) immunoreactivity, collagen-I deposition, radiation injury score (RIS) and intestinal serosal thickening. These findings indicate the need for further development of Solulin as a prophylactic and/or therapeutic agent to mitigate radiation-induced intestinal damage. PMID:27459702

  10. Recombinant Thrombomodulin (Solulin) Ameliorates Early Intestinal Radiation Toxicity in a Preclinical Rat Model.

    PubMed

    Pathak, Rupak; Wang, Junru; Garg, Sarita; Aykin-Burns, Nukhet; Petersen, Karl-Uwe; Hauer-Jensen, Martin

    2016-08-01

    Intestinal radiation toxicity occurs during and after abdominopelvic radiotherapy. Endothelial cells play a significant role in modulating radiation-induced intestinal damage. We demonstrated that the endothelial cell surface receptor thrombomodulin (TM), a protein with anticoagulant, anti-inflammatory and antioxidant properties, mitigates radiation-induced lethality in mice. The goal of this study was to determine whether recombinant TM (Solulin) can protect the intestine from toxicity in a clinically relevant rat model. A 4 cm loop of rat small bowel was exposed to fractionated 5 Gy X radiation for 9 consecutive days. The animals were randomly assigned to receive daily subcutaneous injections of vehicle or Solulin (3 mg/kg/day or 10 mg/kg/day) for 27 days starting 4 days before irradiation. Early intestinal injury was assessed two weeks after irradiation by quantitative histology, morphometry, immunohistochemistry and luminol bioluminescence imaging. Solulin treatment significantly ameliorated intestinal radiation injury, made evident by a decrease in myeloperoxidase (MPO) activity, transforming growth factor beta (TGF-β) immunoreactivity, collagen-I deposition, radiation injury score (RIS) and intestinal serosal thickening. These findings indicate the need for further development of Solulin as a prophylactic and/or therapeutic agent to mitigate radiation-induced intestinal damage. PMID:27459702

  11. Cancer Statistics: Cancer of the Small Intestine

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 10,090 % of All New Cancer Cases 0.6% Estimated Deaths in 2016 1,330 % of All Cancer ... intestine cancer is rare. Common Types of Cancer Estimated New Cases 2016 Estimated Deaths 2016 1. Breast ...

  12. The effect of small intestine heterogeneity on irreversible electroporation treatment planning.

    PubMed

    Phillips, Mary

    2014-09-01

    Nonthermal irreversible electroporation (NTIRE) is an ablation modality that utilizes microsecond electric fields to produce nanoscale defects in the cell membrane. This results in selective cell death while preserving all other molecules, including the extracellular matrix. Here, finite element analysis and experimental results are utilized to examine the effect of NTIRE on the small intestine due to concern over collateral damage to this organ during NTIRE treatment of abdominal cancers. During previous studies, the electrical treatment parameters were chosen based on a simplified homogeneous tissue model. The small intestine, however, has very distinct layers, and a more realistic model is needed to further develop this technology for precise clinical applications. This study uses a two-dimensional finite element solution of the Laplace and heat conduction equations to investigate how small intestine heterogeneities affect the electric field and temperature distribution. Experimental results obtained by applying NTIRE to the rat small intestine in vivo support the heterogeneous effect of NTIRE on the tissue. The numerical modeling indicates that the electroporation parameters chosen for this study avoid thermal damage to the tissue. This is supported by histology obtained from the in vivo study, which showed preservation of extracellular structures. The finite element model also indicates that the heterogeneous structure of the small intestine has a significant effect on the electric field and volume of cell ablation during electroporation and could have a large impact on the extent of treatment. The heterogeneous nature of the tissue should be accounted for in clinical treatment planning. PMID:24907451

  13. Gastric or rectal instillation of short-chain fatty acids stimulates epithelial cell proliferation of small and large intestine in rats.

    PubMed

    Ichikawa, Hirofumi; Shineha, Ryuzaburo; Satomi, Susumu; Sakata, Takashi

    2002-05-01

    Short-chain fatty acids stimulate gut epithelial cell proliferation in vivo, although the difference between oral and rectal routes is unknown. Accordingly, we examined the effect of oral or rectal administration of these acids. We instilled a mixture of acetic acid, propionic acid, and n-butyric acid (150, 60, and 60 mmol/liter, respectively; pH 6.5) or saline (270 mM, pH 6.5) into the stomach (2 ml) or rectum (1 ml) three times daily for five days in rats fed an elemental diet. We measured crypt cell production rate of the jejunum, ileum, and distal colon of these rats. The crypt cell production rate of these segments was higher in rats with gastric or rectal instillation of short-chain fatty acids than in saline controls. The rectal route was slightly more effective than the gastric route. The above results indicated that the instillation of short-chain fatty acids orally or rectally stimulated gut epithelial cell proliferation. PMID:12018914

  14. Intestinal Absorption and Metabolism of Epimedium Flavonoids in Osteoporosis Rats.

    PubMed

    Zhou, Jing; Ma, Yi Hua; Zhou, Zhong; Chen, Yan; Wang, Ying; Gao, Xia

    2015-10-01

    Herba Epimdii is a traditional Chinese medicine used to treat osteoporosis. Its main pharmacological ingredients are flavonoids. In previous studies conducted in healthy animals, we showed that epimedium flavonoids could be hydrolyzed into secondary glycosides or aglycon by intestinal flora or enzymes, thereby enhancing their absorption and antiosteoporosis activity. To study the medicine in the pathologic state, epimedium flavonoids were incubated with intestinal mucosa and feces in vitro and intestinal perfusion in situ to explore the differences in absorption and metabolism between sham and osteoporosis rats. For osteoporosis rats, the hydrolysis rates of icariin, epimedin A, epimedin B, and epimedin C incubated with intestinal flora for 1 hour were reduced by 0.19, 0.26, 0.19, and 0.14, respectively, compared with that in sham rats. Hydrolysis rates were reduced by 0.21, 0.24, 0.08, and 0.31 for icariin, epimedin A, epimedin B, and epimedin C incubated with duodenal enzymes for 1 hour and by 0.13, 0.09, 0.07, and 0.47 for icariin, epimedin A, epimedin B, and epimedin C incubated with jejunum enzymes, respectively, compared with the sham group. In addition, the apparent permeability coefficient and elimination percentage of the four epimedium flavonoids in the duodenum, jejunum, ileum, and colon decreased by 29%-44%, 32%-50%, 40%-56%, and 27%-53% compared with that in sham rats, respectively. The main metabolites of the four epimedium flavonoids were the same for the two groups after intestinal perfusion, or flora and enzyme incubation. In conclusion, the amount and activity of intestinal flora and enzymes changed in ovariectomized rats, which affected the intestinal absorption and hydrolysis of epimedium flavonoids whose structures contain 7-glucose. PMID:26135008

  15. Enteroscopy in small intestinal inflammatory diseases.

    PubMed

    Gay, G J; Delmotte, J S

    1999-01-01

    The development of new semilong enteroscopes, videopush enteroscope (VPE), has modified the diagnostic and therapeutic approach to inflammatory intestinal diseases owing to the biopsy and therapeutic capacities. In Crohn's Disease, VPE is useful in nonusual clinical presentations: occult intestinal bleeding and in the treatment by dilatation of jejunal and ileal strictures. In atrophic coeliac disease (ACD) VPE is mandatory each time oesogastroduodenoscopy biopsies are noninformative in order to obtain pathologic jejunal biopsis. In addition, in refractory ACD and in the case of jejunal blood loss ACD, VPE is mandatory in the search for ulcerative jejunitis and lymphoma. The management of chronic diarrhea of the adult, classic endoscopy remains the gold standard procedure and is carried out first but in patients with negative results, VPE can proceed immediately. Good results can only be obtained if VPE is performed by endoscopist who is highly interested in this field of investigation. PMID:9834320

  16. Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids.

    PubMed

    Finkbeiner, Stacy R; Freeman, Jennifer J; Wieck, Minna M; El-Nachef, Wael; Altheim, Christopher H; Tsai, Yu-Hwai; Huang, Sha; Dyal, Rachel; White, Eric S; Grikscheit, Tracy C; Teitelbaum, Daniel H; Spence, Jason R

    2015-01-01

    Short bowel syndrome (SBS) is characterized by poor nutrient absorption due to a deficit of healthy intestine. Current treatment practices rely on providing supportive medical therapy with parenteral nutrition; while life saving, such interventions are not curative and are still associated with significant co-morbidities. As approaches to lengthen remaining intestinal tissue have been met with only limited success and intestinal transplants have poor survival outcomes, new approaches to treating SBS are necessary. Human intestine derived from embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs), called human intestinal organoids (HIOs), have the potential to offer a personalized and scalable source of intestine for regenerative therapies. However, given that HIOs are small three-dimensional structures grown in vitro, methods to generate usable HIO-derived constructs are needed. We investigated the ability of hESCs or HIOs to populate acellular porcine intestinal matrices and artificial polyglycolic/poly L lactic acid (PGA/PLLA) scaffolds, and examined the ability of matrix/scaffolds to thrive when transplanted in vivo. Our results demonstrate that the acellular matrix alone is not sufficient to instruct hESC differentiation towards an endodermal or intestinal fate. We observed that while HIOs reseed acellular porcine matrices in vitro, the HIO-reseeded matrices do not thrive when transplanted in vivo. In contrast, HIO-seeded PGA/PLLA scaffolds thrive in vivo and develop into tissue that looks nearly identical to adult human intestinal tissue. Our results suggest that HIO-seeded PGA/PLLA scaffolds are a promising avenue for developing the mucosal component of tissue engineered human small intestine, which need to be explored further to develop them into fully functional tissue. PMID:26459240

  17. Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids

    PubMed Central

    Finkbeiner, Stacy R.; Freeman, Jennifer J.; Wieck, Minna M.; El-Nachef, Wael; Altheim, Christopher H.; Tsai, Yu-Hwai; Huang, Sha; Dyal, Rachel; White, Eric S.; Grikscheit, Tracy C.; Teitelbaum, Daniel H.; Spence, Jason R.

    2015-01-01

    ABSTRACT Short bowel syndrome (SBS) is characterized by poor nutrient absorption due to a deficit of healthy intestine. Current treatment practices rely on providing supportive medical therapy with parenteral nutrition; while life saving, such interventions are not curative and are still associated with significant co-morbidities. As approaches to lengthen remaining intestinal tissue have been met with only limited success and intestinal transplants have poor survival outcomes, new approaches to treating SBS are necessary. Human intestine derived from embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs), called human intestinal organoids (HIOs), have the potential to offer a personalized and scalable source of intestine for regenerative therapies. However, given that HIOs are small three-dimensional structures grown in vitro, methods to generate usable HIO-derived constructs are needed. We investigated the ability of hESCs or HIOs to populate acellular porcine intestinal matrices and artificial polyglycolic/poly L lactic acid (PGA/PLLA) scaffolds, and examined the ability of matrix/scaffolds to thrive when transplanted in vivo. Our results demonstrate that the acellular matrix alone is not sufficient to instruct hESC differentiation towards an endodermal or intestinal fate. We observed that while HIOs reseed acellular porcine matrices in vitro, the HIO-reseeded matrices do not thrive when transplanted in vivo. In contrast, HIO-seeded PGA/PLLA scaffolds thrive in vivo and develop into tissue that looks nearly identical to adult human intestinal tissue. Our results suggest that HIO-seeded PGA/PLLA scaffolds are a promising avenue for developing the mucosal component of tissue engineered human small intestine, which need to be explored further to develop them into fully functional tissue. PMID:26459240

  18. The migrating myoelectric complex of the small intestine

    NASA Astrophysics Data System (ADS)

    Telford, Gordon L.; Sarna, Sushil K.

    1991-10-01

    Gastric and small intestinal myoelectric and motor activity is divided into two main patterns, fed and fasted. During fasting, the predominant pattern of activity is the migrating myoelectric complex (MMC), a cyclically occurring pattern of electric and mechanical activity that is initiated in the stomach and duodenum almost simultaneously and, from there, propagates the length of the small intestine. Cyclic motor activity also occurs in the lower esophageal sphincter, the gallbladder, and the sphincter of Oddi with a duration that is related to the MMC in the small intestine. Of the possible mechanisms for initiation of the MMC in the small intestine (extrinsic neural control, intrinsic neural control, and hormonal control), intrinsic neural control via a series of coupled is the most likely. The keep this sentence in! hormone motilin also plays a role in the initiation of MMCs. After a meal, in man the MMC is disrupted and replaced by irregular contractions. The physiologic role of the MMC is to clear the stomach and small intestine of residual food, secretions, and desquamated cells and propel them to the colon. Disruption of the MMC cycle is associated with bacterial overgrowth in some patients, an observation that supports the proposed cleansing function of the MMC cycle.

  19. Small intestinal amyogenesia and dysmyogenesia induced by morphine and loperamide.

    PubMed

    Sarna, S K; Otterson, M F

    1990-02-01

    We studied the effects of morphine and loperamide on small bowel myoelectric and contractile activity in 12 conscious dogs. After initially producing premature migrating myoelectric complexes, both substances destabilized and obliterated electrical control activity (ECA). The obliteration of ECA occurred mainly in the proximal half of the small intestine. During ECA obliteration, the base line was almost flat at the usual amplification. At higher amplification, the base line exhibited irregular low level fluctuations that could not be related to electrical response activity (ERA) bursts or contractions. The mean time lag for obliteration of ECA in the proximal small intestine decreased at higher doses of morphine infusion. During the destabilization and obliteration of ECA, contractions and ERA bursts occurred in unusual patterns. The ERA bursts and contractions were generally discoordinated. However, in the proximal small intestine some contractions migrated rapidly and uninterrupted at 32 +/- 7 cm/s over long distances (124 +/- 24 cm). ECA destabilization and obliteration were reversed in approximately 15-30 min after the ingestion of a meal or intravenous administration of atropine, hexamethonium, or naloxone. We conclude that during the absence or destabilization of ECA, the ERA bursts and contractions occur in an uncontrolled manner. These two states were called "amyogenesia" and "dysmyogenesia," respectively. The unusual patterns of contractions during small intestinal amyogenesia and dysmyogenesia may be one of the factors in delayed intestinal transit produced by morphine and loperamide. PMID:1968317

  20. Stigmasterol reduces plasma cholesterol levels and inhibits hepatic synthesis and intestinal absorption in the rat.

    PubMed

    Batta, Ashok K; Xu, Guorong; Honda, Akira; Miyazaki, Teruo; Salen, Gerald

    2006-03-01

    Plant sterols compete with cholesterol (cholest-5-en-3beta-ol) for intestinal absorption to limit absorption and lower plasma concentrations of cholesterol. Stigmasterol (24-ethyl-cholesta-5,22-dien-3beta-ol; Delta(22) derivative of sitosterol [24-ethyl-cholest-5-en-3beta-ol]), but not campesterol (24-methyl-cholest-5-en-3beta-ol) and sitosterol, is reported to inhibit cholesterol biosynthesis via inhibition of sterol Delta(24)-reductase in human Caco-2 and HL-60 cell lines. We studied the effect of feeding 0.5% stigmasterol on plasma and liver sterols and intestinal cholesterol and sitosterol absorption in 12 wild-type Kyoto (WKY) and 12 Wistar rats. After 3 weeks of feeding, cholesterol and sitosterol absorption was determined in 6 rats from each group by plasma dual-isotope ratio method. After 3 more weeks, plasma and hepatic sterols and hepatic enzyme activities were determined in all rats. After feeding stigmasterol, baseline plasma cholesterol was 1.3 times and plant sterols 3 times greater in WKY compared with Wistar rats. Stigmasterol feeding lowered plasma cholesterol by approximately 11%, whereas plasma campesterol and sitosterol levels were virtually unchanged in both rat strains, and stigmasterol constituted 3.2% of plasma sterols in WKY rats and 1% in Wistar rats. After 6 weeks of feeding, cholesterol and sitosterol absorption decreased 23% and 30%, respectively, in WKY, and 22% and 16%, respectively, in the Wistar rats as compared with untreated rats. The intestinal bacteria in both rat strains metabolized stigmasterol to mainly the 5beta-H stanol (>40%), with only small amounts of 5alpha-H derivative (approximately 1.5%), whereas the C-22 double bond was resistant to bacterial metabolism. Hepatic stigmasterol levels increased from 11 microg/g liver tissue to 104 mug/g in WKY rats and from 5 microg/g liver tissue to 21 microg/g in Wistar rats. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was suppressed 4-fold in the WKY and almost 1.8-fold

  1. Central actions of calcitonin on body temperature and intestinal motility in rats: evidence for different mediations.

    PubMed

    Fargeas, M J; Fioramonti, J; Buéno, L

    1985-06-01

    The effects of intracerebroventricular (i.c.v.) administration of calcitonin and PGE2 on intestinal motility and body temperature were examined in conscious rats chronically fitted with intraparietal electrodes in the small intestine, a cannula in a cerebral lateral ventricle and a subcutaneous thermistor probe. Both calcitonin and PGE2 restored the fasted pattern of intestinal motility in fed rats and induced an increase in body temperature. Indomethacin, an inhibitor of the cyclooxygenase with calcium antagonistic properties, and TMB-8, an intracellular calcium antagonist, blocked the effects of calcitonin on intestinal motility and body temperature. Piroxicam, an inhibitor of the cyclooxygenase which does not affect calcium uptake blocked the thermic but not the intestinal effects of calcitonin. TMB-8 but not indomethacin or piroxicam partially blocked the effects of PGE2 on both intestinal motility and body temperature. It is concluded that the central hyperthermic effect of calcitonin is mediated through the formation and the release of prostaglandins whereas the central action of calcitonin on digestive motility results from intracerebral effects on calcium fluxes. PMID:3875880

  2. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.

    PubMed

    Qin, Ying; Naito, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-11-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intestinal epithelial cells were incubated with 70 µM polaprezinc for 24 h, and then stimulated with or without 15 mM acetylsalicylic acid for a further 15 h. Subsequent cellular viability was quantified by fluorometric assay based on cell lysis and staining. Acetylsalicylic acid-induced cell death was also qualified by fluorescent microscopy of Hoechst33342 and propidium iodide. Heat shock proteins 70 protein expression after adding polaprezinc or acetylsalicylic acid was assessed by western blotting. To investigate the role of Heat shock protein 70, Heat shock protein 70-specific small interfering RNA was applied. Cell viability was quantified by fluorometric assay based on cell lysis and staining and apoptosis was analyzed by fluorescence-activated cell sorting. We found that acetylsalicylic acid significantly induced apoptosis of rat intestinal epithelial cells in a dose- and time-dependent manner. Polaprezinc significantly suppressed acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells at its late phase. At the same time, polaprezinc increased Heat shock protein 70 expressions of rat intestinal epithelial cells in a time-dependent manner. However, in Heat shock protein 70-silenced rat intestinal epithelial cells, polaprezinc could not suppress acetylsalicylic acid -induced apoptosis at its late phase. We conclude that polaprezinc-increased Heat shock protein 70 expression might be an important mechanism by which polaprezinc suppresses acetylsalicylic

  3. SOME DETERMINANTS OF INTESTINAL CADMIUM TRANSPORT IN THE RAT

    EPA Science Inventory

    The hypothesis was tested that Cd absorption from the intestinal lumen is mediated by cellular transport systems. Cd is readily extracted from glucose-saline during perfusion of jejunal segments in the living rat. Over periods as long as 40 minutes, essentially all extracted Cd i...

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

    SciTech Connect

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

    1986-03-01

    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 (/sup 3/H)-biotin and (/sup 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 ..mu..M 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.

  5. MICROBIAL SUCCESSION AND INTESTINAL ENZYME ACTIVITIES IN THE DEVELOPING RAT

    EPA Science Inventory

    The succession of gastrointestinal flora in the developing rat was studied, concomitant with studies of intestinal enzyme activity. Aerobes and anaerobes were identified as members of 4 major bacterial groups, i.e., Lactobacilli spp., Gram positive enterococci, Gram negative rods...

  6. Paneth cells: maestros of the small intestinal crypts.

    PubMed

    Clevers, Hans C; Bevins, Charles L

    2013-01-01

    Paneth cells are highly specialized epithelial cells of the small intestine, where they coordinate many physiological functions. First identified more than a century ago on the basis of their readily discernible secretory granules by routine histology, these cells are located at the base of the crypts of Lieberkühn, tiny invaginations that line the mucosal surface all along the small intestine. Investigations over the past several decades determined that these cells synthesize and secrete substantial quantities of antimicrobial peptides and proteins. More recent studies have determined that these antimicrobial molecules are key mediators of host-microbe interactions, including homeostatic balance with colonizing microbiota and innate immune protection from enteric pathogens. Perhaps more intriguing, Paneth cells secrete factors that help sustain and modulate the epithelial stem and progenitor cells that cohabitate in the crypts and rejuvenate the small intestinal epithelium. Dysfunction of Paneth cell biology contributes to the pathogenesis of chronic inflammatory bowel disease. PMID:23398152

  7. Ultrastructural and immunohistochemical analysis of intestinal myofibroblasts during the early organogenesis of the human small intestine.

    PubMed

    Artells, Rosa; Navarro, Alfons; Diaz, Tània; Monzó, Mariano

    2011-03-01

    Intestinal myofibroblasts (IMFs), also known as pericryptal fibroblasts, are found at the basement membrane of the intestinal epithelium. They are characterized by well-developed endoplasmic reticulum, cytoplasmic fibers, and fibrous extensions called fibronexi. IMFs have structural features in common both with fibroblasts and smooth cells. Vimentin, desmin, and α-smooth-muscle actin (α-SM) are markers commonly used to discriminate between IMFs and smooth muscle cells. Immunohistochemical studies have shown that, when α-SM and vimentin are positive in both IMFs and smooth muscle cells, desmin is negative in IMFs but positive in smooth muscle cells. In the adult intestine, IMFs play an important role in various functions, especially in tissue repair and scar formation during wound healing. In the embryonic intestine, however, wound healing does not occur, and to date, no studies have investigated the first appearance and subsequent evolution of IMFs. In this study, we have examined the human small intestine in embryos at 7, 9, and 11 weeks of development by ultrastructural and immunohistochemical analysis to shed light on the formation of IMFs during these early phases of organogenesis. At 7 weeks, the embryonic mesenchymal cells are similar to proto-myofibroblasts and may be the precursors of the IMFs detected at 9 weeks and more abundantly at 11 weeks by immunohistochemistry. These IMFs seem to mediate information flow between the epithelium and the mesenchyme and thus contribute to the development of the small intestine. PMID:21284092

  8. Role of Intestinal Cytochrome P450 Enzymes in Diclofenac-Induced Toxicity in the Small Intestine

    PubMed Central

    Zhu, Yi

    2012-01-01

    The aim of this study was to determine the role of small intestinal (SI) cytochrome P450 (P450) enzymes in the metabolic activation of diclofenac (DCF), a widely used nonsteroidal anti-inflammatory drug, and DCF-induced intestinal toxicity. DCF induces intestinal ulcers in humans and mice, but the underlying mechanisms, including the necessity for drug bioactivation in the target tissues and the sources and identities of reactive intermediates, are not fully understood. We found that the number of DCF-induced (at 50 mg/kg p.o.) intestinal ulcers was significantly smaller in an intestinal epithelium (IE)-specific P450 reductase (CPR) knockout (IE-Cpr-null) mouse model, which has little P450 activity in the IE, than in wild-type (WT) mice, determined at 14 h after DCF administration. The involvement of intestinal P450 enzymes was confirmed by large reductions (>80–90%) in the rates of in vitro formation, in SI microsomal reactions, of hydroxylated DCF metabolites and reactive intermediates, trapped as DCF-glutathione (GSH) conjugates, in the IE-Cpr-null, compared with WT mice. The SI levels of DCF-GSH conjugates (at 4 h after dosing) and DCF-protein adducts (at 14 h after dosing) were significantly lower in IE-Cpr-null than in WT mice. In additional experiments, we found that pretreatment of mice with grapefruit juice, which is known to inhibit SI P450 activity, ameliorated DCF-induced intestinal toxicity in WT mice. Our results not only strongly support the notion that SI P450 enzymes play an important role in DCF-induced intestinal toxicity, but also illustrate the possibility of preventing DCF-induced intestinal toxicity through dietary intervention. PMID:22892338

  9. Removal of luminal content protects the small intestine during hemorrhagic shock but is not sufficient to prevent lung injury

    PubMed Central

    Altshuler, Angelina E; Richter, Michael D; Modestino, Augusta E; Penn, Alexander H; Heller, Michael J; Schmid-Schönbein, Geert W

    2013-01-01

    The small intestine plays a key role in the pathogenesis of multiple organ failure following circulatory shock. Current results show that reduced perfusion of the small intestine compromises the mucosal epithelial barrier, and the intestinal contents (including pancreatic digestive enzymes and partially digested food) can enter the intestinal wall and transport through the circulation or mesenteric lymph to other organs such as the lung. The extent to which the luminal contents of the small intestine mediate tissue damage in the intestine and lung is poorly understood in shock. Therefore, rats were assigned to three groups: No-hemorrhagic shock (HS) control and HS with or without a flushed intestine. HS was induced by reducing the mean arterial pressure (30 mmHg; 90 min) followed by return of shed blood and observation (3 h). The small intestine and lung were analyzed for hemorrhage, neutrophil accumulation, and cellular membrane protein degradation. After HS, animals with luminal contents had increased neutrophil accumulation, bleeding, and destruction of E-cadherin in the intestine. Serine protease activity was elevated in mesenteric lymph fluid collected from a separate group of animals subjected to intestinal ischemia/reperfusion. Serine protease activity was elevated in the plasma after HS but was detected in lungs only in animals with nonflushed lumens. Despite removal of the luminal contents, lung injury occurred in both groups as determined by elevated neutrophil accumulation, permeability, and lung protein destruction. In conclusion, luminal contents significantly increase intestinal damage during experimental HS, suggesting transport of luminal contents across the intestinal wall should be minimized. PMID:24303180

  10. Hormone induced changes in lactase glycosylation in developing rat intestine.

    PubMed

    Chaudhry, Kamaljit Kaur; Mahmood, Safrun; Mahmood, Akhtar

    2008-11-01

    Lactase exists in both soluble and membrane-bound forms in suckling rat intestine. The distribution of lactase and its glycosylated isoforms in response to thyroxine or cortisone administration has been studied in suckling rats. 75% of lactase activity was detected, associated with brush borders, compared to 24% in the soluble fraction of 8-day-old rats. Thyroxine treatment enhanced soluble lactase activity to 34%, whereas particulate fraction was reduced to 67% compared to controls. Cortisone administration reduced soluble lactase activity from 24% in controls to 12% with a concomitant increase in membrane-bound activity to 89%. Western blot analysis revealed lactase signal, corresponding to 220 kDa in both the soluble and membrane fractions, which corroborated the enzyme activity data. The elution pattern of papain solubilized lactase from agarose-Wheat Germ agglutinin, or Concanavalin A or Jacalin agglutinin columns was different in the suckling and adult rat intestines. Also the elution profile of lactase activity from agarose-lectin columns was modulated in cortisone, thyroxine, and insulin injected pups, which suggests differences in glycosylated isoforms of lactase under these conditions. These findings suggest the role of these hormones in inducing changes in lactase glycosylation during postnatal development of intestine, which may contribute to adult-type hypolactasia in rats. PMID:18712286

  11. The Epidemiology and Pathogenesis of Neoplasia in the Small Intestine

    PubMed Central

    SCHOTTENFELD, DAVID; BEEBE-DIMMER, JENNIFER L.; VIGNEAU, FAWN D.

    2013-01-01

    PURPOSE: The mucosa of the small intestine encompasses about 90% of the luminal surface area of the digestive system, but only 2% of the total annual gastrointestinal cancer incidence in the United States. METHODS: The remarkable contrast in age-standardized cancer incidence between the small and large intestine has been reviewed with respect to the cell type patterns, demographic features, and molecular characteristics of neoplasms. RESULTS: Particularly noteworthy is the predominance of adenocarcinoma in the colon, which exceeds 98% of the total incidence by cell type, in contrast to that of 30% to 40% in the small intestine, resulting in an age-standardized ratio of rates exceeding 50-fold. The prevalence of adenomas and carcinomas is most prominent in the duodenum and proximal jejunum. The positive correlation in global incidence rates of small and large intestinal neoplasms and the reciprocal increases in risk of second primary adenocarcinomas suggest that there are common environmental risk factors. The pathophysiology of Crohn inflammatory bowel disease and the elevated risk of adenocarcinoma demonstrate the significance of the impaired integrity of the mucosal barrier and of aberrant immune responses to luminal indigenous and potentially pathogenic microorganisms. CONCLUSION: In advancing a putative mechanism for the contrasting mucosal susceptibilities of the small and large intestine, substantial differences are underscored in the diverse taxonomy, concentration and metabolic activity of anaerobic organisms, rate of intestinal transit, changing pH, and the enterohepatic recycling and metabolism of bile acids. Experimental and epidemiologic studies are cited that suggest that the changing microecology, particularly in the colon, is associated with enhanced metabolic activation of ingested and endogenously formed procarcinogenic substrates. PMID:19064190

  12. Reconstructive cranioplasty using a porcine small intestinal submucosal graft.

    PubMed

    Sheahan, D E; Gillian, T D

    2008-05-01

    A six-year-old border collie was presented with a solid mass on the dorsal cranium. Histological examination showed the mass to be a multilobular tumour of bone. A magnetic resonance imaging scan confirmed deformation of the dorsal cranium with compression of the cerebral hemispheres. A craniotomy was performed to excise the mass and overlying skin, resulting in a substantial deficit of calvarium and skin. A cranioplasty using a small intestinal submucosal (SIS) graft was performed to reconstruct the calvarial defect. A local myocutaneous advancement flap was elevated and positioned over the cranioplasty to close the skin deficit. The outcome of this reconstruction was aesthetic and functional. The small intestinal submucosal graft provided satisfactory mechanical support and was a suitable physical barrier in place of the calvarial bone. Histological examination of the small intestinal submucosal graft 128 days after implantation showed that the graft had been replaced by a dense network of collagenous tissue, with small focal areas of partially mineralised woven bone merging with a fibrocartilaginous matrix of the deeper margin. Histological examination also confirmed regrowth of the multilobular tumour of bone in the region of the small intestinal submucosal graft indicating that it is only a suitable implant if adequate surgical margins are obtained. PMID:18373537

  13. How Is Small Intestine Adenocarcinoma Diagnosed?

    MedlinePlus

    ... normal bowel movement and is flushed away. Double-balloon enteroscopy (endoscopy) Regular upper endoscopy cannot look very ... goes forward a small distance, and then a balloon at its end is inflated to anchor it. ...

  14. Role of cyclooxygenase-2 in intestinal injury in neonatal rats

    PubMed Central

    LU, HUI; ZHU, BING

    2014-01-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature neonates. The pathogenesis of NEC remains poorly understood. The present study aimed to investigate the dynamic change and role of cyclooxygenase-2 (COX-2) in neonatal rats with intestinal injury. Wistar rats, <24 h in age, received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileal tissues were collected at 1, 3, 6, 12 and 24 h following the LPS challenge for histological evaluation of NEC and for measurements of COX-2 mRNA. The correlation between the degree of intestinal injury and expression of COX-2 mRNA was determined. The LPS-injected pups showed a significant increase in injury scores compared to the control, and the most deteriorating change was at 12 h. COX-2 mRNA expression was upregulated following LPS injection. There was a significantly positive correlation between COX-2 mRNA and the grade of intestinal injury within 12 h, whereas COX-2 mRNA expression had a significantly negative correlation with the severity of intestinal injury at 24 h. COX-2 plays an important role in LPS-induced intestinal injury and the repair processes. Caution should be exerted concerning the potential therapeutic uses of COX-2 inhibitors or promoters in NEC. PMID:25279162

  15. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

    PubMed Central

    Onal, Ozkan; Yetisir, Fahri; Sarer, A. Ebru Salman; Zeybek, N. Dilara; Onal, C. Oztug; Yurekli, Banu; Celik, H. Tugrul; Sirma, Ayse; Kılıc, Mehmet

    2015-01-01

    Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented

  16. Leukocyte Trafficking to the Small Intestine and Colon.

    PubMed

    Habtezion, Aida; Nguyen, Linh P; Hadeiba, Husein; Butcher, Eugene C

    2016-02-01

    Leukocyte trafficking to the small and large intestines is tightly controlled to maintain intestinal immune homeostasis, mediate immune responses, and regulate inflammation. A wide array of chemoattractants, chemoattractant receptors, and adhesion molecules expressed by leukocytes, mucosal endothelium, epithelium, and stromal cells controls leukocyte recruitment and microenvironmental localization in intestine and in the gut-associated lymphoid tissues (GALTs). Naive lymphocytes traffic to the gut-draining mesenteric lymph nodes where they undergo antigen-induced activation and priming; these processes determine their memory/effector phenotypes and imprint them with the capacity to migrate via the lymph and blood to the intestines. Mechanisms of T-cell recruitment to GALT and of T cells and plasmablasts to the small intestine are well described. Recent advances include the discovery of an unexpected role for lectin CD22 as a B-cell homing receptor GALT, and identification of the orphan G-protein-coupled receptor 15 (GPR15) as a T-cell chemoattractant/trafficking receptor for the colon. GPR15 decorates distinct subsets of T cells in mice and humans, a difference in species that could affect translation of the results of mouse colitis models to humans. Clinical studies with antibodies to integrin α4β7 and its vascular ligand mucosal vascular addressin cell adhesion molecule 1 are proving the value of lymphocyte trafficking mechanisms as therapeutic targets for inflammatory bowel diseases. In contrast to lymphocytes, cells of the innate immune system express adhesion and chemoattractant receptors that allow them to migrate directly to effector tissue sites during inflammation. We review the mechanisms for innate and adaptive leukocyte localization to the intestinal tract and GALT, and discuss their relevance to human intestinal homeostasis and inflammation. PMID:26551552

  17. Small intestinal model for electrically propelled capsule endoscopy.

    PubMed

    Woo, Sang Hyo; Kim, Tae Wan; Mohy-Ud-Din, Zia; Park, Il Young; Cho, Jin-Ho

    2011-01-01

    The aim of this research is to propose a small intestine model for electrically propelled capsule endoscopy. The electrical stimulus can cause contraction of the small intestine and propel the capsule along the lumen. The proposed model considered the drag and friction from the small intestine using a thin walled model and Stokes' drag equation. Further, contraction force from the small intestine was modeled by using regression analysis. From the proposed model, the acceleration and velocity of various exterior shapes of capsule were calculated, and two exterior shapes of capsules were proposed based on the internal volume of the capsules. The proposed capsules were fabricated and animal experiments were conducted. One of the proposed capsules showed an average (SD) velocity in forward direction of 2.91 ± 0.99 mm/s and 2.23 ± 0.78 mm/s in the backward direction, which was 5.2 times faster than that obtained in previous research. The proposed model can predict locomotion of the capsule based on various exterior shapes of the capsule. PMID:22177218

  18. Functional CCR9 expression is associated with small intestinal metastasis.

    PubMed

    Letsch, Anne; Keilholz, Ulrich; Schadendorf, Dirk; Assfalg, Geraldine; Asemissen, Anne Marie; Thiel, Eckhard; Scheibenbogen, Carmen

    2004-03-01

    In general, metastases to the small intestine are rare, and mostly occur in melanoma. CCR9 has been shown to be the principal chemokine receptor for the thymus expressed chemokine (TECK), a chemokine selectively expressed in the small intestine and thymus. Here we show that CCR9 is highly expressed on melanoma cells and all melanoma cell lines isolated from small intestinal metastases, and on a proportion of cell lines from other sites. Only melanoma cells and cell lines from small intestinal metastases, however, were responsive to the CCR9 ligand TECK, as assessed by receptor downregulation and by actin polymerization. CCR9 expression was also found on the adenocarcinoma cell line CaCo-2 expressing characteristics of enterocytic differentiation, but not on any other cell line isolated from colorectal, breast, and lung cancer. Our data provide evidence that the aberrant functional cell surface expression of an organ-specific chemokine receptor is associated with metastasis to this site. The regulation of receptor function seems to be a critical step in the metastatic process. PMID:15086554

  19. Local actions of trimebutine maleate in canine small intestine.

    PubMed

    Daniel, E E; Kostolanska, F; Allescher, H D; Ahmad, S; Fox, J E

    1988-06-01

    A study of the local actions of trimebutine (TMB) maleate and its N-diesmethyl metabolite (TMB-M) was carried out in the gastrointestinal tract of anesthetized dogs. In the unstimulated small intestine, but not in the stomach or colon, i.a. TMB and TMB-M caused activation of circular muscle. Like the activation by i.a. [Met5]-enkephalin, this was antagonized by naloxone. In field-stimulated segments of stomach and small intestine circular muscle, TMB or TMB-M, like dynorphin-1-13 or [Met5]-enkephalin, inhibited the phasic and tonic contractions which were mediated mostly by cholinergic, postganglionic nerves. However, the inhibitory effects of dynorphin-1-13 or [Met5]-enkephalin on small intestine were antagonized by naloxone whereas those of TMB sometimes or those of TMB-M usually were not. TMB or TMB-M did not affect responses to i.a. acetylcholine, but high doses reduced the contractile responses to subsequent field stimulation and excitatory responses to [Met5]-enkephalin. We concluded that the excitatory local actions of TMB or TMB-M on small intestine involved opioid receptors probably of the mu or delta types. Inhibitory local actions on nerve-mediated responses, however, may not have involved opioid receptors. Comparison of these data to results when TMB or TMB-M were given i.v. suggests that these agents also have peripheral actions to affect gastrointestinal motility at sites outside the gastrointestinal tract. PMID:2898521

  20. Intestinal maturation in the rat: the role of enteral nutrients.

    PubMed

    Castillo, R O; Pittler, A; Costa, F

    1988-01-01

    In order to investigate the role of enteral nutrients in intestinal maturation, an animal model was developed consisting of provision of intravenous nutrient infusions to immature suckling rats over the period of weaning. Age- and litter-matched controls were provided identical amounts of the parenteral solution by entered cannula using the same model. At the end of the period of weaning, animals were killed and the intestines removed for measurement of morphologic parameters and disaccharidase, DNA, and protein levels. The absence of enteral nutrients during weaning resulted in striking inhibition of intestinal growth, diminution in mucosal cell mass, and delayed development of lactase. Although the appearance of sucrase was not affected by the lack of enteral nutrients, sucrase levels rose to only one-third of control levels. Jejunoileal gradients were not present in animals deprived of enteral nutrients but were present in animals receiving enteral nutrients. These results are distinct from adult animals treated in identical experimental fashion and indicate that major parameters of intestinal maturation are altered by the absence of intraluminal nutrients. A critical role for intraluminal nutrients in regulation of intestinal development is therefore suggested. The animal model developed for these studies is well suited for investigation of the interactions of the intraluminal environment with intestinal maturation. PMID:3141647

  1. Angiotensin receptors and angiotensin I-converting enzyme in rat intestine

    SciTech Connect

    Duggan, K.A.; Mendelsohn, F.A.; Levens, N.R. )

    1989-10-01

    The purpose of this study was to map the distribution of angiotensin II (ANG II) receptors and ANG I-converting enzyme (ACE) in rat intestine. ANG II binding sites were visualized by in vitro autoradiography using iodinated (Sar1, Ile8)ANG II. The distribution of ACE was mapped using an iodinated derivative of lisinopril. Male Sprague-Dawley rats were killed and the interior of the whole intestine washed with ice-cold saline. Segments of duodenum, jejunum, ileum, and colon were quickly frozen in a mixture of isopentane and dry ice. Twenty-micron frozen sections were thaw-mounted onto gelatin-coated slides, incubated with either ligand, and exposed to X-ray film. After exposure and subsequent development, the films were quantitated by computerized densitometry. ANG II receptors were most dense in the colon, followed by the ileum, duodenum, and jejunum. Within each segment of intestine, specific ANG II binding sites were localized exclusively to the muscularis. In contrast, ACE was present in both the mucosa and the muscularis. The colocalization of ANG II receptors and ACE may suggest a role for locally generated ANG II in the control of intestinal function. The luminal orientation of ACE in the mucosa of the small intestine may suggest that at this site ACE serves primarily to hydrolyze dietary peptides.

  2. Involvement of concentrative nucleoside transporter 1 in intestinal absorption of trifluorothymidine, a novel antitumor nucleoside, in rats.

    PubMed

    Okayama, Takashige; Yoshisue, Kunihiro; Kuwata, Keizo; Komuro, Masahito; Ohta, Shigeru; Nagayama, Sekio

    2012-02-01

    ααα-Trifluorothymidine (TFT), an anticancer nucleoside analog, is a potent thymidylate synthase inhibitor. TFT exerts its antitumor activity primarily by inducing DNA fragmentation after incorporation of the triphosphate form of TFT into the DNA. Although an oral combination of TFT and a thymidine phosphorylase inhibitor has been clinically developed, there is little information regarding TFT absorption. Therefore, we investigated TFT absorption in the rat small intestine. After oral administration of TFT in rats, more than 75% of the TFT was absorbed. To identify the uptake transport system, uptake studies were conducted by using everted sacs prepared from rat small intestines. TFT uptake was saturable, significantly reduced under Na(+)-free conditions, and strongly inhibited by the addition of an endogenous pyrimidine nucleoside. From these results, we suggested the involvement of concentrative nucleoside transporters (CNTs) in TFT absorption into rat small intestine. In rat small intestines, the mRNAs coding for rat CNT1 (rCNT1) and rCNT2, but not for rCNT3, were predominantly expressed. To investigate the roles of rCNT1 and rCNT2 in TFT uptake, we conducted uptake assays by using Xenopus laevis oocytes injected with rCNT1 complementary RNA (cRNA) and rCNT2 cRNA. TFT uptake by X. laevis oocytes injected with rCNT1 cRNA, and not rCNT2 cRNA, was significantly greater than that by water-injected oocytes. In addition, in situ single-pass perfusion experiments performed using rat jejunum regions showed that thymidine, a substrate for CNT1, strongly inhibited TFT uptake. In conclusion, TFT is absorbed via rCNT1 in the intestinal lumen in rats. PMID:22076553

  3. Adaptive cytoprotection in the small intestine: role of mucus.

    PubMed

    Cepinskas, G; Specian, R D; Kvietys, P R

    1993-05-01

    Gastric mucosal injury induced by strong irritants can be dramatically reduced by pretreating the mucosa with mild forms of the same irritant. This phenomenon has been termed "adaptive cytoprotection." The aim of the present study was to use in vivo and in vitro approaches to study adaptive cytoprotection in the small intestine using physiologically relevant concentrations of oleic acid. Anesthetized rats were instrumented for perfusion of the proximal jejunum with 10 or 40 mM oleic acid (in 20 mM sodium taurocholate). Mucosal epithelial integrity was continuously monitored by measuring the blood-to-lumen clearance of 51Cr-labeled EDTA. Perfusion of the lumen with 40 mM oleic acid produced a 10-fold increase in 51Cr-EDTA clearance, which was not affected by a previous perfusion with 10 mM oleic acid, i.e., no adaptive cytoprotection. In another series of experiments, oleic acid was placed in the lumen rather than perfused, and mucosal epithelial integrity was assessed histologically. Intraluminal placement of 10 mM oleic acid resulted in the generation of a mucus layer over the epithelium. Subsequent placement of 40 mM oleic acid did not produce significant epithelial cell injury, i.e., adaptive cytoprotection. In in vitro studies, mucin (1, 5, and 10 mg/ml) was layered over confluent monolayers of Caco-2 cells prior to addition of 2 mM oleic acid in 4 mM sodium taurocholate. The epithelial cell injury induced by oleic acid was inhibited by mucin in a dose-dependent manner. Further studies indicate that mucin does not prevent, but simply delays, the onset of cell injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8498518

  4. Breath Testing for Small Intestinal Bacterial Overgrowth: Should We Bother?

    PubMed

    Pimentel, Mark

    2016-03-01

    The hydrogen breath test is based on following breath hydrogen levels after the administration of a carbohydrate (most commonly lactulose) to a patient with suspected small intestinal bacterial overgrowth. The test is based on the interaction between the administered carbohydrate and the intestinal bacteria. The resulting fermentation produces hydrogen. A positive breath test is based on a breath hydrogen rise prior to the expected arrival time in the highly microbial cecum. Despite renewed enthusiasm for breath testing in recent years due to associations with conditions such as irritable bowel syndrome, breath testing poses many challenges. In this argument against breath testing, several pitfalls that complicate breath testing will be described. PMID:26902227

  5. Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity

    PubMed Central

    Zhong, Ze-yu; Sun, Bin-bin; Shu, Nan; Xie, Qiu-shi; Tang, Xian-ge; Ling, Zhao-li; Wang, Fan; Zhao, Kai-jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-zhu; Liu, Xiao-dong

    2016-01-01

    Aim: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. Methods: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Results: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestineintestinesmall intestine, and particularly in ileal valve. Furthermore, ciprofloxacin (10–2000 μmol/L) dose-dependently inhibited β-glucuronidase activity in distal small intestine content or E coli incubated in vitro, but did not affect that in proximal small intestine content or bovine liver incubated in vitro. After receiving 6 oral doses or 15 intravenous doses of diclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Conclusion: Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via

  6. Small-intestinal or colonic microbiota as a potential amino acid source in animals.

    PubMed

    Bergen, Werner G

    2015-02-01

    Factors affecting physiological impacts of the microbiome on protein nutrition are discussed for hind-gut fermenters (humans, pigs, rodents). The microbiome flourishes in all gastrointestinal organs, and is a major source of amino acids to fore-gut fermenting animals. In humans, rats and pigs the net effect of microbiome biomass synthesis on amino acid requirements is much less certain. Dietary proteins, amino acids, peptides, endogenous-secreted protein and recycled urea may all be utilized as nitrogen source by growing bacteria in the small intestine and colon. The inclusions of radiolabelled amino acid precursors will result in labeled bacteria which can be digested and absorbed in the ileum and to some degree in the colon. This does not necessarily indicate a significant nutritional role of the microbiome in humans, pigs and rodents. The physiological attributes required for small-intestinal and colon microbiome utilization are a vigorous proteolytic digestion with pancreatic or intestinal enzymes and the presence of amino acid transporters. Findings to date seem to suggest that these two physiological attributes for effective bacterial protein utilization are present in the small intestine; however, these attributes have a much lower capacity/impact in the colon. The gastrointestinal microbiome is likely a protein source of medium to high nutritional quality, but overall the microbiome is not an important amino acid source in humans and animals fed amino acids at requirement levels. PMID:25466904

  7. Effect of indigestible saccharides on B lymphocyte response of intestinal mucosa and cecal fermentation in rats.

    PubMed

    Kudoh, K; Shimizu, J; Wada, M; Takita, T; Kanke, Y; Innami, S

    1998-02-01

    The effects of water-soluble and -insoluble indigestible saccharides (IDS) on immune responses of the intestinal tract were studied. Male 4-week-old Sprague Dawley rats were fed for three weeks on diets containing several kinds of IDS at 5%. The results revealed that the proportion of kappa-light chain and IgA-presenting lymphocytes in small intestinal and cecal mucosa differed in increased number depending on the type of IDS. The response of colonic mucosa was not pronounced. The amounts of short-chain fatty acid (SCFA) and lactic acid in the cecal contents of the other test groups except the celfur group tended to be higher than those in the cellulose group, particularly in the lactulose group where many acids showed significant increases. The correlation between the proportion of kappa-light chain and IgA-presenting lymphocytes in the cecal mucosa and lactic acid in the cecal contents was significant, but that between the proportion of both lymphocytes and SCFA was not. Based on the above, we concluded that the oral administration of IDS induces the proliferation of kappa-light chain and IgA-producing B lymphocytes in small intestinal and cecal mucosa, but the degree of response differs depending on the type of IDS. It is thus suggested that IDS are involved in the intestinal immune system of rats. PMID:9591238

  8. Activation of rat intestinal mucosal mast cells by fat absorption.

    PubMed

    Ji, Yong; Sakata, Yasuhisa; Yang, Qing; Li, Xiaoming; Xu, Min; Yoder, Stephanie; Langhans, Wolfgang; Tso, Patrick

    2012-06-01

    Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D(2) (PGD(2)) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in lymphatic histamine and PGD(2), ∼20-fold increase in lymphatic RMCPII, but only onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII into lymph increased dose dependently with the amount of lipid fed. In addition, i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major composite in Liposyn II) significantly increased the lymphatic RMCPII concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not alter lymph RMCPII secretion. Immunohistochemistry image revealed the degranulation of MMC into lamina propria after lipid feeding. These novel findings indicate that intestinal MMC are activated and degranulate to release MMC mediators to the circulation during fat absorption. This action of fatty acid is dose and chain length dependent. PMID:22461027

  9. Small intestine histomorphometry of beef cattle with divergent feed efficiency

    PubMed Central

    2013-01-01

    Background The provision of feed is a major cost in beef production. Therefore, the improvement of feed efficiency is warranted. The direct assessment of feed efficiency has limitations and alternatives are needed. Small intestine micro-architecture is associated with function and may be related to feed efficiency. The objective was to verify the potential histomorphological differences in the small intestine of animals with divergent feed efficiency. Methods From a population of 45 feedlot steers, 12 were selected with low-RFI (superior feed efficiency) and 12 with high-RFI (inferior feed efficiency) at the end of the finishing period. The animals were processed at 13.79 ± 1.21 months of age. Within 1.5 h of slaughter the gastrointestinal tract was collected and segments from duodenum and ileum were harvested. Tissue fragments were processed, sectioned and stained with hematoxylin and eosin. Photomicroscopy images were taken under 1000x magnification. For each animal 100 intestinal crypts were imaged, in a cross section view, from each of the two intestinal segments. Images were analyzed using the software ImageJ®. The measurements taken were: crypt area, crypt perimeter, crypt lumen area, nuclei number and the cell size was indirectly calculated. Data were analyzed using general linear model and correlation procedures of SAS®. Results Efficient beef steers (low-RFI) have a greater cellularity (indicated by nuclei number) in the small intestinal crypts, both in duodenum and ileum, than less efficient beef steers (high-RFI) (P < 0.05). The mean values for the nuclei number of the low-RFI and high-RFI groups were 33.16 and 30.30 in the duodenum and 37.21 and 33.65 in the ileum, respectively. The average size of the cells did not differ between feed efficiency groups in both segments (P ≥ 0.10). A trend was observed (P ≤ 0.10) for greater crypt area and crypt perimeter in the ileum for cattle with improved feed efficiency. Conclusion

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

    PubMed Central

    2013-01-01

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

  11. Intestinal Inflammation in Rats Induces Metallothionein in Colonic Submucosa

    PubMed Central

    Al-Gindan, Yasmin; Shawarby, Mohammed; Noto, Amy; Taylor, Carla G.

    2009-01-01

    The aim of the current study was to determine if induction of metallothionein (MT) via acute or chronic dietary zinc supplementation attenuates intestinal inflammation, and to investigate the relationship with site-specific intestinal MT determined by immunolocalization. Growing rats were assigned to zinc-deficient (ZD), acute zinc-treated (ZT), pair-fed, control or chronic Zn-supplemented (ZS) groups. Half the rats in each dietary group received 5% dextran sulphate sodium (DSS) in their drinking water for 4 days. DSS treatment produced acute intestinal inflammation in the colon only, however, dietary zinc deficiency, acute zinc treatment or chronic zinc supplementation did not alter the severity of ulceration. Serum zinc concentrations were attenuated in the DSS-challenged ZT and ZS groups suggesting that zinc was being utilized in some capacity in response to inflammation. DSS-challenge induced MT immunostaining in the colonic submucosa, however, MT was not associated with histological improvements in the present study. The site-specific MT induction in colonic submucosa during intestinal inflammation requires further clarification as a component of the host defense. PMID:19308267

  12. Insights into Embryo Defenses of the Invasive Apple Snail Pomacea canaliculata: Egg Mass Ingestion Affects Rat Intestine Morphology and Growth

    PubMed Central

    Gimeno, Eduardo J.; Heras, Horacio

    2014-01-01

    Background The spread of the invasive snail Pomacea canaliculata is expanding the rat lungworm disease beyond its native range. Their toxic eggs have virtually no predators and unusual defenses including a neurotoxic lectin and a proteinase inhibitor, presumably advertised by a warning coloration. We explored the effect of egg perivitellin fluid (PVF) ingestion on the rat small intestine morphology and physiology. Methodology/Principal Findings Through a combination of biochemical, histochemical, histopathological, scanning electron microscopy, cell culture and feeding experiments, we analyzed intestinal morphology, growth rate, hemaglutinating activity, cytotoxicity and cell proliferation after oral administration of PVF to rats. PVF adversely affects small intestine metabolism and morphology and consequently the standard growth rate, presumably by lectin-like proteins, as suggested by PVF hemaglutinating activity and its cytotoxic effect on Caco-2 cell culture. Short-term effects of ingested PVF were studied in growing rats. PVF-supplemented diet induced the appearance of shorter and wider villi as well as fused villi. This was associated with changes in glycoconjugate expression, increased cell proliferation at crypt base, and hypertrophic mucosal growth. This resulted in a decreased absorptive surface after 3 days of treatment and a diminished rat growth rate that reverted to normal after the fourth day of treatment. Longer exposure to PVF induced a time-dependent lengthening of the small intestine while switching to a control diet restored intestine length and morphology after 4 days. Conclusions/Significance Ingestion of PVF rapidly limits the ability of potential predators to absorb nutrients by inducing large, reversible changes in intestinal morphology and growth rate. The occurrence of toxins that affect intestinal morphology and absorption is a strategy against predation not recognized among animals before. Remarkably, this defense is rather similar to

  13. Stress-induced breakdown of intestinal barrier function in the rat: reversal by wood creosote.

    PubMed

    Kuge, Tomoo; Greenwood-Van Meerveld, Beverley; Sokabe, Masahiro

    2006-07-24

    Our previous studies demonstrated that wood creosote (Seirogan) inhibits intestinal secretion and normalizes the transport of electrolytes and water in rats subjected to restraint stress. The goal of the present study was to examine whether wood creosote has a protective effect against stress-induced breakdown of intestinal barrier function. F-344 rats were subjected to 90-min water avoidance stress (WAS) with wood creosote (30 mg/kg) or vehicle administered intragastrically 30 min prior to WAS. Sham stressed rats received wood creosote or vehicle treatment but did not experience the WAS. All rats were euthanized at the end of the WAS or sham-stress and the jejunum and colon were isolated. Epithelial transport was studied in modified Ussing chambers. Spontaneous secretion was assessed by electrophysiological measurement of the short circuit current (I(sc)) while electrical conductance (G) was calculated from the potential difference (PD) and I(sc) using Ohm's law. Intestinal permeability was defined by the mucosal-to-serosal flux of horseradish peroxidase (HRP). WAS significantly elevated basal I(sc) and G and increased epithelial permeability to HRP in the jejunum but not in the colon. Wood creosote resulted in a significant reduction of the stress-induced increase in I(sc), G and the mucosal-to-serosal flux of HRP compared to the vehicle-treated group. Wood creosote caused no significant effects in sham-stressed rats. The results suggest that oral administration of wood creosote may prevent stress-induced diarrhea by preventing aversive effects on small intestinal secretion and barrier function. PMID:16643959

  14. Green tea (Camellia sinensis) alleviates arsenic-induced damages to DNA and intestinal tissues in rat and in situ intestinal loop by reinforcing antioxidant system.

    PubMed

    Acharyya, Nirmallya; Sajed Ali, Sk; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit

    2015-09-01

    This study elucidates the protective role of Green tea (Camellia sinensis or CS) against arsenic-induced mutagenic DNA-breakage/intestinal (small) damages in female rats. Intestinal epithelial cells receive ingested arsenic initially. Though, the possibility of damages in this tissue is immense and the therapeutic strategies against this damage are of great concern, reports on either issue are scanty. Our earlier study on arsenic-exposed human unveils a link between carcinogenesis and mutagenic DNA damage. Here, we demonstrate that supplementation of CS-extract (10 mg/mL water) with NaAsO2 (0.6 ppm)/100 g b.w. for 28 days to rats offered a significant protection against arsenic-induced oxidative damages to DNA and intestinal (small) tissues by buttressing antioxidant systems. Necrotic and apoptotic damages and their CS-protection are shown in DNA-fragmentation, comet-assay, and histoarchitecture (hematoxylin and eosin and periodic acid-schiff staining) results. Only arsenic exposure significantly decreased intestinal superoxide dismutase, catalase activities, and level of soluble thiol with a concomitant increase in malondialdehyde/conjugated dienes. Alteration of serum necrotic marker lactate dehydrogenase and the metabolic inflammatory marker c-reactive protein also indicate the impairment may be occurring at transcription and/or cellular signal transduction level. In addition, in situ incubation in rat intestinal loop filled for 24 h with NaAsO2 alone (250 µM) or with aqueous CS-extract (250 mg/mL) suggests that small intestinal epithelial cells are significantly protected by CS against arsenic-associated necrotic/mutagenic damages, which is observed in DNA-breakage studies. In conclusion, besides intensifying endogenous antioxidant system, CS polyphenols also offer a direct role on free radical scavenging activity that is associated to the protection from mutagenic DNA-breakages and prevention of tissue necrosis/carcinogenesis generated by arsenic. PMID

  15. [Emergency surgery of tumors of the small intestine].

    PubMed

    Meo, G; Aghemo, B; Laguzzi, B; Borello, M

    1978-09-15

    Ten cases of serious complications requiring emergency surgery in patients with tumours of the small intestine are presented: 3 cases of peritonitis due to perforation of a fibroleiomyoma, a jejunal adenocarcinoma, and an ileal lymphosarcoma; 3 invaginations (1 ileocolic due to an ileal polyp, and 2 ileoileal due to lymphoma and polypoid metastasis of melanoma; 3 stenosis (ileal owing to metastasis of melanoma, and duodenal and of the duodenojejunal flexure due to histologically unascertained neoplasias); 1 massive enterorrhagia from ileal anaplastic carcinoma. The frequency of such pictures is not negligible when assessed in terms of emergency surgical pathology and compared with other emergency situations arising in patients with tumours. Preoperative diagnosis is difficult even from the clinical history. Tumours of the small intestine appear to give rise to such complications in their initial stages. PMID:581225

  16. The small intestinal maltase-glucoamylase activity increases during the postnatal growth in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The small intestinal maltase-glucoamylase (MGAM) contributes to the starch digestion pathway in the small intestine. This study investigated ontogenic changes of MGAM in the hydrolysis of amylose along the longitudinal axis of the small intestine. Jejunal tissue was collected from pigs belonging t...

  17. Vagal glucoreceptors in the small intestine of the cat.

    PubMed Central

    Mei, N

    1978-01-01

    1. In anaesthetized cats, the unitary activity of seventy-eight sensory vagal neurones was recorded in nodose ganglia by means of extracellular glass microelectrodes. 2. These neurones were stimulated by perfusion of the small intestine (duodenum and first part of jejunum) with glucose or other different carbohydrates at concentrations of 1--20 g/l. (i.e. 55--1100 m-osmole/l.). 3. The neurones were slowly adapting to stimulation and their discharge frequency was always low (1--30 Hz). 4. The activity of these neurones depended on the particular carbohydrate used and on its concentration: the discharge frequency generally increased when the concentration rose. 5. The neurones were of the C type (conduction velocities: 0.8--1.4 m/sec; mean, 1.1 m/sec). 6. In contrast with the known neurones connected to the gastro-intestinal tension receptors, they were not obviously activated by intestinal contractions or distensions. 7. In the same way, the stimuli which produced the response of other known endings, i.e. the mucosal receptors, were not effective; these stimuli included in particular stroking of the mucosa, over-distension of the bowel, intestinal perfusion with alkaline or acid solutions. On the other hand, the use of substances other than glucose (KCl and NaCl of the same osmolarity) showed that the osmotic pressure was not directly related to the receptor activation. 8. Therefore it is proposed to call the endings corresponding to these neurones 'glucoreceptors'. 9. The effect of glycaemia and intestinal motility were also studied. These variables acted presumably by changing the intestinal absorption rate. 10. The functional characteristics of the glucoreceptors (in particular the short latency of their response) strongly suggested that they were located close to the intestinal epithelium. 11. An ultrastructural study was performed in an attempt to identify the histological site of the receptors. Many non-medullated fibres were observed in the villi, especially

  18. Diversity of human small intestinal Streptococcus and Veillonella populations.

    PubMed

    van den Bogert, Bartholomeus; Erkus, Oylum; Boekhorst, Jos; de Goffau, Marcus; Smid, Eddy J; Zoetendal, Erwin G; Kleerebezem, Michiel

    2013-08-01

    Molecular and cultivation approaches were employed to study the phylogenetic richness and temporal dynamics of Streptococcus and Veillonella populations in the small intestine. Microbial profiling of human small intestinal samples collected from four ileostomy subjects at four time points displayed abundant populations of Streptococcus spp. most affiliated with S. salivarius, S. thermophilus, and S. parasanguinis, as well as Veillonella spp. affiliated with V. atypica, V. parvula, V. dispar, and V. rogosae. Relative abundances varied per subject and time of sampling. Streptococcus and Veillonella isolates were cultured using selective media from ileostoma effluent samples collected at two time points from a single subject. The richness of the Streptococcus and Veillonella isolates was assessed at species and strain level by 16S rRNA gene sequencing and genetic fingerprinting, respectively. A total of 160 Streptococcus and 37 Veillonella isolates were obtained. Genetic fingerprinting differentiated seven Streptococcus lineages from ileostoma effluent, illustrating the strain richness within this ecosystem. The Veillonella isolates were represented by a single phylotype. Our study demonstrated that the small intestinal Streptococcus populations displayed considerable changes over time at the genetic lineage level because only representative strains of a single Streptococcus lineage could be cultivated from ileostoma effluent at both time points. PMID:23614882

  19. Nature of elevated rat intestinal carbohydrase activities after high-carbohydrate diet feeding

    SciTech Connect

    Tsuboi, K.K.; Kwong, L.K.; Yamada, K.; Sunshine, P.; Koldovsky, O.

    1985-10-01

    Adult rats that were maintained on a low-carbohydrate intake showed rapid increase in the activities of sucrase, maltase, and lactase along the length of the small intestine when they were fed a high-starch diet. In the present study, the authors have identified these activity increases, and showed that they reflect proportional accumulations in enzyme-protein of sucrase-isomaltase, maltase-glucoamylase, and neutral lactase. It was determined that each of these enzymes exists in adult rat intestine in single immunoreactive form and accounts as a group for all sucrase, cellobiase, and most maltase and lactase activities. Dietary change from low to high carbohydrate (starch) resulted in an increase in (TH)leucine accumulation in each of the enzymes, without a change in the amount of label accumulation in total intestinal proteins. The increase in label accumulation in the brush-border carbohydrase pools was matched generally by proportional elevation in the pool concentrations of sucrase-isomaltase and lactase but not maltase. These studies suggest that the elevation of intestinal carbohydrase concentrations induced by high-carbohydrate feeding may involve selective stimulation of their synthesis.

  20. Ontogenic timing mechanism initiates the expression of rat intestinal sucrase activity

    SciTech Connect

    Yeh, K.Y.; Holt, P.R.

    1986-03-01

    Morphologic and enzymic differentiation occurs in rat small intestinal epithelium during 16-20 days of postnatal life. This change is considered to be initiated by an ontogenic timing mechanism and is modulated by extrinsic systemic and luminal factors. The importance of the ontogenic timing was tested directly using a transplantation technique in which jejunal isografts from newborn (day 0) and 5-day-old (day 5) rats were implanted under the skin of newborn (day 0) hosts. Isografts showing cryptvillus architecture were obtained in 44% and 21% of transplants, respectively. Day 0 isografts and host intestine expressed sucrase activity at about 16-18 days of age and showed similar crypt cell labeling and epithelial migration after (3H)thymidine injection. Day 5 isografts expressed sucrase activity when the hosts were 13 days of age, whereas host intestine showed no detectable sucrase activity. Isograft lactase activities in both experimental transplant models were significantly higher than host intestinal lactase up to 28 days of age, suggesting that luminal factors are important in modulating lactase activity during the first 4 wk of postnatal life. It is concluded that (a) no systemic factors at day 13 inhibit the expression of sucrase activity and (b) an ontogenic timing mechanism in the jejunum initiates the expression of sucrase activity.

  1. Intestinal effects of long-lasting spermine ingestion by suckling rats.

    PubMed

    Deloyer, Patricia; Peulen, Olivier; Dandrifosse, Guy

    2005-11-01

    Spermine ingestion induces the precocious maturation of the small intestine in suckling rats. Previous observations suggest that spermine-induced intestinal maturation is a two-step phenomenon. The first step is the elimination of immature enterocytes (4-10 h post spermine ingestion) and the second step is the replacement of previous immature cells by adult-type enterocytes (2-3 days post initial spermine administration). The spermine-induced maturation is reversible when spermine administration is stopped. This work was undertaken in order to check whether the extension of polyamine administration (for 3-7 days) after the appearance of spermine-induced maturation can retain the mature state of the small intestine. Our results indicate that extension of spermine administration does not prevent some parameters (sucrase and maltase specific activities) reverting to a typical 'immature' value while others remain at a typical 'mature' level (mucosal weight and lactase specific activity). Our results show that there are at least two different mechanisms in required for the control of spermine-induced maturation of the small intestine. PMID:16143722

  2. Magnesium sulfate-induced water secretion in hamster small intestine

    SciTech Connect

    Reichelderfer, M.; Pero, B.; Lorenzsonn, V.; Olsen, W.A.

    1984-05-01

    Possible mechanisms of magnesium sulfate (MgSO/sup 4/)-induced diarrhea were studied. In vivo perfusion of hamster small intestine with an isotonic electrolyte solution containing 50 mM MgSO/sub 4/ produced nearly three times as much fluid secretion as did a solution containing an equiosmotic amount of mannitol. It was found that magnesium was absorbed at a faster rate than mannitol under these conditions, suggesting that differences in solute permeability do not explain the differences in secretory rates. Magnesium ion rather than sulfate appeared largely responsible for the effect as replacement of sulfate with chloride did not diminish the response. MgSO/sub 4/ perfusion of a proximal intestinal segment did not affect water transport in an isolated distal segment suggesting that release of cholecystokinin or alterations in serum levels of other hormones were not responsible. Intestinal permeability, morphology, and cyclic nucleotide levels were normal after MgSO/sub 4/ perfusion. Thus, MgSO/sub 4/-induced diarrhea cannot be explained by the usual mechanisms, and additional processes responsible for intestinal secretion must exist.

  3. Cholesterol modulates alkaline phosphatase activity of rat intestinal microvillus membranes.

    PubMed

    Brasitus, T A; Dahiya, R; Dudeja, P K; Bissonnette, B M

    1988-06-25

    Experiments were conducted, using a nonspecific lipid transfer protein, to vary the cholesterol/phospholipid molar ratio of rat proximal small intestinal microvillus membranes in order to assess the possible role of cholesterol in modulating enzymatic activities of this plasma membrane. Cholesterol/phospholipid molar ratios from 0.71 to 1.30 were produced from a normal value of 1.05 by incubation with the transfer protein and an excess of either phosphatidylcholine or cholesterol/phosphatidylcholine liposomes for 60 min at 37 degrees C. Cholesterol loading or depletion of the membranes was accompanied by a decrease or increase, respectively, in their lipid fluidity, as assessed by steady-state fluorescence polarization techniques using the lipid-soluble fluorophore 1,6-diphenyl-1,3,5-hexatriene. Increasing the cholesterol/phospholipid molar ratio also decreased alkaline phosphatase specific activity by approximately 20-30%, whereas decreasing this ratio increased this enzymatic activity by 20-30%. Sucrase, maltase, and lactase specific activities were not affected in these same preparations. Since the changes in alkaline phosphatase activity could be secondary to alterations in fluidity, cholesterol, or both, additional experiments were performed using benzyl alcohol, a known fluidizer. Benzyl alcohol (25 mM) restored the fluidity of cholesterol-enriched preparations to control levels, did not change the cholesterol/phospholipid molar ratio, and failed to alter alkaline phosphatase activity. These findings, therefore, indicate that alterations in the cholesterol content and cholesterol/phospholipid molar ratio of microvillus membranes can modulate alkaline phosphatase but not sucrase, maltase, or lactase activities. Moreover, membrane fluidity does not appear to be an important physiological regulator of these enzymatic activities. PMID:3379034

  4. Fermentation of dietary fibre components in the rat intestinal tract.

    PubMed

    Nyman, M; Asp, N G

    1982-05-01

    1. The fermentative breakdown of dietary fibre from various sources in the intestinal tract was studied using rat balance experiments and gas-liquid chromatograhic analysis of dietary fibre monomers in feed and faces. 2. On a basal diet with 690 g maize starch/kg but no added fibre, small but detectable amounts of polymeric glucose, rhamnose, arabinose, xylose, galactose, mannose and uronic acids, i.e. sugars occurring in dietary fibre, were excreted in faeces. 3. Dietary fibre in wheat bran was rather resistant to fermentation; 63% was recovered in the faeces. Guar gum, on the other hand, was almost completely fermented, whereas 19 and 25% of the uronic acids in low and high methoxylated pectin respectively, were excreted in faeces. The various constituents of sugar-beet dietary fibre (approximately equal amounts of arabinose-based hemicellulose, pectin and non-starch glucan (cellulose)) showed quite variable availability for micro-organisms in that 6-12% of the arabinose, 17-25% of the uronic acids, and 52-58% of the cellulose were recovered in the faeces. 4. Faecal nitrogen excretion increased on addition of any one of the dietary fibre preparations studied, resulting in decreased true and apparent protein digestibility values. 5. The faecal dry weight increment was most pronounced when feeding bran and could then almost be accounted for by the remaining fibre and by protein. The less-prominent bulking effect of guar gum and pectins, that were much more extensively fermented, could be only partly explained by dietary fibre and protein. PMID:6282300

  5. The mechanism of intestinal absorption of phosphatidylcholine in rats

    PubMed Central

    Parthasarathy, Sampath; Subbaiah, Papasani V.; Ganguly, Jagannath

    1974-01-01

    1. The mechanism of absorption of phosphatidylcholine was studied in rats by injecting into the intestine phosphatidylcholine specifically labelled either in the fatty acid or in the glycerol moiety or with 32P, when considerable amounts of 1-acyl-lysophosphatidylcholine were found in the intestinal lumen. 2-([14C]Acyl)phosphatidylcholine gave markedly more radioactive unesterified fatty acids in the lumen, compared with the 1-([14C]acyl) derivative. Some of the radioactivity from either the fatty acid or the glycerol moiety of the injected phosphatidylcholine appeared in the mucosal triacylglycerols. 2. Injection of 32P-labelled phosphatidylcholine or 32P-labelled lysophosphatidylcholine led to the appearance of radioactive glycerylphosphorylcholine, glycerophosphate and Pi in the mucosa. 3. Rat mucosa was found to contain a highly active glycerylphosphorylcholine diesterase. 4. It was concluded that the dietary phosphatidylcholine is hydrolysed in the intestinal lumen by the pancreatic phospholipase A to 1-acylglycerylphosphorylcholine, which on entering the mucosal cell is partly reacylated to phosphatidylcholine, and the rest is further hydrolysed to glycerylphosphorylcholine, glycerophosphate, glycerol and Pi. The fatty acids and glycerophosphate are then reassembled to give triacylglycerols via the Kennedy (1961) pathway. PMID:4374941

  6. Acylation of lysolecithin in the intestinal mucosa of rats

    PubMed Central

    Subbaiah, P. V.; Sastry, P. S.; Ganguly, J.

    1970-01-01

    1. The presence of an active acyl-CoA–lysolecithin (1-acylglycerophosphorylcholine) acyltransferase was demonstrated in rat intestinal mucosa. 2. ATP and CoA were necessary for the incorporation of free [1-14C]oleic acid into lecithin (phosphatidylcholine). 3. The reaction was about 20 times as fast with [1-14C]oleoyl-CoA as with free oleic acid, CoA and ATP. 4. With 1-acylglycerophosphorylcholine as the acceptor, both oleic acid and palmitic acid were incorporated into the β-position of lecithin; the incorporation of palmitic acid was 60% of that of oleic acid. 5. Of the various analogues of lysolecithin tested as acyl acceptors from [1-14C]oleoyl CoA, a lysolecithin with a long-chain fatty acid at the 1-position was most efficient. 6. The enzyme was mostly present in the brush-border-free particulate fraction of the intestinal mucosa. 7. Of the various tissues of rats tested for the activity, intestinal mucosa was found to be the most active, with testes, liver, kidneys and spleen following it in decreasing order. PMID:5484668

  7. Effects of penehyclidine hydrochloride in small intestinal damage caused by limb ischemia-reperfusion

    PubMed Central

    Zhang, Yan; Leng, Yu-Fang; Xue, Xing; Zhang, Yue; Wang, Tao; Kang, Yu-Qing

    2011-01-01

    AIM: To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion (LIR) injury. METHODS: Male Wistar rats were randomly divided into three groups (36 rats each): the sham-operation group (group S), lower limb ischemia-reperfusion group (group LIR), and penehyclidine hydrochloride post-conditioning group (group PHC). Each group was divided into subgroups (n = 6 in each group) according to ischemic-reperfusion time, i.e. immediately 0 h (T1), 1 h (T2), 3 h (T3), 6 h (T4), 12 h (T5), and 24 h (T6). Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanter for 3 h. In group PHC, 0.15 mg/kg of penehyclidine hydrochloride was injected into the tail vein immediately after 3 h of bilateral hind-limb ischemia. The designated rats were sacrificed at different time-points of reperfusion; diamine oxidase (DAO), superoxide dismutase (SOD) activity, myeloperoxidase (MPO) of small intestinal tissue, plasma endotoxin, DAO, tumor necrosis factor-α (TNF-α), and interleukin (IL)-10 in serum were detected in the rats. RESULTS: The pathological changes in the small intestine were observed under light microscope. The levels of MPO, endotoxin, serum DAO, and IL-10 at T1-T6, and TNF-α level at T1-T4 increased in groups LIR and PHC (P < 0.05) compared with those in group S, but tissue DAO and SOD activity at T1-T6 decreased (P < 0.05). In group PHC, the tissue DAO and SOD activity at T2-T6, and IL-10 at T2-T5 increased to higher levels than those in group LIR (P < 0.05); however, the levels of MPO, endotoxin, and DAO in the blood at T2-T6, and TNF-α at T2 and T4 decreased (P < 0.05). CONCLUSION: Penehyclidine hydrochloride post-conditioning may reduce the permeability of the small intestines after LIR. Its protection mechanisms may be related to inhibiting oxygen free radicals and inflammatory

  8. Age characteristics of changes in invertase activity of the mucous membrane of the small intestine

    NASA Technical Reports Server (NTRS)

    Rakhimov, K. R.; Aleksandrova, N. V.

    1980-01-01

    Rats of varying ages were subjected to stress from heat, cold, and hydrocortisone injection. Invertase activity in homogenates of small intestine mucous membranes was studied following sacrifice. Invertase activity was low in young animals, but increased sharply in 30 day old ones, remaining at a relatively constant level until old age. The study concludes that the stress hormone (corticosteroids, etc.) levels in the blood, which affects the formation of enteric enzyme levels and activities, and that age related peculiarities in invertase activity are a consequence of altered hormone status and epitheliocyte sensitivity.

  9. Nitric oxide decreases intestinal haemorrhagic lesions in rat anaphylaxis independently of mast cell activation

    PubMed Central

    Tavares, J. Carvalho; Moreno, A.

    1997-01-01

    The purpose of this study is to assess the role of nitric oxide (NO) in the intestinal lesions of passive anaphylaxis, since this experimental model resembles necrotizing enterocolitis. Sprague-Dawley rats were sensitized with IgE anti-dinitrophenol monoclonal antibody. Extravasation of protein-rich plasma and haemorrhagia were measured in the small intestine. Plasma histamine was measured to assess mast cell activation. The effect of exogenous NO on the lesions was assessed by using two structurally unrelated NO-donors: sodium nitroprusside and S-nitroso-Nacetyl-penicillamine (SNAP). An increased basal production of NO was observed in cells taken after anaphylaxis, associated with a reduced response to platelet-activating factor, interleukin 1beta, and IgE/DNP-bovine serum albumin complexes. The response to bacterial lipopolysaccharide and dibutyryl cyclic adenosine monophosphate (AMP) was enhanced 24 h after challenge, but at earlier times was not significantly different from that observed in controls. Treatment with either sodium nitroprusside or SNAP produced a significant reduction of the haemorrhagic lesions, which are a hallmark of rat anaphylaxis. The extravasation of protein-rich plasma was not influenced by NO-donors. The increase of plasma histamine elicited by the anaphylactic challenge was not influenced by SNAP treatment. NO-donors protect intestinal haemorrhagic lesions of rat anaphylaxis by a mechanism apparently independent of mast cell histamine release. PMID:18472830

  10. Intestinal absorption of dolichol from emulsions and liposomes in rats.

    PubMed

    Kimura, T; Takeda, K; Kageyu, A; Toda, M; Kurosaki, Y; Nakayama, T

    1989-02-01

    The intestinal absorption of dolichol from various dosage forms was investigated using the intestinal loop and everted sac methods in the rat. The in situ loop experiments showed that the absorption of dolichol from a triglyceride emulsion was dependent on the chain-length of the triglyceride; the absorption from a tri-n-butyrin emulsion in 1 h was 18.0% of the dose; and the absorption from an HCO-60 suspension was 4.3%. The liposomal preparation enhanced the absorption up to 39.1% of the dose. In in vitro experiments, 25.0% and 13.2% of dolichol were taken up by everted sacs of the jejunum and the ileum, respectively. On the other hand, phospholipids composing liposomes were not absorbed under these conditions. The above results suggest that the absorption mechanism from liposomal preparations may be as follows: dolichol is released from the liposomes into the aqueous phase adjacent to the surface of the intestine and is subsequently partitioned into the intestinal tissue. PMID:2743494

  11. Inhibition of Protease-activated Receptor 1 Ameliorates Intestinal Radiation Mucositis in a Preclinical Rat Model

    SciTech Connect

    Wang, Junru; Kulkarni, Ashwini; Chintala, Madhu; Fink, Louis M.; Hauer-Jensen, Martin

    2013-01-01

    Purpose: To determine, using a specific small-molecule inhibitor of protease-activated receptor 1 (PAR1) signaling, whether the beneficial effect of thrombin inhibition on radiation enteropathy development is due to inhibition of blood clotting or to cellular (PAR1-mediated) thrombin effects. Methods and Materials: Rats underwent fractionated X-irradiation (5 Gy Multiplication-Sign 9) of a 4-cm small-bowel segment. Early radiation toxicity was evaluated in rats receiving PAR1 inhibitor (SCH602539, 0, 10, or 15 mg/kg/d) from 1 day before to 2 weeks after the end of irradiation. The effect of PAR1 inhibition on development of chronic intestinal radiation fibrosis was evaluated in animals receiving SCH602539 (0, 15, or 30 mg/kg/d) until 2 weeks after irradiation, or continuously until termination of the experiment 26 weeks after irradiation. Results: Blockade of PAR1 ameliorated early intestinal toxicity, with reduced overall intestinal radiation injury (P=.002), number of myeloperoxidase-positive (P=.03) and proliferating cell nuclear antigen-positive (P=.04) cells, and collagen III accumulation (P=.005). In contrast, there was no difference in delayed radiation enteropathy in either the 2- or 26-week administration groups. Conclusion: Pharmacological blockade of PAR1 seems to reduce early radiation mucositis but does not affect the level of delayed intestinal radiation fibrosis. Early radiation enteropathy is related to activation of cellular thrombin receptors, whereas platelet activation or fibrin formation may play a greater role in the development of delayed toxicity. Because of the favorable side-effect profile, PAR1 blockade should be further explored as a method to ameliorate acute intestinal radiation toxicity in patients undergoing radiotherapy for cancer and to protect first responders and rescue personnel in radiologic/nuclear emergencies.

  12. Inflammatory myofibroblastic tumor of the small intestine: A case report

    PubMed Central

    Amouei, Abdolhamid; Ehsani, Fatemeh; Vaghefi, Marzie; Tabatabai, Seyed Mostafa; Yazdian Anari, Pouria

    2016-01-01

    Introduction Inflammatory myofibroblastic tumor (IMT) is a rare benign tumor. Usually seen in children and adolescents, this inflammatory tumor can affect all the organs. Presentation of case In this case, a five-year-old child experienced the sudden onset of symptoms and the enlargement of abdominal mass 20 days before referral. The patient did not have any symptoms of nausea, vomit, and abdominal pain. In the laparotomy, a large and sticky solid mass, attached to the ileum with the mesenteric origin, sized 10 × 8 cm was observed and completely resected. Discussion This tumor rarely emerges in the small intestine, and there are a few patients with intestinal manifestation. In this case report, the tumor had an origin of the small intestine mesenteric and it had invaded to the ileum. Conclusion Despite using some radiographic methods such as medical ultrasound and computerized tomography (CT) scan to diagnose the disease, the definitive diagnosis is merely possible thorough complete surgical resection. PMID:27046103

  13. Microbial influences on the small intestinal response to radiation injury

    PubMed Central

    Packey, Christopher D.; Ciorba, Matthew A.

    2014-01-01

    Purpose of review Injury to the small bowel from ionizing radiation occurs commonly in patients undergoing cancer therapy and less commonly in instances of accidental radiation overexposure. Several lines of evidence now suggest that dynamic interactions between the host’s enteric microbiota and innate immune system are important in modulating the intestinal response to radiation. Here, we will review recent developments in the area of acute radiation enteropathy and examine the current state of knowledge regarding the impact of host–microbial interactions in the process. Recent findings There is promise in the development and testing of new clinical biomarkers including serum citrulline. Toll-like receptor agonists and innate immune system signaling pathways including nuclear factor-kappa B profoundly alter intestinal epithelial cell apoptosis and crypt survival after radiation exposure. Germ-free conditions, probiotics and antibiotics are each identified as modifiers of disease development and course. A human study suggested that luminal microbiota composition may influence the host’s intestinal response to radiation and may change in those developing postradiation diarrhea. Summary New knowledge implies that investigations aimed at deciphering the microbiome–host interactions before and after small bowl radiation injury may eventually allow prediction of disease course and offer opportunities for the development of novel therapeutic or prophylactic strategies. PMID:20040865

  14. Ulceration of the small intestine in children with coeliac disease.

    PubMed Central

    Eltumi, M; Brueton, M J; Francis, N

    1996-01-01

    BACKGROUND: Ulceration of the small intestine in children has not been previously described. PATIENTS: Two children, aged 12 and 18 months, presented with a history of failure to thrive and intractable diarrhoea. RESULTS AND CONCLUSIONS: Upper gastrointestinal endoscopy showed multiple ulcers involving the first and second parts of the duodenum. Histology of biopsy specimens taken from these sites confirmed ulceration and showed other features consistent with a diagnosis of coeliac disease. They both showed pronounced clinical improvement and satisfactory linear growth on a gluten free diet. A year later the diagnosis of coeliac disease was confirmed on a biopsy controlled gluten challenge, and repeat endoscopy showed complete resolution of the intestinal ulceration. Images p614-a PMID:8944575

  15. [Preventive effect of changzhankang in experimental intestinal adhesions in rats].

    PubMed

    Wang, Y Q; Wei, J Q; Dai, D Z

    1991-08-01

    Intestinal adhesions were induced in rats by stabbing the terminal part of the ileum. Adhesion prevention by ibuprofen and changzhankang (CZK), which was composed by traditional Chinese medicines, was evaluated with a grading system. All of the 13 rats in the non-treated group created severe adhesions. The severity was significantly modified by orally administered CZK of 20 g/kg (in crude drugs) once or twice daily for five days (P less than 0.01 and P less than 0.05 compared with the non-treated). Intramuscular injection of ibuprofen (35 mg/kg, 3 times daily) also alleviated the severity of adhesions. There was no significant difference between the ibuprofen-treated and CZK-treated groups though some of the rats were virtually free from adhesion formation in the latter. It is plausible to expect CZK to become a promising drug used in treating intestinal adhesions, for the natural drug has greater security and less side effects than synthesized drugs. PMID:1954667

  16. Quantitative prediction of intestinal glucuronidation of drugs in rats using in vitro metabolic clearance data.

    PubMed

    Furukawa, Takako; Nakamori, Fumihiro; Tetsuka, Kazuhiro; Naritomi, Yoichi; Moriguchi, Hiroyuki; Yamano, Katsuhiro; Terashita, Shigeyuki; Teramura, Toshio

    2012-01-01

    UDP-glucuronosyltransferase (UGT) is highly expressed in the small intestine and catalyzes the glucuronidation of small molecules, which may affect the oral bioavailability of drugs. However, no method of predicting the in vivo observed fraction of absorbed drug (F(a)F(g)) affected by UGT has yet been established. Here, we investigated the relationship between F(a)F(g) and in vitro clearance of nine UGT substrates (ketoprofen, tolcapone, telmisartan, raloxifene, entacapone, resveratrol, buprenorphine, quercetin, and ezetimibe) via UGT in intestinal microsomes (CL(int, UGT)) in rats. F(a)F(g) was calculated from pharmacokinetic parameters after intravenous and oral administration or using the portal-systemic concentration difference method, with values ranging from 0.027 (ezetimibe) to 1 (tolcapone). Glucuronides of model compounds were observed in the portal plasma after oral administration, with CL(int, UGT) values ranging from 57.8 (tolcapone) to 19,200 µL/min/mg (resveratrol). An inverse correlation between F(a)F(g) and CL(int, UGT) was observed for most compounds and was described using a simplified intestinal availability model reported previously. This model gave accurate predictions of F(a)F(g) values for three in-house compounds. Our results show that F(a)F(g) in rats is affected by UGT and can be predicted using CL(int, UGT). This work should hasten the development of a method to predict F(a)F(g) in humans. PMID:21970858

  17. Activation of Protease Activated Receptor 2 by Exogenous Agonist Exacerbates Early Radiation Injury in Rat Intestine

    SciTech Connect

    Wang Junru; Boerma, Marjan; Kulkarni, Ashwini; Hollenberg, Morley D.; Hauer-Jensen, Martin

    2010-07-15

    Purpose: Protease-activated receptor-2 (PAR{sub 2}) is highly expressed throughout the gut and regulates the inflammatory, mitogenic, fibroproliferative, and nociceptive responses to injury. PAR{sub 2} is strikingly upregulated and exhibits increased activation in response to intestinal irradiation. We examined the mechanistic significance of radiation enteropathy development by assessing the effect of exogenous PAR{sub 2} activation. Methods and Materials: Rat small bowel was exposed to localized single-dose radiation (16.5 Gy). The PAR{sub 2} agonist (2-furoyl-LIGRLO-NH{sub 2}) or vehicle was injected intraperitoneally daily for 3 days before irradiation (before), for 7 days after irradiation (after), or both 3 days before and 7 days after irradiation (before-after). Early and delayed radiation enteropathy was assessed at 2 and 26 weeks after irradiation using quantitative histologic examination, morphometry, and immunohistochemical analysis. Results: The PAR{sub 2} agonist did not elicit changes in the unirradiated (shielded) intestine. In contrast, in the irradiated intestine procured 2 weeks after irradiation, administration of the PAR{sub 2} agonist was associated with more severe mucosal injury and increased intestinal wall thickness in all three treatment groups (p <.05) compared with the vehicle-treated controls. The PAR{sub 2} agonist also exacerbated the radiation injury score, serosal thickening, and mucosal inflammation (p <.05) in the before and before-after groups. The short-term exogenous activation of PAR{sub 2} did not affect radiation-induced intestinal injury at 26 weeks. Conclusion: The results of the present study support a role for PAR{sub 2} activation in the pathogenesis of early radiation-induced intestinal injury. Pharmacologic PAR{sub 2} antagonists might have the potential to reduce the intestinal side effects of radiotherapy and/or as countermeasures in radiologic accidents or terrorism scenarios.

  18. Carbon Monoxide Inhalation Protects Rat Intestinal Grafts from Ischemia/Reperfusion Injury

    PubMed Central

    Nakao, Atsunori; Kimizuka, Kei; Stolz, Donna B.; Neto, Joao Seda; Kaizu, Takashi; Choi, Augustine M. K.; Uchiyama, Takashi; Zuckerbraun, Brian S.; Nalesnik, Michael A.; Otterbein, Leo E.; Murase, Noriko

    2003-01-01

    Carbon monoxide (CO), a byproduct of heme catalysis by heme oxygenases, has been shown to exert anti-inflammatory effects. This study examines the cytoprotective efficacy of inhaled CO during intestinal cold ischemia/reperfusion injury associated with small intestinal transplantation. Orthotopic syngenic intestinal transplantation was performed in Lewis rats after 6 hours of cold preservation in University of Wisconsin solution. Three groups were examined: normal untreated controls, control intestinal transplant recipients kept in room air, and recipients exposed to CO (250 ppm) for 1 hour before and 24 hours after surgery. In air grafts, mRNA levels for interleukin-6, cyclooxygenase-2, intracellular adhesion molecule (ICAM-1), and inducible nitric oxide synthase rapidly increased after intestinal transplant. Histopathological analysis revealed severe mucosal erosion, villous congestion, and inflammatory infiltrates. CO effectively blocked an early up-regulation of these mediators, showed less severe histopathological changes, and resulted in significantly improved animal survival of 92% from 58% in air-treated controls. CO also significantly reduced mRNA for proapoptotic Bax, while it up-regulated anti-apoptotic Bcl-2. These changes in CO-treated grafts correlated with well-preserved CD31+ vascular endothelial cells, less frequent apoptosis/necrosis in intestinal epithelial and capillary endothelial cells, and improved graft tissue blood circulation. Protective effects of CO in this study were mediated via soluble guanylyl cyclase, because 1H-(1,2,4)oxadiazole (4,3-α) quinoxaline-1-one (soluble guanylyl cyclase inhibitor) completely reversed the beneficial effect conferred by CO. Perioperative CO inhalation at a low concentration resulted in protection against ischemia/reperfusion injury to intestinal grafts with prolonged cold preservation. PMID:14507665

  19. Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

    PubMed Central

    2014-01-01

    Background WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc’s anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Methods Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation. Results Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p < 0.05), with improved jejunum histology (p < 0.0001). Zinc supplementation diminished bacterial translocation only in lactose-challenged undernourished rats (p = 0.03) compared with the untreated challenged controls and reduced intestinal IL-1β and TNF-α cytokines to control levels. Conclusion Altogether our findings provide novel mechanisms of zinc action in the setting of diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea. PMID:25095704

  20. Multiple Small Intestine Perforations after Organophosphorous Poisoning: A Case Report.

    PubMed

    Mahajan, Rubina Khullar; Rajan, Sudha Jasmine; Peter, John Victor; Suryawanshi, Mayur Keshav

    2016-03-01

    Organophosphate poisoning has significant gastrointestinal manifestations including vomiting, diarrhea, cramps and increased salivation. We report an uncommon gastrointestinal complication of multiple small intestinal perforations following organophosphorus poisoning. A 28-year old male presented after ingesting dichlorvos mixed with alcohol. Following the initial cholinergic symptoms, the patient developed severe shock with fever, attributed to aspiration pneumonia. Despite appropriate antibiotics, shock was persistent. Over the next 24-hours, he developed abdominal distension, loose stools and high nasogastric aspirates. Computed tomography showed pneumoperitonium. Exploratory laparotomy revealed six perforations in the jejunum and ileum. The involved portion of the bowel was resected and re-anastomosed, following which only 80-cm of small bowel was left. Postoperatively, shock resolved over 72-hours. However, over the next few days, patient developed features of anastomotic leak. Since only a small portion of the small bowel was preserved, a conservative approach was adopted. He deteriorated further and finally succumbed to the illness. PMID:27134898

  1. Multiple Small Intestine Perforations after Organophosphorous Poisoning: A Case Report

    PubMed Central

    Rajan, Sudha Jasmine; Peter, John Victor; Suryawanshi, Mayur Keshav

    2016-01-01

    Organophosphate poisoning has significant gastrointestinal manifestations including vomiting, diarrhea, cramps and increased salivation. We report an uncommon gastrointestinal complication of multiple small intestinal perforations following organophosphorus poisoning. A 28-year old male presented after ingesting dichlorvos mixed with alcohol. Following the initial cholinergic symptoms, the patient developed severe shock with fever, attributed to aspiration pneumonia. Despite appropriate antibiotics, shock was persistent. Over the next 24-hours, he developed abdominal distension, loose stools and high nasogastric aspirates. Computed tomography showed pneumoperitonium. Exploratory laparotomy revealed six perforations in the jejunum and ileum. The involved portion of the bowel was resected and re-anastomosed, following which only 80-cm of small bowel was left. Postoperatively, shock resolved over 72-hours. However, over the next few days, patient developed features of anastomotic leak. Since only a small portion of the small bowel was preserved, a conservative approach was adopted. He deteriorated further and finally succumbed to the illness. PMID:27134898

  2. Modulation of small intestinal homeostasis along with its microflora during acclimatization at simulated hypobaric hypoxia.

    PubMed

    Adak, Atanu; Ghosh; Mondal, Keshab Chandra

    2014-11-01

    At high altitude (HA) hypobaric hypoxic environment manifested several pathophysiological consequences of which gastrointestinal (GI) disorder are very common phenomena. To explore the most possible clue behind this disorder intestinal flora, the major player of the GI functions, were subjected following simulated hypobaric hypoxic treatment in model animal. For this, male albino rats were exposed to 55 kPa (approximately 4872.9 m) air pressure consecutively for 30 days for 8 h/day and its small intestinal microflora, their secreted digestive enzymes and stress induced marker protein were investigated of the luminal epithelia. It was observed that population density of total aerobes significantly decreased, but the quantity of total anaerobes and Escherichia coli increased significantly after 30 days of hypoxic stress. The population density of strict anaerobes like Bifidobacterium sp., Bacteroides sp. and Lactobacillus sp. and obligate anaerobes like Clostridium perfringens and Peptostreptococcus sp. were expanded along with their positive growth direction index (GDI). In relation to the huge multiplication of anaerobes the amount of gas formation as well as content of IgA and IgG increased in duration dependent manner. The activity of some luminal enzymes from microbial origin like a-amylase, gluco-amylase, proteinase, alkaline phosphatase and beta-glucuronidase were also elevated in hypoxic condition. Besides, hypoxia induced in formation of malondialdehyde along with significant attenuation of catalase, glutathione peroxidase, superoxide dismutase activity and lowered GSH/GSSG pool in the intestinal epithelia. Histological study revealed disruption of intestinal epithelial barrier with higher infiltration of lymphocytes in lamina propia and atrophic structure. It can be concluded that hypoxia at HA modified GI microbial imprint and subsequently causes epithelial barrier dysfunction which may relate to the small intestinal dysfunction at HA. PMID:25434105

  3. Effect of emodin on small intestinal peristalsis of mice and relevant mechanism

    PubMed Central

    Zhang, Hong-Quan; Zhou, Cheng-Hua; Wu, Yu-Qing

    2005-01-01

    AIM: To investigate the effect of emodin on small intestinal peristalsis of mice and to explore its relevant mechanisms. METHODS: The effect of emodin on small intestinal peristalsis of mice was observed by charcoal powder propelling test of small intestine. The contents of motilin and somatostatin in small intestine of mice were determinated by radioimmunoassay. The electrical potential difference (PD) related to Na+ and glucose transport was measured across the wall of reverted intestinal sacs. Na+–K+-ATPase activity of small intestinal mucosa was measured by spectroscopic analysis. RESULTS: Different dosages of emodin can improve small intestinal peristalsis of mice. Emodin increased the content of motilin, while reduced the content of somatostatin in small intestine of mice significantly. Emodin 0.2, 0.4, 0.8, and 1.6 g/L decreased PD when there was glucose. However, emodin had little effect when glucose was free. The Na+–K+-ATPase activity of small intestinal mucosa of mice in emodin groups was inhibited obviously. CONCLUSION: Emodin can enhance the function of small intestinal peristalsis of mice by mechanisms of promoting secretion of motilin, lowering the content of somatostatin and inhibiting Na+–K+-ATPase activity of small intestinal mucosa. PMID:15918207

  4. Orazipone, a locally acting immunomodulator, ameliorates intestinal radiation injury: A preclinical study in a novel rat model

    SciTech Connect

    Boerma, Marjan; Wang, Junru; Richter, Konrad K.; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2006-10-01

    Purpose: Intestinal radiation injury (radiation enteropathy) is relevant to cancer treatment, as well as to radiation accidents and radiation terrorism scenarios. This study assessed the protective efficacy of orazipone, a locally-acting small molecule immunomodulator. Methods and Materials: Male rats were orchiectomized, a 4-cm segment of small bowel was sutured to the inside of the scrotum, a proximal anteperistaltic ileostomy was created for intraluminal drug administration, and intestinal continuity was re-established by end-to-side anastomosis. After three weeks postoperative recovery, the intestine in the 'scrotal hernia' was exposed locally to single-dose or fractionated X-radiation. Orazipone (30 mg/kg/day) or vehicle was administered daily through the ileostomy, either during and after irradiation, or only after irradiation. Structural, cellular, and molecular aspects of intestinal radiation toxicity were assessed two weeks after irradiation. Results: Orazipone significantly ameliorated histologic injury and transforming growth factor-{beta} immunoreactivity levels, both after single-dose and fractionated irradiation. Intestinal wall thickness was significantly reduced after single-dose and nonsignificantly after fractionated irradiation. Mucosal surface area and numbers of mast cells were partially restored by orazipone after single-dose irradiation. Conclusions: This work (1) demonstrates the utility of the ileostomy rat model for intraluminal administration of response modifiers in single-dose and fractionated radiation studies; (2) shows that mucosal immunomodulation during and/or after irradiation ameliorates intestinal toxicity; and (3) highlights important differences between single-dose and fractionated radiation regimens.

  5. Effect of dietary fat on the distribution of mucosal mass and cell proliferation along the small intestine.

    PubMed Central

    Jenkins, A P; Thompson, R P

    1992-01-01

    This study investigated how substitution of long chain triglycerides for glucose in a mixed diet affects the overall small intestinal mucosal mass and the distribution of mucosal mass and cell proliferation along the small intestine. Four groups of eight female Wistar rats (180-200 g) were isocalorically fed mixed diets containing the essential fatty acid rich oil Efamol substituted for glucose at concentrations of 1.2%, 10%, 25%, and 50% total calories for 20 to 23 days. The small intestine was divided into three equal length segments and whole gut weights, mucosal weights, protein and DNA determined. Cell proliferation was estimated from the two hour accumulation of vincristine arrested metaphases in microdissected crypts at points 0%, 17%, 33%, 50%, 66%, and 100% small intestinal length. There were no differences between groups in parameters of overall small intestinal or distal segment mucosal mass. With increasing levels of fat, however, there was a significant trend for the mucosal mass of the proximal segment to fall and that of the middle segment to rise. The pattern of two hour metaphase accumulation reflected these changes. These regional changes in mucosal mass and cell proliferation may reflect differences in the sites of absorption of fat and glucose. PMID:1541418

  6. Temporal profile of intestinal tissue expression of intestinal fatty acid-binding protein in a rat model of necrotizing enterocolitis

    PubMed Central

    Simões, Ana Leda Bertoncini; Figueira, Rebeca Lopes; Gonçalves, Frances Lilian Lanhellas; Mitidiero, Luís Felipe Tsuyoshi; Silva, Orlando Castro e; Peiró, José Luis; Sbragia, Lourenço

    2016-01-01

    OBJECTIVES: Necrotizing enterocolitis is a severe multifactorial intestinal disorder that primarily affects preterm newborns, causing 20-40% mortality and morbidity. Intestinal fatty acid-binding protein has been reported to be a biomarker for the detection of intestinal injuries. Our aim was to assess intestinal tissue injury and the molecular expression of intestinal fatty acid-binding protein over time in a necrotizing enterocolitis model. METHODS: A total of 144 Newborn rats were divided into two groups: 1) Control, which received breastfeeding (n=72) and 2) Necrotizing Enterocolitis, which received formula feeding and underwent hypoxia and hypothermia (n=72). A total of six time points of ischemia (2 times a day for 3 days; 12 pups for each time point) were examined. Samples were collected for analysis of body weight, morphological and histological characteristics, intestinal weight, intestinal weight/body weight ratio, injury grade, and intestinal fatty acid-binding protein levels. RESULTS: Body and intestinal weights were lower in the Necrotizing Enterocolitis group than in the Control group (p<0.005 and p<0.0005, respectively). The intestinal weight/body weight ratio was higher in the Necrotizing Enterocolitis group than in the Control group (p<0.005) only at the sixth ischemia time point. The Necrotizing Enterocolitis group displayed higher expression of intestinal fatty acid-binding protein (p<0.0005) and showed greater tissue damage than the Control group. CONCLUSION: Intestinal fatty acid-binding protein was an efficient marker of ischemic injury to the intestine and a good correlation was demonstrated between the time of ischemic injury and the grade of intestinal injury. PMID:27464299

  7. SIM2 maintains innate host defense of the small intestine.

    PubMed

    Chen, Kuan-Jung; Lizaso, Analyn; Lee, Ying-Hue

    2014-12-01

    The single-minded 2 (SIM2) protein is a basic helix-loop-helix transcription factor regulating central nervous system (CNS) development in Drosophila. In humans, SIM2 is located within the Down syndrome critical region on chromosome 21 and may be involved in the development of mental retardation phenotype in Down syndrome. In this study, knockout of SIM2 expression in mice resulted in a gas distention phenotype in the gastrointestinal tract. We found that SIM2 is required for the expression of all cryptdins and numerous other antimicrobial peptides (AMPs) expressed in the small intestine. The mechanism underlying how SIM2 controls AMP expression involves both direct and indirect regulations. For the cryptdin genes, SIM2 regulates their expression by modulating transcription factor 7-like 2, a crucial regulator in the Wnt/β-catenin signaling pathway, while for other AMP genes, such as RegIIIγ, SIM2 directly activates their promoter activity. Our results establish that SIM2 is a crucial regulator in controlling expression of intestinal AMPs to maintain intestinal innate immunity against microbes. PMID:25277798

  8. Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children

    PubMed Central

    Haque, Rashidul; Kirkpatrick, Beth D.; Alam, Masud; Lu, Miao; Kabir, Mamun; Kakon, Shahria Hafiz; Islam, Bushra Zarin; Afreen, Sajia; Musa, Abu; Khan, Shaila Sharmeen; Colgate, E. Ross; Carmolli, Marya P.; Ma, Jennie Z.

    2016-01-01

    ABSTRACT Recent studies suggest small intestine bacterial overgrowth (SIBO) is common among developing world children. SIBO’s pathogenesis and effect in the developing world are unclear. Our objective was to determine the prevalence of SIBO in Bangladeshi children and its association with malnutrition. Secondary objectives included determination of SIBO’s association with sanitation, diarrheal disease, and environmental enteropathy. We performed a cross-sectional analysis of 90 Bangladeshi 2-year-olds monitored since birth from an impoverished neighborhood. SIBO was diagnosed via glucose hydrogen breath testing, with a cutoff of a 12-ppm increase over baseline used for SIBO positivity. Multivariable logistic regression was performed to investigate SIBO predictors. Differences in concomitant inflammation and permeability between SIBO-positive and -negative children were compared with multiple comparison adjustment. A total of 16.7% (15/90) of the children had SIBO. The strongest predictors of SIBO were decreased length-for-age Z score since birth (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.03 to 0.60) and an open sewer outside the home (OR, 4.78; 95% CI, 1.06 to 21.62). Recent or frequent diarrheal disease did not predict SIBO. The markers of intestinal inflammation fecal Reg 1β (116.8 versus 65.6 µg/ml; P = 0.02) and fecal calprotectin (1,834.6 versus 766.7 µg/g; P = 0.004) were elevated in SIBO-positive children. Measures of intestinal permeability and systemic inflammation did not differ between the groups. These findings suggest linear growth faltering and poor sanitation are associated with SIBO independently of recent or frequent diarrheal disease. SIBO is associated with intestinal inflammation but not increased permeability or systemic inflammation. PMID:26758185

  9. Defective small intestinal anion secretion, dipeptide absorption, and intestinal failure in suckling NBCe1-deficient mice.

    PubMed

    Yu, Qin; Liu, Xuemei; Liu, Yongjian; Riederer, Brigitte; Li, Taolang; Tian, De-An; Tuo, Biguang; Shull, Gary; Seidler, Ursula

    2016-08-01

    The electrogenic Na(+)HCO3 (-) cotransporter NBCe1 (Slc4a4) is strongly expressed in the basolateral enterocyte membrane in a villous/surface predominant fashion. In order to better understand its physiological function in the intestine, isolated mucosae in miniaturized Ussing chambers and microdissected intestinal villi or crypts loaded with the fluorescent pH-indicator BCECF were studied from the duodenum, jejunum, and colon of 14- to 17-days-old slc4a4-deficient (KO) and WT mice. NBCe1 was active in the basal state in all intestinal segments under study, most likely to compensate for acid loads imposed upon the enterocytes. Upregulation of other basolateral base uptake mechanism occurs, but in a segment-specific fashion. Loss of NBCe1 resulted in severely impaired Cl(-) and fluid secretory response, but not HCO3 (-) secretory response to agonist stimulation. In addition, NBCe1 was found to be active during transport processes that load the surface enterocytes with acid, such as Slc26a3 (DRA)-mediated luminal Cl(-)/HCO3 (-) exchange or PEPT1-mediated H(+)/dipeptide uptake. Possibly because of the high energy demand for hyperventilation in conjunction with the fluid secretory and nutrient absorptive defects and the relative scarcity of compensatory mechanisms, NBCe1-deficient mice developed progressive jejunal failure, worsening of metabolic acidosis, and death in the third week of life. Our data suggest that the electrogenic influx of base via NBCe1 maintains enterocyte anion homeostasis and pHi control. Its loss impairs small intestinal Cl(-) and fluid secretion as well as the neutralization of acid loads imposed on the enterocytes during nutrient and electrolyte absorption. PMID:27228994

  10. Intestinal toxicity of oral warfarin intake in rats.

    PubMed

    Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Demenesku, Jelena; Ninkov, Marina; Mileusnic, Dina; Zolotarevski, Lidija; Subota, Vesna; Kataranovski, Dragan; Kataranovski, Milena

    2016-08-01

    Though warfarin is extensively used in the prevention and treatment of thromboembolic processes in humans, adverse effects of warfarin therapy have been recognized. Intestinal hemorrhage is one of the hazards of anticoagulant therapy, but the mechanisms of warfarin toxicity are virtually unknown. In this work, the effects of 30 days oral warfarin (0.35 mg/l and 3.5 mg/l) intake on rat's gut were examined. Both doses resulted in prolongation of prothrombin time. Systemic effects of higher warfarin dose (increases in plasma AST, proteinuria, hematuria, changes in peripheral blood hematological parameters) were seen. Warfarin intake resulted in histologically evident tissue damage, leukocyte infiltration and intestinal inflammation [increases in myeloperoxidase activity, malondialdehyde content, superoxide dismutase and catalase activity, proinflammatory cytokine (IFN-γ, IL-17) concentrations in intestinal homogenates]. In contrast, suppression of gut-draining mesenteric lymph node (MLN) cell activity [proliferation responsiveness, production of IFN-γ and IL-17 to T lymphocyte mitogen Concanavalin A stimulation] was noted. Inhibition of regulatory cytokine IL-10 production by MLN cells, suggests commitment of MLN to the suppression of all inflammatory activities and creation of the microenvironment which is non-permissive for induction of potentially harmful immune response. These novel findings indicate the need of staying alert for (adverse) effects of warfarin therapy. PMID:27181730

  11. Hydrolysis of pyrethroids by human and rat tissues: Examination of intestinal, liver and serum carboxylesterases

    SciTech Connect

    Crow, J. Allen; Borazjani, Abdolsamad; Potter, Philip M.; Ross, Matthew K. . E-mail: mross@cvm.msstate.edu

    2007-05-15

    Hydrolytic metabolism of pyrethroid insecticides in humans is one of the major catabolic pathways that clear these compounds from the body. Rodent models are often used to determine the disposition and clearance rates of these esterified compounds. In this study the distribution and activities of esterases that catalyze pyrethroid metabolism have been investigated in vitro using several human and rat tissues, including small intestine, liver and serum. The major esterase in human intestine is carboxylesterase 2 (hCE2). We found that the pyrethroid trans-permethrin is effectively hydrolyzed by a sample of pooled human intestinal microsomes (5 individuals), while deltamethrin and bioresmethrin are not. This result correlates well with the substrate specificity of recombinant hCE2 enzyme. In contrast, a sample of pooled rat intestinal microsomes (5 animals) hydrolyze trans-permethrin 4.5-fold slower than the sample of human intestinal microsomes. Furthermore, it is demonstrated that pooled samples of cytosol from human or rat liver are {approx} 2-fold less hydrolytically active (normalized per mg protein) than the corresponding microsomal fraction toward pyrethroid substrates; however, the cytosolic fractions do have significant amounts ({approx} 40%) of the total esteratic activity. Moreover, a 6-fold interindividual variation in carboxylesterase 1 protein expression in human hepatic cytosols was observed. Human serum was shown to lack pyrethroid hydrolytic activity, but rat serum has hydrolytic activity that is attributed to a single CE isozyme. We purified the serum CE enzyme to homogeneity to determine its contribution to pyrethroid metabolism in the rat. Both trans-permethrin and bioresmethrin were effectively cleaved by this serum CE, but deltamethrin, esfenvalerate, alpha-cypermethrin and cis-permethrin were slowly hydrolyzed. Lastly, two model lipase enzymes were examined for their ability to hydrolyze pyrethroids. However, no hydrolysis products could be

  12. Morphology of the small intestinal mucosal surface of broilers in relation to age, diet formulation, small intestinal microflora and performance.

    PubMed

    van Leeuwen, P; Mouwen, J M V M; van der Klis, J D; Verstegen, M W A

    2004-02-01

    1. Three experiments were performed to relate morphological characteristics of the small intestinal mucosal surface to age, dietary factors, small intenstinal microflora and performance of broilers. Characterisation of the small intestinal mucosal surface using a dissecting microscope was based on the orientation of the villi, villus shape and the presence of convoluted villi. 2. In Trial 1, the morphological changes of the mucosal surface were studied weekly in the period from 7 to 28 d of age. At d 7 mainly tongue- and leaf-shaped villi together with some ridge-shaped ones were observed in the middle section of the small intestine, displaying a regular zigzag pattern on 53% of the mucosal surface. During the period from d 7 to 14, the area with ridge-shaped villi increased from 7 to 63% and did not change significantly over the next 2 weeks. 3. In Trial 2, three protein sources, soy isolate (SI), wheat gluten (WG), hydrolysed wheat gluten (HWG) and SI with added L-glutamine (SI + Gln), were studied with respect to their effect as dietary components on villus morphology in the mid-small intestine and performance. Diets were fed with (0 to 14 d) and without pectin (14 to 21 d). Feed conversion ratio on the HWG diet improved in comparison to the native WG diet. During the period 0 to 14 d of age the mucosal area with zigzag-oriented villi increased when the pectin diet was supplemented with Gln. Moreover, weight gain of birds fed the SI + Gln diet increased in the period 41 to 21 d. 4. In Trial 3, a study was made of the morphological response of the villi to a stimulation of microbial activity in the digesta after addition of highly methylated pectin to the soybean meal (SBM) diet. This was performed with and without inoculation of a non-virulent Salmonella typhimurium on d 7. By d 21 the birds fed the pectin diet showed impaired weight gain and higher feed conversion. The pectin affected the mucosal surface by decreasing the area with the zigzag pattern and

  13. Transport of nattokinase across the rat intestinal tract.

    PubMed

    Fujita, M; Hong, K; Ito, Y; Misawa, S; Takeuchi, N; Kariya, K; Nishimuro, S

    1995-09-01

    Intraduodenal administration of nattokinase (NK) at a dose of 80 mg/kg, resulted in the degradation of fibrinogen in plasma suggesting transport of NK across the intestinal tract in normal rats. The action of NK on the cleavage of fibrinogen in the plasma from blood samples drawn at intervals after intraduodenal administration of the enzyme was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis with an anti-fibrinogen gamma chain antibody. The 270 kDa fragment carrying antigenic sites for the binding of the anti-fibrinogen gamma chain antibody appeared within 0.5 h and was then degraded gradually to a 105 kDa fragment via a 200 kDa fragment. This suggests that fibrinogen was degraded to a 105 kDa fragment via several intermediates (270 and 200 kDa). In parallel with the degradation process, plasma recalcification times were remarkably prolonged NK was also detected in the plasma from blood samples drawn 3 and 5 h after administration of the enzyme by SDS-PAGE and Western blotting analysis with an anti-NK antibody. The results indicate that NK is absorbed from the rat intestinal tract and that NK cleaves fibrinogen in plasma after intraduodenal administration of the enzyme. PMID:8845803

  14. Catabolism of (+)-catechin and (-)-epicatechin by rat intestinal microbiota.

    PubMed

    Takagaki, Akiko; Nanjo, Fumio

    2013-05-22

    Catabolism of (+)-catechin (+C) and (-)-epicatechin (EC) by rat intestinal microbiota was examined in vitro. +C and EC metabolites isolated were identified by LC-MS and NMR analyses. As a result, 4-hydroxy-5-(3-hydroxyphenyl)valeric acid (C-5 and EC-5), 4-oxo-5-(3,4-dihydorxyphenyl)valeric acid (EC-7), 4-oxo-5-(3-hydorxyphenyl)valeric acid (EC-8), and 1-(4-hydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propan-2-ol (EC-13) were identified as new metabolites of +C or EC. From the measurement of optical rotation, each of the +C and EC metabolites possessing the same chemical structure and chiral carbon was inferred to have an enantiomeric relationship to each other and to maintain the configurations at the 3-position of the original catechins. On the basis of these findings together with previous information, the proposed metabolic pathway of +C and EC by rat intestinal microbiota was updated. PMID:23621128

  15. Increased Intestinal Absorption of Genistein by Coadministering Verapamil in Rats.

    PubMed

    Xie, Baogang; Wang, Huiyun; Zou, Huiqin; Liu, Yalan; Kong, Xiangyu; Fang, Xiuzhong

    2016-10-01

    Combination of genistein (GT) and verapamil, a P-glycoprotein (P-gp) inhibitor, can increase GT absorption in situ perfusion technology in rat. To date, little information is yet available about the effect of verapamil on oral absorption of GT in vivo. In this study, a simple and reproducible HPLC-UV method was developed and validated for determination of total GT in rat plasma. Based on this, a pharmacokinetic experiment was designed to characterize biopharmaceutical properties of GT with or without coadministration of verapamil (10.0, 20.0, 30.0 mg/kg) in rats. The coadministration of verapamil (30.0 mg/kg) with GT caused a significant increase of the maximum GT plasma concentration (1.31-fold vs. GT, P < 0.05) and area under the curve (1.39-fold vs. GT, P < 0.05). Our data show that verapamil would increase intestinal absorption of GT in rat, suggesting there is some drug-nutrition interaction between verapamil and GT. PMID:27604118

  16. Disposition of enalapril in the perfused rat intestine-liver preparation: absorption, metabolism and first-pass effect.

    PubMed

    Pang, K S; Cherry, W F; Ulm, E H

    1985-06-01

    A new procedure, namely the in situ perfused rat intestine-liver preparation, was introduced to examine the roles of the intestine and the liver in the elimination of enalapril, a new angiotensin-converting enzyme inhibitor. The in situ perfused rat intestine preparation was used to determine the rate and extent of enalapril absorption after an-intraduodenal dose. In the former technique, enalapril in blood perfusate (10 ml/min) was delivered via the superior mesenteric artery into the once-through perfused rat intestine-liver preparation, with sampling effected in reservoir, portal vein and hepatic vein. The ease of sampling, proximal and distal to the intestine and liver, allowed the direct estimation of the extraction ratios by the intestine and the liver. The steady-state intestinal extraction ratio of enalapril was small (0.04 +/- 0.066) compared to that for the liver (0.74 +/- 0.06), indicating that the liver was responsible for most of the hydrolytic conversion of enalapril to its pharmacologically active diacid metabolite, enalaprilat. Moreover, no trend in the values of the extraction ratios by both organs was apparent among the input concentrations of enalapril (0.55, 2.6 and 13.3 microM) used. Portal venous plasma consisted mainly of enalapril and was devoid of enalaprilat, whereas both enalapril and enalaprilat were detected in bile and hepatic venous plasma. With the latter technique, an intraduodenal injection of a tracer dose of [14C]enalapril (0.14-0.39 mumol) was made close to the pyloric sphinctor, whereas the intestine preparation was recirculated (7.5 ml/min) with blank perfusate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2989498

  17. The Responses of Rat Intestinal Brush Border and Cytosol Peptide Hydrolase Activities to Variation in Dietary Protein Content DIETARY REGULATION OF INTESTINAL PEPTIDE HYDROLASES

    PubMed Central

    Nicholson, J. Alex; McCarthy, Denis M.; Kim, Young S.

    1974-01-01

    The effects of variation in dietary protein content on small intestinal brush border and cytosol peptide hydrolase activities have been investigated. One group of rats was fed a high protein diet (55% casein) and another group was fed a low protein diet (10% casein). After 1 wk, brush border peptide hydrolase activity (L-leucyl-β-naphthylamide as substrate) and cytosol peptide hydrolase activity (L-prolyl-L-leucine as substrate) were determined in mucosae taken from the proximal, middle, and distal small intestine. As judged by several parameters, brush border peptide hydrolase activity was significantly greater in rats fed the high protein diet when data for corresponding segments were compared. In contrast, no significant difference was seen in cytosol peptide hydrolase activity. In a second study, brush border and cytosol peptide hydrolase activities were determined in the proximal intestine by utilizing an additional three peptide substrates: L-leucyl-L-alanine, L-phenylalanylglycine, and glycyl-L-phenylalanine. Sucrase, maltase, and alkaline phosphatase activities were also determined. As before, brush border peptide hydrolase activities were significantly greater in rats fed the high protein diet. However, activities of the nonproteolytic brush border enzymes did not vary significantly with diet. In contrast to the results obtained with L-prolyl-L-leucine as substrate for the cytosol enzymes, cytosol activity against the three additional peptide substrates was greater in rats fed the high protein diet. It is suggested that the brush border peptide hydrolase response to variation in dietary protein content represents a functional adaptation analogous to the regulation of intestinal disaccharidases by dietary carbohydrates. The implication of the differential responses of the cytosol peptide hydrolases is uncertain, since little is known of the functional role of these nonorgan-specific enzymes. PMID:4430719

  18. Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis

    PubMed Central

    Sassoon, Catherine S.; Zhu, Ercheng; Fang, Liwei; Subramanian, Veedamali S.; Said, Hamid M.

    2016-01-01

    Objective Thiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 (THTR-1) and thiamin transporter-2 (THTR-2)), and mitochondrial thiamin pyrophosphate transporter (MTPPT). Design Randomized, controlled study Setting Research laboratory at a Veterans Affairs Medical Center Subjects Twenty-four Sprague-Dawley rats were randomized into controls, mild, moderate and severe sepsis with equal number of animals in each group. Measurements and Main Results Sepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25 %, 50 % and 75 % of cecal length, defined as severe, moderate and mild sepsis, respectively. Control animals underwent laparotomy only. After 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [3H]thiamin. Expressions of THTR-1, THTR-2, and MTPPT proteins and mRNA were measured. Proinflammatory cytokines (IL-1β and IL-6), and adenosine triphosphate (ATP) were also measured. Sepsis inhibited [3H]thiamin uptake and the inhibition was a function of sepsis severity. Both cell membranes thiamin transporters and MTPPT expression levels were suppressed; also levels of ATP in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham operated controls. Conclusions For the first time we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and MTPPT, leading to ATP depletion. PMID:27065466

  19. Small intestinal brush border enzymes in cystic fibrosis.

    PubMed

    Van Biervliet, S; Eggermont, E; Carchon, H; Veereman, G; Deboeck, K

    1999-01-01

    The study concerns the maltase, saccharase, lactase and alkaline phosphatase activity in small intestinal biopsy specimens from 61 consecutively admitted, untreated, Caucasian cystic fibrosis patients. A group of 319 age matched controls admitted during the same time period for undefined gastrointestinal or nutritional disorders acted as the controls. In order to eliminate morphological damage as a confounding factor, the enzyme activities were studied in small intestinal biopsy specimens having both normal stereomicroscopic and histological features. It was shown that neither maltase nor saccharase activity was different in the two groups, in contrast to lactase and alkaline phophatase activity, that was significantly lower in cystic fibrosis patients. The differences could not be explained by the nutritional status as judged by the body mass index. Lactase activity is known to be easily affected by numerous enteropathies. As the information on alkaline phosphatase activity is limited, the low activity is discussed in more detail. Taking into account the literature data, the low alkaline phosphatase activity is tentatively attributed either to enhanced release from the brush border or to the faulty handling of alkaline phophatase protein in the post-golgi compartments secondary to the accumulation of incorrectly glycosylated CFTR in the same cell structures. PMID:10547891

  20. Protective effect of salvianolic acid B on NASH rat liver through restoring intestinal mucosal barrier function

    PubMed Central

    Wang, Ying-Chun; Jin, Qing-Mei; Kong, Wei-Zong; Chen, Juan

    2015-01-01

    Aim: To investigate the effect of Salvianolic acid B (Sal B) on the disease progress of NASH and change of intestinal barrier function. Methods: Sixty Sprague-Dawley (SD) rats were randomly divided into control group, model group and treated group, with the former given normal diet and the latter 2 groups rats fed high-fat diet. In treated group, rats were infused through the stomach with 1 mg/ml Sal B every day at a dose of 20 mL/kg body weight. All animals were killed at the 24th week and plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), endotoxin (ET) and diamine oxdase (DAO) were analyzed using the blood samples. The histopathology of liver was observed by H&E staining. The expression changes of tight junction protein occludin and ZO-1 were analyzed by immunocytochemistry. Ultrastructural morphology of small intestinal tissues was investigated by transmission electron microscopy. Results: Plasma levels of ALT, AST, TG, TC, ET and DAO were significantly higher in model group than those in both control group and group treated with Sal B. In model group, vacuolated swelling of the cytoplasm with aggregates of chronic inflammatory cells was observed in the liver tissue but not in Sal B-treated group. NAFLD Activity Score in the treated group was significantly lower than that in model group. Immunohistochemical staining showed that Sal B administration recovered the expression of occludin and ZO-1, which was downregulated in the model group. Transmission electron microscopy analysis demonstrated that cell surface microvilli and major intercellular junctional complex including tight junction, gap junction and adherens junction were restored in Sal B-treated group. Conclusion: Sal B exerted protective function against high-fat diet-induced liver damage by restoring healthy barrier function of intestine in NASH rat model. PMID:26191218

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

    PubMed

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

    2015-09-01

    A range of in vitro, ex vivo, and in vivo approaches are currently used for drug development. Highly predictive human intestinal absorption models remain lagging behind the times because of numerous variables concerning permeability through gastrointestinal tract in humans. However, there is a clear need for a drug permeability model early in the drug development process that can balance the requirements for high throughput and effective predictive potential. The present study developed a medium throughput screening Snapwell (MTS-Snapwell) ex vivo model to provide an alternative method to classify drug permeability. Rat small intestine tissue segments were mounted in commercial Snapwell™ inserts. Unidirectional drug transport (A-B) was measured by collecting samples at different time points. Viability of intestinal tissue segments was measured by examining transepithelial electric resistance (TEER) and phenol red and caffeine transport. As a result, the apparent permeability (Papp; ×10(-6) cm/s) was determined for atenolol (10.7 ± 1.2), caffeine (17.6 ± 3.1), cimetidine (6.9 ± 0.1), metoprolol (12.6 ± 0.7), theophylline (15.3 ± 1.6) and, ranitidine (3.8 ± 0.4). All drugs were classified in high/low permeability according to Biopharmaceutics Classification System showing high correlation with human data (r = 0.89). These findings showed a high correlation with human data (r = 0.89), suggesting that this model has potential predictive capacity for paracellular and transcellular passively absorbed molecules. PMID:25690454

  2. Pediatric small intestine bacterial overgrowth in low-income countries.

    PubMed

    Donowitz, Jeffrey R; Petri, William A

    2015-01-01

    Small intestine bacterial overgrowth (SIBO) occurs when colonic quantities of commensal bacteria are present in the small bowel. SIBO is associated with conditions of disrupted gastrointestinal (GI) motility leading to stasis of luminal contents. Recent data show that SIBO is also found in children living in unsanitary conditions who do not have access to clean water. SIBO leads to impaired micronutrient absorption and increased GI permeability, both of which may contribute to growth stunting in children. SIBO also disrupts mucosal immunity and has been implicated in oral vaccination underperformance and the development of celiac disease. SIBO in the setting of the impoverished human habitats may be an under-recognized cause of pediatric morbidity and mortality in the developing world. PMID:25486880

  3. Pediatric Small Intestinal Bacterial Overgrowth in Low-Income Countries

    PubMed Central

    Donowitz, Jeffrey R.; Petri, William A.

    2015-01-01

    Small intestine bacterial overgrowth (SIBO) occurs when colonic quantities of commensal bacteria are present in the small bowel. SIBO is associated with conditions of disrupted GI motility leading to stasis of luminal contents. Recent data show that SIBO is also found in children living in unsanitary conditions that do not have access to clean water. SIBO leads to impaired micronutrient absorption and increased GI permeability, both of which may contribute to growth stunting in children. SIBO also disrupts mucosal immunity and has been implicated in oral vaccination underperformance and the development of celiac disease. SIBO in the setting of the impoverished human habitat may be an under recognized cause of pediatric morbidity and mortality in the developing world. PMID:25486880

  4. Garlic inhibits microsomal triglyceride transfer protein gene expression in human liver and intestinal cell lines and in rat intestine.

    PubMed

    Lin, Marie C; Wang, Er-Jia; Lee, Catherine; Chin, K T; Liu, Depei; Chiu, Jen-Fu; Kung, Hsiang-Fu

    2002-06-01

    Epidemiologic studies have suggested that fresh garlic has lipid-lowering activity. Because the microsomal triglyceride transfer protein (MTP) plays a pivotal role in the assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins, we evaluated the effect of garlic on the expression of the MTP gene in vitro in cell lines and in vivo in rats. Fresh garlic extract (FGE) reduced MTP mRNA levels in both the human hepatoma HepG2 and intestinal carcinoma Caco-2 cells in dose-dependent fashion; significant reductions were detected with 3 g/L FGE. Maximal 72 and 59% reductions, respectively, were observed with 6 g/L FGE. To evaluate the in vivo effect of garlic on MTP gene expression, rats were given a single oral dose of fresh garlic homogenate (FGH), with hepatic and intestinal MTP mRNA measured 3 h after dosing. Rats fed FGH had significantly (46% of the control) lower intestinal MTP mRNA levels compared with the control rats, whereas hepatic MTP mRNA levels were not affected. These results suggest a new mechanism for the hypolipidemic effect of fresh garlic. Long-term dietary supplementation of fresh garlic may exert a lipid-lowering effect partly through reducing intestinal MTP gene expression, thus suppressing the assembly and secretion of chylomicrons from intestine to the blood circulation. PMID:12042427

  5. Intestinal transport of hexoses in the rat following chronic heat exposure

    NASA Technical Reports Server (NTRS)

    Carpenter, M.; Musacchia, X. J.

    1979-01-01

    The study examines intestinal transport of sugars (D-glucose and D-galactose) in vitro and assesses organ maintenance in chronically heat-exposed rats. The results suggest that the response of intestinal absorption to heat exposure in the rat involves changes in intestinal weight and in glucose utilization. Despite the reduction in total intestinal weight, the ability of intestinal tissue to transport hexose per unit weight remains stable. Differences in intestinal weight and glucose utilization between pair-fed and heat-exposed animals suggest that the intestinal response to chronic heat exposure is not solely a function of the amount of food consumed. Alterations of hexose transport appear to be related to altered glucose metabolism and not altered transport capacity.

  6. Blood and small intestine cell kinetics under radiation exposures: Mathematical modeling

    NASA Astrophysics Data System (ADS)

    Smirnova, O. A.

    2009-12-01

    Mathematical models which describe the dynamics of two vital body systems (hematopoiesis and small intestinal epithelium) in mammals exposed to acute and chronic radiation are developed. These models, based on conventional biological theories, are implemented as systems of nonlinear differential equations. Their variables and constant parameters have clear biological meaning, that provides successful identification and verification of the models in hand. It is shown that the predictions of the models qualitatively and quantitatively agree with the respective experimental data for small laboratory animals (mice, rats) exposed to acute/chronic irradiation in wide ranges of doses and dose rates. The explanation of a number of radiobiological effects, including those of the low-level long-term exposures, is proposed proceeding from the modeling results. All this bears witness to the validity of employment of the developed models, after a proper identification, in investigation and prediction of radiation effects on the hematopoietic and small intestinal epithelium systems in various mammalian species, including humans. In particular, the models can be used for estimating effects of irradiation on astronauts in the long-term space missions, such as Lunar colonies and Mars voyages.

  7. In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

    SciTech Connect

    Tassinari, Roberta; La Rocca, Cinzia; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca; Stecca, Laura

    2015-06-23

    In European Union, titanium dioxide (TiO{sub 2}) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO{sub 2} NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO{sub 2} NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO{sub 2} NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm{sup 2} levels of TiO{sub 2} NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO{sub 2} NP toxicity by direct exposure both in vivo and in vitro models.

  8. In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

    NASA Astrophysics Data System (ADS)

    Tassinari, Roberta; La Rocca, Cinzia; Stecca, Laura; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca

    2015-06-01

    In European Union, titanium dioxide (TiO2) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO2 NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO2 NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO2 NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm2 levels of TiO2 NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO2 NP toxicity by direct exposure both in vivo and in vitro models.

  9. Impaired expression of acyl-CoA-synthetase 5 in epithelial tumors of the small intestine.

    PubMed

    Gassler, Nikolaus; Schneider, Armin; Kopitz, Jürgen; Schnölzer, Martina; Obermüller, Nicholas; Kartenbeck, Jürgen; Otto, Herwart F; Autschbach, Frank

    2003-10-01

    Fatty acids are implicated in tumorigenesis, but data are limited concerning endogenous fatty acid metabolism of tumor cells in adenomas and adenocarcinomas of the small intestine. The recently cloned human acyl-CoA-synthetase 5 (ACS5) is predominantly found in the small intestine and represents a key enzyme in providing cytosolic acyl-CoA thioesters. Protein synthesis and mRNA expression of ACS5 were studied in human intestinal tissues using different methods, including a newly established monoclonal antibody. In the healthy small intestine, expression of ACS5 was restricted to the villus surface epithelium but was not detectable in enterocytes lining crypts. ACS5 protein and mRNA were progressively diminished in epithelial cells of adenomas and adenocarcinomas of the small intestine. In conclusion, altered expression of ACS5 is probably related to the adenoma-carcinoma sequence of small intestinal epithelial tumors due to an impaired acyl-CoA thioester synthesis. PMID:14608540

  10. Role of Staging in Patients with Small Intestinal Neuroendocrine Tumours.

    PubMed

    Clift, Ashley Kieran; Faiz, Omar; Al-Nahhas, Adil; Bockisch, Andreas; Liedke, Marc Olaf; Schloericke, Erik; Wasan, Harpreet; Martin, John; Ziprin, Paul; Moorthy, Krishna; Frilling, Andrea

    2016-01-01

    Small bowel neuroendocrine tumours are the commonest malignancy arising in the small intestine and have substantially increased in incidence in recent decades. Patients with small bowel neuroendocrine tumours commonly develop lymph node and/or distant metastases. Here, we examine the role of staging in 84 surgically treated patients with small bowel neuroendocrine tumours, comparing diagnostic information yielded from morphological, functional and endoscopic modalities. Furthermore, we correlate pre-operative staging with intra-operative findings in a sub-cohort of 20 patients. The vast majority of patients had been histologically confirmed to have low-grade (Ki-67 <2%) disease; however, lymph node and distant metastases were observed in 74 (88.1%) and 51 (60.7%) of patients at presentation, respectively. Liver metastases were evident in 48 (57.1%) patients, with solely peritoneal and bone metastases observed in 2 (2.4%) and 1 (1.2%) patients, respectively. Forty patients (47.6%) received multimodal treatment. In our sub-cohort analysis, pre-operative imaging understaged disease in 14/20 (70%) when compared with intra-operative findings. In patients with multifocal primary tumours and miliary liver metastases, no imaging modality was able to detect entire disease spread. Overall, presently available imaging modalities heavily underestimate disease stage, with meticulous intra-operative abdominal examination being superior to any imaging technology. Multimodal treatment has an important role in prolonging survival. PMID:26394880

  11. Establishment of a biochemically active intestinal ecosystem in ex-germfree rats.

    PubMed Central

    Midtvedt, T; Carlstedt-Duke, B; Höverstad, T; Midtvedt, A C; Norin, K E; Saxerholt, H

    1987-01-01

    A time course study for the establishment of some biochemical microbial intestinal functions was undertaken in ex-germfree rats conventionalized, i.e., colonized with conventional flora, in three different ways: untreated (group 1); contact with visitor rats (group 2); inoculated with intestinal contents from conventional rats (group 3). The first two groups of rats were inoculated with the intestinal contents from conventional rats after being out of the germfree isolators for 4 weeks. The biochemical parameters studied were degradation of mucin, inactivation of tryptic activity, conversion of cholesterol to coprostanol and of bilirubin to urobilinogen, degradation of beta-aspartylglycine, and formation of short-chain fatty acids. The results showed that the way in which the microbes were introduced and the microbial biochemical functions themselves were of importance. In several cases, social contacts, i.e., contact with visitor rats, were just as effective for the functionally adequate establishment of microbial intestinal functions as was inoculation with intestinal contents from conventional rats. Some of the biochemical parameters studied were established after a few days, whereas the establishment of others was markedly delayed. When inoculated after 4 weeks, all rats in the first two groups were colonized with conventional flora within 1 week. The results indicate that the model system described is suitable when studying buildup mechanisms in intestinal ecosystem(s). PMID:3124742

  12. Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function.

    PubMed

    Grant, Christa N; Mojica, Salvador Garcia; Sala, Frederic G; Hill, J Ryan; Levin, Daniel E; Speer, Allison L; Barthel, Erik R; Shimada, Hiroyuki; Zachos, Nicholas C; Grikscheit, Tracy C

    2015-04-15

    Short bowel syndrome (SBS) is a devastating condition in which insufficient small intestinal surface area results in malnutrition and dependence on intravenous parenteral nutrition. There is an increasing incidence of SBS, particularly in premature babies and newborns with congenital intestinal anomalies. Tissue-engineered small intestine (TESI) offers a therapeutic alternative to the current standard treatment, intestinal transplantation, and has the potential to solve its biggest challenges, namely donor shortage and life-long immunosuppression. We have previously demonstrated that TESI can be generated from mouse and human small intestine and histologically replicates key components of native intestine. We hypothesized that TESI also recapitulates native small intestine function. Organoid units were generated from mouse or human donor intestine and implanted into genetically identical or immunodeficient host mice. After 4 wk, TESI was harvested and either fixed and paraffin embedded or immediately subjected to assays to illustrate function. We demonstrated that both mouse and human tissue-engineered small intestine grew into an appropriately polarized sphere of intact epithelium facing a lumen, contiguous with supporting mesenchyme, muscle, and stem/progenitor cells. The epithelium demonstrated major ultrastructural components, including tight junctions and microvilli, transporters, and functional brush-border and digestive enzymes. This study demonstrates that tissue-engineered small intestine possesses a well-differentiated epithelium with intact ion transporters/channels, functional brush-border enzymes, and similar ultrastructural components to native tissue, including progenitor cells, whether derived from mouse or human cells. PMID:25573173

  13. Flavonoids as drugs at the small intestinal level.

    PubMed

    Wenzel, Uwe

    2013-12-01

    Flavonoids represent a biologically active class of secondary plant compounds. For selected members there is convincing evidence regarding their beneficial effects on human health. Accordingly these compounds are tested as supporting or alternative therapies for a number of diseases such as cancer or type-II diabetes. Subsequent to their ingestion a first site of interference are digestive enzymes and transporters in the small intestine. Through interactions with glucose transporters in the apical membranes of enterocytes flavonoid glycosides and also some aglycones appear to reduce postprandial hyperglycaemia in diabetic patients. Moreover, many flavonoids have been shown to interfere with ATP-dependent drug-efflux transporters which are relevant for the resistance of cancer cells versus various cytostatic drugs and makes them candidates to overcome multidrug-resistance. PMID:24094625

  14. Link between hypothyroidism and small intestinal bacterial overgrowth.

    PubMed

    Patil, Anant D

    2014-05-01

    Altered gastrointestinal (GI) motility is seen in many pathological conditions. Reduced motility is one of the risk factors for development of a small intestinal bacterial overgrowth (SIBO). Hypothyroidism is associated with altered GI motility. The aim of this article was to study the link between hypothyroidism, altered GI motility and development of SIBO. Published literature was reviewed to study the association of altered GI motility, SIBO and hypothyroidism. Altered GI motility leads to SIBO. SIBO is common in patients with hypothyroidism. Patients with chronic GI symptoms in hypothyroidism should be evaluated for the possibility of SIBO. Both antibiotics and probiotics have been studied and found to be effective in management of SIBO. PMID:24944923

  15. Plasma serotonin in horses undergoing surgery for small intestinal colic

    PubMed Central

    Torfs, Sara C.; Maes, An A.; Delesalle, Catherine J.; Pardon, Bart; Croubels, Siska M.; Deprez, Piet

    2015-01-01

    This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI colic were collected at several pre- and post-operative time points. Serotonin concentrations were determined using liquid-chromatography tandem mass spectrometry. Results were compared with those for 24 healthy control animals. The serotonin concentrations in PPP were significantly lower (P < 0.01) in pre- and post-operative samples from surgical SI colic horses compared to controls. However, no association with postoperative ileus or non-survival could be demonstrated at any time point. In this clinical study, plasma serotonin was not a suitable prognostic factor in horses with SI surgical colic. PMID:25694668

  16. Link between hypothyroidism and small intestinal bacterial overgrowth

    PubMed Central

    Patil, Anant D.

    2014-01-01

    Altered gastrointestinal (GI) motility is seen in many pathological conditions. Reduced motility is one of the risk factors for development of a small intestinal bacterial overgrowth (SIBO). Hypothyroidism is associated with altered GI motility. The aim of this article was to study the link between hypothyroidism, altered GI motility and development of SIBO. Published literature was reviewed to study the association of altered GI motility, SIBO and hypothyroidism. Altered GI motility leads to SIBO. SIBO is common in patients with hypothyroidism. Patients with chronic GI symptoms in hypothyroidism should be evaluated for the possibility of SIBO. Both antibiotics and probiotics have been studied and found to be effective in management of SIBO. PMID:24944923

  17. Gamma/delta intraepithelial lymphocytes in the mouse small intestine.

    PubMed

    Ogata, Masaki; Itoh, Tsunetoshi

    2016-09-01

    Although many studies of intraepithelial lymphocytes (IELs) have been reported, most of them have focused on αβ-IELs; little attention has been paid to γδ-IELs. The function of γδ-IELs remains largely unclear. In this article, we briefly review a number of reports on γδ-IELs, especially those in the small intestine, along with our recent studies. We found that γδ-IELs are the most abundant (comprising >70 % of the) IELs in the duodenum and the jejunum, implying that it is absolutely necessary to investigate the function(s) of γδ-IELs when attempting to delineate the in vivo defense system of the small intestine. Intraperitoneal injection of anti-CD3 mAb stimulated the γδ-IELs and caused rapid degranulation of them. Granzyme B released from their granules induced DNA fragmentation of duodenal and jejunal epithelial cells (paracrine) and of the IELs themselves (autocrine). However, perforin (Pfn) was not detected, and DNA fragmentation was induced even in Pfn-knockout mice; our system was therefore found to present a novel type of in vivo Pfn-independent DNA fragmentation. We can therefore consider γδ-IELs to be a novel type of large granular lymphocyte without Pfn. Fragmented DNA was repaired in the cells, indicating that DNA fragmentation alone cannot be regarded as an unambiguous marker of cell death or apoptosis. Finally, since the response was so rapid and achieved without the need for accessory cells, it seems that γδ-IELs respond readily to various stimuli, are activated only once, and die 2-3 days after activation in situ without leaving their site. Taken together, these results suggest that γδ-IELs are not involved in the recognition of specific antigen(s) and are not involved in the resulting specific killing or exclusion of the relevant antigen(s). PMID:27056578

  18. Organ culture of mucosal biopsies of human small intestine.

    PubMed

    Browning, T H; Trier, J S

    1969-08-01

    In vitro experiments of small intestinal mucosal function and metabolism utilizing excised tissue have been limited to a few hours by rapid epithelial cell necrosis which occurs with current incubation methods. We describe a method for culturing human mucosal biopsies for up to 24 hr employing organ culture methodology and demonstrate its potential application to studies of mucosal function. Peroral biopsies were placed in organ culture plates and maintained with modified Trowell's medium in 95% O(2)-5% CO(2) at 37 degrees C for 6-24 hr. To study cell proliferation, 2 muc of thymidine-(3)H was added per ml of medium. To study fat absorption, biopsies were exposed to micellar solutions of linolenic acid, monoolein, and taurodeoxycholate in Krebs-Ringer buffer for 15 min after culture in vitro for 24 hr. After 24 hr of culture, villi were shorter and wider. Cells in the lamina were reduced in number. Light and electron microscopic morphology of epithelial cells compared favorably to those of control biopsies except in occasional areas of partial necrosis. Some absorptive cells were more cuboidal and contained more lysosomes; many appeared entirely normal. Most crypt cells appeared normal; some contained increased glycogen and lysosomes. Mitoses were present, and labeled cells were abundant in crypts of biopsies after 6 hr of incubation with thymidine-(3)H-containing medium. By 24 hr. labeled cells migrated to the base of the villi. When biopsies cultured in vitro were subsequently exposed to micellar lipid, numerous lipid droplets were identified in the cytoplasm of absorptive cells. Thus, after 24 hr in vitro under these culture conditions, many human small intestinal epithelial cells maintain near normal morphology, epithelial cell proliferation proceeds, and fat absorption occurs. PMID:5796354

  19. In vivo characterization of ischemic small intestine using bioimpedance measurements.

    PubMed

    Strand-Amundsen, R J; Tronstad, C; Kalvøy, H; Gundersen, Y; Krohn, C D; Aasen, A O; Holhjem, L; Reims, H M; Martinsen, Ø G; Høgetveit, J O; Ruud, T E; Tønnessen, T I

    2016-02-01

    The standard clinical method for the assessment of viability in ischemic small intestine is still visual inspection and palpation. This method is non-specific and unreliable, and requires a high level of clinical experience. Consequently, viable tissue might be removed, or irreversibly damaged tissue might be left in the body, which may both slow down patient recovery. Impedance spectroscopy has been used to measure changes in electrical parameters during ischemia in various tissues. The physical changes in the tissue at the cellular and structural levels after the onset of ischemia lead to time-variant changes in the electrical properties. We aimed to investigate the use of bioimpedance measurement to assess if the tissue is ischemic, and to assess the ischemic time duration. Measurements were performed on pigs (n = 7) using a novel two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. After induction of anaesthesia, an ischemic model with warm, full mesenteric arterial and venous occlusion on 30 cm of the jejunum was implemented. Electrodes were placed on the serosal surface of the ischemic jejunum, applying a constant voltage, and measuring the resulting electrical admittance. As a control, measurements were done on a fully perfused part of the jejunum in the same porcine model. The changes in tan δ (dielectric parameter), measured within a 6 h period of warm, full mesenteric occlusion ischemia in seven pigs, correlates with the onset and duration of ischemia. Tan δ measured in the ischemic part of the jejunum differed significantly from the control tissue, allowing us to determine if the tissue was ischemic or not (P < 0.0001, F = (1,75.13) 188.19). We also found that we could use tan δ to predict ischemic duration. This opens up the possibility of real-time monitoring and assessment of the presence and duration of small intestinal ischemia. PMID:26805916

  20. Three dimensional human small intestine models for ADME-Tox studies.

    PubMed

    Yu, Jiajie; Carrier, Rebecca L; March, John C; Griffith, Linda G

    2014-10-01

    In vitro human small intestine models play a crucial part in preclinical drug development. Although conventional 2D systems possess many advantages, such as facile accessibility and high-throughput capability, they can also provide misleading results due to their relatively poor recapitulation of in vivo physiology. Significant progress has recently been made in developing 3D human small intestine models, suggesting that more-reliable preclinical results could be obtained by recreating the 3D intestinal microenvironment in vitro. Although there are still many challenges, 3D human small intestine models have the potential to facilitate drug screening and drug development. PMID:24853950

  1. Mixing and Transport in the Small Intestine: A Lattice-Boltzmann Model

    NASA Astrophysics Data System (ADS)

    Banco, Gino; Brasseur, James; Wang, Yanxing; Aliani, Amit; Webb, Andrew

    2007-11-01

    The two primary functions of the small intestine are absorption of nutrients into the blood stream and transport of material along the gut for eventual evacuation. The primary transport mechanism is peristalsis. The time scales for absorption, however, rely on mixing and transport of molecules between the bulk flow and epithelial surface. Two basic motions contribute to mixing: peristalsis and repetitive segmental contraction of short segments of the gut. In this study we evaluate the relative roles of peristalsis vs. segmental contraction on the degree of mixing and time scales of nutrient transport to the epithelium using a two-dimensional model of flow and mixing in the small intestine. The model uses the lattice-Boltzmann framework with second-order moving boundary conditions and passive scalar (Sc = 10). Segmental and peristaltic contractions were parameterized using magnetic resonance imaging data from rat models. The Reynolds numbers (1.9), segment lengths (33 mm), max radii (2.75 mm) and occlusion ratios (0.33) were matched for direct comparison. Mixing is quantified by the rate of dispersion of scalar from an initial concentration in the center of the segment. We find that radial mixing is more rapid with segmental than peristaltic motion, that radial dispersion is much more rapid than axial, and that axial is comparable between the motions.

  2. Propofol Attenuates Small Intestinal Ischemia Reperfusion Injury through Inhibiting NADPH Oxidase Mediated Mast Cell Activation

    PubMed Central

    Gan, Xiaoliang; Xing, Dandan; Su, Guangjie; Li, Shun; Luo, Chenfang; Irwin, Michael G.; Xia, Zhengyuan; Li, Haobo; Hei, Ziqing

    2015-01-01

    Both oxidative stress and mast cell (MC) degranulation participate in the process of small intestinal ischemia reperfusion (IIR) injury, and oxidative stress induces MC degranulation. Propofol, an anesthetic with antioxidant property, can attenuate IIR injury. We postulated that propofol can protect against IIR injury by inhibiting oxidative stress subsequent from NADPH oxidase mediated MC activation. Cultured RBL-2H3 cells were pretreated with antioxidant N-acetylcysteine (NAC) or propofol and subjected to hydrogen peroxide (H2O2) stimulation without or with MC degranulator compound 48/80 (CP). H2O2 significantly increased cells degranulation, which was abolished by NAC or propofol. MC degranulation by CP further aggravated H2O2 induced cell degranulation of small intestinal epithelial cell, IEC-6 cells, stimulated by tryptase. Rats subjected to IIR showed significant increases in cellular injury and elevations of NADPH oxidase subunits p47phox and gp91phox protein expression, increases of the specific lipid peroxidation product 15-F2t-Isoprostane and interleukin-6, and reductions in superoxide dismutase activity with concomitant enhancements in tryptase and β-hexosaminidase. MC degranulation by CP further aggravated IIR injury. And all these changes were attenuated by NAC or propofol pretreatment, which also abrogated CP-mediated exacerbation of IIR injury. It is concluded that pretreatment of propofol confers protection against IIR injury by suppressing NADPH oxidase mediated MC activation. PMID:26246867

  3. Chlorogenic Acid Decreases Intestinal Permeability and Increases Expression of Intestinal Tight Junction Proteins in Weaned Rats Challenged with LPS

    PubMed Central

    Ruan, Zheng; Liu, Shiqiang; Zhou, Yan; Mi, Shumei; Liu, Gang; Wu, Xin; Yao, Kang; Assaad, Houssein; Deng, Zeyuan; Hou, Yongqing; Wu, Guoyao; Yin, Yulong

    2014-01-01

    Chlorogenic acid, a natural phenolic acid present in fruits and plants, provides beneficial effects for human health. The objectives of this study were to investigate whether chlorogenic acid (CHA) could improve the intestinal barrier integrity for weaned rats with lipopolysaccharide (LPS) challenge. Thirty-two weaned male Sprague Dawley rats (21±1 d of age; 62.26±2.73 g) were selected and randomly allotted to four treatments, including weaned rat control, LPS-challenged and chlorogenic acid (CHA) supplemented group (orally 20 mg/kg and 50 mg/kg body). Dietary supplementation with CHA decreased (P<0.05) the concentrations of urea and albumin in the serum, compared to the LPS-challenged group. The levels of IFN-γ and TNF-α were lower (P<0.05) in the jejunal and colon of weaned rats receiving CHA supplementation, in comparison with the control group. CHA supplementation increased (P<0.05) villus height and the ratio of villus height to crypt depth in the jejunal and ileal mucosae under condictions of LPS challenge. CHA supplementation decreased (P<0.05) intestinal permeability, which was indicated by the ratio of lactulose to mannitol and serum DAO activity, when compared to weaned rats with LPS challenge. Immunohistochemical analysis of tight junction proteins revealed that ZO-1 and occludin protein abundances in the jejunum and colon were increased (P<0.05) by CHA supplementation. Additionally, results of immunoblot analysis revealed that the amount of occludin in the colon was also increased (P<0.05) in CHA-supplemented rats. In conclusion, CHA decreases intestinal permeability and increases intestinal expression of tight junction proteins in weaned rats challenged with LPS. PMID:24887396

  4. Precision cut intestinal slices are an appropriate ex vivo model to study NSAID-induced intestinal toxicity in rats.

    PubMed

    Niu, Xiaoyu; de Graaf, Inge A M; van der Bij, Hendrik A; Groothuis, Geny M M

    2014-10-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used therapeutic agents, however, they are associated with a high prevalence of intestinal side effects. In this investigation, rat precision cut intestinal slices (PCIS) were evaluated as an ex vivo model to study NSAID-induced intestinal toxicity. Firstly, PCIS were incubated with 0-200 μM diclofenac (DCF), one of the most intensively studied NSAIDs, to investigate whether they could correctly reflect the toxic mechanisms. DCF induced intestinal toxicity in PCIS was shown by morphological damage and ATP depletion. DCF induced endoplasmic-reticulum (ER) stress, mitochondrial injury and oxidative stress were reflected by up-regulated HSP-70 (heat shock protein 70) and BiP (binding immunoglobulin protein) gene expression, caspase 9 activation, GSH (glutathione) depletion and HO-1 (heme oxygenase 1) gene up-regulation respectively. Furthermore, DCF intestinal metabolites, which gave rise to protein adduct but not toxicity, were detected in PCIS. Secondly, PCIS were incubated with various concentrations of five NSAIDs. Typical NSAID-induced morphological changes were observed in PCIS. The ex vivo toxicity ranking (diflunisal> diclofenac = indomethacin > naproxen ≫ aspirin) showed good correlation with published in vitro and in vivo data, with diflunisal being the only exception. In conclusion, PCIS correctly reflect the various mechanisms of DCF-induced intestinal toxicity, and can serve as an ex vivo model for the prediction of NSAID-induced intestinal toxicity. PMID:25014874

  5. Metabolism of green tea catechins by the human small intestine.

    PubMed

    Schantz, Markus; Erk, Thomas; Richling, Elke

    2010-10-01

    Numerous studies have shown that green tea polyphenols can be degraded in the colon, and there is abundant knowledge about the metabolites of these substances that appear in urine and plasma after green tea ingestion. However, there is very little information on the extent and nature of intestinal degradation of green tea catechins in humans. Therefore, the aim of this study was to examine in detail the microbial metabolism and chemical stability of these polyphenols in the small intestine using a well-established ex vivo model. For this purpose, fresh ileostomy fluids from two probands were incubated for 24 h under anaerobic conditions with (+)-catechin (C), (-)-epicatechin (EC), (-)-epicatechin 3-O-gallate (ECG), (-)-epigallocatechin (EGC), (-)-epigallocatchin 3-O-gallate (EGCG) and gallic acid (GA). After lyophilisation and extraction, metabolites were separated, identified and quantified by high performance liquid chromatography-photodiode array detection (HPLC-DAD) and HPLC-ESI-tandem mass spectrometry. Two metabolites of EC and C (3', 4', 5'-trihydroxyphenyl-γ-valerolactone and 3', 4'-dihydroxyphenyl-γ-valerolactone) were identified. In addition, 3', 4', 5'-trihydroxyphenyl-γ-valerolactone was detected as a metabolite of EGC, and (after 24-h incubation) pyrogallol as a degradation product of GA. Cleavage of the GA esters of EGCG and ECG was also observed, with variations dependent on the sources (probands) of the ileal fluids, which differed substantially microbiotically. The results provide new information about the degradation of green tea catechins in the gastrointestinal tract, notably that microbiota-dependent liberation of GA esters may occur before these compounds reach the colon. PMID:20931601

  6. Basement membrane components are potent promoters of rat intestinal epithelial cell differentiation in vitro.

    PubMed

    Hahn, U; Stallmach, A; Hahn, E G; Riecken, E O

    1990-02-01

    Basement membranes have been implicated in morphogenesis and cell differentiation. In this study, the effect of basement membrane components on intestinal epithelial cell maturation in a mesenchyme-free environment was investigated. Fetal rat small intestinal epithelial cells (from the 14th-17th day of gestation) were exposed to basement membrane-derived proteins (laminin, collagen type IV, and a complex basement membrane-enriched extract from the Engelbreth-Holm-Swarm sarcoma) and other extracellular matrix proteins (collagen type I and fibronectin) coated onto Petri dishes. The cells attached readily only to fibronectin and basement membrane proteins. For 5 days the developing epithelial colonies were monitored in vitro, assessing morphological and functional parameters of cell maturation. Colonies grown on laminin and the basement membrane extract were larger and of greater cell density. An increase in alkaline phosphatase and lactase activity was observed after 3-4 days in these colonies which could be enhanced to yield 90%-100% positive cells by the addition of dexamethasone to the medium while no sucrase-isomaltase activity was elicited. Electron microscopy confirmed a high degree of cellular polarization illustrated by tight junctions and apical microvilli in epithelial cells grown on a basement membrane-like support. In contrast, none of the other proteins stimulated the cells to mature in vitro. The authors conclude that certain basement membrane components actively promote fetal intestinal epithelial cell differentiation. PMID:2295387

  7. Distinct adhesion of probiotic strain Lactobacillus casei ATCC 393 to rat intestinal mucosa.

    PubMed

    Saxami, Georgia; Ypsilantis, Petros; Sidira, Marianthi; Simopoulos, Constantinos; Kourkoutas, Yiannis; Galanis, Alex

    2012-08-01

    Adhesion to the intestine represents a critical parameter for probiotic action. In this study, the adhesion ability of Lactobacillus casei ATCC 393 to the gastrointestinal tract of Wistar rats was examined after single and daily administration of fermented milk containing either free or immobilized cells on apple pieces. The adhesion of the probiotic cells at the large intestine (cecum and colon) was recorded at levels ≥6 logCFU/g (suggested minimum levels for conferring a probiotic effect) following daily administration for 7 days by combining microbiological and strain-specific multiplex PCR analysis. Single dose administration resulted in slightly reduced counts (5 logCFU/g), while they were lower at the small intestine (duodenum, jejunum, ileum) (≤3 logCFU/g), indicating that adhesion was a targeted process. Of note, the levels of L. casei ATCC 393 were enhanced in the cecal and colon fluids both at single and daily administration of immobilized cells (6 and 7 logCFU/g, respectively). The adhesion of the GI tract was transient and thus daily consumption of probiotic products containing the specific strain is suggested as an important prerequisite for retaining its levels at an effective concentration. PMID:22554894

  8. Pore alterations of the endothelial lining of rat fenestrated intestinal capillaries exposed to acute stress.

    PubMed

    Aosa, Taishi; Chiba, Seiichi; Kitamura, Hirokazu; Ina, Keisuke; Tatsukawa, Shuji; Moriwaki, Chinatsu; Wei, Huixing; Gotoh, Koro; Masaki, Takayuki; Kakuma, Tetsuya; Shibata, Hirotaka; Fujikura, Yoshihisa

    2016-07-01

    Stress-induced inflammatory responses in the portal system are characterized by elevations in serum concentrations of interleukin-6 (IL-6) and endotoxins such as lipopolysaccharides (LPS). LPS translocation from the intestinal to the capillary lumen occurs via LPS endocytosis by the capillary endothelium. Because the capillary endothelium of the small intestinal submucosa is fenestrated, we determined the role of pore modifications within the fenestrated endothelium in relaying inflammatory stress responses in the portal vein. We evaluated changes in the diameter and density of endothelial pores of the lamina propria of intestinal villi induced by continuous light (CL) exposure for 48 h and the correlation between these changes and serum IL-6 concentration in the portal vein in a rat model. We found significant increases in both the pore diameter and density, accompanied by a significant increase in portal IL-6 concentration; these changes were significantly attenuated by pretreatment with propranolol, a beta adrenergic receptor antagonist. In contrast, intravenous noradrenaline administration mimicked CL-induced modifications of the diameter and density of pores and the elevation of portal vein IL-6 concentration. These findings suggested that stress-induced inflammatory responses in the portal system may be a part of the modifications of the endothelial pores triggered by sympathetic activation. PMID:26728293

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

    SciTech Connect

    Simko, V.; Kelley, R.E.

    1988-02-01

    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 /sup 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 /sup 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.

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

    SciTech Connect

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

    1986-07-01

    Calcium absorption in the large intestine of the rat was investigated in vivo. After a single injection of /sup 45/CaCl/sub 2/ into the cecum, 26.0 +/- 2.5% (mean +/- SE, n = 9) of the /sup 45/CaCl/sub 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 /sup 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 /sup 45/Ca was given orally, whereas when /sup 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 /sup 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.

  11. Glucagon-like peptide-2 increases small intestinal mass of calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glucagon-like peptide-2 (GLP-2) is a 33-amino acid hormone secreted from the gastrointestinal tract in response to luminal nutrients that potently increases small intestinal mass in non-ruminants. However, the effects of GLP-2 on small intestinal mass and morphology of ruminants is unknown. Eight Ho...

  12. Prostaglandins are not involved in the differentiation or growth of cultured small intestinal cells.

    PubMed

    Stange, E F; Schneider, A; Preclik, G; Ditschuneit, H

    1986-01-01

    Prostaglandins have been reported to exert trophic effects on gastrointestinal tissues. To determine whether there is a direct interaction with enterocytes, prostaglandins PGE2, PGF2 alpha, PGA2, PGB2 and the stable PGE2 derivative suleprost as well as the prostacyclin derivative nileprost were tested in rabbit ileal mucosa under organ culture conditions. At concentrations between 10(-9) and 10(-5) M, none of the prostaglandins significantly affected biopsy DNA or protein content, or the activity of the brush border enzymes alkaline phosphatase, lactase, sucrase or maltase. The inhibition of endogenous prostaglandin synthesis with indomethacin also failed to alter these parameters. Moreover, the growth rate of a rat duodenal crypt cell line was unaffected when cultured in the presence of PGE2, PGF2 alpha or indomethacin. Thus, there was no evidence for a direct effect of exogenous or endogenous prostaglandins or their deficiency on the differentiation or growth in cultured small intestinal cells. PMID:3817331

  13. In vitro small intestinal epithelial cell growth on a nanocomposite polycaprolactone scaffold

    PubMed Central

    Gupta, Ashish; Vara, Dina S.; Punshon, Geoffrey; Sales, Kevin M.; Winslet, Marc C.; Seifalian, Alexander M.

    2009-01-01

    Tissue engineering of the small intestine remains experimental despite worldwide attempts to develop a functional substitute for short bowel syndrome. Most published studies have reported predominant use of PLLA (poly-L-lactide acid)/PGA (polyglycolic acid) copolymer as the scaffold material, and studies have been limited by in vivo experiments. This lack of progress has inspired a fresh perspective and provoked further investigation and development in this field of tissue engineering. In the present paper, we exploit a relatively new nanocomposite of POSS (polyhedral oligomeric silsesquioxane) and PCL [poly(caprolactone-urea)urethane] as a material to develop porous scaffolds using a solvent casting/particulate leaching technique to fabricate porous scaffolds in different pore sizes and porosities. Scaffolds were characterized for pore morphology and porosity using scanning electron microscopy and micro-computed tomography. Rat intestinal epithelial cells were then seeded on to the polymer scaffolds for an in vitro study of cell compatibility and proliferation, which was assessed by Alamar Blue™ and lactate dehydrogenase assays performed for 21 days post-seeding. The results obtained demonstrate that POSS–PCL nanocomposite was produced as a macroporous scaffold with porosity over the range of 40–80% and pore size over the range of 150–250 μm. This scaffold was shown to support epithelial cell proliferation and growth. In conclusion, as a further step in investigating small intestinal tissue engineering, the nanocomposite employed in this study may prove to be a useful alternative to poly(lactic-co-glycolic acid) in the future. PMID:19860739

  14. Breath testing for small intestinal bacterial overgrowth: maximizing test accuracy.

    PubMed

    Saad, Richard J; Chey, William D

    2014-12-01

    The diagnosis of small intestinal bacterial overgrowth (SIBO) has increased considerably owing to a growing recognition of its association with common bowel symptoms including chronic diarrhea, bloating, abdominal distention, and the irritable bowel syndrome. Ideally, an accurate and objective diagnosis of SIBO should be established before initiating antibiotic treatment. Unfortunately, no perfect test exists for the diagnosis of SIBO. The current gold standard, small-bowel aspiration and quantitative culture, is limited by its high cost, invasive nature, lack of standardization, sampling error, and need for dedicated infrastructure. Although not without shortcomings, hydrogen breath testing provides the simplest noninvasive and widely available diagnostic modality for suspected SIBO. Carbohydrates such as lactulose and glucose are the most widely used substrates in hydrogen breath testing, with glucose arguably providing greater testing accuracy. Lactose, fructose, and sorbitol should not be used as substrates in the assessment of suspected SIBO. The measurement of methane in addition to hydrogen can increase the sensitivity of breath testing for SIBO. Diagnostic accuracy of hydrogen breath testing in SIBO can be maximized by careful patient selection for testing, proper test preparation, and standardization of test performance as well as test interpretation. PMID:24095975

  15. [Adult Case of Invagination Due to Small Intestinal Metastases of Malignant Melanoma].

    PubMed

    Ikeda, Atsushi; Kanazawa, Akifumi; Miura, Yoshiyuki; Hosoda, Yohei; Esaki, Hidekazu; Inoue, Naoya; Awane, Masaaki; Tsunekawa, Shoji; Taki, Yoshiro; Imamura, Masayuki

    2015-11-01

    An 84-year-old woman was diagnosed with malignant melanoma after resection of a nasal cavity tumor in February 2008. In April 2010, she underwent small bowel resection because of ileus due to small intestinal metastases. She was diagnosed with ileus again in October 2010. Computed tomography (CT) and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed invagination of the small intestine and small intestinal metastases. We performed a palliative small bowel resection. She had a good postoperative course and was discharged 2 weeks after surgery. Oral intake was possible for 6 months until her death. PMID:26805140

  16. Effect of intestinal resection, type of dietary fat and time on biliary lipid secretion in rats.

    PubMed

    Gómez-Ayala, A E; Lisbona, F; López-Aliaga, I; Barrionuevo, M; Pallarés, I; Alférez, M J; Hartiti, S; Campos, M S

    1994-01-01

    The effects of time and the type of dietary fat on biliary physiology in rats with 50% resection of the distal small intestine were investigated. The effects of ursodeoxycholic acid as an exogenous source of bile acid added to the diet were also studied. The fat composition of all diets was the same in quantitative terms (4%), and differed only in the type of lipid supplied: olive oil (diet A) or one-third medium chain triglycerides, one-third sunflower seed oil and one-third olive oil (diet B). In resected rats given diet A for 1 or 3 months, there was a decrease in biliary secretion of cholesterol and phospholipids, and in the lithogenic index, with respect to the control group. Resected rats fed diet B for 1 or 3 months showed increases in biliary secretion of cholesterol and phospholipids, and in the lithogenic index, in comparison with resected rats fed diet A. The addition of ursodeoxycholic acid to diet B led to the decoupling of bile acid and bile lipid secretion. PMID:8011314

  17. The effects of aluminum, iron, chromium, and yttrium on rat intestinal smooth muscle in vitro.

    PubMed

    Cunat, L; Membre, H; Marchal, L; Chaussidon, M; Burnel, D

    1998-01-01

    The modification of peristaltic activity in the presence of several metal ions has been investigated in the rat intestine by the isolated organ technique. The metals tested modify the intestinal movements: aluminum, chromium, and yttrium cause a decrease of amplitude, while iron showed no effect. By use of microscopic techniques, the presence of yttrium hydroxide was observed in the intestinal tissues. Iron also appears as a precipitate outside of the intestinal serosal, which may explain why iron did not modify the peristaltism. Chromium and aluminum were not apparent to microscope, despite being detected and quantified in the tissues by means of atomic emission spectrometer. We conclude that the trivalent ions of these elements may operate differently on the mechanisms of intestinal contractions: yttrium precipitates in intercellular spaces, iron precipitates outside the intestines, and chromium and aluminum remain in solution and are distributed homogeneously in the smooth intestinal muscle. PMID:9845462

  18. Thiamine intestinal transport and phosphorylation : a study in vitro of potential inhibitors of small intestinal thiamine-pyrophosphokinase using a crude enzymatic preparation.

    PubMed

    Basilico, V; Ferrari, G; Rindi, G; D'Andrea, G

    1979-12-01

    Using as enzymatic source the cytoplasmatic fraction of enterocytes isolated from the rat small intestine, thiamine-pyrophosphokinase activity was studied with a radiometric method using [thiazole-2-(14)C] thiamine. The Km value for thiamine was 2.14 X 10(-6) M and V 0.87 nmol of thiamine pyrophosphate mg-1 protein h-1. Eleven thiamine structural analogs and derivatives were assayed for their inhibitory action on the small intestine thiamine-pyrophosphokinase activity. Their Ki values were : pyrithiamine, 2.25 X 10(-6) M; thiamine monophosphate, 4 X 10(-6) M; 2'-ethylthiamine, 8 X 10(-6) M; 2'-butylthiamine, 6 X 10(-6) M; chloroethylthiamine and dimethalium, 1.5 X 10(-5) M; amprolium, 1.8 X 10(-4) M; L-582571, 1.65 X 10(-4) M; oxythiamine, 4.2 X 10(-3) M. Of the miscellaneous compounds tested (toxopyrimidine, Na-pyrophosphate, choline, L-phenylalanine, ethyl-urethane and 5-fluorouracil), none had any inhibitory action on intestinal thiamine-pyrophosphokinase activity, even if used at concentrations hundred times higher than that of labelled thiamine. PMID:94830

  19. Effect of nutritional rehabilitation on the development of intestinal brush border disaccharidases of postnatally malnourished weanling rats.

    PubMed

    Rossi, T M; Lee, P C; Young, C M; Lerner, A; Lebenthal, E

    1986-08-01

    The reversibility of the effects of postnatal malnutrition on the intestinal brush border enzymes and somatic and intestinal weights were examined using either ad libitum or restricted feedings. Malnutrition was induced in the immediate postnatal period by expanding newborn rat litters to 20 pups/dam. At 21 days of age, malnourished pups exhibited significantly decreased body and intestinal weights as compared to those from control litters. Malnourished pups also had significantly elevated lactase specific activities whereas sucrase and maltase activities were not affected in the proximal small intestine. With subsequent nutritional rehabilitation by an ad libitum (food available 24 h/day) or restricted feeding regimen (food available 2 h/day), body and intestinal weights remained significantly depressed by 56 days in malnourished as compared to control animals. Rats on 2-h feedings consumed approximately 35% of the food consumed by their ad libitum-fed counterparts. Comparison of the ratio of weight gained to the amount of food consumed did not demonstrate a greater food efficiency with any particular feeding pattern. With ad libitum or restricted feedings, lactase specific activity in the proximal segment attained control values by 14 days. Restricted feedings resulted in an apparent elevation of specific activity of sucrase and of maltase, when rats were sacrificed at one chosen time point. Multiple time studies in a 24-h cycle showed that maximal elevations in enzyme activities were associated with feeding time. There were no significant differences in mean specific daily enzyme activities between the two feeding regimens. Restricted feedings show no advantage in enzyme efficiency or in promoting the rate of recovery of the intestine after postnatal malnutrition. PMID:3090509

  20. Ultrasound Elasticity Imaging for Detecting Intestinal Fibrosis and Inflammation in Rats and Humans With Crohn’s Disease

    PubMed Central

    Stidham, Ryan W.; Xu, Jingping; Johnson, Laura A.; Kim, Kang; Moons, David S.; Mckenna, Barbara J.; Rubin, Jonathan M.; Higgins, Peter D. R.

    2016-01-01

    BACKGROUND Intestinal fibrosis causes many complications of Crohn’s disease (CD). Available biomarkers and imaging modalities lack sufficient accuracy to distinguish intestinal inflammation from fibrosis. Transcutaneous ultrasound elasticity imaging (UEI) is a promising, noninvasive approach for measuring tissue mechanical properties. We hypothesized that UEI could differentiate inflammatory from fibrotic bowel wall changes in both animal models of colitis and humans with CD. METHODS Female Lewis rats underwent weekly trinitrobenzene sulfonic acid enemas yielding models of acute inflammatory colitis (n = 5) and chronic intestinal fibrosis (n = 6). UEI scanning used a novel speckle-tracking algorithm to estimate tissue strain. Resected bowel segments were evaluated for evidence of inflammation and fibrosis. Seven consecutive patients with stenotic CD were studied with UEI and their resected stenotic and normal bowel segments were evaluated by ex vivo elastometry and histopathology. RESULTS Transcutaneous UEI normalized strain was able to differentiate acutely inflamed (−2.07) versus chronic fibrotic (−1.10) colon in rat models of inflammatory bowel disease (IBD; P = .037). Transcutaneous UEI normalized strain also differentiated stenotic (−0.87) versus adjacent normal small bowel (−1.99) in human CD (P = .0008), and this measurement also correlated well with ex vivo elastometry (r = −0.81). CONCLUSIONS UEI can differentiate inflammatory from fibrotic intestine in rat models of IBD and can differentiate between fibrotic and unaffected intestine in a pilot study in humans with CD. UEI represents a novel technology with potential to become a new objective measure of progression of intestinal fibrosis. Prospective clinical studies in CD are needed. PMID:21784048

  1. Management of intestinal failure in inflammatory bowel disease: Small intestinal transplantation or home parenteral nutrition?

    PubMed Central

    Harrison, Elizabeth; Allan, Philip; Ramu, Amrutha; Vaidya, Anil; Travis, Simon; Lal, Simon

    2014-01-01

    Inflammatory bowel disease and Crohn’s disease in particular, is a common cause of intestinal failure. Current therapeutic options include home parenteral nutrition and intestinal transplantation. For most patients, home intravenous therapy including parenteral nutrition, with a good probability of long-term survival, is the favoured choice. However, in selected patients, with specific features that may shorten survival or complicate home parenteral nutrition, intestinal transplantation presents a viable alternative. We present survival, complications, quality of life and economic considerations that currently influence individualised decision-making between home parenteral nutrition and intestinal transplantation. PMID:24696601

  2. Regional intestinal absorption and biliary excretion of fluvastatin in the rat: possible involvement of mrp2.

    PubMed

    Lindahl, Anders; Sjöberg, Asa; Bredberg, Ulf; Toreson, Helena; Ungell, Anna-Lena; Lennernäs, Hans

    2004-01-01

    the small intestine and 6% from the colon when given as an immediate release formulation. The corresponding values for an extended release formulation were 21% and 74%, respectively. In conclusion, fluvastatin exhibits dose-dependent pharmacokinetics in the rat. The rate of absorption (Cmax, Tmax, and Cmax/AUC(lqc)) from the intestinal tract is both region and dose-dependent in the rat. This may be due to the involvement of mrp2 in the intestine and/or in the liver. These absorption properties have to be considered in the development of an extended release formulation of fluvastatin. PMID:16026004

  3. Increased phospholipase A2 and decreased lysophospholipase activity in the small intestinal mucosa after ischaemia and revascularisation.

    PubMed Central

    Otamiri, T; Franzén, L; Lindmark, D; Tagesson, C

    1987-01-01

    The influence of ischaemia and revascularisation on lipid peroxidation and phospholipid metabolism in the rat small intestinal mucosa was investigated. Two hours of total ischaemia followed by five minutes of revascularisation caused not only accumulation of malondialdehyde in the mucosa, but also increased activity of phospholipase A2, decreased activity of lysophospholipase, and increased ratio between lysophosphatidylcholine and phosphatidylcholine. Pretreatment with the phospholipase A2 inhibitor, quinacrine, prevented the increases in mucosal phospholipase A2 activity and lysophosphatidylcholine/phosphatidylcholine ratio after ischaemia and morphological examinations revealed that the mucosa was then also protected against ischaemic injury. These findings point to the possibility that activation of phospholipase A2 and accumulation of lysophosphoglycerides could be involved in mediating the mucosal injury caused by small intestinal ischaemia. Images Fig. 7 PMID:3428670

  4. Compensation by the residual intestine after intestinal resection in the rat. I. Influence of amount of tissue removed.

    PubMed

    Hanson, W R; Osborne, J W; Sharp, J G

    1977-04-01

    Thirty days after resection of 10 to 80% of the midportion of the small intestine, excluding the duodenum, several cell kinetic parameters were investigated in the residual intestine. The degree of intestinal response increased in a stepwise fashion as the amount of tissue removed was increased. The response involved marked increases in: DNA synthesis per crypt expressed as disintegrations per minute of tritium (3H) reflecting (3H)thymidine incorporation, cells per crypt column, 3H-labelled cells per crypt column, cells per villus column, and thickness of all intestinal wall components. These changes occureed throughout the small intestine even at lesser resections. "Crypt profiles'' reflected changes in cell counts, but when the labeling frequency of proliferative cells was expressed as a percentage of the total crypt height, there was no change. The total number of crypts in the duodenum remained unchanged and the total number of cyrpts in the residual jejunum plus ileum decreased proportionally to the amount of tissue removed. Intestinal compensation occurred by increasing the size of the structures present in the residual intestine, not by increasing the number of structural units. PMID:838224

  5. Pinin modulates expression of an intestinal homeobox gene, Cdx2, and plays an essential role for small intestinal morphogenesis

    PubMed Central

    Joo, Jeong-Hoon; Taxter, Timothy J.; Munguba, Gustavo C.; Kim, Yong H.; Dhaduvai, Kanthi; Dunn, Nicholas W.; Degan, William J.; Oh, S. Paul; Sugrue, Stephen P.

    2010-01-01

    Pinin (Pnn), a nuclear speckle-associated protein, has been shown to function in maintenance of epithelial integrity through altering expression of several key adhesion molecules. Here we demonstrate that Pnn plays a crucial role in small intestinal development by influencing expression of an intestinal homeobox gene, Cdx2. Conditional inactivation of Pnn within intestinal epithelia resulted in significant downregulation of a caudal type homeobox gene, Cdx2, leading to obvious villus dysmorphogenesis and severely disrupted epithelial differentiation. Additionally, in Pnn-deficient small intestine, we observed upregulated Tcf/Lef reporter activity, as well as misregulated expression/distribution of β-catenin and Tcf4. Since regulation of Cdx gene expression has been closely linked to Wnt/β-catenin signaling activity, we explored the possibility of Pnn’s interaction with β-catenin, a major effector of the canonical Wnt signaling pathway. Co-immunoprecipitation assays revealed that Pnn, together with its interaction partner CtBP2, a transcriptional co-repressor, was in a complex with β-catenin. Moreover, both of these proteins were found to be recruited to the proximal promoter area of Cdx2. Taken together, our results suggest that Pnn is essential for tight regulation of Wnt signaling and Cdx2 expression during small intestinal development. PMID:20637749

  6. Role of interleukin-1 beta, interleukin-6, and TNF-alpha in intestinal maturation induced by dietary spermine in rats.

    PubMed

    Kaouass, M; Deloyer, P; Gouders, I; Peulen, O; Dandrifosse, G

    1997-04-01

    In the present investigation, the authors aimed to evaluate the role of cytokines in intestinal postnatal maturation induced by dietary polyamines. Neonatal rats were administered either saline (8 mumol) orally. Spermine increased interleukin-1 beta (IL-1 beta), IL-6, and TNF-alpha plasma concentration. The maximum concentrations of IL-1 beta, IL-6, and TNF-alpha were, respectively, observed at 4, 4, and 8 h posttreatment. Intraperitoneal (i.p.) injection of IL-1 beta increased the specific activity of sucrase in whole small intestine, whereas the specific activities of maltase and lactase were significantly enhanced only in the jejunum. IL-6 elicited sucrase and increased maltase specific activity in the whole small intestine, but lactase specific activity was not affected. TNF-alpha had no effect on sucrase and maltase specific activity, but a slight augmentation of lactase specific activity was detected in the jejunum. Spermine and spermidine content in the intestine was increased by i.p. injection of IL-1 beta and IL-6. Corticosterone secretion was elevated by single i.p. injection of IL-1 beta, IL-6, or TNF-alpha. These findings suggest that spermine could induce postnatal intestinal development and corticosterone secretion through a cytokine-dependent mechanism. PMID:9225134

  7. Intestine.

    PubMed

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients. PMID:26755265

  8. Intestinal morphology adjustments caused by dietary restriction improves the nutritional status during the aging process of rats.

    PubMed

    de Oliveira Belém, Mônica; Cirilo, Carla Possani; de Santi-Rampazzo, Ana Paula; Schoffen, João Paulo Ferreira; Comar, Jurandir Fernando; Natali, Maria Raquel Marçal; de Almeida Araújo, Eduardo José

    2015-09-01

    During the aging process, the body's systems change structurally and loss of function can occur. Ingesting a smaller amount of food has been considered a plausible proposal for increased longevity with the quality of life. However, the effects of dietary restriction (DR) during aging are still poorly understood, especially for organs of the digestive system. This study aimed to describe the body weight, oxidative status and possible morphological changes of the intestinal wall of rats submitted to DR during the aging process (7 to 18months old). Twelve 7-month-old male Wistar rats fed ad libitum since birth were assigned to two groups: control group (CG, n=6) fed ad libitum from 7 to 18months old; and dietary restriction group (DRG, n=6) fed 50% of the amount of chow consumed by the CG from 7 to 18months old. The body weight, feed and water intake were monitored throughout the experiment. Blood, periepididymal adipose tissue (PAT) and retroperitoneal adipose tissue (RAT), and the small intestine were collected at 18months old. The blood was collected to evaluate its components and oxidative status. Sections from the duodenum and ileum were stained with HE, PAS and AB pH2.5 for morphometric analyses of the intestinal wall components, and to count intraepithelial lymphocytes (IELs), goblet cells and cells in mitosis in the epithelium. DR rats showed a reduction in weight, naso-anal length, PAT, RAT and intestinal length; however, they consumed more water. Blood parameters indicate that the DR rats remained well nourished. In addition, they showed lower lipid peroxidation. Hypertrophy of the duodenal mucosa and atrophy of the ileal mucosa were observed. The number of goblet cells and IELs was reduced, but the mitotic index remained unaltered in both duodenum and ileum. In conclusion, 50% dietary restriction for rats from 7 to 18months old contributed to improving their nutritional parameters but, to achieve this, adjustments were required in the structure of the body

  9. The virtual intestine: in silico modeling of small intestinal electrophysiology and motility and the applications.

    PubMed

    Du, Peng; Paskaranandavadivel, Niranchan; Angeli, Timothy R; Cheng, Leo K; O'Grady, Gregory

    2016-01-01

    The intestine comprises a long hollow muscular tube organized in anatomically and functionally discrete compartments, which digest and absorb nutrients and water from ingested food. The intestine also plays key roles in the elimination of waste and protection from infection. Critical to all of these functions is the intricate, highly coordinated motion of the intestinal tract, known as motility, which is coregulated by hormonal, neural, electrophysiological and other factors. The Virtual Intestine encapsulates a series of mathematical models of intestinal function in health and disease, with a current focus on motility, and particularly electrophysiology. The Virtual Intestine is being cohesively established across multiple physiological scales, from sub/cellular functions to whole organ levels, facilitating quantitative evaluations that present an integrative in silico framework. The models are also now finding broad physiological applications, including in evaluating hypotheses of slow wave pacemaker mechanisms, smooth muscle electrophysiology, structure-function relationships, and electromechanical coupling. Clinical applications are also beginning to follow, including in the pathophysiology of motility disorders, diagnosing intestinal ischemia, and visualizing colonic dysfunction. These advances illustrate the emerging potential of the Virtual Intestine to effectively address multiscale research challenges in interdisciplinary gastrointestinal sciences. PMID:26562482

  10. Unsuccessful alloplastic esophageal replacement with porcine small intestinal submucosa.

    PubMed

    Doede, Thorsten; Bondartschuk, Michail; Joerck, Carsten; Schulze, Eberhard; Goernig, Matthias

    2009-04-01

    In general, there is no perfect method for esophageal replacement under consideration of the numerous associated risks and complications. The aim of this study was to examine a new material--small intestinal submucosa (SIS)--in alloplastic esophageal replacement. We implanted tubular SIS prosthesis about 4 cm in length in the cervical esophagus of 14 piglets (weight 9-13 kg). For the first 10 days, the animals were fed parenterally, supplemented by free given water, followed by an oral feeding phase. Four weeks after surgery, the animals were sacrificed. Only 1 of the 14 animals survived the study period of 4 weeks. The other piglets had to be sacrificed prematurely because of severe esophageal stenosis. On postmortem exploration, the prosthesis could not be found either macroscopically or histologically. Sutures between the prosthesis and the cervical muscles did not improve the results. Until now, the use of alloplastic materials in esophageal replacement has failed irrespective of the kind of material. As well as in our experiments, severe stenosis had been reported in several animal studies. The reasons for this unacceptable high rate of stenosis after alloplastic esophageal replacement seem to be multifactorial. Possible solutions could be transanastomotic splints, less inert materials, the decrease of anastomotic tension by stay sutures, the use of adult stem cells, and tissue engineering. PMID:19335409

  11. The Effects of Boron Derivatives on Lipid Absorption from the Intestine and on Bile Lipids and Bile Acids of Sprague Dawley Rats

    PubMed Central

    Hall, Iris H.; Reynolds, David J.; Wong, O. T.; Sood, A.; Spielvogel, B. F.

    1995-01-01

    N,N-dimethyl-n-octadecylamine borane 1 at 8 mg/kg/day, tetrakis-u-(trimethylamine boranecarboxylato)-bis(trimethyl-carboxyborane)-dicopper(II) 2 at 2.5 mg/kg/day and trimethylamine-carboxyborane 3 at 8 mg/kg/day were evaluated for their effects on bile lipids, bile acids, small intestinal absorption of cholesterol and cholic acid and liver and small intestinal enzyme activities involved in lipid metabolism. The agent administered orally elevated rat bile excretion of lipids, e.g. cholesterol and phospholipids, and compounds 2 and 3 increased the bile flow rate. These agents altered the composition of the bile acids, but there was no significant increase in lithocholic acid which is most lithogenic agent in rats. The three agents did decrease cholesterol absorption from isolated in situ intestinal duodenum loops in the presence of drug. Hepatic and small intestinal mucosa enzyme activities, e.g. ATP-dependent citrate lyase, acyl CoA cholesterol acyl transferase, cholsterol-7-α -hydroxylase, sn glycerol-3-phosphate acyl transferase, phosphatidylate phosphohydrolase, and lipoprotein lipase, were reduced. However, the boron derivatives 1 and 3 decreased hepatic HMG-CoA reductase activity, the regulatory enzyme for cholesterol synthesis, but the compounds had no effects on small intestinal mucosa HMG-CoA reductase activity. There was no evidence of hepatic cell damage afforded by the drugs based on clinical chemistry values which would induce alterations in bile acid concentrations after treatment of the rat. PMID:18472747

  12. Absorption of thiamine and nicotinic acid in the rat intestine during fasting and immobilization stress

    NASA Technical Reports Server (NTRS)

    Kirilyuk, O. G.; Khmelevskiy, Y. V.

    1980-01-01

    By perfusion of isolated sections of intestine with a solution containing thiamine at a concentration of 3.1 micromole, it was established that thiamine absorption in animals fasted for 72 hours decreased by 28 percent, whereas absorption increased by 12 percent in rats after 24 hour immobilization. After immobilization, absorption of label in the intestinal mucosa increased. Na K ATPase activity in the intestinal mucosa decreased by 10 percent during fasting, and it increased with immobilization of the animals. Activity of Na K ATPase in the intestinal mucosa cells determined the absorption rate of thiamine and nicotinic acid at the level of vitamin transport through the plasma membranes of the enterocytes.

  13. Hormone induced expression of brush border lactase in suckling rat intestine.

    PubMed

    Chaudhry, Kamaljit Kaur; Mahmood, Safrun; Mahmood, Akhtar

    2008-05-01

    The postnatal development of intestine is associated with a decline in brush border lactase activity in rodents. This is similar to adulthood hypolactasia, a phenomenon prevalent in humans worldwide. In the present study, the effect of luminal proteases from adult rat intestine was studied in vitro on intestinal lactase activity in saline control, thyroxine, insulin and cortisone treated rat pups. Lactase levels were determined by enzyme analysis and Western blotting. mRNA levels encoding lactase were determined by Northern blotting. Administration of thyroxine for 4 days reduced (P<0.05) lactase activity, but insulin treatment had no effect in 8-day-old rat intestine. However, cortisone administration augmented (P<0.01) lactase activity, under these conditions. Western blot analysis showed decreased lactase signal corresponding to 220-kDa protein band in thyroxine treated animals. However, the intensity of lactase signal was high in cortisone treated animals compared to controls. mRNA levels encoding lactase showed a 6.8-kb mRNA transcript in saline and hormone treated rats. mRNA levels encoding lactase were increased in cortisone treated animals but were reduced in thyroxine injected pups compared to controls. Microvillus membranes from saline (P<0.01) and thyroxine (P<0.05) or insulin (P<0.01) treated rats upon incubation with luminal wash from adult rat intestine showed a significant decline in lactase activity. These findings suggest that thyroxine, insulin or cortisone induced changes in lactase expression in suckling rat intestine make it susceptible to luminal proteases, which may in part be responsible for observed maturational decline in lactase activity in adult rat intestine. PMID:18273561

  14. Intestinal permeability of forskolin by in situ single pass perfusion in rats.

    PubMed

    Liu, Zhen-Jun; Jiang, Dong-bo; Tian, Lu-Lu; Yin, Jia-Jun; Huang, Jian-Ming; Weng, Wei-Yu

    2012-05-01

    The intestinal permeability of forskolin was investigated using a single pass intestinal perfusion (SPIP) technique in rats. SPIP was performed in different intestinal segments (duodenum, jejunum, ileum, and colon) with three concentrations of forskolin (11.90, 29.75, and 59.90 µg/mL). The investigations of adsorption and stability were performed to ensure that the disappearance of forskolin from the perfusate was due to intestinal absorption. The results of the SPIP study indicated that forskolin could be absorbed in all segments of the intestine. The effective permeability (P (eff)) of forskolin was in the range of drugs with high intestinal permeability. The P (eff) was highest in the duodenum as compared to other intestinal segments. The decreases of P (eff) in the duodenum and ileum at the highest forskolin concentration suggested a saturable transport process. The addition of verapamil, a P-glycoprotein inhibitor, significantly enhanced the permeability of forskolin across the rat jejunum. The absorbed fraction of dissolved forskolin after oral administration in humans was estimated to be 100 % calculated from rat P (eff). In conclusion, dissolved forskolin can be absorbed readily in the intestine. The low aqueous solubility of forskolin might be a crucial factor for its poor oral bioavailability. PMID:22411728

  15. Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves.

    PubMed Central

    Stead, R H; Tomioka, M; Quinonez, G; Simon, G T; Felten, S Y; Bienenstock, J

    1987-01-01

    Inflammatory or allergic conditions, as well as situations where healing and repair processes occur, are characterized by the presence of increased numbers of mast cells. Previous work on the effect of neuropeptides on mast cell mediator release showed that only substance P caused such release from intestinal mucosal mast cells [Shanahan, F., Denburg, J. A., Fox, J., Bienenstock, J. & Befus, A. D. (1985) J. Immunol. 135, 1331-1337]. Accordingly, we investigated the microanatomical relationship between mast cells and enteric nerves in normal rat intestine and parasite-infected rat intestine, in which mucosal mast cell hyperplasia occurs. Combined immunohistochemistry for neuron-specific enolase and staining with alcian blue at pH 0.5 was employed on paraffin-embedded sections of normal and Nippostrongylus brasiliensis-infected rat jejunum. Sixty-seven percent of intestinal mucosal mast cells were touching subepithelial nerves, and an additional 20% were within 2 micron of nerves. Assessment of the proportion of the lamina propria occupied by mast cells (12.5%), the average mast cell area (121 +/- 28 microns 2), and the density of enteric nerves (one per 788 +/- 151 microns 2) suggested that the association was 5 times greater than would be expected by chance alone (P less than 0.0001). In consecutive sections, the nerves in contact with mast cells were also shown to contain substance P and/or calcitonin-gene-related peptide. Electron microscopy confirmed this association: 8% of the mast cells in infected rats exhibited membrane-membrane contact with unmyelinated axons containing 70- to 170-nm dense-core vesicles, and an additional 31% were situated less than 250 nm from nerves. Other mast cells appeared to embrace nerve bundles through the projection of lamellopodia. These data provide systematic quantitative evidence that a structural foundation for communication between the immune and nervous systems exists in the rat gastrointestinal tract. Images PMID:2437589

  16. Differentiation-dependent regulation of intestinal vitamin B2 uptake: studies utilizing human-derived intestinal epithelial Caco-2 cells and native rat intestine

    PubMed Central

    Subramanian, Veedamali S.; Ghosal, Abhisek; Subramanya, Sandeep B.; Lytle, Christian

    2013-01-01

    Intestinal epithelial cells undergo differentiation as they move from the crypt to the villi, a process that is associated with up- and downregulation in expression of a variety of genes, including those involved in nutrient absorption. Whether the intestinal uptake process of vitamin B2 [riboflavin (RF)] also undergoes differentiation-dependent regulation and the mechanism through which this occurs are not known. We used human-derived intestinal epithelial Caco-2 cells and native rat intestine as models to address these issues. Caco-2 cells showed a significantly higher carrier-mediated RF uptake in post- than preconfluent cells. This upregulation was associated with a significantly higher level of protein and mRNA expression of the RF transporters hRFVT-1 and hRFVT-3 in the post- than preconfluent cells; it was also accompanied with a significantly higher rate of transcription of the respective genes (SLC52A1 and SLC52A3), as indicated by the higher level of expression of heterogeneous nuclear RNA and higher promoter activity in post- than preconfluent cells. Studies with native rat intestine also showed a significantly higher RF uptake by epithelial cells of the villus tip than epithelial cells of the crypt; this again was accompanied by a significantly higher level of expression of the rat RFVT-1 and RFVT-3 at the protein, mRNA, and heterogeneous nuclear RNA levels. These findings show, for the first time, that the intestinal RF uptake process undergoes differentiation-dependent upregulation and suggest that this is mediated (at least in part) via transcriptional mechanisms. PMID:23413253

  17. Vasoactive intestinal peptide receptors in rat liver after partial hepatectomy.

    PubMed Central

    Guijarro, L G; Couvineau, A; Rodriguez-Pena, M S; Juarranz, M G; Rodriguez-Henche, N; Arilla, E; Laburthe, M; Prieto, J C

    1992-01-01

    We describe the status of vasoactive intestinal peptide (VIP) receptors in regenerating liver. VIP-stimulated adenylate cyclase activity was markedly decreased in proliferating liver 3 days after partial (70%) hepatectomy. This was associated with a reduced efficacy of VIP (53% compared with controls), with no change in the potency of the peptide (ED50 0.8 nM). In contrast, forskolin- and guanosine 5'-[beta gamma-imido]triphosphate (Gpp[NH]p)-stimulated enzyme activities were not decreased after hepatectomy. The expression of Gs protein subunits (alpha and beta) was studied by cholera toxin-catalysed ADP ribosylation of alpha s and by immunoblotting of alpha s and beta subunits. Both subunits were increased in regenerating liver, further suggesting that the decreased response to VIP was not related to a decreased expression of Gs proteins. In fact, the reduced adenylate cyclase response to VIP in regenerating liver was associated with quantitative and structural changes in VIP receptors. Equilibrium binding data obtained with 125I-VIP indicated the presence of two classes of binding sites, the Kds of which were not altered after hepatectomy. In contrast, changes in binding capacity (Bmax.) were as follows: 0.11 +/- 0.01 and 0.05 +/- 0.01 pmol/mg of protein for high-affinity sites in control and hepatectomized rats respectively; and 2.3 +/- 0.2 and 0.65 +/- 0.03 pmol/mg of protein for low-affinity sites in control and hepatectomized rats respectively. Moreover, affinity labelling experiments showed that the M(r) value of 125I-VIP-receptor complexes was higher in regenerating liver than in quiescent hepatocytes, e.g. 58,000 and 53,000 respectively. It is concluded that VIP receptors are altered in regenerating liver, resulting in a decreased response of adenylate cyclase to the neuropeptide. Images Fig. 3. Fig. 4. Fig. 6. PMID:1322136

  18. Mechanical Characteristics of a Polymer Spring Device used to Lengthen Small Intestine

    NASA Astrophysics Data System (ADS)

    Steinberger, Douglas J.

    Short Bowel Syndrome (SBS) is a condition that occurs due to an insufficient amount of small intestine needed for nutrient absorption and water regulation of the body. A compression spring device is being developed in order to provide a mechanical stimulus to the tissue, as this type of force has been shown to promote lengthening of the tissue. The research completed in this thesis investigated the mechanical characteristics of the spring device and attempted to relate it to the functionality in rat and porcine intestinal tissue. Results from the evaluation of the springs show that Poly(epsilon-caprolactone), or PCL, is a sufficient polymer to use for creating a biodegradable device as the spring dimensions can be adjusted through variations in the diameter, thickness, and band size in order to provide an adequate spring constant for multiple animal types. Design of the springs, however, need to take into account the size of the gelatin capsule used, the amount of plastic deformation and creep behavior of the spring under compression for an extended time period, and the variation in the mechanical properties of the animal soft tissue that requires lengthening. Integration of the spring in-continuity requires a feature that will provide a mechanical resistance to force that is greater than the force of the spring in the compressed state. The spring still requires further development and any design should also take into account the possibility of intestinal perforations or obstructions. The polymer spring device provides a good means towards developing a treatment option for SBS, and other potential soft tissue lengthening needs of the body.

  19. Differential response to DNA damage may explain different cancer susceptibility between small and large intestine.

    PubMed

    Hong, Mee Young; Turner, Nancy D; Carroll, Raymond J; Chapkin, Robert S; Lupton, Joanne R

    2005-07-01

    Although large intestine (LI) cancer is the second-leading cause of cancer-related deaths in the United States, small intestine (SI) cancer is relatively rare. Because oxidative DNA damage is one possible initiator of tumorigenesis, we investigated if the SI is protected against cancer because of a more appropriate response to oxidative DNA damage compared with the LI. Sixty rats were allocated to three treatment groups: 3% dextran sodium sulfate (DSS, a DNA-oxidizing agent) for 48 hrs, withdrawal (DSS for 48 hrs + DSS withdrawal for 48 hrs), or control (no DSS). The SI, compared with the LI, showed greater oxidative DNA damage (P < 0.001) as determined using a quantitative immunohistochemical analysis of 8-oxodeoxyguanosine (8-oxodG). The response to the DNA adducts in the SI was greater than in the LI. The increase of TdT-mediated dUTP-biotin nick end labeling (TUNEL)-positive apoptosis after DSS treatment was greater in the SI compared with the LI (P < 0.001), and there was a positive correlation (P = 0.031) between DNA damage and apoptosis in the SI. Morphologically, DSS caused an extensive loss of crypt structure shown in lower crypt height (P = 0.006) and the number of intact crypts (P = 0.0001) in the LI, but not in the SI. These data suggest that the SI may be more protected against cancer by having a more dynamic response to oxidative damage that maintains crypt morphology, whereas the response of the LI makes it more susceptible to loss of crypt architecture. These differential responses to oxidative DNA damage may contribute to the difference in cancer susceptibility between these two anatomic sites of the intestine. PMID:15985621

  20. Intestinal transport of 3,6'-disinapoylsucrose, a major active component of Polygala tenuifolia, using Caco-2 cell monolayer and in situ rat intestinal perfusion models.

    PubMed

    Chen, Ying; Liu, Xinmin; Pan, Ruile; Zhu, Xiaoxin; Steinmetz, André; Liao, Yonghong; Wang, Ning; Peng, Bo; Chang, Qi

    2013-10-01

    3,6'-Disinapoylsucrose is a major active component of the herb Polygala tenuifolia which has long been used for relieving tranquilization, uneasiness of the mind, and improving learning and memory. Our previous study found that 3,6'-disinapoylsucrose had a very low oral bioavailability. Its mechanisms of absorption in the small intestine have so far been unclear. In the present study, the absorption mechanisms of 3,6'-disinapoylsucrose were investigated by using the Caco-2 cell monolayer and in situ rat intestinal perfusion models. The 3,6'-disinapoylsucrose concentration was determined by an LC/MS/MS method. In a Caco-2 cell transport study, the results showed that 3,6'-disinapoylsucrose had very limited intestinal permeability with average apparent permeability coefficient values around (1.11-1.34) × 10(-7) cm/s from the apical (A) to the basolateral (B) side and (1.37-1.42) × 10(-7) cm/s from B to A, at concentrations of 5, 20, and 33 µM. No concentration dependence in the 3,6'-disinapoylsucrose transport was observed. The apparent permeability coefficient value of 3,6'-disinapoylsucrose (5 µM) from A to B greatly increased to 4.49 × 10(-7) and 1.81 × 10(-7) cm/s, respectively, when the cells were preincubated with EDTA (17 mM) and sodium caprate (5.14 mM). No significant effect on the 3,6'-disinapoylsucrose transport by the inhibitors including verapamil, cyclosporine A, and sodium azide was observed. Similar results were found in the small intestinal perfusion study. The apparent permeability coefficient value of 3,6'-disinapoylsucrose greatly increased from 3.97 × 10(-6) to 23.4 × 10(-6) and 20.0 × 10(-6) cm/s in the presence of EDTA (17 mM) and sodium caprate (5.14 mM), respectively, in perfusion buffer. An in vitro stability evaluation of 3,6'-disinapoylsucrose in the gastrointestinal tract showed that it was relatively stable both in the stomach and small intestine contents, while it was found to be more instable in the colon contents. All of the

  1. Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats

    PubMed Central

    XUE, TONG-MIN; TAO, LI-DE; ZHANG, JIE; ZHANG, PEI-JIAN; LIU, XIA; CHEN, GUO-FENG; ZHU, YI-JIA

    2016-01-01

    The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF-κBp65 expression levels, with reduced expression of Bcl-2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF-α and IL-1 were significantly reduced in the IP group. Immunohistochemistry for Bcl-2 and Bax indicated that Bcl-2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro-inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury. PMID:26821057

  2. Rat intestinal trehalase. Studies of the active site.

    PubMed

    Chen, C C; Guo, W J; Isselbacher, K J

    1987-11-01

    Rat intestinal trehalase was solubilized, purified and reconstituted into proteoliposomes. With octyl glucoside as the solubilizing detergent, the purified protein appeared as a single band on SDS/polyacrylamide-gel electrophoresis with an apparent molecular mass of 67 kDa. Kinetic studies indicated that the active site of this enzyme can be functionally divided into two adjacent regions, namely a binding site (with pKa 4.8) and a catalytic site (with pKa 7.2). Other findings suggested that the catalytic site contains a functional thiol group, which is sensitive to inhibition by N-ethylmaleimide, Hg2+ and iodoacetate. Substrate protection and iodoacetate labelling of the thiol group demonstrated that only a protein of 67 kDa was labelled. Furthermore, sucrose and phlorizin protected the thiol group, but Tris-like inhibitors did not. Structure-inhibition analysis of Tris-like inhibitors, the pH effect of Tris inhibition and Tris protection of 1-(3-dimethylaminopropyl)-3-ethylcarbodi-imide inactivation permitted characterization and location of a separate site containing a carboxy group for Tris binding, which may also be the binding region. On the basis of these findings, a possible structure for the active site of trehalase is proposed. PMID:3426558

  3. Starches of varied digestibilities differentially modify intestinal function in rats.

    PubMed

    Lajvardi, A; Mazarin, G I; Gillespie, M B; Satchithanandam, S; Calvert, R J

    1993-12-01

    Starches of different digestibilities may enter the colon to different extents and alter colonic function. Male Fischer 344 rats were fed diets containing 25% cooked potato starch, arrowroot starch, high amylose cornstarch or raw potato starch for 6 wk. Fecal weight, transit time, colonic thymidine kinase activity (a marker for cell proliferation), and weight, starch content and pH of the cecum and proximal and distal colon were measured. Raw potato starch was much less completely digested than high amylose cornstarch, resulting in a 32-fold greater amount of undigested starch entering the cecum in the raw potato starch group. Both the high amylose cornstarch and raw potato starch diets significantly enhanced fecal weight and produced large intestinal hypertrophy, effects that were greatest in the raw potato starch group. Raw potato starch feeding was associated with the highest level of thymidine kinase activity, although the differences in thymidine kinase activity among the four groups were not significant. This diet also produced a 50% longer transit time. Entry of a large amount of raw potato starch into the colon resulted in greater luminal acidity, greater luminal bulk and slower transit. A much smaller amount of starch entered the colon in the high amylose cornstarch group and resulted in fecal bulking but no alteration in transit. PMID:8263598

  4. Studies on the phospholipases of rat intestinal mucosa

    PubMed Central

    Subbaiah, P. V.; Ganguly, J.

    1970-01-01

    1. Subcellular distribution and characteristics of different phospholipases of rat intestinal mucosa were studied. 2. The presence of free fatty acid was necessary for the maximal hydrolysis of lecithin (phosphatidylcholine), but there was no accumulation of lysolecithin (1 or 2-acylglycerophosphorylcholine);lysolecithin accumulated when the reaction was carried out in the presence of sodium deoxycholate and at or above pH8.0. 3. The fatty acid-activated phospholipase B as well as lysolecithinase showed optimum activity at pH6.5, whereas for the phospholipase A it was about pH8.6. 4. The bulk of the phospholipase A was present in the microsomal fraction, whereas the phospholipase B and lysolecithinase activities were distributed between the microsomal and soluble fractions of the mucosal homogenate. 5. Phospholipase A was equally distributed between the brush border and brush-border-free particulate fraction, with the brush border having highest specific activity, whereas the other two activities were distributed between the brush-border-free particulate and soluble fractions. 6. Various treatments showed marked differences between the phospholipase A and phospholipase B activities, but not between phospholipase B and lysolecithinase activities. 7. By using (β[1-14C]-oleoyl) lecithin it was shown that the mucosal phospholipase A was specific for the β-ester linkage of the lecithin molecule. PMID:5484667

  5. The protective role of montelukast against intestinal ischemia-reperfusion injury in rats

    PubMed Central

    Wu, Shenbao; Zhu, Xuxing; Jin, Zhonghai; Tong, Xiuping; Zhu, Liqin; Hong, Xiaofei; Zhu, Xianfei; Liu, Pengfei; Shen, Weidong

    2015-01-01

    Several drugs are effective in attenuating intestinal ischemia-reperfusion injury (IRI); however little is known about the effect of montelukast. Fifty rats were randomly assigned to 3 groups: model group (operation with clamping), sham group (operation without clamping), and study group (operation with clamping and 0.2, 2 and 20 mg/kg montelukast pretreatment). Intestinal ischemia-reperfusion was performed by occlusion (clamping) of the arteria mesenterica anterior for 45 min, followed by 24 h reperfusion. Intestinal IRI in the model group led to severe damage of the intestinal mucosa, liver and kidney. The Chiu scores of the intestines from the study group (2 and 20 mg/kg) were lower than that of the model group. Intestinal IRI induced a marked increase in CysLTR1, Caspase-8 and -9 expression in intestine, liver and kidney, which were markedly reduced by preconditioning with 2 mg/kg montelukast. Preconditioning with 2 g/kg montelukast significantly attenuated hepatic tissue injury and kidney damage, and decreased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in plasma after intestinal IRI. In conclusion, preconditioning with montelukast could attenuate intestinal IRI and the subsequent systemic inflammatory response in rats. PMID:26497763

  6. The protective role of montelukast against intestinal ischemia-reperfusion injury in rats.

    PubMed

    Wu, Shenbao; Zhu, Xuxing; Jin, Zhonghai; Tong, Xiuping; Zhu, Liqin; Hong, Xiaofei; Zhu, Xianfei; Liu, Pengfei; Shen, Weidong

    2015-01-01

    Several drugs are effective in attenuating intestinal ischemia-reperfusion injury (IRI); however little is known about the effect of montelukast. Fifty rats were randomly assigned to 3 groups: model group (operation with clamping), sham group (operation without clamping), and study group (operation with clamping and 0.2, 2 and 20 mg/kg montelukast pretreatment). Intestinal ischemia-reperfusion was performed by occlusion (clamping) of the arteria mesenterica anterior for 45 min, followed by 24 h reperfusion. Intestinal IRI in the model group led to severe damage of the intestinal mucosa, liver and kidney. The Chiu scores of the intestines from the study group (2 and 20 mg/kg) were lower than that of the model group. Intestinal IRI induced a marked increase in CysLTR1, Caspase-8 and -9 expression in intestine, liver and kidney, which were markedly reduced by preconditioning with 2 mg/kg montelukast. Preconditioning with 2 g/kg montelukast significantly attenuated hepatic tissue injury and kidney damage, and decreased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in plasma after intestinal IRI. In conclusion, preconditioning with montelukast could attenuate intestinal IRI and the subsequent systemic inflammatory response in rats. PMID:26497763

  7. Fasciola hepatica: antibody coating of juvenile flukes in the intestinal lumen of resistant rats.

    PubMed

    Burden, D J; Hughes, D L; Hammet, N C

    1982-01-01

    Newly excysted juvenile Fasciola hepatica, when placed in isolated loops of intestine prepared in previously infected rats, acquired a surface covering of rat immunoglobulin. IgG, IgA, IgE and IgM were all involved. This immunoglobulin coating was sloughed off when the flukes were maintained in vitro for three hours. PMID:7045997

  8. Vascular Endothelial Growth Factor (VEGF) Bioavailability Regulates Angiogenesis and Intestinal Stem and Progenitor Cell Proliferation during Postnatal Small Intestinal Development

    PubMed Central

    Holoyda, Kathleen A.; Hou, Xiaogang; Fowler, Kathryn L.; Grikscheit, Tracy C.

    2016-01-01

    Background Vascular endothelial growth factor (VEGF) is a highly conserved, master regulatory molecule required for endothelial cell proliferation, organization, migration and branching morphogenesis. Podocoryne carnea and drosophila, which lack endothelial cells and a vascular system, express VEGF homologs, indicating potential roles beyond angiogenesis and vasculogenesis. The role of VEGF in the development and homeostasis of the postnatal small intestine is unknown. We hypothesized regulating VEGF bioavailability in the postnatal small intestine would exhibit effects beyond the vasculature and influence epithelial cell stem/progenitor populations. Methods VEGF mutant mice were created that overexpressed VEGF in the brush border of epithelium via the villin promotor following doxycycline treatment. To decrease VEGF bioavailability, sFlt-1 mutant mice were generated that overexpressed the soluble VEGF receptor sFlt-1 upon doxycycline administration in the intestinal epithelium. Mice were analyzed after 21 days of doxycycline administration. Results Increased VEGF expression was confirmed by RT-qPCR and ELISA in the intestine of the VEGF mutants compared to littermates. The VEGF mutant duodenum demonstrated increased angiogenesis and vascular leak as compared to littermate controls. The VEGF mutant duodenum revealed taller villi and increased Ki-67-positive cells in the transit-amplifying zone with reduced Lgr5 expression. The duodenum of sFlt-1 mutants revealed shorter villi and longer crypts with reduced proliferation in the transit-amplifying zone, reduced expression of Dll1, Bmp4 and VE-cadherin, and increased expression of Sox9 and EphB2. Conclusions Manipulating VEGF bioavailability leads to profound effects on not only the intestinal vasculature, but epithelial stem and progenitor cells in the intestinal crypt. Elucidation of the crosstalk between VEGF signaling in the vasculature, mesenchyme and epithelial stem/progenitor cell populations may direct future

  9. The impact of non-steroidal anti-inflammatory drugs on the small intestinal epithelium

    PubMed Central

    Handa, Osamu; Naito, Yuji; Fukui, Akifumi; Omatsu, Tatsushi; Yoshikawa, Toshikazu

    2014-01-01

    The small intestine has been called as a dark continent of digestive tract and it had been very difficult to diagnose or treat the disease of small intestine. However recent technological development including video capsule endoscopy or balloon-assisted endoscopy has made us to aware the various diseases of small intestine. By using capsule endoscopy, many researchers reported that more than 70% of patients treated continuously with non-steroidal anti-inflammatory drugs (NSAID) exhibit the mucosal damage of small intestine. In some cases, NSAID not only causes mucosal damage but also results in life threatening bleeding from small intestine, which had not been prevented or cured by gastro-protective drug or anti-gastric acid secretion drug administration. Therefore to investigate and identify the effective drug that protects small intestine from mucosal damage is urgently expected. In spite of extensive investigation in clinical field, only a few drugs such as misoprostol, a synthetic prostaglandin E1 analogue, has been reported as an effective one but is not satisfactory enough to fulfill the requirement of patients who suffer from NSAID-induced mucosal damage of small intestine. And now, extensive study is being performed using several gastro-mucoprotective drugs by many researchers. In this review, we introduce the current clinical situation in small intestinal injury of patients under NSAID treatment, and to summarize the molecular mechanism by which NSAID, including acetyl salicylic acid, cause small intestinal damage. In addition, we present results of clinical trials performed so far, and refer the possible preventive method or treatment in the near future. PMID:24426183

  10. Effect of the acupoints ST-36 (Zusanli) and SP-6 (Sanyinjiao) on intestinal myoelectric activity of Wistar rats.

    PubMed

    Tabosa, A; Yamamura, Y; Forno, E R; Mello, L E A M

    2002-06-01

    Despite its ancient use as a therapeutic tool to treat several ailments, acupuncture still faces the challenge of scrutiny by Western science both in terms of its efficacy and in terms of the characterization of its effects and mechanisms of actions underlying these effects. We investigated under well-controlled and carefully characterized conditions the influence of electrical stimulation of acupuncture points ST-36 (Zusanli) and SP-6 (Sanyinjiao) on the myoelectric activity of the small intestine of 38 adult male Wistar rats. Electrical recordings obtained by means of four electrodes chronically implanted in the small intestine were used to assess the effects of acupuncture (electroacupuncture stimulation set at 2 Hz, intermittent stimulation, 1 V, for 30 min). Immobilization of the animals was associated with a consistent decrease (-8 +/- 7%) in the myoelectric activity of the small intestine as measured by means of the root mean square. Conversely, acupuncture was able to significantly increase (overshoot) this activity compared to baseline (+44 +/- 7%). In contrast, immobilized animals subjected to sham acupuncture had only modest (nonsignificant) increases in myoelectric activity (+9 +/- 6%). Using carefully controlled conditions we confirmed previous noncontrolled studies on the ability of acupuncture to alter intestinal motility. The characterization of the topographic and temporal profiles of the effects observed here represents a basis for future dissection of the physiological and pharmacological systems underlying these effects. PMID:12045840

  11. Bleeding from the small intestine and aortic regurgitation in Noonan syndrome.

    PubMed

    Yoshino, Hiroshi; Okumachi, Yasuyo; Akisaki, Taichi; Yasuda, Hisafumi; Hara, Kenta; Yokono, Koichi; Akita, Hozuka

    2011-01-01

    A 62-year-old man was admitted to our hospital because of melena. On admission physical examination revealed that he had typical features of Noonan syndrome (NS). Investigation via upper endoscopy with the single balloon demonstrated oozing from the small intestine. Bleeding sometimes occurs in patients with NS. We speculated that coagulation defects or vascular malformations might have been present at the first visit in this case. However, coagulation function was normal. By upper endoscopy with the single balloon we clearly revealed the angioectasia in the small intestine. This case documents the first association among NS, aortic regurgitation and angioectasia in the small intestine. PMID:22041367

  12. Intrapelvic prosthesis to prevent injury of the small intestine with high dosage pelvic irradiation

    SciTech Connect

    Sugarbaker, P.H.

    1983-09-01

    The major complication to delivering tumoricidal dosages of radiation to the pelvis is radiation damage to the loops of the small intestine located within the radiation field. To exclude the small intestine from the pelvis after extensive pelvic surgical treatment, prosthetic materials are used. A transabdominal baffle made of prosthetic mesh separates pelvic and abdominal cavities. A Silastic implant, usually used in the reconstruction of the breast, is used in the pelvis to occupy space. In so doing, all of the small intestine can be excluded from the pelvic cavity and dosages of radiation to 6,500 rads can be administered.

  13. Immunoglobulin synthesis and antibody content in the small intestine of the rabbit.

    PubMed Central

    Menzel, J; Rowley, D

    1975-01-01

    The concentration of immunoglobulin and specific antibody in the serum and the intestinal fluid and the rate of synthesis of immunoglobulin in the small intestine was measured in normal and immunized rabbits. IgA was found to be the predominant immunoglobulin in the intestinal fluid. IgA and IgG were secreted at rates of 4-3 mug/cm/hr and 1-3 mug/cm/hr respectively. Specific anti-Vibrio cholerae antibodies in the intestine were found mainly in the IgA class after oral immunization. PMID:1204251

  14. Activation of caspases in intestinal villus epithelial cells of normal and nematode infected rats

    PubMed Central

    Hyoh, Y; Ishizaka, S; Horii, T; Fujiwara, A; Tegoshi, T; Yamada, M; Arizono, N

    2002-01-01

    Background: Small intestinal epithelial cells (IEC) show apoptosis in physiological turnover of cells and in certain inflammatory diseases. Aims: To investigate the role of caspases in the progression of IEC apoptosis in vivo. Methods: IEC were separated along the villus-crypt axis from the jejunum of normal and Nippostrongylus brasiliensis infected rats at 4°C. Caspases were examined by a fluorometric assay method, histochemistry, and immunoblotting. Results: Villus cell rich IEC from normal rats exhibited a high level of caspase-3-like activity whereas activities of caspase-1, -8, and -9 were negligible. Immunoblotting analysis of villus cell rich IEC revealed partial cleavage of procaspase-3 into a 17 kDa molecule as well as cleavage of a caspase-3 substrate, poly(ADP-ribose) polymerase (PARP), whereas in crypt cell rich IEC, caspase-3 cleavage was less significant. Caspase-3 activity was also observed histochemically in villus epithelium on frozen sections of the normal small intestine. IEC prepared at 4°C did not reveal nuclear degradation whereas subsequent incubation in a suspension at 37°C induced intense nuclear degradation within one hour in accordance with increases in active caspase-3. This apoptosis was partially suppressed by the caspase inhibitor Z-VAD-fmk. Nematode infected animals showed villus atrophy together with significant increases in levels of caspase-3 in IEC but not of caspase-1, -8, or -9. Conclusion: Caspase-3 may have an important role in the physiological replacement of IEC as well as in progression of IEC apoptosis induced by nematode infection. PMID:11772970

  15. Impaired function of the intestinal barrier in a novel sub-health rat model

    PubMed Central

    FENG, SISI; LIU, WEIDONG; ZUO, SHENGNAN; XIE, TINGYAN; DENG, HUI; ZHANG, QIUHUAN; ZHONG, BAIYUN

    2016-01-01

    Sub-health is a state featuring a deterioration in physiological function between health and illness, and the sub-health condition has surfaced as life-threatening in humans. The aim of the present study was to establish a sub-health model in rats, and investigate the function of the intestinal barrier in the sub-health rats and rats following intervention. To establish a sub-health model, the rats were subjected to a high-fat and sugar diet, motion restriction and chronic stress. Their serum glucose and triglyceride levels, immune function and adaptability were then measured. The levels of diamine oxidase and D-lactic acid in the plasma were analyzed as markers of the intestinal permeability. The protein and mRNA expression levels of anti-apoptotic YWHAZ in the colonic tissue was detected using immunohistochemical and reverse transcription-quantitative polymerase chain reaction analyses In the present study, the sub-health rat model was successfully established, and sub-health factors increased the intestinal permeability and reduced the expression of YWHAZ. Providing sub-health rats with normal living conditions did not improve the function of the intestinal barrier. In conclusion, the results of the present study demonstrated that intestinal disorders in the sub-health rat model may result from the damage caused by reduce intestinal barrier function as well as the decreased expression levels of YWHAZ. Additionally, rats in the sub-health condition did not recover following subsequent exposure to normal living conditions, suggesting that certain exercises or medical intervention may be necessary to improve sub-health symptoms. PMID:26957295

  16. Ascites Drainage Leading to Intestinal Adhesions at the Mesentery of the Small Intestine with Fatal Outcome

    PubMed Central

    Kettler, B.; Schrem, H.; Klempnauer, J.; Grannas, G.

    2014-01-01

    A common problem in patients with chronic liver diseases and liver cirrhosis is the development of ascites. First line therapy for ascites is the restriction of sodium intake and a diuretic treatment. Paracentesis is indicated in patients with large compromising volumes of ascites. In selected cases, permanent drainage of ascites over prolonged periods of time may be indicated. In the case presented here, a 66-year-old male patient, who was hospitalized with liver cirrhosis caused by alcoholic abuse, required permanent drainage of ascites. After three weeks of continuous ascites drainage, he developed bacterial peritonitis. Conventional attempts to remove the catheter by transcutaneous pulling failed and we thus decided to perform a median laparotomy to remove the catheter surgically. Intraoperatively an adhesion of the ascites drain (a so called ‘basket catheter’) to the mesentery very close to the small intestine was found, approximately 50 mm distal of the ligament suspensorium duodeni (ligament of Treitz). The basket catheter used for this patient was especially designed to drain infections, not fluids. We solved the adhesion, removed the basket catheter, placed a new surgical drain and finished the operation. The patient developed a rupture of his abdominal fascia suture 12 days later, which was caused by massive ascites and complicated by hepatorenal syndrome type I. The patient was taken to the operating theater again. After the second operation, the chronic liver failure decompensated and the patient died. Ascites caused by liver cirrhosis is still a medical challenge. The indication for the use of the correct percutaneous catheter for permanent paracentesis should be carefully considered. Some catheters are obviously not suited to drain ascites and may lead to fatal outcomes. PMID:24453504

  17. Phytohemagglutinin derived from red kidney bean (Phaseolus vulgaris): a cause for intestinal malabsorption associated with bacterial overgrowth in the rat.

    PubMed

    Banwell, J G; Boldt, D H; Meyers, J; Weber, F L

    1983-03-01

    Plant lectins or carbohydrate binding proteins interact with membrane receptors on cellular surfaces but their antinutritional effects are poorly defined. Studies were conducted to determine the effects of phytohemagglutinin, a lectin derived from raw red kidney bean (Phaseolus vulgaris), on small intestinal absorptive function and morphology, and on the intestinal microflora. Phytohemagglutinin was isolated in purified form by thyroglobulin-sepharose 4B affinity chromatography. Red kidney bean and phytohemagglutinin (6% and 0.5%, respectively, of dietary protein) were fed in a purified casein diet to weanling rats for up to 21 days. Weight loss, associated with malabsorption of lipid, nitrogen, and vitamin B12, developed in comparison with animals pair-fed isonitrogenous casein diets. Antinutritional effects of red kidney bean were reversible on reinstitution of a purified casein diet. An increase in bacterial colonization of the jejunum and ileum occurred in red kidney bean- and phytohemagglutin-fed animals. When antibiotics were included in the diet, malabsorption of [3H]triolein and 57Co-vitamin B12 in red kidney bean-fed animals was partially reversed and, in germ-free animals, purified phytohemagglutinin had no demonstrable antinutritional effect. Mucosal disaccharidase activity was reduced in red kidney bean- and phytohemagglutinin-fed animals, but intestinal mucosal morphology was unchanged. Dietary administration of phytohemagglutinin, alone or as a component of red kidney bean, caused intestinal dysfunction, which was associated with, and dependent upon, small intestinal bacterial overgrowth. Adherence of enteric bacteria to the mucosal surface was enhanced by phytohemagglutinin which may have facilitated small intestinal bacterial overgrowth. PMID:6822324

  18. Effect of intestinal fluid flux on ibuprofen absorption in the rat intestine.

    PubMed

    Lane, Majella E; Levis, Karl A; Corrigan, Owen I

    2006-02-17

    Previously the apparent permeability coefficient (P(app)) of ibuprofen was observed to vary depending on the perfusion medium employed. The present work explores the possible contributions to these differences. Studies were undertaken using an in situ single pass rat gut technique. Lumenal drug concentrations and plasma drug levels were assayed by HPLC. Absorption rate constants (k(0)) were determined from fractions of drug unabsorbed from the intestineat steady state. Plasma data were fitted to a two compartment open model with zero-order input. Significant differences in net fluid flux were observed between the various buffered perfusion media, with fluxes varying from -0.044+/-0.006 ml min(-1) to +0.057+/-0.013 ml min(-1), the lower and negative values occurring for lower pH media and the larger positive values tending to occur with media of higher pH. A linear relationship was found between the P(app) of ibuprofen and net water flux (y=1.13+11.3x; r(2)=0.80). Apparent zero-order rate constants for ibuprofen appearance in plasma correlated well with absorption rate constants estimated from steady state lumenal drug concentration [k(0(gut))]. From the linear relationship between P(app) and fluid flux a normalized P(app) for ibuprofen (i.e. the P(app) in the absence of net fluid flux) of 1.1 x 10(-4)cms(-1) was determined Net lumenal fluid flux is dependent on perfusion medium composition and significantly alters ibuprofen absorption. The differences observed for P(app) were reflected in systemic drug absorption concentrations. The findings of these studies underline the importance of standardizing the osmolarity of experimental media used for the determination of intestinal permeability data. PMID:16376032

  19. Effect of oral supplementation of Lactobacillus reuteri in reduction of intestinal absorption of aflatoxin B(1) in rats.

    PubMed

    Hernandez-Mendoza, Adrián; González-Córdova, Aarón Fernando; Vallejo-Cordoba, Belinda; Garcia, Hugo Sergio

    2011-06-01

    The goals of this work were to assess the ability of Lactobacillus reuteri to bind aflatoxin B(1) in the intestinal tract and determine its effect on intestinal absorption of the toxin dispensed in either single or multiple doses in a murine model. Male Wistar rats were used, and two experiments were conducted after bacteria were implanted. Experiment one involved a single-oral dose of toxin, and the subsequent flow cytometric analysis of bacteria isolated from the small intestine and treated with specific FITC-labeled AFB(1) antibodies. The second experiment was carried out supplying the toxin in 7 oral sub-doses, and the later quantification of AFB(1)-Lys adducts in blood samples by ELISA assay. The results demonstrated that L. reuteri was able to bind AFB(1) in the intestinal tract, mostly in the duodenum. Furthermore, the AFB(1)-Lys adducts were present at significantly lower levels in those animals receiving AFB(1) plus bacteria than in those receiving only AFB(1). Our findings confirm that probiotic bacteria could act as biological barriers in normal intestinal conditions thereby reducing the bioavailability of AFB(1) ingested orally in a single or multiple doses, thus avoiding its toxic effects. PMID:21298677

  20. Sodium recirculation and isotonic transport in toad small intestine.

    PubMed

    Nedergaard, S; Larsen, E H; Ussing, H H

    1999-04-01

    Isolated small intestine of toad (Bufo bufo) was mounted on glass tubes for perfusion studies with oxygenated amphibian Ringer's solution containing glucose and acetate. Under open-circuit conditions (Vt = -3.9 +/- 1.8 mV, N = 14) the preparation generated a net influx of 134Cs+. The time course of unidirectional 134Cs+-fluxes was mono-exponential with similar rate constants for influx and outflux when measured in the same preparation. The flux-ratio was time invariant from the beginning of appearance of the tracers to steady state was achieved. Thus, just a single pathway, the paracellular pathway, is available for transepithelial transport of Cs+. From the ratio of unidirectional Cs+-fluxes the paracellular force was calculated to be, 18.2 +/- 1.5 mV (N = 6), which is directed against the small transepithelial potential difference. The paracellular netflux of cesium ions, therefore, is caused by solvent drag. The flux of 134Cs+ entering and trapped by the cells was of a magnitude similar to that passing the paracellular route. Therefore, independent of the convective flux of 134Cs+, every second 134Cs+ ion flowing into the lateral space was pumped into the cells rather than proceeding, via the low resistance pathway, to the serosal bath. It is thus indicated that the paracellular convective flow of 134Cs+ is driven by lateral Na+/K+-pumps. Transepithelial unidirectional 42K+ fluxes did not reach steady state within an observation period of 70 min, indicating that components of the fluxes in both directions pass the large cellular pool of potassium ions. The ratio of unidirectional 24Na+ fluxes was time-variant and declined from an initial value of 3.66 +/- 0.34 to a significantly smaller steady-state value of 2.57 +/- 0.26 (P < 0.001, N = 5 paired observations), indicating that sodium ions pass the epithelium both via the paracellular and the cellular pathway. Quantitatively, the larger ratio of paracellular Na+ fluxes, as compared to that of paracellular Cs

  1. The metabolic profile of acteoside produced by human or rat intestinal bacteria or intestinal enzyme in vitro employed UPLC-Q-TOF-MS.

    PubMed

    Cui, Qingling; Pan, Yingni; Xu, Xiaotong; Zhang, Wenjie; Wu, Xiao; Qu, Shouhe; Liu, Xiaoqiu

    2016-03-01

    Acteoside, the main and representative phenylethanoid glycosides of Herba Cistanches, possesses wide bioactivities but low oral bioavailability. It may serve as the prodrug and be converted into the active forms in gastrointestinal tract, which mainly occurred in intestinal tract composed of intestinal bacteria and intestinal enzyme. Intestinal bacteria, a new drug target, take a significant role on exerting pharmacological effects of drugs by oral administration. In this paper, acteoside was incubated with human or rat intestinal bacteria or rat intestinal enzyme for 36 h to seek metabolites responsible for pharmacodynamics. The samples were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Besides the parent compound, 14 metabolites were detected and identified based on their retention times and fragmentation patterns in their MS spectra including 8 degradation metabolites, 2 isomers in intestinal bacteria and intestinal enzyme samples and 4 parent metabolites only found in intestinal enzymes. The metabolic pathway of acteoside was thus proposed. Identification of these metabolites of acteoside by the intestinal bacteria or intestinal enzyme gave an insight to clarify pharmacological mechanism of traditional Chinese medicines and identify the real active molecules. PMID:26705842

  2. In vivo longitudinal cellular imaging of small intestine by side-view endomicroscopy

    PubMed Central

    Ahn, Jinhyo; Choe, Kibaek; Wang, Taejun; Hwang, Yoonha; Song, Eunjoo; Kim, Ki Hean; Kim, Pilhan

    2015-01-01

    Visualization of cellular dynamics in the gastrointestinal tract of living mouse model to investigate the pathophysiology has been a long-pursuing goal. Especially, for chronic disease such as Crohn’s disease, a longitudinal observation of the luminal surface of the small intestine in the single mouse is highly desirable to investigate the complex pathogenesis in sequential time points. In this work, by utilizing a micro-GRIN lens based side-view endomicroscope integrated into a video-rate confocal microscopy system, we successfully performed minimally-invasive in vivo cellular-level visualization of various fluorescent cells and microvasculature in the small intestinal villi. Also, with a transgenic mouse universally expressing photoconvertible protein, Kaede, we demonstrated repetitive cellular-level confocal endoscopic visualization of same area in the small intestinal lumen of a single mouse, which revealed the continuous homeostatic renewal of the small intestinal epithelium. PMID:26504646

  3. Gastric emptying and small intestinal transit in the piebald mouse model for Hirschsprung's disease

    SciTech Connect

    Cooke, H.J.; Pitman, K.; Starr, G.; Wood, J.D.

    1984-08-01

    Gastric emptying and small intestinal transit were investigated in the piebald mouse model for Hirschsprung's disease. These mice exhibited aganglionosis of the terminal segment of the large intestine. This condition was accompanied by fecal stasis and megacolon. Gastric emptying of saline or milk meals was slower in the mice with aganglionic or induced megacolon than in the normal mice, but the rate of emptying was faster than after administration of morphine (10 mg/kg). In the small intestine, the distribution of the radiolabeled marker and the advancing edge of the marker profile were abnormal in the mice with megacolon. There were small differences between the megacolonic and normal mice in the distance traversed by the advancing edge of the intraluminal profile of the marker. These results are evidence for disturbances of gastric and small intestinal motor function that occur in mice secondary to development of megacolon.

  4. Plasma exchange in small intestinal transplantation between ABO-incompatible individuals: A case report

    PubMed Central

    ZHANG, QIUHUI; HU, XINGBIN; XIA, AIJUN; YI, JING; AN, QUNXING; ZHANG, XIANQING

    2014-01-01

    The aim of this study was to investigate the application of plasma exchange in small intestinal transplantation between ABO blood type-incompatible patients. A small intestinal transplantation case between ABO-incompatible individuals is hereby presented and analyzed. The main treatment included plasma exchange, splenectomy and immunosuppression. The patient undergoing small intestinal transplantation exhibited stable vital signs. A mild acute rejection reaction developed ~2 weeks after the surgery, which the patient successfully overcame. The subsequent colonoscopy and pathological examination revealed no signs of acute rejection. In conclusion, plasma exchange in combination with anti-immune rejection therapy proved to be an effective scheme for the management of small intestinal transplantation between ABO-incompatible patients. PMID:24649066

  5. Effects of psychological stress on small intestinal motility and bacteria and mucosa in mice

    PubMed Central

    Wang, Shao-Xuan; Wu, Wan-Chun

    2005-01-01

    AIM: To investigate the effects of psychological stress on small intestinal motility and bacteria and mucosa in mice, and to explore the relationship between small intestinal dysfunction and small intestinal motility and bacteria and mucosa under psychological stress. METHODS: Sixty mice were randomly divided into psychological stress group and control group. Each group were subdivided into small intestinal motility group (n = 10), bacteria group (n = 10), and D-xylose administered to stomach group (n = 10). An animal model with psychological stress was established housing the mice with a hungry cat in separate layers of a two-layer cage. A semi-solid colored marker (carbon-ink) was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (Escherichia coli) and anaerobes (Lactobacilli). The quantitation of bacteria was expressed as log10(colony forming units/g). D-xylose levels in plasma were measured for estimating the damage of small intestinal mucosa. RESULTS: Small intestinal transit was inhibited (39.80±9.50% vs 58.79±11.47%, P<0.01) in mice after psychological stress, compared with the controls. Psychological stress resulted in quantitative alterations in the aerobes (E. coli). There was an increase in the number of E. coli in the proximal small intestinal flora (1.78±0.30 log10(CFU/g) vs 1.37±0.21 log10(CFU/g), P<0.01), and there was decrease in relative proportion of Lactobacilli and E. coli of stressed mice (0.53±0.63 vs 1.14±1.07, P<0.05), while there was no significant difference in the anaerobes (Lactobacilli) between the two groups (2.31±0.70 log10(CFU/g) vs 2.44±0.37 log10(CFU/g), P>0.05). D-xylose concentrations in plasma in psychological stress mice were significantly higher than those in the control group (2.90±0.89 mmol/L vs 0.97±0.33 mmol/L, P<0.01). CONCLUSION: Small intestinal dysfunction under psychological stress may be related to the

  6. Use of simulated intestinal fluids with Caco-2 cells and rat ileum.

    PubMed

    Patel, N; Forbes, B; Eskola, S; Murray, J

    2006-02-01

    In most in vitro studies of oral drug permeability, little attempt is made to reproduce the gastrointestinal lumenal environment. The aim of this study was to evaluate the compatibility of simulated intestinal fluid (SIF) solutions with Caco-2 cell monolayers and Ussing chamber-mounted rat ileum under standard permeability experiment protocols. In preliminary experiments, fasted-state simulated intestinal fluid (FaSSIF) and fed-state simulated intestinal fluid (FeSSIF) solutions based on the dissolution medium formulae of Dressman and co-workers (1998) were modified for compatibility with Caco-2 cells to produce FaS-SIF and FeSSIF "transport" solutions for use with in vitro permeability models. For Caco-2 cells exposed to FaSSIF and FESSIF transport solutions, the transepithelial electrical resistance was maintained for over 4 h and mannitol permeability was equivalent to that in control (Hank's Balanced Salt Solution-treated) cell layers. Scanning electron microscopy revealed that microvilli generally maintained a normal distribution, although some shortening of microvilli and occasional small areas of denudation were observed. For rat ileum in the Ussing chambers, the potential difference (PD) collapsed to zero over 120 min when exposed to the FaSSIF transport solution and an even faster collapse of the PD was observed when the FeSSIF transport solution was used. Electron micrographs revealed erosion of the villi tips and substantial denudation of the microvilli after exposure of ileal tissue to FaSSIF and FeSSIF solutions, and permeability to mannitol was increased by almost two-fold. This study indicated that FaSSIF and FeSSIF transport solutions can be used with Caco-2 monolayers to evaluate drug permeability, but rat ileum in Ussing chambers is adversely affected by these solutions. Metoprolol permeability in Caco-2 experiments was reduced by 33% using the FaSSIF and 75% using the FeSSIF compared to permeability measured using HBSS. This illustrates that

  7. Small bowel preservation for intestinal transplantation: a review.

    PubMed

    Roskott, Anne Margot C; Nieuwenhuijs, Vincent B; Dijkstra, Gerard; Koudstaal, Lyan G; Leuvenink, Henri G D; Ploeg, Rutger J

    2011-02-01

    Intestinal transplantation has become the therapy of choice for patients with intestinal failure and life-threatening complications from total parenteral nutrition. Results, however, remain inferior as compared with other transplant types with the quality of the organ graft as the most important factor of outcome after transplantation. The intestine is extremely sensitive to ischemia. Unfortunately, a relatively long ischemic preservation period is inevitable. The current standard in organ preservation [cold storage (CS) with University of Wisconsin solution] was developed for kidney/liver preservation and is suboptimal for the intestinal graft despite good results for other organs. This review aimed at appraising the results from the use of previously applied and recently developed preservation solutions and techniques to identify key areas for improvement. As the studies available do not reveal the most effective method for intestinal preservation, an optimal strategy will result from a synergistic effect of different vital elements identified from a review of published material from the literature. A key factor is the composition of the solution using a low-viscosity solution to facilitate washout of blood, including amino acids to improve viability, impermeants and colloids to prevent edema, and buffer for pH-homeostasis. Optimizing conditions include a vascular flush before CS and luminal preservation. The most effective composition of the luminal solution and a practical, clinically applicable optimal technique are yet to reach finality. Short-duration oxygenated arterial and/or luminal perfusion have to be considered. Thus, a tailor-made approach to luminal preservation solution and technique need further investigation in transplant models and the human setting to develop the ultimate technique meeting the physiologic demands of the intestinal graft during preservation. PMID:21083772

  8. Activation of CCR9/CCL25 in Cutaneous Melanoma Mediates Preferential Metastasis to the Small Intestine

    PubMed Central

    Amersi, Farin F.; Terando, Alicia M.; Goto, Yasufumi; Scolyer, Richard A.; Thompson, John F.; Tran, Andy N.; Faries, Mark B.; Morton, Donald L.; Hoon, Dave S.B.

    2009-01-01

    Purpose Specific chemokines and their respective receptors have been implicated in distant tumor cell metastasis. Cutaneous melanoma has a distinct pattern of metastasis, preferentially targeting the submucosa of the small intestine. However, the underlying pathogenic mechanism remains unknown. Migration of CCR9(+) lymphocytes to the small intestine is known to occur in response to the chemoattractant effects of CCL25 (thymus-expressed chemokine). The integrin heterodimers αβ are also known to be important mediators of cellular adhesion. We hypothesize that the mechanism of small intestinal metastasis by melanoma is via the CCR9-CCL25 axis and specific integrins. Experimental Design Quantitative reverse transcription-PCR, flow cytometry, and immunohistochemistry were used to assess melanoma tumors for CCR9 and CCL25. Integrin expression was assessed using flow cytometry. CCR9 expression by quantitative reverse transcription-PCR was assessed in primary (n = 23) and metastatic (n = 198) melanomas, and melanoma lines derived from small intestinal metastases (n = 23). Results We showed CCR9 expression in 88 of 102 paraffin-embedded metastatic melanomas from the small intestine, 8 of 8 melanoma lines derived from metastases in the small intestine, and 0 of 96 metastatic melanomas from other sites. In vitro migration and invasion studies done on CCR9(+) melanoma lines showed migration in response to CCL25 that was inhibited by anti-CCR9 antibody or by short interfering RNA CCR9. Flow cytometric analysis confirmed CCR9 expression by melanomas to the small intestine and showed concomitant α4β1 integrin expression. Conclusions Our findings show that functionally active CCR9 on melanoma cells facilitates metastasis to the small intestine. The CCR9-CCL25 axis may explain the high incidence of melanoma metastasis to this specific location. PMID:18245522

  9. Tissue content of mercury in rats given methylmercuric chloride orally: influence of intestinal flora

    SciTech Connect

    Rowland, I.R.; Davies, M.J.; Evans, J.G.

    1980-05-01

    The effect of intestinal flora on the absorption and disposition of mercury in tissues was investigated using conventional rats, and rats treated with antibiotics to eliminate their gut flora. Antibiotic-treated rats given (/sup 203/Hg) -labeled methylmercuric chloride orally had significantly more mercury in their tissues, especially in kidney, brain, lung, blood, and skeletal muscle, and also excreted less mercury in the feces than conventional rats. Furthermore, in the kidneys of the antibiotic-treated rats, the proportion of mercury present as organic mercury was greater than in the kidneys of the conventional rats. The results support the hypothesis that the metabolism of methylmercuric chloride by the gut flora reduces the tissue content of mercury. When rats were administered 10 mg methylmercuric chloride/Kg.day for 6 days, four or five of those given antibiotics developed neurological symptoms of toxicity, whereas only one of five conventional rats given methylmercuric chloride was affected.

  10. Prenatal Intestinal Obstruction Affects the Myenteric Plexus and Causes Functional Bowel Impairment in Fetal Rat Experimental Model of Intestinal Atresia

    PubMed Central

    Khen-Dunlop, Naziha; Sarnacki, Sabine; Victor, Anais; Grosos, Celine; Menard, Sandrine; Soret, Rodolphe; Goudin, Nicolas; Pousset, Maud; Sauvat, Frederique; Revillon, Yann; Cerf-Bensussan, Nadine; Neunlist, Michel

    2013-01-01

    Background Intestinal atresia is a rare congenital disorder with an incidence of 3/10 000 birth. About one-third of patients have severe intestinal dysfunction after surgical repair. We examined whether prenatal gastrointestinal obstruction might effect on the myenteric plexus and account for subsequent functional disorders. Methodology/Principal Findings We studied a rat model of surgically induced antenatal atresia, comparing intestinal samples from both sides of the obstruction and with healthy rat pups controls. Whole-mount preparations of the myenteric plexus were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (nNOS). Quantitative reverse transcription PCR was used to analyze mRNAs for inflammatory markers. Functional motility and permeability analyses were performed in vitro. Phenotypic studies were also performed in 8 newborns with intestinal atresia. In the experimental model, the proportion of nNOS-immunoreactive neurons was similar in proximal and distal segments (6.7±4.6% vs 5.6±4.2%, p = 0.25), but proximal segments contained a higher proportion of ChAT-immunoreactive neurons (13.2±6.2% vs 7.5±4.3%, p = 0.005). Phenotypic changes were associated with a 100-fold lower concentration-dependent contractile response to carbachol and a 1.6-fold higher EFS-induced contractile response in proximal compared to distal segments. Transcellular (p = 0.002) but not paracellular permeability was increased. Comparison with controls showed that modifications involved not only proximal but also distal segments. Phenotypic studies in human atresia confirmed the changes in ChAT expression. Conclusion Experimental atresia in fetal rat induces differential myenteric plexus phenotypical as well as functional changes (motility and permeability) between the two sides of the obstruction. Delineating these changes might help to identify markers predictive of motility dysfunction and to define guidelines for post-surgical care. PMID:23667464

  11. Ileocolonic transfer of solid chyme in small intestinal neuropathies and myopathies

    SciTech Connect

    Greydanus, M.P.; Camilleri, M.; Colemont, L.J.; Phillips, S.F.; Brown, M.L.; Thomforde, G.M. )

    1990-07-01

    The aims of this study were to assess gastric emptying, small bowel transit and colonic filling in patients with motility disorders, with particular attention to the patterns of colonic filling. Gastrointestinal transit was assessed using a previously validated radiolabeled mixed meal. Fourteen patients with clinical and manometric features of chronic intestinal pseudoobstruction classified as intestinal neuropathy and 6 as intestinal myopathy, were studied. The results were compared with those from 10 healthy controls studied similarly. Gastric emptying and small bowel transit of solids were significantly slower in both groups of patients than in healthy controls (P less than 0.05). In health, the ileocolonic transit of solid chyme was characterized by intermittent bolus transfers. The mean size of boluses transferred to the colon (expressed as a percentage of ingested radiolabel) was significantly less (P less than 0.05) in patients with intestinal myopathy (10% +/- 4% (SEM)) than in healthy controls (25% +/- 4%) or in patients with intestinal neuropathy (25% +/- 4%). The intervals between bolus transfer of solids (plateaus in the colonic filling curve) were longer (P less than 0.05) in myopathies (212 +/- 89 minutes) than in health (45 +/- 7 minutes) or neuropathies (53 +/- 11 minutes). Thus, gastric emptying and small bowel transit were delayed in small bowel neuropathies and myopathies. Bolus filling of the colon was less frequent and less effective in patients with myopathic intestinal pseudoobstruction, whereas bolus transfer was preserved in patients with neuropathic intestinal pseudoobstruction.

  12. Maturation of jejunoileal gradients in rat intestine: the role of intraluminal nutrients.

    PubMed

    Castillo, R O; Feng, J J; Stevenson, D K; Kwong, L K

    1992-01-01

    Jejunoileal gradients of intestinal function are thought to be established during the third week of life in the rat when postnatal intestinal maturation occurs. In order to investigate the normal development of jejunoileal gradients and whether either the absence of intraluminal nutrients or the form in which they are provided affected the development of jejunoileal gradients, gradients for mucosal DNA, protein, lactase and sucrase were studied in suckling rats undergoing normal weaning and compared to gradients in rats receiving no intraluminal nutrients or rats receiving nutrients in elemental form. In suckling animals, preexisting jejunoileal gradients for DNA and protein persisted through the weaning period, gradients for lactase formed by rapid decline of ileal function and sucrase gradients formed by rapid increase in jejunal activities. Intraluminal nutrients in elemental form resulted in the formation of jejunoileal gradients similar to those in intestines of normally weaned rats. The lack of intraluminal nutrients resulted in no qualitative differences in the expression of jejunoileal gradients for sucrase, but provision of elemental nutrients resulted in increased jejunoileal differences for this enzyme. The lack of intraluminal nutrients resulted in no gradients for DNA, less pronounced jejunoileal differences for protein and delayed maturational decline of ileal lactase which prevented development of jejunoileal gradients for the enzyme. These studies indicate that the formation of jejunoileal gradients in the maturing rat intestine for the parameters investigated require intraluminal nutrients regardless of the form in which they are provided for their normal expression. PMID:1467373

  13. Nitroreduction and formation of hemoglobin adducts in rats with a human intestinal microflora

    SciTech Connect

    Scheepers, P.T.J.; Straetemans, M.M.E.; Koopman, J.P.; Bos, R.P.

    1994-10-01

    In the covalent binding of nitroarenes to macromolecules, nitroreduction is an important step. The intestinal microflora represents an enormous potential of bacterial nitroreductase activity. As a consequence, the in vivo nitroreduction of orally administerednitroarenes is primarily located in the intestine. In this study, we have investigated the nitroreduction of 2-nitrofluorene (2-NF) by a human microflora in female Wistar rats. Germ-free (FG) rats were equipped with a bacterial flora derived from human feces. Nontreated GF rats and GF animals equipped with a conventional rat flora were used as controls. The composition of the human and the conventional microflora isolated from the rats were consistent with the microflora of the administered feces. In the rats receiving only sunflower seed oil, no adducts were detected. The animals equipped with a human or rat microflora that received 2-aminofluorene (2-AF) formed 2-AF hemoglobin (Hb)-adducts at average levels mean {+-} 0.003 and 0.043 {+-} 0.010 {mu}mole/g Hb, respectively. In the FG rats, an adduct level of 0.57 {+-} 0.09 was determined after 2-AF administration and non adducts were detected after 2-NF administration. The results show that nitroreduction by an acquired human intestinal microflora and subsequent adduct formation can be studied in the rate in vivo. 21 refs., 3 tabs.

  14. Parenteral Nutrition Suppresses the Bactericidal Response of the Small Intestine

    PubMed Central

    Omata, Jiro; Pierre, Joseph F; Heneghan, Aaron F; Tsao, Francis HC; Sano, Yoshifumi; Jonker, Mark A; Kudsk, Kenneth A

    2012-01-01

    Background Parenteral nutrition (PN) increases infectious risk in critically ill patients compared with enteral feeding. Previously, we demonstrated that PN feeding suppresses the concentration of the Paneth cell antimicrobial protein secretory phospholipase A2 (sPLA2) in the gut lumen. sPLA2 and other Paneth cell proteins are released in response to bacterial components, such as lipopolysaccharide (LPS), and they modulate the intestinal microbiome. Since the Paneth cell protein sPLA2 was suppressed with PN feeding, we hypothesized PN would diminish the responsiveness of the small bowel to LPS through reduced secretions and as a result exhibit less bactericidal activity. Methods The distal ileum was harvested from ICR mice, washed, and randomized for incubation with LPS (0, 1, or 10 μg/mL). Culture supernatant was collected and sPLA2 Activity was measured. Bactericidal activity of the ileum segment secretions was assessed against P. aeruginosa with and without a sPLA2 inhibitor at two concentrations, 100nM and 1μM. ICR mice were randomized to Chow or PN for 5 days. Tissue was collected for immunohistochemistry (IHC) and ileal segments were incubated with LPS (0 or 10 μg/mL). sPLA2 activity and bactericidal activity were measured in secretions from ileal segments. Results The ileal segments responded to 10 ug/mL LPS with significantly greater sPLA2 activity and bactericidal activity. The bactericidal activity of secretions from LPS stimulated tissue was suppressed 50% and 70%, respectively, with the addition of the sPLA2-inhibitor. Chow displayed greater sPLA2 in the Paneth cell granules and secreted higher levels of sPLA2 than PN before and after LPS. Accordingly, media collected from Chow was more bactericidal than PN. IHC confirmed a reduction in Paneth cell granules after PN. Conclusions This work demonstrates that ileal segments secrete bactericidal secretions after LPS exposure and the inhibition of the Paneth cell antimicrobial protein sPLA2 significantly

  15. [A Case of Small Intestinal Metastases from Renal Cell Carcinoma with Massive Bleeding].

    PubMed

    Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Ohtani, Hiroshi; Sakurai, Katsunobu; Yamazoe, Sadaaki; Kimura, Kenjiro; Toyokawa, Takahiro; Amano, Ryosuke; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Ohira, Masaichi; Ohsawa, Masahiko; Hirakawa, Kosei

    2015-11-01

    A 66-year-old man underwent laparoscopic right nephrectomy for renal cell carcinoma (T2b, N0, M1, clear cell, Grade 3). He was treated with targeted therapy for lung metastases after nephrectomy. Despite the targeted therapy, he was paralyzed in the lower half of the body due to the spinal metastases. Therefore, an osteoplastic laminectomy and domelaminectomy for the spinal metastases was performed. The FDG-PET examination, which was performed after the operation, revealed lung, liver, bone, and small intestinal metastases. After a while, he suffered from continuous massive melena. Double balloon enteroscopy revealed a hemorrhagic tumor in the small intestine, and an emergency operation was performed. A partial resection of the small intestine was performed for the 3 tumors. The histopathological diagnosis was small intestinal metastasis from renal cell carcinoma. It is well known that renal cell carcinoma often develops metastases to the lung, bone, and liver. However, small intestinal metastasis from renal cell carcinoma is rare. Although small intestinal metastasis from renal cell carcinoma often accompanies metastases to other organs, a palliative operation might improve the quality of life in patients with symptomatic tumors. PMID:26805327

  16. Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy

    PubMed Central

    Park, Sang Won; Chen, Sean W.C.; Kim, Mihwa; Brown, Kevin M.; Kolls, Jay K.; D’Agati, Vivette D.; Lee, H. Thomas

    2010-01-01

    Patients with acute kidney injury (AKI) frequently suffer from extra-renal complications including hepatic dysfunction and systemic inflammation. We aimed to determine the mechanisms of AKI induced hepatic dysfunction and systemic inflammation. Mice subjected to AKI [renal ischemia reperfusion (IR) or nephrectomy] rapidly developed acute hepatic dysfunction and suffered significantly worse hepatic IR injury. After AKI, rapid peri-portal hepatocyte necrosis, vacuolization, neutrophil infiltration and pro-inflammatory mRNA upregulation were observed suggesting an intestinal source of hepatic injury. Small intestine histology after AKI demonstrated profound villous lacteal capillary endothelial apoptosis, disruption of vascular permeability and epithelial necrosis. After ischemic or non-ischemic AKI, plasma TNF-α, IL-17A and IL-6 increased significantly. Small intestine appears to be the source of IL-17A as IL-17A levels were higher in the portal circulation and small intestine compared to the levels measured from the systemic circulation and liver. Wild type mice treated with neutralizing antibodies against TNF-α, IL-17A or IL-6 or mice deficient in TNF-α, IL-17A, IL-17A receptor or IL-6 were protected against hepatic and small intestine injury due to ischemic or non-ischemic AKI. For the first time, we implicate the increased release of IL-17A from small intestine together with induction of TNF-α and IL-6 as a cause of small intestine and liver injury after ischemic or non-ischemic AKI. Modulation of the inflammatory response and cytokine release in the small intestine after AKI may have important therapeutic implications in reducing complications arising from AKI. PMID:20697374

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

    PubMed

    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. PMID:9018501

  18. Rifaximin Alters Intestinal Bacteria and Prevents Stress-Induced Gut Inflammation and Visceral Hyperalgesia in Rats

    PubMed Central

    Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y.; Owyang, Chung

    2014-01-01

    Background & Aims Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. Methods We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction and 454 pyrosequencing were used to analyze bacterial 16S rRNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Results Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Conclusions Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. PMID:24161699

  19. Intestinal leiomyoma

    MedlinePlus

    Leiomyoma - intestine ... McLaughlin P, Maher MM. The duodenum and small intestine. In: Adam A, Dixon AK, Gillard JH, Schaefer- ... Roline CE, Reardon RF. Disorders of the small intestine. In: Marx JA, Hockberger RS, Walls RM, et ...

  20. Role of GATA factors in development, differentiation, and homeostasis of the small intestinal epithelium

    PubMed Central

    Aronson, Boaz E.; Stapleton, Kelly A.

    2014-01-01

    The small intestinal epithelium develops from embryonic endoderm into a highly specialized layer of cells perfectly suited for the digestion and absorption of nutrients. The development, differentiation, and regeneration of the small intestinal epithelium require complex gene regulatory networks involving multiple context-specific transcription factors. The evolutionarily conserved GATA family of transcription factors, well known for its role in hematopoiesis, is essential for the development of endoderm during embryogenesis and the renewal of the differentiated epithelium in the mature gut. We review the role of GATA factors in the evolution and development of endoderm and summarize our current understanding of the function of GATA factors in the mature small intestine. We offer perspective on the application of epigenetics approaches to define the mechanisms underlying context-specific GATA gene regulation during intestinal development. PMID:24436352

  1. Peutz-Jeghers syndrome with small intestinal malignancy and cervical carcinoma

    PubMed Central

    Li, Lian-Jie; Wang, Zhi-Qing; Wu, Bao-Ping

    2008-01-01

    We report a case of 30-year-old woman with Peutz-Jeghers syndrome (PJS). Because of small intestinal obstruction, she received the small intestinal polypectomy in 2001, and the pathological diagnosis was Peutz-Jeghers polyp canceration (mucinous adenocarcinoma, infiltrating full-thickness of the intestine). The patient did not feel uncomfortable after 6 mo of chemotherapy and other management. We kept a follow-up study on her and found that she suffered from cervical cancer in 2007, with a pathological diagnosis of cervical adenosquamous carcinoma.The patient presented with typical features of PJS, but without a family history. The PJS accompanied with both small intestinal and cervical malignancies has not been reported so far in the world. PMID:19109876

  2. Chronic nifedipine dosing enhances cephalexin bioavailability and intestinal absorption in conscious rats.

    PubMed

    Berlioz, F; Lepére-Prevot, B; Julien, S; Tsocas, A; Carbon, C; Rozé, C; Farinotti, R

    2000-11-01

    Cephalexin, a beta-lactam antibiotic, is rapidly absorbed via the di-and tripeptide intestinal transporters, as for many peptidomimetic drugs. Acute nifedipine has been shown to increase intestinal absorption of several beta-lactams: amoxicillin and cefixime in humans, and cephalexin in the rat. We showed previously that the nervous system was involved in the increasing effect of nifedipine on cephalexin intestinal absorption in anesthetized rats. The aim of the present study was 2-fold: 1) to investigate whether the effect of nifedipine is maintained in conscious rats, and 2) to determine whether the nifedipine effect will persist during chronic nifedipine administration. Acute and chronic oral administration of nifedipine significantly increased oral cephalexin area under the plasma concentration-time curve (34 and 25%, respectively) and maximum concentration in plasma (57 and 51%, respectively), while the distribution and elimination parameters of intra-arterial cephalexin were not affected by acute or chronic nifedipine administration. In conclusion, acute nifedipine effect on intestinal absorption of cephalexin is independent of anesthesia in rats. Since nifedipine could still enhance cephalexin intestinal absorption after a 7-day b.i.d. treatment, it can be envisaged to apply this effect to increase bioavailability of poorly absorbed peptidomimetic drugs in man. PMID:11038150

  3. Titanium dioxide induced inflammation in the small intestine

    PubMed Central

    Nogueira, Carolina Maciel; de Azevedo, Walter Mendes; Dagli, Maria Lucia Zaidan; Toma, Sérgio Hiroshi; Leite, André Zonetti de Arruda; Lordello, Maria Laura; Nishitokukado, Iêda; Ortiz-Agostinho, Carmen Lúcia; Duarte, Maria Irma Seixas; Ferreira, Marcelo Alves; Sipahi, Aytan Miranda

    2012-01-01

    AIM: To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO2) and microparticles (MPTiO2) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO2 (100 mg/kg body weight) as NPTiO2 (66 nm), or MPTiO2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4+ and CD8+ T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immunohistochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4+ cells (cells/mm2) in duodenum: NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum: NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum: NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE): IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99 ± 019 (P < 0.05); IFNγ: NP 15.85 ± 9

  4. [Study on intestinal absorption of formononetin in Millettia nitita var. hirsutissima in rats].

    PubMed

    Liu, Ya-Li; Xiong, Xian-Bing; Su, Dan; Song, Yong-Gui; Zhang, Ling; Yang, Shi-Lin

    2013-10-01

    To use the single-pass intestine perfusion (SPIP) model and HPLC to determine the concentration of formononetin, the effect of quality concentrations of formononetin, different intestinal segments and P-glycoprotein inhibitor on intestinal absorption of formononetin, in order to observe the intestinal absorption mechanism of formononetin from Millettia nitita var. hirsutissima in rats. The experimental results showed that the qulaity concentration of formononetin in the perfusate had no significant effect on the absorption rate constant (K(a)) and the apparent absorption coefficient (P(app)); K(a) and P(app) of formononetin in duodenum, jejunum and ileum showed no significant difference. However, K(a) was significantly higher than that in colon (P < 0.05), with significant difference between that in intestinum tenue and colon. P-glycoprotein inhibitor verapamil showed significant difference in K(a) and P(app) in intestinal segments (P < 0.05). This indicated that the absorption mechanism of formononein in rat intestinal tracts passive diffusion, without any saturated absorption. Formononein is absorbed well in all intestines. Their absorption windows were mainly concentrated in the intestinum tenue, without specific absorption sites. Formononein may be the substrate of P-glycoprotein. PMID:24490575

  5. Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid.

    PubMed

    Navab, Mohamad; Hough, Greg; Buga, Georgette M; Su, Feng; Wagner, Alan C; Meriwether, David; Chattopadhyay, Arnab; Gao, Feng; Grijalva, Victor; Danciger, Janet S; Van Lenten, Brian J; Org, Elin; Lusis, Aldons J; Pan, Calvin; Anantharamaiah, G M; Farias-Eisner, Robin; Smyth, Susan S; Reddy, Srinivasa T; Fogelman, Alan M

    2013-12-01

    We recently reported that levels of unsaturated lysophosphatidic acid (LPA) in the small intestine significantly correlated with the extent of aortic atherosclerosis in LDL receptor-null (LDLR⁻/⁻) mice fed a Western diet (WD). Here we demonstrate that WD increases unsaturated (but not saturated) LPA levels in the small intestine of LDLR⁻/⁻ mice and causes changes in small intestine gene expression. Confirmation of microarray analysis by quantitative RT-PCR showed that adding transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F) to WD prevented many WD-mediated small intestine changes in gene expression. If instead of feeding WD, unsaturated LPA was added to chow and fed to the mice: i) levels of LPA in the small intestine were similar to those induced by feeding WD; ii) gene expression changes in the small intestine mimicked WD-mediated changes; and iii) changes in plasma serum amyloid A, total cholesterol, triglycerides, HDL-cholesterol levels, and the fast-performance liquid chromatography lipoprotein profile mimicked WD-mediated changes. Adding Tg6F (but not control tomatoes) to LPA-supplemented chow prevented the LPA-induced changes. We conclude that: i) WD-mediated systemic inflammation and dyslipidemia may be in part due to WD-induced increases in small intestine LPA levels; and ii) Tg6F reduces WD-mediated systemic inflammation and dyslipidemia by preventing WD-induced increases in LPA levels in the small intestine. PMID:24085744

  6. Intestinal elimination of ofloxacin enantiomers in the rat: evidence of a carrier-mediated process.

    PubMed Central

    Rabbaa, L; Dautrey, S; Colas-Linhart, N; Carbon, C; Farinotti, R

    1996-01-01

    The aim of this work was to examine the mechanism involved in intestinal elimination of the two optical isomers of ofloxacin in the rat. An intestinal segment was isolated in situ and perfused with saline, while drug solution was administered via the carotid artery. Blood samples and intestinal effluents were collected and analyzed by a high-performance liquid chromatography method. We observed saturable and stereoselective intestinal elimination of the ofloxacin enantiomers. The elimination process favored the R-(+) form of the molecule. After a parenteral dose of 20 mg of racemic ofloxacin per kg of body weight, intestinal clearances were 0.23 +/- 0.03 versus 0.30 +/- 0.03 ml/min for S-(-)- and R-(+)-ofloxacin, respectively. Ciprofloxacin and pefloxacin interfered with ofloxacin elimination and significantly reduced the intestinal clearance of S-(-)- and R-(+)-ofloxacin. With concomitant ciprofloxacin, intestinal clearances became 0.13 +/- 0.02 versus 0.17 +/- 0.03 ml/min and 0.14 +/- 0.01 versus 0.19 +/- 0.05 ml/min with pefloxacin for S-(-)- and R-(+)-ofloxacin, respectively. Those findings argue for the presence of a common transport system in the rat intestine with variable affinities for fluoroquinolones. In addition, verapamil and quinidine, two P-glycoprotein blockers, significantly reduced the intestinal elimination of both ofloxacin isomers (with concomitant verapamil, intestinal clearances were 0.12 +/- 0.02 versus 0.18 +/- 0.03 ml/min for S-(-)- and R-(+)-ofloxacin, respectively, while with concomitant quinidine, values were 0.18 +/- 0.01 versus 0.23 +/- 0.01 ml/min without modifying their areas under the concentration-time curve in serum. Similar results were found with another fluoroquinolone, ciprofloxacin, in previous work. P-glycoprotein appears to be involved in the intestinal elimination of fluoroquinolones in rats. The characterization of fluoroquinolone intestinal elimination has significant clinical relevance for the better evaluation of the

  7. Bacterial Overgrowth in the Cystic Fibrosis Transmembrane Conductance Regulator Null Mouse Small Intestine

    PubMed Central

    Norkina, Oxana; Burnett, Tim G.; De Lisle, Robert C.

    2004-01-01

    We recently reported the inflammation of the cystic fibrosis (CF) mouse small intestine, and we hypothesized bacterial overgrowth as a possible cause. Quantitative PCR of bacterial 16S genomic DNA in the CF mouse small intestine revealed an increase of greater than 40-fold compared to controls. Sequencing of 16S PCR products and Gram staining showed that the majority of bacteria in the CF mouse intestine were gram negative. Bacteria were observed to colonize the mucus that accumulates in the intestinal lumen of mice with CF. Impaired Paneth cell defenses were suggested by observation of partially dispersed Paneth granules in the mucus plugs of CF mouse intestinal crypts, and this mucus was strongly immunoreactive for Paneth cell bactericidal products. The role of bacterial overgrowth in intestinal inflammation in CF was tested by treating mice with oral antibiotics (ciprofloxacin and metronidazole) for 3 weeks, which reduced bacterial load in the CF mouse small intestine over 400-fold. Antibiotic treatment decreased the expression of the inflammation-related genes mast cell protease 2, leucine-rich α2 glycoprotein/leucine-rich high endothelial venule glycoprotein, suppressor of cytokine signaling 3, hematopoietic cell transcript 1, and resistin-like molecule β/found in inflammatory zone 2, all of which were no longer expressed at levels significantly different from control levels. The reduction of intestinal bacteria also significantly improved the growth of CF mice but had no effect on the growth of wild-type mice. These data suggest that bacterial overgrowth in the CF mouse small intestine has a role in inflammation and contributes to the failure to thrive in this mouse model of CF. PMID:15385508

  8. Rat milk and dietary long arginine3 insulin-like growth factor I promote intestinal growth of newborn rat pups.

    PubMed

    Staley, M D; Gibson, C A; Herbein, J F; Grosvenor, C E; Baumrucker, C R

    1998-10-01

    Newborn rat pups were artificially reared by the pup in cup (PIC) method to determine whether dietary long arginine3 IGF-I (long R3 IGF-I), an IGF-I analog with high receptor affinity and low IGF binding protein (IGFBP) affinity, had efficacy on intestinal growth. IGF effects are mediated by IGFBP and receptor interactions, hence dietary-induced changes in intestinal IGF-II receptor patterns and IGFBP-3 message levels were investigated. Intestinal micrographs of pups fed rat milk replacer (RMR) for 3 d showed flattened villi with low cell counts and appeared similar to newborn intestines. Mother-fed (MF) controls and long R3 IGF-I-fed pups showed increased villi height and cell counts when compared with RMR pups, with long R3 IGF-I fed pups showing the greatest increase. At birth IGF-II-specific binding was not uniform in the intestine; specific binding was higher in the proximal intestinal section than in the distal intestinal section. However, after 3 d of MF treatment, specific binding had reversed and the distal section showed higher IGF-II-specific binding. Three days of RMR feeding did not change IGF-II-specific binding from that of the newborn pup. An IGFBP-3 message was identified in intestinal epithelium by in situ hybridization. Northern analysis of IGFBP-3 message showed a decline over time, but the change was not influenced by dietary treatments. In summary, milk-borne growth factors have the potential to affect intestinal growth within 3 d of treatment. PMID:9773839

  9. Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

    PubMed

    Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-02-29

    In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium. PMID:26707414

  10. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine

    PubMed Central

    Koestler, Benjamin J; Waters, Christopher M

    2014-01-01

    The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intracellular c-di-GMP to promote biofilm formation. We have also shown that this bile-mediated increase of intracellular c-di-GMP is negated by bicarbonate, and that this interaction is dependent on pH, suggesting that V. cholerae uses these 2 environmental cues to sense and adapt to its relative location in the small intestine. Increased intracellular c-di-GMP by bile is attributed to increased c-di-GMP synthesis by 3 diguanylate cyclases (DGCs) and decreased expression of one phosphodiesterase (PDE) in the presence of bile. The molecular mechanisms by which bile controls the activity of the 3 DGCs and the regulators of bile-mediated transcriptional repression of the PDE are not yet known. Moreover, the impact of varying concentrations of bile and bicarbonate at different locations within the small intestine and the response of V. cholerae to these cues remains unclear. The native microbiome and pharmaceuticals, such as omeprazole, can impact bile and pH within the small intestine, suggesting these are potential unappreciated factors that may alter V. cholerae pathogenesis. PMID:25621620

  11. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine.

    PubMed

    Koestler, Benjamin J; Waters, Christopher M

    2014-01-01

    The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intracellular c-di-GMP to promote biofilm formation. We have also shown that this bile-mediated increase of intracellular c-di-GMP is negated by bicarbonate, and that this interaction is dependent on pH, suggesting that V. cholerae uses these 2 environmental cues to sense and adapt to its relative location in the small intestine. Increased intracellular c-di-GMP by bile is attributed to increased c-di-GMP synthesis by 3 diguanylate cyclases (DGCs) and decreased expression of one phosphodiesterase (PDE) in the presence of bile. The molecular mechanisms by which bile controls the activity of the 3 DGCs and the regulators of bile-mediated transcriptional repression of the PDE are not yet known. Moreover, the impact of varying concentrations of bile and bicarbonate at different locations within the small intestine and the response of V. cholerae to these cues remains unclear. The native microbiome and pharmaceuticals, such as omeprazole, can impact bile and pH within the small intestine, suggesting these are potential unappreciated factors that may alter V. cholerae pathogenesis. PMID:25621620

  12. Role of iron in the intestinal uptake of cadmium in the newborn rat

    SciTech Connect

    Leon, L.

    1983-01-01

    There is evidence that suckling rats have a greater capacity for intestinal transport of heavy metals than do mature animals. It has been suggested that iron transport mechanisms provide a way for non-essential metals like Cd to be absorbed. The effect of iron on intestinal uptake of cadmium (/sup 109/Cd) was investigated in suckling (14 day old), adolescent (28 day old) and young adult rats (42 day old) using an in situ incubation technique. In the presence of 0.4 and 2.0 mM Fe SO/sub 4/, intestinal uptake of Cd was significantly decreased in 14 day old pups. When dams and pups were placed on an iron deficient diet (ID) tissue iron levels decreased in 28 and 42 day old rats but not in 14 day old rats. The results of the present studies suggest that intestinal cadmium transport in the suckling, adolescent and young adult rat is mediated, at least in part, by iron transport pathways.

  13. Subcloning, localization, and expression of the rat intestinal sodium-hydrogen exchanger isoform 8.

    PubMed

    Xu, Hua; Chen, Rongji; Ghishan, Fayez K

    2005-07-01

    Apically expressed intestinal and renal sodium-hydrogen exchangers (NHEs) play a major role in Na(+) absorption. Our previous studies on NHE ontogeny have shown that NHE-2 and NHE-3 are expressed at very low levels in young animals. Furthermore, single and/or double NHE-2 and NHE-3 knockout mice display no obvious abnormalities before weaning. These observations suggest that other transporter(s) may be involved in intestinal Na+ absorption during early life. The present studies were designed to clone the novel rat intestinal NHE-8 cDNA and to decipher the NHE-8 protein localization and gene expression pattern during different developmental stages. The rat NHE-8 cDNA has 2,160 bp and encodes a 575-amino acid protein. An antibody against NHE-8 protein was developed. Immunohistochemistry staining indicated apical localization of NHE-8 protein in rat intestinal epithelial cells. The apical localization of NHE-8 was also confirmed by its presence in brush-border membrane and its absence in basolateral membrane preparations. Northern blotting utilizing a NHE-8-specific probe demonstrated higher NHE-8 mRNA expression in young animals compared with adult animals. Western blot analysis revealed a similar pattern. Tissue distribution with multiple human tissue RNA blot showed that NHE-8 was expressed in multiple tissues including the gastrointestinal tract. In conclusion, we have cloned the full-length NHE-8 cDNA from rat intestine and further showed its apical localization in intestinal epithelial cells. We have also shown that NHE-8 gene expression and protein expression were regulated during ontogeny. Our data suggests that NHE-8 may play an important role in intestinal Na+ absorption during early life. PMID:15731506

  14. Effects of Clostridium perfringens Beta-Toxin on the Rabbit Small Intestine and Colon▿

    PubMed Central

    Vidal, Jorge E.; McClane, Bruce A.; Saputo, Juliann; Parker, Jaquelyn; Uzal, Francisco A.

    2008-01-01

    Clostridium perfringens type B and type C isolates, which produce beta-toxin (CPB), cause fatal diseases originating in the intestines of humans or livestock. Our previous studies demonstrated that CPB is necessary for type C isolate CN3685 to cause bloody necrotic enteritis in a rabbit ileal loop model and also showed that purified CPB, in the presence of trypsin inhibitor (TI), can reproduce type C pathology in rabbit ileal loops. We report here a more complete characterization of the effects of purified CPB in the rabbit small and large intestines. One microgram of purified CPB, in the presence of TI, was found to be sufficient to cause significant accumulation of hemorrhagic luminal fluid in duodenal, jejunal, or ileal loops treated for 6 h with purified CPB, while no damage was observed in corresponding loops receiving CPB (no TI) or TI alone. In contrast to the CPB sensitivity of the small intestine, the colon was not affected by 6 h of treatment with even 90 μg of purified CPB whether or not TI was present. Time course studies showed that purified CPB begins to induce small intestinal damage within 1 h, at which time the duodenum is less damaged than the jejunum or ileum. These observations help to explain why type B and C infections primarily involve the small intestine, establish CPB as a very potent and fast-acting toxin in the small intestines, and confirm a key role for intestinal trypsin as an innate intestinal defense mechanism against CPB-producing C. perfringens isolates. PMID:18625730

  15. Laminin α5 influences the architecture of the mouse small intestinal mucosa

    PubMed Central

    Mahoney, Zhen X.; Stappenbeck, Thaddeus S.; Miner, Jeffrey H.

    2008-01-01

    Summary The mammalian intestine displays two distinct patterns of mucosal organization. The small intestine contains mucosal epithelial invaginations called crypts of Lieberkühn that are continuous with evaginations into the lumen called villi. The colon also contains crypts, but its epithelial surface is lined by flat surface cuffs. The epithelial cells of both organs communicate with the underlying mesenchyme through a basement membrane that is composed of a variety of extracellular matrix proteins, including members of the laminin family. The basement membranes of the small intestine and colon contain distinct laminin subtypes; notably, the villus basement membrane is rich in laminin α5. Here we show that diminution of laminin α5 in a mouse model led to a compensatory deposition of colonic laminins that resulted in a transformation from a small intestinal to a colonic mucosal architecture. The alteration in mucosal architecture was associated with reduced levels of nuclear p27Kip1, a cell cycle regulator, and altered intestinal epithelial cell proliferation, migration, and differentiation. Our results suggest that laminin α5 plays a crucial role in establishing and maintaining the specific mucosal pattern of the mouse small intestine. PMID:18628307

  16. Studies on rat intestinal epithelial cell receptors for serotonin and opiates.

    PubMed Central

    Gaginella, T S; Rimele, T J; Wietecha, M

    1983-01-01

    We have employed the receptor-ligand binding technique in an attempt to determine if specific binding sites (receptors) for serotonin and opiates are present on rat intestinal epithelial cell membranes. A wide variety of ligands for serotonin and opiate receptors bound to specific receptor sites in rat brain. However, the same ligands failed to bind in a specific (receptor-related) manner to isolated membranes of rat ileal and colonic cells. Additional washing of the tissue pellet (to remove soluble peptidases), pretreatment with p-chlorophenylalanine (to deplete endogenous serotonin), alteration of sodium concentration (to antagonize the effects of putative endogenous inhibitors of opiate ligand binding), changes in incubation time, temperature, tissue protein and tritiated ligand concentration failed to yield meaningful results with the enterocyte membranes. We conclude that, as assessed under the present conditions, serotonergic and opiate receptors are not present or are not accessible on rat intestinal epithelial cell membranes. PMID:6308215

  17. Comparison of human liver and small intestinal glutathione S-transferase-catalyzed busulfan conjugation in vitro.

    PubMed

    Gibbs, J P; Yang, J S; Slattery, J T

    1998-01-01

    The apparent oral clearance of busulfan has been observed to vary as much as 10-fold in the population of children and adults receiving high-dose busulfan. The only identified elimination pathway for busulfan involves glutathione conjugation. The reaction is predominantly catalyzed by glutathione S-transferase (GST) A1-1, which is present in both liver and intestine. The purpose of this study was to compare busulfan Vmax/Km in cytosol prepared from adult human liver and small intestine. Tetrahydrothiophenium ion formation rate per milligram of cytosolic protein was constant along the length (assessed in 30-cm segments) of three individual small intestines. A 30-cm-long intestinal segment 90-180 cm from the pylorus was chosen to be representative of intestinal cytosolic busulfan conjugating activity. Busulfan Vmax/Km (mean +/- SD) in cytosol prepared from 23 livers and 12 small intestines was 0.166 +/- 0.066 and 0.176 +/- 0.085 microl/min/mg cytosolic protein, respectively, in incubations with 5 microM busulfan, 1 mM glutathione, and 2 mg of cytosolic protein. The relative content of GSTalpha (A1-1, A1-2, and A2-2) was compared for human liver and intestinal cytosol using Western blot. The levels of GSTalpha in liver and intestinal cytosol were 1.12 +/- 0.56 and 1.36 +/- 0.32 integrated optimal density units/5 microg cytosolic protein, respectively. Busulfan conjugation in vitro was comparable per milligram of cytosolic protein in liver and intestinal cytosol. PMID:9443852

  18. Characteristic and Functional Analysis of a Newly Established Porcine Small Intestinal Epithelial Cell Line

    PubMed Central

    Wang, Jing; Hu, Guangdong; Lin, Zhi; He, Lei; Xu, Lei; Zhang, Yanming

    2014-01-01

    The mucosal surface of intestine is continuously exposed to both potential pathogens and beneficial commensal microorganisms. Recent findings suggest that intestinal epithelial cells, which once considered as a simple physical barrier, are a crucial cell lineage necessary for maintaining intestinal immune homeostasis. Therefore, establishing a stable and reliable intestinal epithelial cell line for future research on the mucosal immune system is necessary. In the present study, we established a porcine intestinal epithelial cell line (ZYM-SIEC02) by introducing the human telomerase reverse transcriptase (hTERT) gene into small intestinal epithelial cells derived from a neonatal, unsuckled piglet. Morphological analysis revealed a homogeneous cobblestone-like morphology of the epithelial cell sheets. Ultrastructural indicated the presence of microvilli, tight junctions, and a glandular configuration typical of the small intestine. Furthermore, ZYM-SIEC02 cells expressed epithelial cell-specific markers including cytokeratin 18, pan-cytokeratin, sucrase-isomaltase, E-cadherin and ZO-1. Immortalized ZYM-SIEC02 cells remained diploid and were not transformed. In addition, we also examined the host cell response to Salmonella and LPS and verified the enhanced expression of mRNAs encoding IL-8 and TNF-α by infection with Salmonella enterica serovars Typhimurium (S. Typhimurium). Results showed that IL-8 protein expression were upregulated following Salmonella invasion. TLR4, TLR6 and IL-6 mRNA expression were upregulated following stimulation with LPS, ZYM-SIEC02 cells were hyporeponsive to LPS with respect to IL-8 mRNA expression and secretion. TNFα mRNA levels were significantly decreased after LPS stimulation and TNF-α secretion were not detected challenged with S. Typhimurium neither nor LPS. Taken together, these findings demonstrate that ZYM-SIEC02 cells retained the morphological and functional characteristics typical of primary swine intestinal epithelial

  19. Effects of mosapride on motility of the small intestine and caecum in normal horses after jejunocaecostomy.

    PubMed

    Okamura, Kouichi; Sasaki, Naoki; Kikuchi, Takuya; Murata, Aya; Lee, Inhyung; Yamada, Haruo; Inokuma, Hisashi

    2009-06-01

    The purpose of the present study was to evaluate the prokinetic effects of mosapride with non-invasive assessment of myoelectrical activity in the small intestine and caecum of healthy horses after jejunocaecostomy. Six horses underwent celiotomy and jejunocaecostomy, and were treated with mosapride (treated group) at 1.5 mg/kg per osos once daily for 5 days after surgery. The other six horses did not receive treatment and were used as controls (non-treated group). The electrointestinography (EIG) maximum amplitude was used to measure intestinal motility. Motility significantly decreased following surgery. In the treated group, the EIG maximum amplitude of the small intestine was significantly higher than in the controls from day 6 approximately 31 after treatment. These findings clearly indicate that mosapride could overcome the decline of intestinal motility after jejunocaecostomy in normal horses. PMID:19461212

  20. Effects of mosapride on motility of the small intestine and caecum in normal horses after jejunocaecostomy

    PubMed Central

    Okamura, Kouichi; Kikuchi, Takuya; Murata, Aya; Lee, Inhyung; Yamada, Haruo; Inokuma, Hisashi

    2009-01-01

    The purpose of the present study was to evaluate the prokinetic effects of mosapride with non-invasive assessment of myoelectrical activity in the small intestine and caecum of healthy horses after jejunocaecostomy. Six horses underwent celiotomy and jejunocaecostomy, and were treated with mosapride (treated group) at 1.5 mg/kg per osos once daily for 5 days after surgery. The other six horses did not receive treatment and were used as controls (non-treated group). The electrointestinography (EIG) maximum amplitude was used to measure intestinal motility. Motility significantly decreased following surgery. In the treated group, the EIG maximum amplitude of the small intestine was significantly higher than in the controls from day 6~31 after treatment. These findings clearly indicate that mosapride could overcome the decline of intestinal motility after jejunocaecostomy in normal horses. PMID:19461212

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

    SciTech Connect

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

    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.

  2. Self-Microemulsifying Drug Delivery System: Formulation and Study Intestinal Permeability of Ibuprofen in Rats

    PubMed Central

    Subudhi, Bharat Bhushan; Mandal, Surjyanarayan

    2013-01-01

    The study was aimed at developing a self-microemulsifying drug delivery system (SMEDDS) of Ibuprofen for investigating its intestinal transport behavior using the single-pass intestinal perfusion (SPIP) method in rat. Methods. Ibuprofen loaded SMEDDS (ISMEDDS) was developed and was characterized. The permeability behavior of Ibuprofen over three different concentrations (20, 30, and 40 µg/mL) was studied in each isolated region of rat intestine by SPIP method at a flow rate of 0.2 mL/min. The human intestinal permeability was predicted using the Lawrence compartment absorption and transit (CAT) model since effective permeability coefficients (Peff) values for rat are highly correlated with those of human, and comparative intestinal permeability of Ibuprofen was carried out with plain drug suspension (PDS) and marketed formulation (MF). Results. The developed ISMEDDS was stable, emulsified upon mild agitation with 44.4 nm ± 2.13 and 98.86% ± 1.21 as globule size and drug content, respectively. Higher Peff in colon with no significant Peff difference in jejunum, duodenum, and ileum was observed. The estimated human absorption of Ibuprofen for the SMEDDS was higher than that for PDS and MF (P < 0.01). Conclusion. Developed ISMEDDS would possibly be advantageous in terms of minimized side effect, increased bioavailability, and hence the patient compliance. PMID:26555973

  3. Localization of NK1 receptors and roles of substance-P in subepithelial fibroblasts of rat intestinal villi.

    PubMed

    Furuya, Sonoko; Furuya, Kishio; Shigemoto, Ryuichi; Sokabe, Masahiro

    2010-11-01

    Subepithelial fibroblasts of the intestinal villi, which form a contractile cellular network beneath the epithelium, are in close contact with epithelial cells, nerve varicosities, capillaries, smooth muscles and immune cells, and secrete extracellular matrix molecules, growth factors and cytokines, etc. Cultured subepithelial fibroblasts of the rat duodenal villi display various receptors such as endothelins, ATP, substance-P and bradykinin, and release ATP in response to mechanical stimulation. In this study, the presence of functional NK1 receptors (NK1R) was pharmacologically confirmed in primary culture by Ca(2+) measurement, and the effects of substance-P were measured in an acute preparation of epithelium-free duodenal villi from 2- to 3-week-old rats using a two-photon laser microscope. Substance-P elicited an increase in the intracellular Ca(2+) concentration and contraction of the subepithelial fibroblasts in culture and the isolated villi. The localization of NK1R and substance-P in the villi was examined by light and electron microscopic immunohistochemistry. NK1R-like immunoreactivity was intensely localized on the plasma membrane of villous subepithelial fibroblasts in 10-day- to 4-week-old rats and mice and was decreased or absent in adulthood. The pericryptal fibroblasts of the small and large intestine were NK1R immuno-negative. These villous subepithelial fibroblasts form synapse-like structures with both substance-P-immunopositive and -immunonegative nerve varicosities. Here, we propose that the mutual interaction between villous subepithelial fibroblasts and afferent neurons via substance-P and ATP plays important roles in the maturation of the structure and function of the small intestine. PMID:20967467

  4. Absorption and elimination of imatinib through the rat intestine in vitro.

    PubMed

    Kralj, Eva; Zakelj, Simon; Trontelj, Jurij; Roškar, Robert; Cernelč, Peter; Kristl, Albin

    2014-01-01

    Imatinib is a potent selective inhibitor of tyrosine kinases and is used primarily in the treatment of chronic myeloid leukemia and the gastrointestinal stromal tumour. Although, it is well established that imatinib is a substrate of several transport proteins which are also active in the intestinal mucosa, the mechanisms of imatinib intestinal absorption and elimination were not systematically investigated yet. To do that, we used a Sweetana-Grass type of diffusion chambers with segments of rat intestine as a model of the intestinal mucosa, measured the permeability coefficients of imatinib and its major metabolite (N-desmethyl imatinib) in both directions with and without specific and general inhibition of active transport, and calculated the efflux ratios. The results show that the good bioavailability of imatinib is highly likely achieved by its active absorption from the intestine and that its active elimination through the intestinal mucosa is mediated by a synergistic activity of organic cation transporter 1 in the basolateral membrane and the added activity of two efflux proteins (P-glycoprotein and breast cancer resistant protein) in the apical membrane of enterocytes of the rat ileum. Interestingly, it was found that N-desmethyl imatinib is only transported by P-glycoprotein. PMID:24219857

  5. Small intestinal ulceration secondary to carcinoid tumour arising in a Meckel's diverticulum.

    PubMed Central

    McCluggage, W G; McConnell, L; Sloan, J M; Ellis, P K; Irwin, S T

    1999-01-01

    A solitary small intestinal ulcer associated with a carcinoid tumour in a nearby Meckel's diverticulum was found in a 77 year old man presenting with massive rectal bleeding. Angiography and a radioisotope study localised the bleeding to the ileum. At operation, the Meckel's diverticulum was identified, with bleeding from an ulcer just distal to it. Pathological examination revealed a small carcinoid tumour confined to the Meckel's diverticulum. Close to the opening of the diverticulum, within the ileum, a well demarcated ulcer was present. Histology showed a non-specific ulcer which eroded a large blood vessel. This is the first documented occurrence of solitary small intestinal ulceration in association with a carcinoid tumour. Carcinoid tumour should be added to the list of possible causes of small intestinal ulceration. The ulceration may be secondary to release of cytokines by the tumour. Images PMID:10343617

  6. The Relation between Peristaltic and Segmental Contraction, Mixing, and Absorption in the Small Intestine

    NASA Astrophysics Data System (ADS)

    Banco, Gino; Brasseur, James; Wang, Yanxing; Ailiani, Amit; Neuberger, Thomas; Webb, Andrew

    2009-11-01

    The physiology and mechanics of the small intestine originates with lumen-scale fluid motions generated by enterically controlled muscle wall contractions. Although complex in appearance, we have shown with principle component decomposition of gut motion from a rat model that simpler component structure may integrate to produce basic peristaltic and segmental motions. To couple these measured modes with fluid mixing and nutrient absorption we have developed 2-D and axisymmetric models of the gut using the lattice-Boltzmann framework with scalar and second order moving boundary conditions. Previous models indicated that peristalsis is detrimental to absorption and therefore that gut motility is likely bimodal, transitioning between peristalsis and segmental modes to optimize the transport of chyme vs. nutrient absorption. However we have since discovered that more complex control is possible due to potential transitions between ``trapped'' vs. ``nontrapped'' peristaltic fluid motions, depending on occlusion ratio. These transitions lead to an important distinction between 2-D and axisymmetric models and indicate that gut motility may be more finely controlled than previously thought. [Supported by NSF

  7. Tissue engineered esophagus scaffold constructed with porcine small intestinal submucosa and synthetic polymers.

    PubMed

    Fan, Mei-Rong; Gong, Mei; Da, Lin-Cui; Bai, Lin; Li, Xiu-Qun; Chen, Ke-Fei; Li-Ling, Jesse; Yang, Zhi-Ming; Xie, Hui-Qi

    2014-02-01

    Acellular porcine small intestinal submucosa (SIS) has been successfully used for reconstructing esophagus with half circumferential defects. However, repairing full circumferential esophageal defects with SIS has been restricted due to the latter's poor mechanical properties. In the present study, synthetic polyesters biomaterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and poly(lactide-co-glycolide) (PLGA) have been used to improve the mechanical properties of SIS. Feasibility of SIS/PHBHHx-PLGA composite material scaffold for esophageal tissue engineering has been assessed through a series of testing. The appropriate mixing ratio of PHBHHx and PLGA polymers has been determined as 5:5 by mechanical testing and in vitro degradation experiment. The morphology of constructed membranous and tubular scaffolds was also characterized. As confirmed by enzyme-linked immunosorbent assay, the contents of VEGF and TGF-β have respectively reached 657 ± 18 ng mL(-1) and 130 ± 4 pg mL(-1) within the SIS/PHBHHx-PLGA specimens. Biocompatibility of the SIS/PHBHHx-PLGA specimens with rat bone marrow mesenchymal stem cells (MSCs) was also evaluated by scanning electron microscopy and a live-dead cell viability assay. Actin filaments of MSCs on the composite materials were labeled. Biological safety of the extract from SIS/PHBHHx-PLGA specimens, measured as hemolysis rate, was all lower than 5%. Compared with SIS and SIS/PHBHHx-PLGA specimens, inflammatory reaction provoked by the PHBHHx-PLGA specimens in rats was however more severe. Our results have suggested that SIS/PHBHHx-PLGA composite material can offer a new approach for esophageal tissue engineering. PMID:24457267

  8. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation.

    PubMed

    Becker, Amy M; Callahan, Derrick J; Richner, Justin M; Choi, Jaebok; DiPersio, John F; Diamond, Michael S; Bhattacharya, Deepta

    2015-01-01

    Specific G protein coupled receptors (GPRs) regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs) of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation. PMID:26197390

  9. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation

    PubMed Central

    Becker, Amy M.; Callahan, Derrick J.; Richner, Justin M.; Choi, Jaebok; DiPersio, John F.; Diamond, Michael S.; Bhattacharya, Deepta

    2015-01-01

    Specific G protein coupled receptors (GPRs) regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs) of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation. PMID:26197390

  10. Age-associated modifications of intestinal permeability and innate immunity in human small intestine.

    PubMed

    Man, Angela L; Bertelli, Eugenio; Rentini, Silvia; Regoli, Mari; Briars, Graham; Marini, Mario; Watson, Alastair J M; Nicoletti, Claudio

    2015-10-01

    The physical and immunological properties of the human intestinal epithelial barrier in aging are largely unknown. Ileal biopsies from young (7-12 years), adult (20-40 years) and aging (67-77 years) individuals not showing symptoms of gastrointestinal (GI) pathologies were used to assess levels of inflammatory cytokines, barrier integrity and cytokine production in response to microbial challenges. Increased expression of interleukin (IL)-6, but not interferon (IFN)γ, tumour necrosis factor (TNF)-α and IL-1β was observed during aging; further analysis showed that cluster of differentiation (CD)11c(+) dendritic cells (DCs) are one of the major sources of IL-6 in the aging gut and expressed higher levels of CD40. Up-regulated production of IL-6 was accompanied by increased expression of claudin-2 leading to reduced transepithelial electric resistance (TEER); TEER could be restored in in vitro and ex vivo cultures by neutralizing anti-IL-6 antibody. In contrast, expression of zonula occludens-1 (ZO-1), occludin and junctional-adhesion molecule-A1 did not vary with age and overall permeability to macromolecules was not affected. Finally, cytokine production in response to different microbial stimuli was assessed in a polarized in vitro organ culture (IVOC). IL-8 production in response to flagellin declined progressively with age although the expression and distribution of toll-like receptor (TLR)-5 on intestinal epithelial cells (IECs) remained unchanged. Also, flagellin-induced production of IL-6 was less pronounced in aging individuals. In contrast, TNF-α production in response to probiotics (VSL#3) did not decline with age; however, in our experimental model probiotics did not down-regulate the production of IL-6 and expression of claudin-2. These data suggested that aging affects properties of the intestinal barrier likely to impact on age-associated disturbances, both locally and systemically. PMID:25948052

  11. Hydroxyethyl Starch (HES 130/0.4) Impairs Intestinal Barrier Integrity and Metabolic Function: Findings from a Mouse Model of the Isolated Perfused Small Intestine

    PubMed Central

    Dombrowsky, Heike; Zitta, Karina; Bein, Berthold; Krause, Thorsten; Goldmann, Torsten; Frerichs, Inez; Steinfath, Markus; Weiler, Norbert; Albrecht, Martin

    2015-01-01

    Background The application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine. Methods An isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-to-pyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups. Results Compared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces. Conclusion A vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small

  12. Intestinal absorption of triglyceride and vitamin D3 in aged and young rats

    SciTech Connect

    Holt, P.R.; Dominguez, A.A.

    1981-12-01

    (3H)Trioleyl glycerol (TO) and (14C)vitamin D3 were perfused intraduodenally for 5 hr in aged (19-21 months) and young adult (4-5 months) Sprague-Dawley rats. The rate of intestinal uptake from the gastrointestinal lumen and transport into the body of these lipids were decreased in the aged animals. Since the distribution of TO lipolytic products in the lumen was unchanged, reduced intestinal uptake rate probably occurred at the mucosal membrane. Furthermore, in the aged rats, the rate of transintestinal transport of both trioleyl glycerol and vitamin D3 was impaired. No evidence for impaired mucosal TO reesterification or for accumulation of vitamin D3 metabolites was found, suggesting that intestinal lipid accumulation resulted from a defect in lipoprotein assembly or in discharge from the mucosal cell. Impaired absorption of lipids may contribute to malnutrition and osteopenia of advancing age.

  13. Mass spectrometric profiling of lipids in intestinal tissue from rats fed cereals processed for medical conditions.

    PubMed

    Dowlatshahi Pour, Masoumeh; Jennische, Eva; Lange, Stefan; Ewing, Andrew G; Malmberg, Per

    2016-06-01

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used for lipid profiling of intestine tissue sections from rats fed specially processed cereals and rats fed ordinary feed as a control. This cereal is known to increase the activity of antisecretory factor in plasma and the exact mechanism for the activation process at the cellular level is unclear. ToF-SIMS has been used to track food induced changes in lipid content in intestinal tissue sections to gain insight into the possible mechanisms involved. Data from 20 intestine sections belonging to four different rats from each group of control and specially processed cereals-fed rats were obtained using the stage scan macroraster with a lateral resolution of 5 μm. Data were subsequently subjected to orthogonal partial least squares discriminant analysis. The data clearly show that changes of certain lipids are induced by the specially processed cereal feed. Scores plots show a well-defined separation between the two groups. The corresponding loading plots reveal that the groups separate mainly due to changes of vitamin E, phosphocholine, and phosphosphingolipid fragments, and that for the c18:2 fatty acid. The observed changes in lipids might give insight into the working mechanisms of antisecretory factor in the body, and this has been successfully used to understand the working mechanism of specially processed cereal-induced antisecretory factor activation in intestine. PMID:26753787

  14. Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status

    PubMed Central

    Willing, Benjamin P.; Croxen, Matthew A.; Dufour, Nicolas; Dion, Sara; Wachtel, Sarah; Denamur, Erick; Finlay, B. Brett

    2016-01-01

    Uropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ΔPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated. Intestinal colonization was measured, and cytokine expression was determined in various organs recovered from mice after oral challenge. UPEC strain 536 efficiently colonized the mouse digestive tract, and prior Enterobacteriaceae colonization was found to impact strain 536 colonization efficiency. An innate immune response, detected as the production of TNFα, IL-6 and IL-10 cytokines, was activated in the ileum 48 hours after oral challenge with strain 536, and returned to baseline within 8 days, without a drop in fecal pathogen load. Although inflammation was detected in the ileum, histology was normal at the time of cytokine peak. Comparison of cytokine secretion 48h after oral gavage with E. coli strain 536, CFT073, MG1655 or ΔPAI-536 showed that inflammation was more pronounced with UPECs than with non-pathogenic or attenuated strains. Pathogenicity islands also seemed to be involved in host detection, as IL-6 intestinal secretion was increased after administration of E. coli strain 536, but not after administration of ΔPAI-536. In conclusion, UPEC colonization of the mouse digestive tract activates acute phase inflammatory cytokine secretion but does not trigger any pathological changes, illustrating the opportunistic nature of UPECs. This digestive tract colonization model will be useful for studying the factors controlling the switch from commensalism to pathogenicity. PMID:27096607

  15. Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates

    PubMed Central

    Dautrey, S; Felice, K; Petiet, A; Lacour, B; Carbon, C; Farinotti, R

    1999-01-01

    Two in vivo models, in the rat, were used to investigate, in the presence of different substrates, the overall and net intestinal elimination of ciprofloxacin: an open-intestinal perfusion model and an intestinal loop model respectively.In the presence of quinidine, verapamil and cyclosporin (substrates of the P-glycoprotein (P-gp)), plasma AUCs of ciprofloxacin were 1.5–2 fold increased, while biliary clearance (1.5–2 fold), intestinal overall and net clearances (2–4 fold and 1.5–8 fold respectively) decreased. The weak effect obtained with cyclosporin as compared to verapamil and especially quinidine, suggests, for ciprofloxacin, the existence of transport systems distinct from the P-gp, as the OCT1 transporter which could be inhibited by quinidine.With cephalexin and azlocillin, two β-lactam antibiotics, plasma AUCs of ciprofloxacin increased and biliary and intestinal overall clearances decreased in a similar fashion (1.3–2 fold), suggesting the involvement of organic anion and/or cation transporters.In the presence of structural analogues, the effect was dependent on the compound administered: Sparfloxacin had no effect on intestinal clearance of ciprofloxacin. In contrast, with pefloxacin, overall intestinal clearance of ciprofloxacin was decreased and net intestinal clearance increased.The specificity of ciprofloxacin intestinal transport appears to be different from P-gp as outlined by the lack of competition with sparfloxacin, a P-gp substrate. Ciprofloxacin intestinal elimination seems to be mediated by organic anion and/or cation transporters and a mechanism sensitive to quinidine and verapamil. PMID:10455332

  16. Intraepithelial lymphocytes express junctional molecules in murine small intestine

    SciTech Connect

    Inagaki-Ohara, Kyoko . E-mail: INAGAKI@med.miyazaki-u.ac.jp; Sawaguchi, Akira; Suganuma, Tatsuo; Matsuzaki, Goro; Nawa, Yukifumi

    2005-06-17

    Intestinal intraepithelial lymphocytes (IEL) that reside at basolateral site regulate the proliferation and differentiation of epithelial cells (EC) for providing a first line of host defense in intestine. However, it remains unknown how IEL interact and communicate with EC. Here, we show that IEL express junctional molecules like EC. We identified mRNA expression of the junctional molecules in IEL such as zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM) (tight junction), {beta}-catenin and E-cadherin (adherens junction), and connexin26 (gap junction). IEL constitutively expressed occludin and E-cadherin at protein level, while other T cells in the thymus, spleen, liver, mesenteric lymph node, and Peyer's patches did not. {gamma}{delta} IEL showed higher level of these expressions than {alpha}{beta} IEL. The expression of occludin was augmented by anti-CD3 Ab stimulation. These results suggest the possibility of a novel role of IEL concerning epithelial barrier and communication between IEL and EC.

  17. Effect of Ozone on Intestinal Epithelial Homeostasis in a Rat Model

    PubMed Central

    Sukhotnik, Igor; Starikov, Alona; Coran, Arnold G.; Pollak, Yulia; Sohotnik, Rima; Shaoul, Ron

    2015-01-01

    Background: The positive effects of ozone therapy have been described in many gastrointestinal disorders. The mechanisms of this positive effect of ozone therapy are poorly understood. The purpose of the present study was to investigate whether the use of ozone may potentiate the gut intestinal mucosal homeostasis in a rat model. Methods: Adult rats weighing 250–280 g were randomly assigned to one of three experimental groups of 8 rats each: 1) Control rats were given 2 mL of water by gavage and intraperitoneally (IP) for 5 days; 2) O3-PO rats were treated with 2 mL of ozone/oxygen mixture by gavage and 2 mL of water IP for 5 days; 3) O3-IP rats were treated with 2 mL of water by gavage and 2 mL of ozone/oxygen mixture IP for 5 days. Rats were sacrificed on day 6. Bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, and cell proliferation and apoptosis were evaluated following sacrifice. Results: The group of O3-IP rats demonstrated a greater jejunal and ileal villus height and crypt depth, a greater enterocyte proliferation index in jejunum, and lower enterocyte apoptosis in ileum compared to control animals. Oral administration of the ozone/oxygen mixture resulted in a less significant effect on cell turnover. Conclusions: Treatment with an ozone/oxygen mixture stimulates intestinal cell turnover in a rat model. Intraperitoneal administration of ozone resulted in a more significant intestinal trophic effect than oral administration. PMID:25717388

  18. Comparative assessment of two indices of drug induced permeability changes in the perfused rat intestine.

    PubMed

    Lane, Majella E; Levis, Karl; McDonald, George S A; Corrigan, Owen I

    2006-04-01

    In the present study, two indices of acute intestinal permeability changes were investigated as measurements of drug induced intestinal damage. The first method was based on 14C-polyethylene glycol (PEG) 4000 permeability assessment and the second was based on histological evaluation of the intestine. The test compounds were ibuprofen, ketoprofen and naproxen and the alanine, glycine and phenylalanine amide derivatives of ibuprofen. Perfusion studies were carried out using a rat model. Post-perfusion, the gut was fixed and tissue changes were assessed and scored. Ibuprofen, ketoprofen and naproxen altered the barrier properties of the intestine to PEG 4000 with significantly higher scores (p<0.05) for gastrointestinal toxicity relative to blank buffer. For ketoprofen, PEG 4000 permeability and intestinal damage scores increased with increasing ketoprofen concentration. Ibuprofen amide derivatives did not induce significant histological damage or PEG 4000 permeability when compared with ibuprofen. A correlation coefficient of 0.91 is obtained when intestinal damage scores are plotted against PEG 4000 permeability for all compounds. Both indices are proposed as rapid and useful measures of drug induced acute intestinal damage. PMID:16476530

  19. Characterization of intestinal absorption of mizoribine mediated by concentrative nucleoside transporters in rats.

    PubMed

    Mori, Nobuhiro; Yokooji, Tomoharu; Kamio, Yoshihiro; Murakami, Teruo

    2008-05-31

    Mizoribine, an imidazole nucleoside, is an inhibitor of purine synthesis and has been used as an orally available immunosuppressive agent in human renal transplantation. In the present study, the intestinal absorption of mizoribine was characterized by examining the contribution of concentrative nucleoside transporters (CNT1, CNT2) in rats. When mizoribine was administered orally in conscious rats, the bioavailability of mizoribine estimated by urinary excretion percentage of unchanged mizoribine was a dose dependent: 53.1+/-6.0% at 5 mg/kg and 24.0+/-5.1% at 20 mg/kg. In in-situ loop studies, the disappearance rate, or absorption rate, of mizoribine from the intestinal lumen was comparable between 1 and 5 mg/kg, but significantly lower at 25 mg/kg. Coadministration of adenosine (a substrate of both CNT1 and CNT2), thymidine (a CNT1 substrate) and inosine (a CNT2 substrate) significantly suppressed the intestinal mizoribine absorption, depending on the nucleoside concentrations coadministered. Gemcitabine (a pyrimidine nucleoside analogue, a CNT1 substrate) and ribavirin (a purine nucleoside analog, a CNT2 substrate) also significantly suppressed the mizoribine intestinal absorption. Bile salts such as sodium cholate and sodium glycocholate (10 mM) also significantly suppressed the intestinal mizoribine absorption, but not ribavirin absorption. Mizoribine is an amphoteric compound, however, the suppression of intestinal absorption by bile salts was not ascribed to the electrostatic interaction or micellar formation between mizoribine and bile salts. In conclusion, the intestinal absorption of mizoribine is mediated by CNT1 and CNT2, and nucleoside-derived drugs such as gemcitabine and ribavirin can suppress the intestinal absorption of mizoribine. Bile salts such as sodium glycocholate were also found to cause interaction with mizoribine. PMID:18371949

  20. EFFECTS OF HELIUM PRECONDITIONING ON INTESTINAL ISCHEMIA AND REPERFUSION INJURY IN RATS.

    PubMed

    Du, Lei; Zhang, Rongjia; Luo, Tianhang; Nie, Mingming; Bi, Jianwei

    2015-10-01

    Intestinal ischemia-reperfusion (I/R) injury can occur in clinical settings such as organ transplantation, cardiopulmonary bypass and trauma. The noble gas helium attenuates I/R injury in a number of animal organs and thus may offer a strategy for reducing I/R-induced intestinal injury in clinical settings. In the present study, we used four different helium preconditioning (HPC) profiles to investigate the potential beneficial effect of HPC on I/R-induced intestinal injury. Male Sprague-Dawley rats were pretreated with three cycles of air breathing for 5 min combined with three cycles of breathing a 70% helium:30% oxygen mixture for either 2, 5, 10, or 15 min, after which they were subjected to 60-min intestinal ischemia and 60-min reperfusion. Sixty minutes after reperfusion, the intestinal tissues of the variously treated rats were analyzed using histology, immunohistochemistry, terminal dUTP nick-end labeling staining, myeloperoxidase activity assay, Western blotting, and enzyme-linked immunosorbent assay for tumor necrosis factor α and macrophage inflammatory protein 1α. Intestinal permeability was assayed by measuring fluorescein isothiocyanate-dextran release in blood samples. The results showed that the HPC profile consisting of three cycles of 10 or 15 min of helium breathing and three cycles of 5 min of air breathing reduced I/R-induced intestinal injury, cell apoptosis, and the inflammatory response. However, the 2- or 5-min helium breathing did not confer any protective effects. It seems that longer helium episodes should be used in HPC profiles designed to attenuate intestinal I/R injury. PMID:26052960

  1. [Gastrointestinal stromal tumors. A case of small intestine stromal tumor (SIST) with an uncertain biological aspect].

    PubMed

    Quaglino, F; Borello, M; Cumbo, P; Pietribiasi, F; Poma, A; Seglie, E; Do, D

    2000-05-01

    Tumors of the small intestine are relatively rare. The diagnosis is difficult to establish because the symptoms are vague and non-specific. Although the small intestine constitutes 75% of the length and over 90% of the mucosal surface area of the gastrointestinal tract, only 1 to 2% of gastrointestinal malignancies occur in this segment. Metastases are usually present at the time of diagnosis. The outcome of these patients can be improved if the possibility of a malignant small bowel tumor is considered in all cases of unexplained abdominal pain or gastrointestinal bleeding, especially in younger age. Malignant tumors occur with increasing frequency in distal small bowel with a preponderance of malignant lesions in the ileum compared with the jejunum and the duodenum. Adenocarcinoma is the most common tumor of the primary malignant small bowel tumors, followed by carcinoid, lymphoma and leiomyosarcoma. Mesenchymal tumors of the gastrointestinal tract, traditionally regarded as smooth muscle tumors, have demonstrated different cellular differentiations based on immunohistochemical and ultrastructural features. Therefore the terms leiomyoma and leiomyosarcoma have been replaced by a more encompassing term, gastrointestinal stromal tumor (GIST). The majority of GISTs occurs in the stomach; stromal tumors involving the small intestine (SISTs) are far less common but seem to have greater malignant potential. The clinical a case of a small intestinal stromal tumor (SIST), localised in the jejunum and characterised by an uncertain histological aspect, is presented and a review of the literature is made. PMID:10953571

  2. Recombinant Human Epidermal Growth Factor Accelerates Recovery of Mouse Small Intestinal Mucosa After Radiation Damage

    SciTech Connect

    Lee, Kang Kyoo; Jo, Hyang Jeong; Hong, Joon Pio; Lee, Sang-wook Sohn, Jung Sook; Moon, Soo Young; Yang, Sei Hoon; Shim, Hyeok; Lee, Sang Ho; Ryu, Seung-Hee; Moon, Sun Rock

    2008-07-15

    Purpose: To determine whether systemically administered recombinant human epidermal growth factor (rhEGF) accelerates the recovery of mouse small intestinal mucosa after irradiation. Methods and Materials: A mouse mucosal damage model was established by administering radiation to male BALB/c mice with a single dose of 15 Gy applied to the abdomen. After irradiation, rhEGF was administered subcutaneously at various doses (0.04, 0.2, 1.0, and 5.0 mg/kg/day) eight times at 2- to 3-day intervals. The evaluation methods included histologic changes of small intestinal mucosa, change in body weight, frequency of diarrhea, and survival rate. Results: The recovery of small intestinal mucosa after irradiation was significantly improved in the mice treated with a high dose of rhEGF. In the mice that underwent irradiation without rhEGF treatment, intestinal mucosal ulceration, mucosal layer damage, and severe inflammation occurred. The regeneration of villi was noticeable in mice treated with more than 0.2 mg/kg rhEGF, and the villi recovered fully in mice given more than 1 mg/kg rhEGF. The frequency of diarrhea persisting for more than 3 days was significantly greater in the radiation control group than in the rhEGF-treated groups. Conclusions: Systemic administration of rhEGF accelerates recovery from mucosal damage induced by irradiation. We suggest that rhEGF treatment shows promise for the reduction of small intestinal damage after irradiation.

  3. Laparoscopic resection of synchronous gastric cancer and primary small intestinal lymphoma: a case report.

    PubMed

    Chen, Ding-Wei; Pan, Yu; Yan, Jia-Fei; Mou, Yi-Ping

    2014-05-28

    Synchronous gastric cancer and primary small intestinal lymphoma are extremely rare. A 49-year-old woman was referred to our hospital with a history of upper abdominal pain for two weeks and was diagnosed with synchronous cancer. During hospitalization, the patient underwent laparoscopic distal gastrectomy + resection of bilateral ovaries + partial resection of both small intestine and descending colon. Pathological examination revealed a synchronous cancer consisting of early gastric cancer with poorly differentiated adenocarcinoma located in mucosa, with lymph node metastasis (3+/29) (T1N1M0, stage IB); and diffuse large B cell lymphoma of small intestine involving descending colon and bilateral ovaries, with lymph node metastasis (2+/5) (Ann Arbor IIE). The patient recovered well, without any obvious complications and was discharged on post-operative day 7. The patient received six cycles of chemotherapy after operation. She has been doing well with no evidence of recurrence for 13 mo. PMID:24876758

  4. Involvement of Concentrative Nucleoside Transporter 1 in Intestinal Absorption of Trifluridine Using Human Small Intestinal Epithelial Cells.

    PubMed

    Takahashi, Koichi; Yoshisue, Kunihiro; Chiba, Masato; Nakanishi, Takeo; Tamai, Ikumi

    2015-09-01

    TAS-102, which is effective for refractory metastatic colorectal cancer, is a combination drug of anticancer trifluridine (FTD; which is derived from pyrimidine nucleoside) and FTD-metabolizing enzyme inhibitor tipiracil hydrochloride (TPI) at a molecular ratio of 1:0.5. To evaluate the intestinal absorption mechanism of FTD, the uptake and transcellular transport of FTD by human small intestinal epithelial cell (HIEC) monolayer as a model of human intestinal epithelial cells was investigated. The uptake and membrane permeability of FTD by HIEC monolayers were saturable, Na(+) -dependent, and inhibited by nucleosides. These transport characteristics are mostly comparable with those of concentrative nucleoside transporters (CNTs). Moreover, the uptake of FTD by CNT1-expressing Xenopus oocytes was the highest among human CNT transporters. The obtained Km and Vmax values of FTD by CNT1 were 69.0 μM and 516 pmol/oocyte/30 min, respectively. The transcellular transport of FTD by Caco-2 cells, where CNT1 is heterologously expressed, from apical to basolateral side was greater than that by Mock cells. In conclusion, these results demonstrated that FTD exhibits high oral absorption by the contribution of human CNT1. PMID:25900515

  5. Pro-oxidant environment of the colon compared to the small intestine may contribute to greater cancer susceptibility.

    PubMed

    Sanders, Lisa M; Henderson, Cara E; Hong, Mee Young; Barhoumi, Rola; Burghardt, Robert C; Carroll, Raymond J; Turner, Nancy D; Chapkin, Robert S; Lupton, Joanne R

    2004-05-28

    The colon and small intestine have inherent differences (e.g. redox status) that may explain the variation in cancer occurrence at these two sites. This study examined basal and induced (oxidative challenge) reactive oxygen species (ROS) generation, antioxidant enzyme activity and oxidative DNA damage. Basal ROS and antioxidant enzyme activities in the colon were greater than in the small intestine. During oxidative stress, 8-oxo-deoxyguanosine (8-oxodG) DNA adducts in the colon exceeded levels in the small intestine concomitant with increased ROS. Thus the colon responds to oxidative stress less effectively than the small intestine, possibly contributing to increased cancer incidence at this site. PMID:15142673

  6. Toxic Effects of Maternal Zearalenone Exposure on Intestinal Oxidative Stress, Barrier Function, Immunological and Morphological Changes in Rats

    PubMed Central

    Liu, Min; Gao, Rui; Meng, Qingwei; Zhang, Yuanyuan; Bi, Chongpeng; Shan, Anshan

    2014-01-01

    The present study was conducted to investigate the effects of maternal zearalenone (ZEN) exposure on the intestine of pregnant Sprague-Dawley (SD) rats and its offspring. Ninety-six pregnant SD rats were randomly divided into four groups and were fed with diets containing ZEN at concentrations of 0.3 mg/kg, 48.5 mg/kg, 97.6 mg/kg or 146.0 mg/kg from gestation days (GD) 1 to 7. All rats were fed with mycotoxin-free diet until their offspring were weaned at three weeks of age. The small intestinal fragments from pregnant rats at GD8, weaned dams and pups were collected and studied for toxic effects of ZEN on antioxidant status, immune response, expression of junction proteins, and morphology. The results showed that ZEN induced oxidative stress, affected the villous structure and reduced the expression of junction proteins claudin-4, occludin and connexin43 (Cx43) in a dose-dependent manner in pregnant rats. Different effects on the expression of cytokines were also observed both in mRNA and protein levels in these pregnant groups. Ingestion of high levels of ZEN caused irreversible damage in weaned dams, such as oxidative stress, decreased villi hight and low expression of junction proteins and cytokines. Decreased expression of jejunal interleukin-8 (IL-8) and increased expression of gastrointestinal glutathione peroxidase (GPx2) mRNA were detected in weaned offspring, indicating long-term damage caused by maternal ZEN. We also found that the Nrf2 expression both in mRNA and protein levels were up-regulated in the ZEN-treated groups of pregnant dams and the high-dose of ZEN group of weaned dams. The data indicate that modulation of Nrf2-mediated pathway is one of mechanism via which ZEN affects gut wall antioxidant and inflammatory responses. PMID:25180673

  7. Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome

    PubMed Central

    Otani, Koji; Watanabe, Toshio; Shimada, Sunao; Takeda, Shogo; Itani, Shigehiro; Higashimori, Akira; Nadatani, Yuji; Nagami, Yasuaki; Tanaka, Fumio; Kamata, Noriko; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Fujiwara, Yasuhiro; Arakawa, Tetsuo

    2016-01-01

    The inflammasome is a large, multiprotein complex that consists of a nucleotide-binding oligomerization domain-like receptor (NLR), an apoptosis-associated speck-like protein containing a caspase recruitment domain, and pro-caspase-1. Activation of the inflammasome results in cleavage of pro-caspase-1 into cleaved caspase-1, which promotes the processing of pro-interleukin (IL)-1β into mature IL-1β. We investigated the effects of colchicine on non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal injury and activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Colchicine treatment inhibited indomethacin-induced small intestinal injury by 86% (1 mg/kg) and 94% (3 mg/kg) as indicated by the lesion index 24 h after indomethacin administration. Colchicine inhibited the protein expression of cleaved caspase-1 and mature IL-1β, without affecting the mRNA expression of NLRP3 and IL-1β. Although treatment with recombinant IL-1β (0.1 μg/kg) did not change the severity of small intestinal damage, the preventive effects of colchicine were abolished by supplementation with the same dose of recom